N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through activation of AMPK and p38 MAPK.

PubMed

Lee, Wei-Hwa; Wu, Hsueh-Hsia; Huang, Wei-Jan; Li, Yi-Ning; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

2015-03-11

Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes.

Effect of salicylate on outer hair cell plasma membrane viscoelasticity: studies using optical tweezers

NASA Astrophysics Data System (ADS)

Ermilov, Sergey A.; Brownell, William E.; Anvari, Bahman

2004-06-01

The plasma membrane (PM) of mammalian outer hair cells (OHCs) generates mechanical forces in response to changes in the transmembrane electrical potential. The resulting change in the cell length is known as electromotility. Salicylate (Sal), the anionic, amphipathic derivative of aspirin induces reversible hearing loss and decreases electromotile response of the OHCs. Sal may change the local curvature and mechanical properties of the PM, eventually resulting in reduced electromotility or it may compete with intracellular monovalent anions, particularly Cl-, which are essential for electromotility. In this work we have used optical tweezers to study the effects of Sal on viscoelastic properties of the OHC PM when separated from the underlying composite structures of the cell wall. In this procedure, an optically trapped microsphere is brought in contact with PM and subsequently pulled away to form a tether. We measured the force exerted on the tether as a function of time during the process of tether growth at different pulling rates. Effective tether viscosity, steady-state tethering force extrapolated to zero pulling rate, and the time constant for tether growth were estimated from the measurements of the instantaneous tethering force. The time constant for the tether growth measured for the OHC basal end decreased 1.65 times after addition of 10 mM Sal, which may result from an interaction between Sal and cholesterol, which is more prevalent in the PM of OHC basal end. The time constants for the tether growth calculated for the OHC lateral wall and control human embryonic kidney cells as well as the other calculated viscoelastic parameters remained the same after Sal perfusion, favoring the hypothesis of competitive inhibition of electromotility by salicylate.

Differences in cholinergic responses from outer hair cells of rat and guinea pig.

PubMed

Chen, C; LeBlanc, C; Bobbin, R P

1996-09-01

A cholinergic receptor on outer hair cells (OHC) in guinea pig cochlea induces a K+ current when it is activated by acetylcholine and suberyldicholine but not by nicotine or muscarine (Bobbin, 1995). This unusual receptor may contain an alpha 9-subunit. However, the pharmacology of the alpha 9-subunit cloned from rat and expressed in Xenopus oocytes does not completely match that obtained for the ACh receptor in guinea pig OHCs. The response to 1,1-dimethyl-4-phenylpiperazinium (DMPP) is large in guinea pig OHCs and small in oocytes containing receptors of the alpha 9-subunit. Therefore, we compared the effects of cholinergic receptor agonists in rat and guinea pig OHCs using the whole-cell variant of the patch-clamp technique. ACh caused the largest outward K+ current in OHCs from both rat and guinea pig. Carbachol- and suberyldicholine-induced responses were similar in magnitude in OHCs of rat and guinea pig. However, DMPP produced a small response in OHCs from rat and a large response in OHCs from guinea pig. At a concentration of 100 microM, muscarine, oxotremorine M, nicotine and cytisine induced little response in guinea pig OHCs and none in rat OHCs. Results suggest that the ACh receptor on rat OHCs is similar to the alpha 9-subunit-containing receptor expressed in oocytes but different from the ACh receptor on guinea pig OHCs.

Shape deformation of the organ of Corti associated with length changes of outer hair cell

NASA Technical Reports Server (NTRS)

Zimmermann, U.; Fermin, C.

1996-01-01

Cochlear outer hair cells (OHC) are commonly assumed to function as mechanical effectors as well as sensory receptors in the organ of Corti (OC) of the inner ear. OHC in vitro and in organ explants exhibit mechanical responses to electrical, chemical or mechanical stimulation which may represent an aspect of their effector process that is expected in vivo. A detailed description, however, of an OHC effector operation in situ is still missing. Specifically, little is known as to how OHC movements influence the geometry of the OC in situ. Previous work has demonstrated that the motility of isolated OHCs in response to electrical stimulation and to K(+)-gluconate is probably under voltage control and causes depolarisation (shortening) and hyperpolarization (elongation). This work was undertaken to investigate if the movements that were observed in isolated OHC, and which are induced by ionic stimulation, could change the geometry of the OC. A synchronized depolarization of OHC was induced in guinea pig cochleae by exposing the entire OC to artificial endolymph (K+). Subsequent morphometry of mid-modiolar sections from these cochleae revealed that the distance between the basilar membrane (BM) and the reticular lamina (RL) had decreased considerably. Furthermore, in the three upper turns OHC had significantly shortened in all rows. The results suggest that OHC can change their length in the organ of Corti (OC) thus deforming the geometry of the OC. The experiments reveal a tonic force generation within the OC that may change the position of RL and/or BM, contribute to damping, modulate the BM-RL-distance and control the operating points of RL and sensory hair bundles. Thus, the results suggest active self-adjustments of cochlear mechanics by slow OHC length changes. Such mechanical adjustments have recently been postulated to correspond to timing elements of animal communication, speech or music.

Basilar membrane vibration after targeted removal of the third row of OHCs and Deiters cells

NASA Astrophysics Data System (ADS)

Xia, Anping; Udagawa, Tomokatsu; Raphael, Patrick D.; Cheng, Alan G.; Steele, Charles R.; Applegate, Brian E.; Oghalai, John S.

2018-05-01

The mammalian cochlea has three rows of outer hair cells (OHCs) that amplify the basilar membrane (BM) traveling wave with high gain and exquisite sharpness. However, it is unclear why three rows of OHCs are needed to achieve this. We used a novel transgenic mouse with the diphtheria toxin receptor in Lgr5-positive cells (Lgr5DTR-EGFP/+ mouse) that allowed us to ablate the third row of OHCs and Deiters cells (D) in adulthood via DT injection, after normal cochlear function had developed. We then used volumetric optical coherence tomography (VOCTV) to investigate the impacts of this manipulation of cochlear amplification in the apical turn. As expected, Lgr5DTR-EGFP/+ control mice had sharply-tuned vibratory responses. However, Lgr5DTR-EGFP/+ mice had broad tuning with a 20 dB increase in vibratory thresholds. The Q10dB was ˜1 in Lgr5DTR-EGFP/+ mice, whereas it was ˜3 in control mice. The characteristic frequency was lower in Lgr5DTR-EGFP/+ mice compared to controls (7.5 vs. 9.0 kHz). The gain of cochlear amplification was substantially lower in Lgr5DTR-EGFP/+ mice compared to controls (22 vs. 50). In the post-mortem period, the vibratory responses in Lgr5DTR-EGFP/+ mice were identical to controls. Together, these results demonstrate the substantial importance of the third row of OHCs and Deiters cells to normal cochlear amplification.

Outer Hair Cell Electromotility in vivo

NASA Astrophysics Data System (ADS)

Ramamoorthy, Sripriya; Nuttall, Alfred L.

2011-11-01

The effectiveness of outer hair cell (OHC) electro-motility in vivo has been challenged by the expected low-pass filtering of the transmembrane potential due to the cell's own capacitance. The OHC electromotility is characterized here by an electromechanical ratio defined as the ratio of the OHC contraction to the transmembrane potential. This ratio has been measured in isolated cells to be approximately 26 nm/mV. We estimate the OHC electromechanical ratio in vivo from the recently measured displacements of the reticular lamina and the basilar membrane near the 19 kHz characteristic frequency in the basal region of guinea pig cochlea. Our analysis strongly suggests OHC electromotility process is effective for cochlear amplification in vivo at least around the characteristic frequency of the basal location in spite of the low-pass filtering.

Distribution of protein motors along the lateral wall of the outer hair cell.

PubMed

Wada, H; Usukura, H; Takeuchi, S; Sugawara, M; Kakehata, S; Ikeda, K

2001-12-01

The outer hair cell (OHC) plays an important role in the normal functioning of the cochlea, and cochlear amplification is believed to be based on OHC electromotility. This electromotility putatively arises from a conformational change of molecules, i.e., 'protein motors', which would be distributed along the plasma membrane. Although it has been assumed that protein motors are distributed in a restricted area of the plasma membrane, details of such distribution remain unclarified. In this study, first, in order to understand the difference in the stiffness along the cell axis, the local deformation of the OHC in response to hypotonic stimulation is analyzed by measuring the displacement of microspheres attached randomly to the lateral wall of the cell. As a result, the stiffness is expected to be constant throughout the region except in the apical part of the cell, and the stiffness of the apical part is expected to be higher than that of the other regions. Then, the local elongation and contraction of the OHC in response to sinusoidal voltage stimulation are analyzed by measuring the displacement of the microspheres in the same way as in the case of the hypotonic stimulation. From the two measurements mentioned above, it is concluded that there are no motors in the apical and basal parts of the cell, and that the motors are equally distributed along the cell lateral wall in the middle part of the cell.

Acetylcholine, carbachol, and GABA induce no detectable change in the length of isolated outer hair cells.

PubMed

Bobbin, R P; Fallon, M; Puel, J L; Bryant, G; Bledsoe, S C; Zajic, G; Schacht, J

1990-08-01

The mechanical and electrical properties of cochlear outer hair cells (OHCs) are suggested to modulate transduction by inner hair cells. These properties of OHCs are presumably regulated by efferent neurons which use several transmitters including acetylcholine (Ach) and gamma aminobutyric acid (GABA). Since it had been suggested that Ach causes isolated OHCs to shorten visibly, this study was designed to investigate whether GABA also alters the length of OHCs. OHCs were isolated from the guinea pig cochlea by mechanical dispersion after collagenase treatment. Cells were initially selected by strict morphological criteria. In addition they were only included in further studies if they attained a constant length during 10 min of superfusion with buffer solution. Neither GABA (20 microM: 100 microM), Ach (5 mM; 10 microM with 10 microM eserine) or carbachol (10 microM; 100 microM) altered OHC length when applied in iso-osmotic Hank's balanced salt solution (total number of cells tested, 72). If a change in length occurred it must have been smaller than 0.3 microns, our detection ability. In contrast, high potassium and variations in osmolarity changed hair cell length by 3-10% in agreement with other reports.

Is the Cochlear Amplifier a Fluid Pump?

NASA Astrophysics Data System (ADS)

Karavitaki, K. D.; Mountain, D. C.

2003-02-01

We have visualized and quantified the effects of electrically evoked motility of outer hair cells (OHCs) within the organ of Corti using an excised cochlear preparation. We found that OHC motility induces oscillatory fluid flow in the tunnel of Corti (TC) and this flow is present at physiologically relevant frequencies. We also show, using a simple one-dimensional hydromechanical model of the TC, that a fluid wave within the tunnel can travel without significant attenuation for distances larger than the wavelength of the cochlear traveling wave. These results in combination with a recent hypothesis that fluid flow within the tunnel is necessary for cochlear amplification suggest that the function of the OHCs is to act as a fluid pump.

Imaging Electrically Evoked Micromechanical Motion within the Organ of Corti of the Excised Gerbil Cochlea

PubMed Central

Karavitaki, K. Domenica; Mountain, David C.

2007-01-01

The outer hair cell (OHC) of the mammalian inner ear exhibits an unusual form of somatic motility that can follow membrane-potential changes at acoustic frequencies. The cellular forces that produce this motility are believed to amplify the motion of the cochlear partition, thereby playing a key role in increasing hearing sensitivity. To better understand the role of OHC somatic motility in cochlear micromechanics, we developed an excised cochlea preparation to visualize simultaneously the electrically-evoked motion of hundreds of cells within the organ of Corti (OC). The motion was captured using stroboscopic video microscopy and quantified using cross-correlation techniques. The OC motion at ∼2–6 octaves below the characteristic frequency of the region was complex: OHC, Deiter's cell, and Hensen's cell motion were hundreds of times larger than the tectorial membrane, reticular lamina (RL), and pillar cell motion; the inner rows of OHCs moved antiphasic to the outer row; OHCs pivoted about the RL; and Hensen's cells followed the motion of the outer row of OHCs. Our results suggest that the effective stimulus to the inner hair cell hair bundles results not from a simple OC lever action, as assumed by classical models, but by a complex internal motion coupled to the RL. PMID:17277194

[Identification and analysis of the proteins interacted with Prestin in cochlear outer hair cells of guinea pig].

PubMed

Luo, X; Wang, J Y; Zhang, F L; Xia, Y

2018-01-07

Objective: To explore the regulation and mechanism of Prestin protein by identifying the proteins interacted with Prestin in cochlear outer hair cell(OHC) and analyzing their biological function. Methods: Co-immunoprecipitation combined mass spectrometry technology was used to isolate and identify the proteins interacted with Prestin protein of OHC, bioinformatics was used to construct Prestin protein interaction network. The proteins interacted with Prestin in OHC of guinea pig were determined by matching primary interaction mass spectrometry with protein interaction network, and annotated their functions. Results: The results of co-immunoprecipitation combined with mass spectrometry showed that 116 kinds of credible proteins could interact with Prestin. By constructing Prestin protein interaction network, matching the results of mass spectrometry and analyzing of sub-cellular localization, eight kinds of proteins were confirmed that they interacted with Prestin directly, namely EEF2, HSP90AB1, FN1, FLNA, EEF1A1, HSP90B1, ATP5A1, and ERH, respectively, which were mainly involved in the synthesis and transportation, transmembrane folding and localization, structural stability and signal transduction of Prestin protein. Conclusion: EEF2, HSP90AB1, FN1, FLNA, EEF1A1, HSP90B1, ATP5A1 and ERH provide molecular basis for sensory amplification function of OHCs by participating in biotransformation, transmembrane folding and localization, signal transduction and other biological processes of Prestin protein.

Mass spectrometric detection of 27-hydroxycholesterol in breast cancer exosomes.

PubMed

Roberg-Larsen, Hanne; Lund, Kaja; Seterdal, Kristina Erikstad; Solheim, Stian; Vehus, Tore; Solberg, Nina; Krauss, Stefan; Lundanes, Elsa; Wilson, Steven Ray

2017-05-01

Exosomes from cancer cells are rich sources of biomarkers and may contain elevated levels of lipids of diagnostic value. 27-Hydroxycholesterol (27-OHC) is associated with proliferation and metastasis in estrogen receptor positive (ER+) breast cancer. In this study, we investigated the levels of 27-OHC, and other sidechain-hydroxylated oxysterols in exosomes. To study both cytoplasmic and exosomal oxysterol samples of limited size, we have developed a capillary liquid chromatography-mass spectrometry platform that outperforms our previously published systems regarding chromatographic resolution, analysis time and sensitivity. In the analyzed samples, the quantified level of cytoplasmic 27-OHC using this platform fitted with mRNA levels of 27-OHC's corresponding enzyme, CYP27A1. We find clearly increased levels of 27-OHC in exosomes (i.e., enrichment) from an ER+ breast cancer cell line (MCF-7) compared to exosomes derived from an estrogen receptor (ER-) breast cancer cell line (MDA-MB-231) and other control exosomes (non-cancerous cell line (HEK293) and human pooled serum). The exosomal oxysterol profile did not reflect cytoplasmic oxysterol profiles in the cells of origin; cytoplasmic 27-OHC was low in ER+ MCF-7 cells while high in MDA-MB-231 cells. Other control cancer cells showed varied cytoplasmic oxysterol levels. Hence, exosome profiling in cancer cells might provide complementary information with the possibility of diagnostic value. Copyright © 2016 Elsevier Ltd. All rights reserved.

7-Hydroxycoumarin prevents UVB-induced activation of NF-κB and subsequent overexpression of matrix metalloproteinases and inflammatory markers in human dermal fibroblast cells.

PubMed

Karthikeyan, Ramasamy; Kanimozhi, Govindasamy; Prasad, Nagarajan Rajendra; Agilan, Balupillai; Ganesan, Muthusamy; Mohana, Shanmugham; Srithar, Gunaseelan

2016-08-01

Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage. Human dermal fibroblasts (HDFa) were subjected to single UVB-irradiation (18mJ/cm(2)) resulting in reactive oxygen species (ROS) generation, oxidative DNA damage and upregulation of nuclear factor kappa B (NF-κB) expression. Further, it has been observed that there was a significant cytokine production (TNF-α and IL-6) in UVB irradiated HDFa cells. Our results show that 7-hydroxycoumarin (7-OHC) prevents UVB-induced activation of NF-κB thereby subsequently preventing the overexpression of TNF-α and IL-6 in HDFa cells. Further, 7-OHC prevents UVB-induced activation of cyclooxygenase-2 (COX-2) expression, an inflammatory mediator in skin cells. Moreover, 7-OHC inhibited mRNA expression pattern of matrix metalloproteinases (MMP-1 and MMP-9) in UVB irradiated skin cells. Furthermore, 7-OHC restored antioxidant status, thereby scavenging the excessively generated ROS; consequently preventing the oxidative DNA damage. It has also been noticed that 7-OHC prevents UVB mediated DNA damage through activation of DNA repair enzymes such as XRCC1 and HOGG1. In this study, we treated HDFa cells with 7-OHC before and after UVB irradiation and we found that pretreatment showed better results when compared to posttreatment. Further, 7-OHC showed 9.8416 sun protection factor (SPF) value and it absorbs photons in the UVB wavelength rage. Thus, it has been concluded that sunscreen property, free radical scavenging potential and prevention of NF-κB activation play a role for photoprotective property of 7-OHC. Copyright © 2016 Elsevier B.V. All rights reserved.

Three-dimensional current flow in a large-scale model of the cochlea and the mechanism of amplification of sound.

PubMed

Mistrík, Pavel; Mullaley, Chris; Mammano, Fabio; Ashmore, Jonathan

2009-03-06

The mammalian inner ear uses its sensory hair cells to detect and amplify incoming sound. It is unclear whether cochlear amplification arises uniquely from a voltage-dependent mechanism (electromotility) associated with outer hair cells (OHCs) or whether other mechanisms are necessary, for the voltage response of OHCs is apparently attenuated excessively by the membrane electrical filter. The cochlea contains many thousands of hair cells organized in extensive arrays, embedded in an electrically coupled system of supporting cells. We have therefore constructed a multi-element, large-scale computational model of cochlear sound transduction to study the underlying potassium (K+) recirculation. We have included experimentally determined parameters of cochlear macromechanics, which govern sound transduction, and data on hair cells' electrical parameters including tonotopical variation in the membrane conductance of OHCs. In agreement with the experiment, the model predicts an exponential decay of extracellular longitudinal K+ current spread. In contrast to the predictions from isolated cells, it also predicts low attenuation of the OHC transmembrane receptor potential (-5 dB per decade) in the 0.2-30 kHz range. This suggests that OHC electromotility could be driven by the transmembrane potential. Furthermore, the OHC electromotility could serve as a single amplification mechanism over the entire hearing range.

24(S)-Hydroxycholesterol induces RIPK1-dependent but MLKL-independent cell death in the absence of caspase-8.

PubMed

Vo, Diep-Khanh Ho; Urano, Yasuomi; Takabe, Wakako; Saito, Yoshiro; Noguchi, Noriko

2015-07-01

24(S)-Hydroxycholesterol (24S-OHC), which is enzymatically produced in the brain, is known to play an important role in maintaining brain cholesterol homeostasis. We have previously reported that 24S-OHC induces a type of non-apoptotic programmed necrosis in neuronal cells expressing little caspase-8. Necroptosis has been characterized as a type of programmed necrosis in which activation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) is involved in the signaling pathway. In the present study, we investigated the involvement of these three proteins in 24S-OHC-induced cell death. We found that RIPK1 but neither RIPK3 nor MLKL was expressed in human neuroblastoma SH-SY5Y cells, while all three proteins were expressed in human T lymphoma caspase-8-deficient Jurkat (Jurkat(Cas8-/-)) cells. In Jurkat(Cas8-/-) cells, tumor necrosis factor α (TNFα)-induced cell death was significantly suppressed by treatment with respective inhibitors of RIPK1, RIPK3, and MLKL. In contrast, only RIPK1 inhibitor showed significant suppression of 24S-OHC-induced cell death, and even this was less prominent than was observed in TNFα-induced cell death. In Jurkat(Cas8-/-) cells, knockdown of either RIPK1 or RIPK3 caused moderate but significant suppression of 24S-OHC-induced cell death, but no such effect was observed as a result of knockdown of MLKL. Collectively, these results suggest that, for both SH-SY5Y cells and Jurkat(Cas8-/-) cells, 24S-OHC-induced cell death is dependent on RIPK1 but not on MLKL. We therefore conclude that, in the absence of caspase-8 activity, 24S-OHC induces a necroptosis-like cell death which is RIPK1-dependent but MLKL-independent. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between hearing function and myasthenia gravis: A contemporary review.

PubMed

Ralli, Massimo; Altissimi, Giancarlo; Di Stadio, A; Mazzei, Filippo; Turchetta, Rosaria; Cianfrone, Giancarlo

2017-10-01

There is increasing evidence of a connection between hearing function and myasthenia gravis (MG). Studies of the pathophysiological basis of this relationship suggest that acetylcholine receptors (AChRs) on outer hair cells (OHCs) play a central role. In patients with MG, autoantibodies against AChRs induce a progressive loss of AChRs on OHCs, decreasing their electromotility. The stapedial reflex decay test can be altered in MG patients, and can be used as an additional tool for diagnosis and monitoring. Transient evoked and distortion product otoacoustic emissions are the main diagnostic tool for monitoring OHC functionality in MG patients, and can be used to record subclinical hearing alterations before the onset of clinically evident hearing loss. Understanding the association between MG and hearing dysfunction requires a multidisciplinary approach. Otolaryngologists should take this relationship into account when approaching patients with a diagnosis of myasthenia gravis and "in patients with MG" with ण128;œin MG patients, and the progress of hearing alterations should always be monitored in patients with MG.

Actuation of flexoelectric membranes in viscoelastic fluids with applications to outer hair cells

PubMed Central

Herrera-Valencia, E. E.; Rey, Alejandro D.

2014-01-01

Liquid crystal flexoelectric actuation uses an imposed electric field to create membrane bending, and it is used by the outer hair cells (OHCs) located in the inner ear, whose role is to amplify sound through generation of mechanical power. Oscillations in the OHC membranes create periodic viscoelastic flows in the contacting fluid media. A key objective of this work on flexoelectric actuation relevant to OHCs is to find the relations and impact of the electromechanical properties of the membrane, the rheological properties of the viscoelastic media, and the frequency response of the generated mechanical power output. The model developed and used in this work is based on the integration of: (i) the flexoelectric membrane shape equation applied to a circular membrane attached to the inner surface of a circular capillary and (ii) the coupled capillary flow of contacting viscoelastic phases, such that the membrane flexoelectric oscillations drive periodic viscoelastic capillary flows, as in OHCs. By applying the Fourier transform formalism to the governing equation, analytical expressions for the transfer function associated with the curvature and electrical field and for the power dissipation of elastic storage energy were found. PMID:25332388

Membrane recycling at the infranuclear pole of the outer hair cell

NASA Astrophysics Data System (ADS)

Harasztosi, Csaba; Harasztosi, Emese; Gummer, Anthony W.

2015-12-01

Rapid endocytic activity of outer hair cells (OHCs) in the guinea-pig cochlea has been already studied using the fluorescent membrane marker FM1-43. It was demonstrated that vesicles were endocytosed at the apical pole of OHCs and transcytosed to the basolateral membrane and through a central strand towards the nucleus. The significance of endocytic activity in the infranuclear region is still not clear. Therefore, in this study endocytic activity at the synaptic pole of OHCs was investigated. Confocal laser scanning microscopy was used to visualize dye uptake of OHCs isolated from the guinea-pig cochlea. Signal intensity changes were quantified in the apical and basal poles relative to the signal at the membrane. Data showed no significant difference in fluorescent signal intensity changes between the opposite poles of the OHC. These results suggest that endocytic activities in both the basal and the apical poles contribute equally to the membrane recycling of OHCs.

Regional up-regulation of NOX2 contributes to the differential vulnerability of outer hair cells to neomycin.

PubMed

Qi, Meihao; Qiu, Yang; Zhou, Xueying; Tian, Keyong; Zhou, Ke; Sun, Fei; Yue, Bo; Chen, Fuquan; Zha, Dingjun; Qiu, Jianhua

2018-06-02

In hearing loss induced by aminoglycoside antibiotics, the outer hair cells (OHCs) in the basal turn are always more susceptible than OHCs in the apical turn, while the underlying mechanisms remain unknown. In this study, we reported that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs among different turns, at a relatively low level. However, after neomycin treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in vitro studies demonstrated that inhibition of NOX2 significantly alleviated neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our study shows that regional up-expression of NOX2 and subsequent increase of ROS in OHCs of the basal turn is an important factor contributing to the vulnerability of OHCs there, which should shed light on the prevention of hearing loss induced by aminoglycoside antibiotics. Copyright © 2018 Elsevier Inc. All rights reserved.

Recent advances in the development and function of type II spiral ganglion neurons in the mammalian inner ear

PubMed Central

Zhang, Kaidi D.; Coate, Thomas M.

2016-01-01

In hearing, mechanically sensitive hair cells (HCs) in the cochlea release glutamate onto spiral ganglion neurons (SGNs) to relay auditory information to the central nervous system (CNS). There are two main SGN subtypes, which differ in morphology, number, synaptic targets, innervation patterns and firing properties. About 90-95% of SGNs are the type I SGNs, which make a single bouton connection with inner hair cells (IHCs) and have been well described in the canonical auditory pathway for sound detection. However, less attention has been given to the type II SGNs, which exclusively innervate outer hair cells (OHCs). In this review, we emphasize recent advances in the molecular mechanisms that control how type II SGNs develop and form connections with OHCs, and exciting new insights into the function of type II SGNs. PMID:27760385

Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendrocytes.

PubMed

Ragot, Kévin; Mackrill, John J; Zarrouk, Amira; Nury, Thomas; Aires, Virginie; Jacquin, Agnès; Athias, Anne; Pais de Barros, Jean-Paul; Véjux, Anne; Riedinger, Jean-Marc; Delmas, Dominique; Lizard, Gérard

2013-07-01

There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system (CNS). It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin-forming cells in the CNS. To this end, 158N murine oligodendrocytes were treated with 7KC or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and caspase-3 activation. In contrast, under treatment with 27-hydroxycholesterol (27OHC), no cell death was observed. When the cells were stained with Fura-2, no significant Ca(2+) rise was found with the different oxysterols, whereas strong signals were detected with ionomycin used as positive control. At concentrations which induced apoptosis, 7KC but not 7βOHC accumulated in lipid rafts. Although not cytotoxic, 27OHC was mainly detected in lipid rafts. It is noteworthy that α-tocopherol (but not ellagic acid and resveratrol) was able to counteract 7KC- and 7βOHC-induced apoptosis and to decrease the accumulation of 7KC and 27OHC in lipid rafts. Thus, in 158N cells, the ability of oxysterols to trigger a mode of cell death by apoptosis involving GSK-3 and caspase-3 activation is independent of the increase in the Ca(2+) level and of their accumulation in lipid raft microdomains. Copyright © 2013 Elsevier Inc. All rights reserved.

Cyclodextrins and Iatrogenic Hearing Loss: New Drugs with Significant Risk

PubMed Central

Crumling, Mark A.; King, Kelly A.; Duncan, R. Keith

2017-01-01

Cyclodextrins are a family of cyclic oligosaccharides with widespread usage in medicine, industry and basic sciences owing to their ability to solubilize and stabilize guest compounds. In medicine, cyclodextrins primarily act as a complexing vehicle and consequently serve as powerful drug delivery agents. Recently, uncomplexed cyclodextrins have emerged as potent therapeutic compounds in their own right, based on their ability to sequester and mobilize cellular lipids. In particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD) has garnered attention because of its cholesterol chelating properties, which appear to treat a rare neurodegenerative disorder and to promote atherosclerosis regression related to stroke and heart disease. Despite the potential health benefits, use of HPβCD has been linked to significant hearing loss in several species, including humans. Evidence in mice supports a rapid onset of hearing loss that is dose-dependent. Ototoxicity can occur following central or peripheral drug delivery, with either route resulting in the preferential loss of cochlear outer hair cells (OHCs) within hours of dosing. Inner hair cells and spiral ganglion cells are spared at doses that cause ~85% OHC loss; additionally, no other major organ systems appear adversely affected. Evidence from a first-to-human phase 1 clinical trial mirrors animal studies to a large extent, indicating rapid onset and involvement of OHCs. All patients in the trial experienced some permanent hearing loss, although a temporary loss of function can be observed acutely following drug delivery. The long-term impact of HPβCD use as a maintenance drug, and the mechanism(s) of ototoxicity, are unknown. β-cyclodextrins preferentially target membrane cholesterol, but other lipid species and proteins may be directly or indirectly involved. Moreover, as cholesterol is ubiquitous in cell membranes, it remains unclear why OHCs are preferentially susceptible to HPβCD. It is possible that HPβCD acts upon several targets—for example, ion channels, tight junctions (TJ), membrane integrity, and bioenergetics—that collectively increase the sensitivity of OHCs over other cell types. PMID:29163061

How are Inner Hair Cells Stimulated? Evidence for multiple mechanical drives

PubMed Central

Guinan, John J.

2013-01-01

Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap changes reveals three IHC drives in addition to classic SHEAR. For upward basilar-membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA-SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL, compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby producing an outward (away from the IHCs) radial fluid flow which is the OHC-MOTILITY drive. For upward BM motion, the force that moves the TM upward also compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC-MOTILITY drive provides another mechanism, in addition to BM motion amplification, that uses active processes to enhance the output of the cochlea. The ability of these IHC drives to explain previously anomalous data provides strong, although indirect, evidence that these drives are significant and presents a new view of how the cochlea works at frequencies below 3 kHz. PMID:22959529

In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells.

PubMed

Erostegui, C; Norris, C H; Bobbin, R P

1994-04-01

Acetylcholine (ACh) is the major neurotransmitter released from the efferent fibers in the cochlea onto the outer hair cells (OHCs). The type of ACh receptor on OHCs and the events subsequent to receptor activation are unclear. Therefore we studied the effect of agonists and antagonists of the ACh receptor on isolated OHCs from the guinea pig. OHCs were recorded from in whole cell voltage and current clamp configuration. ACh induced an increase in outward K+ current (IACh) which hyperpolarized the OHCs. No desensitization to ACh application was observed. Cs+ replaced K+ in carrying the IACh. The IACh is Ca(2+)-dependent, time and voltage sensitive, and different from the IKCa induced by depolarization of the membrane potential. When tested at 100 microM, several agonists also induced outward current responses (acetylcholine > suberyldicholine > or = carbachol > DMPP) whereas nicotine, cytisine and muscarine did not. The IACh response to 10 microM ACh was blocked by low concentrations of traditional and non-traditional-nicotinic antagonists (strychnine > curare > bicuculline > alpha-bungarotoxin > thimethaphan) and by higher concentrations of muscarinic antagonists (atropine > 4-DAMP > AF-DX 116 > pirenzepine). Pharmacologically, the ACh receptor on OHCs is nicotinic.

Caspase-3 activation in the guinea pig cochlea exposed to salicylate.

PubMed

Feng, Hao; Yin, Shi-Hua; Tang, An-Zhou; Cai, Hong-Wu; Chen, Ping; Tan, Song-Hua; Xie, Li-Hong

2010-07-19

In the current study, we explored whether chronic salicylate exposure could induce apoptosis in outer hair cells (OHCs) and spiral ganglion neurons (SGNs) of the cochlea. Guinea pig received sodium salicylate (400 mg/kg/d) or saline vehicle for 10 consecutive days. Programmed cell death (PCD) executioner was evaluated with immunohistochemistry detection of activated caspase-3. Apoptosis was examined with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Repeated salicylate administration activated caspase-3 and caused apoptosis in OHCs and SGNs (p<0.01 vs. saline control for both measures and in both cell types). Cell counting showed a significant loss in OHCs (p<0.01 vs. saline control), but not in inner hair cells (IHCs). Transmission electron microscopy (TEM) revealed chromatin condensation and nucleus margination in salicylate-treated cochlea. Scanning electron microscopy (SEM) demonstrated stereociliary bundles breakdown and fusion at the apical of OHCs, villous matter was discovered to attach on the surface of SGNs. These findings suggest that long-term administration of high-dose salicylate can activate caspase-3 pathway to induce OHC and SGN apoptosis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Transitory endolymph leakage induced hearing loss and tinnitus: depolarization, biphasic shortening and loss of electromotility of outer hair cells

NASA Technical Reports Server (NTRS)

Zenner, H. P.; Reuter, G.; Zimmermann, U.; Gitter, A. H.; Fermin, C.; LePage, E. L.

1994-01-01

There are types of deafness and tinnitus in which ruptures or massive changes in the ionic permeability of the membranes lining the endolymphatic space [e.g., of the reticular lamina (RL)] are believed to allow potassium-rich endolymph to deluge the low [K+] perilymphatic fluid (e.g., in the small spaces of Nuel). This would result in a K+ intoxication of sensory and neural structures. Acute attacks of Meniere's disease have been suggested to be an important example for this event. The present study investigated the effects of transiently elevated [K+] due to the addition of artificial endolymph to the basolateral cell surface of outer hair cells (OHC) in replicating endolymph-induced K+ intoxication of the perilymph in the small spaces of Nuel. The influence of K+ intoxication of the basolateral OHC cell surface on the transduction was then examined. Intoxication resulted in an inhibition of the physiological repolarizing K+ efflux from hair cells. This induced unwanted depolarizations of the hair cells, interfering with mechanoelectrical transduction. A pathological longitudinal OHC shortening was also found, with subsequent compression of the organ of Corti possibly influencing the micromechanics of the mechanically active OHC. Both micromechanical and electrophysiological alterations are proposed to contribute to endolymph leakage induced attacks of deafness and possibly also to tinnitus. Moreover, repeated or long-lasting K+ intoxications of OHC resulted in a chronic and complete loss of OHC motility. This is suggested to be a pathophysiological basis in some patients with chronic hearing loss resulting from Meniere's syndrome.

Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier

PubMed Central

Gao, Jiangang; Wang, Xiang; Wu, Xudong; Aguinaga, Sal; Huynh, Kristin; Jia, Shuping; Matsuda, Keiji; Patel, Manish; Zheng, Jing; Cheatham, MaryAnn; He, David Z.; Dallos, Peter; Zuo, Jian

2007-01-01

The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (C1) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In C1/C1 knockin mice, localization of C1-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from C1/C1 mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by-cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in C1/C1 or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification. PMID:17640919

The development, distribution and density of the PMCA2 calcium pump in rat cochlear hair cells

PubMed Central

Chen, Qingguo; Mahendrasingam, Shanthini; Tickle, Jacqueline A.; Hackney, Carole M.; Furness, David N.; Fettiplace, Robert

2012-01-01

Calcium is tightly regulated in cochlear outer hair cells (OHCs). It enters mainly via mechanotransducer (MT) channels and is extruded by the PMCA2 isoform of the plasma membrane calcium ATPase, mutations in which cause hearing loss. To assess how pump expression matches the demands of Ca2+ homeostasis, the distribution of PMCA2 at different cochlear locations during development was quantified using immunofluorescence and post-embedding immunogold labeling. The PMCA2 isoform was confined to stereociliary bundles, first appearing at the base of the cochlea around post-natal day 0 (P0) followed by the middle and then the apex by P3, and was unchanged after P8. The developmental appearance matches maturation of the MT channels in rat OHCs. High-resolution immunogold labeling in adult rats showed PMCA2 was distributed along the membranes of all three rows of OHC stereocilia at similar densities and at about a quarter the density in IHC stereocilia. The difference between OHCs and inner hair cells (IHCs) is similar to the ratio of their MT channel resting open probabilities. Gold particle counts revealed no difference in PMCA2 density between low- and high-frequency OHC bundles despite larger MT currents in high-frequency OHCs. The PMCA2 density in OHC stereocilia was determined in low- and high-frequency regions from calibration of immunogold particle counts as 2200/μm2 from which an extrusion rate of ~200 ions·s−1 per pump was inferred. The limited ability of PMCA2 to extrude the Ca2+ load through MT channels may constitute a major cause of OHC vulnerability and high-frequency hearing loss. PMID:22672315

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

PubMed Central

CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

2010-01-01

The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E2 in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E2-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels. PMID:22993572

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

PubMed

Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

2010-05-01

The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

Low-frequency bias tone suppression of auditory-nerve responses to low-level clicks and tones.

PubMed

Nam, Hui; Guinan, John J

2016-11-01

We used low-frequency "bias" tones (BT's) to explore whether click and tone responses are affected in the same way by cochlear active processes. In nonlinear systems the responses to clicks are not always simply related to the responses to tones. Cochlear amplifier gain depends on the incremental slope of the outer-hair-cell (OHC) stereocilia mechano-electric transduction (MET) function. BTs transiently change the operating-point of OHC MET channels and can suppress cochlear-amplifier gain by pushing OHC METs into low-slope saturation regions. BT effects on single auditory-nerve (AN) fibers have been studied on tone responses but not on click responses. We recorded from AN fibers in anesthetized cats and compared tone and click responses using 50 Hz BTs at 70-120 dB SPL to manipulate OHC stereocilia position. BTs can also excite and thereby obscure the BT suppression. We measured AN-fiber response synchrony to BTs alone so that we could exclude suppression measurements when the BT synchrony might obscure the suppression. BT suppression of low-level tone and click responses followed the traditional pattern of twice-a-BT-cycle suppression with more suppression at one phase than the other. The major suppression phases of most fibers were tightly grouped with little difference between click and tone suppressions, which is consistent with low-level click and tone responses being amplified in the same way. The data are also consistent with the operating point of the OHC MET function varying smoothly from symmetric in the base to offset in the apex, and, in contrast, with the IHC MET function being offset throughout the cochlea. As previously reported, bias-tones presented alone excited AN fibers at one or more phases, a phenomena termed "peak splitting" with most BT excitation phases ∼¼ cycle before or after the major suppression phase. We explain peak splitting as being due to distortion in multiple fluid drives to inner-hair-cell stereocilia. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of platelet activating factor with and without receptor antagonist (WEB2170) on morphology of isolated cochlear outer hair cells.

PubMed

Jung, Timothy T K; John, Earnest O; Park, Seong Kook; Park, Yong Soo; Rhee, Chong-Ku

2004-02-01

Platelet activating factor (PAF), generated from biologically active phospholipids, has been implicated as a potent inflammatory mediator and has been shown to be involved in many pathological processes, especially in inflammation and allergy. It has been suspected that PAF may be one of the inflammatory mediators in middle ear effusion that can induce sensorineural hearing loss, as observed in chronic otitis media. The PAF receptor antagonist WEB2170 has been studied extensively, and its inhibitory effects against various PAF actions are well proven in otologic systems. The purpose of our study was to determine the effect of superfusion of PAF and WEB2170 on morphological changes in isolated cochlear outer hair cells (OHCs). Isolated OHCs from adult chinchilla cochleas were exposed to albumin-phosphate-buffered saline solution (1 mg/mL), WEB2170 (5 mg/30 mL), PAF (1 micromol/L), or both PAF (I micromol/L) and WEB2170 (5 mg/30 mL). All experiments were performed at an osmolality of 305 +/- 5 mOsm at room temperature for 30 minutes. The cells were observed with an inverted microscope; the images were stored and analyzed on the Image Pro-Plus program. The OHCs exposed to control albumin-phosphate-buffered saline solution or to WEB2170 did not show any significant change in cell shape or length. The cells exposed to 1 micromol/L of PAF showed ballooning and significant shortening of the mean cell length in 15 to 20 minutes. These morphological changes in OHCs can be prevented by pretreating OHCs with WEB2170. This study demonstrated that exposure to PAF causes morphological changes in isolated OHCs that can be prevented by the PAF receptor antagonist WEB2170.

Paraquat initially damages cochlear support cells leading to anoikis-like hair cell death.

PubMed

Zhang, Jianhui; Sun, Hong; Salvi, Richard; Ding, Dalian

2018-07-01

Paraquat (PQ), one of the most widely used herbicides, is extremely dangerous because it generates the highly toxic superoxide radical. When paraquat was applied to cochlear organotypic cultures, it not only damaged the outer hair cells (OHCs) and inner hair cells (IHCs), but also caused dislocation of the hair cell rows. We hypothesized that the dislocation arose from damage to the support cells (SCs) that anchors hair cells within the epithelium. To test this hypothesis, rat postnatal cochlear cultures were treated with PQ. Shortly after PQ treatment, the rows of OHCs separated from one another and migrated radially away from IHCs suggesting loss of cell-cell adhesion that hold the hair cells in proper alignment. Hair cells dislocation was associated with extensive loss of SCs in the organ of Corti, loss of tympanic border cells (TBCs) beneath the basilar membrane, the early appearance of superoxide staining and caspase-8 labeling in SCs below the OHCs and disintegration of E-cadherin and β-catenin in the organ of Corti. Damage to the TBCs and SCs occurred prior to loss of OHC or IHC loss suggesting a form of detachment-induced apoptosis referred to as anoikis. Copyright © 2018 Elsevier B.V. All rights reserved.

Response to a pure tone in a nonlinear mechanical-electrical-acoustical model of the cochlea.

PubMed

Meaud, Julien; Grosh, Karl

2012-03-21

In this article, a nonlinear mathematical model is developed based on the physiology of the cochlea of the guinea pig. The three-dimensional intracochlear fluid dynamics are coupled to a micromechanical model of the organ of Corti and to electrical potentials in the cochlear ducts and outer hair cells (OHC). OHC somatic electromotility is modeled by linearized piezoelectric relations whereas the OHC hair-bundle mechanoelectrical transduction current is modeled as a nonlinear function of the hair-bundle deflection. The steady-state response of the cochlea to a single tone is simulated in the frequency domain using an alternating frequency time scheme. Compressive nonlinearity, harmonic distortion, and DC shift on the basilar membrane (BM), tectorial membrane (TM), and OHC potentials are predicted using a single set of parameters. The predictions of the model are verified by comparing simulations to available in vivo experimental data for basal cochlear mechanics. In particular, the model predicts more amplification on the reticular lamina (RL) side of the cochlear partition than on the BM, which replicates recent measurements. Moreover, small harmonic distortion and DC shifts are predicted on the BM, whereas more significant harmonic distortion and DC shifts are predicted in the RL and TM displacements and in the OHC potentials. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.

PubMed

Olt, Jennifer; Mburu, Philomena; Johnson, Stuart L; Parker, Andy; Kuhn, Stephanie; Bowl, Mike; Marcotti, Walter; Brown, Steve D M

2014-01-01

Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs) and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs) and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.

Cytoskeletal Stability in the Auditory Organ In Vivo: RhoA Is Dispensable for Wound Healing but Essential for Hair Cell Development.

PubMed

Anttonen, Tommi; Belevich, Ilya; Laos, Maarja; Herranen, Anni; Jokitalo, Eija; Brakebusch, Cord; Pirvola, Ulla

2017-01-01

Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We have studied the role of F-actin belts during wound healing in the developing and adult cochlea of mice in vivo . We show that the thick belts serve as intracellular scaffolds that preserve the positions of surviving cells in the cochlear sensory epithelium. Junctions associated with the thick F-actin belts did not readily disassemble during wound healing. To compensate for this, basolateral membranes of SCs participated in the closure of surface breach. Because not only neighboring but also distant SCs contributed to wound healing by basolateral protrusions, this event appears to be triggered by contact-independent diffusible signals. In the search for regulators of wound healing, we inactivated RhoA in SCs, which, however, did not limit wound healing. RhoA inactivation in developing outer hair cells (OHCs) caused myosin II delocalization from the perijunctional domain and apical cell-surface enlargement. These abnormalities led to the extrusion of OHCs from the epithelium. These results demonstrate the importance of stability of the apical domain, both in wound repair by SCs and in development of OHCs, and that only this latter function is regulated by RhoA . Because the correct cytoarchitecture of the cochlear sensory epithelium is required for normal hearing, the stability of cell apices should be maintained in regenerative and protective interventions.

The spatial and temporal representation of a tone on the guinea pig basilar membrane

NASA Astrophysics Data System (ADS)

Nilsen, K. E.; Russell, I. J.

2000-10-01

School of Biological Sciences, University of Sussex, Falmer Brighton, BN1 9QG, United Kingdom In the mammalian cochlea, the basilar membrane's (BM) mechanical responses are amplified, and frequency tuning is sharpened through active feedback from the electromotile outer hair cells (OHCs). To be effective, OHC feedback must be delivered to the correct region of the BM and introduced at the appropriate time in each cycle of BM displacement. To investigate when OHCs contribute to cochlear amplification, a laser-diode interferometer was used to measure tone-evoked BM displacements in the basal turn of the guinea pig cochlea. Measurements were made at multiple sites acrossthe width of the BM, which are tuned to the same characteristic frequency (CF). In response to CF tones, the largest displacements occur in the OHC region and phase lead those measured beneath the outer pillar cells and adjacent to the spiral ligament by about 90°. Postmortem, responses beneath the OHCs are reduced by up to 65 dB, and all regions across the width of the BM move in unison. We suggest that OHCs amplify BM responses to CF tones when the BM is moving at maximum velocity. In regions of the BM where OHCs contribute to its motion, the responses are compressive and nonlinear. We measured the distribution of nonlinear compressive vibrations along the length of the BM in response to a single frequency tone and estimated that OHC amplification is restricted to a 1.25- to 1.40-mm length of BM centered on the CF place.

ATP activates P2x receptors and requires extracellular Ca(++) participation to modify outer hair cell nonlinear capacitance.

PubMed

Yu, Ning; Zhao, Hong-Bo

2008-11-01

Intracochlear ATP is an important mediator in regulating hearing function. ATP can activate ionotropic purinergic (P2x) and metabotropic purinergic (P2y) receptors to influence cell functions. In this paper, we report that ATP can activate P2x receptors directly to modify outer hair cell (OHC) electromotility, which is an active cochlear amplifier determining hearing sensitivity and frequency selectivity in mammals. We found that ATP, but not UTP, a P2y receptor agonist, reduced the OHC electromotility-associated nonlinear capacitance (NLC) and shifted its voltage dependence to the right (depolarizing) direction. Blockage of the activation of P2x receptors by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), suramin, and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) could block the ATP effect. This modification also required extracellular Ca(++) participation. Removal of extracellular Ca(++) abolished the ATP effect. However, chelation of intracellular Ca(++) concentration by a fast calcium-chelating reagent 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA, 10 mM) did not affect the effect of ATP on NLC. The effect is also independent of K(+) ions. Substitution of Cs(+) for intracellular or extracellular K(+) did not affect the ATP effect. Our findings indicate that ATP activates P2x receptors instead of P2y receptors to modify OHC electromotility. Extracellular Ca(++) is required for this modification.

Response Growth With Sound Level in Auditory-Nerve Fibers After Noise-Induced Hearing Loss

PubMed Central

Heinz, Michael G.; Young, Eric D.

2010-01-01

People with sensorineural hearing loss are often constrained by a reduced acoustic dynamic range associated with loudness recruitment; however, the neural correlates of loudness and recruitment are still not well understood. The growth of auditory-nerve (AN) activity with sound level was compared in normal-hearing cats and in cats with a noise-induced hearing loss to test the hypothesis that AN-fiber rate-level functions are steeper in impaired ears. Stimuli included best-frequency and fixed-frequency tones, broadband noise, and a brief speech token. Three types of impaired responses were observed. 1) Fibers with rate-level functions that were similar across all stimuli typically had broad tuning, consistent with outer-hair-cell (OHC) damage. 2) Fibers with a wide dynamic range and shallow slope above threshold often retained sharp tuning, consistent with primarily inner-hair-cell (IHC) damage. 3) Fibers with very steep rate-level functions for all stimuli had thresholds above approximately 80 dB SPL and very broad tuning, consistent with severe IHC and OHC damage. Impaired rate-level slopes were on average shallower than normal for tones, and were steeper in only limited conditions. There was less variation in rate-level slopes across stimuli in impaired fibers, presumably attributable to the lack of suppression-induced reductions in slopes for complex stimuli relative to BF-tone slopes. Sloping saturation was observed less often in impaired fibers. These results illustrate that AN fibers do not provide a simple representation of the basilar-membrane I/O function and suggest that both OHC and IHC damage can affect AN response growth. PMID:14534289

Auditory-Nerve Responses to Clicks at Low Levels, and the Initial Peak at High Levels, are Suppressed at Opposite Bias-Tone Phases

NASA Astrophysics Data System (ADS)

Nam, Hui; Guinan, John J.

2011-11-01

Apical auditory nerve (AN) fibers show two click-response regions that are both strongly inhibited by medial olivocochlear (MOC) efferents: (1) ringing responses from low- level (LL) clicks that are thought to be enhanced by a "cochlear amplifier," and (2) AN initial peak (ANIPr) responses from moderate-to-high level (˜70-100 dB pSPL) rarefaction clicks. Since MOC fibers synapse and act on outer hair cells (OHCs), the MOC inhibition of these responses indicates that OHC processes are heavily involved in the production of both LL and ANIPr responses. Using AN recordings in anesthetized cats, we explored the role of OHC stereocilia position in the production of these click-response regions by presenting rarefaction clicks at different phases of 50 Hz, 70-110 dB SPL bias tones. Bias effects on LL responses followed the traditional biasing pattern of twice-a-bias-tone-cycle suppression with more suppression at one phase than the other. This suppression is attributable to the bias tone moving the OHC stereocilia toward low-slope, saturation regions of the mechano-electric transduction function with the rest position being closer to one saturation region. A somewhat similar pattern was found for ANIPr responses except that the bias phases of the largest suppressions were different in ANIPr versus LL responses, usually by ˜180 degrees. The data are consistent with the LL and ANIPr responses both being due to active processes in OHCs that are controlled by OHC stereocilia position. The different phases of the LL and ANIPr suppressions indicate that different mechanisms, and perhaps different vibration patterns in the organ of Corti, are involved in the production of LL and ANIPr responses.

Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging

NASA Astrophysics Data System (ADS)

Zholudeva, Lyandysha V.; Ward, Kristina G.; Nichols, Michael G.; Smith, Heather Jensen

2015-05-01

Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs.

Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging

PubMed Central

Zholudeva, Lyandysha V.; Ward, Kristina G.; Nichols, Michael G.; Smith, Heather Jensen

2015-01-01

Abstract. Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs. PMID:25688541

Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?

PubMed

La Marca, Valeria; Maresca, Bernardetta; Spagnuolo, Maria Stefania; Cigliano, Luisa; Dal Piaz, Fabrizio; Di Iorio, Giuseppe; Abrescia, Paolo

2016-04-01

24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Laser selective microablation of sensitized intracellular components within auditory receptor cells

NASA Astrophysics Data System (ADS)

Harris, David M.; Evans, Burt N.; Santos-Sacchi, Joseph

1995-05-01

A laser system can be coupled to a light microscope for laser microbeam ablation and trapping of single cells in vitro. We have extended this technology by sensitization of target structures with vital dyes to provide selective ablation of specific subcellular components. Isolated auditory receptor cells (outer hair cells, OHCs) are known to elongate and contract in response to electrical, chemical and mechanical stimulation. Various intracellular structures are candidate components mediating motility of OHCs, but the exact mechanism(s) is currently unknown. In ongoing studies of OHC motility, we have used the microbeam for selective ablation of lateral wall components and of an axial cytoskeletal core that extends from the nucleus to the cell apex. Both the area beneath the subsurface cistemae of the lateral wall and the core are rich in mitochondria. OHCs isolated from guinea pig cochlea are suspended in L- 15 medium containing 2.0 (mu) M Rhodamine 123, a porphyrin with an affinity for mitochondria. A spark-pumped nitrogen laser pumping a dye cell (Coumarin 500) was aligned on the optical axis of a Nikon Optiphot-2 to produce a 3 ns, 0.5 - 10 micrometers spot (diameter above ablation threshold w/50X water immersion, N.A. 0.8), and energy at the target approximately equals 10 (mu) J/pulse. At short incubation times in Rh123 irradiation caused local blebbing or bulging of cytoplastic membrane and thus loss of the OHC's cylindrical shape. At longer Rh123 incubation times when the central axis of the cell was targeted we observed cytoplasmic clearing, immediate cell elongation (approximately equals 5%) and clumping of core material at nuclear and apical attachments. Experiments are underway to examine the significance of these preliminary observations.

Membrane Composition Tunes the Outer Hair Cell Motor

NASA Astrophysics Data System (ADS)

Rajagopalan, L.; Sfondouris, J.; Oghalai, J. S.; Pereira, F. A.; Brownell, W. E.

2009-02-01

Cholesterol and docosahexaenoic acid (DHA), an ω-3 fatty acid, affect membrane mechanical properties in different ways and modulate the function of membrane proteins. We have probed the functional consequence of altering cholesterol and DHA levels in the membranes of OHCs and prestin expressing HEK cells. Large, dynamic and reversible changes in prestin-associated charge movement and OHC motor activity result from altering the concentration of membrane cholesterol. Increasing membrane cholesterol shifts the q/V function ~ 50 mV in the hyperpolarizing direction, possibly a response related to increases in membrane stiffness. The voltage shift is linearly related to total membrane cholesterol. Increasing cholesterol also decreases the total charge moved in a linear fashion. Decreasing membrane cholesterol shifts the q/V function ~ 50 mV in the depolarizing direction with little or no effect on the amount of charge moved. In vivo increases in membrane cholesterol transiently increase but ultimately lead to decreases in DPOAE. Docosahexaenoic acid shifts the q/V function in the hyperpolarizing direction < 15 mV and increases total charge moved. Tuning of cochlear function by membrane cholesterol contributes to the exquisite temporal and frequency processing of mammalian hearing by optimizing the cochlear amplifier.

Stable Expression of the Motor Protein Prestin in Chinese Hamster Ovary Cells

NASA Astrophysics Data System (ADS)

Iida, Koji; Konno, Kazuaki; Oshima, Takeshi; Tsumoto, Kouhei; Ikeda, Katsuhisa; Kumagai, Izumi; Kobayashi, Toshimitsu; Wada, Hiroshi

Mammalian hearing sensitivity relies on a mechanical amplification mechanism involving the outer hair cells (OHCs), which rapidly alter their longitudinal length in response to changes in their membrane potential. The molecular basis of this mechanism is thought to be a motor protein embedded in the lateral membrane of the OHCs. Recently, this motor protein was identified and termed prestin. Since then, prestin has been researched intensively to elucidate the behavior of the OHCs. However, little progress in the study of prestin at the molecular level has been made because no method of obtaining an adequate amount of prestin has been established. In this study, therefore, an attempt was made to construct a stable expression system of prestin using Chinese hamster ovary (CHO) cells. The expression of prestin in the transfected CHO cells and the activity of prestin on CHO cells were confirmed by immunofluorescence and whole-cell patch-clamp measurements, respectively.

27-hydroxycholesterol induces the transition of MCF7 cells into a mesenchymal phenotype.

PubMed

Torres, Cristian G; Ramírez, María E; Cruz, Pamela; Epuñan, María J; Valladares, Luis E; Sierralta, Walter D

2011-08-01

A decrease in the expression of E-cadherin and β-catenin, paralleling the loss of adherens junction complex, was observed in MCF7 cells exposed for longer than 48 h to 2 µM 27-hydroxycholesterol (27OHC), indicating an epithelial-mesenchymal transition (EMT). Upon removal of 27OHC from the culture medium, the cells released by the exposure of 72 h to the oxysterol grew as loosely packed cell groups. In these cells, accumulation of E-cadherin and β-catenin in the cytoplasm and the prolonged expression of epidermal growth factor receptor 2 (EGFR2/neu) in the plasma membrane were observed, suggesting that the acquired phenotype was related to the expression of this tyrosine kinase-growth factor receptor. The results presented here are discussed on the basis of the claimed relationship between 27OHC, hypercholesterolemia, macrophage infiltration and therapy-resistant ERα+ breast cancer incidence.

Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea.

PubMed

Takeda-Nakazawa, Hiroko; Harada, Narinobu; Shen, Jing; Kubo, Nobuo; Zenner, Hans-Peter; Yamashita, Toshio

2007-08-01

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca2+-free solution. L-NG-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca2+ concentrations ([Ca2+]i) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca2+ response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca2+]i increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca2+ response via the NO-cGMP-PKG pathway by a feedback mechanism.

Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea.

PubMed

Takeda-Nakazawa, Hiroko; Harada, Narinobu; Shen, Jing; Kubo, Nobuo; Zenner, Hans-Peter; Yamashita, Toshio

2007-05-01

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca(2+)-free solution. L-N(G)-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca(2+) concentrations ([Ca(2+)](i)) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca(2+) response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca(2+)](i) increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca(2+) response via the NO-cGMP-PKG pathway by a feedback mechanism.

Effects of Blast Overpressure on Neurons and Glial Cells in Rat Organotypic Hippocampal Slice Cultures

PubMed Central

Miller, Anna P.; Shah, Alok S.; Aperi, Brandy V.; Budde, Matthew D.; Pintar, Frank A.; Tarima, Sergey; Kurpad, Shekar N.; Stemper, Brian D.; Glavaski-Joksimovic, Aleksandra

2015-01-01

Due to recent involvement in military conflicts, and an increase in the use of explosives, there has been an escalation in the incidence of blast-induced traumatic brain injury (bTBI) among US military personnel. Having a better understanding of the cellular and molecular cascade of events in bTBI is prerequisite for the development of an effective therapy that currently is unavailable. The present study utilized organotypic hippocampal slice cultures (OHCs) exposed to blast overpressures of 150 kPa (low) and 280 kPa (high) as an in vitro bTBI model. Using this model, we further characterized the cellular effects of the blast injury. Blast-evoked cell death was visualized by a propidium iodide (PI) uptake assay as early as 2 h post-injury. Quantification of PI staining in the cornu Ammonis 1 and 3 (CA1 and CA3) and the dentate gyrus regions of the hippocampus at 2, 24, 48, and 72 h following blast exposure revealed significant time dependent effects. OHCs exposed to 150 kPa demonstrated a slow increase in cell death plateauing between 24 and 48 h, while OHCs from the high-blast group exhibited a rapid increase in cell death already at 2 h, peaking at ~24 h post-injury. Measurements of lactate dehydrogenase release into the culture medium also revealed a significant increase in cell lysis in both low- and high-blast groups compared to sham controls. OHCs were fixed at 72 h post-injury and immunostained for markers against neurons, astrocytes, and microglia. Labeling OHCs with PI, neuronal, and glial markers revealed that the blast-evoked extensive neuronal death and to a lesser extent loss of glial cells. Furthermore, our data demonstrated activation of astrocytes and microglial cells in low- and high-blasted OHCs, which reached a statistically significant difference in the high-blast group. These data confirmed that our in vitro bTBI model is a useful tool for studying cellular and molecular changes after blast exposure. PMID:25729377

Inner hair cell stereocilia movements captured in-situ by a high-speed camera with subpixel image processing

NASA Astrophysics Data System (ADS)

Wang, Yanli; Puria, Sunil; Steele, Charles R.; Ricci, Anthony J.

2018-05-01

Mechanical stimulation of the stereocilia hair bundles of the inner and outer hair cells (IHCs and OHCs, respectively) drives IHC synaptic release and OHC electromotility. The modes of hair-bundle motion can have a dramatic influence on the electrophysiological responses of the hair cells. The in vivo modes of motion are, however, unknown for both IHC and OHC bundles. In this work, we are developing technology to investigate the in situ hair-bundle motion in excised mouse cochleae, for which the hair bundles of the OHCs are embedded in the tectorial membrane but those of the IHCs are not. Motion is generated by pushing onto the stapes at 1 kHz with a glass probe coupled to a piezo stack, and recorded using a high-speed camera at 10,000 frames per second. The motions of individual IHC stereocilia and the cell boundary are analyzed using 2D and 1D Gaussian fitting algorithms, respectively. Preliminary results show that the IHC bundle moves mainly in the radial direction and exhibits a small degree of splay, and that the stereocilia in the second row move less than those in the first row, even in the same focal plane.

Hair cells in motion: Imaging the organ of Corti

NASA Astrophysics Data System (ADS)

Mountain, David C.; Karavitaki, K. Domenica

2003-10-01

The mammalian cochlea contains two types of sensory cells, inner hair cells (IHCs) and outer hair cells (OHCs). The IHCs provide the vast majority of the synaptic input to the auditory nerve while the OHCs express a unique motor protein, prestin, and appear to participate in an electromechanical feedback loop that amplifies the motion of the organ of Corti (OC). To study this amplification process we have employed stroboscopic video microscopy to quantify the motion of various elements of the OC. Extracellular electrical stimulation was used to excite OHC motility and a computer-controlled high-intensity light-emitting diode (LED) is used to illuminate the organ OC in an excised cochlear preparation. Motion is measured by extracting small regions of interest (ROIs) from the images and cross-correlating the ROIs taken during electrical stimulation with a reference image from the same ROIs taken with no stimulation. The observed motion is quite complex with several vibration modes observed. One of the major findings is that there appears to be oscillatory fluid flow within the tunnel of Corti suggesting that the OHC contractions are pumping fluid longitudinally within the organ. [Work funded by NIDCD.

Blocking caspase-3-dependent pathway preserves hair cells from salicylate-induced apoptosis in the guinea pig cochlea.

PubMed

Feng, Hao; Yin, Shi-Hua; Tang, An-Zhou

2011-07-01

In the present study, we aim to explore whether the caspase-3-dependent pathway is involved in the apoptotic cell death that occurs in the hair cells (HCs) of guinea pig cochlea following a salicylate treatment. Guinea pigs received sodium salicylate (Na-SA), at a dose of 200 mg·kg(-1)·d(-1) i.p., as a vehicle for 5 consecutive days. In some experiments, N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (zDEVD-FMK), a specific apoptosis inhibitor, was directly applied into the cochlea via the round window niche (RWN) prior to salicylate treatment for determination of caspase-3 activation. Alterations in auditory function were evaluated with auditory brainstem responses (ABR) thresholds. Caspase-3 activity was determined by measuring the proteolytic cleavage product of caspase-3 (N-terminated peptide substrate). DNA fragmentation within the nuclei was examined with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Ultrastructure variation in the target cell was assessed by electron microscopy (EM). Salicylate treatment initiated an obvious elevation in ABR thresholds with a maximum average shift of 60 dB sound pressure level (SPL), and caused significant apoptosis in both inner (IHCs) and outer (OHCs) hair cells resulted from an evident increasing in immunoreactivity to caspase-3 protease. Transmission electron microscopy (TEM) displayed chromatin condensation and nucleus margination accompanied by cell body shrinkage in the OHCs, but not in the IHCs. Scanning electron microscopy (SEM) showed breakdown, fusion, and loss in the stereociliary bundles at the apex of OHCs rather than IHCs. zDEVD-FMK pretreatment prior to salicylate injection substantially attenuated an expression of the apoptotic protease and protected HCs against apoptotic death, followed by a moderate relief in the thresholds of ABR, an alleviation in the submicroscopic structure was also identified. In particular, disorientation and insertion in the hair bundles at the apex of OHCs was exhibited though no classic apoptotic change found. The above changes were either prevented or significantly attenuated by zDEVD-FMK. These findings indicate that salicylate could damage cochlear hair cells via inducing apoptosis associated with caspase-3 activation.

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

PubMed

Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

2018-01-16

Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Are hormonal components of oral contraceptives associated with impaired female sexual function? A questionnaire-based online survey of medical students in Germany, Austria, and Switzerland.

PubMed

Wallwiener, Christian W; Wallwiener, Lisa-Maria; Seeger, Harald; Schönfisch, Birgitt; Mueck, Alfred O; Bitzer, Johannes; Zipfel, Stephan; Brucker, Sara Y; Taran, Florin-Andrei; Wallwiener, Markus

2015-10-01

To investigate in a large cohort of young university women whether different progestins and different ethinyl estradiol (EE) dosages in oral hormonal contraceptives (OHCs) adversely affect sexual function. Female medical students from German, Austrian, and Swiss universities (14/1/1) completed an anonymous online questionnaire comprising the 19 Female Sexual Function Index (FSFI) questions and 17 additional questions concerning demographics, lifestyle, sexual activity, and contraceptive use. OHCs were categorized by EE dose (≤20, <20 to ≤30, and >30 µg) and partially androgenic or antiandrogenic progestins. FSFI scores were analyzed by contraceptive method using descriptive statistics and standard nonparametric tests. We analyzed 2612 questionnaires submitted by respondents aged ≤30 years [mean age (SD) 23.5 (2.5) years]. Of 2126 contraceptive users, 1535 (72.2 %) used OHCs. Median FSFI total scores (ranges) were 28.2 (2.0-36.0) for all respondents. Median FSFI was significantly lower in non-users (24.4) versus users (28.7) of contraception (p < 0.001). Stratified analysis showed that 279/486 (57.4 %) respondents using no contraceptives, 563/1535 (36.7 %) using OHCs, 71/227 (31.3 %) using non-oral hormonal contraceptives, and 96/351 (27.4 %) using non-hormonal contraceptives were at risk for female sexual dysfunction (FSFI total score <26.55). FSFI scores for the three EE dosage categories and progestin components did not differ significantly. For OHCs, the FSFI score was lower than for other contraceptives but there was no significant association with EE dose or progestins, possibly due to small sample sizes. Further research needs to clarify the role of OHCs in female sexual function.

On Membrane Motor Activity and Chloride Flux in the Outer Hair Cell: Lessons Learned from the Environmental Toxin Tributyltin

PubMed Central

Song, Lei; Seeger, Achim; Santos-Sacchi, Joseph

2005-01-01

The outer hair cell (OHC) underlies mammalian cochlea amplification, and its lateral membrane motor, prestin, which drives the cell's mechanical activity, is modulated by intracellular chloride ions. We have previously described a native nonselective conductance (GmetL) that influences OHC motor activity via Cl flux across the lateral membrane. Here we further investigate this conductance and use the environmental toxin tributyltin (TBT) to better understand Cl-prestin interactions. Capitalizing on measures of prestin-derived nonlinear capacitance to gauge Cl flux across the lateral membrane, we show that the Cl ionophore TBT, which affects neither the motor nor GmetL directly, is capable of augmenting the native flux of Cl in OHCs. These observations were confirmed using the chloride-sensitive dye MQAE. Furthermore, the compound's potent ability, at nanomolar concentrations, to equilibrate intra- and extracellular Cl concentrations is shown to surpass the effectiveness of GmetL in promoting Cl flux, and secure a quantitative analysis of Cl-prestin interactions in intact OHCs. Using malate as an anion replacement, we quantify chloride effects on the nonlinear charge density and operating voltage range of prestin. Our data additionally suggest that ototoxic effects of organotins can derive from their disruption of OHC Cl homeostasis, ultimately interfering with anionic modulation of the mammalian cochlear amplifier. Notably, this observation identifies a new environmental threat for marine mammals by TBT, which is known to accumulate in the food chain. PMID:15596517

Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

NASA Astrophysics Data System (ADS)

Harasztosi, Csaba; Gummer, Anthony W.

2011-11-01

The voltage-dependent chloride-channel blocker anthracene-9-carboxylic acid (9AC) has been found to reduce the imaginary but not the real part of the mechanical impedance of the organ of Corti, suggesting that the effective stiffness of outer hair cells (OHCs) is reduced by 9AC. To examine whether 9AC interacts directly with the motor protein prestin to reduce the membrane component of the impedance, the patch-clamp technique in whole-cell configuration was used to measure the nonlinear capacitance (NLC) of isolated OHCs and, as control, prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9AC significantly reduced the NLC of both OHCs and HEK293 cells. Intracellular 9AC did not influence the blocking effect of the extracellular applied drug. These results suggest that 9AC interacts directly with prestin, reducing the effective stiffness of the motor, and that the interaction is extracellular.

Perceptual consequences of normal and abnormal peripheral compression: Potential links between psychoacoustics and speech perception

NASA Astrophysics Data System (ADS)

Oxenham, Andrew J.; Rosengard, Peninah S.; Braida, Louis D.

2004-05-01

Cochlear damage can lead to a reduction in the overall amount of peripheral auditory compression, presumably due to outer hair cell (OHC) loss or dysfunction. The perceptual consequences of functional OHC loss include loudness recruitment and reduced dynamic range, poorer frequency selectivity, and poorer effective temporal resolution. These in turn may lead to a reduced ability to make use of spectral and temporal fluctuations in background noise when listening to a target sound, such as speech. We tested the effect of OHC function on speech reception in hearing-impaired listeners by comparing psychoacoustic measures of cochlear compression and sentence recognition in a variety of noise backgrounds. In line with earlier studies, we found weak (nonsignificant) correlations between the psychoacoustic tasks and speech reception thresholds in quiet or in steady-state noise. However, when spectral and temporal fluctuations were introduced in the masker, speech reception improved to an extent that was well predicted by the psychoacoustic measures. Thus, our initial results suggest a strong relationship between measures of cochlear compression and the ability of listeners to take advantage of spectral and temporal masker fluctuations in recognizing speech. [Work supported by NIH Grants Nos. R01DC03909, T32DC00038, and R01DC00117.

Excess plasma membrane and effects of ionic amphipaths on mechanics of outer hair cell lateral wall.

PubMed

Morimoto, Noriko; Raphael, Robert M; Nygren, Anders; Brownell, William E

2002-05-01

The interaction between the outer hair cell (OHC) lateral wall plasma membrane and the underlying cortical lattice was examined by a morphometric analysis of cell images during cell deformation. Vesiculation of the plasma membrane was produced by micropipette aspiration in control cells and cells exposed to ionic amphipaths that alter membrane mechanics. An increase of total cell and vesicle surface area suggests that the plasma membrane possesses a membrane reservoir. Chlorpromazine (CPZ) decreased the pressure required for vesiculation, whereas salicylate (Sal) had no effect. The time required for vesiculation was decreased by CPZ, indicating that CPZ decreases the energy barrier required for vesiculation. An increase in total volume is observed during micropipette aspiration. A deformation-induced increase in hydraulic conductivity is also seen in response to micropipette-applied fluid jet deformation of the lateral wall. Application of CPZ and/or Sal decreased this strain-induced hydraulic conductivity. The impact of ionic amphipaths on OHC plasma membrane and lateral wall mechanics may contribute to their effects on OHC electromotility and hearing.

Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea.

PubMed

Jin, Yecheng; Ren, Naixia; Li, Shiwei; Fu, Xiaolong; Sun, Xiaoyang; Men, Yuqin; Xu, Zhigang; Zhang, Jian; Xie, Yue; Xia, Ming; Gao, Jiangang

2016-06-03

Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell-intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter's cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Gαi/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs.

27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain.

PubMed

Zhang, D-D; Yu, H-L; Ma, W-W; Liu, Q-R; Han, J; Wang, H; Xiao, R

2015-08-06

Cholesterol metabolism is important for neuronal function in the central nervous system (CNS). The oxysterol 27-hydroxycholesterol (27-OHC) is a cholesterol metabolite that crosses the blood-brain barrier (BBB) and may be a useful substitutive marker for neurodegenerative diseases. However, the effects of 27-OHC on learning and memory and the underlying mechanisms are unclear. To determine this mechanism, we investigated learning and memory and cholesterol metabolism in rat brain following the injection of various doses of 27-OHC into the caudal vein. We found that 27-OHC increased cholesterol levels and upregulated the expression of liver X receptor-α (LXR-α) and adenosine triphosphate (ATP)-binding cassette transporter protein family member A1 (ABCA1). In addition, 27-OHC decreased the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low-density lipoprotein receptor (LDLR) in rat brain tissues. These findings suggest that 27-OHC may negatively modulate cognitive effects and cholesterol metabolism in the brain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Compartmentalization of the outer hair cell demonstrated by slow diffusion in the extracisternal space.

PubMed

Gliko, Olga; Saggau, Peter; Brownell, William E

2009-08-19

In the outer hair cell (OHC), the extracisternal space (ECiS) is a conduit and reservoir of the molecular and ionic substrates of the lateral wall, including those necessary for electromotility. To determine the mechanisms through which molecules are transported in the ECiS of the OHC, we selectively imaged the time-dependent spatial distribution of fluorescent molecules in a <100 nm layer near the cell/glass interface of the recording chamber after their photolytic activation in a diffraction-limited volume. The effective diffusion coefficient was calculated using the analytical solution of the diffusion equation. It was found that diffusion in the ECiS is isotropic and not affected by depolarizing the OHC. Compared with free solution, the diffusion of 10 kDa dextran was slowed down in both the ECiS and the axial core by a factor of 4.6 and 1.6, respectively.

Sex differences in distortion product otoacoustic emissions as a function of age in CBA mice.

PubMed

Guimaraes, Patricia; Zhu, Xiaoxia; Cannon, Trinitia; Kim, SungHee; Frisina, Robert D

2004-06-01

Age-related hearing loss--presbycusis--is the number one communication problem of the aged. A major contributor to presbycusis is the progressive degeneration of cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions (DPOAEs) are effective in vivo, physiological measures of hearing, assessing the health and functioning of the OHCs in mammals. We and others have previously demonstrated that DPOAE amplitudes decline with age in humans and mice. The present study's objective was to measure age-related declines in the OHCs in CBA mice (slow, progressive age-related hearing loss) by comparing DPOAEs and auditory brainstem responses (ABRs) generated from females and males. Young adult (2.1-2.9 months) and middle-aged CBA (14.0-16.4 months) mice were tested, as well as old CBAs (24.3-29.0 months). DPOAE-grams were obtained with L1 = 65 and L2 = 50 dB SPL, f1/f2 = 1.25, using eight points per octave covering a frequency range from 5.6 to 44.8 kHz (geometric mean frequency). ABRs ranged from 3 to 48 kHz. Analyses revealed that DPOAE levels decreased with age for middle-aged and old male CBAs, but for female CBAs, declines did not occur until old age - after menopause. In contrast, ABR amplitudes for female and male young adult and middle-aged CBAs were the same. Female ABR thresholds were lower than males for old CBAs. In conclusion, we discovered that pre-menopausal CBA female mice have healthier OHCs relative to middle-aged males, but much of this relative advantage is lost post-menopause. Understanding sex differences in age-related sensory disorders will be quite helpful for the goals of preventing, slowing or curing sensory problems in old age for both women and men.

Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK

PubMed Central

Hill, Kayla; Yuan, Hu; Wang, Xianren

2016-01-01

Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL. SIGNIFICANCE STATEMENT Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy. PMID:27413159

[Effects of neuroactive substances on intracellular free Ca2+ concentration in isolated outer hair cells of the guinea pig cochlea].

PubMed

Yang, J; Wang, J; Wei, S

1998-10-01

To measure the effects of neuro-active substances on intracellular free Ca2+ concentration ([Ca2+]i) in isolated outer hair cells(OHCs) of the guinea pig cochlea. The fura-2 microfluorimetry was used to measure changes of [Ca2+]i in OHCs of the guinea pig cochlea after application of acetylcholine, ATP and carbacholine. Acetylcholine, ATP and carbacholine increased [Ca2+]i (acetylcholine: 0.74 +/- 0.12 mumol/L, ATP: 0.65 +/- 0.11 mumol/L, carbacholine: 1.16 +/- 0.27 mumol/L) in OHCs in the presence of extracellular Ca2+. In the absence of extracellular Ca2+, however, only ATP induced a gradual and small [Ca2+]i elevation, whereas other substances did not. Acetylcholine and carbacholine, the cholinergic mascarinic agonists, increased [Ca2+]i in OHCs by acting at receptor-induced ion channel resulting in Ca2+ efflux. ATP-induced elevation of [Ca2+]i without Ca2+ in extracellular medium is due to a release of Ca2+ from an intracellular reservoir.

Choline acetyltransferase (ChAT) immunoelectron microscopy distinguishes at least three types of efferent synapses in the organ of Corti.

PubMed

Eybalin, M; Pujol, R

1987-01-01

Using anatomical criteria, the olivo-cochlear fibers ending in the organ of Corti (efferent fibers) have recently been separated into two systems: a lateral system innervating principally the inner hair cell (IHC) area and a medial system innervating mainly the outer hair cells (OHCs). Electrophysiological and biochemical experiments suggest that acetylcholine may be a neurotransmitter of these efferent fibers. However, efferent synapses that use acetylcholine as neurotransmitter have not yet been identified at the electron microscopic level. Using a pre-embedding immunoelectron microscopic technique with a monoclonal antibody against choline acetyltransferase (ChAT), we localized ChAT-immunostained fibers below both the IHCs and OHCs. In the inner spiral bundle, one type of ChAT-immunostained fibers was vesiculated and formed axo-dendritic synapses with the afferent auditory dendrites contacting the inner hair cells. A second type of ChAT-immunostained fibers seen in the inner spiral bundle was unvesiculated. Unstained vesiculated varicosities synapsing with the auditory dendrites were also seen in the inner spiral bundle. At the OHC level, ChAT immunostaining was found in nearly all the terminals synapsing with the OHCs. The finding of two types of ChAT-immunostained efferent synapses in the organ of Corti, i.e. axo-dendritic synapses in the inner spiral bundle and axo-somatic synapses with the OHCs, supports the hypothesis that both the lateral and the medial olivo-cochlear systems use acetylcholine as a neurotransmitter. The finding of numerous unstained synapses in the inner spiral bundle, and some below OHCs, together with previous data about putative cochlear neurotransmitters, suggests the possibility of additional non-cholinergic olivo-cochlear systems. It might soon appear useful to reclassify efferents according to the nature of the different neurotransmitters/co-transmitters found in the various efferent synapses of the organ of Corti.

Noise-induced nitrotyrosine increase and outer hair cell death in guinea pig cochlea.

PubMed

Han, Wei-ju; Shi, Xiao-rui; Nuttall, Alfred

2013-01-01

Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea. Thirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL (A-weighted) for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide (PI), a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine (NT) in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope. Either after noise exposure or after SIN1 perfusion, outer hair cells (OHCs) death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis. Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiology of noise-induced hearing loss.

4-aminopyridine in scala media reversibly alters the cochlear potentials and suppresses electrically evoked oto-acoustic emissions.

PubMed

Kirk, D L; Yates, G K

1998-01-01

Iontophoresis of 4-aminopyridine into scala media of the guinea pig cochlea caused elevation of the thresholds of the compound action potential of the auditory nerve, loss of amplitude of the extracellular cochlear microphonic response (CM), increase in the endocochlear potential (EP) and reduction in the amplitude of electrically evoked oto-acoustic emissions (EEOAEs). These changes were reversible over 10-20 min. The reciprocity of the changes in the CM and the EP was consistent with an interruption of both DC and AC currents through outer hair cells (OHCs), probably by blockade of mechano-electrical transduction (MET) channels in OHCs. Reductions in EEOAEs were consistent with the extrinsically applied generating current entering the OHC via the MET channels. Implications for the activation of OHC electromotility in vivo are discussed.

Effect of infrasound on cochlear damage from exposure to a 4 kHz octave band of noise.

PubMed

Harding, Gary W; Bohne, Barbara A; Lee, Steve C; Salt, Alec N

2007-03-01

Infrasound (i.e., <20 Hz for humans; <100 Hz for chinchillas) is not audible, but exposure to high-levels of infrasound will produce large movements of cochlear fluids. We speculated that high-level infrasound might bias the basilar membrane and perhaps be able to minimize noise-induced hearing loss. Chinchillas were simultaneously exposed to a 30 Hz tone at 100 dB SPL and a 4 kHz OBN at either 108 dB SPL for 1.75 h or 86 dB SPL for 24h. For each animal, the tympanic membrane (TM) in one ear was perforated ( approximately 1 mm(2)) prior to exposure to attenuate infrasound transmission to that cochlea by about 50 dB SPL. Controls included animals that were exposed to the infrasound only or the 4 kHz OBN only. ABR threshold shifts (TSs) and DPOAE level shifts (LSs) were determined pre- and post-TM-perforation and immediately post-exposure, just before cochlear fixation. The cochleae were dehydrated, embedded in plastic, and dissected into flat preparations of the organ of Corti (OC). Each dissected segment was evaluated for losses of inner hair cells (IHCs) and outer hair cells (OHCs). For each chinchilla, the magnitude and pattern of functional and hair cell losses were compared between their right and left cochleae. The TM perforation produced no ABR TS across frequency but did produce a 10-21 dB DPOAE LS from 0.6 to 2 kHz. The infrasound exposure alone resulted in a 10-20 dB ABR TS at and below 2 kHz, no DPOAE LS and no IHC or OHC losses. Exposure to the 4 kHz OBN alone at 108 dB produced a 10-50 dB ABR TS for 0.5-12 kHz, a 10-60 dB DPOAE LS for 0.6-16 kHz and severe OHC loss in the middle of the first turn. When infrasound was present during exposure to the 4 kHz OBN at 108 dB, the functional losses and OHC losses extended much further toward the apical and basal tips of the OC than in cochleae exposed to the 4 kHz OBN alone. Exposure to only the 4 kHz OBN at 86 dB produces a 10-40 dB ABR TS for 3-12 kHz and 10-30 dB DPOAE LS for 3-8 kHz but little or no OHC loss in the middle of the first turn. No differences were found in the functional and hair-cell losses from exposure to the 4 kHz OBN at 86 dB in the presence or absence of infrasound. We hypothesize that exposure to infrasound and an intense 4 kHz OBN increases cochlear damage because the large fluid movements from infrasound cause more intermixing of cochlear fluids through the damaged reticular lamina. Simultaneous infrasound and a moderate 4 kHz OBN did not increase cochlear damage because the reticular lamina rarely breaks down during this moderate level exposure.

Effect of infrasound on cochlear damage from exposure to a 4-kHz octave band of noise

PubMed Central

Harding, Gary W.; Bohne, Barbara A.; Lee, Steve C.; Salt, Alec N.

2008-01-01

Infrasound (i.e., < 20 Hz for humans; < 100 Hz for chinchillas) is not audible, but exposure to high levels of infrasound will produce large movements of cochlear fluids. We speculated that high-level infrasound might bias the basilar membrane and perhaps be able to minimize noise-induced hearing loss. Chinchillas were simultaneously exposed to a 30 Hz tone at 100 dB SPL and a 4-kHz OBN at either 108 dB SPL for 1.75 h or 86 dB SPL for 24 h. For each animal, the tympanic membrane (TM) in one ear was perforated (~1 mm2) prior to exposure to attenuate infrasound transmission to that cochlea by about 50 dB SPL. Controls included animals that were exposed to the infrasound only or the 4-kHz OBN only. ABR threshold shifts (TSs) and DPOAE level shifts (LSs) were determined pre- and post-TM-perforation and immediately post-exposure, just before cochlear fixation. The cochleae were dehydrated, embedded in plastic, and dissected into flat preparations of the organ of Corti (OC). Each dissected segment was evaluated for losses of inner hair cells (IHCs) and outer hair cells (OHCs). For each chinchilla, the magnitude and pattern of functional and hair cell losses were compared between their right and left cochleae. The TM perforation produced no ABR TS across frequency but did produce a 10–21 dB DPOAE LS from 0.6–2 kHz. The infrasound exposure alone resulted in a 10–20 dB ABR TS at and below 2 kHz, no DPOAE LS and no IHC or OHC losses. Exposure to the 4-kHz OBN alone at 108 dB produced a 10–50 dB ABR TS for 0.5–12 kHz, a 10–60 dB DPOAE LS for 0.6–16 kHz and severe OHC loss in the middle of the first turn. When infrasound was present during exposure to the 4-kHz OBN at 108 dB, the functional losses and OHC losses extended much further toward the apical and basal tips of the OC than in cochleae exposed to the 4-kHz OBN alone. Exposure to only the 4-kHz OBN at 86 dB produces a 10–40 dB ABR TS for 3–12 kHz and 10–30 dB DPOAE LS for 3–8 kHz but little or no OHC loss in the middle of the first turn. No differences were found in the functional and hair-cell losses from exposure to the 4-kHz OBN at 86 dB in the presence or absence of infrasound. We hypothesize that exposure to infrasound and an intense 4-kHz OBN increases cochlear damage because the large fluid movements from infrasound cause more intermixing of cochlear fluids through the damaged reticular lamina. Simultaneous infrasound and a moderate 4-kHz OBN did not increase cochlear damage because the reticular lamina rarely breaks down during this moderate level exposure. PMID:17300889

Impact of Social Processes in Online Health Communities on Patient Empowerment in Relationship With the Physician: Emergence of Functional and Dysfunctional Empowerment.

PubMed

Petrič, Gregor; Atanasova, Sara; Kamin, Tanja

2017-03-13

Substantial research demonstrates the importance of online health communities (OHCs) for patient empowerment, although the impact on the patient-physician relationship is understudied. Patient empowerment also occurs in relationship with the physician, but studies of OHCs mostly disregard this. The question also remains about the nature and consequences of this empowerment, as it might be based on the limited validity of some information in OHCs. The main purpose of this study was to examine the impact of social processes in OHCs (information exchange with users and health professional moderators, social support, finding meaning, and self-expressing) on functional and dysfunctional patient empowerment in relationship with the physician (PERP). This impact was investigated by taking into account moderating role of eHealth literacy and physician's paternalism. An email list-based Web survey on a simple random sample of 25,000 registered users of the most popular general OHC in Slovenia was conducted. A total of 1572 respondents completed the survey. The analyses were conducted on a subsample of 591 regular users, who had visited a physician at least once in the past 2 years. To estimate the impact of social processes in OHC on functional and dysfunctional PERP, we performed a series of hierarchical regression analyses. To determine the moderating role of eHealth literacy and the perceived physician characteristics, interactions were included in the regression analyses. The mean age of the respondents in the sample was 37.6 years (SD 10.3) and 83.3% were females. Factor analyses of the PERP revealed a five-factor structure with acceptable fit (root-mean-square error of approximation =.06). Most important results are that functional self-efficacy is positively predicted by information exchange with health professional moderators (beta=.12, P=.02), information exchange with users (beta=.12, P=.05), and giving social support (beta=.13, P=.02), but negatively predicted with receiving social support (beta=-.21, P<.001). Functional control is also predicted by information exchange with health professional moderators (beta=.16, P=.005). Dysfunctional control and competence are inhibited by information exchanges with health professionals (beta=-.12, P=.03), whereas dysfunctional self-efficacy is inhibited by self-expressing (beta=-.12, P=.05). The process of finding meaning likely leads to the development of dysfunctional competences and control if the physician is perceived to be paternalistic (beta=.14, P=.03). Under the condition of high eHealth literacy, the process of finding meaning will inhibit the development of dysfunctional competences and control (beta=-.17, P=.01). Social processes in OHCs do not have a uniform impact on PERP. This impact is moderated by eHealth literacy and physician paternalism. Exchanging information with health professional moderators in OHCs is the most important factor for stimulating functional PERP as well as diminishing dysfunctional PERP. Social support in OHCs plays an ambiguous role, often making patients behave in a strategic, uncooperative way toward physicians. ©Gregor Petrič, Sara Atanasova, Tanja Kamin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.03.2017.

Impact of Social Processes in Online Health Communities on Patient Empowerment in Relationship With the Physician: Emergence of Functional and Dysfunctional Empowerment

PubMed Central

Atanasova, Sara; Kamin, Tanja

2017-01-01

Background Substantial research demonstrates the importance of online health communities (OHCs) for patient empowerment, although the impact on the patient-physician relationship is understudied. Patient empowerment also occurs in relationship with the physician, but studies of OHCs mostly disregard this. The question also remains about the nature and consequences of this empowerment, as it might be based on the limited validity of some information in OHCs. Objective The main purpose of this study was to examine the impact of social processes in OHCs (information exchange with users and health professional moderators, social support, finding meaning, and self-expressing) on functional and dysfunctional patient empowerment in relationship with the physician (PERP). This impact was investigated by taking into account moderating role of eHealth literacy and physician’s paternalism. Method An email list–based Web survey on a simple random sample of 25,000 registered users of the most popular general OHC in Slovenia was conducted. A total of 1572 respondents completed the survey. The analyses were conducted on a subsample of 591 regular users, who had visited a physician at least once in the past 2 years. To estimate the impact of social processes in OHC on functional and dysfunctional PERP, we performed a series of hierarchical regression analyses. To determine the moderating role of eHealth literacy and the perceived physician characteristics, interactions were included in the regression analyses. Results The mean age of the respondents in the sample was 37.6 years (SD 10.3) and 83.3% were females. Factor analyses of the PERP revealed a five-factor structure with acceptable fit (root-mean-square error of approximation =.06). Most important results are that functional self-efficacy is positively predicted by information exchange with health professional moderators (beta=.12, P=.02), information exchange with users (beta=.12, P=.05), and giving social support (beta=.13, P=.02), but negatively predicted with receiving social support (beta=−.21, P<.001). Functional control is also predicted by information exchange with health professional moderators (beta=.16, P=.005). Dysfunctional control and competence are inhibited by information exchanges with health professionals (beta=−.12, P=.03), whereas dysfunctional self-efficacy is inhibited by self-expressing (beta=−.12, P=.05). The process of finding meaning likely leads to the development of dysfunctional competences and control if the physician is perceived to be paternalistic (beta=.14, P=.03). Under the condition of high eHealth literacy, the process of finding meaning will inhibit the development of dysfunctional competences and control (beta=−.17, P=.01). Conclusions Social processes in OHCs do not have a uniform impact on PERP. This impact is moderated by eHealth literacy and physician paternalism. Exchanging information with health professional moderators in OHCs is the most important factor for stimulating functional PERP as well as diminishing dysfunctional PERP. Social support in OHCs plays an ambiguous role, often making patients behave in a strategic, uncooperative way toward physicians. PMID:28288953

Biophysical Mechanisms Underlying Hearing Loss Associated with a Shortened Tectorial Membrane

NASA Astrophysics Data System (ADS)

Oghalai, John S.; Xia, Anping; Liu, Christopher C.; Gao, Simon S.; Applegate, Brian E.; Puria, Sunil; Rousso, Itay; Steele, Charles

2011-11-01

The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Herein, we summarize key experimental data and modeling analyses that describe how biophysical alterations to these connections underlie hearing loss. The heterozygous C1509G mutation in alpha tectorin produces partial congenital hearing loss that progresses in humans. We engineered this mutation in mice, and histology revealed that the TM was shortened. DIC imaging of freshly-dissected cochlea as well as imaging with optical coherence tomography indicated that the TM is malformed and only stimulates the first row of OHCs. Noise exposure produced acute threshold shifts that fully recovered in Tecta+/+ mice although there was some OHC loss within all three rows at the cochlear base. In contrast, threshold shifts only partially recovered in TectaC1509G/+ mice. This was associated with OHC loss more apically and nearly entirely within the first row. Young's modulus of the TM, measured using atomic force microscopy, was substantially reduced at the middle and basal regions. Both the wild-type and heterozygous conditions were simulated in a computational model. This demonstrated that the normalized stress distribution levels between the TM and the tall cilia were significantly elevated in the middle region of the heterozygous cochlea. Another feature of the TectaC1509G/+ mutation is higher prestin expression within all three rows of OHCs. This increased electricallyevoked movements of the reticular lamina and otoacoustic emissions. Furthermore, electrical stimulation was associated with an increased risk of OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling of the TM from some OHCs not only leads to partial hearing loss, but also puts the OHCs that remain coupled at higher risk. Both the mechanics of the malformed TM and increased electromotility contribute to this higher risk profile.

Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag+CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack

PubMed Central

Park, Ki Duk; Park, Kyung Seok; Lee, Kwang-Woo; Kim, Sung-Min; Lee, Jaeick

2016-01-01

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Hydroxycholesterols (OHCs), metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We aimed to develop a sensitive and reliable method for the quantitative analysis of three major OHCs (24S-, 25-, and 27-OHCs), and to evaluate their concentration in the cerebrospinal fluid (CSF) and serum of patients with NMO. The levels of the three OHCs in the serum and CSF were measured using liquid chromatography-silver ion coordination ionspray tandem mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry with picolinyl ester derivatization, respectively. The linear range was 5–250 ng/mL for 24S- and 27-OHC, and 0.5–25 ng/mL for 25-OHC in serum, and was 0.1–5 ng/mL for 24S- and 27-OHC, and 0.03–1 ng/mL for 25-OHC in CSF. Precision and accuracy were 0.5%–14.7% and 92.5%–109.7%, respectively, in serum, and were 0.8%–7.7% and 94.5%–119.2%, respectively, in CSF. Extraction recovery was 82.7%–90.7% in serum and 68.4%–105.0% in CSF. When analyzed in 26 NMO patients and 23 control patients, the 25-OHC (0.54 ± 0.96 ng/mL vs. 0.09 ± 0.04 ng/mL, p = 0.032) and 27-OHC (2.68 ± 3.18 ng/mL vs. 0.68 ± 0.25 ng/mL, p = 0.005) were increased in the CSF from NMO patients. When we measured the OHCCSF index that controls the effects of blood–brain barrier disruption on the level of OHC in the CSF, the 27-OHCCSF index was associated with disability (0.723; 95% confidence interval (CI)– 0.181, 0.620; p = 0.002), while the 24-OHCCSF index (0.518; 95% CI– 1.070, 38.121; p = 0.040) and 25-OHCCSF index (0.677; 95% CI– 4.313, 18.532; p = 0.004) were associated with the number of white blood cells in the CSF of NMO patients. Our results imply that OHCs in the CNS could play a role in the pathogenesis of NMO. PMID:27942009

Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

PubMed

Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David

2018-06-26

The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Noise Levels during Aerobics and the Potential Effects on Distortion Product Otoacoustic Emissions

ERIC Educational Resources Information Center

Torre, Peter, III; Howell, Jennifer C.

2008-01-01

The purpose of this study was to measure noise levels during aerobics classes and to examine how outer hair cell (OHC) function, using distortion product otoacoustic emissions (DPOAEs), may be affected by this exposure. Fifty individuals (48 women and 2 men, ages 19-41 years) participated in 50-min aerobics classes. Noise levels were measured…

Two-Dimensional Cochlear Micromechanics Measured In Vivo Demonstrate Radial Tuning within the Mouse Organ of Corti

PubMed Central

Lee, Hee Yoon; Raphael, Patrick D.; Xia, Anping; Kim, Jinkyung; Grillet, Nicolas; Applegate, Brian E.; Ellerbee Bowden, Audrey K.

2016-01-01

The exquisite sensitivity and frequency discrimination of mammalian hearing underlie the ability to understand complex speech in noise. This requires force generation by cochlear outer hair cells (OHCs) to amplify the basilar membrane traveling wave; however, it is unclear how amplification is achieved with sharp frequency tuning. Here we investigated the origin of tuning by measuring sound-induced 2-D vibrations within the mouse organ of Corti in vivo. Our goal was to determine the transfer function relating the radial shear between the structures that deflect the OHC bundle, the tectorial membrane and reticular lamina, to the transverse motion of the basilar membrane. We found that, after normalizing their responses to the vibration of the basilar membrane, the radial vibrations of the tectorial membrane and reticular lamina were tuned. The radial tuning peaked at a higher frequency than transverse basilar membrane tuning in the passive, postmortem condition. The radial tuning was similar in dead mice, indicating that this reflected passive, not active, mechanics. These findings were exaggerated in TectaC1509G/C1509G mice, where the tectorial membrane is detached from OHC stereocilia, arguing that the tuning of radial vibrations within the hair cell epithelium is distinct from tectorial membrane tuning. Together, these results reveal a passive, frequency-dependent contribution to cochlear filtering that is independent of basilar membrane filtering. These data argue that passive mechanics within the organ of Corti sharpen frequency selectivity by defining which OHCs enhance the vibration of the basilar membrane, thereby tuning the gain of cochlear amplification. SIGNIFICANCE STATEMENT Outer hair cells amplify the traveling wave within the mammalian cochlea. The resultant gain and frequency sharpening are necessary for speech discrimination, particularly in the presence of background noise. Here we measured the 2-D motion of the organ of Corti in mice and found that the structures that stimulate the outer hair cell stereocilia, the tectorial membrane and reticular lamina, were sharply tuned in the radial direction. Radial tuning was similar in dead mice and in mice lacking a tectorial membrane. This suggests that radial tuning comes from passive mechanics within the hair cell epithelium, and that these mechanics, at least in part, may tune the gain of cochlear amplification. PMID:27488636

Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins

PubMed Central

Yamashita, Tetsuji; Hakizimana, Pierre; Wu, Siva; Hassan, Ahmed; Jacob, Stefan; Temirov, Jamshid; Fang, Jie; Mellado-Lagarde, Marcia; Gursky, Richard; Horner, Linda; Leibiger, Barbara; Leijon, Sara; Centonze, Victoria E.; Berggren, Per-Olof; Frase, Sharon; Auer, Manfred; Brownell, William E.; Fridberger, Anders; Zuo, Jian

2015-01-01

Nature’s fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5’s active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases. PMID:26352669

Personas in online health communities.

PubMed

Huh, Jina; Kwon, Bum Chul; Kim, Sung-Hee; Lee, Sukwon; Choo, Jaegul; Kim, Jihoon; Choi, Min-Je; Yi, Ji Soo

2016-10-01

Many researchers and practitioners use online health communities (OHCs) to influence health behavior and provide patients with social support. One of the biggest challenges in this approach, however, is the rate of attrition. OHCs face similar problems as other social media platforms where user migration happens unless tailored content and appropriate socialization is supported. To provide tailored support for each OHC user, we developed personas in OHCs illustrating users' needs and requirements in OHC use. To develop OHC personas, we first interviewed 16 OHC users and administrators to qualitatively understand varying user needs in OHC. Based on their responses, we developed an online survey to systematically investigate OHC personas. We received 184 survey responses from OHC users, which informed their values and their OHC use patterns. We performed open coding analysis with the interview data and cluster analysis with the survey data and consolidated the analyses of the two datasets. Four personas emerged-Caretakers, Opportunists, Scientists, and Adventurers. The results inform users' interaction behavior and attitude patterns with OHCs. We discuss implications for how these personas inform OHCs in delivering personalized informational and emotional support. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping auditory nerve firing density using high-level compound action potentials and high-pass noise masking a

PubMed Central

Earl, Brian R.; Chertoff, Mark E.

2012-01-01

Future implementation of regenerative treatments for sensorineural hearing loss may be hindered by the lack of diagnostic tools that specify the target(s) within the cochlea and auditory nerve for delivery of therapeutic agents. Recent research has indicated that the amplitude of high-level compound action potentials (CAPs) is a good predictor of overall auditory nerve survival, but does not pinpoint the location of neural damage. A location-specific estimate of nerve pathology may be possible by using a masking paradigm and high-level CAPs to map auditory nerve firing density throughout the cochlea. This initial study in gerbil utilized a high-pass masking paradigm to determine normative ranges for CAP-derived neural firing density functions using broadband chirp stimuli and low-frequency tonebursts, and to determine if cochlear outer hair cell (OHC) pathology alters the distribution of neural firing in the cochlea. Neural firing distributions for moderate-intensity (60 dB pSPL) chirps were affected by OHC pathology whereas those derived with high-level (90 dB pSPL) chirps were not. These results suggest that CAP-derived neural firing distributions for high-level chirps may provide an estimate of auditory nerve survival that is independent of OHC pathology. PMID:22280596

Perceived healthcare provider reactions to patient and caregiver use of online health communities.

PubMed

Rupert, Douglas J; Moultrie, Rebecca R; Read, Jennifer Gard; Amoozegar, Jacqueline B; Bornkessel, Alexandra S; O'Donoghue, Amie C; Sullivan, Helen W

2014-09-01

Many Internet users seek health information through online health communities (OHCs) and other social media. Yet few studies assess how individuals use peer-generated health information, and many healthcare providers (HCPs) believe OHCs interfere with patient-provider relationships. This study explored how individuals use OHC content in clinical discussions and how HCPs react to it. We conducted in-person and virtual focus groups with patients/caregivers who visited OHCs (n=89). A trained moderator asked about reasons for membership, sharing OHC content with providers, HCP reactions, and preferred roles for HCPs. Two researchers independently coded verbatim transcripts (NVivo 9.2) and conducted thematic response analysis. Participants described OHCs as supplementing information from HCPs, whom they perceived as too busy for detailed discussions. Almost all participants shared OHC content with HCPs, although only half cited OHCs as the source. Most HCPs reacted negatively to OHC content, making participants feel disempowered. Despite these reactions, participants continued to use OHCs, and most desired HCP feedback on the accuracy of OHC content. Individuals do not use OHCs to circumvent HCPs but instead to gather more in-depth information. HCPs should discuss OHC content with patients to help them avoid misinformation and make more informed decisions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

IHC-TM connect-disconnect and efferent control V.

PubMed

Crane, H D

1982-07-01

Four previous papers in this series have explored how the idea of a set of disconnected inner hair cells (IHCs) that can "impact" the tectorial membrane (TM) is consistent with psychophysical data. This paper extends the model and explores the potential for mechanical interaction between the IHCs and outer hair cells (OHCs). In particular, it is speculated that the advantage of IHC-TM disconnect is extended dynamic range, and that movement of the movement of the OHCs and TM, under efferent control, constitutes a mechanical servo system for adjusting IHC-TM spacing along the cochlear partition to achieve this extended range.

Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis.

PubMed

Huang, Kevin M; Liang, Sherry; Yeung, Steven; Oiyemhonlan, Etuajie; Cleveland, Kristan H; Parsa, Cyrus; Orlando, Robert; Meyskens, Frank L; Andresen, Bradley T; Huang, Ying

2017-10-01

In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P + cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol on UV-induced neoplastic transformation. Both carvedilol and 4-OHC (1 μmol/L) blocked transformation induced by chronic UV (15 mJ/cm 2 ) exposure for 8 weeks. However, EGF-mediated transformation was inhibited by only carvedilol but not by 4-OHC. Carvedilol (1 and 5 μmol/L), but not 4-OHC, attenuated UV-induced AP-1 and NF-κB luciferase reporter activity, suggesting a potential anti-inflammatory activity. In a single-dose UV (200 mJ/cm 2 )-induced skin inflammation mouse model, carvedilol (10 μmol/L), applied topically after UV exposure, reduced skin hyperplasia and the levels of cyclobutane pyrimidine dimers, IL1β, IL6, and COX-2 in skin. In SKH-1 mice exposed to gradually increasing levels of UV (50-150 mJ/cm 2 ) three times a week for 25 weeks, topical administration of carvedilol (10 μmol/L) after UV exposure increased tumor latency compared with control (week 18 vs. 15), decreased incidence and multiplicity of squamous cell carcinomas, while 4-OHC had no effect. These data suggest that carvedilol has a novel chemopreventive activity and topical carvedilol following UV exposure may be repurposed for preventing skin inflammation and cancer. Cancer Prev Res; 10(10); 598-606. ©2017 AACR . ©2017 American Association for Cancer Research.

Selective damage to cochlear efferents by the choline neurotoxin ethylcholine mustard aziridinium ion (AF64A) in the chinchilla.

PubMed

Smith, D W; Mount, R J; Callahan, J W

1989-10-01

The cholinotoxin ethylcholine mustard aziridinium ion (AF64A) was diluted in artificial perilymph to concentrations ranging from 10-100 microM, injected unilaterally into the bulla of chinchillas, and allowed to passively diffuse across the round window membrane. Following 21-day survival, the animals were sacrificed and ears removed and embedded in epoxy for histological evaluation under both light and transmission electron microscopy. At 10 microM concentration, selective degeneration of efferent fibers was observed in the efferent terminals on outer hair cells (OHC), tunnel radial fibers, tunnel spiral bundle, and the inner spiral bundle. Serial sections of the middle turn of an animal at 10 microM concentrations showed normal efferent terminals on approximately 50% of OHCs. At the higher concentrations non-specific damage was seen in OHCs, afferents, and some supporting cells. These data suggest that low doses AF64A produces selective damage to cochlear efferent terminals and fibers in the chinchilla.

Drive mechanisms to the inner and outer hair cell stereocilia

NASA Astrophysics Data System (ADS)

Maftoon, Nima; Motallebzadeh, Hamid; Guinan, John J.; Puria, Sunil

2018-05-01

It has been long believed that inner hair cell (IHC) stimulation can be gleaned from the classic ter-Kuile shear motion between the reticular lamina (RL) and tectorial membrane (TM). The present study explores this and other IHC stimulation mechanisms using a finite-element-model representation of an organ of Corti (OoC) cross section with fluid-structure interaction. A 3-D model of a cross section of the OoC including soft tissue and the fluid in the sub-tectorial space, tunnel of Corti and above the TM was formulated based on anatomical measurements from the gerbil apical turn. The outer hair cells (OHCs), Deiter's cells and their phalangeal processes are represented as Y-shaped building-block elements. Each of the IHC and OHC bundles is represented by a single sterocilium. Linearized Navier-Stokes equations coupled with linear-elastic equations discretized with tetrahedral elements are solved in the frequency domain. We evaluated the dynamic changes in the OoC motion including sub-tectorial gap dimensions for 0.1 to 10 kHz input frequencies. Calculations show the classic ter-Kuile motion but more importantly they show that the gap-height changes which produce oscillatory radial flow in the subtectorial space. Phase changes in the stereocilia across OHC rows and the IHC are also observed.

[Immunolocalization of choline acetyltransferase in 2 types of efferent synapses of the organ of Corti].

PubMed

Eybalin, M; Pujol, R

1985-01-01

The efferent (olivo-cochlear) innervation of the organ of Corti was studied using a monoclonal antibody against choline acetyltransferase (ChAT). In the inner spiral bundle (ISB), below the inner hair cells (IHCs), the anti-ChAT immunoreactivity was observed within unvesiculated fibers and vesiculated varicosities. Unreactive varicosities, at least as numerous as the immunoreactive ones, were also detected. Both types of vesiculated varicosities synapsed with the dendrites of the primary auditory neurons (afferent fibers) connected to the IHCs. At the outer hair cell (OHC) level, nearly all the vesiculated terminals making axo-somatic synapses with the OHCs were anti-ChAT immunoreactive. Only few terminals synapsing with the OHCs were unreactive. These findings allowed the differentiation of at least three types of efferent synapses in the organ of Corti. In the ISB, a first population of axo-dendritic synapses seems to be cholinergic whereas a second population might use another neurotransmitter. At the OHC level, our results support the hypothesis that acetylcholine is the neurotransmitter of nearly all the large axo-somatic synapses. The rare unreactive axo-somatic synapses could constitute a fourth and minor type of efferent synapse. Thus, it would be helpful to subclassify the efferent innervations of the organ of Corti according to their neurochemical nature. A re-evaluation of the whole body of available electrophysiological data would be also necessary, as until now, acetylcholine was considered as being the only efferent cochlear neurotransmitter.

Novel Spectro-Temporal Codes and Computations for Auditory Signal Representation and Separation

DTIC Science & Technology

2013-02-01

responses are shown). Bottom right panel (c) shows the Frequency responses of the tunable bandpass filter ( BPF ) triplets that adapt to the incoming...signal. One BPF triplet is associated with each fixed filter, such that coarse filtering of the fixed gammatone filters is followed by additional, finer...is achieved using a second layer of narrower bandpass filters ( BPFs , Q=8) that emulate the filtering functions of outer hair cells (OHCs). In the

The final stage of cholinergic differentiation occurs below inner hair cells during development of the rodent cochlea.

PubMed

Bergeron, Adam L; Schrader, Angela; Yang, Dan; Osman, Abdullah A; Simmons, Dwayne D

2005-12-01

To gain further insights into the cholinergic differentiation of presynaptic efferent terminals in the inner ear, we investigated the expression of the high-affinity choline transporter (ChT1) in comparison to other presynaptic and cholinergic markers. In the adult mammalian cochlea, cholinergic axons from medial olivocochlear (OC) neurons form axosomatic synapses with outer hair cells (OHCs), whereas axons from lateral OC neurons form axodendritic synapses on afferent fibers below inner hair cells (IHCs). Mouse brain and cochlea homogenates reveal at least two ChT1 isoforms: a nonglycosylated approximately 73 kDa protein and a glycosylated approximately 45 kDa protein. In mouse brain, ChT1 is preferentially expressed by neurons in periolivary regions of the superior olive consistent with the location of medial OC neurons. In the adult mouse cochlea, ChT1-positive terminals are located almost exclusively below OHCs consistent with a medial OC innervation. Between postnatal day 2 (P2) and P4, ChT1-positive terminals are below IHCs and occur after the expression of growth-associated protein 43, synapsin, and the vesicular acetylcholine transporter. By P15, ChT1-positive terminals are mostly on OHCs. Accounting for differences in gestational age, the developmental expression of ChT1 in the rat cochlea is similar to the mouse. However, in older rats ChT1-positive terminals are below IHCs and OHCs. In both rat and mouse, our observations indicate that the onset of ChT1 expression occurs after efferent terminals are below IHCs and express other presynaptic and cholinergic markers. In the mouse, but not in the rat, ChT1 may preferentially identify medial OC neurons.

VisOHC: Designing Visual Analytics for Online Health Communities

PubMed Central

Kwon, Bum Chul; Kim, Sung-Hee; Lee, Sukwon; Choo, Jaegul; Huh, Jina; Yi, Ji Soo

2015-01-01

Through online health communities (OHCs), patients and caregivers exchange their illness experiences and strategies for overcoming the illness, and provide emotional support. To facilitate healthy and lively conversations in these communities, their members should be continuously monitored and nurtured by OHC administrators. The main challenge of OHC administrators' tasks lies in understanding the diverse dimensions of conversation threads that lead to productive discussions in their communities. In this paper, we present a design study in which three domain expert groups participated, an OHC researcher and two OHC administrators of online health communities, which was conducted to find with a visual analytic solution. Through our design study, we characterized the domain goals of OHC administrators and derived tasks to achieve these goals. As a result of this study, we propose a system called VisOHC, which visualizes individual OHC conversation threads as collapsed boxes–a visual metaphor of conversation threads. In addition, we augmented the posters' reply authorship network with marks and/or beams to show conversation dynamics within threads. We also developed unique measures tailored to the characteristics of OHCs, which can be encoded for thread visualizations at the users' requests. Our observation of the two administrators while using VisOHC showed that it supports their tasks and reveals interesting insights into online health communities. Finally, we share our methodological lessons on probing visual designs together with domain experts by allowing them to freely encode measurements into visual variables. PMID:26529688

VisOHC: Designing Visual Analytics for Online Health Communities.

PubMed

Kwon, Bum Chul; Kim, Sung-Hee; Lee, Sukwon; Choo, Jaegul; Huh, Jina; Yi, Ji Soo

2016-01-01

Through online health communities (OHCs), patients and caregivers exchange their illness experiences and strategies for overcoming the illness, and provide emotional support. To facilitate healthy and lively conversations in these communities, their members should be continuously monitored and nurtured by OHC administrators. The main challenge of OHC administrators' tasks lies in understanding the diverse dimensions of conversation threads that lead to productive discussions in their communities. In this paper, we present a design study in which three domain expert groups participated, an OHC researcher and two OHC administrators of online health communities, which was conducted to find with a visual analytic solution. Through our design study, we characterized the domain goals of OHC administrators and derived tasks to achieve these goals. As a result of this study, we propose a system called VisOHC, which visualizes individual OHC conversation threads as collapsed boxes-a visual metaphor of conversation threads. In addition, we augmented the posters' reply authorship network with marks and/or beams to show conversation dynamics within threads. We also developed unique measures tailored to the characteristics of OHCs, which can be encoded for thread visualizations at the users' requests. Our observation of the two administrators while using VisOHC showed that it supports their tasks and reveals interesting insights into online health communities. Finally, we share our methodological lessons on probing visual designs together with domain experts by allowing them to freely encode measurements into visual variables.

Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions.

PubMed

Czuba, Ewelina; Steliga, Aleksandra; Lietzau, Grażyna; Kowiański, Przemysław

2017-08-01

The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules. In physiological conditions maintaining the optimal cholesterol concentration is important for the energetic metabolism, composition of cell membranes and myelination. However, a growing body of evidence indicates the consequences of the cholesterol homeostasis dysregulation in several pathophysiological processes. There is a causal relationship between hypercholesterolemia and 1) development of type 2 diabetes due to long-term high-fat diet consumption, 2) significance of the oxidative stress consequences for cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance on progression of the neurodegenerative brain diseases. In this review, we summarize the current state of knowledge concerning the cholesterol influence upon functioning of the NVU under physiological and pathological conditions.

Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

PubMed Central

Wen, Xingxing; Ding, Shan; Cai, Hui; Wang, Junyi; Wen, Lu; Yang, Fan; Chen, Gang

2016-01-01

Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine strategies forms an effective therapeutic approach for treating hearing loss. Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but its influence on such distribution in the cochlea remains largely unknown. Herein, we report the first systematic comparison of poly(lactic/glycolic acid) nanoparticles (PLGA NPs) with or without surface modification of hydrophilic molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that were surface modified with poloxamer 407 (P407), chitosan, or methoxy poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929 and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues. Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest cellular uptake and prominent fluorescence in cochlear imaging. More importantly, we provide novel evidence that the surface-modified NPs reached the organ of Corti and were transported into the OHCs at a higher level. Together, these observations suggest that surface modification with hydrophilic molecules will allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in efficient hearing loss therapy. PMID:27877041

Energy flow in passive and active 3D cochlear model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yanli; Steele, Charles; Puria, Sunil

Energy flow in the cochlea is an important characteristic of the cochlear traveling wave, and many investigators, such as von Békésy and Lighthill, have discussed this phenomenon. Particularly after the discovery of the motility of the outer hair cells (OHCs), the nature of the power gain of the cochlea has been a fundamental research question. In the present work, direct three-dimensional (3D) calculations of the power on cross sections of the cochlea and on the basilar membrane are performed based on a box model of the mouse cochlea. The distributions of the fluid pressure and fluid velocity in the scalamore » vestibuli are presented. The power output from the OHCs and the power loss due to fluid viscous damping are calculated along the length of the cochlea. This work provides a basis for theoretical calculations of the power gain of the OHCs from mechanical considerations.« less

Energy flow in passive and active 3D cochlear model

NASA Astrophysics Data System (ADS)

Wang, Yanli; Puria, Sunil; Steele, Charles

2015-12-01

Energy flow in the cochlea is an important characteristic of the cochlear traveling wave, and many investigators, such as von Békésy and Lighthill, have discussed this phenomenon. Particularly after the discovery of the motility of the outer hair cells (OHCs), the nature of the power gain of the cochlea has been a fundamental research question. In the present work, direct three-dimensional (3D) calculations of the power on cross sections of the cochlea and on the basilar membrane are performed based on a box model of the mouse cochlea. The distributions of the fluid pressure and fluid velocity in the scala vestibuli are presented. The power output from the OHCs and the power loss due to fluid viscous damping are calculated along the length of the cochlea. This work provides a basis for theoretical calculations of the power gain of the OHCs from mechanical considerations.

11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo.

PubMed

Mitić, Tijana; Shave, Steven; Semjonous, Nina; McNae, Iain; Cobice, Diego F; Lavery, Gareth G; Webster, Scott P; Hadoke, Patrick W F; Walker, Brian R; Andrew, Ruth

2013-07-01

11β-Hydroxysteroid dehydrogenase 1 (11βHSD1; EC 1.1.1.146) generates active glucocorticoids from inert 11-keto metabolites. However, it can also metabolize alternative substrates, including 7β-hydroxy- and 7-keto-cholesterol (7βOHC, 7KC). This has been demonstrated in vitro but its consequences in vivo are uncertain. We used genetically modified mice to investigate the contribution of 11βHSD1 to the balance of circulating levels of 7KC and 7βOHC in vivo, and dissected in vitro the kinetics of the interactions between oxysterols and glucocorticoids for metabolism by the mouse enzyme. Circulating levels of 7KC and 7βOHC in mice were 91.3±22.3 and 22.6±5.7 nM respectively, increasing to 1240±220 and 406±39 nM in ApoE(-/-) mice receiving atherogenic western diet. Disruption of 11βHSD1 in mice increased (p<0.05) the 7KC/7βOHC ratio in plasma (by 20%) and also in isolated microsomes (2 fold). The 7KC/7βOHC ratio was similarly increased when NADPH generation was restricted by disruption of hexose-6-phosphate dehydrogenase. Reduction and oxidation of 7-oxysterols by murine 11βHSD1 proceeded more slowly and substrate affinity was lower than for glucocorticoids. in vitro 7βOHC was a competitive inhibitor of oxidation of corticosterone (Ki=0.9 μM), whereas 7KC only weakly inhibited reduction of 11-dehydrocorticosterone. However, supplementation of 7-oxysterols in cultured cells, secondary to cholesterol loading, preferentially slowed reduction of glucocorticoids, rather than oxidation. Thus, in mouse, 11βHSD1 influenced the abundance and balance of circulating and tissue levels of 7βOHC and 7KC, promoting reduction of 7KC. In health, 7-oxysterols are unlikely to regulate glucocorticoid metabolism. However, in hyperlipidaemia, 7-oxysterols may inhibit glucocorticoid metabolism and modulate signaling through corticosteroid receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

Cochlear transducer operating point adaptation.

PubMed

Zou, Yuan; Zheng, Jiefu; Ren, Tianying; Nuttall, Alfred

2006-04-01

The operating point (OP) of outer hair cell (OHC) mechanotransduction can be defined as any shift away from the center position on the transduction function. It is a dc offset that can be described by percentage of the maximum transduction current or as an equivalent dc pressure in the ear canal. The change of OP can be determined from the changes of the second and third harmonics of the cochlear microphonic (CM) following a calibration of its initial value. We found that the initial OP was dependent on sound level and cochlear sensitivity. From CM generated by a lower sound level at 74 dB SPL to avoid saturation and suppression of basal turn cochlear amplification, the OHC OP was at constant 57% of the maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz best frequency location using a blunt probe. The force applied over the scala tympani induced an OP change as if the organ of Corti moved toward the scala vestibuli (SV) direction. During an application of the constant force, the second harmonic of the CM partially recovered toward the initial level, which could be described by two time constants. Removing the force induced recovery of the second harmonic to its normal level described by a single time constant. The force applied over the SV caused an opposite result. These data indicate an active mechanism for OHC transduction OP.

Modelling three-dimensional cochlear micromechanics within the guinea pig organ of Corti

NASA Astrophysics Data System (ADS)

Ni, Guangjian; Elliott, Stephen J.

2018-05-01

The active amplification process in the mammalian cochlea depends on a complex interaction between cells within the organ of Corti. A three-dimensional (3D) model was developed using the finite element method based on anatomy for the apical end in the guinea pig cochlea, which is comprised of 3D discrete hair cells, 3D continuous membranes and fluid. The basilar membrane, tectorial membrane and the reticular lamina are modelled with orthotropic materials. The Y-shape structures formed by the outer hair cell (OHC), the Deiters' cell and Deiters' cell phalangeal process are also included to account for the structural longitudinal coupling. The motion within the organ of Corti was first simulated in response to a pressure difference loading on the basilar membrane, in order to calculate the passive vibration pattern. Then, the outer hair cells somatic electromotility was implemented by applying a voltage across the OHC walls to investigate its contribution to membranes motion.

Exploring the benefits and challenges of health professionals' participation in online health communities: Emergence of (dis)empowerment processes and outcomes.

PubMed

Atanasova, Sara; Kamin, Tanja; Petrič, Gregor

2017-02-01

Various online applications and service has led to the development of online health communities (OHCs), which in addition to the peer-to-peer communication offer patients and other users also interaction with health professionals. While the benefits and challenges of patients and other users' participation in OHCs have been extensively studied, a thorough examination of how health professionals as moderators (i.e., those who provide clinical expertise to patients and other users in OHCs) experience participation in OHCs is lacking. The aim of this study is to explore the main benefits and challenges of health professional moderators' participation in the OHCs. The study undertakes an exploratory qualitative study, with in-depth semi-structured interviews with health professional moderators (n=7) participating in the largest OHC in Slovenia, Med.Over.Net. The data was analysed using inductive thematic analysis approach and principles of grounded theory. Four themes of health professional moderators' experiences were identified: (a) benefits of addressing OHC users' health-related needs, (b) challenges of addressing OHC users' health-related needs, (c) health professional moderators' benefits, and (d) health professional moderators' challenges. This small study demonstrates that health professional participating in OHCs as moderators perceive themselves as facilitators of patients and other OHC's users empowering processes and outcomes, in which OHC's users improve their health literacy, develop skills, expand their social support, and gain other important resources necessary when dealing with health-related issues. Health professional moderator's role, however, also involves several duties, responsibilities and limitations that are often experienced as difficulties in providing patients and other users with adequate counselling and online medical service. OHCs also represent an important terrain for personal and professional empowerment of health professional moderators, although the presence of disempowering processes also needs to be noted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Responses of the ear to low frequency sounds, infrasound and wind turbines

PubMed Central

Salt, Alec N.; Hullar, Timothy E.

2010-01-01

Infrasonic sounds are generated internally in the body (by respiration, heartbeat, coughing, etc) and by external sources, such as air conditioning systems, inside vehicles, some industrial processes and, now becoming increasingly prevalent, wind turbines. It is widely assumed that infrasound presented at an amplitude below what is audible has no influence on the ear. In this review, we consider possible ways that low frequency sounds, at levels that may or may not be heard, could influence the function of the ear. The inner ear has elaborate mechanisms to attenuate low frequency sound components before they are transmitted to the brain. The auditory portion of the ear, the cochlea, has two types of sensory cells, inner hair cells (IHC) and outer hair cells (OHC), of which the IHC are coupled to the afferent fibers that transmit “hearing” to the brain. The sensory stereocilia (“hairs”) on the IHC are “fluid coupled” to mechanical stimuli, so their responses depend on stimulus velocity and their sensitivity decreases as sound frequency is lowered. In contrast, the OHC are directly coupled to mechanical stimuli, so their input remains greater than for IHC at low frequencies. At very low frequencies the OHC are stimulated by sounds at levels below those that are heard. Although the hair cells in other sensory structures such as the saccule may be tuned to infrasonic frequencies, auditory stimulus coupling to these structures is inefficient so that they are unlikely to be influenced by airborne infrasound. Structures that are involved in endolymph volume regulation are also known to be influenced by infrasound, but their sensitivity is also thought to be low. There are, however, abnormal states in which the ear becomes hypersensitive to infrasound. In most cases, the inner ear’s responses to infrasound can be considered normal, but they could be associated with unfamiliar sensations or subtle changes in physiology. This raises the possibility that exposure to the infrasound component of wind turbine noise could influence the physiology of the ear. PMID:20561575

Responses of the ear to low frequency sounds, infrasound and wind turbines.

PubMed

Salt, Alec N; Hullar, Timothy E

2010-09-01

Infrasonic sounds are generated internally in the body (by respiration, heartbeat, coughing, etc) and by external sources, such as air conditioning systems, inside vehicles, some industrial processes and, now becoming increasingly prevalent, wind turbines. It is widely assumed that infrasound presented at an amplitude below what is audible has no influence on the ear. In this review, we consider possible ways that low frequency sounds, at levels that may or may not be heard, could influence the function of the ear. The inner ear has elaborate mechanisms to attenuate low frequency sound components before they are transmitted to the brain. The auditory portion of the ear, the cochlea, has two types of sensory cells, inner hair cells (IHC) and outer hair cells (OHC), of which the IHC are coupled to the afferent fibers that transmit "hearing" to the brain. The sensory stereocilia ("hairs") on the IHC are "fluid coupled" to mechanical stimuli, so their responses depend on stimulus velocity and their sensitivity decreases as sound frequency is lowered. In contrast, the OHC are directly coupled to mechanical stimuli, so their input remains greater than for IHC at low frequencies. At very low frequencies the OHC are stimulated by sounds at levels below those that are heard. Although the hair cells in other sensory structures such as the saccule may be tuned to infrasonic frequencies, auditory stimulus coupling to these structures is inefficient so that they are unlikely to be influenced by airborne infrasound. Structures that are involved in endolymph volume regulation are also known to be influenced by infrasound, but their sensitivity is also thought to be low. There are, however, abnormal states in which the ear becomes hypersensitive to infrasound. In most cases, the inner ear's responses to infrasound can be considered normal, but they could be associated with unfamiliar sensations or subtle changes in physiology. This raises the possibility that exposure to the infrasound component of wind turbine noise could influence the physiology of the ear. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Assessment of outer hair cell function and blood antioxidant status of rabbits exposed to noise and metal welding fumes.

PubMed

Mirzaee, Ramazan; Allameh, Abdolamir; Mortazavi, Seyed Bagher; Khavanin, Ali; Kazemnejad, Anoshirvan; Akbary, Mehdi

2007-06-01

To investigate the interaction between welding fumes and noise in causation of hearing impairment. Groups of rabbits (n=6) were exposed to noise, welding fumes or combination of both prior to Distortion Product Otoacoustic-Emissions (DPOAEs) analysis. The function of outer hair cells (OHCs) was examined by DPOAE assessment over a broad range of frequencies. Variations in DPOAE amplitude were compared between control (n=6) and exposed (n=18) groups. The DPOAEs levels measured at different frequencies (1379-6299 Hz) were found to decrease significantly (P<0.05) in rabbits exposed to 110 dB sound pressure level (SPL) broadband noise (8h/day, 12 days). In rabbits, exposed to carbon-steel welding fumes alone (157 mg/m(3)), the threshold shift was limited to the high frequencies (2759-6299 Hz), whereas, mixed exposure to noise and fumes resulted in reduction of DPOAEs at all the frequencies. Changes in DPOAEs were associated with increased susceptibility of erythrocytes to oxidation (P<0.05). Exposure to noise or fumes alone or simultaneously, suppressed total antioxidant ability of plasma as measured by ferric reducing ability of plasma (FRAP). Noise alone or in combination with fumes resulted in depletion of blood glutathione (GSH). Despite suppression of FRAP in the exposed groups, GSH was found to remain unchanged due to welding fumes suggesting that antioxidants other than GSH are affected by toxicants present in metal welding fumes. Exposure to very high levels of welding fumes can increase noise-related effects on OHC function by extending hearing threshold shift to wide band frequencies.

Physicochemical and functional properties of coconut (Cocos nucifera L) cake dietary fibres: Effects of cellulase hydrolysis, acid treatment and particle size distribution.

PubMed

Zheng, Yajun; Li, Yan

2018-08-15

Effects of cellulase hydrolysis, acid treatment and particle size distribution on the structure, physicochemical and functional properties of coconut cake dietary fiber (DCCDF) were studied. Results showed that both the cellulase hydrolysis and acid treatment contributed to the structural modification of DCCDF as evident from XRD, FT-IR and SEM analysis. Moreover, the cellulase hydrolysis enhanced soluble carbohydrate content, water holding capacity (WHC) and swelling capacity (WSC), α-amylase inhibition activity (α-AAIR), glucose dialysis retardation index (GDRI) and cation-exchange capacity (CEC) of DCCDF; but it had undesirable effects on colour, oil holding capacity (OHC) and emulsifying capacity (EC). On other hand, acid treatment decreased the WHC, WSC and GDRI, but improved the colour, CEC, OHC and emulsion stability of DCCDF. Furthermore, the WHC, WSC and EC of DCCDF increased as the particle size reduced from 250 to 167 μm, while the GDRI, OHC, α-AAIR and emulsion stability decreased with decreasing particle size. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evidence-Based Modification of Intratympanic Gentamicin Injections in Patients With Intractable Vertigo

PubMed Central

Zhai, Feng; Liu, Jian-Ping; Dai, Chun-Fu; Wang, Qi; Steyger, Peter S.

2013-01-01

Objectives To compare the cochlear distribution of low-dose fluorescent gentamicin after intra-tympanic administration in guinea pig (GPs) with clinical data of low dose intra-tympanic gentamicin in patients with intractable vertigo. Materials and Methods Purified gentamicin-Texas Red (GTTR) was injected intratympanically into GPs and the cochlear distribution and time course of GTTR fluorescence in outer hair cells (OHCs) was determined using confocal microscopy. Results GTTR was rapidly taken up by OHCs, particularly in the subcuticular zone. GTTR was distributed in the cochlea in a decreasing baso-apical gradient, and was retained within OHCs without significant decrease in fluorescence until 4 weeks after injection. Conclusion OHCs rapidly take up GTTR after intra-tympanic administration with slow clearance. Clinical Application A modified low-dose titration intratympanic approach was applied to patients with intractable Ménière’s Disease (MD) based on our animal data and the clinical outcome was followed. After the modified intratympanic injections for MD patients, vertigo control was achieved in 89% patients, with hearing deterioration identified in 16% patients. The 3-week interval titration injection technique thereby had a relatively high vertigo control rate with a low risk of hearing loss, and is a viable alternative to other intratympanic injection protocols. PMID:20393376

Physicochemical Properties of Dietary Fibers from Artocarpus camansi Fruit

NASA Astrophysics Data System (ADS)

Suryanti, V.; Kusumaningsih, T.; Rumingtyas, Y. S.

2017-04-01

The objective of this work was to investigate the dietary fiber (DF) contents of Artocorpus camansi (breadnut) fruit and examine their physicochemical properties, such as water-holding capacity (WAC), oil-holding capacity (OHC) and water absorption capacity (WAC). This fruit flour contained of both water soluble fibers (SDF), such as pectin (1.95%) and gum (0.4%), and water insoluble fibers (IDF) (89.25%). The IDF content of this fruit was significantly high in respect to other DF sources. The WHC, OHC and WAC of IDF were 4.10, 2.60 and 4.0%, respectively. Moreover, the WHC, OHC and WHC of total dietary fibers (TDF) were 4.2, 4.3 and 4.6%, respectively. The results showed that the DF of fruit flour had good physicochemical properties. The findings suggested that there is a potential application of A. camansi of fruit as functional ingredients in the food industry.

Basilar membrane and reticular lamina motion in a multi-scale finite element model of the mouse cochlea

NASA Astrophysics Data System (ADS)

Soons, Joris; Dirckx, Joris; Steele, Charles; Puria, Sunil

2015-12-01

A multi-scale finite element (FE) model of the mouse cochlea, based on its anatomy and material properties is presented. The important feature in the model is a lattice of 400 Y-shaped structures in the longitudinal direction, each formed by Deiters cells, phalangeal processes and outer hair cells (OHC). OHC somatic motility is modeled by an expansion force proportional to the shear on the stereocilia, which in turn is proportional to the pressure difference between the scala vestibule and scala tympani. Basilar membrane (BM) and reticular lamina (RL) velocity compare qualitatively very well with recent in vivo measurements in guinea pig [2]. Compared to the BM, the RL is shown to have higher amplification and a shift to higher frequencies. This comes naturally from the realistic Y-shaped cell organization without tectorial membrane tuning.

Analyzing and Predicting User Participations in Online Health Communities: A Social Support Perspective.

PubMed

Wang, Xi; Zhao, Kang; Street, Nick

2017-04-24

Online health communities (OHCs) have become a major source of social support for people with health problems. Members of OHCs interact online with similar peers to seek, receive, and provide different types of social support, such as informational support, emotional support, and companionship. As active participations in an OHC are beneficial to both the OHC and its users, it is important to understand factors related to users' participations and predict user churn for user retention efforts. This study aimed to analyze OHC users' Web-based interactions, reveal which types of social support activities are related to users' participation, and predict whether and when a user will churn from the OHC. We collected a large-scale dataset from a popular OHC for cancer survivors. We used text mining techniques to decide what kinds of social support each post contained. We illustrated how we built text classifiers for 5 different social support categories: seeking informational support (SIS), providing informational support (PIS), seeking emotional support (SES), providing emotional support (PES), and companionship (COM). We conducted survival analysis to identify types of social support related to users' continued participation. Using supervised machine learning methods, we developed a predictive model for user churn. Users' behaviors to PIS, SES, and COM had hazard ratios significantly lower than 1 (0.948, 0.972, and 0.919, respectively) and were indicative of continued participations in the OHC. The churn prediction model based on social support activities offers accurate predictions on whether and when a user will leave the OHC. Detecting different types of social support activities via text mining contributes to better understanding and prediction of users' participations in an OHC. The outcome of this study can help the management and design of a sustainable OHC via more proactive and effective user retention strategies. ©Xi Wang, Kang Zhao, Nick Street. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.04.2017.

Analyzing and Predicting User Participations in Online Health Communities: A Social Support Perspective

PubMed Central

Wang, Xi; Street, Nick

2017-01-01

Background Online health communities (OHCs) have become a major source of social support for people with health problems. Members of OHCs interact online with similar peers to seek, receive, and provide different types of social support, such as informational support, emotional support, and companionship. As active participations in an OHC are beneficial to both the OHC and its users, it is important to understand factors related to users’ participations and predict user churn for user retention efforts. Objective This study aimed to analyze OHC users’ Web-based interactions, reveal which types of social support activities are related to users’ participation, and predict whether and when a user will churn from the OHC. Methods We collected a large-scale dataset from a popular OHC for cancer survivors. We used text mining techniques to decide what kinds of social support each post contained. We illustrated how we built text classifiers for 5 different social support categories: seeking informational support (SIS), providing informational support (PIS), seeking emotional support (SES), providing emotional support (PES), and companionship (COM). We conducted survival analysis to identify types of social support related to users’ continued participation. Using supervised machine learning methods, we developed a predictive model for user churn. Results Users’ behaviors to PIS, SES, and COM had hazard ratios significantly lower than 1 (0.948, 0.972, and 0.919, respectively) and were indicative of continued participations in the OHC. The churn prediction model based on social support activities offers accurate predictions on whether and when a user will leave the OHC. Conclusions Detecting different types of social support activities via text mining contributes to better understanding and prediction of users’ participations in an OHC. The outcome of this study can help the management and design of a sustainable OHC via more proactive and effective user retention strategies. PMID:28438725

Maternal 27-hydroxycholesterol concentrations during the course of pregnancy and in pregnancy pathologies.

PubMed

Winkler, Brigitte Sophia; Pecks, Ulrich; Najjari, Laila; Kleine-Eggebrecht, Nicola; Maass, Nicolai; Mohaupt, Markus; Escher, Geneviève

2017-04-04

The oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis. Pregnancy pathologies like preeclampsia (PE), HELLP-syndrome (HELLP), intrauterine growth restriction (IUGR) and intrahepatic cholestasis in pregnancy (ICP) are linked to disturbances in lipid metabolism. In the present study, we hypothesized a specific gestational regulation of 27-OHC and compromised 27-OHC levels due to placental and hepatic diseases in pregnancy resulting in a dysregulation of lipid metabolism. The 27-OHC was measured by gas-chromatography-mass spectrometry (GC-MS) and related to cholesterol concentrations. In the longitudinal cohort, a complete set of samples of healthy patients (n = 33) obtained at three different time points throughout gestation and once post-partum was analyzed. In the cross sectional cohort, patients with pregnancy pathologies (IUGR n = 14, PE n = 14, HELLP n = 7, ICP n = 7) were matched to a control group (CTRL) of equal gestational ages. The 27-OHC levels already increased in the first trimester despite lower TC concentrations (p < 0.05). During the course of pregnancy, a subtle rise in 27-OHC concentrations results in an overall decrease of 27-OHC/TC ratio in between the first (p < 0.05) and second trimester. The ratio remains stable thereafter including the post-partum period. No significant differences have been observed in pregnancy pathologies as compared to the CTRL group. In conclusion, 27-OHC may have a compensatory role in cholesterol metabolism early in pregnancy. The conserved 27-OHC/TC ratio in pregnancy pathologies suggest that neither the placenta nor the liver is majorly involved in the regulation of 27-OHC metabolism.

Decadal changes in South Pacific sea surface temperatures and the relationship to the Pacific decadal oscillation and upper ocean heat content

NASA Astrophysics Data System (ADS)

Linsley, Braddock K.; Wu, Henry C.; Dassié, Emilie P.; Schrag, Daniel P.

2015-04-01

Decadal changes in Pacific sea surface temperatures (SSTs) and upper ocean heat content (OHC) remain poorly understood. We present an annual average composite coral Sr/Ca-derived SST time series extending back to 1791 from Fiji, Tonga, and Rarotonga (FTR) in the Pacific Decadal Oscillation (PDO) sensitive region of the southwest Pacific. Decadal SST maxima between 1805 and 1830 Common Era (C.E.) indicate unexplained elevated SSTs near the end of the Little Ice Age. The mean period of decadal SST variability in this region has a period near 25 years. Decades of warmer (cooler) FTR SST co-occur with PDO negative (positive) phases since at least ~1930 C.E. and positively correlate with South Pacific OHC (0-700 m). FTR SST is also inversely correlated with decadal changes in equatorial Pacific SST as measured by coral Sr/Ca. Collectively, these results support the fluctuating trade wind-shallow meridional overturning cell mechanism for decadal modulation of Pacific SSTs and OHC.

Identification, synthesis and regulatory function of the N-acylated homoserine lactone signals produced by Pseudomonas chlororaphis HT66.

PubMed

Peng, Huasong; Ouyang, Yi; Bilal, Muhammad; Wang, Wei; Hu, Hongbo; Zhang, Xuehong

2018-01-22

Pseudomonas chlororaphis HT66 isolated from the rice rhizosphere is an important plant growth-promoting rhizobacteria that produce phenazine-1-carboxamide (PCN) in high yield. Phenazine production is regulated by a quorum sensing (QS) system that involves the N-acylated homoserine lactones (AHLs)-a prevalent type of QS molecule. Three QS signals were detected by thin layer chromatography (TLC) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS), which identified to be N-(3-hydroxy hexanoyl)-L-homoserine lactone (3-OH-C6-HSL), N-(3-hydroxy octanoyl)-L-homoserine lactone (3-OH-C8-HSL) and N-(3-hydroxy decanoyl)-L-homoserine lactone (3-OH-C10-HSL). The signal types and methods of synthesis were different from that in other phenazine-producing Pseudomonas strains. By non-scar deletion and heterologous expression techniques, the biosynthesis of the AHL-signals was confirmed to be only catalyzed by PhzI, while other AHLs synthases i.e., CsaI and HdtS were not involved in strain HT66. In comparison to wild-type HT66, PCN production was 2.3-folds improved by over-expression of phzI, however, phzI or phzR mutant did not produce PCN. The cell growth of HT66∆phzI mutant was significantly decreased, and the biofilm formation in phzI or phzR inactivated strains of HT66 decreased to various extents. In conclusion, the results demonstrate that PhzI-PhzR system plays a critical role in numerous biological processes including phenazine production.

Ocean heat content estimation from in situ observations at the National Centers for Environmental Information: Improvements and Uncertainties

NASA Astrophysics Data System (ADS)

Boyer, T.; Locarnini, R. A.; Mishonov, A. V.; Reagan, J. R.; Seidov, D.; Zweng, M.; Levitus, S.

2017-12-01

Ocean heat uptake is the major factor in sequestering the Earth's Energy Imbalance (EEI). Since 2000, the National Centers for Environmental Information (NCEI) have been estimating historical ocean heat content (OHC) changes back to the 1950s, as well as monitoring recent OHC. Over these years, through worldwide community efforts, methods of calculating OHC have substantially improved. Similarly, estimation of the uncertainty of ocean heat content calculations provide new insight into how well EEI estimates can be constrained using in situ measurements and models. The changing ocean observing system, especially with the near-global year-round coverage afforded by Argo, has also allowed more confidence in regional and global OHC estimates and provided a benchmark for better understanding of historical OHC changes. NCEI is incorporating knowledge gained through these global efforts into the basic methods, instrument bias corrections, uncertainty measurements, and temporal and spatial resolution capabilities of historic OHC change estimation and recent monitoring. The nature of these improvements and their consequences for estimation of OHC in relation to the EEI will be discussed.

Neuromonitoring of cochlea and auditory nerve with multiple extracted parameters during induced hypoxia and nerve manipulation

NASA Astrophysics Data System (ADS)

Bohórquez, Jorge; Özdamar, Özcan; Morawski, Krzysztof; Telischi, Fred F.; Delgado, Rafael E.; Yavuz, Erdem

2005-06-01

A system capable of comprehensive and detailed monitoring of the cochlea and the auditory nerve during intraoperative surgery was developed. The cochlear blood flow (CBF) and the electrocochleogram (ECochGm) were recorded at the round window (RW) niche using a specially designed otic probe. The ECochGm was further processed to obtain cochlear microphonics (CM) and compound action potentials (CAP).The amplitude and phase of the CM were used to quantify the activity of outer hair cells (OHC); CAP amplitude and latency were used to describe the auditory nerve and the synaptic activity of the inner hair cells (IHC). In addition, concurrent monitoring with a second electrophysiological channel was achieved by recording compound nerve action potential (CNAP) obtained directly from the auditory nerve. Stimulation paradigms, instrumentation and signal processing methods were developed to extract and differentiate the activity of the OHC and the IHC in response to three different frequencies. Narrow band acoustical stimuli elicited CM signals indicating mainly nonlinear operation of the mechano-electrical transduction of the OHCs. Special envelope detectors were developed and applied to the ECochGm to extract the CM fundamental component and its harmonics in real time. The system was extensively validated in experimental animal surgeries by performing nerve compressions and manipulations.

Across-frequency behavioral estimates of the contribution of inner and outer hair cell dysfunction to individualized audiometric loss

PubMed Central

Johannesen, Peter T.; Pérez-González, Patricia; Lopez-Poveda, Enrique A.

2014-01-01

Identifying the multiple contributors to the audiometric loss of a hearing impaired (HI) listener at a particular frequency is becoming gradually more useful as new treatments are developed. Here, we infer the contribution of inner (IHC) and outer hair cell (OHC) dysfunction to the total audiometric loss in a sample of 68 hearing aid candidates with mild-to-severe sensorineural hearing loss, and for test frequencies of 0.5, 1, 2, 4, and 6 kHz. It was assumed that the audiometric loss (HLTOTAL) at each test frequency was due to a combination of cochlear gain loss, or OHC dysfunction (HLOHC), and inefficient IHC processes (HLIHC), all of them in decibels. HLOHC and HLIHC were estimated from cochlear I/O curves inferred psychoacoustically using the temporal masking curve (TMC) method. 325 I/O curves were measured and 59% of them showed a compression threshold (CT). The analysis of these I/O curves suggests that (1) HLOHC and HLIHC account on average for 60–70 and 30–40% of HLTOTAL, respectively; (2) these percentages are roughly constant across frequencies; (3) across-listener variability is large; (4) residual cochlear gain is negatively correlated with hearing loss while residual compression is not correlated with hearing loss. Altogether, the present results support the conclusions from earlier studies and extend them to a wider range of test frequencies and hearing-loss ranges. Twenty-four percent of I/O curves were linear and suggested total cochlear gain loss. The number of linear I/O curves increased gradually with increasing frequency. The remaining 17% I/O curves suggested audiometric losses due mostly to IHC dysfunction and were more frequent at low (≤1 kHz) than at high frequencies. It is argued that in a majority of listeners, hearing loss is due to a common mechanism that concomitantly alters IHC and OHC function and that IHC processes may be more labile in the apex than in the base. PMID:25100940

Adenosine receptors regulate susceptibility to noise-induced neural injury in the mouse cochlea and hearing loss.

PubMed

Vlajkovic, Srdjan M; Ambepitiya, Kaushi; Barclay, Meagan; Boison, Detlev; Housley, Gary D; Thorne, Peter R

2017-03-01

Our previous studies have shown that the stimulation of A 1 adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A 1 AR and A 2A AR null mice (A 1 AR -/- and A 2A AR -/- ). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 h to induce cochlear injury and hearing loss. Auditory thresholds and input/output functions were assessed using auditory brainstem responses (ABR) before and two weeks post-exposure. The loss of outer hair cells (OHC), afferent synapses and spiral ganglion neurons (SGN) were assessed by quantitative histology. A 1 AR -/- mice (6-8 weeks old) displayed a high frequency hearing loss (ABR threshold shift and reduced ABR wave I and II amplitudes). This hearing loss was further aggravated by acute noise exposure and exceeded the hearing loss in the WT and A 2A AR -/- mice. All mice experienced the loss of OHC, synaptic ribbons and SGN after noise exposure, but the loss of SGN was significantly higher in A 1 AR -/- mice than in the A 2A AR -/- and WT genotypes. The A 2A AR -/- demonstrated better preservation of OHC and afferent synapses and the minimal loss of SGN after noise exposure. The findings suggest that the loss of A 1 AR expression results in an increased susceptibility to cochlear neural injury and hearing loss, whilst absence of A 2A AR increases cochlear resistance to acoustic trauma. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Parenteral Papaverine and Piracetam Administration on Cochlea Following Acoustic Trauma

PubMed Central

Yurtsever Kum, Nurcan; Yilmaz, Yavuz F.; Gurgen, Seren G.; Kum, Rauf O.; Ozcan, Muge; Unal, Adnan

2018-01-01

Introduction: Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to investigate the effects of parenteral papaverine and piracetam administration following an acoustic trauma on hearing function with histopathologic correlation. Materials and Methods: Eighteen Wistar albino rats exposed to noise for 8 h in a free environment were included. We divided the study population into three groups, and performed daily intraperitoneal injections of papaverine, piracetam, and saline, respectively, throughout the study. We investigated the histopathologic effects of cellular apoptosis on inner hair cells (IHCs) and outer hair cells (OHCs) and compared the distortion product otoacoustic emissions (DPOAEs) thresholds among the groups. Results and Discussion: On the 3rd and 7th days, DPOAE thresholds at 8 kHz were significantly higher both in papaverine and piracetam groups compared with the control group (P = 0.004 for 3rd day, P = 0.016 and P = 0.028 for 7th day, respectively). On the 14th day, piracetam group had significantly higher mean thresholds at 8 kHz (P = 0.029); however, papaverine group had similar mean thresholds compared to the control group (P = 0.200). On the 3rd and 7th days following acoustic trauma, both IHC and OHC loss were significantly lower in both papaverine and piracetam groups. On the 7th day, the mean amount of apoptotic IHCs and OHCs identified using Caspase-3 method were significantly lower in both groups, but the mean amount identified using terminal deoxynucleotidyl transferase dUTP nick end labeling method were similar in both groups compared to the control group. Conclusion: We demonstrated the effects of papaverine and piracetam on the recovery of cochlear damage due to acoustic trauma on experimental animals using histopathologic and electrophysiologic examinations. PMID:29676295

Effects of parenteral papaverine and piracetam administration on cochlea following acoustic trauma.

PubMed

Kum, Nurcan Yurtsever; Yilmaz, Yavuz F; Gurgen, Seren G; Kum, Rauf O; Ozcan, Muge; Unal, Adnan

2018-01-01

Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to investigate the effects of parenteral papaverine and piracetam administration following an acoustic trauma on hearing function with histopathologic correlation. Eighteen Wistar albino rats exposed to noise for 8 h in a free environment were included. We divided the study population into three groups, and performed daily intraperitoneal injections of papaverine, piracetam, and saline, respectively, throughout the study. We investigated the histopathologic effects of cellular apoptosis on inner hair cells (IHCs) and outer hair cells (OHCs) and compared the distortion product otoacoustic emissions (DPOAEs) thresholds among the groups. On the 3 rd and 7 th days, DPOAE thresholds at 8 kHz were significantly higher both in papaverine and piracetam groups compared with the control group (P = 0.004 for 3 rd day, P = 0.016 and P = 0.028 for 7 th day, respectively). On the 14 th day, piracetam group had significantly higher mean thresholds at 8 kHz (P = 0.029); however, papaverine group had similar mean thresholds compared to the control group (P = 0.200). On the 3 rd and 7 th days following acoustic trauma, both IHC and OHC loss were significantly lower in both papaverine and piracetam groups. On the 7 th day, the mean amount of apoptotic IHCs and OHCs identified using Caspase-3 method were significantly lower in both groups, but the mean amount identified using terminal deoxynucleotidyl transferase dUTP nick end labeling method were similar in both groups compared to the control group. We demonstrated the effects of papaverine and piracetam on the recovery of cochlear damage due to acoustic trauma on experimental animals using histopathologic and electrophysiologic examinations.

Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear

PubMed Central

Taylor, Ruth R.; Lovett, Michael; Jagger, Daniel J.

2017-01-01

Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice. Affected animals were profoundly deaf. Severe hair bundle defects were identified in all outer and inner hair cells (OHC, IHC) in the cochlea and in hair cells of vestibular macular organs, but hair cells in cristae were essentially unaffected. Evidence suggested the disorder was likely due to gene disruption by a randomly inserted transgene construct. Whole-genome sequencing identified interruption of the SorCS2 (Sortilin-related VPS-10 domain containing protein) locus. Real-time-qPCR demonstrated disrupted expression of SorCS2 RNA in cochlear tissue from affected mice and this was confirmed by SorCS2 immuno-labelling. In all affected hair cells, stereocilia were shorter than normal, but abnormalities of bundle morphology and organisation differed between hair cell types. Bundles on OHC were grossly misshapen with significantly fewer stereocilia than normal. However, stereocilia were organised in rows of increasing height. Bundles on IHC contained significantly more stereocilia than normal with some longer stereocilia towards the centre, or with minimal height differentials. In early postnatal mice, kinocilia (primary cilia) of IHC and of OHC were initially located towards the lateral edge of the hair cell surface but often became surrounded by stereocilia as bundle shape and apical surface contour changed. In macular organs the kinocilium was positioned in the centre of the cell surface throughout maturation. There was disruption of the signalling pathway controlling intrinsic hair cell apical asymmetry. LGN and Gαi3 were largely absent, and atypical Protein Kinase C (aPKC) lost its asymmetric distribution. The results suggest that SorCS2 plays a role upstream of the intrinsic polarity pathway and that there are differences between hair cell types in the deployment of the machinery that generates a precisely organised hair bundle. PMID:28346477

Factors associated with re-entry to out-of-home care among children in England.

PubMed

Mc Grath-Lone, Louise; Dearden, Lorraine; Harron, Katie; Nasim, Bilal; Gilbert, Ruth

2017-01-01

Exiting and re-entering out-of-home care (OHC) is considered a disruption to permanence which may have long-lasting, negative consequences for children due to a lack of stability and continuity. Each year approximately one-third of children in OHC in England exit, but information is lacking on rates of re-entries and associated factors. Using national administrative data, we calculated rates of re-entry among children exiting OHC from 2007 to 2012, identified key child and care factors associated with re-entry using Cox proportional hazards modelling, and developed a simple probability calculator to estimate which groups of children are most likely to re-enter OHC within three months. Between 2007 and 2012 re-entries to OHC in England decreased (from 23.3% to 14.4% within one year of exit, p<0.001), possibly due to concurrent changes in the way children exited OHC. Overall, more than one-third of children exiting OHC in 2008 re-entered within five years (35.3%, N=4076), but rates of re-entry varied by child and care characteristics including age, ethnicity, mode of exit, and placement stability. Based on these associated factors, we developed a calculator that can estimate the likelihood of rapid re-entry to OHC for a group of children and could be used by social care practitioners or service planners. Our findings provide insight into which groups of children are most likely to re-enter OHC, who may benefit from additional support or ongoing monitoring. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cognitive function in patients with stable coronary heart disease: Related cerebrovascular and cardiovascular responses.

PubMed

Gayda, Mathieu; Gremeaux, Vincent; Bherer, Louis; Juneau, Martin; Drigny, Joffrey; Dupuy, Olivier; Lapierre, Gabriel; Labelle, Véronique; Fortier, Annik; Nigam, Anil

2017-01-01

Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD) sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and [Formula: see text] peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC), 20 age-matched old healthy controls (OHC) and 25 patients with stable CHD were recruited. Cognitive function assessment included short term-working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamic (impedance cardiography) and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy) were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher [Formula: see text] peak, maximal cardiac index (CI max), cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery) and cognitive function (for all items) (P<0.05). Compared to OHC, CHD patients had lower [Formula: see text] peak, CI max, cerebral oxygenation-perfusion (during recovery) and short term-working memory, processing speed, cognitive inhibition and flexibility and long-term verbal memory (P<0.05). [Formula: see text] peak and CI max were related to exercise cerebral oxygenation-perfusion and cognitive function (P<0.005). Cerebral oxygenation-perfusion (exercise) was related to cognitive function (P<0.005). Stable CHD patients have a worse cognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with [Formula: see text] peak, CI max and cerebral oxygenation-perfusion.

Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation

PubMed Central

Dias, Irundika H.K.; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M.; Polidori, Maria C.; Lip, Gregory Y.H.; Griffiths, Helen R.

2014-01-01

Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4 μg oxLDL and 25 µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. PMID:25048970

Ocean heat content and ocean energy budget: make better use of historical global subsurface temperature dataset

NASA Astrophysics Data System (ADS)

Cheng, L.; Zhu, J.

2016-02-01

Ocean heat content (OHC) change contributes substantially to global sea level rise, also is a key metric of the ocean/global energy budget, so it is a vital task for the climate research community to estimate historical OHC. While there are large uncertainties regarding its value, here we review the OHC calculation by using the historical global subsurface temperature dataset, and discuss the sources of its uncertainty. The presentation briefly introduces how to correct to the systematic biases in expendable bathythermograph (XBT) data, a alternative way of filling data gaps (which is main focus of this talk), and how to choose a proper climatology. A new reconstruction of historical upper (0-700 m) OHC change will be presented, which is the Institute of Atmospheric Physics (IAP) version of historical upper OHC assessment. The authors also want to highlight the impact of observation system change on OHC calculation, which could lead to bias in OHC estimates. Furthermore, we will compare the updated observational-based estimates on ocean heat content change since 1970s with CMIP5 results. This comparison shows good agreement, increasing the confidence of the climate models in representing the climate history.

Using Online Health Communities to Deliver Patient-Centered Care to People With Chronic Conditions

PubMed Central

2013-01-01

Background Our health care system faces major threats as the number of people with multiple chronic conditions rises dramatically. Objective To study the use of Online Health Communities (OHCs) as a tool to facilitate high-quality and affordable health care for future generations. Methods OHCs are Internet-based platforms that unite either a group of patients, a group of professionals, or a mixture of both. Members interact using modern communication technologies such as blogs, chats, forums, and wikis. We illustrate the use of OHCs for ParkinsonNet, a professional network for Parkinson disease whose participants—both patients and professionals—use various types of OHCs to deliver patient-centered care. Results We discuss several potential applications in clinical practice. First, due to rapid advances in medical knowledge, many health professionals lack sufficient expertise to address the complex health care needs of chronic patients. OHCs can be used to share experiences, exchange knowledge, and increase disease-specific expertise. Second, current health care delivery is fragmented, as many patients acquire relationships with multiple professionals and institutions. OHCs can bridge geographical distances and enable interdisciplinary collaboration across institutions and traditional echelons. Third, chronic patients lack adequate tools to self-manage their disease. OHCs can be used to actively engage and empower patients in their health care process and to tailor care to their individual needs. Personal health communities of individual patients offer unique opportunities to store all medical information in one central place, while allowing transparent communication across all members of each patient’s health care team. Conclusions OHCs are a powerful tool to address some of the challenges chronic care faces today. OHCs help to facilitate communication among professionals and patients and support coordination of care across traditional echelons, which does not happen spontaneously in busy practice. PMID:23803284

Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

PubMed

Gabrielsen, Kristin Møller; Krokstad, Julie Stene; Villanger, Gro Dehli; Blair, David A D; Obregon, Maria-Jesus; Sonne, Christian; Dietz, Rune; Letcher, Robert J; Jenssen, Bjørn Munro

2015-01-01

Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Online cancer communities as informatics intervention for social support: conceptualization, characterization, and impact

PubMed Central

O’Carroll Bantum, Erin; Owen, Jason; Bakken, Suzanne; Elhadad, Noémie

2017-01-01

Objectives: The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities. Target audience: The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial. Scope: The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients. PMID:27402140

Organo-halogenated contaminants (OHCs) in the sediments from the Soan River, Pakistan: OHCs(adsorbed TOC) burial flux, status and risk assessment.

PubMed

Malik, Riffat Naseem; Mehboob, Fouzia; Ali, Usman; Katsoyiannis, Athanasios; Schuster, Jasmin K; Moeckel, Claudia; Jones, Kevin C

2014-05-15

In this study, regression analysis revealed that TOC is the principal factor in controlling the fate of organo-halogenated contaminants (OHCs: PCBs, PBDEs, OCPs) in Soan River, Pakistan. The OHCs(adsorbed TOC) burial flux (OHCs(adsorbed TOC)Bf; mg/cm(2)·yr) was calculated in the following ranges: ∑PCBs (0.07-0.31), ∑PBDEs (0.005-0.029), ∑HCHs (0.015-0.046) and ∑DDTs (0.007-0.039). Apart from OHCs(adsorbed TOC)Bf, the levels of OHCs were in the following order: PCBs>DDTs>PBDEs>HCH>Chlordane>HCB. PBDEs and PCB congener patterns showed following order respectively: BDE-149>-153>-18>-138>-44 and PCB-149>-153>-18>-138>-44. DDT isomers and metabolites' pattern were p,p'-DDT>p,p'-DDD>p,p'-DDE>o,p'-DDT>o,p'-DDD>o,p'-DDE and HCHs were β-HCH>α-HCH>γ-HCH>δ-HCH. PBDE composition had similarities to penta-BDE and DE-71 mixtures and PCBs with commercial products Aroclor-1254 and -1260. (DDE+DDD)/∑DDTs and p,p'-DDT/p,p'-DDE suggested the recent input of DDTs in sediments while α/γ-HCH indicated past usage of lindane and technical mixtures. Risk assessment suggested that Soan River and its tributaries are potentially at risk against most of the OHCs. Copyright © 2014 Elsevier B.V. All rights reserved.

Online cancer communities as informatics intervention for social support: conceptualization, characterization, and impact.

PubMed

Zhang, Shaodian; O'Carroll Bantum, Erin; Owen, Jason; Bakken, Suzanne; Elhadad, Noémie

2017-03-01

The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities. The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial. The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.

DPOAE in estimation of the function of the cochlea in tinnitus patients with normal hearing.

PubMed

Sztuka, Aleksandra; Pospiech, Lucyna; Gawron, Wojciech; Dudek, Krzysztof

2010-02-01

The most probable place generating tinnitus in the auditory pathway is the outer hair cells (OHCs) inside the cochlea. Otoacoustic emissions are used to assess their activity. The objective of the investigation was to measure the features of distortion product otoacoustic emissions (DPOAE) in a group of tinnitus patients without hearing loss, estimate the diagnostic value of the parameters for the analysis of cochlear function in the patients, emphasizing those most useful in localizing tinnitus generators, and determine the hypothetical influence of hyperacusis and misophony on DPOAE parameters in tinnitus patients. The material consisted of 44 patients with tinnitus and without hearing loss. In the control group were 33 patients without tinnitus with the same state of hearing. The tinnitus patients were divided into three subgroups: those with hyperacusis, those with misophonia, and those with neither. After collecting medical history and performing clinical examination of all the patients, tonal and impedance audiometry, ABR, and discomfort level were evaluated. Then DPOAE were measured using three procedures. First the amplitudes of two points per octave were assessed, second the "fine structure" method with 16-20 points per octave (f2/f1=1.22, L1=L2=70 dB), and the third procedure included recording the growth function in three series for input tones of f2=2002, 4004, and 6006Hz (f2/f1=1.22) and L1=L2 levels increasing by increments of 5 dB in each series. Hyperacusis was found in 63% and misophonia in 10% of the tinnitus patients with no hearing loss. DPOAE amplitudes in recordings with two points per octave and the fine structure method are very valuable parameters for estimating cochlear function in tinnitus patients with normal hearing. Function growth rate cannot be the only parameter in measuring DPOAE in tinnitus patients, including subjects with hyperacusis and misophonia. The markedly higher DPOAE amplitudes in the group of tinnitus patients without hearing loss suggest that tinnitus may be caused by increased motility of the OHCs induced by decreasing efferent fiber activity, and not by OHC failure. Hyperacusis significantly increases the amplitude of DPOAE in tinnitus patients with no hearing loss. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Efferent feedback can explain many hearing phenomena

NASA Astrophysics Data System (ADS)

Holmes, W. Harvey; Flax, Matthew R.

2015-12-01

The mixed mode cochlear amplifier (MMCA) model was presented at the last Mechanics of Hearing workshop [4]. The MMCA consists principally of a nonlinear feedback loop formed when an efferent-controlled outer hair cell (OHC) is combined with the cochlear mechanics and the rest of the relevant neurobiology. Essential elements of this model are efferent control of the OHC motility and a delay in the feedback to the OHC. The input to the MMCA is the passive travelling wave. In the MMCA amplification is localized where both the neural and tuned mechanical systems meet in the Organ of Corti (OoC). The simplest model based on this idea is a nonlinear delay line resonator (DLR), which is mathematically described by a nonlinear delay-differential equation (DDE). This model predicts possible Hopf bifurcations and exhibits its most interesting behaviour when operating near a bifurcation. This contribution presents some simulation results using the DLR model. These show that various observed hearing phenomena can be accounted for by this model, at least qualitatively, including compression effects, two-tone suppression and some forms of otoacoustic emissions (OAEs).

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death

PubMed Central

Kenyon, Emma J.; Kirkwood, Nerissa K.; Kitcher, Siân R.; O’Reilly, Molly; Cantillon, Daire M.; Goodyear, Richard J.; Secker, Abigail; Baxendale, Sarah; Bull, James C.; Waddell, Simon J.; Whitfield, Tanya T.; Ward, Simon E.; Kros, Corné J.; Richardson, Guy P.

2017-01-01

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red–conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem. PMID:29263311

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

PubMed

Kenyon, Emma J; Kirkwood, Nerissa K; Kitcher, Siân R; O'Reilly, Molly; Derudas, Marco; Cantillon, Daire M; Goodyear, Richard J; Secker, Abigail; Baxendale, Sarah; Bull, James C; Waddell, Simon J; Whitfield, Tanya T; Ward, Simon E; Kros, Corné J; Richardson, Guy P

2017-12-21

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red-conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem.

The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit

PubMed Central

Aedo, Cristian; Terreros, Gonzalo; León, Alex; Delano, Paul H.

2016-01-01

Background and Objective The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC) of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC) neurons and OHCs via alpha-9/10 nicotinic receptors. Methods We used wild type (WT) and alpha-9 nicotinic receptor knock-out (KO) mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR). Results Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes. Conclusion These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I) and superior olivary complex (ABR wave III) responses are mediated through MOC synapses. PMID:27195498

Different effects of propofol and isoflurane on cochlear blood flow and hearing function in Guinea pigs.

PubMed

Xiao, Ying; Wen, Jian; Bai, Yanxia; Duan, Na; Jing, G X

2014-01-01

To investigate the effects of isoflurane and propofol on mean arterial pressure (MAP), cochlear blood flow (CoBF), distortion-product otoacoustic emission (DPOAE), and the ultrastructure of outer hair cells (OHCs) in guinea pig cochleae. Forty-eight male guinea pigs were randomly assigned to one of six treatment groups. Groups 1 to 3 were infused (i.v.) with a loading dose of propofol (5 mg/kg) for 5 min and three maintenance doses (10, 20, or 40 mg kg-1·h-1, respectively) for 115 min. Groups 4 to 6 were inhaled with isoflurane at concentrations of 1.15 vol%, 2.30 vol% or 3.45 vol% respectively for 120 min. CoBF and MAP were recorded prior to and at 5 min intervals during drug administration. DPOAE was measured before, immediately after, and 1 h after administration. Following the final DPOAE test, cochleae were examined using scanning electron microscopy. Propofol treatment reduced MAP in a dose-dependent manner. CoBF and DPOAE showed increases at propofol maintenance doses of 10 and 20 mg kg-1·h-1. Inhalation of isoflurane at concentrations of 2.30 vol% and 3.45 vol% reduced MAP and CoBF. DPOAE amplitude increased following inhalation of 1.15 vol% isoflurane, but decreased following inhalations of 2.30 vol% and 3.45 vol%. Cochlear structure was changed following inhalation of either 2.30 vol% or 3.45 vol% isoflurane. Propofol could decrease MAP and increase both CoBF and DPOAE without affecting OHC structure. Inhalation of isoflurane at concentrations >2.30 vol% decreased CoBF and DPOAE, and produced injury to OHCs.

Parameterization of single-scattering properties of snow

NASA Astrophysics Data System (ADS)

Räisänen, P.; Kokhanovsky, A.; Guyot, G.; Jourdan, O.; Nousiainen, T.

2015-02-01

Snow consists of non-spherical grains of various shapes and sizes. Still, in many radiative transfer applications, single-scattering properties of snow have been based on the assumption of spherical grains. More recently, second-generation Koch fractals have been employed. While they produce a relatively flat phase function typical of deformed non-spherical particles, this is still a rather ad-hoc choice. Here, angular scattering measurements for blowing snow conducted during the CLimate IMpacts of Short-Lived pollutants In the Polar region (CLIMSLIP) campaign at Ny Ålesund, Svalbard, are used to construct a reference phase function for snow. Based on this phase function, an optimized habit combination (OHC) consisting of severely rough (SR) droxtals, aggregates of SR plates and strongly distorted Koch fractals is selected. The single-scattering properties of snow are then computed for the OHC as a function of wavelength λ and snow grain volume-to-projected area equivalent radius rvp. Parameterization equations are developed for λ = 0.199-2.7 μm and rvp = 10-2000 μm, which express the single-scattering co-albedo β, the asymmetry parameter g and the phase function P11 as functions of the size parameter and the real and imaginary parts of the refractive index. The parameterizations are analytic and simple to use in radiative transfer models. Compared to the reference values computed for the OHC, the accuracy of the parameterization is very high for β and g. This is also true for the phase function parameterization, except for strongly absorbing cases (β > 0.3). Finally, we consider snow albedo and reflected radiances for the suggested snow optics parameterization, making comparisons to spheres and distorted Koch fractals.

Parameterization of single-scattering properties of snow

NASA Astrophysics Data System (ADS)

Räisänen, P.; Kokhanovsky, A.; Guyot, G.; Jourdan, O.; Nousiainen, T.

2015-06-01

Snow consists of non-spherical grains of various shapes and sizes. Still, in many radiative transfer applications, single-scattering properties of snow have been based on the assumption of spherical grains. More recently, second-generation Koch fractals have been employed. While they produce a relatively flat phase function typical of deformed non-spherical particles, this is still a rather ad hoc choice. Here, angular scattering measurements for blowing snow conducted during the CLimate IMpacts of Short-Lived pollutants In the Polar region (CLIMSLIP) campaign at Ny Ålesund, Svalbard, are used to construct a reference phase function for snow. Based on this phase function, an optimized habit combination (OHC) consisting of severely rough (SR) droxtals, aggregates of SR plates and strongly distorted Koch fractals is selected. The single-scattering properties of snow are then computed for the OHC as a function of wavelength λ and snow grain volume-to-projected area equivalent radius rvp. Parameterization equations are developed for λ = 0.199-2.7 μm and rvp = 10-2000 μm, which express the single-scattering co-albedo β, the asymmetry parameter g and the phase function P11 as functions of the size parameter and the real and imaginary parts of the refractive index. The parameterizations are analytic and simple to use in radiative transfer models. Compared to the reference values computed for the OHC, the accuracy of the parameterization is very high for β and g. This is also true for the phase function parameterization, except for strongly absorbing cases (β > 0.3). Finally, we consider snow albedo and reflected radiances for the suggested snow optics parameterization, making comparisons to spheres and distorted Koch fractals.

Parameterization of single-scattering properties of snow

NASA Astrophysics Data System (ADS)

Räisänen, Petri; Kokhanovsky, Alexander; Guyot, Gwennole; Jourdan, Olivier; Nousiainen, Timo

2015-04-01

Snow consists of non-spherical ice grains of various shapes and sizes, which are surrounded by air and sometimes covered by films of liquid water. Still, in many studies, homogeneous spherical snow grains have been assumed in radiative transfer calculations, due to the convenience of using Mie theory. More recently, second-generation Koch fractals have been employed. While they produce a relatively flat scattering phase function typical of deformed non-spherical particles, this is still a rather ad-hoc choice. Here, angular scattering measurements for blowing snow conducted during the CLimate IMpacts of Short-Lived pollutants In the Polar region (CLIMSLIP) campaign at Ny Ålesund, Svalbard, are used to construct a reference phase function for snow. Based on this phase function, an optimized habit combination (OHC) consisting of severely rough (SR) droxtals, aggregates of SR plates and strongly distorted Koch fractals is selected. The single-scattering properties of snow are then computed for the OHC as a function of wavelength λ and snow grain volume-to-projected area equivalent radius rvp. Parameterization equations are developed for λ=0.199-2.7 μm and rvp = 10-2000 μm, which express the single-scattering co-albedo β, the asymmetry parameter g and the phase function as functions of the size parameter and the real and imaginary parts of the refractive index. Compared to the reference values computed for the OHC, the accuracy of the parameterization is very high for β and g. This is also true for the phase function parameterization, except for strongly absorbing cases (β > 0.3). Finally, we consider snow albedo and reflected radiances for the suggested snow optics parameterization, making comparisons with spheres and distorted Koch fractals. Further evaluation and validation of the proposed approach against (e.g.) bidirectional reflectance and polarization measurements for snow is planned. At any rate, it seems safe to assume that the OHC selected here provides a substantially better basis for representing the single-scattering properties of snow than spheres do. Moreover, the parameterizations developed here are analytic and simple to use, and they can also be applied to the treatment of dirty snow following (e.g.) the approach of Kokhanovsky (The Cryosphere, 7, 1325-1331, doi:10.5194/tc-7-1325-2013, 2013). This should make them an attractive option for use in radiative transfer applications involving snow.

Return-to-work of sick-listed workers without an employment contract--what works?

PubMed

Vermeulen, Sylvia J; Tamminga, Sietske J; Schellart, Antonius Jm; Ybema, Jan Fekke; Anema, Johannes R

2009-07-14

In the past decade flexible labour market arrangements have emerged as a significant change in the European Union labour market. Studies suggest that these new types of labour arrangements may be linked to ill health, an increased risk for work disability, and inadequate vocational rehabilitation. Therefore, the objectives of this study were: 1. to examine demographic characteristics of workers without an employment contract sick-listed for at least 13 weeks, 2. to describe the content and frequency of occupational health care (OHC) interventions for these sick-listed workers, and 3. to examine OHC interventions as possible determinants for return-to-work (RTW) of these workers. A cohort of 1077 sick-listed workers without an employment contract were included at baseline, i.e. 13 weeks after reporting sick. Demographic variables were available at baseline. Measurement of cross-sectional data took place 4-6 months after inclusion. Primary outcome measures were: frequency of OHC interventions and RTW-rates. Measured confounding variables were: gender, age, type of worker (temporary agency worker, unemployed worker, or remaining worker without employment contract), level of education, reason for absenteeism (diagnosis), and perceived health. The association between OHC interventions and RTW was analysed with a logistic multiple regression analysis. At 7-9 months after the first day of reporting sick only 19% of the workers had (partially or completely) returned to work, and most workers perceived their health as fairly poor or poor. The most frequently reported (49%) intervention was 'the OHC professional discussed RTW'. However, the intervention 'OHC professional made and discussed a RTW action plan' was reported by only 19% of the respondents. The logistic multiple regression analysis showed a significant positive association between RTW and the interventions: 'OHC professional discussed RTW'; and 'OHC professional made and discussed a RTW action plan'. The intervention 'OHC professional referred sick-listed worker to a vocational rehabilitation agency' was significantly associated with no RTW. This is the first time that characteristics of a large cohort of sick-listed workers without an employment contract were examined. An experimental or prospective study is needed to explore the causal nature of the associations found between OHC interventions and RTW.

Improved estimates of ocean heat content from 1960 to 2015.

PubMed

Cheng, Lijing; Trenberth, Kevin E; Fasullo, John; Boyer, Tim; Abraham, John; Zhu, Jiang

2017-03-01

Earth's energy imbalance (EEI) drives the ongoing global warming and can best be assessed across the historical record (that is, since 1960) from ocean heat content (OHC) changes. An accurate assessment of OHC is a challenge, mainly because of insufficient and irregular data coverage. We provide updated OHC estimates with the goal of minimizing associated sampling error. We performed a subsample test, in which subsets of data during the data-rich Argo era are colocated with locations of earlier ocean observations, to quantify this error. Our results provide a new OHC estimate with an unbiased mean sampling error and with variability on decadal and multidecadal time scales (signal) that can be reliably distinguished from sampling error (noise) with signal-to-noise ratios higher than 3. The inferred integrated EEI is greater than that reported in previous assessments and is consistent with a reconstruction of the radiative imbalance at the top of atmosphere starting in 1985. We found that changes in OHC are relatively small before about 1980; since then, OHC has increased fairly steadily and, since 1990, has increasingly involved deeper layers of the ocean. In addition, OHC changes in six major oceans are reliable on decadal time scales. All ocean basins examined have experienced significant warming since 1998, with the greatest warming in the southern oceans, the tropical/subtropical Pacific Ocean, and the tropical/subtropical Atlantic Ocean. This new look at OHC and EEI changes over time provides greater confidence than previously possible, and the data sets produced are a valuable resource for further study.

Improved estimates of ocean heat content from 1960 to 2015

PubMed Central

Cheng, Lijing; Trenberth, Kevin E.; Fasullo, John; Boyer, Tim; Abraham, John; Zhu, Jiang

2017-01-01

Earth’s energy imbalance (EEI) drives the ongoing global warming and can best be assessed across the historical record (that is, since 1960) from ocean heat content (OHC) changes. An accurate assessment of OHC is a challenge, mainly because of insufficient and irregular data coverage. We provide updated OHC estimates with the goal of minimizing associated sampling error. We performed a subsample test, in which subsets of data during the data-rich Argo era are colocated with locations of earlier ocean observations, to quantify this error. Our results provide a new OHC estimate with an unbiased mean sampling error and with variability on decadal and multidecadal time scales (signal) that can be reliably distinguished from sampling error (noise) with signal-to-noise ratios higher than 3. The inferred integrated EEI is greater than that reported in previous assessments and is consistent with a reconstruction of the radiative imbalance at the top of atmosphere starting in 1985. We found that changes in OHC are relatively small before about 1980; since then, OHC has increased fairly steadily and, since 1990, has increasingly involved deeper layers of the ocean. In addition, OHC changes in six major oceans are reliable on decadal time scales. All ocean basins examined have experienced significant warming since 1998, with the greatest warming in the southern oceans, the tropical/subtropical Pacific Ocean, and the tropical/subtropical Atlantic Ocean. This new look at OHC and EEI changes over time provides greater confidence than previously possible, and the data sets produced are a valuable resource for further study. PMID:28345033

Improved estimates of ocean heat content from 1960 to 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lijing; Trenberth, Kevin E.; Fasullo, John

Earth’s energy imbalance (EEI) drives the ongoing global warming and can best be assessed across the historical record (that is, since 1960) from ocean heat content (OHC) changes. An accurate assessment of OHC is a challenge, mainly because of insufficient and irregular data coverage. We provide here updated OHC estimates with the goal of minimizing associated sampling error. We performed a subsample test, in which subsets of data during the datarich Argo era are colocated with locations of earlier ocean observations, to quantify this error. Our results provide a new OHC estimate with an unbiased mean sampling error and withmore » variability on decadal and multidecadal time scales (signal) that can be reliably distinguished fromsampling error (noise) with signal-to-noise ratios higher than 3. The inferred integrated EEI is greater than that reported in previous assessments and is consistent with a reconstruction of the radiative imbalance at the top of atmosphere starting in 1985. We found that changes in OHC are relatively small before about 1980; since then, OHC has increased fairly steadily and, since 1990, has increasingly involved deeper layers of the ocean. In addition,OHC changes in sixmajor oceans are reliable on decadal timescales. All ocean basins examined have experienced significant warming since 1998, with the greatest warming in the southern oceans, the tropical/subtropical Pacific Ocean, and the tropical/subtropical Atlantic Ocean. This new look at OHC and EEI changes over time provides greater confidence than previously possible, and the data sets produced are a valuable resource for further study.« less

EFFECTS OF INTERPERSONAL TRUST AMONG USERS OF ONLINE HEALTH COMMUNITIES ON PATIENT TRUST IN AND SATISFACTION WITH THEIR PHYSICIAN.

PubMed

Audrain-Pontevia, Anne-Françoise; Menvielle, Loick

2018-01-01

Online Health Communities (OHCs) are increasingly being used by patients in the Web 2.0 era. Today's patients have instant access to a great deal of medical information and contacts. Despite the considerable development of OHCs, little is known regarding the impact on the patient-physician relationship. This research aims at filling this gap and examines how interpersonal trust on peer-to-peer OHCs influences two key relational variables, namely patient trust in the physician and patient satisfaction with the physician. It also investigates their influences on the patient's attitude toward the physician. Drawing on both the relational and medical literatures, we propose a research model that brings out the relationships between interpersonal trust in OHCs, and patients' trust, satisfaction and attitude toward the physician. We then conduct a quantitative survey of 512 OHC users in France, using structural equation modeling to test our hypotheses. Our findings indicate that interpersonal trust in OHCs exerts a positive influence on both patients' trust in and satisfaction with their physician. It also highlights that these two relational variables have a positive influence on patient attitude toward the physician. Our findings also indicate that patient trust influences patient satisfaction with the physician. This research highlights the importance of OHCs, which can be seen as valuable instruments for enhancing patient-physician relationships. It shows that healthcare managers should seek to enhance interpersonal trust among OHC users, because this trust has a positive influence on patient satisfaction with, trust in and attitude toward the physician.

Improved estimates of ocean heat content from 1960 to 2015

DOE PAGES

Cheng, Lijing; Trenberth, Kevin E.; Fasullo, John; ...

2017-03-10

Earth’s energy imbalance (EEI) drives the ongoing global warming and can best be assessed across the historical record (that is, since 1960) from ocean heat content (OHC) changes. An accurate assessment of OHC is a challenge, mainly because of insufficient and irregular data coverage. We provide here updated OHC estimates with the goal of minimizing associated sampling error. We performed a subsample test, in which subsets of data during the datarich Argo era are colocated with locations of earlier ocean observations, to quantify this error. Our results provide a new OHC estimate with an unbiased mean sampling error and withmore » variability on decadal and multidecadal time scales (signal) that can be reliably distinguished fromsampling error (noise) with signal-to-noise ratios higher than 3. The inferred integrated EEI is greater than that reported in previous assessments and is consistent with a reconstruction of the radiative imbalance at the top of atmosphere starting in 1985. We found that changes in OHC are relatively small before about 1980; since then, OHC has increased fairly steadily and, since 1990, has increasingly involved deeper layers of the ocean. In addition,OHC changes in sixmajor oceans are reliable on decadal timescales. All ocean basins examined have experienced significant warming since 1998, with the greatest warming in the southern oceans, the tropical/subtropical Pacific Ocean, and the tropical/subtropical Atlantic Ocean. This new look at OHC and EEI changes over time provides greater confidence than previously possible, and the data sets produced are a valuable resource for further study.« less

Prestin and the cholinergic receptor of hair cells: positively-selected proteins in mammals

PubMed Central

Elgoyhen, Ana Belén; Franchini, Lucía F.

2010-01-01

The hair cells of the vertebrate inner ear posses active mechanical processes to amplify their inputs. The stereocilia bundle of various vertebrate animals can produce active movements. Though standard stereocilia-based mechanisms to promote amplification persist in mammals, an additional radically different mechanism evolved: the so called somatic electromotility which refers to the elongation/contraction of the outer hair cells’ (OHC) cylindrical cell body in response to membrane voltage changes. Somatic electromotility in OHCs, as the basis for cochlear amplification, is a mammalian novelty and it is largely dependent upon the properties of the unique motor protein prestin. We review recent literature which has demonstrated that although the gene encoding prestin is present in all vertebrate species, mammalian prestin has been under positive selective pressure to acquire motor properties, probably rendering it fit to serve somatic motility in outer hair cells. Moreover, we discuss data which indicates that a modified α10 nicotinic cholinergic receptor subunit has coevolved in mammals, most likely to give the auditory feedback system the capability to control somatic electromotility. PMID:20056140

The Subpolar North Atlantic Ocean Heat Content Variability and its Decomposition.

PubMed

Zhang, Weiwei; Yan, Xiao-Hai

2017-10-23

The Subpolar North Atlantic (SPNA) is one of the most important areas to global climate because its ocean heat content (OHC) is highly correlated with the Atlantic Meridional Overturning Circulation (AMOC), and its circulation strength affects the salt transport by the AMOC, which in turn feeds and sustains the strength of the AMOC. Moreover, the recent global surface warming "hiatus" may be attributed to the SPNA as one of the major planetary heat sinks. Although almost synchronized before 1996, the OHC has greater spatial disparities afterwards, which cannot be explained as driven by the North Atlantic Oscillation (NAO). Temperature decomposition reveals that the western SPNA OHC is mainly determined by the along isopycnal changes, while in the eastern SPNA along isopycnal changes and isopycnal undulation are both important. Further analysis indicates that heat flux dominates the western SPNA OHC, but in the eastern SPNA wind forcing affects the OHC significantly. It is worth noting that the along isopycnal OHC changes can also induce heaving, thus the observed heaving domination in global oceans cannot mask the extra heat in the ocean during the recent "hiatus".

Animal models for transdermal drug delivery.

PubMed

Panchagnula, R; Stemmer, K; Ritschel, W A

1997-06-01

The purpose of this investigation was to compare the permeation characteristics of two different compounds (extremely polar and nonpolar), i.e., tritium-labeled water (W) and 14C-labeled 7-hydroxycoumarin (7-OHC), among 16 different species, including human skin. Snake skin exhibited highest permeability for both W and 7-OHC. Permeability and lag time values of W and 7-OHC across Brattleboro rat and hairless guinea pig are very close to human skin. Skin thickness in micrometers (full thickness, epidermis and stratum corneum, and stratum corneum), and number of hair follicles present in each cm2 were determined for each species. There was no relationship between number of hair follicles and permeability values for both W and 7-OHC. The skin thickness (full) was related to the relative permeability values of W, whereas for 7-OHC it was not.

Vibration of the organ of Corti within the cochlear apex in mice

PubMed Central

Gao, Simon S.; Wang, Rosalie; Raphael, Patrick D.; Moayedi, Yalda; Groves, Andrew K.; Zuo, Jian; Applegate, Brian E.

2014-01-01

The tonotopic map of the mammalian cochlea is commonly thought to be determined by the passive mechanical properties of the basilar membrane. The other tissues and cells that make up the organ of Corti also have passive mechanical properties; however, their roles are less well understood. In addition, active forces produced by outer hair cells (OHCs) enhance the vibration of the basilar membrane, termed cochlear amplification. Here, we studied how these biomechanical components interact using optical coherence tomography, which permits vibratory measurements within tissue. We measured not only classical basilar membrane tuning curves, but also vibratory responses from the rest of the organ of Corti within the mouse cochlear apex in vivo. As expected, basilar membrane tuning was sharp in live mice and broad in dead mice. Interestingly, the vibratory response of the region lateral to the OHCs, the “lateral compartment,” demonstrated frequency-dependent phase differences relative to the basilar membrane. This was sharply tuned in both live and dead mice. We then measured basilar membrane and lateral compartment vibration in transgenic mice with targeted alterations in cochlear mechanics. Prestin499/499, Prestin−/−, and TectaC1509G/C1509G mice demonstrated no cochlear amplification but maintained the lateral compartment phase difference. In contrast, SfswapTg/Tg mice maintained cochlear amplification but did not demonstrate the lateral compartment phase difference. These data indicate that the organ of Corti has complex micromechanical vibratory characteristics, with passive, yet sharply tuned, vibratory characteristics associated with the supporting cells. These characteristics may tune OHC force generation to produce the sharp frequency selectivity of mammalian hearing. PMID:24920025

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

PubMed

Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

2016-03-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative

PubMed Central

SUN, BAOGUO; MENG, JUN; XIANG, TING; ZHANG, LEI; DENG, LIUXIANG; CHEN, YAN; LUO, HAOXUAN; YANG, ZHANGBIN; CHEN, ZEXIONG; ZHANG, SHIJUN

2016-01-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire. PMID:26997998

Acoustic input and efferent activity regulate the expression of molecules involved in cochlear micromechanics

PubMed Central

Lamas, Veronica; Arévalo, Juan C.; Juiz, José M.; Merchán, Miguel A.

2015-01-01

Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major molecules involved in OHC electromotility, both at the transcriptional and posttranscriptional levels. PMID:25653600

Consensuses and discrepancies of basin-scale ocean heat content changes in different ocean analyses

NASA Astrophysics Data System (ADS)

Wang, Gongjie; Cheng, Lijing; Abraham, John; Li, Chongyin

2018-04-01

Inconsistent global/basin ocean heat content (OHC) changes were found in different ocean subsurface temperature analyses, especially in recent studies related to the slowdown in global surface temperature rise. This finding challenges the reliability of the ocean subsurface temperature analyses and motivates a more comprehensive inter-comparison between the analyses. Here we compare the OHC changes in three ocean analyses (Ishii, EN4 and IAP) to investigate the uncertainty in OHC in four major ocean basins from decadal to multi-decadal scales. First, all products show an increase of OHC since 1970 in each ocean basin revealing a robust warming, although the warming rates are not identical. The geographical patterns, the key modes and the vertical structure of OHC changes are consistent among the three datasets, implying that the main OHC variabilities can be robustly represented. However, large discrepancies are found in the percentage of basinal ocean heating related to the global ocean, with the largest differences in the Pacific and Southern Ocean. Meanwhile, we find a large discrepancy of ocean heat storage in different layers, especially within 300-700 m in the Pacific and Southern Oceans. Furthermore, the near surface analysis of Ishii and IAP are consistent with sea surface temperature (SST) products, but EN4 is found to underestimate the long-term trend. Compared with ocean heat storage derived from the atmospheric budget equation, all products show consistent seasonal cycles of OHC in the upper 1500 m especially during 2008 to 2012. Overall, our analyses further the understanding of the observed OHC variations, and we recommend a careful quantification of errors in the ocean analyses.

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

PubMed

Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

2015-12-01

Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of Biologists Ltd.

High frequency measures of OHC nonlinear capacitance (NLC) and their significance: Why measures stray away from predictions

NASA Astrophysics Data System (ADS)

Santos-Sacchi, Joseph

2018-05-01

Measures of membrane capacitance (Cm) can be used to assess important characteristics of voltage-dependent membrane proteins (e.g., channels and transporters). In particular, a protein's time-dependent voltage-sensor charge movement is equivalently represented as a frequency-dependent component of Cm, telling much about the kinetics of the protein's conformational behavior. Recently, we have explored the frequency dependence of OHC voltage-dependent capacitance (aka nonlinear capacitance, NLC) to query rates of conformational switching within prestin (SLC26a5), the cell's lateral membrane molecular motor 1. Following removal of confounding stray capacitance effects, high frequency Cm measures using wide-band stimuli accurately reveal unexpected low pass behavior in prestin's molecular motions.

Return-to-work of sick-listed workers without an employment contract – what works?

PubMed Central

Vermeulen, Sylvia J; Tamminga, Sietske J; Schellart, Antonius JM; Ybema, Jan Fekke; Anema, Johannes R

2009-01-01

Background In the past decade flexible labour market arrangements have emerged as a significant change in the European Union labour market. Studies suggest that these new types of labour arrangements may be linked to ill health, an increased risk for work disability, and inadequate vocational rehabilitation. Therefore, the objectives of this study were: 1. to examine demographic characteristics of workers without an employment contract sick-listed for at least 13 weeks, 2. to describe the content and frequency of occupational health care (OHC) interventions for these sick-listed workers, and 3. to examine OHC interventions as possible determinants for return-to-work (RTW) of these workers. Methods A cohort of 1077 sick-listed workers without an employment contract were included at baseline, i.e. 13 weeks after reporting sick. Demographic variables were available at baseline. Measurement of cross-sectional data took place 4–6 months after inclusion. Primary outcome measures were: frequency of OHC interventions and RTW-rates. Measured confounding variables were: gender, age, type of worker (temporary agency worker, unemployed worker, or remaining worker without employment contract), level of education, reason for absenteeism (diagnosis), and perceived health. The association between OHC interventions and RTW was analysed with a logistic multiple regression analysis. Results At 7–9 months after the first day of reporting sick only 19% of the workers had (partially or completely) returned to work, and most workers perceived their health as fairly poor or poor. The most frequently reported (49%) intervention was 'the OHC professional discussed RTW'. However, the intervention 'OHC professional made and discussed a RTW action plan' was reported by only 19% of the respondents. The logistic multiple regression analysis showed a significant positive association between RTW and the interventions: 'OHC professional discussed RTW'; and 'OHC professional made and discussed a RTW action plan'. The intervention 'OHC professional referred sick-listed worker to a vocational rehabilitation agency' was significantly associated with no RTW. Conclusion This is the first time that characteristics of a large cohort of sick-listed workers without an employment contract were examined. An experimental or prospective study is needed to explore the causal nature of the associations found between OHC interventions and RTW. PMID:19602219

Non-tip auditory-nerve responses that are suppressed by low-frequency bias tones originate from reticular lamina motion.

PubMed

Nam, Hui; Guinan, John J

2017-12-14

Recent cochlear mechanical measurements show that active processes increase the motion response of the reticular lamina (RL) at frequencies more than an octave below the local characteristic frequency (CF) for CFs above 5 kHz. A possible correlate is that in high-CF (>5 kHz) auditory-nerve (AN) fibers, responses to frequencies 1-3 octaves below CF ("tail" frequencies) can be inhibited by medial olivocochlear (MOC) efferents. These results indicate that active processes enhance the sensitivity of tail-frequency RL and AN responses. Perhaps related is that some apical low-CF AN fibers have tuning-curve (TC) "side-lobe" response areas at frequencies above and below the TC-tip that are MOC inhibited. We hypothesized that the tail and side-lobe responses are enhanced by the same active mechanisms as CF cochlear amplification. If responses to CF, tail-frequency, and TC-side-lobe tones are all enhanced by prestin motility controlled by outer-hair-cell (OHC) transmembrane voltage, then they should depend on OHC stereocilia position in the same way. To test this, we cyclically changed the OHC-stereocilia mechano-electric-transduction (MET) operating point with low-frequency "bias" tones (BTs) and increased the BT level until the BT caused quasi-static OHC MET saturation that reduced or "suppressed" the gain of OHC active processes. While measuring cat AN-fiber responses, 50 Hz BT level series, 70-120 dB SPL, were run alone and with CF tones, or 2.5 kHz tail-frequency tones, or side-lobe tones. BT-tone-alone responses were used to exclude BT sound levels that produced AN responses that might obscure BT suppression. Data were analyzed to show the BT phase that suppressed the tone responses at the lowest sound level. We found that AN responses to CF, tail-frequency, and side-lobe tones were suppressed at the same BT phase in almost all cases. The data are consistent with the enhancement of responses to CF, tail-frequency, and side-lobe tones all being due to the same OHC-stereocilia MET-dependent active process. Thus, OHC active processes enhance AN responses at frequencies outside of the cochlear-amplified TC-tip region in both high- and low-frequency cochlear regions. The data are consistent with the AN response enhancements being due to enhanced RL motion that drives IHC-stereocilia deflection by traditional RL-TM shear and/or by changing the RL-TM gap. Since tail-frequency basilar membrane (BM) motion is not actively enhanced, the tail-frequency IHC drive is from a vibrational mode little present on the BM, not a "second filter" of BM motion. Copyright © 2017 Elsevier B.V. All rights reserved.

Finite-element model of the active organ of Corti

PubMed Central

Elliott, Stephen J.; Baumgart, Johannes

2016-01-01

The cochlear amplifier that provides our hearing with its extraordinary sensitivity and selectivity is thought to be the result of an active biomechanical process within the sensory auditory organ, the organ of Corti. Although imaging techniques are developing rapidly, it is not currently possible, in a fully active cochlea, to obtain detailed measurements of the motion of individual elements within a cross section of the organ of Corti. This motion is predicted using a two-dimensional finite-element model. The various solid components are modelled using elastic elements, the outer hair cells (OHCs) as piezoelectric elements and the perilymph and endolymph as viscous and nearly incompressible fluid elements. The model is validated by comparison with existing measurements of the motions within the passive organ of Corti, calculated when it is driven either acoustically, by the fluid pressure or electrically, by excitation of the OHCs. The transverse basilar membrane (BM) motion and the shearing motion between the tectorial membrane and the reticular lamina are calculated for these two excitation modes. The fully active response of the BM to acoustic excitation is predicted using a linear superposition of the calculated responses and an assumed frequency response for the OHC feedback. PMID:26888950

Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.

PubMed

Majumder, Paromita; Moore, Paulette A; Richardson, Guy P; Gale, Jonathan E

2017-01-01

Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 μM for both IHC and OHC. We used 250 μM neomycin in subsequent hair-cell death assays. At 100 μM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not support the use of phenoxybenzamine as a therapeutic agent in mammalian inner ear. Our findings do share parallels with the observations from the zebrafish lateral line model but they also highlight the necessity for validation in the mammalian system and the potential for differential effects on sensory hair cells from different species, in different systems and even between cells in the same organ.

Controlling Mitochondrial Dynamics to Mitigate Noise-Induced Hearing Loss

DTIC Science & Technology

2016-10-01

exposure significantly reduced noise-induced auditory threshold shifts in our mouse model of NIHL. Additionally, protection against outer hair cell...and at 6 hours post-noise exposure. ‐ Perform analysis of outer auditory hair cells and synaptic ribbons from the different treatment groups...have made progress towards the completion of the outer hair cell counts (OHC) for this Subtask, particularly for study groups (1) mdivi-1/vehicle, and

New Casemix Classification as an Alternative Method for Budget Allocation in Thai Oral Healthcare Service: A Pilot Study

PubMed Central

Wisaijohn, Thunthita; Pimkhaokham, Atiphan; Lapying, Phenkhae; Itthichaisri, Chumpot; Pannarunothai, Supasit; Igarashi, Isao; Kawabuchi, Koichi

2010-01-01

This study aimed to develop a new casemix classification system as an alternative method for the budget allocation of oral healthcare service (OHCS). Initially, the International Statistical of Diseases and Related Health Problem, 10th revision, Thai Modification (ICD-10-TM) related to OHCS was used for developing the software “Grouper”. This model was designed to allow the translation of dental procedures into eight-digit codes. Multiple regression analysis was used to analyze the relationship between the factors used for developing the model and the resource consumption. Furthermore, the coefficient of variance, reduction in variance, and relative weight (RW) were applied to test the validity. The results demonstrated that 1,624 OHCS classifications, according to the diagnoses and the procedures performed, showed high homogeneity within groups and heterogeneity between groups. Moreover, the RW of the OHCS could be used to predict and control the production costs. In conclusion, this new OHCS casemix classification has a potential use in a global decision making. PMID:20936134

New casemix classification as an alternative method for budget allocation in thai oral healthcare service: a pilot study.

PubMed

Wisaijohn, Thunthita; Pimkhaokham, Atiphan; Lapying, Phenkhae; Itthichaisri, Chumpot; Pannarunothai, Supasit; Igarashi, Isao; Kawabuchi, Koichi

2010-01-01

This study aimed to develop a new casemix classification system as an alternative method for the budget allocation of oral healthcare service (OHCS). Initially, the International Statistical of Diseases and Related Health Problem, 10th revision, Thai Modification (ICD-10-TM) related to OHCS was used for developing the software "Grouper". This model was designed to allow the translation of dental procedures into eight-digit codes. Multiple regression analysis was used to analyze the relationship between the factors used for developing the model and the resource consumption. Furthermore, the coefficient of variance, reduction in variance, and relative weight (RW) were applied to test the validity. The results demonstrated that 1,624 OHCS classifications, according to the diagnoses and the procedures performed, showed high homogeneity within groups and heterogeneity between groups. Moreover, the RW of the OHCS could be used to predict and control the production costs. In conclusion, this new OHCS casemix classification has a potential use in a global decision making.

Children Placed In Out-of-Home Care as Midlife Adults: Are They Still Disadvantaged or Have They Caught Up With Their Peers?

PubMed

Brännström, Lars; Vinnerljung, Bo; Forsman, Hilma; Almquist, Ylva B

2017-08-01

International research has consistently reported that children placed in out-of-home care (OHC) have poor outcomes in young adulthood. Yet, little is known about their outcomes in midlife. Using prospective data from a cohort of more than 14,000 Swedes born in 1953, of which nearly 9% have been placed in OHC, this study examines whether there is developmental continuity or discontinuity of disadvantage reaching into middle age in OHC children, compared to same-aged peers. Outcome profiles, here conceptualized as combinations of adverse outcomes related to education, economic hardship, unemployment, and mental health problems, were assessed in 1992-2008 (ages 39-55). Results indicate that having had experience of OHC was associated with 2-fold elevated odds of ending up in the most disadvantaged outcome profile, controlling for observed confounding factors. These findings suggest that experience of OHC is a strong marker for disadvantaged outcomes also in midlife.

Finite element modelling of human auditory periphery including a feed-forward amplification of the cochlea.

PubMed

Wang, Xuelin; Wang, Liling; Zhou, Jianjun; Hu, Yujin

2014-08-01

A three-dimensional finite element model is developed for the simulation of the sound transmission through the human auditory periphery consisting of the external ear canal, middle ear and cochlea. The cochlea is modelled as a straight duct divided into two fluid-filled scalae by the basilar membrane (BM) having an orthotropic material property with dimensional variation along its length. In particular, an active feed-forward mechanism is added into the passive cochlear model to represent the activity of the outer hair cells (OHCs). An iterative procedure is proposed for calculating the nonlinear response resulting from the active cochlea in the frequency domain. Results on the middle-ear transfer function, BM steady-state frequency response and intracochlear pressure are derived. A good match of the model predictions with experimental data from the literatures demonstrates the validity of the ear model for simulating sound pressure gain of middle ear, frequency to place map, cochlear sensitivity and compressive output for large intensity input. The current model featuring an active cochlea is able to correlate directly the sound stimulus in the ear canal with the vibration of BM and provides a tool to explore the mechanisms by which sound pressure in the ear canal is converted to a stimulus for the OHCs.

Mechanical Excitation of IHC Stereocilia: An Attempt to Fit Together Diverse Evidence

NASA Astrophysics Data System (ADS)

Guinan, John J.

2011-11-01

The output of the cochlea is controlled by the bending of inner-hair-cell (IHC) stereocilia, but the mechanisms that produce this bending are poorly understood. Relevant evidence comes from several sources: measurements of cochlear motion from in-vitro and live preparations, as well as inferences about cochlear motions from responses of auditory-nerve fibers. The common conception that IHC excitation is due to shearing between the reticular lamina (RL) and the tectorial membrane (TM) does not explain the data. A hypothesis is presented that fits many of the observations into a coherent picture of how IHCs are excited. The key new concept is that stretching of outer-hair-cell (OHC) stereocilia (defined broadly) changes the RL-TM gap and produces fluid flow within the gap that bends the IHC stereocilia. Changes in the RL-TM gap and the resulting bending of IHC stereocilia provide a mechanism by which OHC active processes can enhance cochlear output without a corresponding enhancement of basilar-membrane motion.

Analysis of the cochlear amplifier fluid pump hypothesis.

PubMed

Zagadou, Brissi Franck; Mountain, David C

2012-04-01

We use analysis of a realistic three-dimensional finite-element model of the tunnel of Corti (ToC) in the middle turn of the gerbil cochlea tuned to the characteristic frequency (CF) of 4 kHz to show that the anatomical structure of the organ of Corti (OC) is consistent with the hypothesis that the cochlear amplifier functions as a fluid pump. The experimental evidence for the fluid pump is that outer hair cell (OHC) contraction and expansion induce oscillatory flow in the ToC. We show that this oscillatory flow can produce a fluid wave traveling in the ToC and that the outer pillar cells (OPC) do not present a significant barrier to fluid flow into the ToC. The wavelength of the resulting fluid wave launched into the tunnel at the CF is 1.5 mm, which is somewhat longer than the wavelength estimated for the classical traveling wave. This fluid wave propagates at least one wavelength before being significantly attenuated. We also investigated the effect of OPC spacing on fluid flow into the ToC and found that, for physiologically relevant spacing between the OPCs, the impedance estimate is similar to that of the underlying basilar membrane. We conclude that the row of OPCs does not significantly impede fluid exchange between ToC and the space between the row of OPC and the first row of OHC-Dieter's cells complex, and hence does not lead to excessive power loss. The BM displacement resulting from the fluid pumped into the ToC is significant for motion amplification. Our results support the hypothesis that there is an additional source of longitudinal coupling, provided by the ToC, as required in many non-classical models of the cochlear amplifier.

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

PubMed

Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

2017-06-01

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Organohalogenated contaminants (OHCs) in the serum and hair of pet cats and dogs: biosentinels of indoor pollution.

PubMed

Ali, Nadeem; Malik, Riffat Naseem; Mehdi, Toufeer; Eqani, Syed Ali Musstjab Akber Shah; Javeed, Aqeel; Neels, Hugo; Covaci, Adrian

2013-04-01

Concentrations of different classes of organohalogenated contaminants (OHCs) viz., polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), bromophenols (BPs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and their metabolites were determined in cat and dog serum and hair samples from Pakistan. The major DDT metabolite, p,p'-DDE, was the major OHC in cat serum (N=20) and ranged between 1 and 2150 ng/g lipid weight (lw). p,p'-DDE was not detected in dog serum (N=16). In contrary to other OHCs, levels of ∑HO-PCBs were significantly higher in dog serum (median=6.0 ng/g lw) than cat serum (median=2.2 ng/g lw). Levels of most OHCs were significantly higher (p<0.05) in cat serum than those found in human serum from the same region, in particular for ∑PBDEs (ranged 1-1280 ng/g lw). Significantly lower levels of OCPs (p<0.05) were detected in dog serum than in human serum. The concentrations of ∑BPs were seven times higher in cat serum (median 112 ng/g lw) than dog serum (median 16 ng/g lw). To the best of our knowledge, this is the first time that NBFRs, e.g. 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), and bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), were detected in cat and dog's hair. BTBPE had the highest detection frequency (30%) in the serum samples. In cat and dog hair samples, the order of importance of OHCs was ∑OCPs>∑NBFRs>∑PBDEs>∑PCB, with the highest concentrations being around 38 ng/g hair. In paired hair-serum cat samples (N=12), ∑DDTs (r=0.65, p=0.001) were significantly correlated, while for all other OHCs no significant correlations (p<0.001) were observed in both cats and dogs. Our findings on both hair and serum samples suggested that pet dogs do not bioaccumulate DDTs. Our results are also in agreement with the hypothesis that pets may serve as biosentinels for indoor pollution. This is the first study to document the presence of OHCs in pets from Pakistan and provides baseline information for future monitoring of OHCs in pets. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-centennial upper-ocean heat content reconstruction using online data assimilation

NASA Astrophysics Data System (ADS)

Perkins, W. A.; Hakim, G. J.

2017-12-01

The Last Millennium Reanalysis (LMR) provides an advanced paleoclimate ensemble data assimilation framework for multi-variate climate field reconstructions over the Common Era. Although reconstructions in this framework with full Earth system models remain prohibitively expensive, recent work has shown improved ensemble reconstruction validation using computationally inexpensive linear inverse models (LIMs). Here we leverage these techniques in pursuit of a new multi-centennial field reconstruction of upper-ocean heat content (OHC), synthesizing model dynamics with observational constraints from proxy records. OHC is an important indicator of internal climate variability and responds to planetary energy imbalances. Therefore, a consistent extension of the OHC record in time will help inform aspects of low-frequency climate variability. We use the Community Climate System Model version 4 (CCSM4) and Max Planck Institute (MPI) last millennium simulations to derive the LIMs, and the PAGES2K v.2.0 proxy database to perform annually resolved reconstructions of upper-OHC, surface air temperature, and wind stress over the last 500 years. Annual OHC reconstructions and uncertainties for both the global mean and regional basins are compared against observational and reanalysis data. We then investigate differences in dynamical behavior at decadal and longer time scales between the reconstruction and simulations in the last-millennium Coupled Model Intercomparison Project version 5 (CMIP5). Preliminary investigation of 1-year forecast skill for an OHC-only LIM shows largely positive spatial grid point local anomaly correlations (LAC) with a global average LAC of 0.37. Compared to 1-year OHC persistence forecast LAC (global average LAC of 0.30), the LIM outperforms the persistence forecasts in the tropical Indo-Pacific region, the equatorial Atlantic, and in certain regions near the Antarctic Circumpolar Current. In other regions, the forecast correlations are less than the persistence case but still positive overall.

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

PubMed

Castelo-Branco, C; Dávila Guardia, J

2015-02-01

The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

Damage to cochlear efferents following AF64A intoxication.

PubMed

Smith, D W; Mount, R J

1993-07-01

Damage to cochlear efferents in chinchillas was assessed using transmission electron microscopy following unilateral treatment with the cholinotoxin ethylcholine mustard aziridinium ion (AF64A). AF64A was diluted in artificial perilymph to concentrations ranging from 0.5 to 100 microM. Survival times ranged from 1 to 12 weeks. At concentrations above 10 microM, widespread damage was noted to efferent fibers within the inner spiral bundle (ISB), tunnel spiral bundle (TSB), tunnel radial fibers (TRF) and efferent terminals at the base of OHCs. This damage included degeneration of fibers and terminals, delamination of mitochondria, vacuolization, and loss of cell membrane. However, at high concentrations, non-specific damage was also noted as thinnings or discontinuities of the membrane of OHCs and afferent fibers. At concentrations between 3 and 10 microM, selective damage was observed to efferent fibers within the ISB, TSB, TRF, and to terminals at the base of the OHCs, with all other structures appearing normal. At concentrations of 0.5 and 1 microM, damage was limited to efferent fibers within the TSB and ISB below the inner hair cells. In general, insult was greatest to middle- and basal-turn efferents, and longer survival times did not produce greater damage to, or loss of, efferents. These data suggest that at low concentrations, AF64A produces a partial yet selective degeneration of cochlear efferents within both the medial and lateral tracts, and that at the lowest concentrations used in these studies, AF64A produces a preferential insult on lateral olivocochlear efferents.

Piezo- and Flexoelectric Membrane Materials Underlie Fast Biological Motors in the Ear

PubMed Central

Breneman, Kathryn D.; Rabbitt, Richard D.

2010-01-01

The mammalian inner ear is remarkably sensitive to quiet sounds, exhibits over 100dB dynamic range, and has the exquisite ability to discriminate closely spaced tones even in the presence of noise. This performance is achieved, in part, through active mechanical amplification of vibrations by sensory hair cells within the inner ear. All hair cells are endowed with a bundle of motile microvilli, stereocilia, located at the apical end of the cell, and the more specialized outer hair cells (OHC’s) are also endowed with somatic electromotility responsible for changes in cell length in response to perturbations in membrane potential. Both hair bundle and somatic motors are known to feed energy into the mechanical vibrations in the inner ear. The biophysical origin and relative significance of the motors remains a subject of intense research. Several biological motors have been identified in hair cells that might underlie the motor(s), including a cousin of the classical ATP driven actin-myosin motor found in skeletal muscle. Hydrolysis of ATP, however, is much too slow to be viable at audio frequencies on a cycle-by-cycle basis. Heuristically, the OHC somatic motor behaves as if the OHC lateral wall membrane were a piezoelectric material and the hair bundle motor behaves as if the plasma membrane were a flexoelectric material. We propose these observations from a continuum materials perspective are literally true. To examine this idea, we formulated mathematical models of the OHC lateral wall “piezoelectric” motor and the more ubiquitous “flexoelectric” hair bundle motor. Plausible biophysical mechanisms underlying piezo- and flexoelectricity were established. Model predictions were compared extensively to the available data. The models were then applied to study the power conversion efficiency of the motors. Results show that the material properties of the complex membranes in hair cells provide them with the ability to convert electrical power available in the inner ear cochlea into useful mechanical amplification of sound induced vibrations at auditory frequencies. We also examined how hair cell amplification might be controlled by the brain through efferent synaptic contacts on hair cells and found a simple mechanism to tune hearing to signals of interest to the listener by electrical control of these motors. PMID:21188296

The Generation of Harmonic Distortion and Distortion Products in a Computational Model of the Cochlea

NASA Astrophysics Data System (ADS)

Meaud, Julien; Li, Yizeng; Grosh, Karl

2011-11-01

It is generally agreed that the nonlinear response of the cochlea is due to the forward transduction of the outer hair cell (OHC) hair bundle (HB) and subsequent alteration of the active force applied to the cochlear structures, including the basilar membrane (BM). A mechanical-acoustical-electrical model of the cochlea with three-dimensional fluid representation, and feedback from OHC somatic motility coupled to nonlinear HB mechanotransduction is used to predict nonlinear distortion of the BM response to acoustic stimulus. An efficient alternating frequency time scheme is implemented to solve for the nonlinear stationary dynamics of the cochlea. The model is used to predict the location of maximum generation of nonlinear distortion during pure tone and two-tone stimulation as well as the propagation of the distortion components on the BM.

Questioning cochlear amplification

NASA Astrophysics Data System (ADS)

van der Heijden, Marcel; Versteegh, Corstiaen P. C.

2015-12-01

Thirty years ago it was hypothesized that motile processes inject mechanical energy into cochlear traveling waves. This mechanical amplification, alternatively described as negative damping, is invoked to explain both the sensitivity and the nonlinear compression of cochlear responses. There is a recent trend to present cochlear amplification as an established fact, even though the evidence is at most circumstantial and several thorny problems have remained unresolved. We analyze several of these issues, and present new basilar membrane recordings that allowed us to quantify cochlear energy flow. Specifically, we address the following questions: (1) Does auditory sensitivity require narrowband amplification? (2) Has the "RC problem" (lowpass filtering of outer hair cell receptor potential) been resolved? (3) Can OHC motility improve auditory sensitivity? (4) Is there a net power gain between neighboring locations on the basilar membrane? The analyses indicate that mechanical amplification in the cochlea is neither necessary nor useful, and that realizing it by known forms of motility would reduce sensitivity rather than enhance it. Finally, our experimental data show that the peaking of the traveling wave is realized by focusing the acoustic energy rather than amplifying it. (Abbreviations. BM: basilar membrane; CF: characteristic frequency; IHC: inner hair cell; ME: middle ear; MT; mechanotransducer; OHC: outer hair cell; SPL: sound pressure level.)

The truly disadvantaged? Midlife outcome dynamics of individuals with experiences of out-of-home care.

PubMed

Brännström, Lars; Forsman, Hilma; Vinnerljung, Bo; Almquist, Ylva B

2017-05-01

Little is known about developmental outcomes in midlife of persons who were placed in out-of-home care (OHC) in childhood. Utilizing longitudinal Swedish data from a cohort of more than 14,000 individuals who we can follow from birth (1953) to the age of 55 (2008), this study examines midlife trajectories of social, economic, and health-related disadvantages with a specific focus on the complexity, timing, and duration of disadvantage in individuals with and without childhood experience of OHC. Roughly half of the OHC alumni did not have disadvantaged outcomes in midlife. However, experience of OHC was associated with a two-fold risk for various forms of permanent disadvantage, net of confounding factors. Implications for research, policy, and practice are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zahn, Karl E.; Averill, April; Wallace, Susan S.

5-Hydroxycytosine (5-OHC) is a stable oxidation product of cytosine associated with an increased frequency of C {yields} T transition mutations. When this lesion escapes recognition by the base excision repair pathway and persists to serve as a templating base during DNA synthesis, replicative DNA polymerases often misincorporate dAMP at the primer terminus, which can lead to fixation of mutations and subsequent disease. To characterize the dynamics of DNA synthesis opposite 5-OHC, we initiated a comparison of unmodified dCMP to 5-OHC, 5-fluorocytosine (5-FC), and 5-methylcytosine (5-MEC) in which these bases act as templates in the active site of RB69 gp43, amore » high-fidelity DNA polymerase sharing homology with human replicative DNA polymerases. This study presents the first crystal structure of any DNA polymerase binding this physiologically important premutagenic DNA lesion, showing that while dGMP is stabilized by 5-OHC through normal Watson-Crick base pairing, incorporation of dAMP leads to unstacking and instability in the template. Furthermore, the electronegativity of the C5 substituent appears to be important in the miscoding potential of these cytosine-like templates. While dAMP is incorporated opposite 5-OHC {approx}5 times more efficiently than opposite unmodified dCMP, an elevated level of incorporation is also observed opposite 5-FC but not 5-MEC. Taken together, these data imply that the nonuniform templating by 5-OHC is due to weakened stacking capabilities, which allows dAMP incorporation to proceed in a manner similar to that observed opposite abasic sites.« less

Neuropsychological study of IQ scores in offspring of parents with bipolar I disorder.

PubMed

Sharma, Aditya; Camilleri, Nigel; Grunze, Heinz; Barron, Evelyn; Le Couteur, James; Close, Andrew; Rushton, Steven; Kelly, Thomas; Ferrier, Ian Nicol; Le Couteur, Ann

2017-01-01

Studies comparing IQ in Offspring of Bipolar Parents (OBP) with Offspring of Healthy Controls (OHC) have reported conflicting findings. They have included OBP with mental health/neurodevelopmental disorders and/or pharmacological treatment which could affect results. This UK study aimed to assess IQ in OBP with no mental health/neurodevelopmental disorder and assess the relationship of sociodemographic variables with IQ. IQ data using the Wechsler Abbreviated Scale of Intelligence (WASI) from 24 OBP and 34 OHC from the North East of England was analysed using mixed-effects modelling. All participants had IQ in the average range. OBP differed statistically significantly from OHC on Full Scale IQ (p = .001), Performance IQ (PIQ) (p = .003) and Verbal IQ (VIQ) (p = .001) but not on the PIQ-VIQ split. OBP and OHC groups did not differ on socio-economic status (SES) and gender. SES made a statistically significant contribution to the variance of IQ scores (p = .001). Using a robust statistical model of analysis, the OBP with no current/past history of mental health/neurodevelopmental disorders had lower IQ scores compared to OHC. This finding should be borne in mind when assessing and recommending interventions for OBP.

Radiation-induced defect centers in glass ceramics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, T.E.; Friebele, E.J.; Griscom, D.L.

1989-01-15

Electron spin resonance (ESR) was used to characterize the radiation-induced defect centers in low-thermal-expansion glass ceramics, including two types of Zerodur and Astrositall. The observed ESR spectra can be associated with different types of defect centers: a Zn/sup +/ center, several types of oxygen hole centers (OHCs), an aluminum-oxygen hole center (Al-OHC), an Fe/sup 3 +/ center, Ti/sup 3 +/ and Zr/sup 3 +/ centers, and three types of As centers. An Sb/sup 4 +/ center, which is not observed in Zerodur, is tentatively identified in Astrositall. From the effect of crystallization on the observed defect concentrations in Zerodur andmore » computer simulation of the spectral lines of some of the centers, we infer that among the nine defect centers observed in the Zerodurs, the As-associated centers are located in the glassy phase and/or at the interface between the glassy and crystalline phases, Zn/sup +/ and Al-OHC are in the crystalline phase, and the rest (including most of the OHCs) are in the glassy phase. Radiation-induced compaction in these materials appears to be related to the generation of OHCs in the glass phase.« less

Primary health care centers, extent of challenges and demand for oral health care in Riyadh, Saudi Arabia.

PubMed

Al-Jaber, Abeer; Da'ar, Omar B

2016-11-04

As primary health care (PHC) centers in Saudi Arabia provide standardized preventive and curative oral health care (OHC) services, challenges remain. In addition, evidence of determinants of OHC seeking behavior is unknown. The aim of this study was to identify common challenges faced by patients seeking OHC in PHC centers and assess determinants of demand for OHC in Riyadh. After institutional approval and piloting, 320 adult patients were sampled at two large PHC centers in October 2015. Using a modified version of General Practice Assessment (GAPQ) and New York State Department of Health (NYSDOH) Questionnaires, information about cumulative number of visits to a dentist, patient profiles, provider characteristics, and challenges were collected. We used descriptive statistics to summarize data and employed ordinal regression for analyzing extent of effects of challenges and determinants of demand for OHC. Oral health condition was reported to be good in 31 % of the patients, very good in 25 % of the patients, and fair in 20 % of the patients. More than half (53 %) of patients visited a dentist in the past 12 months once, 20 % twice, and 25 % at least three times. High cost of private clinic and unavailability of dentists were reported as the most common difficulties in seeing a dentist. Patients who were very satisfied with dental care and treatment plan, those with less than excellent oral health conditions and male patients had less number of cumulative visits to a dentist compared with patients with less satisfaction, patients with perceived excellent oral health, and female patients respectively. Our findings provide a strong evidence of challenges faced by patients and determinants of demand for OHC seeking behavior. The findings can inform policy maker not only in patient satisfaction of OHC, but also implications on facilities and health care systems. We conclude with recommendations for future research, especially on oral health preventive measures in PHC centers that correct inherent dental problems and other underlying challenges.

Full-field initialized decadal predictions with the MPI earth system model: an initial shock in the North Atlantic

NASA Astrophysics Data System (ADS)

Kröger, Jürgen; Pohlmann, Holger; Sienz, Frank; Marotzke, Jochem; Baehr, Johanna; Köhl, Armin; Modali, Kameswarrao; Polkova, Iuliia; Stammer, Detlef; Vamborg, Freja S. E.; Müller, Wolfgang A.

2017-12-01

Our decadal climate prediction system, which is based on the Max-Planck-Institute Earth System Model, is initialized from a coupled assimilation run that utilizes nudging to selected state parameters from reanalyses. We apply full-field nudging in the atmosphere and either full-field or anomaly nudging in the ocean. Full fields from two different ocean reanalyses are considered. This comparison of initialization strategies focuses on the North Atlantic Subpolar Gyre (SPG) region, where the transition from anomaly to full-field nudging reveals large differences in prediction skill for sea surface temperature and ocean heat content (OHC). We show that nudging of temperature and salinity in the ocean modifies OHC and also induces changes in mass and heat transports associated with the ocean flow. In the SPG region, the assimilated OHC signal resembles well OHC from observations, regardless of using full fields or anomalies. The resulting ocean transport, on the other hand, reveals considerable differences between full-field and anomaly nudging. In all assimilation runs, ocean heat transport together with net heat exchange at the surface does not correspond to OHC tendencies, the SPG heat budget is not closed. Discrepancies in the budget in the cases of full-field nudging exceed those in the case of anomaly nudging by a factor of 2-3. The nudging-induced changes in ocean transport continue to be present in the free running hindcasts for up to 5 years, a clear expression of memory in our coupled system. In hindcast mode, on annual to inter-annual scales, ocean heat transport is the dominant driver of SPG OHC. Thus, we ascribe a significant reduction in OHC prediction skill when using full-field instead of anomaly initialization to an initialization shock resulting from the poor initialization of the ocean flow.

Controlling Mitochondrial Dynamics to Mitigate Noise-Induced Hearing Loss

DTIC Science & Technology

2017-10-01

protection against outer hair cell loss at the high frequency responsive region of the organ of Corti was observed. Importantly, these findings demonstrated...a high dose would be detrimental to hearing sensitivity or to outer hair cell viability. The 25 and 100 µM doses were similar to the 50 µM dose in...Completion of outer hair cell counts on the 200 µM study group revealed that this higher dose did not reduce OHC survival in the treated ear

Features of Online Health Communities for Adolescents With Type 1 Diabetes

PubMed Central

Ho, Yun-Xian; O’Connor, Brendan H.; Mulvaney, Shelagh A.

2014-01-01

The aim of this exploratory study was to examine diabetes online health communities (OHCs) available to adolescents with type 1 diabetes (T1D). We sought to identify and classify site features and relate them to evidence-based processes for improving self-management. We reviewed 18 OHCs and identified the following five feature categories: social learning and networking, information, guidance, engagement, and personal health data sharing. While features that have been associated with improved self-management were present, such as social learning, results suggest that more guidance or structure would be helpful to ensure that those processes were focused on promoting positive beliefs and behaviors. Enhancing guidance-related features and structure to existing OHCs could provide greater opportunity for effective diabetes self-management support. To support clinical recommendations, more research is needed to quantitatively relate features and participation in OHCs to patient outcomes. PMID:24473058

Effects of piracetam supplementation on cochlear damage occurring in guinea pigs exposed to irradiation.

PubMed

Altas, Enver; Ertekin, Mustafa Vecdi; Kuduban, Ozan; Gundogdu, Cemal; Demirci, Elif; Sutbeyaz, Yavuz

2006-07-01

In this study we aimed to determine the role of piracetam (PIR) in preventing radiation induced cochlear damage after total-cranium irradiation (radiotherapy; RT). Male albino guinea pigs used in the study were randomly divided into three groups. Group 1 (Control group) (n=11) received neither PIR nor irradiation, but received saline solution intraperitoneally (i.p.) and received sham irradiation. Group 2 (RT group) (n=32) was exposed to total cranium irradiation of 33 Gy in 5 fractions of 6.6 Gy/d for five successive days, with a calculated (alpha/beta=3.5) biological effective dose of fractionated irradiation equal to 60 Gy conventional fractionation, then received saline solution for five successive days i.p. Group 3 (PIR+RT group) (n=33) received total cranium irradiation, plus 350 mg/kg per day PIR for five successive days i.p. After the last dose of RT, the guinea pigs were all sacrificed at the 4th, 24th and 96th hours, respectively. Their cochleas were enucleated for histopathologic examination. It was observed that total cranium irradiation (RT group) promoted degeneration in stria vascularis (SV), spiral ganglion cells (SG), outer hair cells (OHC) and inner hair cell (IHC) of cochleas at these times (p<0.05). While in the PIR+RT group, there was no statistically significant difference on radiation-induced cochlear degeneration in SV and OHC at 4th (p>0.05) and IHC at 4th, 24th hours (p>0.05), there was a significant difference on radiation-induced cochlear degeneration in SV and OHC at 24th and 96th hours (p<0.05), IHC at 96th hour (p<0.05) and SG at 4th, 24th and 96th hours (p<0.05). There was no any cochlear degeneration in the control group. Piracetam might reduce radiation-induced cochlear damage in the guinea pig. These results are pioneer to studies that will be performed with PIR for radiation toxicity protection.

Interaction of Tamoxifen and noise induced damage to the cochlea

PubMed Central

Pillai, Jagan A; Siegel, Jonathan H

2011-01-01

Tamoxifen has been used extensively in the treatment of breast cancer and other neoplasms. In addition to its well-known action on estrogen receptors it is also known to acutely block chloride channels that participate in cell volume regulation. Tamoxifen’s role in preventing cochlear outer hair cell (OHC) swelling in vitro suggested that OHC swelling noted following noise exposure could potentially be a therapeutic target for Tamoxifen in its role as a chloride channel blocker to help prevent noise induced hearing loss. To investigate this possiblity, the effects of exposure to Tamoxifen on physiologic measures of cochlear function in the presence and absence of subsequent noise exposure were studied. Male Mongolian gerbils (2–4 months old) were randomly assigned to different groups. Tamoxifen at ~10 mg/kg was administered to one of the groups. Five hours later they were exposed to a one-third octave band of noise centered at 8 kHz in a sound isolation chamber for 30 minutes at 108dB SPL. Compound action potential (CAP) thresholds and distortion product otoacoustic emission (DPOAE) levels were measured 30–35 days following noise exposure. Tamoxifen administration did not produce any changes in CAP thresholds and DPOAE levels when administered by itself in the absence of noise. Tamoxifen causes a significant increase in CAP thresholds from 8–15 kHz following noise exposure compared to CAP thresholds in animals exposed to noise alone. No significant differences were seen in the DPOAE levels the f2 = 8–15 kHz frequency range where maximum noise-induced increases in CAP thresholds were seen. Contrary to our original expectation, it is concluded that Tamoxifen potentiates the degree of damage to the cochlea resulting from noise exposure. PMID:21907781

A FPGA Implementation of the CAR-FAC Cochlear Model.

PubMed

Xu, Ying; Thakur, Chetan S; Singh, Ram K; Hamilton, Tara Julia; Wang, Runchun M; van Schaik, André

2018-01-01

This paper presents a digital implementation of the Cascade of Asymmetric Resonators with Fast-Acting Compression (CAR-FAC) cochlear model. The CAR part simulates the basilar membrane's (BM) response to sound. The FAC part models the outer hair cell (OHC), the inner hair cell (IHC), and the medial olivocochlear efferent system functions. The FAC feeds back to the CAR by moving the poles and zeros of the CAR resonators automatically. We have implemented a 70-section, 44.1 kHz sampling rate CAR-FAC system on an Altera Cyclone V Field Programmable Gate Array (FPGA) with 18% ALM utilization by using time-multiplexing and pipeline parallelizing techniques and present measurement results here. The fully digital reconfigurable CAR-FAC system is stable, scalable, easy to use, and provides an excellent input stage to more complex machine hearing tasks such as sound localization, sound segregation, speech recognition, and so on.

A FPGA Implementation of the CAR-FAC Cochlear Model

PubMed Central

Xu, Ying; Thakur, Chetan S.; Singh, Ram K.; Hamilton, Tara Julia; Wang, Runchun M.; van Schaik, André

2018-01-01

This paper presents a digital implementation of the Cascade of Asymmetric Resonators with Fast-Acting Compression (CAR-FAC) cochlear model. The CAR part simulates the basilar membrane's (BM) response to sound. The FAC part models the outer hair cell (OHC), the inner hair cell (IHC), and the medial olivocochlear efferent system functions. The FAC feeds back to the CAR by moving the poles and zeros of the CAR resonators automatically. We have implemented a 70-section, 44.1 kHz sampling rate CAR-FAC system on an Altera Cyclone V Field Programmable Gate Array (FPGA) with 18% ALM utilization by using time-multiplexing and pipeline parallelizing techniques and present measurement results here. The fully digital reconfigurable CAR-FAC system is stable, scalable, easy to use, and provides an excellent input stage to more complex machine hearing tasks such as sound localization, sound segregation, speech recognition, and so on. PMID:29692700

A rapid analytical method to quantify complex organohalogen contaminant mixtures in large samples of high lipid mammalian tissues.

PubMed

Desforges, Jean-Pierre; Eulaers, Igor; Periard, Luke; Sonne, Christian; Dietz, Rune; Letcher, Robert J

2017-06-01

In vitro investigations of the health impact of individual chemical compounds have traditionally been used in risk assessments. However, humans and wildlife are exposed to a plethora of potentially harmful chemicals, including organohalogen contaminants (OHCs). An alternative exposure approach to individual or simple mixtures of synthetic OHCs is to isolate the complex mixture present in free-ranging wildlife, often non-destructively sampled from lipid rich adipose. High concentration stock volumes required for in vitro investigations do, however, pose a great analytical challenge to extract sufficient amounts of complex OHC cocktails. Here we describe a novel method to easily, rapidly and efficiently extract an environmentally accumulated and therefore relevant contaminant cocktail from large (10-50 g) marine mammal blubber samples. We demonstrate that lipid freeze-filtration with acetonitrile removes up to 97% of blubber lipids, with minimal effect on the efficiency of OHC recovery. Sample extracts after freeze-filtration were further processed to remove residual trace lipids via high-pressure gel permeation chromatography and solid phase extraction. Average recoveries of OHCs from triplicate analysis of killer whale (Orcinus orca), polar bear (Ursus maritimus) and pilot whale (Globicephala spp.) blubber standard reference material (NIST SRM-1945) ranged from 68 to 80%, 54-92% and 58-145%, respectively, for 13 C-enriched internal standards of six polychlorinated biphenyl congeners, 16 organochlorine pesticides and four brominated flame retardants. This approach to rapidly generate OHC mixtures shows great potential for experimental exposures using complex contaminant mixtures, research or monitoring driven contaminant quantification in biological samples, as well as the untargeted identification of emerging contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Full-field versus anomaly initialization in the MiKlip decadal prediction system

NASA Astrophysics Data System (ADS)

Kröger, Jürgen; Pohlmann, Holger; Sienz, Frank; Marotzke, Jochem; Baehr, Johanna; Köhl, Armin; Kameshvar, Modali; Stammer, Detlef; Vamborg, Freja; Müller, Wolfgang

2017-04-01

We show how ocean initialization from full-fields instead of anomalies in the MiKlip decadal prediction system significantly reduces rediction skill of ocean heat content (OHC) in the northern North Atlantic. The MiKlip prediction system, which is based on the Max-Planck-Institute Earth system model (MPI-ESM), is initialized by assimilating selected state parameters from reanalyses. Here, we apply either full-field or anomaly nudging in the ocean. We apply full fields from two different ocean reanalyses. We show that nudging of temperature and salinity in the ocean modifies OHC and also induces changes in mass and heat transports associated with the Atlantic meridional overturning circulation. In the North Atlantic, the OHC tendencies from the ocean reanalyses are adopted quite well by our forecast system, regardless of using full fields or anomalies. The resulting ocean transport, on the other hand, reveals considerable differences between full-field and anomaly nudging. In the assimilations, the ocean heat transport together with the net heat exchange at the surface does not correspond to the induced OHC tendencies, the heat budget is not closed. Discrepancies in the budget in the cases of full-field nudging exceed those in the case of anomaly nudging by a factor of 2-3. The nudging-induced changes in ocean transport continue to be present in the free running hindcasts, a clear expression of memory in our coupled system. In forecast mode, on annual to inter-annual scales, ocean heat ransport appears to be the dominant driver of North Atlantic OHC. Thus, we ascribe a significant reduction in OHC prediction skill when using full-field instead of anomaly initialization to the poor initialization of the ocean flow.

Knowledge Discovery from Posts in Online Health Communities Using Unified Medical Language System.

PubMed

Chen, Donghua; Zhang, Runtong; Liu, Kecheng; Hou, Lei

2018-06-19

Patient-reported posts in Online Health Communities (OHCs) contain various valuable information that can help establish knowledge-based online support for online patients. However, utilizing these reports to improve online patient services in the absence of appropriate medical and healthcare expert knowledge is difficult. Thus, we propose a comprehensive knowledge discovery method that is based on the Unified Medical Language System for the analysis of narrative posts in OHCs. First, we propose a domain-knowledge support framework for OHCs to provide a basis for post analysis. Second, we develop a Knowledge-Involved Topic Modeling (KI-TM) method to extract and expand explicit knowledge within the text. We propose four metrics, namely, explicit knowledge rate, latent knowledge rate, knowledge correlation rate, and perplexity, for the evaluation of the KI-TM method. Our experimental results indicate that our proposed method outperforms existing methods in terms of providing knowledge support. Our method enhances knowledge support for online patients and can help develop intelligent OHCs in the future.

Ocean Heat Content Reveals Secrets of Fish Migrations

PubMed Central

Luo, Jiangang; Ault, Jerald S.; Shay, Lynn K.; Hoolihan, John P.; Prince, Eric D.; Brown, Craig A.; Rooker, Jay R.

2015-01-01

For centuries, the mechanisms surrounding spatially complex animal migrations have intrigued scientists and the public. We present a new methodology using ocean heat content (OHC), a habitat metric that is normally a fundamental part of hurricane intensity forecasting, to estimate movements and migration of satellite-tagged marine fishes. Previous satellite-tagging research of fishes using archival depth, temperature and light data for geolocations have been too coarse to resolve detailed ocean habitat utilization. We combined tag data with OHC estimated from ocean circulation and transport models in an optimization framework that substantially improved geolocation accuracy over SST-based tracks. The OHC-based movement track provided the first quantitative evidence that many of the tagged highly migratory fishes displayed affinities for ocean fronts and eddies. The OHC method provides a new quantitative tool for studying dynamic use of ocean habitats, migration processes and responses to environmental changes by fishes, and further, improves ocean animal tracking and extends satellite-based animal tracking data for other potential physical, ecological, and fisheries applications. PMID:26484541

Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears

PubMed Central

TØ, Bechshøft; Sonne, C; Dietz, R; Born, EW; Muir, DCG; Letcher, RJ; Novak, MA; Henchey, E; Meyer, JS; Jenssen, BM; Villanger, GD

2012-01-01

The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p′-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis. PMID:22575327

Reproductive performance in East Greenland polar bears (Ursus maritimus) may be affected by organohalogen contaminants as shown by physiologically-based pharmacokinetic (PBPK) modelling.

PubMed

Sonne, Christian; Gustavson, Kim; Rigét, Frank F; Dietz, Rune; Birkved, Morten; Letcher, Robert J; Bossi, Rossana; Vorkamp, Katrin; Born, Erik W; Petersen, Gitte

2009-12-01

Polar bears (Ursus maritimus) feed mainly on ringed seal (Phoca hispida) and consume large quantities of blubber and consequently have one of the highest tissue concentrations of organohalogen contaminants (OHCs) worldwide. In East Greenland, studies of OHC time trends and organ system health effects, including reproductive, were conducted during 1990-2006. However, it has been difficult to determine the nature of the effects induced by OHC exposures on wild caught polar bears using body burden data and associated changes in reproductive organs and systems. We therefore conducted a risk quotient (RQ) evaluation to more quantitatively evaluate the effect risk on reproduction (embryotoxicity and teratogenicity) based on the critical body residue (CBR) concept and using a physiologically-based pharmacokinetic (PBPK) model. We applied modelling approaches to PCBs, p,p'-DDE, dieldrin, oxychlordane, HCHs, HCB, PBDEs and PFOS in East Greenland polar bears based on known OHC pharmacokinetics and dynamics in laboratory rats (Rattus rattus). The results showed that subcutaneous adipose tissue concentrations of dieldrin (range: 79-1271 ng g(-1) lw) and PCBs (range: 4128-53,923 ng g(-1) lw) reported in bears in the year 1990 were in the range to elicit possible adverse health effects on reproduction in polar bears in East Greenland (all RQs > or = 1). Similar results were found for PCBs (range: 1928-17,376 ng g(-1) lw) and PFOS (range: 104-2840 ng g(-1) ww) in the year 2000 and for dieldrin (range: 43-640 ng g(-1) lw), PCBs (range: 3491-13,243 ng g(-1) lw) and PFOS (range: 1332-6160 ng g(-1) ww) in the year 2006. The concentrations of oxychlordane, DDTs, HCB and HCHs in polar bears resulted in RQs<1 and thus appear less likely to be linked to reproductive effects. Furthermore, sumRQs above 1 suggested risk for OHC additive effects. Thus, previous suggestions of possible adverse health effects in polar bears correlated to OHC exposure are supported by the present study. This study also indicates that PBPK models may be a supportive tool in the evaluation of possible OHC-mediated health effects for Arctic wildlife.

[A pilot project of the integration of oro-dental care into the primary health care system in Cameroon].

PubMed

Ngapeth-Etoundi, M; Ekoto, E

2001-06-01

The objective of this work is to analyse the situation of the Oral Health Care (OHC) of the population of operational district health unit in Primary Health Care (PHC) and finally integrate the component of OHC. Indeed in many countries in Africa, the World Health Organisation (WHO), in accord with the countries, have set up the policy of PHC. The agreement is that the component of OHC was neglected for quite sometimes in Cameroon. It's for this reason that a pilot project was initiated as a model so that it would be extended to all districts in this country. The method consist in investigation into the prevalence by means of questionnaire and clinical examination of the population of varied age; 900 persons were examined in the Sangmelina health district in order to master the situation of OHC. Oral dental hygiene: 70.5% of the population had a tooth brush, 79% declared they brush their teeth, The state of periodontal tissue: 75% had debris, 70% calculus, 60.7% gingivitis, The prevalence of caries: 66.9% (91.9% had between 21 and 32 teeth), 44.8% follon teeth, 50.8% of this population needed artificial teeth. The situation of the OHC in the health district of Sangmelina requires an effective prevention, consequently the importance of including this situation in PHC program of the said district.

Plasma 27-hydroxycholesterol/cholesterol ratio is increased in low high density lipoprotein-cholesterol healthy subjects.

PubMed

Nunes, Valéria S; Leança, Camila C; Panzoldo, Natália B; Parra, Eliane; Zago, Vanessa; Cazita, Patrícia M; Nakandakare, Edna R; de Faria, Eliana C; Quintão, Eder C R

2013-10-01

Sterol 27-hydroxylase converts cholesterol to 27-hydroxycholesterol (27-OHC) which is widely distributed among tissues and is expressed at high levels in the vascular endothelium and macrophages. There is a continuous flow of this oxysterol from the tissues into the liver, where it is converted to bile acids. Measure plasma concentrations of 27-OHC in subjects that differ according to their plasma HDL-C concentration. Healthy men presenting low HDL-C (<1.03 mmol/L), n=18 or high HDL-C (>1.55 mmol/L), n=18, BMI<30 kg/m² were recruited after excluding secondary causes that might interfere with their plasma lipid concentrations such as smoking, heavy drinking and diabetes. Blood samples were drawn after a 12h fasting period for the measurement of 27-OHC by the combined GC/MS analysis utilizing deuterium-label internal standards. The plasma ratio 27-OHC/total cholesterol (median and range nmoL/mmoL) was 50.41 (27.47-116.00) in the High HDL-C subjects and 63.34 (36.46-91.18) in the Low HDL-C subjects (p=0.0258). Our data indicate that the production of 27-OHC by extrahepatic tissues and its transport to the liver may represent an alternative pathway for a deficient reverse cholesterol transport system when plasma HDL-C is low. © 2013.

Improved One-Way Hash Chain and Revocation Polynomial-Based Self-Healing Group Key Distribution Schemes in Resource-Constrained Wireless Networks

PubMed Central

Chen, Huifang; Xie, Lei

2014-01-01

Self-healing group key distribution (SGKD) aims to deal with the key distribution problem over an unreliable wireless network. In this paper, we investigate the SGKD issue in resource-constrained wireless networks. We propose two improved SGKD schemes using the one-way hash chain (OHC) and the revocation polynomial (RP), the OHC&RP-SGKD schemes. In the proposed OHC&RP-SGKD schemes, by introducing the unique session identifier and binding the joining time with the capability of recovering previous session keys, the problem of the collusion attack between revoked users and new joined users in existing hash chain-based SGKD schemes is resolved. Moreover, novel methods for utilizing the one-way hash chain and constructing the personal secret, the revocation polynomial and the key updating broadcast packet are presented. Hence, the proposed OHC&RP-SGKD schemes eliminate the limitation of the maximum allowed number of revoked users on the maximum allowed number of sessions, increase the maximum allowed number of revoked/colluding users, and reduce the redundancy in the key updating broadcast packet. Performance analysis and simulation results show that the proposed OHC&RP-SGKD schemes are practical for resource-constrained wireless networks in bad environments, where a strong collusion attack resistance is required and many users could be revoked. PMID:25529204

Low-frequency sound affects active micromechanics in the human inner ear

PubMed Central

Kugler, Kathrin; Wiegrebe, Lutz; Grothe, Benedikt; Kössl, Manfred; Gürkov, Robert; Krause, Eike; Drexl, Markus

2014-01-01

Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing. PMID:26064536

High-titer production and strong antimicrobial activity of sophorolipids from Rhodotorula bogoriensis

USDA-ARS?s Scientific Manuscript database

Rhodotorula bogoriensis produces sophorolipids (SLs) that contain 13-hydroxydocosanoic acid (OH-C22) as the lipid moiety. A systematic study was conducted to further understand the fermentative production of SLs containing OH-C22 (C22-SL) by R. bogoriensis. Shake-flask studies showed that R. bogor...

Modeling Scala Media as a Pressure Vessel

NASA Astrophysics Data System (ADS)

Lepage, Eric; Olofsson, A.˚Ke

2011-11-01

The clinical condition known as endolymphatic hydrops is the swelling of scala media and may result in loss in hearing sensitivity consistent with other forms of low-frequency biasing. Because outer hair cells (OHCs) are displacement-sensitive and hearing levels tend to be preserved despite large changes in blood pressure and CSF pressure, it seems unlikely that the OHC respond passively to changes in static pressures in the chambers. This suggests the operation of a major feedback control loop which jointly regulates homeostasis and hearing sensitivity. Therefore the internal forces affecting the cochlear signal processing amplifier cannot be just motile responses. A complete account of the cochlear amplifier must include static pressures. To this end we have added a third, pressure vessel to our 1-D 140-segment, wave-digital filter active model of cochlear mechanics, incorporating the usual nonlinear forward transduction. In each segment the instantaneous pressure is the sum of acoustic pressure and global static pressure. The object of the model is to maintain stable OHC operating point despite any global rise in pressure in the third chamber. Such accumulated pressure is allowed to dissipate exponentially. In this first 3-chamber implementation we explore the possibility that acoustic pressures are rectified. The behavior of the model is critically dependent upon scaling factors and time-constants, yet by initial assumption, the pressure tends to accumulate in proportion to sound level. We further explore setting of the control parameters so that the accumulated pressure either stays within limits or may rise without bound.

Comparison of imaging biomarkers for Alzheimer's disease: amyloid imaging with [18F]florbetapir positron emission tomography and magnetic resonance imaging voxel-based analysis for entorhinal cortex atrophy.

PubMed

Tateno, Amane; Sakayori, Takeshi; Kawashima, Yoshitaka; Higuchi, Makoto; Suhara, Tetsuya; Mizumura, Sunao; Mintun, Mark A; Skovronsky, Daniel M; Honjo, Kazuyoshi; Ishihara, Keiichi; Kumita, Shinichiro; Suzuki, Hidenori; Okubo, Yoshiro

2015-05-01

We compared amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) in subjects clinically diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI), and older healthy controls (OHC) in order to test how these imaging biomarkers represent cognitive decline in AD. Fifteen OHC, 19 patients with MCI, and 19 patients with AD were examined by [(18)F]florbetapir PET to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI and the voxel-based specific regional analysis system for AD to calculate z-score as the degree of entorhinal cortex atrophy, and by mini-mental state examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive component--Japanese version (ADAS-Jcog) for cognitive functions. Both cutoff values for measuring AD-like levels of amyloid (1.099 for SUVR) and entorhinal cortex atrophy (1.60 for z-score) were well differentially diagnosed and clinically defined AD from OHC (84.2% for SUVR and 86.7% for z-score). Subgroup analysis based on beta-amyloid positivity revealed that z-score significantly correlated with MMSE (r = -0.626, p < 0.01) and ADAS-Jcog (r = 0.691, p < 0.01) only among subjects with beta-amyloid. This is the first study to compare [(18)F]florbetapir PET and MRI voxel-based analysis of entorhinal cortex atrophy for AD. Both [(18)F]florbetapir PET and MRI detected changes in AD compared with OHC. Considering that entorhinal cortex atrophy correlated well with cognitive decline only among subjects with beta-amyloid, [18F]florbetapir PET makes it possible to detect AD pathology in the early stage, whereas MRI morphometry for subjects with beta-amyloid provides a good biomarker to assess the severity of AD in the later stage. Copyright © 2014 John Wiley & Sons, Ltd.

Building trusting relationships in online health communities.

PubMed

Zhao, Jing; Ha, Sejin; Widdows, Richard

2013-09-01

This study investigates consumers' use of online health communities (OHCs) for healthcare from a relationship building perspective based on the commitment-trust theory of relationships. The study proposes that perspective taking, empathic concern, self-efficacy, and network density affect the development of both cognitive and affective trust, which together determine OHC members' membership continuance intention (MCI) and knowledge contribution. Data collected from eight existing OHCs (N=255) were utilized to test the hypothesized model. Results show that perspective taking and self-efficacy can increase cognitive trust and affective trust, respectively. Network density contributes to cognitive and affective trust. Both cognitive trust and affective trust influence MCI, while only affective trust impacts members' knowledge contribution behaviors.

EFFECTS OF PREDNISOLONE AND TRIAMCINOLONE ON CORTICOSTEROID LEVELS IN PAROTID FLUID, SERUM, AND URINE.

DTIC Science & Technology

A simultaneous determination was made of 17-OHCS in serum, urine, and parotid fluid, by the Porter-Silber reaction, after the oral administration of...prednisolone, triamcinolone, or placebo to 240 normal human subjects. The data clearly demonstrate the homology of serum and parotid fluid 17-OHCS

Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears.

PubMed

Bechshøft, T Ø; Sonne, C; Dietz, R; Born, E W; Muir, D C G; Letcher, R J; Novak, M A; Henchey, E; Meyer, J S; Jenssen, B M; Villanger, G D

2012-07-01

The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p'-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis. Copyright © 2012 Elsevier Inc. All rights reserved.

Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears.

PubMed

Bentzen, T W; Muir, D C G; Amstrup, S C; O'Hara, T M

2008-11-15

We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. SigmaChlordane concentrations were higher in females, and both SigmaPCBs and SigmaChlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; SigmaPCB>Sigma10PCB>PCB153>SigmaChlordane>Oxychlordane>PCB180>SigmaHCH>beta-HCH>SigmaDDT>p,p-DDE>SigmaPBDE>HCB>Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited.

Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears

USGS Publications Warehouse

Bentzen, T.W.; Muir, D.C.G.; Amstrup, Steven C.; O'Hara, T. M.

2008-01-01

We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. ??Chlordane concentrations were higher in females, and both ??PCBs and ??Chlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; ??PCB > ??10PCB > PCB153 > ??Chlordane > Oxychlordane > PCB180 > ??HCH > ??-HCH > ??DDT > p,p-DDE > ??PBDE > HCB > Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited. ?? 2008 Elsevier B.V.

D-METHIONINE REDUCES TOBRAMYCIN-INDUCED OTOTOXICITY WITHOUT ANTIMICROBIAL INTERFERENCE IN ANIMAL MODELS

PubMed Central

Fox, Daniel J.; Cooper, Morris D.; Speil, Cristian A.; Roberts, Melissa H.; Yanik, Susan C.; Meech, Robert P.; Hargrove, Tim L.; Verhulst, Steven J.; Rybak, Leonard P.; Campbell, Kathleen C. M.

2015-01-01

Background Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested D-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Methods Auditory brainstem responses (ABR) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of D-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic E. coli murine survival and intraperitoneal lavage bacterial counts. Results D-methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20 kHz in the 420 mg/kg/day group. In vitro studies did not detect D-methionine-induced antimicrobial interference. In vivo studies did not detect D-methionine-induced interference in normal or neutropenic mice. Conclusions D-methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest D-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients. PMID:26166286

Fabrications of some kinds of 2-D frameworks consisting of nanosized polyoxomolybdate anion [Mo 36O 112(H 2O) 16] 8- via condensation processes

NASA Astrophysics Data System (ADS)

Eda, Kazuo; Iriki, Yuichi; Kawamura, Kenjiro; Ikuki, Takeshi; Hayashi, Masahiko

2007-12-01

We succeeded to prepare novel [Mo 36O 112(H 2O) 16] 8- ({Mo 36}) compounds by using 1,3-diamino-2-propanol ( βOHC 3-DA) and 1,3,5-tris(aminomethyl)benzene (MES-TA)+1,3-diaminopropane (C 3-DA) as linkers, and determined their crystal structures. We have confirmed they have unique two-dimensional (2-D) molybdenum oxide frameworks, which are formed by condensation of {Mo 36}s. Side-staggered arrays of {Mo 36}s, connected in lying position by eight bridges per a {Mo 36}, are formed in the compound with βOHC 3-DA, while herringbone arrays of {Mo 36}s, connected in standing position by four bridges per a {Mo 36}, are built in the compound with MES-TA+C 3-DA. The latter compound exhibited non-stoichiometric property, and its composition and cell parameters varied depending on the relative concentration of MES-TA in the mother solution.

d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.

PubMed

Fox, Daniel J; Cooper, Morris D; Speil, Cristian A; Roberts, Melissa H; Yanik, Susan C; Meech, Robert P; Hargrove, Tim L; Verhulst, Steven J; Rybak, Leonard P; Campbell, Kathleen C M

2016-07-01

Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested d-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of d-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts. d-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20kHz in the 420mg/kg/day group. In vitro studies did not detect d-methionine-induced antimicrobial interference. In vivo studies did not detect d-methionine-induced interference in normal or neutropenic mice. d-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest d-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients. Published by Elsevier B.V.

Formation of organobromine and organoiodine compounds by engineered TiO2 nanoparticle-induced photohalogenation of dissolved organic matter in environmental waters.

PubMed

Hao, Zhineng; Yin, Yongguang; Wang, Juan; Cao, Dong; Liu, Jingfu

2018-08-01

There are increasing concerns about the adverse effects of released engineered nanoparticles and photochemically formed organohalogen compounds (OHCs) on human health and the environment. Herein, we report that titanium dioxide nanoparticles (TiO 2 NPs) can photocatalytically halogenate dissolved organic matter (DOM) to form a large number of organobromine compounds (OBCs) and organoiodine compounds (OICs), as characterized by negative ion electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. Compared with no OHCs produced in control samples in darkness and/or without TiO 2 NPs under sunlight irradiation, various OBCs and OICs were detected in freshwater and seawater under sunlight irradiation for 12h and 24h even in the presence of 1mgL -1 TiO 2 NPs, indicating the photocatalytic roles TiO 2 NPs played in DOM halogenation. Furthermore, TiO 2 NPs could result in the photodegradation of newly formed OHCs, as evidenced by the intensity and the number of some OHCs decreased with reaction time. In addition, many TiO 2 NP-induced OBCs contained two or three bromine atoms, and/or nitrogen and sulfur elements, belonging to lignin-like, tannin-like, unsaturated hydrocarbon and aliphatic compounds. While the OICs were primarily contained one iodine, and very few consisted of nitrogen and sulfur elements, most were lignin-like and tannin-like compounds. Finally, the OBCs in freshwater were found to be formed mainly via a substitution reaction or addition reaction and were accompanied by other reactions such as photooxidation, while the OBCs in seawater and OICs were formed primarily via substitution reactions. Given the abundance of produced OHCs and their toxicity, our findings call for further studies on the exact structure and toxicity of the formed OHCs, taking account the TiO 2 NP-induced DOM photohalogenation in aquatic environments during the evaluation of the environmental effects of engineered TiO 2 NPs. Copyright © 2018 Elsevier B.V. All rights reserved.

Lessons Learned for Online Health Community Moderator Roles: A Mixed-Methods Study of Moderators Resigning From WebMD Communities

PubMed Central

Marmor, Rebecca; Jiang, Xiaoqian

2016-01-01

Background Online health community (OHC) moderators help facilitate conversations and provide information to members. However, the necessity of the moderator in helping members achieve goals by providing the support they need remains unclear, with some prior research suggesting that moderation is unnecessary or even harmful for close-knit OHCs. Similarly, members’ perceptions of moderator roles are underexplored. Starting January of 2013, WebMD moderators stopped working for WebMD communities. This event provided an opportunity for us to study the perceived role of moderators in OHCs. Objective We examine the OHC members’ perception on OHC moderators by studying their reactions toward the departure of moderators in their communities. We also analyzed the relative posting activity on OHCs before and after the departure of moderators from the communities among all members and those who discussed moderators’ departures. Methods We applied a mixed-methods approach to study the posts of all 55 moderated WebMD communities by querying the terms relating to discussions surrounding moderators’ disappearance from the WebMD community. We performed open and axial coding and affinity diagramming to thematically analyze patients’ reactions to the disappeared moderators. The number of posts and poster groups (members and moderators) were analyzed over time to understand posting patterns around moderators’ departure. Results Of 821 posts retrieved under 95 threads, a total of 166 open codes were generated. The codes were then grouped into 2 main themes with 6 total subthemes. First, patients attempted to understand why moderators had left and what could be done to fill the void left by the missing moderators. During these discussions, the posts revealed that patients believed that moderators played critical roles in the communities by making the communities vibrant and healthy, finding solutions, and giving medical information. Some patients felt personally attached with moderators, expressing they would cease their community participation. On the other hand, patients also indicated that moderators were not useful or sometimes even harmful for peer interactions. The overall communities’ posting activity, which was already in decline, showed no significant difference before and after the moderators’ departure. In fact, the overall posting activities of the communities were declining well before the moderators’ departure. These declining posting activities might be the reason why WebMD removed the moderators. Conclusion Compassionate moderators who provide medical expertise, control destructive member posts, and help answer questions can provide important support for patient engagement in OHCs. Moderators are in general received positively by community members and do not appear to interfere with peer interactions. Members are well aware of the possibility of misinformation spreading in OHCs. Further investigation into the attitudes of less vocal community members should be conducted. PMID:27608721

Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

PubMed Central

Borse, Vikrant; Al Aameri, Raheem F H; Sheehan, Kelly; Sheth, Sandeep; Kaur, Tejbeer; Mukherjea, Debashree; Tupal, Srinivasan; Lowy, Michelle; Ghosh, Sumana; Dhukhwa, Asmita; Bhatta, Puspanjali; Rybak, Leonard P; Ramkumar, Vickram

2017-01-01

Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent. Rats administered oral EGCG demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the basal region of the cochlea and reduced oxidative stress and apoptotic markers. EGCG also protected against the loss of ribbon synapses associated with inner hair cells and Na+/K+ ATPase α1 in the stria vascularis and spiral ligament. In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity, but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio appears critical for mediating its otoprotection. EGCG did not alter cisplatin-induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy in a xenograft tumor model in mice because of its inability to rescue the downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal otoprotective agent for treating cisplatin-induced hearing loss without compromising its antitumor efficacy. PMID:28703809

Inner Ear Gene Transfection in Neonatal Mice Using Adeno-Associated Viral Vector: A Comparison of Two Approaches

PubMed Central

Xia, Li; Yin, Shankai; Wang, Jian

2012-01-01

Local gene transfection is a promising technique for the prevention and/or correction of inner ear diseases, particularly those resulting from genetic defects. Adeno-associated virus (AAV) is an ideal viral vector for inner ear gene transfection because of its safety, stability, long-lasting expression, and its high tropism for many different cell types. Recently, a new generation of AAV vectors with a tyrosine mutation (mut-AAV) has demonstrated significant improvement in transfection efficiency. A method for inner ear gene transfection via the intact round window membrane (RWM) has been developed in our laboratory. This method has not been tested in neonatal mice, an important species for the study of inherited hearing loss. Following a preliminary study to optimize the experimental protocol in order to reduce mortality, the present study investigated inner ear gene transfection in mice at postnatal day 7. We compared transfection efficiency, the safety of the scala tympani injection via RWM puncture, and the trans-RWM diffusion following partial digestion with an enzyme technique. The results revealed that approximately 47% of inner hair cells (IHCs) and 17% of outer hair cells (OHCs) were transfected via the trans-RWM approach. Transfection efficiency via RWM puncture (58% and 19% for IHCs and OHCs, respectively) was slightly higher, but the difference was not significant. PMID:22912830

Role of oxygen hole centres in the photodarkening of ytterbium-doped phosphosilicate fibre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rybaltovsky, A A; Bobkov, K K; Likhachev, M E

2013-11-30

We have studied the photodarkening in active fibres with an ytterbium-doped phosphosilicate glass core under IR irradiation with a pump source (920 nm) and UV irradiation (193 nm). Analysis of absorption and luminescence spectra suggests that such irradiations produce phosphorus – oxygen – hole centres (P-OHCs) in the core glass network and lead to the reduction of the ytterbium ions to a divalent state (Yb{sup 2+}). The photoinduced optical loss in the fibres in the visible range (400 – 700 nm) is mainly due to absorption by the P-OHCs. A quantum-mechanical model is proposed for P-OHC and Yb{sup 2+} formation.more » (nonlinear optical phenomena)« less

Streptococcus pneumoniae-induced ototoxicity in organ of Corti explant cultures.

PubMed

Perny, Michael; Solyga, Magdalena; Grandgirard, Denis; Roccio, Marta; Leib, Stephen L; Senn, Pascal

2017-07-01

Hearing loss remains the most common long-term complication of pneumococcal meningitis (PM) reported in up to 30% of survivors. Streptococcus pneumoniae have been shown to possess different ototoxic properties. Here we present a novel ex vivo experimental setup to examine in detail the pattern of hair cell loss upon exposure to different S. pneumoniae strains, therefore recapitulating pathogen derived aspects of PM-induced hearing loss. Our results show a higher susceptibility towards S. pneumoniae-induced cochlear damage for outer hair cells (OHC) compared to inner hair cells (IHC), which is consistent with in vivo data. S. pneumoniae-induced hair cell loss was both time and dose-dependent. Moreover, we have found significant differences in the level of cell damage between tissue from the basal and the apical turns. This shows that the higher vulnerability of hair cells located at high frequency regions observed in vivo cannot be explained solely by the spatial organisation and bacterial infiltration from the basal portion of the cochlea. Using a wild type D39 strain and a mutant defective for the pneumolysin (PLY) gene, we also have shown that the toxin PLY is an important factor involved in ototoxic damages. The obtained results indicate that PLY can cause both IHC and OHC loss. Finally, we are reporting here for the first time a higher vulnerability of HC located at the basal and middle cochlear region to pneumolysin-induced damage. The detailed description of the susceptibility of hair cells to Streptococcus pneumoniae provided in this report can in the future determine the choice and the development of novel otoprotective therapies during pneumococcal meningitis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Northern North Atlantic Sea Surface Height and Ocean Heat Content Variability

NASA Technical Reports Server (NTRS)

Hakkinen, Sirpa; Rhines, Peter; Worthen, Denise L.

2013-01-01

The evolution of nearly 20 years of altimetric sea surface height (SSH) is investigated to understand its association with decadal to multidecadal variability of the North Atlantic heat content. Altimetric SSH is dominated by an increase of about 14 cm in the Labrador and Irminger seas from 1993 to 2011, while the opposite has occurred over the Gulf Stream region over the same time period. During the altimeter period the observed 0-700 m ocean heat content (OHC) in the subpolar gyre mirrors the increased SSH by its dominantly positive trend. Over a longer period, 1955-2011, fluctuations in the subpolar OHC reflect Atlantic multidecadal variability (AMV) and can be attributed to advection driven by the wind stress ''gyre mode'' bringing more subtropical waters into the subpolar gyre. The extended subpolar warming evident in SSH and OHC during the altimeter period represents transition of the AMV from cold to warm phase. In addition to the dominant trend, the first empirical orthogonal function SSH time series shows an abrupt change 2009-2010 reaching a new minimum in 2010. The change coincides with the change in the meridional overturning circulation at 26.5N as observed by the RAPID (Rapid Climate Change) project, and with extreme behavior of the wind stress gyre mode and of atmospheric blocking. While the general relationship between northern warming and Atlantic meridional overturning circulation (AMOC) volume transport remains undetermined, the meridional heat and salt transport carried by AMOC's arteries are rich with decade-to-century timescale variability.

Observed and simulated full-depth ocean heat-content changes for 1970–2005

DOE PAGES

Cheng, Lijing; Trenberth, Kevin E.; Palmer, Matthew D.; ...

2016-07-26

Greenhouse-gas emissions have created a planetary energy imbalance that is primarily manifested by increasing ocean heat content (OHC). Updated observational estimates of full-depth OHC change since 1970 are presented that account for recent advancements in reducing observation errors and biases. The full-depth OHC has increased by 0.74 [0.68, 0.80]  ×  10 22 J yr −1 (0.46 Wm −2) and 1.22 [1.16–1.29]  ×  10 22 J yr −1 (0.75 Wm −2) for 1970–2005 and 1992–2005, respectively, with a 5 to 95 % confidence interval of the median. The CMIP5 models show large spread in OHC changes, suggesting that some models are not state-of-the-art and require further improvements. However, the ensemble median hasmore » excellent agreement with our observational estimate: 0.68 [0.54–0.82]  ×  10 22 J yr −1 (0.42 Wm −2) from 1970 to 2005 and 1.25 [1.10–1.41]  ×  10 22 J yr −1 (0.77 Wm −2) from 1992 to 2005. These results increase confidence in both the observational and model estimates to quantify and study changes in Earth's energy imbalance over the historical period. We suggest that OHC be a fundamental metric for climate model validation and evaluation, especially for forced changes (decadal timescales).« less

Cochlear partition tuning within the 2nd apical turn of the intact gerbil cochlea

NASA Astrophysics Data System (ADS)

Dong, Wei; Xia, Anping; Puria, Sunil; Applegate, Brian E.; Oghalai, John S.

2018-05-01

Our understanding of cochlear amplification has been mainly informed by observations of the high-frequency basal region. Results from the few existing in vivo studies from the low-frequency apical region have suggested that cochlear amplification may be more broadly tuned and not as nonlinear as in the base. The current study explored micromechanics via sound evoked vibrations of the cochlear partition, including the organ of Corti (OoC), the basilar membrane (BM) and the tectorial membrane (TM), within the 2nd apical turn, corresponding to the 2.5 kHz best frequency region, of the gerbil cochlea using volumetric optical coherence tomography vibrometry (VOCTV), imaged non-invasively through the otic capsule bone in vivo. Sound induced radial displacements below 4 kHz showed similarities and differences to the well-established BM transverse responses at high-frequency basal region. Responses showed broader tuning, but similar gains at the best frequency and similar phase accumulation. The distinct difference found was the presence of compressive nonlinear growth with SPL below the best frequency down to 0.1 kHz observed at the outer hair cell (OHC) and reticular laminar (RL) locations but not in the BM or inner hair cell regions. These relative motions provide further insight on how OHC somatic forces are distributed within the cochlear partition.

OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, Wenbin; Zhou, You; Li, Jiwei

We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpressionmore » resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle.« less

l-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro.

PubMed

Tillinger, Joshua A; Gupta, Chhavi; Ila, Kadri; Ahmed, Jamal; Mittal, Jeenu; Van De Water, Thomas R; Eshraghi, Adrien A

2018-08-01

The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined. Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed. l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001). l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

Spray ignition measurements in a constant volume combustion vessel under engine-relevant conditions

NASA Astrophysics Data System (ADS)

Ramesh, Varun

Pressure-based and optical diagnostics for ignition delay (ID) measurement of a diesel spray from a multi-hole nozzle were investigated in a constant volume combustion vessel (CVCV) at conditions similar to those in a conventional diesel engine at the start of injection (SOI). It was first hypothesized that compared to an engine, the shorter ID in a CVCV was caused by NO, a byproduct of premixed combustion. The presence of a significant concentration of NO+NO2 was confirmed experimentally and by using a multi-zone model of premixed combustion. Experiments measuring the effect of NO on ID were performed at conditions relevant to a conventional diesel engine. Depending on the temperature regime and the nature of the fuel, NO addition was found to advance or retard ignition. Constant volume ignition simulations were capable of describing the observed trends; the magnitudes were different due to the physical processes involved in spray ignition, not modeled in the current study. The results of the study showed that ID is sensitive to low NO concentrations (<100 PPM) in the low-temperature regime. A second source of uncertainty in pressure-based ID measurement is the systematic error associated with the correction used to account for the speed of sound. Simultaneous measurements of volumetric OH chemiluminescence (OHC) and pressure during spray ignition found the OHC to closely resemble the pressure-based heat release rate for the full combustion duration. The start of OHC was always found to be shorter than the pressure-based ID for all fuels and conditions tested by 100 ms. Experiments were also conducted measuring the location and timing of high-temperature ignition and the steady-state lift-off length by high-speed imaging of OHC during spray ignition. The delay period calculated using the measured ignition location and the bulk average speed of sound was in agreement with the delay between OHC and the pressure-based ID. Results of the study show that start of OHC is coupled to detectable heat release and the two measurements are correlated by the time required for the pressure wave to propagate at the speed of sound between the ignition site and the transducer.

Exposure to mixtures of organohalogen contaminants and associative interactions with thyroid hormones in East Greenland polar bears (Ursus maritimus).

PubMed

Villanger, Gro D; Jenssen, Bjørn M; Fjeldberg, Rita R; Letcher, Robert J; Muir, Derek C G; Kirkegaard, Maja; Sonne, Christian; Dietz, Rune

2011-05-01

We investigated the multivariate relationships between adipose tissue residue levels of 48 individual organohalogen contaminants (OHCs) and circulating thyroid hormone (TH) levels in polar bears (Ursus maritimus) from East Greenland (1999-2001, n=62), using projection to latent structure (PLS) regression for four groupings of polar bears; subadults (SubA), adult females with cubs (AdF_N), adult females without cubs (AdF_S) and adult males (AdM). In the resulting significant PLS models for SubA, AdF_N and AdF_S, some OHCs were especially important in explaining variations in circulating TH levels: polybrominated diphenylether (PBDE)-99, PBDE-100, PBDE-153, polychlorinated biphenyl (PCB)-52, PCB-118, cis-nonachlor, trans-nonachlor, trichlorobenzene (TCB) and pentachlorobenzene (QCB), and both negative and positive relationships with THs were found. In addition, the models revealed that DDTs had a positive influence on total 3,5,3'-triiodothyronine (TT3) in AdF_S, and that a group of 17 higher chlorinated ortho-PCBs had a positive influence on total 3,5,3',5'-tetraiodothyronine (thyroxine, TT4) in AdF_N. TH levels in AdM seemed less influenced by OHCs because of non-significant PLS models. TH levels were also influenced by biological factors such as age, sex, body size, lipid content of adipose tissue and sampling date. When controlling for biological variables, the major relationships from the PLS models for SubA, AdF_N and AdF_S were found significant in partial correlations. The most important OHCs that influenced TH levels in the significant PLS models may potentially act through similar mechanisms on the hypothalamic-pituitary-thyroid (HPT) axis, suggesting that both combined effects by dose and response addition and perhaps synergistic potentiation may be a possibility in these polar bears. Statistical associations are not evidence per se of biological cause-effect relationships. Still, the results of the present study indicate that OHCs may affect circulating TH levels in East Greenland polar bears, adding to the "weight of evidence" suggesting that OHCs might interfere with thyroid homeostasis in polar bears. Copyright © 2011 Elsevier Ltd. All rights reserved.

Disruptive effects of persistent organohalogen contaminants on thyroid function in white whales (Delphinapterus leucas) from Svalbard.

PubMed

Villanger, G D; Lydersen, C; Kovacs, K M; Lie, E; Skaare, J U; Jenssen, B M

2011-06-01

We analysed levels of 56 organohalogen contaminants (OHCs) including brominated flame retardants, polychlorinated biphenyls (PCBs), and organochlorine pesticides in the blubber of white (beluga) whales (Delphinapterus leucas) from Svalbard, Norway (N=12; 6 adults [5 males and 1 female] and 6 subadults [4 males and 2 females]) collected in 1996-2001. We also measured circulating levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) in the whales. The results confirm that OHC levels in these white whales are among the highest levels recorded in wildlife from Svalbard, and at the high end of the range when compared to white whales from the North American Arctic. A projection to latent structure (PLS) model (subadults and adult males grouped together) revealed that known or suspected thyroid disruptive contaminants (polybrominated diphenylether [PBDE]-28, -47, -99, -100, and -154, hexachlorobenzene [HCB], and PCB-105) were negatively correlated with circulating levels of total thyroxin (TT4), free T4 (FT4) and free triiodothyronine (FT3). Most of these negative relationships were also confirmed using partial correlations controlling for length (and thus age) of the whales. The positive correlations of TT4, FT4 and FT3 with hexabromocyclododecane (HBCD), α-hexachlorocyclohexane (α-HCH), chlorinated bornanes CHB-40 and CHB-62 revealed by the PLS model were not confirmed by partial correlations. TH levels in the present study appeared to be somewhat lower than levels measured in beluga whales from the Canadian Arctic. However, we were not able to determine if this was caused by different levels of OHCs, or differences in biological factors (e.g. age, sex, moulting status, and season) and analytical methods between the studies. Although the sample sizes were low and statistical models cannot depict the biological cause-effect relationships, this study suggests negative influences of specific OHCs, particularly PBDEs, on thyroid hormone levels in white whales. The impact this might have on individual and population health is unknown. Copyright © 2011 Elsevier B.V. All rights reserved.

Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea pigs.

PubMed

Zhou, Y; Zheng, H; Ruan, F; Chen, X; Zheng, G; Kang, M; Zhang, Q; Sun, X

2012-05-03

To examine the efficiency of hydrogen-rich saline in the treatment of intensive noise-induced cochlear injury. Forty guinea pigs were assigned to one of four groups: HS+NOISE (i.p. injection hydrogen-rich saline), NS+NOISE (i.p. injection normal saline), NOISE ALONE (noise control), and NO TREATMENT (normal control) groups. The HS+NOISE, NS+NOISE, and NOISE ALONE groups were exposed to intensive noise (4 h at 115 dB SPL noise of 4000±100 Hz). The auditory brainstem response (ABR) was used to examine the hearing threshold in each group. Distortion product otoacoustic emission (DPOAE) was used to examine outer hair cell function. We also examined cochlear morphology to evaluate inner and outer hair cell trauma induced by noise exposure. Hydrogen-rich saline was administered twice daily for 6 days (2.5 ml/kg, i.p.) 24 h after noise exposure. Baseline ABR thresholds and DPOAE values were normal in all groups at the measured frequencies (2, 4, 8, and 16 kHz) before noise exposure. The ABR threshold shift was 50-55 dB across the frequencies tested, and average DPOAE declined in the NOISE ALONE, NS+NOISE, and HS+NOISE groups 24 h after noise exposure. However, the changes in cochlear parameters were different between groups. The HS+NOISE group showed a significantly decreased ABR threshold value as compared with the NS+NOISE or NOISE ALONE group (P<0.01) on day 7. The mean DPOAE recovered to some extent in the three noise exposure groups, but at most frequencies the HS+NOISE group showed significantly increased DPOAE on day 7 as compared with the NS+NOISE group or NOISE ALONE group (P<0.01). Surface Corti organ preparations stained with succinate dehydrogenase (SDH) showed that most outer hair cells (OHCs) were still dropsical and a few were missing 7 days after noise exposure in the NS+NOISE group. Only a few OHCs were slightly dropsical in the HS+NOISE group. The numbers of missing hair cells 7 days after noise exposure were significantly greater in the NOISE ONLY and NS+NOISE groups than the HS+NOISE group (P<0.01). Hydrogen-rich saline can alleviate experimental noise-induced hearing loss in guinea pigs, partially by preventing the death of cochlear hair cells after intensive noise exposure. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Comparative fate of organohalogen contaminants in two top carnivores in Greenland: captive sledge dogs and wild polar bears.

PubMed

Verreault, Jonathan; Dietz, Rune; Sonne, Christian; Gebbink, Wouter A; Shahmiri, Soheila; Letcher, Robert J

2008-04-01

The limited knowledge and/or the inability to control physiological condition parameters that influence the fate of organohalogen contaminants (OHCs) has been the foremost confounding aspect in monitoring programs and health risk assessments of wild top predators in the Arctic such as the polar bear (Ursus maritimus). In the present comparative study, we used a potential surrogate Canoidea species for the East Greenland polar bear, the captive sledge dog (Canis familiaris), to investigate some factors that may influence the bioaccumulation and biotransformation of major chlorinated and brominated OHCs in adipose tissue and blood (plasma) of control (fed commercial pork fat) and exposed (fed West Greenland minke whale (Balaenoptera acutorostrata) blubber) adult female sledge dogs. Furthermore, we compared the patterns and concentrations of OHCs and their known or suggested hydroxylated (OH) metabolites (e.g., OH-PCBs) in sledge dogs with those in adipose tissue and blood (plasma) of East Greenland adult female polar bears, and blubber of their main prey species, the ringed seal (Pusa hispida). The two-year feeding regime conducted with sledge dogs led to marked differences in overall adipose tissue (and plasma) OHC residue accumulation between the control and exposed groups. Characteristic prey-to-predator OHC bioaccumulation dynamics for major PCB and PBDE congeners (patterns and concentrations) and biotransformation capacity with respect to PCB metabolite formation and OH-PCB retention distinguished, to some extent, captive sledge dogs and wild polar bears. Based on the present findings, we conclude that the use of surrogate species in toxicological investigations for species in the Canoidea family should be done with great caution, although they remain essential in the context of contaminants research with sensitive arctic top carnivore species such as the polar bear.

ENSO-driven energy budget perturbations in observations and CMIP models

DOE PAGES

Mayer, Michael; Fasullo, John T.; Trenberth, Kevin E.; ...

2016-03-19

Various observation-based datasets are employed to robustly quantify changes in ocean heat content (OHC), anomalous ocean–atmosphere energy exchanges and atmospheric energy transports during El Niño-Southern Oscillation (ENSO). These results are used as a benchmark to evaluate the energy pathways during ENSO as simulated by coupled climate model runs from the CMIP3 and CMIP5 archives. The models are able to qualitatively reproduce observed patterns of ENSO-related energy budget variability to some degree, but key aspects are seriously biased. Area-averaged tropical Pacific OHC variability associated with ENSO is greatly underestimated by all models because of strongly biased responses of net radiation atmore » top-of-the-atmosphere to ENSO. The latter are related to biases of mean convective activity in the models and project on surface energy fluxes in the eastern Pacific Intertropical Convergence Zone region. Moreover, models underestimate horizontal and vertical OHC redistribution in association with the generally too weak Bjerknes feedback, leading to a modeled ENSO affecting a too shallow layer of the Pacific. Vertical links between SST and OHC variability are too weak even in models driven with observed winds, indicating shortcomings of the ocean models. Furthermore, modeled teleconnections as measured by tropical Atlantic OHC variability are too weak and the tropical zonal mean ENSO signal is strongly underestimated or even completely missing in most of the considered models. In conclusion, results suggest that attempts to infer insight about climate sensitivity from ENSO-related variability are likely to be hampered by biases in ENSO in CMIP simulations that do not bear a clear link to future changes.« less

IHC-TM connect-disconnect in relation to sensitization and masking of a HF-tone burst by a LF tone. IV.

PubMed

Crane, H D

1982-05-01

Evidence continues to accumulate that although the outer hair cells (OHCs) of the cochlea are firmly bonded to the tectorial membrane (TM), the inner hair cells (IHCS) are not. This is the fourth in a series of papers that explores how the idea of a set of disconnected hair cells that "impact" the TM is consistent with psychophysical data. The paper extends the exploration to the masking of high-frequency (HF) tone bursts by low-frequency (LF) tones and shows that the model can explain the important features of these complex data.

Allicin protects auditory hair cells and spiral ganglion neurons from cisplatin - Induced apoptosis.

PubMed

Wu, Xianmin; Li, Xiaofei; Song, Yongdong; Li, He; Bai, Xiaohui; Liu, Wenwen; Han, Yuechen; Xu, Lei; Li, Jianfeng; Zhang, Daogong; Wang, Haibo; Fan, Zhaomin

2017-04-01

Cisplatin is a broad-spectrum anticancer drug that is commonly used in the clinic. Ototoxicity is one of the major side effects of this drug, which caused irreversible sensorineural hearing loss. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-apoptotic and anti-oxidative activities in vitro and in vivo studies. We took advantage of C57 mice intraperitoneally injected with cisplatin alone or with cisplatin and allicin combined, to investigate whether allicin plays a protective role in vivo against cisplatin ototoxicity. The result showed that C57 mice in cisplatin group exhibited increased shift in auditory brainstem response, whereas the auditory fuction of mice in allicin + cisplatin group was protected in most frequencies, which was accordance with observed damages of outer hair cells (OHCs) and spiral ganglion neurons (SGNs) in the cochlea. Allicin markedly protected SGN mitochondria from damage and releasing cytochrome c, and significantly reduced pro-apoptosis factor expressions activated by cisplatin, including Bax, cleaved-caspase-9, cleaved-caspase-3and p53. Furthermore, allicin reduced the level of Malondialdehyde (MDA), but increased the level of superoxide dismutase (SOD). All data suggested that allicin could prevent hearing loss induced by cisplatin effectively, of which allicin protected SGNs from apoptosis via mitochondrial pathway while protected OHCs and supporting cells (SCs) from apoptosis through p53 pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Construction and phenotypic characterization of M68, an RruI quorum sensing knockout mutant of the photosynthetic alphaproteobacterium Rhodospirillum rubrum.

PubMed

Condori, Sandra; Atkinson, Steve; Leys, Natalie; Wattiez, Ruddy; Mastroleo, Felice

2016-06-01

Many bacterial species communicate using a complex system known as quorum sensing (QS) in which gene expression is controlled in response to cell density. In this study an N-acylhomoserine lactone (AHL) synthase (Rru_A3396) knockout mutant (M68) of Rhodospirillum rubrum S1H (WT) was constructed and characterized phenotypically under light anaerobic conditions. Results showed that R. rubrum WT produces unsubstituted, 3-OH and 3-oxo-substituted AHLs with acyl chains ranging from 4 to 14 carbons, with 3-OH-C8 being the most abundant. Growth, pigment content and swimming motility were found to be under the control of this LuxI-type QS system. In addition, cultivation in a low shear environment put forward the aggregative phenotype of M68 and linked biofilm formation to QS in R. rubrum S1H. Interestingly, QS-mutant M68 continued to produce decreased levels of 3-OH-C8-HSL, probably due to the presence of an extra HdtS-type AHL synthase. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Biochemical and chemical characterization of pink-pigmented oxidative bacteria.

PubMed Central

Wallace, P L; Hollis, D G; Weaver, R E; Moss, C W

1990-01-01

The biochemical and chemical characteristics were determined for 156 clinical isolates of pink-pigmented bacteria that are similar to but distinct from Methylobacterium extorquens (synonymous with Pseudomonas mesophilica). These isolates were gram-negative, nonfermentative, usually nonvacuolated, coccoid rods; all grew at 35 degrees C and were catalase and urease positive; the majority grew on MacConkey agar and were variable for oxidase production and motility. On the basis of oxidation of xylose and mannitol and hydrolysis of esculin, these 156 strains were subdivided into four groups that were designated "pink coccoid" groups I, II, III, and IV. Groups I, II, and III are similar to an unnamed taxon described by Gilardi and Faur in 1984; only strains of group IV hydrolyze esculin. The cellular fatty acid compositions of strains of groups I, II, and III were essentially identical and differed from strains of group IV by the absence of 3-OH-C14:0 and the presence of C19:0 delta and 2-OH-C19:0 delta. The fatty acid composition of group IV strains was most similar to that of M. extorquens but differed by the presence of small amounts of two C17:1 acids, 3-OH-C16:0, and 2-OH-C18:1. PMID:2332467

Biochemical and chemical characterization of pink-pigmented oxidative bacteria.

PubMed

Wallace, P L; Hollis, D G; Weaver, R E; Moss, C W

1990-04-01

The biochemical and chemical characteristics were determined for 156 clinical isolates of pink-pigmented bacteria that are similar to but distinct from Methylobacterium extorquens (synonymous with Pseudomonas mesophilica). These isolates were gram-negative, nonfermentative, usually nonvacuolated, coccoid rods; all grew at 35 degrees C and were catalase and urease positive; the majority grew on MacConkey agar and were variable for oxidase production and motility. On the basis of oxidation of xylose and mannitol and hydrolysis of esculin, these 156 strains were subdivided into four groups that were designated "pink coccoid" groups I, II, III, and IV. Groups I, II, and III are similar to an unnamed taxon described by Gilardi and Faur in 1984; only strains of group IV hydrolyze esculin. The cellular fatty acid compositions of strains of groups I, II, and III were essentially identical and differed from strains of group IV by the absence of 3-OH-C14:0 and the presence of C19:0 delta and 2-OH-C19:0 delta. The fatty acid composition of group IV strains was most similar to that of M. extorquens but differed by the presence of small amounts of two C17:1 acids, 3-OH-C16:0, and 2-OH-C18:1.

Ill Literates or Illiterates? Investigating the eHealth Literacy of Users of Online Health Communities

PubMed Central

Atanasova, Sara; Kamin, Tanja

2017-01-01

Background Electronic health (eHealth) literacy is an important skill that allows patients to navigate intelligibly through the vast, often misleading Web-based world. Although eHealth literacy has been investigated in general and specific demographic populations, it has not yet been analyzed on users of online health communities (OHCs). Evidence shows that OHCs are important Web 2.0 applications for patients for managing their health, but at the same time, warnings have been expressed regarding the quality and relevance of shared information. No studies exist that investigate levels of eHealth literacy among users of OHCs and differences in eHealth literacy between different types of users. Objective The study aimed to investigate eHealth literacy across different types of users of OHCs based on a revised and extended eHealth literacy scale (eHEALS). Methods The study was based on a cross-sectional Web survey on a simple random sample of 15,000 registered users of the most popular general OHC in Slovenia. The final sample comprised 644 users of the studied OHC. An extended eHEALS (eHEALS-E) was tested with factor analytical procedures, whereas user types were identified with a hierarchical clustering algorithm. The research question was analyzed with analysis of variance (ANOVA) procedure and pairwise comparison tests. Results Factor analysis of the revised and extended eHEALS revealed six dimensions: awareness of sources, recognizing quality and meaning, understanding information, perceived efficiency, validating information, and being smart on the Net. The factor solution demonstrates a good fit to the data (root mean square error of approximation [RMSEA]=.059). The most developed dimension of eHEALS-E is awareness of different Internet sources (mean=3.98, standard deviation [SD]=0.61), whereas the least developed is understanding information (mean=3.11, SD=0.75). Clustering resulted in four user types: active help-seekers (48.3%, 311/644), lurkers (31.8%, 205/644), core relational users (16.9%, 109/644), and low-engaged users (3%, 19/644). Analysis of the research question showed statistically significant differences among user types across all six dimensions of eHEALS-E. Most notably, core relational users performed worse than lurkers on the validating information dimension (P=.01) and worse than active help-seekers on the being smart on the Net dimension (P=.05). Active help-seekers have the highest scores in all dimensions of the eHEALS-E, whereas low-engaged users have statistically significantly lower scores on all dimensions of the eHEALS-E in comparison with the other groups. Conclusions Those who are looking for advice and support in OHCs by making queries are well equipped with eHealth literacy skills to filter potential misinformation and detect bad advice. However, core relational users (who produce the most content in OHCs) have less-developed skills for cross-validating the information obtained and navigating successfully through the perils of the online world. Site managers should monitor their activity to avoid the spread of misinformation that might lead to unhealthy practices. PMID:28978496

Ill Literates or Illiterates? Investigating the eHealth Literacy of Users of Online Health Communities.

PubMed

Petrič, Gregor; Atanasova, Sara; Kamin, Tanja

2017-10-04

Electronic health (eHealth) literacy is an important skill that allows patients to navigate intelligibly through the vast, often misleading Web-based world. Although eHealth literacy has been investigated in general and specific demographic populations, it has not yet been analyzed on users of online health communities (OHCs). Evidence shows that OHCs are important Web 2.0 applications for patients for managing their health, but at the same time, warnings have been expressed regarding the quality and relevance of shared information. No studies exist that investigate levels of eHealth literacy among users of OHCs and differences in eHealth literacy between different types of users. The study aimed to investigate eHealth literacy across different types of users of OHCs based on a revised and extended eHealth literacy scale (eHEALS). The study was based on a cross-sectional Web survey on a simple random sample of 15,000 registered users of the most popular general OHC in Slovenia. The final sample comprised 644 users of the studied OHC. An extended eHEALS (eHEALS-E) was tested with factor analytical procedures, whereas user types were identified with a hierarchical clustering algorithm. The research question was analyzed with analysis of variance (ANOVA) procedure and pairwise comparison tests. Factor analysis of the revised and extended eHEALS revealed six dimensions: awareness of sources, recognizing quality and meaning, understanding information, perceived efficiency, validating information, and being smart on the Net. The factor solution demonstrates a good fit to the data (root mean square error of approximation [RMSEA]=.059). The most developed dimension of eHEALS-E is awareness of different Internet sources (mean=3.98, standard deviation [SD]=0.61), whereas the least developed is understanding information (mean=3.11, SD=0.75). Clustering resulted in four user types: active help-seekers (48.3%, 311/644), lurkers (31.8%, 205/644), core relational users (16.9%, 109/644), and low-engaged users (3%, 19/644). Analysis of the research question showed statistically significant differences among user types across all six dimensions of eHEALS-E. Most notably, core relational users performed worse than lurkers on the validating information dimension (P=.01) and worse than active help-seekers on the being smart on the Net dimension (P=.05). Active help-seekers have the highest scores in all dimensions of the eHEALS-E, whereas low-engaged users have statistically significantly lower scores on all dimensions of the eHEALS-E in comparison with the other groups. Those who are looking for advice and support in OHCs by making queries are well equipped with eHealth literacy skills to filter potential misinformation and detect bad advice. However, core relational users (who produce the most content in OHCs) have less-developed skills for cross-validating the information obtained and navigating successfully through the perils of the online world. Site managers should monitor their activity to avoid the spread of misinformation that might lead to unhealthy practices. ©Gregor Petrič, Sara Atanasova, Tanja Kamin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.10.2017.

Effect of tamoxifen on cholesterol synthesis in HepG2 cells and cultured rat hepatocytes.

PubMed

Holleran, A L; Lindenthal, B; Aldaghlas, T A; Kelleher, J K

1998-12-01

The objective of this study was to investigate the mechanisms by which tamoxifen modifies cholesterol metabolism in cellular models of liver metabolism, HepG2 cells and rat hepatocytes. The effect of tamoxifen on cholesterol and triglyceride-palmitate synthesis was measured using isotopomer spectral analysis (ISA) and gas chromatography-mass spectrometry (GC-MS) and compared with the effects of progesterone, estradiol, the antiestrogen ICI 182,780, and an oxysterol, 25-hydroxycholesterol (25OHC). Cholesterol synthesis in cells incubated in the presence of either [1-(13)C]acetate, [U-13C]glucose, or [4,5-(13)C]mevalonate for 48 hours was reduced in the presence of 10 micromol/L tamoxifen and 12.4 micromol/L 25OHC in both HepG2 cells and rat hepatocytes. The ISA methodology allowed a clear distinction between effects on synthesis and effects on precursor enrichment, and indicated that these compounds did not affect enrichment of the precursors of squalene. Progesterone was effective in both cell types at 30 micromol/L and only in HepG2 cells at 10 micromol/L. Estradiol and ICI 182,780 at 10 micromol/L did not inhibit cholesterol synthesis. None of the compounds altered the synthesis of triglyceride-palmitate in either cell type. Treatment of cells with tamoxifen produced accumulation of three sterol precursors of cholesterol, zymosterol, desmosterol, and delta8 cholesterol. This pattern of precursors indicates inhibition of delta24,25 reduction in addition to the previously described inhibition of delta8 isomerase. We conclude that tamoxifen is an effective inhibitor of the conversion of lanosterol to cholesterol in cellular models at concentrations comparable to those present in the plasma of tamoxifen-treated individuals. Our findings indicate that this mechanism may contribute to the effect of tamoxifen in reducing plasma cholesterol in humans.

Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic.

PubMed

Dietz, Rune; Gustavson, Kim; Sonne, Christian; Desforges, Jean-Pierre; Rigét, Frank F; Pavlova, Viola; McKinney, Melissa A; Letcher, Robert J

2015-07-01

Polar bears (Ursus maritimus) consume large quantities of seal blubber and other high trophic marine mammals and consequently have some of the highest tissue concentrations of organohalogen contaminants (OHCs) among Arctic biota. In the present paper we carried out a risk quotient (RQ) evaluation on OHC-exposed polar bears harvested from 1999 to 2008 and from 11 circumpolar subpopulations spanning from Alaska to Svalbard in order to evaluate the risk of OHC-mediated reproductive effects (embryotoxicity, teratogenicity), immunotoxicity and carcinogenicity (genotoxicity). This RQ evaluation was based on the Critical Body Residue (CBR) concept and a Physiologically-Based Pharmacokinetic Modelling (PBPK) approach using OHC concentrations measured in polar bear adipose or liver tissue. The range of OHC concentrations within polar bear populations were as follows for adipose, sum polychlorinated biphenyls ∑PCBs (1797-10,537 ng/g lw), sum methylsulphone-PCB ∑MeSO2-PCBs (110-672 ng/g lw), sum chlordanes ∑CHLs (765-3477 ng/g lw), α-hexachlorocyclohexane α-HCH (8.5-91.3 ng/g lw), β-hexachlorocyclohexane β-HCH (65.5-542 ng/g lw), sum chlorbenzenes ∑ClBzs (145-304 ng/g lw), dichlorodiphenyltrichloroethane ∑DDTs (31.5-206 ng/g lw), dieldrin (69-249 ng/g lw), polybrominated diphenyl ethers ∑PBDEs (4.6-78.4 ng/g lw). For liver, the perfluorooctanesulfonic acid (PFOS) concentrations ranged from 231-2792 ng/g ww. The total additive RQ from all OHCs ranged from 4.3 in Alaska to 28.6 in East Greenland bears for effects on reproduction, immune health and carcinogenicity, highlighting the important result that the toxic effect threshold (i.e. RQ>1) was exceeded for all polar bear populations assessed. PCBs were the main contributors for all three effect categories, contributing from 70.6% to 94.3% of the total risk and a RQ between 3.8-22.5. ∑MeSO2-PCBs were the second highest effect contributor for reproductive and immunological effects (0.17

High-Frequency Vibration of the Organ of Corti in Vitro

NASA Astrophysics Data System (ADS)

Scherer, M. P.; Nowotny, M.; Dalhoff, E.; Zenner, H.-P.; Gummer, A. W.

2003-02-01

The mechanism by which the electromechanical force generated by the outer hair cells (OHC) produces the exquisite sensitivity, frequency selectivity and dynamic range of the cochlea is unknown. To address this question, we measured the electrically induced radial vibration pattern at different levels within the organ of Corti of the guinea pig. Two in vitro preparations were used: 1) a half turn including modiolar bone and cochlear partition, without tectorial membrane (TM); the basilar membrane (BM) was supported from its tympanal side. 2) A temporal bone preparation, where the bony wall was removed above and below the measurement location to permit introduction of electrodes. In the latter case, the cochlear partition was in its normal mechanical environment, with free swinging BM and with TM. Velocity of BM, reticular lamina (RL), and upper and lower sides of the TM in response to broadband electrical stimulation of the OHCs was measured with a laser Doppler vibrometer. The interferometer was sensitive enough to permit measurement without reflective beads or the like. The frequency range of the stimulation was 480 Hz - 70 kHz. Displacement amplitudes were constant up to 10 kHz, after which they dropped with -14 to -17 dB/oct. Moving across the RL in the radial direction, phase reversals characteristic of pivoting points occurred above the pillar cells and the outer tunnel. No phase reversals were observed on the BM and TM.

Effects of Type 2 Diabetes Mellitus in Patients on Treatment With Glibenclamide and Metformin on Carvedilol Enantiomers Metabolism.

PubMed

Nardotto, Glauco H B; Coelho, Eduardo B; Paiva, Carlos E; Lanchote, Vera L

2017-06-01

Carvedilol is available in clinical practice as a racemate in which (S)-(-)-carvedilol is a β- and α 1 -adrenergic antagonist and (R)-(+)-carvedilol is only an α 1 -adrenergic antagonist. Carvedilol is mainly metabolized by glucuronidation, by CYP2D6 to hydroxyphenylcarvedilol (OHC), and by CYP2C9 to O-desmethylcarvedilol (DMC). This study evaluated the pharmacokinetics of carvedilol enantiomers and their metabolites OHC and DMC in healthy volunteers (n = 13) and in type 2 diabetes mellitus patients with good glycemic control (n = 13). The healthy subjects were enrolled to receive either a 25-mg oral single dose of carvedilol alone (no DDI) or carvedilol simultaneously with 5 mg glibenclamide and 500 mg metformin (DDI), whereas type 2 diabetes mellitus patients who were on long-term treatment with glibenclamide (5 mg/8 h) and metformin (500 mg/8 h) were enrolled to receive only a single oral dose of 25 mg carvedilol. The plasma concentrations of the (R)-(+)-carvedilol, (R)-(+)-DMC, and (R)-(+)-OHC were higher than those of (S)-(-)-carvedilol, (S)-(-)-DMC, and (S)-(-)-OHC in all investigated groups. The pharmacokinetics of the carvedilol enantiomers did not differ between the groups. However, the AUC values of the DMC enantiomers were lower in the type 2 diabetes mellitus patients than in the healthy volunteers (DDI and no DDI) [(R)-(+), 6.9, 10.4, 11.9 ng·h/mL; and (S)-(-), 2.4, 4.3, 4.0 ng·h/mL, respectively]. In contrast, the AUC values of the OHC enantiomers were higher in the type 2 diabetes mellitus patients [(R)-(+), 13.9, 6.6, 4.9 ng·h/mL; and (S)-(-), 7.2, 1.5, 1.5 ng·h/mL], which explains the fact that the carvedilol pharmacokinetics was unchanged. © 2017, The American College of Clinical Pharmacology.

PAROTID FLUID CORTICOSTEROID RESPONSE IN NORMAL SUBJECTS DURING SINGLE-DOSE DEXAMETHASONE SUPPRESSION TESTS.

DTIC Science & Technology

Serum and parotid 17-OHCS measurements were carried out on 6 healthy young adult males during a control week and during a second week in which single...hours after dexamethasone dosage the serum steroid mean decreased by 84.6% and the decrease in parotid fluid concentration was 76.6%. The highly...significant suppression of the level of 17-OHCS in serum was proportionately reflected in the steroid response in parotid fluid. These results suggest that

Organ of Corti Micromechanics with Local Electrical Stimulation

NASA Astrophysics Data System (ADS)

Chen, Fangyi; Zheng, Jiefu; Choudhury, Niloy; Jaques, Steve; Nuttall, Alfred L.

2009-02-01

Optical low coherence interferometry is able to both image and measure the vibration of the cellular and non-cellular structures of the organ of Corti in vivo. In this study we applied an electric current to the basal turn from a pair of electrodes, one in scala tympani and the other in scala vestibuli, at the location corresponding to ~17 kHz when interferometry measurements were made. The coherence gate of the interferometer was positioned 1) at the basilar membrane (BM) near the radial location of the outer hair cells (OHCs) (approximately 1/2 the width of the BM) and 2) at the reticular lamina (RL) where the OHCs are located. We confirmed that electrical stimulation with a frequency sweep (12 kHz -25 kHz) caused a mechanical BM displacement with a peak and a traveling wave-like phase delay as we reported previously using laser Doppler velocimetry and reflective beads on the BM. Reflective beads were not used in the current study. The vibration of the RL had little or no phase delay that would characterize a traveling wave. These data suggest a very high compliance system for the electrically activated cellular structure of the organ.

Ocean heat content variability and change in an ensemble of ocean reanalyses

NASA Astrophysics Data System (ADS)

Palmer, M. D.; Roberts, C. D.; Balmaseda, M.; Chang, Y.-S.; Chepurin, G.; Ferry, N.; Fujii, Y.; Good, S. A.; Guinehut, S.; Haines, K.; Hernandez, F.; Köhl, A.; Lee, T.; Martin, M. J.; Masina, S.; Masuda, S.; Peterson, K. A.; Storto, A.; Toyoda, T.; Valdivieso, M.; Vernieres, G.; Wang, O.; Xue, Y.

2017-08-01

Accurate knowledge of the location and magnitude of ocean heat content (OHC) variability and change is essential for understanding the processes that govern decadal variations in surface temperature, quantifying changes in the planetary energy budget, and developing constraints on the transient climate response to external forcings. We present an overview of the temporal and spatial characteristics of OHC variability and change as represented by an ensemble of dynamical and statistical ocean reanalyses (ORAs). Spatial maps of the 0-300 m layer show large regions of the Pacific and Indian Oceans where the interannual variability of the ensemble mean exceeds ensemble spread, indicating that OHC variations are well-constrained by the available observations over the period 1993-2009. At deeper levels, the ORAs are less well-constrained by observations with the largest differences across the ensemble mostly associated with areas of high eddy kinetic energy, such as the Southern Ocean and boundary current regions. Spatial patterns of OHC change for the period 1997-2009 show good agreement in the upper 300 m and are characterized by a strong dipole pattern in the Pacific Ocean. There is less agreement in the patterns of change at deeper levels, potentially linked to differences in the representation of ocean dynamics, such as water mass formation processes. However, the Atlantic and Southern Oceans are regions in which many ORAs show widespread warming below 700 m over the period 1997-2009. Annual time series of global and hemispheric OHC change for 0-700 m show the largest spread for the data sparse Southern Hemisphere and a number of ORAs seem to be subject to large initialization `shock' over the first few years. In agreement with previous studies, a number of ORAs exhibit enhanced ocean heat uptake below 300 and 700 m during the mid-1990s or early 2000s. The ORA ensemble mean (±1 standard deviation) of rolling 5-year trends in full-depth OHC shows a relatively steady heat uptake of approximately 0.9 ± 0.8 W m-2 (expressed relative to Earth's surface area) between 1995 and 2002, which reduces to about 0.2 ± 0.6 W m-2 between 2004 and 2006, in qualitative agreement with recent analysis of Earth's energy imbalance. There is a marked reduction in the ensemble spread of OHC trends below 300 m as the Argo profiling float observations become available in the early 2000s. In general, we suggest that ORAs should be treated with caution when employed to understand past ocean warming trends—especially when considering the deeper ocean where there is little in the way of observational constraints. The current work emphasizes the need to better observe the deep ocean, both for providing observational constraints for future ocean state estimation efforts and also to develop improved models and data assimilation methods.

Antimicrobial Efficacy of Octenidine Hydrochloride and Calcium Hydroxide with and Without a Carrier: A Broth Dilution Analysis.

PubMed

Varghese, Vinaya Susan; Uppin, Veerendra; Bhat, Kishore; Pujar, Madhu; Hooli, Amruta B; Kurian, Nirmal

2018-01-01

An efficient antimicrobial agent action is required for a predetermined time period for absolute elimination of root canal microbes. Till date, there is limited or no data on the antimicrobial effect of octenidine as an intracanal medicament with chitosan (CTS) as a carrier against Candida albicans and Enterococcus faecalis . The aim of this microbiological study was to compare the antimicrobial efficacy of octenidine hydrochloride (OHC) and calcium hydroxide (Ca[OH] 2 ) as intracanal medicaments, both independently and along with CTS as a carrier molecule against the common resistant endodontic pathogens. A total of 160 single-rooted anterior teeth were selected, root canal preparation was done, and teeth were divided into two groups and contaminated with C. albicans and E. faecalis , which were further divided into four test groups each according to intracanal medicaments used. CTS was used as a vehicle for OHC and Ca(OH) 2 and antimicrobial assessment was performed on day 2 and day 7 following broth dilution method. Dentine samples were collected after each time interval, and the number of colony-forming units was determined. All four medicaments used in this study showed antifungal and antibacterial activity that diminished from day 2 to day 7. Group I (OHC alone) and Group IV (Ca[OH] 2 alone) showed significant antimicrobial activity against C. albicans and E. faecalis , respectively, than the other groups. A combination of OHC + CTS and Ca(OH) 2 + CTS produced inferior results than that of the medicaments used alone.

Processing Robustness for A Phenylethynyl Terminated Polyimide Composite

NASA Technical Reports Server (NTRS)

Hou, Tan-Hung

2004-01-01

The processability of a phenylethynyl terminated imide resin matrix (designated as PETI-5) composite is investigated. Unidirectional prepregs are made by coating an N-methylpyrrolidone solution of the amide acid oligomer (designated as PETAA-5/NMP) onto unsized IM7 fibers. Two batches of prepregs are used: one is made by NASA in-house, and the other is from an industrial source. The composite processing robustness is investigated with respect to the prepreg shelf life, the effect of B-staging conditions, and the optimal processing window. Prepreg rheology and open hole compression (OHC) strengths are found not to be affected by prolonged (i.e., up to 60 days) ambient storage. Rheological measurements indicate that the PETAA-5/NMP processability is only slightly affected over a wide range of B-stage temperatures from 250 deg C to 300 deg C. The OHC strength values are statistically indistinguishable among laminates consolidated using various B-staging conditions. An optimal processing window is established by means of the response surface methodology. IM7/PETAA-5/NMP prepreg is more sensitive to consolidation temperature than to pressure. A good consolidation is achievable at 371 deg C (700 deg F)/100 Psi, which yields an RT OHC strength of 62 Ksi. However, processability declines dramatically at temperatures below 350 deg C (662 deg F), as evidenced by the OHC strength values. The processability of the IM7/LARC(TM) PETI-5 prepreg was found to be robust.

Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults.

PubMed

Petersen, Maria Skaalum; Halling, Jónrit; Damkier, Per; Nielsen, Flemming; Grandjean, Philippe; Weihe, Pál; Brøsen, Kim

2007-10-15

The CYP3A4 enzyme is, along with other cytochrome P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(o-chlorophenyl), 2-(p'-chlorophenyl)ethane (o,p'-DDT) and 1,1,-dichloro-2,2-bis (p-chlorophenyl)ethene (p,p'-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18-60 years, the CYP3A4 activity was determined based on the urinary 6beta-hydroxycortisol/cortisol (6beta-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6beta-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6beta-OHC/FC ratio than men (p=0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6beta-OHC/FC ratios and summation PCB, PCB-TEQ and p,p'-DDE, o,p'-DDT and HCB, respectively, but the associations were statistically significant for men only.

Impact of solar vs. volcanic activity variations on tropospheric temperatures and precipitation during the Dalton Minimum

NASA Astrophysics Data System (ADS)

Anet, J. G.; Muthers, S.; Rozanov, E. V.; Raible, C. C.; Stenke, A.; Shapiro, A. I.; Brönnimann, S.; Arfeuille, F.; Brugnara, Y.; Beer, J.; Steinhilber, F.; Schmutz, W.; Peter, T.

2013-11-01

The aim of this work is to elucidate the impact of changes in solar irradiance and energetic particles vs. volcanic eruptions on tropospheric global climate during the Dalton Minimum (DM, 1780-1840 AD). Separate variations in the (i) solar irradiance in the UV-C with wavelengths λ < 250 nm, (ii) irradiance at wavelengths λ > 250 nm, (iii) in energetic particle spectrum, and (iv) volcanic aerosol forcing were analyzed separately, and (v) in combination, by means of small ensemble calculations using a coupled atmosphere-ocean chemistry-climate-model. Global and hemispheric mean surface temperatures show a significant dependence on solar irradiance at λ > 250 nm. Also, powerful volcanic eruptions in 1809, 1815, 1831 and 1835 significantly decrease global mean temperature by up to 0.5 K for 2-3 yr after the eruption. However, while the volcanic effect is clearly discernible in the southern hemispheric mean temperature, it is less significant in the Northern Hemisphere, partly because the two largest volcanic eruptions occurred in the SH tropics and during seasons when the aerosols were mainly transported southward, partly because of the higher northern internal variability. In the simulation including all forcings, temperatures are in reasonable agreement with the tree-ring-based temperature anomalies of the Northern Hemisphere. Interestingly, the model suggests that solar irradiance changes at λ < 250 nm and in energetic particle spectra have only insignificant impact on the climate during the Dalton Minimum. This downscales the importance of top-down processes (stemming from changes at λ < 250 nm) relative to bottom-up processes (from λ > 250 nm). Reduction of irradiance at λ > 250 nm leads to a significant (up to 2%) decrease of the ocean heat content (OHC) between the 0 and 300 m of depth, whereas the changes in irradiance at λ < 250 nm or in energetic particle have virtually no effect. Also, volcanic aerosol yields a very strong response, reducing the OHC of the upper ocean by up to 1.5%. In the simulation with all forcings, the OHC of the uppermost levels recovers after 8-15 yr after volcanic eruption, while the solar signal and the different volcanic eruptions dominate the OHC changes in the deeper ocean and prevent its recovery during the DM. Finally, the simulations suggest that the volcanic eruptions during the DM had a significant impact on the precipitation patterns caused by a widening of the Hadley cell and a shift of the intertropical convergence zone.

Impact of solar versus volcanic activity variations on tropospheric temperatures and precipitation during the Dalton Minimum

NASA Astrophysics Data System (ADS)

Anet, J. G.; Muthers, S.; Rozanov, E. V.; Raible, C. C.; Stenke, A.; Shapiro, A. I.; Brönnimann, S.; Arfeuille, F.; Brugnara, Y.; Beer, J.; Steinhilber, F.; Schmutz, W.; Peter, T.

2014-05-01

The aim of this work is to elucidate the impact of changes in solar irradiance and energetic particles versus volcanic eruptions on tropospheric global climate during the Dalton Minimum (DM, AD 1780-1840). Separate variations in the (i) solar irradiance in the UV-C with wavelengths λ < 250 nm, (ii) irradiance at wavelengths λ > 250 nm, (iii) in energetic particle spectrum, and (iv) volcanic aerosol forcing were analyzed separately, and (v) in combination, by means of small ensemble calculations using a coupled atmosphere-ocean chemistry-climate model. Global and hemispheric mean surface temperatures show a significant dependence on solar irradiance at λ > 250 nm. Also, powerful volcanic eruptions in 1809, 1815, 1831 and 1835 significantly decreased global mean temperature by up to 0.5 K for 2-3 years after the eruption. However, while the volcanic effect is clearly discernible in the Southern Hemispheric mean temperature, it is less significant in the Northern Hemisphere, partly because the two largest volcanic eruptions occurred in the SH tropics and during seasons when the aerosols were mainly transported southward, partly because of the higher northern internal variability. In the simulation including all forcings, temperatures are in reasonable agreement with the tree ring-based temperature anomalies of the Northern Hemisphere. Interestingly, the model suggests that solar irradiance changes at λ < 250 nm and in energetic particle spectra have only an insignificant impact on the climate during the Dalton Minimum. This downscales the importance of top-down processes (stemming from changes at λ < 250 nm) relative to bottom-up processes (from λ > 250 nm). Reduction of irradiance at λ > 250 nm leads to a significant (up to 2%) decrease in the ocean heat content (OHC) between 0 and 300 m in depth, whereas the changes in irradiance at λ < 250 nm or in energetic particles have virtually no effect. Also, volcanic aerosol yields a very strong response, reducing the OHC of the upper ocean by up to 1.5%. In the simulation with all forcings, the OHC of the uppermost levels recovers after 8-15 years after volcanic eruption, while the solar signal and the different volcanic eruptions dominate the OHC changes in the deeper ocean and prevent its recovery during the DM. Finally, the simulations suggest that the volcanic eruptions during the DM had a significant impact on the precipitation patterns caused by a widening of the Hadley cell and a shift in the intertropical convergence zone.

Lead exposure results in hearing loss and disruption of the cochlear blood-labyrinth barrier and the protective role of iron supplement.

PubMed

Liu, Xinqin; Zheng, Gang; Wu, Yongxiang; Shen, Xuefeng; Jing, Jinfei; Yu, Tao; Song, Han; Chen, Jingyuan; Luo, Wenjing

2013-12-01

This study was designed to investigate the impact of lead (Pb(2+)) on the auditory system and its molecular mechanisms. Pb(AC)2 was administrated to male SD rats aged 21-22 d for 8 weeks at a dose of 300ppm. Male guinea pigs were also administrated with 50mg/kg Pb(AC)2 two times a week for 8 weeks. The auditory nerve-brainstem evoked responses (ABR) was recorded and the morphological changes of the outer hair cells (OHCs) were observed with Phallodin-FITC staining. In addition, the integrity of the blood-labyrinth barrier was observed by TEM and the expression of tight junction proteins (TJPs) in the cochlear stria vascularis was determined by immunofluorescence. Our results showed that Pb(2+) exposure resulted in increased ABR threshold in both rats and guinea pigs. Abnormal shapes and loss of OHCs were found in the cochlear basilar membrane following the Pb(2+) exposure. TEM study showed that the tight junctions between the endothelial cells and the border cells were lost and disrupted. Down-regulation of the occludin, ZO-1 and claudin-5 in the stria vascularis suggested that the increased permeability of the blood-labyrinth barrier may attribute to the Pb(2+)-induced decrease of TJPs' expression. Additionally, Fe(2+) supplement partly reversed the Pb(2+)-induced hearing loss and down-regulation of TJPs. Taken together, these data indicate that the disruption of blood-labyrinth barrier by down-regulating the expression of TJPs plays a role in the Pb(2+)-induced hearing loss, and Fe(2+) supplement protects the auditory system against Pb(2+)-induced toxicity and may have significant clinical implications. Copyright © 2013 Elsevier Inc. All rights reserved.

Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5.

PubMed

Santos-Sacchi, Joseph; Song, Lei

2016-06-07

In general, SLC26 solute carriers serve to transport a variety of anions across biological membranes. However, prestin (SLC26a5) has evolved, now serving as a motor protein in outer hair cells (OHCs) of the mammalian inner ear and is required for cochlear amplification, a mechanical feedback mechanism to boost auditory performance. The mechanical activity of the OHC imparted by prestin is driven by voltage and controlled by anions, chiefly intracellular chloride. Current opinion is that chloride anions control the Boltzmann characteristics of the voltage sensor responsible for prestin activity, including Qmax, the total sensor charge moved within the membrane, and Vh, a measure of prestin's operating voltage range. Here, we show that standard narrow-band, high-frequency admittance measures of nonlinear capacitance (NLC), an alternate representation of the sensor's charge-voltage (Q-V) relationship, is inadequate for assessment of Qmax, an estimate of the sum of unitary charges contributed by all voltage sensors within the membrane. Prestin's slow transition rates and chloride-binding kinetics adversely influence these estimates, contributing to the prevalent concept that intracellular chloride level controls the quantity of sensor charge moved. By monitoring charge movement across frequency, using measures of multifrequency admittance, expanded displacement current integration, and OHC electromotility, we find that chloride influences prestin kinetics, thereby controlling charge magnitude at any particular frequency of interrogation. Importantly, however, this chloride dependence vanishes as frequency decreases, with Qmax asymptoting at a level irrespective of the chloride level. These data indicate that prestin activity is significantly low-pass in the frequency domain, with important implications for cochlear amplification. We also note that the occurrence of voltage-dependent charge movements in other SLC26 family members may be hidden by inadequate interrogation timescales, and that revelation of such activity could highlight an evolutionary means for kinetic modifications within the family to address hearing requirements in mammals. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish.

PubMed

Letcher, Robert J; Bustnes, Jan Ove; Dietz, Rune; Jenssen, Bjørn M; Jørgensen, Even H; Sonne, Christian; Verreault, Jonathan; Vijayan, Mathilakath M; Gabrielsen, Geir W

2010-07-01

Persistent organic pollutants (POPs) encompass an array of anthropogenic organic and elemental substances and their degradation and metabolic byproducts that have been found in the tissues of exposed animals, especially POPs categorized as organohalogen contaminants (OHCs). OHCs have been of concern in the circumpolar arctic for decades. For example, as a consequence of bioaccumulation and in some cases biomagnification of legacy (e.g., chlorinated PCBs, DDTs and CHLs) and emerging (e.g., brominated flame retardants (BFRs) and in particular polybrominated diphenyl ethers (PBDEs) and perfluorinated compounds (PFCs) including perfluorooctane sulfonate (PFOS) and perfluorooctanic acid (PFOA) found in Arctic biota and humans. Of high concern are the potential biological effects of these contaminants in exposed Arctic wildlife and fish. As concluded in the last review in 2004 for the Arctic Monitoring and Assessment Program (AMAP) on the effects of POPs in Arctic wildlife, prior to 1997, biological effects data were minimal and insufficient at any level of biological organization. The present review summarizes recent studies on biological effects in relation to OHC exposure, and attempts to assess known tissue/body compartment concentration data in the context of possible threshold levels of effects to evaluate the risks. This review concentrates mainly on post-2002, new OHC effects data in Arctic wildlife and fish, and is largely based on recently available effects data for populations of several top trophic level species, including seabirds (e.g., glaucous gull (Larus hyperboreus)), polar bears (Ursus maritimus), polar (Arctic) fox (Vulpes lagopus), and Arctic charr (Salvelinus alpinus), as well as semi-captive studies on sled dogs (Canis familiaris). Regardless, there remains a dearth of data on true contaminant exposure, cause-effect relationships with respect to these contaminant exposures in Arctic wildlife and fish. Indications of exposure effects are largely based on correlations between biomarker endpoints (e.g., biochemical processes related to the immune and endocrine system, pathological changes in tissues and reproduction and development) and tissue residue levels of OHCs (e.g., PCBs, DDTs, CHLs, PBDEs and in a few cases perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonates (PFSAs)). Some exceptions include semi-field studies on comparative contaminant effects of control and exposed cohorts of captive Greenland sled dogs, and performance studies mimicking environmentally relevant PCB concentrations in Arctic charr. Recent tissue concentrations in several arctic marine mammal species and populations exceed a general threshold level of concern of 1 part-per-million (ppm), but a clear evidence of a POP/OHC-related stress in these populations remains to be confirmed. There remains minimal evidence that OHCs are having widespread effects on the health of Arctic organisms, with the possible exception of East Greenland and Svalbard polar bears and Svalbard glaucous gulls. However, the true (if any real) effects of POPs in Arctic wildlife have to be put into the context of other environmental, ecological and physiological stressors (both anthropogenic and natural) that render an overall complex picture. For instance, seasonal changes in food intake and corresponding cycles of fattening and emaciation seen in Arctic animals can modify contaminant tissue distribution and toxicokinetics (contaminant deposition, metabolism and depuration). Also, other factors, including impact of climate change (seasonal ice and temperature changes, and connection to food web changes, nutrition, etc. in exposed biota), disease, species invasion and the connection to disease resistance will impact toxicant exposure. Overall, further research and better understanding of POP/OHC impact on animal performance in Arctic biota are recommended. Regardless, it could be argued that Arctic wildlife and fish at the highest potential risk of POP/OHC exposure and mediated effects are East Greenland, Svalbard and (West and South) Hudson Bay polar bears, Alaskan and Northern Norway killer whales, several species of gulls and other seabirds from the Svalbard area, Northern Norway, East Greenland, the Kara Sea and/or the Canadian central high Arctic, East Greenland ringed seal and a few populations of Arctic charr and Greenland shark. Copyright 2009 Elsevier B.V. All rights reserved.

Antimicrobial Efficacy of Octenidine Hydrochloride and Calcium Hydroxide with and Without a Carrier: A Broth Dilution Analysis

PubMed Central

Varghese, Vinaya Susan; Uppin, Veerendra; Bhat, Kishore; Pujar, Madhu; Hooli, Amruta B.; Kurian, Nirmal

2018-01-01

Background: An efficient antimicrobial agent action is required for a predetermined time period for absolute elimination of root canal microbes. Till date, there is limited or no data on the antimicrobial effect of octenidine as an intracanal medicament with chitosan (CTS) as a carrier against Candida albicans and Enterococcus faecalis. Aim: The aim of this microbiological study was to compare the antimicrobial efficacy of octenidine hydrochloride (OHC) and calcium hydroxide (Ca[OH]2) as intracanal medicaments, both independently and along with CTS as a carrier molecule against the common resistant endodontic pathogens. Materials and Methods: A total of 160 single-rooted anterior teeth were selected, root canal preparation was done, and teeth were divided into two groups and contaminated with C. albicans and E. faecalis, which were further divided into four test groups each according to intracanal medicaments used. CTS was used as a vehicle for OHC and Ca(OH)2 and antimicrobial assessment was performed on day 2 and day 7 following broth dilution method. Dentine samples were collected after each time interval, and the number of colony-forming units was determined. Results: All four medicaments used in this study showed antifungal and antibacterial activity that diminished from day 2 to day 7. Group I (OHC alone) and Group IV (Ca[OH]2 alone) showed significant antimicrobial activity against C. albicans and E. faecalis, respectively, than the other groups. Conclusion: A combination of OHC + CTS and Ca(OH)2+ CTS produced inferior results than that of the medicaments used alone. PMID:29599588

Compressive Strength of Notched Poly(Phenylene Sulfide) Aerospace Composite: Influence of Fatigue and Environment

NASA Astrophysics Data System (ADS)

Niitsu, G. T.; Lopes, C. M. A.

2013-08-01

The purpose of this work is to evaluate the influences of fatigue and environmental conditions (-55 °C, 23 °C, and 82 °C/Wet) on the ultimate compression strength of notched carbon-fiber-reinforced poly(phenylene sulfide) composites by performing open-hole compression (OHC) tests. Analysis of the fatigue effect showed that at temperatures of -55 and 23 °C, the ultimate OHC strengths were higher for fatigued than for not-fatigued specimens; this could be attributed to fiber splitting and delamination during fatigue cycling, which reduces the stress concentration at the hole edge, thus increasing the composite strength. This effect of increasing strength for fatigued specimens was not observed under the 82 °C/Wet conditions, since the test temperature near the matrix glass transition temperature ( T g) together with moisture content resulted in matrix softening, suggesting a reduction in fiber splitting during cycling; similar OHC strengths were verified for fatigued and not-fatigued specimens tested at 82 °C/Wet. Analysis of the temperature effect showed that the ultimate OHC strengths decreased with increasing temperature. A high temperature together with moisture content (82 °C/Wet condition) reduced the composite compressive strengths, since a temperature close to the matrix T g resulted in matrix softening, which reduced the lateral support provided by the resin to the 0° fibers, leading to fiber instability failure at reduced applied loads. On the other hand, a low temperature (-55 °C) improved the compressive strength because of possible fiber-matrix interfacial strengthening, increasing the fiber contribution to compressive strength.

A screening of persistent organohalogenated contaminants in hair of East Greenland polar bears.

PubMed

Jaspers, Veerle L B; Dietz, Rune; Sonne, Christian; Letcher, Robert J; Eens, Marcel; Neels, Hugo; Born, Erik W; Covaci, Adrian

2010-10-15

In this pilot study, we report on levels of persistent organohalogenated contaminants (OHCs) in hair of polar bears (Ursus maritimus) from East Greenland sampled between 1999 and 2001. To our knowledge, this is the first study on the validation of polar bear hair as a non-invasive matrix representative of concentrations and profiles in internal organs and blood plasma. Because of low sample weights (13-140mg), only major bioaccumulative OHCs were detected above the limit of quantification: five polychlorinated biphenyl (PCB) congeners (CB 99, 138, 153, 170 and 180), one polybrominated diphenyl ether (PBDE) congener (BDE 47), oxychlordane, trans-nonachlor and β-hexachlorocyclohexane. The PCB profile in hair was similar to that of internal tissues (i.e. adipose, liver, brain and blood), with CB 153 and 180 as the major congeners in all matrices. A gender difference was found for concentrations in hair relative to concentrations in internal tissues. Females (n=6) were found to display negative correlations, while males (n=5) showed positive correlations, although p-values were not found significant. These negative correlations in females may reflect seasonal OHC mobilisation from periphery adipose tissue due to, for example, lactation and fasting. The lack of significance in most correlations may be due to small sample sizes and seasonal variability of concentrations in soft tissues. Further research with larger sample weights and sizes is therefore necessary to draw more definitive conclusions on the usefulness of hair for biomonitoring OHCs in polar bears and other fur mammals. Copyright © 2010 Elsevier B.V. All rights reserved.

Legacy and emerging organohalogenated contaminants in wild edible aquatic organisms: Implications for bioaccumulation and human exposure.

PubMed

Sun, Runxia; Luo, Xiaojun; Li, Qing X; Wang, Tao; Zheng, Xiaobo; Peng, Pingan; Mai, Bixian

2018-03-01

Highly industrialized and urbanized watersheds may receive various contaminants from anthropogenic activities. In this study, legacy and emerging organohalogenated contaminants (OHCs) were measured in edible wild aquatic organisms sampled from the Pearl River and Dongjiang River in a representative industrial and urban region in China. High concentrations of target contaminants were observed. The Pearl River exhibited higher concentrations of OHCs than the Dongjiang River due to high industrialization and urbanization. Agrochemical inputs remained an important source of OHCs in industrialized and urbanized watershed in China, but vigilance is needed for recent inputs of polychlorinated biphenyls (PCBs) originated from e-waste recycling activities. Bioaccumulation of dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), PCBs, polybrominated diphenyl ethers (PBDEs), and Dechlorane Plus (DP) was biological species- and compound-specific, which can be largely attributed to metabolic capability for xenobiotics. No health risk was related to the daily intake of DDTs, HCHs, and PBDEs via consumption of wild edible species investigated for local residents. However, the current exposure to PCBs through consuming fish is of potential health concern. Copyright © 2017 Elsevier B.V. All rights reserved.

Time course of organ of Corti degeneration after noise exposure.

PubMed

Bohne, Barbara A; Kimlinger, Melissa; Harding, Gary W

2017-02-01

From our permanent collection of plastic-embedded flat preparations of chinchilla cochleae, 22 controls and 199 ears from noise-exposed animals were used to determine when, postexposure, hair cell (HC) and supporting cell (SC) degeneration were completed. The exposed ears were divided into four groups based on exposure parameters: 0.5- or 4-kHz octave band of noise at moderate (M) or high (H) intensities. Postexposure survival ranged from <1 h to 2.5 y. Ears fixed ≤ 0-12 h postexposure were called 'acute'. For 'chronic' ears, postexposure survival was ≥7 d for groups 0.5M and 4M, ≥ 1 mo for the 4H group and ≥7 mo for the 0.5H group. The time course of inner-ear degeneration after noise exposure was determined from data in the 0.5H and 4H groups because these groups contained ears with intermediate survival times. Outer hair cells (OHCs) began dying during the exposure. OHC loss slowed down beyond 1 mo but was still present. Conversely, much inner hair cell loss was delayed until 1-3 wk postexposure. Outer pillar and inner pillar losses were present at a low level in acute ears but increased exponentially thereafter. These results are the first to demonstrate quantitatively that hair cells (HCs) and supporting cells (SCs) may continue to degenerate for months postexposure. With short postexposure survivals, the remaining SCs often had pathological changes, including: buckled pillar bodies, shifted Deiters' cell (DC) nuclei, detachment of DCs from the basilar membrane and/or splitting of the reticular lamina. These pathological changes appeared to allow endolymph and perilymph to intermix in the fluid spaces of the organ of Corti, damaging additional HCs, SCs and nerve fibers. This mechanism may account for some postexposure degeneration. In ears exposed to moderate noise, some of these SC changes appeared to be reversible. In ears exposed to high-level noise, these changes appeared to indicate impending degeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of BAPTA and 4AP in scala media on transduction and cochlear gain.

PubMed

Sellick, P M; Robertson, D; Patuzzi, R

2006-01-01

We have injected by iontophoresis 4-amino-pyridine, a K+ channel blocker and BAPTA, (a Ca++ chelator), into scala media of the first three turns of the guinea pig cochlea. We measured the reduction in outer hair cell (OHC) receptor current, as indicated by cochlear microphonic measured in scala media evoked by a 207 Hz tone, and compared this with the elevation of the cochlear action potential (CAP) threshold. We found that in the basal turn, for frequencies between 12 and 21 kHz, CAP threshold was elevated by about 30 dB, while in the second turn, at the 3 kHz place, the maximum elevation was 15 dB. In the third turn, iontophoresis of 4AP and BAPTA reduced CM by similar amounts to that in the basal and second turn, but caused negligible elevation of CAP threshold. We conclude that the gain of the cochlear amplifier is maximal for basal turn frequencies, is halved at 3 kHz, and is reduced to close to one for frequencies below 1 kHz (no active gain). The effect of 4AP and BAPTA on neural threshold and the receptor current represented by CM may be explained by their action on OHC transduction without the involvement of IHCs.

Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene.

PubMed

Cappaert, Natalie L M; Klis, Sjaak F L; Muijser, Hans; Kulig, Beverly M; Ravensberg, Luco C; Smoorenburg, Guido F

2002-01-01

The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2+/-0.8-microg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8+/-0.1 microg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood.

Energy output of a single outer hair cell: Effect of resonance

NASA Astrophysics Data System (ADS)

Iwasa, Kuni H.

2018-05-01

The ability of the mammalian ear in processing high frequency sounds, up to ˜100 kHz, is based on the capability of outer hair cells (OHCs) in responding to stimulation at high frequencies. These cells show a unique motility in their cell body coupled with charge movement. With this motile element, voltage changes generated by stimuli at their hair bundles drive the cell body and that, in turn, amplifies the signal. In vitro experiments show that the movement of these charges significantly increases the membrane capacitance, limiting the motile activity by an additional attenuation of voltage changes. It was found, however, that such an effect is due to the absence of mechanical load. In the presence of mechanical load, particularly inertial load, such as under in vivo conditions, the movement of motile charges should reduce the membrane capacitance, enhancing the mechanical power output.

Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age

PubMed Central

Roze, Elise; Meijer, Lisethe; Bakker, Attie; Van Braeckel, Koenraad N.J.A.; Sauer, Pieter J.J.; Bos, Arend F.

2009-01-01

Background Organohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain. Objective We investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age. Methods This study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2′-bis-(4 chlorophenyl)-1,1′-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3′,4′,5-pentachlorobiphenyl (4OH-CB-107), 4OH-CB-146, 4OH-CB-187, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocyclododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5–6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior. Results Brominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration. Conclusions Our results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern. PMID:20049217

Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age.

PubMed

Roze, Elise; Meijer, Lisethe; Bakker, Attie; Van Braeckel, Koenraad N J A; Sauer, Pieter J J; Bos, Arend F

2009-12-01

Organohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain. We investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age. This study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2'-bis-(4 chlorophenyl)-1,1'-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4OH-CB-107), 4OH-CB-146, 4OH-CB-187, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocyclododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5-6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior. Brominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration. Our results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern.

A review on current knowledge and future prospects of organohalogen contaminants (OHCs) in Asian birds.

PubMed

Abbasi, Naeem Akhtar; Malik, Riffat Naseem; Frantz, Adrien; Jaspers, Veerle Leontina Bernard

2016-01-15

The release of harmful chemicals in the Asian environment has recently increased dramatically due to rising industrial and agricultural activities. About 60% of the global human population is currently living on the Asian continent and may thus be exposed to a large range of different chemicals. Different classes of organohalogen chemicals have indeed been reported in various environmental compartments from Asia including humans and wildlife, but this issue has received less attention in birds. In this article, we reviewed the available literature on levels of legacy persistent organic pollutants (POPs) and various flame retardants (FRs) in Asian avifauna to analyze the existing pool of knowledge as well as to identify the gaps that should be addressed in future research. Furthermore, we discussed the variation in levels of organohalogens based on differences in regions, trophic level, dietary sources and migratory behaviors of species including distribution patterns in different tissues of birds. Although the mass of published literature is very low and even absent in many important regions of Asia, we deduced from the reported studies that levels of almost all classes of organohalogens (OHCs) including FRs were highest in East Asian countries such as Japan, China and South Korea, except for HCHs that were found at maximum levels in birds of South India. Concentrations (ng/g LW) of different OHCs in Asian birds ranged between

Upper ocean O2 trends: 1958-2015

NASA Astrophysics Data System (ADS)

Ito, Takamitsu; Minobe, Shoshiro; Long, Matthew C.; Deutsch, Curtis

2017-05-01

Historic observations of dissolved oxygen (O2) in the ocean are analyzed to quantify multidecadal trends and variability from 1958 to 2015. Additional quality control is applied, and the resultant oxygen anomaly field is used to quantify upper ocean O2 trends at global and hemispheric scales. A widespread negative O2 trend is beginning to emerge from the envelope of interannual variability. Ocean reanalysis data are used to evaluate relationships with changes in ocean heat content (OHC) and oxygen solubility (O2,sat). Global O2 decline is evident after the 1980s, accompanied by an increase in global OHC. The global upper ocean O2 inventory (0-1000 m) changed at the rate of -243 ± 124 T mol O2 per decade. Further, the O2 inventory is negatively correlated with the OHC (r = -0.86; 0-1000 m) and the regression coefficient of O2 to OHC is approximately -8.2 ± 0.66 nmol O2 J-1, on the same order of magnitude as the simulated O2-heat relationship typically found in ocean climate models. Variability and trends in the observed upper ocean O2 concentration are dominated by the apparent oxygen utilization component with relatively small contributions from O2,sat. This indicates that changing ocean circulation, mixing, and/or biochemical processes, rather than the direct thermally induced solubility effects, are the primary drivers for the observed O2 changes. The spatial patterns of the multidecadal trend include regions of enhanced ocean deoxygenation including the subpolar North Pacific, eastern boundary upwelling systems, and tropical oxygen minimum zones. Further studies are warranted to understand and attribute the global O2 trends and their regional expressions.

Disruption of thyroid hormone (TH) levels and TH-regulated gene expression by polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and hydroxylated PCBs in e-waste recycling workers.

PubMed

Zheng, Jing; He, Chun-Tao; Chen, She-Jun; Yan, Xiao; Guo, Mi-Na; Wang, Mei-Huan; Yu, Yun-Jiang; Yang, Zhong-Yi; Mai, Bi-Xian

2017-05-01

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are the primary toxicants released by electronic waste (e-waste) recycling, but their adverse effects on people working in e-waste recycling or living near e-waste sites have not been studied well. In the present study, the serum concentrations of PBDEs, PCBs, and hydroxylated PCBs, the circulating levels of thyroid hormones (THs), and the mRNA levels of seven TH-regulated genes in peripheral blood leukocytes of e-waste recycling workers were analyzed. The associations of the hormone levels and gene expression with the exposure to these contaminants were examined using multiple linear regression models. There were nearly no associations of the TH levels with PCBs and hydroxylated PCBs, whereas elevated hormone (T 4 and T 3 ) levels were associated with certain lower-brominated BDEs. While not statistically significant, we did observe a negative association between highly brominated PBDE congeners and thyroid-stimulating hormone (TSH) levels in the e-waste workers. The TH-regulated gene expression was more significantly associated with the organohalogen compounds (OHCs) than the TH levels in these workers. The TH-regulated gene expression was significantly associated with certain PCB and hydroxylated PCB congeners. However, the expression of most target genes was suppressed by PBDEs (mostly highly brominated congeners). This is the first evidence of alterations in TH-regulated gene expression in humans exposed to OHCs. Our findings indicated that OHCs may interfere with TH signaling and/or exert TH-like effects, leading to alterations in related gene expression in humans. Further research is needed to investigate the mechanisms of action and associated biological consequences of the gene expression disruption by OHCs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transiently-Evoked Otoacoustic Emissions (teoaes) in Monitoring Adult Cis-Platin Patients.

NASA Astrophysics Data System (ADS)

Ribera, John Everett

1995-01-01

There is evidence to suggest that otoacoustic emissions (OAEs) reflect the integrity of cochlear outer hair cell (OHC) function. Cis-platin (CDDP) is a potent ototoxic chemotherapeutic agent that tends to destroy or disable OHCs. Therefore, this study was designed to answer the following questions: (1) Can TEOAEs be used in monitoring for ototoxicity in adult VA oncology patients receiving CDDP treatment? (2) If so, how sensitive are TEOAEs in detecting significant changes when compared to Audiometry in a VA population? and (3) Which of several TEOAE measures is the most sensitive to changes in hearing due to CDDP ototoxicity in a VA population?. In Experiment I, VA Medical Center patients were recruited (control group) and tested using a conventional audiometer and the ILO88 Otoacoustic Analyzer on three separate days. Data from this experiment were used to develop change criteria in each of four TEOAE measures (Reproducibility, Compare, 1 kHz Band Analysis, and OAE Response) for Experiment II. Experiment II was of similar design with the exception that the subjects (experimental group) were patients enrolled from the oncology ward and were administered CDDP after the first and second test sessions. Data from both groups and all test measures revealed (1) that there was no ear effect in any of the test conditions, (2) there was a group (drug) effect, and (3) there was a frequency effect at 2 kHz. Audiometry detected changes in 56% of the experimental subjects, while the number of changes varied among the TEOAE measures studied. Compare agreed with Audiometry more often and performed better than any other TEOAE measure in detecting change. Based on these findings, incorporation of Compare into an audiometric test battery to monitor for ototoxicity in the VA population is feasible. There is evidence to suggest that as measurement techniques are refined TEOAE analysis will become a valid test for monitoring of adult CDDP patients.

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia.

PubMed

Shi, Zongdao; Xie, Huixu; Wang, Ping; Zhang, Qi; Wu, Yan; Chen, E; Ng, Linda; Worthington, Helen V; Needleman, Ian; Furness, Susan

2013-08-13

Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in persons who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions may reduce the risk of VAP in these patients. To assess the effects of OHC on the incidence of VAP in critically ill patients receiving mechanical ventilation in intensive care units (ICUs) in hospitals. We searched the Cochrane Oral Health Group's Trials Register (to 14 January 2013), CENTRAL (The Cochrane Library 2012, Issue 12), MEDLINE (OVID) (1946 to 14 January 2013), EMBASE (OVID) (1980 to 14 January 2013), LILACS (BIREME) (1982 to 14 January 2013), CINAHL (EBSCO) (1980 to 14 January 2013), Chinese Biomedical Literature Database (1978 to 14 January 2013), China National Knowledge Infrastructure (1994 to 14 January 2013), Wan Fang Database (January 1984 to 14 January 2013), OpenGrey and ClinicalTrials.gov (to 14 January 2013). There were no restrictions regarding language or date of publication. We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation. Two review authors independently assessed all search results, extracted data and undertook risk of bias. We contacted study authors for additional information. Trials with similar interventions and outcomes were pooled reporting odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes using random-effects models unless there were fewer than four studies. Thirty-five RCTs (5374 participants) were included. Five trials (14%) were assessed at low risk of bias, 17 studies (49%) were at high risk of bias, and 13 studies (37%) were assessed at unclear risk of bias in at least one domain. There were four main comparisons: chlorhexidine (CHX mouthrinse or gel) versus placebo/usual care, toothbrushing versus no toothbrushing, powered versus manual toothbrushing and comparisons of oral care solutions.There is moderate quality evidence from 17 RCTs (2402 participants, two at high, 11 at unclear and four at low risk of bias) that CHX mouthrinse or gel, as part of OHC, compared to placebo or usual care is associated with a reduction in VAP (OR 0.60, 95% confidence intervals (CI) 0.47 to 0.77, P < 0.001, I(2) = 21%). This is equivalent to a number needed to treat (NNT) of 15 (95% CI 10 to 34) indicating that for every 15 ventilated patients in intensive care receiving OHC including chlorhexidine, one outcome of VAP will be prevented. There is no evidence of a difference between CHX and placebo/usual care in the outcomes of mortality (OR 1.10, 95% CI 0.87 to 1.38, P = 0.44, I(2) = 2%, 15 RCTs, moderate quality evidence), duration of mechanical ventilation (MD 0.09, 95% CI -0.84 to 1.01 days, P = 0.85, I(2) = 24%, six RCTs, moderate quality evidence), or duration of ICU stay (MD -0.21, 95% CI -1.48 to 1.89 days, P = 0.81, I(2) = 9%, six RCTs, moderate quality evidence). There was insufficient evidence to determine whether there is a difference between CHX and placebo/usual care in the outcomes of duration of use of systemic antibiotics, oral health indices, microbiological cultures, caregivers preferences or cost. Only three studies reported any adverse effects, and these were mild with similar frequency in CHX and control groups.From three trials of children aged from 0 to 15 years (342 participants, moderate quality evidence) there is no evidence of a difference between OHC with CHX and placebo for the outcomes of VAP (OR 1.07, 95% CI 0.65 to 1.77, P = 0.79, I(2) = 0%), or mortality (OR 0.73, 95% CI 0.41 to 1.30, P = 0.28, I(2) = 0%), and insufficient evidence to determine the effect on the outcomes of duration of ventilation, duration of ICU stay, use of systemic antibiotics, plaque index, microbiological cultures or adverse effects, in children.Based on four RCTs (828 participants, low quality evidence) there is no evidence of a difference between OHC including toothbrushing (± CHX) compared to OHC without toothbrushing (± CHX) for the outcome of VAP (OR 0.69, 95% CI 0.36 to 1.29, P = 0.24 , I(2) = 64%) and no evidence of a difference for mortality (OR 0.85, 95% CI 0.62 to 1.16, P = 0.31, I(2) = 0%, four RCTs, moderate quality evidence). There is insufficient evidence to determine whether there is a difference due to toothbrushing for the outcomes of duration of mechanical ventilation, duration of ICU stay, use of systemic antibiotics, oral health indices, microbiological cultures, adverse effects, caregivers preferences or cost.Only one trial compared use of a powered toothbrush with a manual toothbrush providing insufficient evidence to determine the effect on any of the outcomes of this review.A range of other oral care solutions were compared. There is some weak evidence that povidone iodine mouthrinse is more effective than saline in reducing VAP (OR 0.35, 95% CI 0.19 to 0.65, P = 0.0009, I(2) = 53%) (two studies, 206 participants, high risk of bias). Due to the variation in comparisons and outcomes among the trials in this group there is insufficient evidence concerning the effects of other oral care solutions on the outcomes of this review. Effective OHC is important for ventilated patients in intensive care. OHC that includes either chlorhexidine mouthwash or gel is associated with a 40% reduction in the odds of developing ventilator-associated pneumonia in critically ill adults. However, there is no evidence of a difference in the outcomes of mortality, duration of mechanical ventilation or duration of ICU stay. There is no evidence that OHC including both CHX and toothbrushing is different from OHC with CHX alone, and some weak evidence to suggest that povidone iodine mouthrinse is more effective than saline in reducing VAP. There is insufficient evidence to determine whether powered toothbrushing or other oral care solutions are effective in reducing VAP.

[DPOAE in tinnitus patients with cochlear hearing loss considering hyperacusis and misophonia].

PubMed

Sztuka, Aleksandra; Pośpiech, Lucyna; Gawron, Wojciech; Dudek, Krzysztof

2006-01-01

The most probable place generating tinnitus in auditory pathway are outer hair cells (OHC) inside cochlea. To asses their activity otoacoustic emission is used. The goal of the investigation was estimation the features of otoemission DPOAE in groups with tinnitus patients with cochlear hearing loss, estimation of diagnostic value of DPOAE parameters for analysis of function of the cochlea in investigated patients emphasizing DPOAE parameters most useful in localizing tinnitus generators and estimation of hypothetic influence of hyperacusis and misophony on parameters of DPOAE in tinnitus patients with cochlear hearing loss. The material of the study were 42 tinnitus patients with cochlear hearing loss. In the control group there were 21 patients without tinnitus with the same type of hearing loss. Then tinnitus patients were divided into three subgroups--with hyperacusis, misophony and without both of them, based on audiologic findings. after taking view on tinnitus and physical examination in all the patients pure tone and impedance audiometry, supratreshold tests, ABR and audiometric average and discomfort level were evaluated. Then otoemission DPOAE was measured in three procedures. First the amplitudes of two points per octave were assessed, in second--"fine structure" method-- 16-20 points per octave (f2/f1 = 1.2, L1 = L2 = 70 dB). Third procedure included recording of growth rate function in three series for input tones of value f2 = 2002, 4004, 6006 Hz (f2/f1= 1.22) and levels L1=L2, growing by degrees of 5dB in each series. DPOAE amplitudes in recording of 2 points per octave and fine structure method are very valuable parameters for estimation of cochlear function in tinnitus patients with cochlear hearing loss. Decreasing of DPOAE amplitudes in patients with cochlear hearing loss and tinnitus suggests significant role of OHC pathology, unbalanced by IHC injury in generation of tinnitus in patients with hearing loss of cochlear localization. DPOAE fine structure provides us the additional information about DPOAE amplitude recorded in two points per octave, spreading the amount of frequencies f2, where differences are noticed in comparison of two groups--tinnitus patients and control. Function growth rate cannot be the only parameter in estimation of DPOAE in tinnitus patients with cochlear hearing loss, also including subjects with hyperacusis and misophony. Hyperacusis has important influence on DPOAE amplitude, increases essentially amplitude of DPOAE in the examined group of tinnitus patients.

Research on gender differences in online health communities.

PubMed

Liu, Xuan; Sun, Min; Li, Jia

2018-03-01

With the growing concern about health issues and the emergence of online communities based on user-generated content (UGC), more and more people are participating in online health communities (OHCs) to exchange opinions and health information. This paper aims to examine whether and how male and female users behave differently in OHCs. Using data from a leading diabetes community in China (Tianmijiayuan), we incorporate three different techniques: topic modeling analysis, sentiment analysis and friendship network analysis to investigate gender differences in chronic online health communities. The results indicated that (1) Male users' posting content was usually more professional and included more medical terms. Comparatively speaking, female users were more inclined to seek emotional support in the health communities. (2) Female users expressed more negative emotions than male users did, especially anxiety and sadness. (3) In addition, male users were more centered and influential in the friendship network than were women. Through these analyses, our research revealed the behavioral characteristics and needs for different gender users in online health communities. Gaining a deeper understanding of gender differences in OHCs can serve as guidance to better meet the information needs, emotional needs and relationship needs of male and female patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Fetal omphalocele ratios predict outcomes in prenatally diagnosed omphalocele.

PubMed

Montero, Freddy J; Simpson, Lynn L; Brady, Paula C; Miller, Russell S

2011-09-01

The objective of the study was to evaluate whether ratios considering omphalocele diameter relative to fetal biometric measurements perform better than giant omphalocele designation at predicting inability to achieve neonatal primary surgical closure. Cases of fetal omphalocele that underwent evaluation between May 2003 and July 2010 were identified. Inclusion was restricted to live births with plan for postnatal repair. Omphalocele diameter upon antenatal ultrasound was compared with abdominal circumference, femur length, and head circumference, yielding the respective omphalocele (O)/abdominal circumference (AC), O/femur length (FL), and O/head circumference (HC) ratios. The absolute measurements were used to classify giant lesions. Omphalocele ratios and giant omphalocele designations were evaluated as predictors of inability to achieve primary repair. Among 25 included cases, staged or delayed closure occurred in 52%. With an optimal cutoff of 0.21 or greater, O/HC best predicted the primary outcome (sensitivity, 84.6%; specificity, 58.3%; odds ratio, 7.7). The O/HC of 0.21 or greater outperformed giant designations. The O/HC of 0.21 or greater best predicted staged or delayed omphalocele closure. Giant omphalocele designation, regardless of definition, poorly predicted outcome. Copyright © 2011 Mosby, Inc. All rights reserved.

Developing and evaluating the implementation of a complex intervention: using mixed methods to inform the design of a randomised controlled trial of an oral healthcare intervention after stroke

PubMed Central

2011-01-01

Background Many interventions delivered within the stroke rehabilitation setting could be considered complex, though some are more complex than others. The degree of complexity might be based on the number of and interactions between levels, components and actions targeted within the intervention. The number of (and variation within) participant groups and the contexts in which it is delivered might also reflect the extent of complexity. Similarly, designing the evaluation of a complex intervention can be challenging. Considerations include the necessity for intervention standardisation, the multiplicity of outcome measures employed to capture the impact of a multifaceted intervention and the delivery of the intervention across different clinical settings operating within varying healthcare contexts. Our aim was to develop and evaluate the implementation of a complex, multidimensional oral health care (OHC) intervention for people in stroke rehabilitation settings which would inform the development of a randomised controlled trial. Methods After reviewing the evidence for the provision of OHC following stroke, multi-disciplinary experts informed the development of our intervention. Using both quantitative and qualitative methods we evaluated the implementation of the complex OHC intervention across patients, staff and service levels of care. We also adopted a pragmatic approach to patient recruitment, the completion of assessment tools and delivery of OHC, alongside an attention to the context in which it was delivered. Results We demonstrated the feasibility of implementing a complex OHC intervention across three levels of care. The complementary nature of the mixed methods approach to data gathering provided a complete picture of the implementation of the intervention and a detailed understanding of the variations within and interactions between the components of the intervention. Information on the feasibility of the outcome measures used to capture impact across a range of components was also collected, though some process orientated uncertainties including eligibility and recruitment rates remain to be further explored within a Phase II exploratory trial. Conclusions Complex interventions can be captured and described in a manner which facilitates evaluation in the form of exploratory and subsequently definitive clinical trials. If effective, the evidence captured relating to the intervention context will facilitate translation into clinical practice. PMID:21729277

Oxysterol-EBI2 signaling in immune regulation and viral infection.

PubMed

Daugvilaite, Viktorija; Arfelt, Kristine Niss; Benned-Jensen, Tau; Sailer, Andreas W; Rosenkilde, Mette M

2014-07-01

The seven transmembrane G protein-coupled receptor Epstein-Barr virus (EBV) induced gene 2 (EBI2; also known as GPR183) was identified in 1993 on the basis of its substantial upregulation in EBV-infected cells. It is primarily expressed in lymphoid cells; most abundantly in B cells. EBI2 is central for the positioning of B cells within the lymphoid organs, a process that is regulated in part by a chemotactic gradient formed by the endogenous lipid agonists, and in part by a fine-tuned regulation of EBI2 cell surface expression. The most potent endogenous EBI2 agonist is 7α, 25-dihydroxyxcholesterol (7α,25-OHC), yet many structurally related oxysterols can bind to an EBI2 pocket that is defined by the upper parts of the transmembrane helices and extracellular receptor regions. EBI2 signals via Gαi, as well as via G protein-independent pathways like β-arrestin recruitment. The concerted action of these pathways leads to cell migration. By genetically interfering with its up- and downregulation, EBI2 was also recently shown to induce cell proliferation, an action that could be inhibited by small molecule antagonists. Here, we focus on the oxysterol-EBI2 axis in immune control, including its role in the EBV life cycle. We also summarize the structural and functional properties of EBI2 interaction with oxysterol agonists and small molecule antagonists and discuss EBI2 as therapeutic target for diseases of the immune system. © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancement of electrically evoked oto-acoustic emissions associated with low-frequency stimulus bias of the basilar membrane towards scala vestibuli.

PubMed

Kirk, D L; Yates, G K

1998-09-01

Electrically evoked oto-acoustic emissions (EEOAEs) are sounds present in the ear canal when ac current is passed into the cochlea. EEOAEs are attributed to the activation of fast electromotile responses in outer hair cells (OHCs). An interesting property of EEOAEs is the phenomenon of "acoustic enhancement," where the emission amplitude is increased by moderate-level sound [D. C. Mountain and A. E. Hubbard, Hear. Res. 42, 195-202 (1989)]. In this report a form of enhancement is described which occurs with displacements of the basilar membrane toward scala vestibuli, during amplitude modulation of the EEOAE waveform by low-frequency tones. This "SV-bias enhancement" possibly consists of two components: (i) a low-level component induced by sound at levels which produce nonlinear growth of the cochlear microphonic and which may be equivalent to the "acoustic enhancement" described previously, and (ii) a high-level component which occurs at sound levels well above those which cause saturation of the cochlear microphonic. The low-level component could be explained by either an increased access of the extrinsically applied current to a membrane-based source of OHC motility, perhaps coupled with a reduction in negative feedback, or an increase in electromotile output during scala vestibuli displacements, but the origin of the high-level component is obscure.

Analyzing the relationships between reflection source DPOAEs and SFOAEs using a computational model

NASA Astrophysics Data System (ADS)

Wen, Haiqi; Bowling, Thomas; Meaud, Julien

2018-05-01

Distortion product otoacoustic emissions (DPOAEs) are sounds generated by the cochlea in response to a stimulus that consists of two primary tones. DPOAEs consist of a mixture of emissions arising from two different mechanisms: nonlinear distortion and coherent reflection. Stimulus Frequency Otoacoustic Emissions (SFOAEs) are sounds generated by the cochlea in response to a pure tone; SFOAEs are commonly hypothesized to be generated due to coherent reflection. Nonlinearity of the outer hair cells (OHCs) provides nonlinear amplification to the traveling wave while reflections occur due to pre-existing micromechanical impedance perturbations. In this work, DPOAEs are obtained from a time domain computational model coupling a lumped parameter middle ear model with a multiphysics mechanical-electrical-acoustical model of cochlea. Cochlear roughness is intro-duced by perturbing the value of the OHC electromechanical coupling coefficient to account for the putative inhomogeneities inside the cochlea. The DPOAEs emitted in the ear canal are decomposed into distortion source and reflection source components. The reflection source component of DPOAEs is compared to SFOAEs obtained using a frequency-domain implementation of the model, to help us understand how distortion source and reflection source contributes to total DPOAEs. Moreover, the group delays of reflection sources OAEs are compared to group delays in the basilar membrane velocity to clarify the relationship between basilar membrane and OAE group delays.

Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

PubMed

Li, Xu; Mao, Xiao-Bo; Hei, Ren-Yi; Zhang, Zhi-Bin; Wen, Li-Ting; Zhang, Peng-Zhi; Qiu, Jian-Hua; Qiao, Li

2011-01-01

A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. The gene and protein expression of the H(2)S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

Urinary excretion values in 2-day food-deprived, unrestrained chimpanzees.

NASA Technical Reports Server (NTRS)

Mcnew, J. J.; Sabbot, I. M.; Hoshizaki, T.; Mandell, A. J.; Spooner, C. E.; Marcus, I.; Adey, W. R.

1972-01-01

A study was conducted to determine the baseline 24-hr urinary excretion values in the young, unrestrained chimpanzee, and also changes in urinary values, if any, induced by the two-day food deprivation stress. Urine was analyzed for volume, osmolarity, creatinine, creatine, urea nitrogen, 17-hydroxycorticosteroids (17-OHCS), 3-methoxy-4-hydroxymandelic acid (VMA), calcium, and inorganic phosphorus. Significant increases due to food deprivation stress were observed for volume, creatine, urea nitrogen, 17-OHCS, VMA, and phosphorus values, with significant decreases in osmolarity and calcium. All values approached normal levels by the second poststress day. No significant changes were observed in creatinine. A comparison is drawn between human and chimpanzee adaptation to stress.

Processing and Properties of Fiber Reinforced Polymeric Matrix Composites. Part 2; Processing Robustness of IM7/PETI Polyimide Composites

NASA Technical Reports Server (NTRS)

Hou, Tan-Hung

1996-01-01

The processability of a phenylethynyl terminated imide (PETI) resin matrix composite was investigated. Unidirectional prepregs were made by coating an N-methylpyrrolidone solution of the amide acid oligomer onto unsized IM7. Two batches of prepregs were used: one was made by NASA in-house, and the other was from an industrial source. The composite processing robustness was investigated with respect to the effect of B-staging conditions, the prepreg shelf life, and the optimal processing window. Rheological measurements indicated that PETI's processability was only slightly affected over a wide range of B-staging temperatures (from 250 C to 300 C). The open hole compression (OHC) strength values were statistically indistinguishable among specimens consolidated using various B-staging conditions. Prepreg rheology and OHC strengths were also found not to be affected by prolonged (i.e., up to 60 days) ambient storage. An optimal processing window was established using response surface methodology. It was found that IM7/PETI composite is more sensitive to the consolidation temperature than to the consolidation pressure. A good consolidation was achievable at 371 C/100 Psi, which yielded an OHC strength of 62 Ksi at room temperature. However, processability declined dramatically at temperatures below 350 C.

Modeling Electrically Evoked Otoacoustic Emissions

NASA Astrophysics Data System (ADS)

Grosh, K.; Deo, N.; Parthasarathi, A. A.; Nuttall, A. L.; Zheng, J. F.; Ren, T. Y.

2003-02-01

Electrical evoked otoacoustic emissions (EEOAE) are used to investigate in vivo cochlear electromechanical function. Round window electrical stimulation gives rise to a broad frequency EEOAE response, from 100 Hz or below to 40 kHz in guinea pigs. Placing bipolar electrodes very close to the basilar membrane (in the scala vestibuli and scala tympani) gives rise to a much narrower frequency range of EEOAE, limited to around 20 kHz when the electrodes are placed near the 18 kHz best frequency place. Model predictions using a three dimensional fluid model in conjunction with a simple model for outer hair cell (OHC) activity are used to interpret the experimental results. The model is solved using a 2.5D finite-element formulation. Predictions show that the high-frequency limit of the excitation is determined by the spatial extent of the current stimulus (also called the current spread). The global peaks in the EEOAE spectra are interpreted as constructive interference between electrically evoked backward traveling waves and forward traveling waves reflected from the stapes. Steady-state response predictions of the model are presented.

Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring.

PubMed

Zhang, Yu-Ping; Huo, Yan-Li; Fang, Zhi-Qin; Wang, Xue-Fang; Li, Jian-Dong; Wang, Hai-Ping; Peng, Wei; Johnson, Alan Kim; Xue, Baojian

2018-05-01

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

PubMed Central

Barker Rasmussen, Bastian; Fog Nielsen, Kristian; Machado, Henrique; Melchiorsen, Jette; Gram, Lone; Sonnenschein, Eva C.

2014-01-01

Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7) HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria. PMID:25419995

Pistachio hull water-soluble polysaccharides as a novel prebiotic agent.

PubMed

Akbari-Alavijeh, Safoura; Soleimanian-Zad, Sabihe; Sheikh-Zeinoddin, Mahmoud; Hashmi, Sarwar

2018-02-01

We isolated and characterized pistachio hull polysaccharides (PHP). The PHP was a heteropolysaccharide mainly contained 75.50% (w/w) total sugar and 9.51% (w/w) uronic acid. As determined by GPC analysis, the polysaccharide with a molecular weight of 3.71×10 6 D (83.2%) was the most dominant fraction. Moreover, HPLC analysis indicated that PHP was predominantly composed of xylose, glucose, arabinose, and fructose with a molar ratio of 1.00:2.50:19.67:28.81. FT-IR and NMR analysis also confirmed the results obtained by HPLC and characterized preliminary structure features of the PHP. Functional properties of the PHP including water holding capacity (WHC: 2.44±0.05g water/g DM), and oil holding capacity (OHC: 11.53±0.04g oil/g DM) were significant compared to inulin used as reference prebiotic (p<0.01). Furthermore, the PHP remained 94.37% undigested in the simulated digestion process and stimulated the growth of L. plantarum PTCC 1896 and L. rhamnosus GG and increased the acetate, propionate and butyrate production over inulin in vitro. Totally, the PHP showed a considerable prebiotic capability and high WHC, OHC suggesting that the PHP is a potent pharmaceutical with good technological properties which can be used in food and drug industries. Copyright © 2017 Elsevier B.V. All rights reserved.

A connection between the Efferent Auditory System and Noise-Induced Tinnitus Generation. Reduced contralateral suppression of TEOAEs in patients with noise-induced tinnitus.

PubMed

Lalaki, Panagiota; Hatzopoulos, Stavros; Lorito, Guiscardo; Kochanek, Krzysztof; Sliwa, Lech; Skarzynski, Henryk

2011-07-01

Subjective tinnitus is an auditory perception that is not caused by external stimulation, its source being anywhere in the auditory system. Furthermore, evidence exists that exposure to noise alters cochlear micromechanics, either directly or through complex feed-back mechanisms, involving the medial olivocochlear efferent system. The aim of this study was to assess the role of the efferent auditory system in noise-induced tinnitus generation. Contralateral sound-activated suppression of TEOAEs was performed in a group of 28 subjects with noise-induced tinnitus (NIT) versus a group of 35 subjects with normal hearing and tinnitus, without any history of exposure to intense occupational or recreational noise (idiopathic tinnitus-IT). Thirty healthy, normally hearing volunteers were used as controls for the efferent suppression test. Suppression of the TEOAE amplitude less than 1 dB SPL was considered abnormal, giving a false positive rate of 6.7%. Eighteen out of 28 (64.3%) patients of the NIT group and 9 out of 35 (25.7%) patients of the IT group showed abnormal suppression values, which were significantly different from the controls' (p<0.0001 and p<0.045, respectively). The abnormal activity of the efferent auditory system in NIT cases might indicate that either the activity of the efferent fibers innervating the outer hair cells (OHCs) is impaired or that the damaged OHCs themselves respond abnormally to the efferent stimulation.

Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings

PubMed Central

2016-01-01

Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or “edge,” due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. PMID:26823515

Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings.

PubMed

Brown, M Christian

2016-03-01

Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or "edge," due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. Copyright © 2016 the American Physiological Society.

Modeling the time-varying and level-dependent effects of the medial olivocochlear reflex in auditory nerve responses.

PubMed

Smalt, Christopher J; Heinz, Michael G; Strickland, Elizabeth A

2014-04-01

The medial olivocochlear reflex (MOCR) has been hypothesized to provide benefit for listening in noisy environments. This advantage can be attributed to a feedback mechanism that suppresses auditory nerve (AN) firing in continuous background noise, resulting in increased sensitivity to a tone or speech. MOC neurons synapse on outer hair cells (OHCs), and their activity effectively reduces cochlear gain. The computational model developed in this study implements the time-varying, characteristic frequency (CF) and level-dependent effects of the MOCR within the framework of a well-established model for normal and hearing-impaired AN responses. A second-order linear system was used to model the time-course of the MOCR using physiological data in humans. The stimulus-level-dependent parameters of the efferent pathway were estimated by fitting AN sensitivity derived from responses in decerebrate cats using a tone-in-noise paradigm. The resulting model uses a binaural, time-varying, CF-dependent, level-dependent OHC gain reduction for both ipsilateral and contralateral stimuli that improves detection of a tone in noise, similarly to recorded AN responses. The MOCR may be important for speech recognition in continuous background noise as well as for protection from acoustic trauma. Further study of this model and its efferent feedback loop may improve our understanding of the effects of sensorineural hearing loss in noisy situations, a condition in which hearing aids currently struggle to restore normal speech perception.

Cochlear compression: perceptual measures and implications for normal and impaired hearing.

PubMed

Oxenham, Andrew J; Bacon, Sid P

2003-10-01

This article provides a review of recent developments in our understanding of how cochlear nonlinearity affects sound perception and how a loss of the nonlinearity associated with cochlear hearing impairment changes the way sounds are perceived. The response of the healthy mammalian basilar membrane (BM) to sound is sharply tuned, highly nonlinear, and compressive. Damage to the outer hair cells (OHCs) results in changes to all three attributes: in the case of total OHC loss, the response of the BM becomes broadly tuned and linear. Many of the differences in auditory perception and performance between normal-hearing and hearing-impaired listeners can be explained in terms of these changes in BM response. Effects that can be accounted for in this way include poorer audiometric thresholds, loudness recruitment, reduced frequency selectivity, and changes in apparent temporal processing. All these effects can influence the ability of hearing-impaired listeners to perceive speech, especially in complex acoustic backgrounds. A number of behavioral methods have been proposed to estimate cochlear nonlinearity in individual listeners. By separating the effects of cochlear nonlinearity from other aspects of hearing impairment, such methods may contribute towards identifying the different physiological mechanisms responsible for hearing loss in individual patients. This in turn may lead to more accurate diagnoses and more effective hearing-aid fitting for individual patients. A remaining challenge is to devise a behavioral measure that is sufficiently accurate and efficient to be used in a clinical setting.

Mechanisms of Hearing Loss after Blast Injury to the Ear

PubMed Central

Cho, Sung-Il; Gao, Simon S.; Xia, Anping; Wang, Rosalie; Salles, Felipe T.; Raphael, Patrick D.; Abaya, Homer; Wachtel, Jacqueline; Baek, Jongmin; Jacobs, David; Rasband, Matthew N.; Oghalai, John S.

2013-01-01

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the body’s most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction. PMID:23840874

Potential Functional Byproducts from Guava Purée Processing.

PubMed

Lim, Si Yi; Tham, Paik Yean; Lim, Hilary Yi Ler; Heng, Wooi Shin; Chang, Ying Ping

2018-05-10

The valorization of guava waste requires compositional and functional studies. We tested three byproducts of guava purée processing, namely refiner, siever, and decanter. We analyzed the chemical composition and quantified the prebiotic activity score and selected carbohydrates; we also determined the water holding (WHC), oil holding (OHC), cation exchange capacities, bile acid binding, and glucose dialysis retardation (GDR) of the solid fraction and the antioxidative and α-amylase inhibitory capacities (AIC) of the ethanolic extract. Refiner contained 7.7% lipid, 7.08% protein and a relatively high phytate content; it had a high prebiotic activity score and possessed the highest binding capacity with deoxycholic acid. Siever contained high levels of low molecular weight carbohydrates and total tannin but relatively low crude fiber and cellulose contents. It had the highest binding with chenodeoxycholic acid (74.8%), and exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. Decanter was rich in cellulose and had a high prebiotic activity score. The WHC and OHC values of decanter were within a narrow range and also exhibited the highest binding with cholic acid (86.6%), and the highest values of GDR and AIC. The refiner waste could be included in animal feed but requires further processing to reduce the high phytate levels. All three guava byproducts had the potential to be a source of antioxidant dietary fiber (DF), a finding that warrants further in vivo study. To differing extents, the guava byproducts exhibited useful physicochemical binding properties and so possessed the potential for health-promoting activity. These byproducts could also be upgraded to other marketable products so the manufacturers of processed guava might be able to develop their businesses sustainably by making better use of them. © 2018 Institute of Food Technologists®.

Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta).

PubMed

Valero, M D; Burton, J A; Hauser, S N; Hackett, T A; Ramachandran, R; Liberman, M C

2017-09-01

Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 h. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12-27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50-75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents. Copyright © 2017 Elsevier B.V. All rights reserved.

Cochlear Damages Caused by Vibration Exposure

PubMed Central

Moussavi Najarkola, Seyyed Ali; Khavanin, Ali; Mirzaei, Ramazan; Salehnia, Mojdeh; Muhammadnejad, Ahad

2013-01-01

Background Many industrial devices have an excessive vibration which can affect human body systems. The effect of vibration on cochlear histology has been as a debatable problem in occupational health and medicine. Objectives Due to limitation present in human studies, the research was conducted to survey the influence of vibration on cochlear histology in an animal model. Materials and Methods Twelve albino rabbits were experimented as: Vibration group (n = 6; exposed to 1.0 m.s-2 r.m.s vertical whole-body vibration at 4 - 8 Hz for 8 hours per day during 5 consecutive days) versus Control group (n = 6; the same rabbits without vibration exposure). After finishing the exposure scenario, all rabbits were killed by CO2 inhalation; their cochleae were extracted and fixed in 10% formaldehyde for 48 hours, decalcified by 10% nitric acid for 24 hours. Specimens were dehydrated, embedded, sectioned 5 µm thick and stained with Hematoxylin and Eosin for light microscopy observations. Results Severely hydropic degenerated and vacuolated inner hair cells (IHCs) were observed in vibration group compared to the control group. Inter and intracellular edema was appeared in supporting cells (SC). Nuclei of outer hair cells (OHCs) seemed to be pyknotic. Slightly thickened basilar membrane (BM) was probably implied to inter cellular edematous. Tectorial Membrane (TM) was not affected pathologically. Conclusions Whole-body vibration could cause cochlear damages in male rabbits, though vibration-induced auditory functional effects might be resulted as subsequent outcome of prolonged high level vibration exposures. PMID:24616783

Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing.

PubMed

Zong, Liang; Chen, Jin; Zhu, Yan; Zhao, Hong-Bo

2017-07-22

Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low frequency regions, first occurring in the high frequency region and then progressively extending to the middle and low frequency regions with mouse age increased. The speed of hearing loss extending was fast in the basal high frequency region and slow in the apical low frequency region, showing a logarithmic function with mouse age. Before postnatal day 25, there were no significant hearing loss and the reduction of active cochlear amplification in the low frequency region. Hearing loss and the reduction of active cochlear amplification also had frequency difference, severe and large in the high frequency regions. These new data indicate that the effect of gap junction on active cochlear amplification is progressive, but, consistent with our previous report, exists in both high and low frequency regions in adulthood. These new data also suggest that cochlear gap junctions may have an important role in age-related hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

17-hydroxycorticosteroids

MedlinePlus

... cortisol. The test may be used to diagnose Cushing syndrome . This is a disorder that occurs when the ... of 17-OHCS may indicate: A type of Cushing syndrome caused by a tumor in the adrenal gland ...

Earth Radiation Imbalance from a Constellation of 66 Iridium Satellites: Climate Science Aspects

NASA Technical Reports Server (NTRS)

Wiscombe, W.; Chiu, CJ. Y.

2012-01-01

The "global warming hiatus" since the 1998 El Nino, highlighted by Meehl et al., and the resulting "missing energy" problem highlighted by Trenberth et al., has opened the door to a more fundamental view of climate change than mere surface air temperature. That new view is based on two variables which are strongly correlated: the rate of change of ocean heat content d(OHC)/dt; and Earth Radiation Imbalance (ERI) at the top of the atmosphere, whose guesstimated range is 0.4 to 0.9 Watts per square meters (this imbalance being mainly due to increasing CO2). The Argo float array is making better and better measurements of OHC. But existing satellite systems cannot measure ERI to even one significant digit. So, climate model predictions of ERI are used in place of real measurements of it, and the satellite data are tuned to the climate model predictions. Some oceanographers say "just depend on Argo for understanding the global warming hiatus and the missing energy", but we don't think this is a good idea because d(OHC)/dt and ERI have different time scales and are never perfectly correlated. We think the ERB community needs to step up to measuring ERI correctly, just as oceanographers have deployed Argo to measure OHC correctly. This talk will overview a proposed constellation of 66 Earth radiation budget instruments, hosted on Iridium satellites, that will actually be able to measure ERI to at least one significant digit, thus enabling a crucial test of climate models. This constellation will also be able to provide ERI at two-hourly time scales and 500-km spatial scales without extrapolations from uncalibrated narrowband geostationary instruments, using the highly successful methods of GRACE to obtain spatial resolution. This high time resolution would make ERI a synoptic variable like temperature, and allow studies of ERI's response to fast-evolving phenomena like dust storms and hurricanes and even brief excursions of Total Solar Irradiance. Time permitting, we will also discuss the emerging view of clear vs. cloudy and its implications for the traditional ERB approach.

ATP-gamma-S shifts the operating point of outer hair cell transduction towards scala tympani.

PubMed

Bobbin, Richard P; Salt, Alec N

2005-07-01

ATP receptor agonists and antagonists alter cochlear mechanics as measured by changes in distortion product otoacoustic emissions (DPOAE). Some of the effects on DPOAEs are consistent with the hypothesis that ATP affects mechano-electrical transduction and the operating point of the outer hair cells (OHCs). This hypothesis was tested by monitoring the effect of ATP-gamma-S on the operating point of the OHCs. Guinea pigs anesthetized with urethane and with sectioned middle ear muscles were used. The cochlear microphonic (CM) was recorded differentially (scala vestibuli referenced to scala tympani) across the basal turn before and after perfusion (20 min) of the perilymph compartment with artificial perilymph (AP) and ATP-gamma-S dissolved in AP. The operating point was derived from the cochlear microphonics (CM) recorded in response low frequency (200 Hz) tones at high level (106, 112 and 118 dB SPL). The analysis procedure used a Boltzmann function to simulate the CM waveform and the Boltzmann parameters were adjusted to best-fit the calculated waveform to the CM. Compared to the initial perfusion with AP, ATP-gamma-S (333 microM) enhanced peak clipping of the positive peak of the CM (that occurs during organ of Corti displacements towards scala tympani), which was in keeping with ATP-induced displacement of the transducer towards scala tympani. CM waveform analysis quantified the degree of displacement and showed that the changes were consistent with the stimulus being centered on a different region of the transducer curve. The change of operating point meant that the stimulus was applied to a region of the transducer curve where there was greater saturation of the output on excursions towards scala tympani and less saturation towards scala vestibuli. A significant degree of recovery of the operating point was observed after washing with AP. Dose response curves generated by perfusing ATP-gamma-S (333 microM) in a cumulative manner yielded an EC(50) of 19.8 microM. The ATP antagonist PPADS (0.1 mM) failed to block the effect of ATP-gamma-S on operating point, suggesting the response was due to activation of metabotropic and not ionotropic ATP receptors. Multiple perfusions of AP had no significant effect (118 and 112 dB) or moved the operating point slightly (106 dB) in the direction opposite of ATP-gamma-S. Results are consistent with an ATP-gamma-S induced transducer change comparable to a static movement of the organ of Corti or reticular lamina towards scala tympani.

Cochlear microphonic broad tuning curves

NASA Astrophysics Data System (ADS)

Ayat, Mohammad; Teal, Paul D.; Searchfield, Grant D.; Razali, Najwani

2015-12-01

It is known that the cochlear microphonic voltage exhibits much broader tuning than does the basilar membrane motion. The most commonly used explanation for this is that when an electrode is inserted at a particular point inside the scala media, the microphonic potentials of neighbouring hair cells have different phases, leading to cancelation at the electrodes location. In situ recording of functioning outer hair cells (OHCs) for investigating this hypothesis is exceptionally difficult. Therefore, to investigate the discrepancy between the tuning curves of the basilar membrane and those of the cochlear microphonic, and the effect of phase cancellation of adjacent hair cells on the broadness of the cochlear microphonic tuning curves, we use an electromechanical model of the cochlea to devise an experiment. We explore the effect of adjacent hair cells (i.e., longitudinal phase cancellation) on the broadness of the cochlear microphonic tuning curves in different locations. The results of the experiment indicate that active longitudinal coupling (i.e., coupling with active adjacent outer hair cells) only slightly changes the broadness of the CM tuning curves. The results also demonstrate that there is a π phase difference between the potentials produced by the hair bundle and the soma near the place associated with the characteristic frequency based on place-frequency maps (i.e., the best place). We suggest that the transversal phase cancellation (caused by the phase difference between the hair bundle and the soma) plays a far more important role than longitudinal phase cancellation in the broadness of the cochlear microphonic tuning curves. Moreover, by increasing the modelled longitudinal resistance resulting the cochlear microphonic curves exhibiting sharper tuning. The results of the simulations suggest that the passive network of the organ of Corti determines the phase difference between the hair bundle and soma, and hence determines the sharpness of the cochlear microphonic tuning curves.

Purification, characterization and antioxidant properties of a novel polysaccharide extracted from Sorghum bicolor (L.) seeds in sausage.

PubMed

Ben Slima, Sirine; Ktari, Naourez; Trabelsi, Imen; Moussa, Hafedh; Makni, Iskandar; Ben Salah, Riadh

2018-01-01

A novel polysaccharide named Sorghum Water-Soluble Polysaccharide (SWSP) was purified from Sorghum bicolor (L.) seeds. It was structurally characterized by high performance liquid chromatography (HPLC), thin layer chromatography (TLC), Fourier transform-infrared spectroscopy analysis (FT-IR), X-ray diffraction (XRD) and mass spectroscopy (MS). HPLC and TLC showed that SWSP is a glucose polymer. The FT-IR spectrum proved the polysaccharide characteristic band of SWSP. XRD and microscopy analyses revealed that SWSP is a semi-crystalline polymer. Functional properties of SWSP were determined based on Water Holding Capacity (WHC), Oil Holding Capacity (OHC) and emulsification properties. SWSP showed good WHC and OHC, recorded at 3.01±0.03 and 1.02±0.03g/g, respectively and exhibited excellent emulsion properties even after 168h (61.5±0.02%). The effect of SWSP on oxidative stability of sausage during storage up to 12days at 4°C was investigated. Results showed a high rate (P<0.05) of oxymyoglobin and low lipid oxidation. The antioxidant activities of SWSP were also studied in vitro. Results demonstrated that the polysaccharides exhibited interesting 1,1-diphenyl-2-picrylhydrazyl (DPPH), ABTS radical scavenging, and ß-carotene bleaching inhibition activities. Overall, this natural polysaccharide was proved to enhance the oxidation stability of sausages, since it can efficiently substitute synthetic antioxidants in meat industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the CFSv2 CMIP5 decadal predictions

NASA Astrophysics Data System (ADS)

Bombardi, Rodrigo J.; Zhu, Jieshun; Marx, Lawrence; Huang, Bohua; Chen, Hua; Lu, Jian; Krishnamurthy, Lakshmi; Krishnamurthy, V.; Colfescu, Ioana; Kinter, James L.; Kumar, Arun; Hu, Zeng-Zhen; Moorthi, Shrinivas; Tripp, Patrick; Wu, Xingren; Schneider, Edwin K.

2015-01-01

Retrospective decadal forecasts were undertaken using the Climate Forecast System version 2 (CFSv2) as part of Coupled Model Intercomparison Project 5. Decadal forecasts were performed separately by the National Center for Environmental Prediction (NCEP) and by the Center for Ocean-Land-Atmosphere Studies (COLA), with the centers using two different analyses for the ocean initial conditions the NCEP Climate Forecast System Reanalysis (CFSR) and the NEMOVAR-COMBINE analysis. COLA also examined the sensitivity to the inclusion of forcing by specified volcanic aerosols. Biases in the CFSv2 for both sets of initial conditions include cold midlatitude sea surface temperatures, and rapid melting of sea ice associated with warm polar oceans. Forecasts from the NEMOVAR-COMBINE analysis showed strong weakening of the Atlantic Meridional Overturning Circulation (AMOC), eventually approaching the weaker AMOC associated with CFSR. The decadal forecasts showed high predictive skill over the Indian, the western Pacific, and the Atlantic Oceans and low skill over the central and eastern Pacific. The volcanic forcing shows only small regional differences in predictability of surface temperature at 2m (T2m) in comparison to forecasts without volcanic forcing, especially over the Indian Ocean. An ocean heat content (OHC) budget analysis showed that the OHC has substantial memory, indicating potential for the decadal predictability of T2m; however, the model has a systematic drift in global mean OHC. The results suggest that the reduction of model biases may be the most productive path towards improving the model's decadal forecasts.

Storm water best management practices for local roadways.

DOT National Transportation Integrated Search

2015-09-01

Local communities and the Ohio Department of Transportation (ODOT) are required by the Ohio : Environmental Protection Agencys (Ohio EPA) statewide Construction General Permit for Storm : Water Discharges OHC000004 (CGP) to select, design, constru...

A paleo-perspective on ocean heat content: Lessons from the Holocene and Common Era

NASA Astrophysics Data System (ADS)

Rosenthal, Yair; Kalansky, Julie; Morley, Audrey; Linsley, Braddock

2017-01-01

The ocean constitutes the largest heat reservoir in the Earth's energy budget and thus exerts a major influence on its climate. Instrumental observations show an increase in ocean heat content (OHC) associated with the increase in greenhouse emissions. Here we review proxy records of intermediate water temperatures from sediment cores and corals in the equatorial Pacific and northeastern Atlantic Oceans, spanning 10,000 years beyond the instrumental record. These records suggests that intermediate waters were 1.5-2 °C warmer during the Holocene Thermal Maximum than in the last century. Intermediate water masses cooled by 0.9 °C from the Medieval Climate Anomaly to the Little Ice Age. These changes are significantly larger than the temperature anomalies documented in the instrumental record. The implied large perturbations in OHC and Earth's energy budget are at odds with very small radiative forcing anomalies throughout the Holocene and Common Era. We suggest that even very small radiative perturbations can change the latitudinal temperature gradient and strongly affect prevailing atmospheric wind systems and hence air-sea heat exchange. These dynamic processes provide an efficient mechanism to amplify small changes in insolation into relatively large changes in OHC. Over long time periods the ocean's interior acts like a capacitor and builds up large (positive and negative) heat anomalies that can mitigate or amplify small radiative perturbations as seen in the Holocene trend and Common Era anomalies, respectively. Evidently the ocean's interior is more sensitive to small external forcings than the global surface ocean because of the high sensitivity of heat exchange in the high-latitudes to climate variations.

Are recent hurricane (Harvey, Irma, Maria) disasters natural?

NASA Astrophysics Data System (ADS)

Trenberth, K. E.; Lijing, C.; Jacobs, P.; Abraham, J. P.

2017-12-01

Yes and no! Hurricanes are certainly natural, but human-caused climate change is supersizing them, and unbridled growth is exacerbating risk of major damages. The addition of heat-trapping gases to the atmosphere has led to observed increases in upper ocean heat content (OHC). This human-caused increase in OHC supports higher sea surface temperatures (SSTs) and atmospheric moisture. These elevated temperatures and increased moisture availability fuel tropical storms, allowing them to grow larger, longer lasting, and more intense, and with widespread heavy rainfalls. Our preliminary analysis of OHC through the August of 2017 shows not only was it by far the highest on record globally, but it was also the highest on record in the Gulf of Mexico prior to hurricane Harvey occurring. The human influence on the climate is also evident in rising sea levels, which increases risks from storm surges. These climatic changes are taking place against a background of growing habitation along coasts, which further increases the risk storms pose to life and property. This combination of planning choice and climatic change illustrates the tragedy of global warming, as evidenced by Harvey in Houston, Irma in the Caribbean and Florida, and Maria in Puerto Rico. However, future damages and loss of life can be mitigated, by stopping or slowing human-caused climate change, and through proactive planning (e.g., better building codes, increased-capacity drainage systems, shelters, and evacuation plans). We discuss the climatic and planning contexts of the unnatural disasters of the 2017 Atlantic Hurricane season, including novel indices of climate-hurricane influence.

Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum

PubMed Central

Mukherjee, Pallavi; Hough, Greg; Chattopadhyay, Arnab; Navab, Mohamad; Fogelman, Hannah R.; Meriwether, David; Williams, Kevin; Bensinger, Steven; Moller, Travis; Faull, Kym F.; Lusis, Aldons J.; Iruela-Arispe, M. Luisa; Bostrom, Kristina I.; Tontonoz, Peter; Reddy, Srinivasa T.; Fogelman, Alan M.

2017-01-01

Feeding LDL receptor (LDLR)-null mice a Western diet (WD) increased the expression of IFN-β in jejunum as determined by quantitative RT-PCR (RT-qPCR), immunohistochemistry (IHC), and ELISA (all P < 0.0001). WD also increased the expression of cholesterol 25-hydroxylase (CH25H) as measured by RT-qPCR (P < 0.0001), IHC (P = 0.0019), and ELISA (P < 0.0001), resulting in increased levels of 25-hydroxycholesterol (25-OHC) in jejunum as determined by LC-MS/MS (P < 0.0001). Adding ezetimibe at 10 mg/kg/day or adding a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) at 0.06% by weight of diet substantially ameliorated these changes. Adding either ezetimibe or Tg6F to WD also ameliorated WD-induced changes in plasma lipids, serum amyloid A, and HDL cholesterol. Adding the same doses of ezetimibe and Tg6F together to WD (combined formulation) was generally more efficacious compared with adding either agent alone. Surprisingly, adding ezetimibe during the preparation of Tg6F, but before addition to WD, was more effective than the combined formulation for all parameters measured in jejunum (P = 0.0329 to P < 0.0001). We conclude the following: i) WD induces IFN-β, CH25H, and 25-OHC in jejunum; and ii) Tg6F and ezetimibe partially ameliorate WD-induced inflammation by preventing WD-induced increases in IFN-β, CH25H, and 25-OHC. PMID:28592401

Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum.

PubMed

Mukherjee, Pallavi; Hough, Greg; Chattopadhyay, Arnab; Navab, Mohamad; Fogelman, Hannah R; Meriwether, David; Williams, Kevin; Bensinger, Steven; Moller, Travis; Faull, Kym F; Lusis, Aldons J; Iruela-Arispe, M Luisa; Bostrom, Kristina I; Tontonoz, Peter; Reddy, Srinivasa T; Fogelman, Alan M

2017-08-01

Feeding LDL receptor (LDLR)-null mice a Western diet (WD) increased the expression of IFN-β in jejunum as determined by quantitative RT-PCR (RT-qPCR), immunohistochemistry (IHC), and ELISA (all P < 0.0001). WD also increased the expression of cholesterol 25-hydroxylase (CH25H) as measured by RT-qPCR ( P < 0.0001), IHC ( P = 0.0019), and ELISA ( P < 0.0001), resulting in increased levels of 25-hydroxycholesterol (25-OHC) in jejunum as determined by LC-MS/MS ( P < 0.0001). Adding ezetimibe at 10 mg/kg/day or adding a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) at 0.06% by weight of diet substantially ameliorated these changes. Adding either ezetimibe or Tg6F to WD also ameliorated WD-induced changes in plasma lipids, serum amyloid A, and HDL cholesterol. Adding the same doses of ezetimibe and Tg6F together to WD (combined formulation) was generally more efficacious compared with adding either agent alone. Surprisingly, adding ezetimibe during the preparation of Tg6F, but before addition to WD, was more effective than the combined formulation for all parameters measured in jejunum ( P = 0.0329 to P < 0.0001). We conclude the following: i ) WD induces IFN-β, CH25H, and 25-OHC in jejunum; and ii ) Tg6F and ezetimibe partially ameliorate WD-induced inflammation by preventing WD-induced increases in IFN-β, CH25H, and 25-OHC. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Correlation of concentration of modified cassava flour for banana fritter flour using simple linear regression

NASA Astrophysics Data System (ADS)

Herminiati, A.; Rahman, T.; Turmala, E.; Fitriany, C. G.

2017-12-01

The purpose of this study was to determine the correlation of different concentrations of modified cassava flour that was processed for banana fritter flour. The research method consists of two stages: (1) to determine the different types of flour: cassava flour, modified cassava flour-A (using the method of the lactid acid bacteria), and modified cassava flour-B (using the method of the autoclaving cooling cycle), then conducted on organoleptic test and physicochemical analysis; (2) to determine the correlation of concentration of modified cassava flour for banana fritter flour, by design was used simple linear regression. The factors were used different concentrations of modified cassava flour-B (y1) 40%, (y2) 50%, and (y3) 60%. The response in the study includes physical analysis (whiteness of flour, water holding capacity-WHC, oil holding capacity-OHC), chemical analysis (moisture content, ash content, crude fiber content, starch content), and organoleptic (color, aroma, taste, texture). The results showed that the type of flour selected from the organoleptic test was modified cassava flour-B. Analysis results of modified cassava flour-B component containing whiteness of flour 60.42%; WHC 41.17%; OHC 21.15%; moisture content 4.4%; ash content 1.75%; crude fiber content 1.86%; starch content 67.31%. The different concentrations of modified cassava flour-B with the results of the analysis provides correlation to the whiteness of flour, WHC, OHC, moisture content, ash content, crude fiber content, and starch content. The different concentrations of modified cassava flour-B does not affect the color, aroma, taste, and texture.

From Help-Seekers to Influential Users: A Systematic Review of Participation Styles in Online Health Communities

PubMed Central

Ali, Kathina; Cunningham, John Alastair; Griffiths, Kathleen Margaret

2015-01-01

Background Understanding how people participate in and contribute to online health communities (OHCs) is useful knowledge in multiple domains. It is helpful for community managers in developing strategies for building community, for organizations in disseminating information about health interventions, and for researchers in understanding the social dynamics of peer support. Objective We sought to determine if any patterns were apparent in the nature of user participation across online health communities. Methods The current study involved a systematic review of all studies that have investigated the nature of participation in an online health community and have provided a quantifiable method for categorizing a person based on their participation style. A systematic search yielded 20 papers. Results Participatory styles were classified as either multidimensional (based on multiple metrics) or unidimensional (based on one metric). With respect to the multidimensional category, a total of 41 different participation styles were identified ranging from Influential Users who were leaders on the board to Topic-Focused Responders who focused on a specific topic and tended to respond to rather than initiate posts. However, there was little overlap in participation styles identified both across OHCs for different health conditions and within OHCs for specific health conditions. Five of the 41 styles emerged in more than one study (Hubs, Authorities, Facilitators, Prime Givers, and Discussants), but the remainder were reported in only one study. The focus of the unidimensional studies was on level of engagement and particularly on high-engaged users. Eight different metrics were used to evaluate level of engagement with the greatest focus on frequency of posts. Conclusions With the exception of high-engaged users based on high post frequency, the current review found little evidence for consistent participatory styles across different health communities. However, this area of research is in its infancy, with most of the studies included in the review being published in the last 2 years. Nevertheless, the review delivers a nomenclature for OHC participation styles and metrics and discusses important methodological issues that will provide a basis for future comparative research in the area. Further studies are required to systematically investigate a range of participatory styles, to investigate their association with different types of online health communities and to determine the contribution of different participatory styles within and across online health communities. PMID:26627369

Oceanographic, Air-sea Interaction, and Environmental Aspects of Artificial Upwelling Produced by Wave-Inertia Pumps for Potential Hurricane Intensity Mitigation

NASA Astrophysics Data System (ADS)

Soloviev, A.; Dean, C.

2017-12-01

The artificial upwelling system consisting of the wave-inertia pumps driven by surface waves can produce flow of cold deep water to the surface. One of the recently proposed potential applications of the artificial upwelling system is the hurricane intensity mitigation. Even relatively small reduction of intensity may provide significant benefits. The ocean heat content (OHC) is the "fuel" for hurricanes. The OHC can be reduced by mixing of the surface layer with the cold water produced by wave-inertia pumps. Implementation of this system for hurricane mitigation has several oceanographic and air-sea interaction aspects. The cold water brought to the surface from a deeper layer has higher density than the surface water and, therefore, tends to sink back down. The mixing of the cold water produced by artificial upwelling depends on environmental conditions such as stratification, regional ocean circulation, and vertical shear. Another aspect is that as the sea surface temperature drops below the air temperature, the stable stratification develops in the atmospheric boundary layer. The stable atmospheric stratification suppresses sensible and latent heat air-sea fluxes and reduces the net longwave irradiance from the sea surface. As a result, the artificial upwelling may start increasing the OHC (though still reducing the sea surface temperature). In this work, the fate of the cold water in the stratified environment with vertical shear has been studied using computational fluid dynamics (CFD) tools. A 3D large eddy simulation model is initialized with observational temperature, salinity, and current velocity data from a sample location in the Straits of Florida. A periodic boundary condition is set along the direction of the current, which allows us to simulate infinite fetch. The model results indicate that the cold water brought to the sea surface by a wave-inertia pump forms a convective jet. This jet plunges into the upper ocean mixed layer and penetrates the thermocline. On the way down, the jet partially mixes with the surrounding water reducing the temperature of the upper ocean. The OHC thus can either reduce or increase, depending on the wave-inertia pump parameters. Based on the model results, we discuss feasibility of the implementation of the artificial upwelling system for hurricane intensity mitigation.

From Help-Seekers to Influential Users: A Systematic Review of Participation Styles in Online Health Communities.

PubMed

Carron-Arthur, Bradley; Ali, Kathina; Cunningham, John Alastair; Griffiths, Kathleen Margaret

2015-12-01

Understanding how people participate in and contribute to online health communities (OHCs) is useful knowledge in multiple domains. It is helpful for community managers in developing strategies for building community, for organizations in disseminating information about health interventions, and for researchers in understanding the social dynamics of peer support. We sought to determine if any patterns were apparent in the nature of user participation across online health communities. The current study involved a systematic review of all studies that have investigated the nature of participation in an online health community and have provided a quantifiable method for categorizing a person based on their participation style. A systematic search yielded 20 papers. Participatory styles were classified as either multidimensional (based on multiple metrics) or unidimensional (based on one metric). With respect to the multidimensional category, a total of 41 different participation styles were identified ranging from Influential Users who were leaders on the board to Topic-Focused Responders who focused on a specific topic and tended to respond to rather than initiate posts. However, there was little overlap in participation styles identified both across OHCs for different health conditions and within OHCs for specific health conditions. Five of the 41 styles emerged in more than one study (Hubs, Authorities, Facilitators, Prime Givers, and Discussants), but the remainder were reported in only one study. The focus of the unidimensional studies was on level of engagement and particularly on high-engaged users. Eight different metrics were used to evaluate level of engagement with the greatest focus on frequency of posts. With the exception of high-engaged users based on high post frequency, the current review found little evidence for consistent participatory styles across different health communities. However, this area of research is in its infancy, with most of the studies included in the review being published in the last 2 years. Nevertheless, the review delivers a nomenclature for OHC participation styles and metrics and discusses important methodological issues that will provide a basis for future comparative research in the area. Further studies are required to systematically investigate a range of participatory styles, to investigate their association with different types of online health communities and to determine the contribution of different participatory styles within and across online health communities.

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

PubMed

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Complete Genome Sequence of Pseudomonas chlororaphis subsp. aurantiaca Reveals a Triplicate Quorum-Sensing Mechanism for Regulation of Phenazine Production

PubMed Central

Morohoshi, Tomohiro; Yamaguchi, Takahito; Xie, Xiaonan; Wang, Wen-zhao; Takeuchi, Kasumi; Someya, Nobutaka

2017-01-01

Pseudomonas chlororaphis subsp. aurantiaca StFRB508 regulates phenazine production through N-acyl-l-homoserine lactone (AHL)-mediated quorum sensing. Two sets of AHL-synthase and AHL-receptor genes, phzI/phzR and aurI/aurR, have been identified from the incomplete draft genome of StFRB508. In the present study, the complete genome of StFRB508, comprising a single chromosome of 6,997,933 bp, was sequenced. The complete genome sequence revealed the presence of a third quorum-sensing gene set, designated as csaI/csaR. An LC-MS/MS analysis revealed that StFRB508 produced six types of AHLs, with the most important AHL being N-(3-hydroxyhexanoyl)-l-homoserine lactone (3-OH-C6-HSL). PhzI mainly catalyzed the biosynthesis of 3-OH-C6-HSL, while AurI and CsaI catalyzed that of N-hexanoyl-l-homoserine lactone and N-(3-oxohexanoyl)-l-homoserine lactone, respectively. A mutation in phzI decreased phenazine production, whereas that in aurI or csaI did not. A phzI aurI csaI triple mutant (508ΔPACI) did not produce phenazine. Phenazine production by 508ΔPACI was stimulated by exogenous AHLs and 3-OH-C6-HSL exerted the strongest effects on phenazine production at the lowest concentration tested (0.1 μM). The plant protection efficacy of 508ΔPACI against an oomycete pathogen was lower than that of wild-type StFRB508. These results demonstrate that the triplicate quorum-sensing system plays an important role in phenazine production by and the biocontrol activity of StFRB508. PMID:28239068

Oxygenated N-Acyl Alanine Methyl Esters (NAMEs) from the Marine Bacterium Roseovarius tolerans EL-164.

PubMed

Bruns, Hilke; Herrmann, Jennifer; Müller, Rolf; Wang, Hui; Wagner Döbler, Irene; Schulz, Stefan

2018-01-26

The marine bacterium Roseovarius tolerans EL-164 (Rhodobacteraceae) can produce unique N-acylalanine methyl esters (NAMEs) besides strucutrally related N-acylhomoserine lactones (AHLs), bacterial signaling compounds widespread in the Rhodobacteraceae. The structures of two unprecedented NAMEs carrying a rare terminally oxidized acyl chain are reported here. The compounds (Z)-N-16-hydroxyhexadec-9-enoyl-l-alanine methyl ester (Z9-16-OH-C16:1-NAME, 3) and (Z)-N-15-carboxypentadec-9-enoyl-l-alanine methyl ester (16COOH-C16:1-NAME, 4) were isolated, and the structures were determined by NMR and MS experiments. Both compounds were synthesized to prove assignments and to test their biological activity. Finally, non-natural, structurally related Z9-3-OH-C16:1-NAME (18) was synthesized to investigate the mass spectroscopy of structurally related NAMEs. Compound 3 showed moderate antibacterial activity against microorganisms such as Bacillus, Streptococcus, Micrococcus, or Mucor strains. In contrast to AHLs, quorum-sensing or quorum-quenching activity was not observed.

On the Stark effect in open shell complexes exhibiting partially quenched electronic angular momentum: Infrared laser Stark spectroscopy of OH–C 2H 2, OH–C 2H 4, and OH–H 2O

DOE PAGES

Moradi, Christopher P.; Douberly, Gary E.

2015-06-22

The Stark effect is considered for polyatomic open shell complexes that exhibit partially quenched electronic angular momentum. Matrix elements of the Stark Hamiltonian represented in a parity conserving Hund's case (a) basis are derived for the most general case, in which the permanent dipole moment has projections on all three inertial axes of the system. Transition intensities are derived, again for the most general case, in which the laser polarization has projections onto axes parallel and perpendicular to the Stark electric field, and the transition dipole moment vector is projected onto all three inertial axes in the molecular frame. Asmore » a result, simulations derived from this model are compared to experimental rovibrational Stark spectra of OH-C 2H 2, OH-C 2H 4, and OH-H 2O complexes formed in helium nanodroplets.« less

Induction of Endothelial Phenotype From Wharton's Jelly-Derived MSCs and Comparison of Their Vasoprotective and Neuroprotective Potential With Primary WJ-MSCs in CA1 Hippocampal Region Ex Vivo.

PubMed

Obtulowicz, Patrycja; Lech, Wioletta; Strojek, Lukasz; Sarnowska, Anna; Domanska-Janik, Krystyna

2016-01-01

Ischemic stroke results in violent impairment of tissue homeostasis leading to severe perturbation within the neurovascular unit (NVU) during the recovery period. The aim of this study was to assess the potential of mesenchymal stem cells (MSCs) originating from Wharton's jelly (WJ) to differentiate into functionally competent cells of endothelial lineage (WJ-EPCs). The protective effect(s) of either primary WJ-MSCs or induced WJ-EPCs was investigated and compared after oxygen-glucose deprivation (OGD) of hippocampal organotypic slices (OHC) in the indirect coculture model. WJ-MSCs, primed in EGM-2 (Lonza commercial medium) under 5% O2, acquired cobblestone endothelial-like morphology, formed capillary-like structures and actively took up DiI-Ac-LDL. Both cell types (WJ-MSCs and WJ-EPCs) were positive for CD73, CD90, CD105, VEGFR-2, and VEGF, but only endothelial-like culture expressed vWF and PECAM-1 markers at significant levels. In the presence of either WJ-MSCs or WJ-EPCs in the compartment below OGD-injured slices, cell death and vascular atrophy in the hypoxia-sensitive CA1 region were substantially decreased. This suggests that a paracrine mechanism may mediate WJ-MSC- and WJ-EPC-dependent protection. Thus, finally, we estimated secretion of the neuro/angio/immunomodulatory molecules IL-6, TGF-β1, and VEGF by these cell cultures. We have found that release of TGF-β1 and IL-6 was TLR ligand [LPS and Poly(I:C)] concentration dependent and stronger in WJ-EPC than WJ-MSC cultures. Simultaneously, the uneven pattern of TLR receptors and modulatory cytokine gene expression was confirmed also on qRT-PCR level, but no significant differences were noticed between WJ-EPC and primary WJ-MSC cultures.

Effects of Incorporation of Jackfruit Rind Powder on Chemical and Functional Properties of Bread

PubMed Central

Felli, Reza; Yang, Tajul Aris; Abdullah, Wan Nadiah Wan; Zzaman, Wahidu

2018-01-01

Nowadays, there is a rising interest towards consuming health beneficial food products. Bread–as one of the most popular food products–could be improved to ‘healthy bread’ by addition of ingredients high in protein, dietary fiber and low in calorie. Incorporating Jackfruit rind powder (JRP) as a by-product rich in dietary fiber in bread, could not only provide health beneficial bread products, but also lead to develop an environmental friendly technology by solving the problem of waste disposal of residues. In this study, addition of jackfruit rind powder (JRP) as a high dietary fiber and functional ingredient in bread was examined. The results showed that incorporation of JRP in bread improved functional properties of flour such as Oil Holding Capacity (OHC), Water Holding Capacity (WHC) and pasting properties. Addition of 5%, 10% and 15% of JRP in wheat flour caused significantly (p < 0.05) higher insoluble, soluble and total dietary fiber in flour and bread products. Results from proximate composition indicated that all breads substituted with JRP, contained significantly (p < 0.05) higher fiber, moisture and fat. Obtained results confirmed that the JRP has great potential in development of functional foods especially functional bread products. PMID:29644019

Effects of Incorporation of Jackfruit Rind Powder on Chemical and Functional Properties of Bread.

PubMed

Felli, Reza; Yang, Tajul Aris; Abdullah, Wan Nadiah Wan; Zzaman, Wahidu

2018-03-01

Nowadays, there is a rising interest towards consuming health beneficial food products. Bread-as one of the most popular food products-could be improved to 'healthy bread' by addition of ingredients high in protein, dietary fiber and low in calorie. Incorporating Jackfruit rind powder (JRP) as a by-product rich in dietary fiber in bread, could not only provide health beneficial bread products, but also lead to develop an environmental friendly technology by solving the problem of waste disposal of residues. In this study, addition of jackfruit rind powder (JRP) as a high dietary fiber and functional ingredient in bread was examined. The results showed that incorporation of JRP in bread improved functional properties of flour such as Oil Holding Capacity (OHC), Water Holding Capacity (WHC) and pasting properties. Addition of 5%, 10% and 15% of JRP in wheat flour caused significantly (p < 0.05) higher insoluble, soluble and total dietary fiber in flour and bread products. Results from proximate composition indicated that all breads substituted with JRP, contained significantly (p < 0.05) higher fiber, moisture and fat. Obtained results confirmed that the JRP has great potential in development of functional foods especially functional bread products.

Catecholamine, Corticosteroid and Ketone Excretion in Exercise and Hypoxia,

DTIC Science & Technology

OHCS excretion tended to be higher during the experimental period and subsequently lower overnight during the hypoxia week. Ketosis occurred in two...subjects. In one of these it could be readily related to previous extraneous stress. Excretion of unidentified ketones in overnight urines was sometimes suspected and occurred beyond doubt following gross ketosis . (Author)

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

Mechanisms underlying recent decadal changes in subpolar North Atlantic Ocean heat content

NASA Astrophysics Data System (ADS)

Piecuch, Christopher G.; Ponte, Rui M.; Little, Christopher M.; Buckley, Martha W.; Fukumori, Ichiro

2017-09-01

The subpolar North Atlantic (SPNA) is subject to strong decadal variability, with implications for surface climate and its predictability. In 2004-2005, SPNA decadal upper ocean and sea-surface temperature trends reversed from warming during 1994-2004 to cooling over 2005-2015. This recent decadal trend reversal in SPNA ocean heat content (OHC) is studied using a physically consistent, observationally constrained global ocean state estimate covering 1992-2015. The estimate's physical consistency facilitates quantitative causal attribution of ocean variations. Closed heat budget diagnostics reveal that the SPNA OHC trend reversal is the result of heat advection by midlatitude ocean circulation. Kinematic decompositions reveal that changes in the deep and intermediate vertical overturning circulation cannot account for the trend reversal, but rather ocean heat transports by horizontal gyre circulations render the primary contributions. The shift in horizontal gyre advection reflects anomalous circulation acting on the mean temperature gradients. Maximum covariance analysis (MCA) reveals strong covariation between the anomalous horizontal gyre circulation and variations in the local wind stress curl, suggestive of a Sverdrup response. Results have implications for decadal predictability.

DisVis: Visualizing Discussion Threads in Online Health Communities.

PubMed

Nakikj, Drashko; Mamykina, Lena

2016-01-01

An increasing number of individuals turn to online health communities (OHC) for information, advice and support about their health condition or disease. As a result of users' active participation, these forums store overwhelming volumes of information, which can make access to this information challenging and frustrating. To help overcome this problem we designed a discussion visualization tool DisVis. DisVis includes features for overviewing, browsing and finding particular information in a discussion. In a between subjects study, we tested the impact of DisVis on individuals' ability to provide an overview of a discussion, find topics of interest and summarize opinions. The study showed that after using the tool, the accuracy of participants' answers increased by 68% (p-value = 0.023) while at the same time exhibiting trends for reducing the time to answer by 38% with no statistical significance (p-value = 0.082). Qualitative interviews showed general enthusiasm regarding tools for improving browsing and searching for information within discussion forums, suggested different usage scenarios, highlighted opportunities for improving the design of DisVis, and outlined new directions for visualizing user-generated content within OHCs.

Methyl chloride via oxyhydrochlorination of methane: A building block for chemicals and fuels from natural gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, R.L.; Brown, S.S.D.; Ferguson, S.P.

1995-12-31

The objectives of this program are to (a) develop a process for converting natural gas to methyl chloride via an oxyhydrochlorination route using highly selective, stable catalysts in a fixed-bed, (b) design a reactor capable of removing the large amount of heat generated in the process so as to control the reaction, (c) develop a recovery system capable of removing the methyl chloride from the product stream and (d) determine the economics and commercial viability of the process. The general approach has been as follows: (a) design and build a laboratory scale reactor, (b) define and synthesize suitable OHC catalystsmore » for evaluation, (c) select first generation OHC catalyst for Process Development Unit (PDU) trials, (d) design, construct and startup PDU, (e) evaluate packed bed reactor design, (f) optimize process, in particular, product recovery operations, (g) determine economics of process, (h) complete preliminary engineering design for Phase II and (i) make scale-up decision and formulate business plan for Phase II. Conclusions regarding process development and catalyst development are presented.« less

Chemical composition and functional characteristics of dietary fiber-rich powder obtained from core of maize straw.

PubMed

Lv, Jin-Shun; Liu, Xiao-Yan; Zhang, Xiao-Pan; Wang, Lin-Shuang

2017-07-15

A novel dietary fiber (MsCDF) based core of maize straw (Core) was prepared by using high boiling solvent of sodium peroxide by high pressure pretreatment (HBSHP). The composition of MsCDF, and several physicochemical properties for MsCDF related to its nutritional quality were investigated. The results revealed that the MsCDF contains high contents total dietary fiber (TDF), soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and two main monosaccharaides, xylose and glucose. Meanwhile, the studies of physicochemical properties of MsCDF indicated that MsCDF performed well water-holding capacity (WHC), oil-holding capacity (OHC), Swelling, solubility (SOL), Glucose dialysis retardation index (GDRI) and adsorption capacity on cholesterol. The results of this study serve as evidence that MsCDF can be used as a functional food additive, Core can be used as a crude material to produce MsCDF and the technology of HBSHP can be used to modify the physico-chemical properties of Core. Copyright © 2017 Elsevier Ltd. All rights reserved.

Utilization of softwood kraft lignin as adhsive for the manufacture of reconstituted wood

Treesearch

Lin-Wu Zhao; Bruce F. Griggs; Chen-Loung Chen; Josef S. Gratzl; Chung-Yun Hse

1994-01-01

Reaction conditions for hydroxymethylation of pine kraft lignin (KL) were optimized by kinetic studies of the reaction. Characterization of the resulting hydroxymethylated kraft lignin (HMKL) indicated that about 0.36 mole of the -CH2OH/C9 unit was introduced into the ognin under the optimal reaction conditions, of which...

Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia.

PubMed

Hua, Fang; Xie, Huixu; Worthington, Helen V; Furness, Susan; Zhang, Qi; Li, Chunjie

2016-10-25

Ventilator-associated pneumonia (VAP) is defined as pneumonia developing in people who have received mechanical ventilation for at least 48 hours. VAP is a potentially serious complication in these patients who are already critically ill. Oral hygiene care (OHC), using either a mouthrinse, gel, toothbrush, or combination, together with aspiration of secretions, may reduce the risk of VAP in these patients. To assess the effects of oral hygiene care on incidence of ventilator-associated pneumonia in critically ill patients receiving mechanical ventilation in hospital intensive care units (ICUs). We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 17 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2015, Issue 11), MEDLINE Ovid (1946 to 17 December 2015), Embase Ovid (1980 to 17 December 2015), LILACS BIREME Virtual Health Library (1982 to 17 December 2015), CINAHL EBSCO (1937 to 17 December 2016), Chinese Biomedical Literature Database (1978 to 14 January 2013), China National Knowledge Infrastructure (1994 to 14 January 2013), Wan Fang Database (January 1984 to 14 January 2013) and VIP Database (January 2012 to 4 May 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials to 17 December 2015. We placed no restrictions on the language or date of publication when searching the electronic databases. We included randomised controlled trials (RCTs) evaluating the effects of OHC (mouthrinse, swab, toothbrush or combination) in critically ill patients receiving mechanical ventilation for at least 48 hours. At least two review authors independently assessed search results, extracted data and assessed risk of bias in included studies. We contacted study authors for additional information. We pooled data from trials with similar interventions and outcomes. We reported risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, using random-effects models unless there were fewer than four studies. We included 38 RCTs (6016 participants). There were four main comparisons: chlorhexidine (CHX) mouthrinse or gel versus placebo/usual care; toothbrushing versus no toothbrushing; powered versus manual toothbrushing; and comparisons of oral care solutions. We assessed the overall risk of bias as low in five trials (13%), high in 26 trials (68%), and unclear in seven trials (18%). We did not consider the risk of bias to be serious when assessing the quality of evidence (GRADE) for VAP incidence, but we downgraded other outcomes for risk of bias.High quality evidence from 18 RCTs (2451 participants, 86% adults) shows that CHX mouthrinse or gel, as part of OHC, reduces the risk of VAP compared to placebo or usual care from 25% to about 19% (RR 0.74, 95% confidence intervals (CI) 0.61 to 0.89, P = 0.002, I 2 = 31%). This is equivalent to a number needed to treat for an additional beneficial outcome (NNTB) of 17 (95% CI 10 to 33), which indicates that for every 17 ventilated patients in intensive care receiving OHC including chlorhexidine, one outcome of VAP would be prevented. There is no evidence of a difference between CHX and placebo/usual care for the outcomes of mortality (RR 1.09, 95% CI 0.96 to 1.23, P = 0.18, I 2 = 0%, 15 RCTs, 2163 participants, moderate quality evidence), duration of mechanical ventilation (MD -0.09 days, 95% CI -1.73 to 1.55 days, P = 0.91, I 2 = 36%, five RCTs, 800 participants, low quality evidence), or duration of intensive care unit (ICU) stay (MD 0.21 days, 95% CI -1.48 to 1.89 days, P = 0.81, I 2 = 9%, six RCTs, 833 participants, moderate quality evidence). There is insufficient evidence to determine the effect of CHX on duration of systemic antibiotics, oral health indices, caregivers' preferences or cost. Only two studies reported any adverse effects, and these were mild with similar frequency in CHX and control groups.We are uncertain as to the effects of toothbrushing (± antiseptics) on the outcomes of VAP (RR 0.69, 95% CI 0.44 to 1.09, P = 0.11, I 2 = 64%, five RCTs, 889 participants, very low quality evidence) and mortality (RR 0.87, 95% CI 0.70 to 1.09, P = 0.24, I 2 = 0%, five RCTs, 889 participants, low quality evidence) compared to OHC without toothbrushing (± antiseptics). There is insufficient evidence to determine whether toothbrushing affects duration of mechanical ventilation, duration of ICU stay, use of systemic antibiotics, oral health indices, adverse effects, caregivers' preferences or cost.Only one trial (78 participants) compared use of a powered toothbrush with a manual toothbrush, providing insufficient evidence to determine the effect on any of the outcomes of this review.Fifteen trials compared various other oral care solutions. There is very weak evidence that povidone iodine mouthrinse is more effective than saline/placebo (RR 0.69, 95% CI 0.50 to 0.95, P = 0.02, I 2 = 74%, three studies, 356 participants, high risk of bias), and that saline rinse is more effective than saline swab (RR 0.47, 95% CI 0.37 to 0.62, P < 0.001, I 2 = 84%, four studies, 488 participants, high risk of bias) in reducing VAP. Due to variation in comparisons and outcomes among trials, there is insufficient evidence concerning the effects of other oral care solutions. OHC including chlorhexidine mouthwash or gel reduces the risk of developing ventilator-associated pneumonia in critically ill patients from 25% to about 19%. However, there is no evidence of a difference in the outcomes of mortality, duration of mechanical ventilation or duration of ICU stay. There is no evidence that OHC including both antiseptics and toothbrushing is different from OHC with antiseptics alone, and some weak evidence to suggest that povidone iodine mouthrinse is more effective than saline/placebo, and saline rinse is more effective than saline swab in reducing VAP. There is insufficient evidence to determine whether powered toothbrushing or other oral care solutions are effective in reducing VAP. There is also insufficient evidence to determine whether any of the interventions evaluated in the studies are associated with adverse effects.

One Health training, research, and outreach in North America

PubMed Central

Stroud, Cheryl; Kaplan, Bruce; Logan, Jenae E.

2016-01-01

Background The One Health (OH) concept, formerly referred to as ‘One Medicine’ in the later part of the 20th century, has gained exceptional popularity in the early 21st century, and numerous academic and non-academic institutions have developed One Health programs. Objectives To summarize One Health training, research, and outreach activities originating in North America. Methods We used data from extensive electronic records maintained by the One Health Commission (OHC) (www.onehealthcommission.org/) and the One Health Initiative (www.onehealthinitiative.com/) and from web-based searches, combined with the corporate knowledge of the authors and their professional contacts. Finally, a call was released to members of the OHC's Global One Health Community listserv, asking that they populate a Google document with information on One Health training, research, and outreach activities in North American academic and non-academic institutions. Results A current snapshot of North American One Health training, research, and outreach activities as of August 2016 has evolved. Conclusions It is clear that the One Health concept has gained considerable recognition during the first decade of the 21st century, with numerous current training and research activities carried out among North American academic, non-academic, government, corporate, and non-profit entities. PMID:27906120

Co-encapsulation of curcumin and resveratrol into novel nutraceutical hyalurosomes nano-food delivery system based on oligo-hyaluronic acid-curcumin polymer.

PubMed

Guo, Chunjing; Yin, Jungang; Chen, Daquan

2018-02-01

In this work, in order to enhance the stability, bioavailability and antioxidant activity of insoluble antioxidants used into juice, yoghourt and nutritional supplements, the oligo-hyalurosomes nano-delivery system (CRHs) based on oligo-hyaluronic acid -curcumin (oHC) polymer loaded curcumin(Cur) and resveratrol (Res) was fabricated with new nanotechnolgy. The rosy biodegradable amphiphilic oHC polymer was successfully synthesized and used to fabricate the hyalurosomes containing both Cur and Res, called CRHs. The CRHs can spontaneously self-assemble into nano-sized spherical shape of average particle size 134.5±5.1nm and Zeta potential -29.4±1.2 at pH 7.4 PBS conditions. In vitro gastrointestinal release test showed a perfect stability and outstanding sustained release character. Moreover, compared to the single formulations and liposomes, CRHs showed a dose-dependent manner with a higher radical scavenging activity. Therefore, the novel CRHs nano-food manifested the hopeful properties for the new effective gastrointestinal formulation and promising new nano-food delivery system in the use of juice, yoghourt and nutritional supplements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simulation of mechano-electrical transduction in the cochlea considering basilar membrane vibration and the ionic current of the inner hair cells

NASA Astrophysics Data System (ADS)

Lee, Sinyoung; Koike, Takuji

2018-05-01

The inner hair cells (IHCs) in the cochlea transduce mechanical vibration of the basilar membrane (BM), caused by sound pressure, to electrical signals that are transported along the acoustic nerve to the brain. The mechanical vibration of the BM and the ionic behaviors of the IHCs have been investigated. However, consideration of the ionic behavior of the IHCs related to mechanical vibration is necessary to investigate the mechano-electrical transduction of the cochlea. In this study, a finite-element model of the BM, which takes into account the non-linear activities of the outer hair cells (OHCs), and an ionic current model of IHC were combined. The amplitudes and phases of the vibration at several points on the BM were obtained from the finite-element model by applying sound pressure. These values were fed into the ionic current model, and changes in membrane potential and calcium ion concentration of the IHCs were calculated. The membrane potential of the IHC at the maximum amplitude point (CF point) was higher than that at the non-CF points. The calcium ion concentration at the CF point was also higher than that at the non-CF points. These results suggest that the cochlea achieves its good frequency discrimination ability through mechano-electrical transduction.

Single Cell Oncogenesis

NASA Astrophysics Data System (ADS)

Lu, Xin

It is believed that cancer originates from a single cell that has gone through generations of evolution of genetic and epigenetic changes that associate with the hallmarks of cancer. In some cancers such as various types of leukemia, cancer is clonal. Yet in other cancers like glioblastoma (GBM), there is tremendous tumor heterogeneity that is likely to be caused by simultaneous evolution of multiple subclones within the same tissue. It is obvious that understanding how a single cell develops into a clonal tumor upon genetic alterations, at molecular and cellular levels, holds the key to the real appreciation of tumor etiology and ultimate solution for therapeutics. Surprisingly very little is known about the process of spontaneous tumorigenesis from single cells in human or vertebrate animal models. The main reason is the lack of technology to track the natural process of single cell changes from a homeostatic state to a progressively cancerous state. Recently, we developed a patented compound, photoactivatable (''caged'') tamoxifen analogue 4-OHC and associated technique called optochemogenetic switch (OCG switch), which we believe opens the opportunity to address this urgent biological as well as clinical question about cancer. We propose to combine OCG switch with genetically engineered mouse models of head and neck squamous cell carcinoma and high grade astrocytoma (including GBM) to study how single cells, when transformed through acute loss of tumor suppressor genes PTEN and TP53 and gain of oncogenic KRAS, can develop into tumor colonies with cellular and molecular heterogeneity in these tissues. The abstract is for my invited talk in session ``Beyond Darwin: Evolution in Single Cells'' 3/18/2016 11:15 AM.

Regulon Studies and In Planta Role of the BraI/R Quorum-Sensing System in the Plant-Beneficial Burkholderia Cluster

PubMed Central

Coutinho, Bruna G.; Mitter, Birgit; Talbi, Chouhra; Sessitsch, Angela; Bedmar, Eulogio J.; Halliday, Nigel; James, Euan K.; Cámara, Miguel

2013-01-01

The genus Burkholderia is composed of functionally diverse species, and it can be divided into several clusters. One of these, designated the plant-beneficial-environmental (PBE) Burkholderia cluster, is formed by nonpathogenic species, which in most cases have been found to be associated with plants. It was previously established that members of the PBE group share an N-acyl-homoserine lactone (AHL) quorum-sensing (QS) system, designated BraI/R, that produces and responds to 3-oxo-C14-HSL (OC14-HSL). Moreover, some of them also possess a second AHL QS system, designated XenI2/R2, producing and responding to 3-hydroxy-C8-HSL (OHC8-HSL). In the present study, we performed liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis to determine which AHL molecules are produced by each QS system of this group of bacteria. The results showed that XenI2/R2 is mainly responsible for the production of OHC8-HSL and that the BraI/R system is involved in the production of several different AHLs. This analysis also revealed that Burkholderia phymatum STM815 produces greater amounts of AHLs than the other species tested. Further studies showed that the BraR protein of B. phymatum is more promiscuous than other BraR proteins, responding equally well to several different AHL molecules, even at low concentrations. Transcriptome studies with Burkholderia xenovorans LB400 and B. phymatum STM815 revealed that the BraI/R regulon is species specific, with exopolysaccharide production being the only common phenotype regulated by this system in the PBE cluster. In addition, BraI/R was shown not to be important for plant nodulation by B. phymatum strains or for endophytic colonization and growth promotion of maize by B. phytofirmans PsJN. PMID:23686262

A Multirelational Social Network Analysis of an Online Health Community for Smoking Cessation.

PubMed

Zhao, Kang; Wang, Xi; Cha, Sarah; Cohn, Amy M; Papandonatos, George D; Amato, Michael S; Pearson, Jennifer L; Graham, Amanda L

2016-08-25

Online health communities (OHCs) provide a convenient and commonly used way for people to connect around shared health experiences, exchange information, and receive social support. Users often interact with peers via multiple communication methods, forming a multirelational social network. Use of OHCs is common among smokers, but to date, there have been no studies on users' online interactions via different means of online communications and how such interactions are related to smoking cessation. Such information can be retrieved in multirelational social networks and could be useful in the design and management of OHCs. To examine the social network structure of an OHC for smoking cessation using a multirelational approach, and to explore links between subnetwork position (ie, centrality) and smoking abstinence. We used NetworkX to construct 4 subnetworks based on users' interactions via blogs, group discussions, message boards, and private messages. We illustrated topological properties of each subnetwork, including its degree distribution, density, and connectedness, and compared similarities among these subnetworks by correlating node centrality and measuring edge overlap. We also investigated coevolution dynamics of this multirelational network by analyzing tie formation sequences across subnetworks. In a subset of users who participated in a randomized, smoking cessation treatment trial, we conducted user profiling based on users' centralities in the 4 subnetworks and identified user groups using clustering techniques. We further examined 30-day smoking abstinence at 3 months postenrollment in relation to users' centralities in the 4 subnetworks. The 4 subnetworks have different topological characteristics, with message board having the most nodes (36,536) and group discussion having the highest network density (4.35×10(-3)). Blog and message board subnetworks had the most similar structures with an in-degree correlation of .45, out-degree correlation of .55, and Jaccard coefficient of .23 for edge overlap. A new tie in the group discussion subnetwork had the lowest probability of triggering subsequent ties among the same two users in other subnetworks: 6.33% (54,142/855,893) for 2-tie sequences and 2.13% (18,207/855,893) for 3-tie sequences. Users' centralities varied across the 4 subnetworks. Among a subset of users enrolled in a randomized trial, those with higher centralities across subnetworks generally had higher abstinence rates, although high centrality in the group discussion subnetwork was not associated with higher abstinence rates. A multirelational approach revealed insights that could not be obtained by analyzing the aggregated network alone, such as the ineffectiveness of group discussions in triggering social ties of other types, the advantage of blogs, message boards, and private messages in leading to subsequent social ties of other types, and the weak connection between one's centrality in the group discussion subnetwork and smoking abstinence. These insights have implications for the design and management of online social networks for smoking cessation.

A Multirelational Social Network Analysis of an Online Health Community for Smoking Cessation

PubMed Central

Wang, Xi; Cha, Sarah; Cohn, Amy M; Papandonatos, George D; Amato, Michael S; Pearson, Jennifer L; Graham, Amanda L

2016-01-01

Background Online health communities (OHCs) provide a convenient and commonly used way for people to connect around shared health experiences, exchange information, and receive social support. Users often interact with peers via multiple communication methods, forming a multirelational social network. Use of OHCs is common among smokers, but to date, there have been no studies on users’ online interactions via different means of online communications and how such interactions are related to smoking cessation. Such information can be retrieved in multirelational social networks and could be useful in the design and management of OHCs. Objective To examine the social network structure of an OHC for smoking cessation using a multirelational approach, and to explore links between subnetwork position (ie, centrality) and smoking abstinence. Methods We used NetworkX to construct 4 subnetworks based on users’ interactions via blogs, group discussions, message boards, and private messages. We illustrated topological properties of each subnetwork, including its degree distribution, density, and connectedness, and compared similarities among these subnetworks by correlating node centrality and measuring edge overlap. We also investigated coevolution dynamics of this multirelational network by analyzing tie formation sequences across subnetworks. In a subset of users who participated in a randomized, smoking cessation treatment trial, we conducted user profiling based on users’ centralities in the 4 subnetworks and identified user groups using clustering techniques. We further examined 30-day smoking abstinence at 3 months postenrollment in relation to users’ centralities in the 4 subnetworks. Results The 4 subnetworks have different topological characteristics, with message board having the most nodes (36,536) and group discussion having the highest network density (4.35×10−3). Blog and message board subnetworks had the most similar structures with an in-degree correlation of .45, out-degree correlation of .55, and Jaccard coefficient of .23 for edge overlap. A new tie in the group discussion subnetwork had the lowest probability of triggering subsequent ties among the same two users in other subnetworks: 6.33% (54,142/855,893) for 2-tie sequences and 2.13% (18,207/855,893) for 3-tie sequences. Users’ centralities varied across the 4 subnetworks. Among a subset of users enrolled in a randomized trial, those with higher centralities across subnetworks generally had higher abstinence rates, although high centrality in the group discussion subnetwork was not associated with higher abstinence rates. Conclusions A multirelational approach revealed insights that could not be obtained by analyzing the aggregated network alone, such as the ineffectiveness of group discussions in triggering social ties of other types, the advantage of blogs, message boards, and private messages in leading to subsequent social ties of other types, and the weak connection between one’s centrality in the group discussion subnetwork and smoking abstinence. These insights have implications for the design and management of online social networks for smoking cessation. PMID:27562640

Quorum Sensing in a Methane-Oxidizing Bacterium.

PubMed

Puri, Aaron W; Schaefer, Amy L; Fu, Yanfen; Beck, David A C; Greenberg, E Peter; Lidstrom, Mary E

2017-03-01

Aerobic methanotrophic bacteria use methane as their sole source of carbon and energy and serve as a major sink for the potent greenhouse gas methane in freshwater ecosystems. Dissecting the molecular details of how these organisms interact in the environment may increase our understanding of how they perform this important ecological role. Many bacterial species use quorum sensing (QS) systems to regulate gene expression in a cell density-dependent manner. We have identified a QS system in the genome of Methylobacter tundripaludum , a dominant methane oxidizer in methane enrichments of sediment from Lake Washington (Seattle, WA). We determined that M. tundripaludum produces primarily N -3-hydroxydecanoyl-l-homoserine lactone (3-OH-C 10 -HSL) and that its production is governed by a positive feedback loop. We then further characterized this system by determining which genes are regulated by QS in this methane oxidizer using transcriptome sequencing (RNA-seq) and discovered that this system regulates the expression of a putative nonribosomal peptide synthetase biosynthetic gene cluster. Finally, we detected an extracellular factor that is produced by M. tundripaludum in a QS-dependent manner. These results identify and characterize a mode of cellular communication in an aerobic methane-oxidizing bacterium. IMPORTANCE Aerobic methanotrophs are critical for sequestering carbon from the potent greenhouse gas methane in the environment, yet the mechanistic details of chemical interactions in methane-oxidizing bacterial communities are not well understood. Understanding these interactions is important in order to maintain, and potentially optimize, the functional potential of the bacteria that perform this vital ecosystem function. In this work, we identify a quorum sensing system in the aerobic methanotroph Methylobacter tundripaludum and use both chemical and genetic methods to characterize this system at the molecular level. Copyright © 2017 American Society for Microbiology.

Examining Mechanisms of Pyrethroid Resistance in Eggs of Two Populations of the Chagas' Disease Vector Triatoma infestans (Hemiptera: Reduviidae).

PubMed

Roca-Acevedo, G; Picollo, M I; Capriotti, N; Sierra, I; Santo-Orihuela, P L

2015-09-01

Chagas disease is a zoonosis transmitted to man by blood-sucking triatomine bugs found in the Americas. Triatoma infestans (Klug, 1834) is the main vector of Chagas' disease in Argentina. The control of this illness relies heavily on vector control through the use of insecticide. However, resistance to pyrethroid insecticides associated with ineffective field treatments has been increasingly reported in T. infestans from Argentina and Bolivia. There are few reports on the expression and causes of resistance in eggs of resistant populations, and even fewer studies on insecticide resistance throughout embryonic development. In this study, we explore the biochemical and molecular mechanisms potentially associated with the deltamethrin resistance assessed in the developing eggs of the Argentinean (Campo Largo) and Bolivian (Entre Ríos) T. infestans populations.We found measurable activity of monooxigenases and pyrethroid esterases throughout embryonic development. The pyrethroid esterase activity grew steadily throughout development in all the studied populations and was highest in eggs 12 d old. Mean enzyme activity increased from 13.6 to 16.3 and 22.2 picomol 7-hydroxycoumarin/min (7-OHC) in eggs of 4-, 7-, and 12 d old from the susceptible reference bug colony. Mean activity of resistant populations increased from 16.0 to 25.9 picomol 7-OHC/min in eggs of 4- to 12 d old in Entre Ríos population, and from 15.9 to 28.9 picomol 7-OHC/min in Campo Largo population. Molecular analysis of susceptible and resistant developing eggs detected L1014F mutation in both resistant populations, but no L925I mutation was found in any of the studied populations.Higher esterase activity and L1014F presence justify the resistance to pyrethroid throughout developing eggs of both studied T. infestans populations. The description of resistance profiles including resistance mechanisms involved will allow a rational design of campaigns for the control of Chagas disease transmission. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor.

PubMed

Verbitsky, M; Rothlin, C V; Katz, E; Elgoyhen, A B

2000-10-01

The rat alpha9 nicotinic acetylcholine receptor (nAChR) was expressed in Xenopus laevis oocytes and tested for its sensitivity to a wide variety of cholinergic compounds. Acetylcholine (ACh), carbachol, choline and methylcarbachol elicited agonist-evoked currents, giving maximal or near maximal responses. Both the nicotinic agonist suberyldicholine as well as the muscarinic agonists McN-A-343 and methylfurtrethonium behaved as weak partial agonists of the receptor. Most classical cholinergic compounds tested, being either nicotinic (nicotine, epibatidine, cytisine, methyllycaconitine, mecamylamine, dihydro-beta-erythroidine), or muscarinic (muscarine, atropine, gallamine, pilocarpine, bethanechol) agonists and antagonists, blocked the recombinant alpha9 receptor. Block by nicotine, epibatidine, cytisine, methyllycaconitine and atropine was overcome at high ACh concentrations, suggesting a competitive type of block. The present results indicate that alpha9 displays mixed nicotinic-muscarinic features that resemble the ones described for the cholinergic receptor of cochlear outer hair cells (OHCs). We suggest that alpha9 contains the structural determinants responsible for the pharmacological properties of the native receptor.

Roles of quorum sensing molecules from Rhizobium etli RT1 in bacterial motility and biofilm formation.

PubMed

Dixit, Swarnita; Dubey, Ramesh Chand; Maheshwari, Dinesh Kumar; Seth, Prahlad Kishore; Bajpai, Vivek K

Strain RT1 was isolated from root nodules of Lens culinaris (a lentil) and characterized as Rhizobium etli (a Gram-negative soil-borne bacterium) by 16S rDNA sequencing and phylogenetic analysis. The signaling molecules produced by R. etli (RT1) were detected and identified by high-performance liquid chromatography coupled with mass spectrometry. The most abundant and biologically active N-acyl homoserine lactone molecules (3-oxo-C 8 -HSL and 3-OH-C 14 -HSL) were detected in the ethyl acetate extract of RT1. The biological role of 3-oxo-C 8 -HSL was evaluated in RT1. Bacterial motility and biofilm formation were affected or modified on increasing concentrations of 3-oxo-C 8 -HSL. Results confirmed the existence of cell communication in RT1 mediated by 3-oxo-C 8 -HSL, and positive correlations were found among quorum sensing, motility and biofilm formation in RT1. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

The Historical Context of the 2017 Hurricane Season's Ocean Warmth

NASA Astrophysics Data System (ADS)

Jacobs, P.; Akella, S.; Trenberth, K. E.; Lijing, C.; Abraham, J. P.

2017-12-01

Public discussion of the unusually active 2017 North Atlantic Hurricane Season quickly focused on the role of sea surface temperatures (SSTs) in the North Atlantic. Some meteorologists characterized them as near-normal, while climate-focused voices tended to characterize them as warmer than average, placing them in the context of anthropogenic warming. Much of this divergence in views can be explained by the relatively recent, relatively warm baseline (1981-2010) used for daily SST information, such as provided by OISSTv2. Longer term records of SSTs, such as HadISST, HadSST, and ERSST only attempt to provide monthly averages, while tropical cyclones have lifetimes on the timescale of days. Further, hurricanes create a cold wake which can impact storm movement and intensity, as well as subsequent storms, but is gradually wiped out by the sun. This process is further complicated by the role of ocean heat content (OHC), an increase in which can mitigate the impact of upwelled water. Here we examine the statistical characteristics of daily SSTs and OHC during the satellite record, including their temporal autocorrelation, and use this information in conjunction with longer term monthly records to bound what we can and cannot confidently say about the longer term historical context of the storms Harvey, Irma, and Maria.

Processing and Properties of Vacuum Assisted Resin Transfer Molded Phenylethynyl Terminated Imide Composites

NASA Technical Reports Server (NTRS)

Cano, Roberto J.; Ghose, Sayata; Watson, Kent A.; Chunchu, Prasad B.; Jensen, Brian J.; Connell, John W.

2012-01-01

Polyimide composites are very attractive for applications that require a high strength to weight ratio and thermal stability. Recent work at NASA Langley Research Center (LaRC) has concentrated on developing new polyimide resin systems that can be processed without the use of an autoclave for advanced aerospace applications. Due to their low melt viscosities and long melt stability, certain phenylethynyl terminated imides (PETI) can be processed into composites using high temperature vacuum assisted resin transfer molding (HT-VARTM). VARTM has shown the potential to reduce the manufacturing cost of composite structures. In the current study, two PETI resins, LARC(Trademark) PETI-330 and LARC(Trademark) PETI-9, were infused into carbon fiber preforms at 260 C and cured at temperatures up to 371 C. Photomicrographs of polished cross sections were taken and void contents, determined by acid digestion, were below 4.5%. Mechanical properties including short block compression (SBC), compression after impact (CAI), and open hole compression (OHC) were determined at room temperature, 177 C, and 288 C. Both PETI-9 and PETI-330 composites demonstrated very good retention of mechanical properties at elevated temperatures. SBC and OHC properties after aging for 1000 hours at temperatures up to 288 C were also determined.

Extraction and characterization of three polysaccharides extracted from Opuntia ficus indica cladodes.

PubMed

Bayar, Nadia; Kriaa, Mouna; Kammoun, Radhouane

2016-11-01

The chemical extraction and the characterization of polysaccharides from mucilage (MC), pectin (PC) and total pectic mucilage fraction (TFC) of Opuntia ficus indica cladodes as well as the evaluation of their antioxidant activities was investigated. The FTIR spectroscopic analysis revealed the presence of carboxyl and hydroxyl groups corresponding to polysaccharides. Uronic acid and the total sugar contents of PC were higher than those of TFC and MC whereas ash content of MC was considerably more important. In addition, the findings showed that all the samples had little protein content and low average molecular weight compared to the results mentioned in literature. Furthermore, MC reached not only the highest water (WHC) and oil holding (OHC) capacities (7.81g/g and 1.34g/g, respectively) but also the highest antioxidant properties (DPPH and ABTS scavenging activities, β-carotene bleaching inhibition activity and reducing power). However, PC had the strongest emulsifying and foaming properties. As for TFC, it had low WHC, OHC and emulsifying properties whereas it had higher foaming properties than MC and greater antioxidant properties compared to PC. These outcomes can encourage the use of PC as a surfactant and MC and TFC as natural antioxidants in food and pharmaceutical industries. Copyright © 2016 Elsevier B.V. All rights reserved.

The Roles of Climate Change and Climate Variability in the 2017 Atlantic Hurricane Season

NASA Technical Reports Server (NTRS)

Lim, Young-Kwon; Schubert, Siegfried D.; Kovach, Robin; Molod, Andrea M.; Pawson, Steven

2018-01-01

The 2017 hurricane season was extremely active with six major hurricanes, the third most on record. The sea-surface temperatures (SSTs) over the eastern Main Development Region (EMDR), where many tropical cyclones (TCs) developed during active months of August/September, were approximately 0.96 degrees Centigrade above the 1901-2017 average (warmest on record): about 0.42 degrees Centigrade from a long-term upward trend and the rest (around 80 percent) attributed to the Atlantic Meridional Mode (AMM). The contribution to the SST from the North Atlantic Oscillation over the EMDR was a weak warming, while that from ENSO was negligible. Nevertheless, ENSO, the NAO, and the AMM all contributed to favorable wind shear conditions, while the AMM also produced enhanced atmospheric instability. Compared with the strong hurricane years of 2005-2010, the ocean heat content (OHC) during 2017 was larger across the tropics, with higher SST anomalies over the EMDR and Caribbean Sea. On the other hand, the dynamical/thermodynamical atmospheric conditions, while favorable for enhanced TC activity, were less prominent than in 2005-2010 across the tropics. The results suggest that unusually warm SST in the EMDR together with the long fetch of the resulting storms in the presence of record-breaking OHC were key factors in driving the strong TC activity in 2017.

Stimulus dependent properties of mammalian cochlear hair cell mechanoelectrical transduction

NASA Astrophysics Data System (ADS)

Scharr, A. L.; Ricci, Anthony

2018-05-01

Cochlear hair cell stereocilia move semi-independently, shaping the force transfer to mechanoelectrical transduction (MET) channels, as indicated by the MET current response. Semi-independent movement of stereocilia was evoked by stimulating inner hair cell (IHC) bundles from acutely dissected rat cochlea with stiff probes ranging in size from 1 to 10 µm. MET current responses were recorded using whole-cell patch-clamp electrophysiology. Small probes directly displaced stereocilia they contacted, and recruited adjacent stereocilia depending on stimulus magnitude. We inferred that the recruitment of stereocilia resulted in less uniform and less synchronous movement. Step displacements using smaller probes resulted in smaller current responses (from 1 nA for large probes to 0.3 nA for small, p <.0001), slower rate of current activation, as measured from the linear portion (from 4 nA/ms to 1 nA/ms, p <.0001), slower time constants of adaptation, as measured from double exponential fits from peak to steady state current (fast component: from 0.6 to 1.2 ms, p =.004; slow component: from 8 ms to 12 ms, p =.001) and less complete adaptation (from 95% to 30%, p <.0001). These results indicate that the mechanical properties of less coherent bundles greatly affect force transfer to MET channels as indicated by the electrical response of the cell. Thus, outer hair cells (OHCs), with their bundles embedded in the tectorial membrane, may exhibit synchronous MET activation and therefore time-dependent adaptation where fast adaptation provides a high pass filter. Hair cells with free standing bundles, like inner hair cells (IHC), may exhibit more asynchronous MET activation and adaptation, in which case adaptation would not provide this additional filter.

Beyond generalized hair cells: Molecular cues for hair cell types

PubMed Central

Jahan, Israt; Pan, Ning; Kersigo, Jennifer; Fritzsch, Bernd

2012-01-01

Basic helix-loop-helix (bHLH) transcription factors (TFs) are crucial for inner ear neurosensory development. The proneural TF Atoh1 regulates the differentiation of hair cells (HCs) whereas Neurog1 and Neurod1 regulate specification and differentiation of neurons, respectively, but also affect HC development. Expression of Delta and Jagged ligands in nascent HCs and Notch receptors in supporting cells induce supporting cell differentiation through the regulation of neurogenic bHLH TFs (such as Hes1, Hes5) and suppression of limited Atoh1 expression. In sensorineural hearing loss, HCs are lost followed by supporting cells and progressive degeneration of neurons, at least in rodents. Regaining complete hearing may require reconstituting the organ of Corti (OC) from scratch, including the two types of HCs, inner (IHC) and outer (OHC) hair cells with the precise sorting of two types of afferent (type I and II) and efferent (lateral, LOC and medial, MOC olivo-cochlear) innervation. We review effects of bHLH TF dosage and their cross-regulation to differentiate HC types in the OC. We categorize findings of specific gene expressions in HCs: 1. as markers without meaning for the regeneration task, 2. as stabilizers who are needed to maintain or complete differentiation, and 3. as decision making genes, expressed and acting early enough to be useful in this process. Only one TF has been characterized that fits the last aspect: Atoh1. We propose that temporal and intensity variations of Atoh1 are naturally modulated to differentiate specific types of HCs. Importantly, the molecular means to modify the Atoh1 expression are at least partially understood and can be readily implemented in the attempts to regenerate specific types of HCs. PMID:23201032

FREE 17-HYDROXYCORTICOSTERIOD CONCENTRATION OF PAROTID FLUID FOLLOWING INTRAVENOUS ADMINISTRATION OF CORTISOL,

DTIC Science & Technology

In an attempt to determine the time required for adrenocortical steroids to pass from the bloodstream to parotid fluid, twenty subjects were given...intravenous injections of cortisol and parotid fluid was collected continuously for 120 minutes after injection. Additional studies were carried out...with intramuscular injections and oral administration of cortisol. The parotid fluid free 17-OHCS mean rose from 3.51 (S.D. = 1.57) to 21.34 (S.D

[Effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in the guinea pig].

PubMed

Feng, B; Jiang, S; Yang, W; Han, D; Zhang, S

2001-02-01

To define the effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in guinea pigs. The animals involved in the study were exposed to 8 Hz infrasound at 135dB SPL for 90 minutes in a reverberant chamber. The sinusoidal pendular test (SPT), auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were respectively detected pre-exposure and at 0(within 2 hrs), 2 and 5 day after exposure. The ultrastructures of the inner ear were observed by scanning electron microscopy. The slow-phase velocity and the frequency of the vestibular nystagmus elicited by sinusoidal pendular test (SPT) declined slightly following infrasound exposure, but the changes were not significant (P > 0.05). No differences in the ABR thresholds, the latencies and the interval peak latencies of I, III, V waves were found between the normal and the experimental groups, and among experimental groups. The amplitudes of DPOAE at any frequency declined remarkably in all experimental groups. The ultrastructures of the inner ear were damaged to different extent. Infrasound could transiently depress the excitability of the vestibular end-organs, decrease the function of OHC in the organ of Corti and cause damage to the inner ear of guinea pigs.

Progress in Cochlear Physiology after Békésy

PubMed Central

Guinan, John J.; Salt, Alec; Cheatham, Mary Ann

2012-01-01

In the fifty years since Békésy was awarded the Nobel Prize, cochlear physiology has blossomed. Many topics that are now current are things Békésy could not have imagined. In this review we start by describing progress in understanding the origin of cochlear gross potentials, particularly the cochlear microphonic, an area in which Békésy had extensive experience. We then review progress in areas of cochlear physiology that were mostly unknown to Békésy, including: (1) stereocilia mechano-electrical transduction, force production, and response amplification, (2) outer hair cell (OHC) somatic motility and its molecular basis in prestin, (3) cochlear amplification and related micromechanics, including the evidence that prestin is the main motor for cochlear amplification, (4) the influence of the tectorial membrane, (5) cochlear micromechanics and the mechanical drives to inner hair cell stereocilia, (6) otoacoustic emissions, and (7) olivocochlear efferents and their influence on cochlear physiology. We then return to a subject that Békésy knew well: cochlear fluids and standing currents, as well as our present understanding of energy dependence on the lateral wall of the cochlea. Finally, we touch on cochlear pathologies including noise damage and aging, with an emphasis on where the field might go in the future. PMID:22633944

SMAD4 Defect Causes Auditory Neuropathy Via Specialized Disruption of Cochlear Ribbon Synapses in Mice.

PubMed

Liu, Ke; Ji, Fei; Yang, Guan; Hou, Zhaohui; Sun, Jianhe; Wang, Xiaoyu; Guo, Weiwei; Sun, Wei; Yang, Weiyan; Yang, Xiao; Yang, Shiming

2016-10-01

More than 100 genes have been associated with deafness. However, SMAD4 is rarely considered a contributor to deafness in humans, except for its well-defined role in cell differentiation and regeneration. Here, we report that a SMAD4 defect in mice can cause auditory neuropathy, which was defined as a mysterious hearing and speech perception disorder in human for which the genetic background remains unclear. Our study showed that a SMAD4 defect induces failed formation of cochlear ribbon synapse during the earlier stage of auditory development in mice. Further investigation found that there are nearly normal morphology of outer hair cells (OHCs) and post-synapse spiral ganglion nerves (SGNs) in SMAD4 conditional knockout mice (cKO); however, a preserved distortion product of otoacoustic emission (DPOAE) and cochlear microphonic (CM) still can be evoked in cKO mice. Moreover, a partial restoration of hearing detected by electric auditory brainstem response (eABR) has been obtained in the cKO mice using electrode stimuli toward auditory nerves. Additionally, the ribbon synapses in retina are not affected by this SMAD4 defect. Thus, our findings suggest that this SMAD4 defect causes auditory neuropathy via specialized disruption of cochlear ribbon synapses.

Exploring the impact of word-of-mouth about Physicians' service quality on patient choice based on online health communities.

PubMed

Lu, Naiji; Wu, Hong

2016-11-26

Health care service is a high-credence service and patients may face difficulties ascertaining service quality in order to make choices about their available treatment options. Online health communities (OHCs) provide a convenient channel for patients to search for physicians' information, such as Word-of-Mouth (WOM), particularly on physicians' service quality evaluated by other patients. Existing studies from other service domains have proved that WOM impacts consumer choice. However, how patients make a choice based on physicians' WOM has not been studied, particularly with reference to different patient characteristics and by using real data. One thousand eight hundred fifty three physicians' real data were collected from a Chinese online health community. The data were analyzed using ordinary least squares (OLS) method. The study found that functional quality negatively moderated the relationship between technical quality and patient choice, and disease risk moderated the relationship between physicians' service quality and patient choice. Our study recommends that hospital managers need to consider the roles of both technical quality and functional quality seriously. Physicians should improve their medical skills and bedside manners based on the severity and type of disease to provide better service.

Probing the early stages of solvation of cis-pinate dianions by water, acetonitrile, and methanol: a photoelectron spectroscopy and theoretical study.

PubMed

Hou, Gao-Lei; Kong, Xiang-Tao; Valiev, Marat; Jiang, Ling; Wang, Xue-Bin

2016-02-07

cis-Pinic acid is one of the most important oxidation products of α-pinene--a key monoterpene compound in biogenic emission processes. Molecular level understanding of its interaction with water in cluster formation is an important and necessary prerequisite for ascertaining its role in the aerosol formation processes. In this work, we studied the structures and energetics of the solvated clusters of cis-pinate (cis-PA(2-)), the doubly deprotonated dicarboxylate of cis-pinic acid, with H2O, CH3OH, and CH3CN by negative ion photoelectron spectroscopy and ab initio theoretical calculations. We found that cis-PA(2-) prefers being solvated alternately on the two -CO2(-) groups with increase of solvent coverage, a well-known solvation pattern that has been observed in microhydrated linear dicarboxylate dianion (DCn(2-)) clusters. Experiments and calculations further reveal an intriguing feature for the existence of the asymmetric type isomers for cis-PA(2-)(H2O)2 and cis-PA(2-)(CH3OH)2, in which both solvent molecules interact with only one of the -CO2(-) groups, a phenomenon that has not been observed in DCn(2-) water clusters and exhibits that the subtle effect of the rigid four-membered carbon ring brought on the cis-PA(2-) solvation. The dominant interactions between cis-PA(2-) and solvent molecules form bidentate O(-)...H-O H-bonds for H2O, O(-)...H-O and O(-)...H-C H-bonds for CH3OH, and tridentate O(-)...H-C H-bonds for CH3CN. The formation of inter-solvent H-bonds between H2O and CH3CN is found to be favorable in mixed solvent clusters, different from that between H2O and CH3OH. These findings have important implications for understanding the mechanism of cluster growth and the formation of atmospheric organic aerosols, as well as for rationalizing the nature of structure-function relationship of proteins containing carboxylate groups in various solvent environments.

Sustained Flight Operations in Navy P-3 Aircraft.

DTIC Science & Technology

1990-04-01

an entire week to eliminate any test overlap or bias and to allow for full recovery between tests. 3 The aerobic capacity test was performed on a...techniques, and an automated chemistry analyzer (Baker Instruments, Allentown, PA). Urinary 17-OHCS was analyzed by the Porter and Silber method (30) as...Grandjean (Eds.), Meth gy in Human Fatigue Assessment, International Publications Service , New York, NY, 1971, pp. 31-41. 18. Angus, R.G. and Heslegrave, R.M

Interannual variability in global mean sea level estimated from the CESM Large and Last Millennium Ensembles

DOE PAGES

Fasullo, John T.; Nerem, Robert S.

2016-10-31

To better understand global mean sea level (GMSL) as an indicator of climate variability and change, contributions to its interannual variation are quantified in the Community Earth System Model (CESM) Large Ensemble and Last Millennium Ensemble. Consistent with expectations, the El Niño/Southern Oscillation (ENSO) is found to exert a strong influence due to variability in rainfall over land (PL) and terrestrial water storage (TWS). Other important contributors include changes in ocean heat content (OHC) and precipitable water (PW). The temporal evolution of individual contributing terms is documented. The magnitude of peak GMSL anomalies associated with ENSO generally are of themore » order of 0.5 mm·K -1 with significant inter-event variability, with a standard deviation (σ) that is about half as large The results underscore the exceptional rarity of the 2010/2011 La Niña-related GMSL drop and estimate the frequency of such an event to be about only once in every 75 years. In addition to ENSO, major volcanic eruptions are found to be a key driver of interannual variability. Associated GMSL variability contrasts with that of ENSO as TWS and PW anomalies initially offset the drop due to OHC reductions but short-lived relative to them. Furthermore, responses up to 25 mm are estimated for the largest eruptions of the Last Millennium.« less

Interannual variability in global mean sea level estimated from the CESM Large and Last Millennium Ensembles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fasullo, John T.; Nerem, Robert S.

To better understand global mean sea level (GMSL) as an indicator of climate variability and change, contributions to its interannual variation are quantified in the Community Earth System Model (CESM) Large Ensemble and Last Millennium Ensemble. Consistent with expectations, the El Niño/Southern Oscillation (ENSO) is found to exert a strong influence due to variability in rainfall over land (PL) and terrestrial water storage (TWS). Other important contributors include changes in ocean heat content (OHC) and precipitable water (PW). The temporal evolution of individual contributing terms is documented. The magnitude of peak GMSL anomalies associated with ENSO generally are of themore » order of 0.5 mm·K -1 with significant inter-event variability, with a standard deviation (σ) that is about half as large The results underscore the exceptional rarity of the 2010/2011 La Niña-related GMSL drop and estimate the frequency of such an event to be about only once in every 75 years. In addition to ENSO, major volcanic eruptions are found to be a key driver of interannual variability. Associated GMSL variability contrasts with that of ENSO as TWS and PW anomalies initially offset the drop due to OHC reductions but short-lived relative to them. Furthermore, responses up to 25 mm are estimated for the largest eruptions of the Last Millennium.« less

Present Concepts in Internal Medicine. Volume 13, Number 1. Endocrinology Research Symposium,

DTIC Science & Technology

1980-01-01

Liddle suppression test in which dexamethasone 0.5 mg q6h (2 mg/day) is given for two days with collection of urine 17-OHCS. 3 Confirmation of the...diagnosis is best established by measurement of urine free cortisol which has the advantage of not being elevated in obesity.4 False negatives occur in 10...experience (in the absence of conditions causing false positive responses) the presence of elevated urine free cortisol (> 100 Vg/24 h) and lack of

Frequently Asked Questions about Monitored Natural Attenuation in Groundwater

DTIC Science & Technology

2014-02-01

Natural Attenuation of Fuels and Chlorinated Solvents book (600 citations) I? • MNA Since 2000 Although there was tremendous progress in technical and...faster with Scenario Scenario Scenario heterogen. 7 8 8 slower with Scenario Scenario Scenario heterogen. 10 I I 12 fractured / • Scenario 13...DC. 7 (W OHC-17 ( 1 E5 yr) ~ 1,2DCA VC Ethylene Glycol (W I RD-7 AH-17 (72 yr) • Mechanisms ORP CEC Sediment iron oxide Sulfur TDS CA

Prickle1 regulates neurite outgrowth of apical spiral ganglion neurons but not hair cell polarity in the murine cochlea

PubMed Central

Kersigo, Jennifer; Wu, Shu; Fritzsch, Bernd; Bassuk, Alexander G.

2017-01-01

In the mammalian organ of Corti (OC), the stereocilia on the apical surface of hair cells (HCs) are uniformly organized in a neural to abneural axis (or medial-laterally). This organization is regulated by planar cell polarity (PCP) signaling. Mutations of PCP genes, such as Vangl2, Dvl1/2, Celsr1, and Fzd3/6, affect the formation of HC orientation to varying degrees. Prickle1 is a PCP signaling gene that belongs to the prickle / espinas / testin family. Prickle1 protein is shown to be asymmetrically localized in the HCs of the OC, and this asymmetric localization is associated with loss of PCP in Smurf mutants, implying that Prickle1 is involved in HC PCP development in the OC. A follow-up study found no PCP polarity defects after loss of Prickle1 (Prickle1-/-) in the cochlea. We show here strong Prickle1 mRNA expression in the spiral ganglion by in situ hybridization and β-Gal staining, and weak expression in the OC by β-Gal staining. Consistent with this limited expression in the OC, cochlear HC PCP is unaffected in either Prickle1C251X/C251X mice or Prickle1f/f; Pax2-cre conditional null mice. Meanwhile, type II afferents of apical spiral ganglion neurons (SGN) innervating outer hair cells (OHC) have unusual neurite growth. In addition, afferents from the apex show unusual collaterals in the cochlear nuclei that overlap with basal turn afferents. Our findings argue against the role of Prickle1 in regulating hair cell polarity in the cochlea. Instead, Prickle1 regulates the polarity-related growth of distal and central processes of apical SGNs. PMID:28837644

Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction.

PubMed

Fetoni, Anna R; Eramo, Sara L M; Paciello, Fabiola; Rolesi, Rolando; Podda, Maria Vittoria; Troiani, Diana; Paludetti, Gaetano

2014-06-01

To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

Did hydrographic sampling capture global and regional deep ocean heat content trends accurately between 1990-2010?

NASA Astrophysics Data System (ADS)

Garry, Freya; McDonagh, Elaine; Blaker, Adam; Roberts, Chris; Desbruyères, Damien; King, Brian

2017-04-01

Estimates of heat content change in the deep oceans (below 2000 m) over the last thirty years are obtained from temperature measurements made by hydrographic survey ships. Cruises occupy the same tracks across an ocean basin approximately every 5+ years. Measurements may not be sufficiently frequent in time or space to allow accurate evaluation of total ocean heat content (OHC) and its rate of change. It is widely thought that additional deep ocean sampling will also aid understanding of the mechanisms for OHC change on annual to decadal timescales, including how OHC varies regionally under natural and anthropogenically forced climate change. Here a 0.25˚ ocean model is used to investigate the magnitude of uncertainties and biases that exist in estimates of deep ocean temperature change from hydrographic sections due to their infrequent timing and sparse spatial distribution during 1990 - 2010. Biases in the observational data may be due to lack of spatial coverage (not enough sections covering the basin), lack of data between occupations (typically 5-10 years apart) and due to occupations not closely spanning the time period of interest. Between 1990 - 2010, the modelled biases globally are comparatively small in the abyssal ocean below 3500 m although regionally certain biases in heat flux into the 4000 - 6000 m layer can be up to 0.05 Wm-2. Biases in the heat flux into the deep 2000 - 4000 m layer due to either temporal or spatial sampling uncertainties are typically much larger and can be over 0.1 Wm-2 across an ocean. Overall, 82% of the warming trend below 2000 m is captured by observational-style sampling in the model. However, at 2500 m (too deep for additional temperature information to be inferred from upper ocean Argo) less than two thirds of the magnitude of the global warming trend is obtained, and regionally large biases exist in the Atlantic, Southern and Indian Oceans, highlighting the need for widespread improved deep ocean temperature sampling. In addition to bias due to infrequent sampling, moving the timings of occupations by a few months generates relatively large uncertainty due to intra-annual variability in deep ocean model temperature, further strengthening the case for high temporal frequency observations in the deep ocean (as could be achieved using deep ocean autonomous float technologies). Biases due to different uncertainties can have opposing signs and differ in relative importance both regionally and with depth revealing the importance of reducing all uncertainties (both spatial and temporal) simultaneously in future deep ocean observing design.

Compression Fracture of CFRP Laminates Containing Stress Intensifications.

PubMed

Leopold, Christian; Schütt, Martin; Liebig, Wilfried V; Philipkowski, Timo; Kürten, Jonas; Schulte, Karl; Fiedler, Bodo

2017-09-05

For brittle fracture behaviour of carbon fibre reinforced plastics (CFRP) under compression, several approaches exist, which describe different mechanisms during failure, especially at stress intensifications. The failure process is not only initiated by the buckling fibres, but a shear driven fibre compressive failure beneficiaries or initiates the formation of fibres into a kink-band. Starting from this kink-band further damage can be detected, which leads to the final failure. The subject of this work is an experimental investigation on the influence of ply thickness and stacking sequence in quasi-isotropic CFRP laminates containing stress intensifications under compression loading. Different effects that influence the compression failure and the role the stacking sequence has on damage development and the resulting compressive strength are identified and discussed. The influence of stress intensifications is investigated in detail at a hole in open hole compression (OHC) tests. A proposed interrupted test approach allows identifying the mechanisms of damage initiation and propagation from the free edge of the hole by causing a distinct damage state and examine it at a precise instant of time during fracture process. Compression after impact (CAI) tests are executed in order to compare the OHC results to a different type of stress intensifications. Unnotched compression tests are carried out for comparison as a reference. With this approach, a more detailed description of the failure mechanisms during the sudden compression failure of CFRP is achieved. By microscopic examination of single plies from various specimens, the different effects that influence the compression failure are identified. First damage of fibres occurs always in 0°-ply. Fibre shear failure leads to local microbuckling and the formation and growth of a kink-band as final failure mechanisms. The formation of a kink-band and finally steady state kinking is shifted to higher compressive strains with decreasing ply thickness. Final failure mode in laminates with stress intensification depends on ply thickness. In thick or inner plies, damage initiates as shear failure and fibre buckling into the drilled hole. The kink-band orientation angle is changing with increasing strain. In outer or thin plies shear failure of single fibres is observed as first damage and the kink-band orientation angle is constant until final failure. Decreasing ply thickness increases the unnotched compressive strength. When stress intensifications are present, the position of the 0°-layer is critical for stability under compression and is thus more important than the ply thickness. Central 0°-layers show best results for OHC and CAI strength due to higher bending stiffness and better supporting effect of the adjacent layers.

Compression Fracture of CFRP Laminates Containing Stress Intensifications

PubMed Central

Schütt, Martin; Philipkowski, Timo; Kürten, Jonas; Schulte, Karl

2017-01-01

For brittle fracture behaviour of carbon fibre reinforced plastics (CFRP) under compression, several approaches exist, which describe different mechanisms during failure, especially at stress intensifications. The failure process is not only initiated by the buckling fibres, but a shear driven fibre compressive failure beneficiaries or initiates the formation of fibres into a kink-band. Starting from this kink-band further damage can be detected, which leads to the final failure. The subject of this work is an experimental investigation on the influence of ply thickness and stacking sequence in quasi-isotropic CFRP laminates containing stress intensifications under compression loading. Different effects that influence the compression failure and the role the stacking sequence has on damage development and the resulting compressive strength are identified and discussed. The influence of stress intensifications is investigated in detail at a hole in open hole compression (OHC) tests. A proposed interrupted test approach allows identifying the mechanisms of damage initiation and propagation from the free edge of the hole by causing a distinct damage state and examine it at a precise instant of time during fracture process. Compression after impact (CAI) tests are executed in order to compare the OHC results to a different type of stress intensifications. Unnotched compression tests are carried out for comparison as a reference. With this approach, a more detailed description of the failure mechanisms during the sudden compression failure of CFRP is achieved. By microscopic examination of single plies from various specimens, the different effects that influence the compression failure are identified. First damage of fibres occurs always in 0°-ply. Fibre shear failure leads to local microbuckling and the formation and growth of a kink-band as final failure mechanisms. The formation of a kink-band and finally steady state kinking is shifted to higher compressive strains with decreasing ply thickness. Final failure mode in laminates with stress intensification depends on ply thickness. In thick or inner plies, damage initiates as shear failure and fibre buckling into the drilled hole. The kink-band orientation angle is changing with increasing strain. In outer or thin plies shear failure of single fibres is observed as first damage and the kink-band orientation angle is constant until final failure. Decreasing ply thickness increases the unnotched compressive strength. When stress intensifications are present, the position of the 0°-layer is critical for stability under compression and is thus more important than the ply thickness. Central 0°-layers show best results for OHC and CAI strength due to higher bending stiffness and better supporting effect of the adjacent layers. PMID:28872623

Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved.

PubMed

Simões Pires, Elisa Nicoloso; Frozza, Rudimar Luiz; Hoppe, Juliana Bender; Menezes, Bruna de Melo; Salbego, Christianne Gazzana

2014-04-04

Berberine is an alkaloid derived from herb the Berberis sp. and has long-term use in Oriental medicine. Studies along the years have demonstrated its beneficial effect in various neurodegenerative and neuropsychiatric disorders. The subject of this study was to evaluate whether berberine protects against delayed neuronal cell death in organotypic hippocampal culture (OHC) exposed to oxygen and glucose deprivation (OGD) and the cell signaling mechanism related to its effect. Hippocampal slices were obtained from 6 to 8-days-old male Wistar rat and cultured for 14 days. Following, the cultures were exposed for 1h to OGD and then treated with Berberine (10 and 20μM). After 24h recovery, propidium iodide (PI) uptake was analyzed and a decrease was observed in PI uptake on OGD Ber-treated culture, which means a decrease in cellular death. Western blot analysis showed that proteins Akt, GSK3β, ERK and JNK appear to play a role in berberine-mediated neuroprotection. Furthermore, capase-3 activity of OGD Ber-treated culture was diminished by control level in a fluorimetry assay. These findings suggest that berberine-mediated neuroprotection after ischemia involves Akt/GSK3β/ERK 1/2 survival/apoptotic signaling pathway as well as JNK and caspase-3 activity inhibition. Copyright © 2014 Elsevier B.V. All rights reserved.

Highly Depleted Ethane and Slightly Depleted Methanol in Comet 21P/Giacobini-Zinner: Application of Empirical g-Factors for CH3OH Near 50K

NASA Technical Reports Server (NTRS)

DiSanti, Michael A.; Bonev, Boncho P.; Mumma, Michael J.; Villanueva, Geronimo L.

2010-01-01

We report high resolution (lambda/delta lambda approximately 24,000) observations of Comet 21 P/Giacobini-Zinner (21P) between approximately 2.85 -- 3.54 micrometers, obtained with NIRSPEC at Keck 2 on UT 2005 June 03 (R(sub h) = 1.12 AU, delta = 1.45 AU). These simultaneously sampled multiple emissions from the v7 band of C2H6 and the v2 and v3 bands of CH3OH, together with several hot bands of H2O, permitting a direct measure of parent volatile abundances in 21P. Our spectra reveal highly depleted C2H6 (0.13-0.14 percent relative to H2O) and CH3OH/C2H6 approximately 10, consistent with previously published abundances from observations in the IR [1,2] and millimeter sub-mm (reporting CH3OH/H2O [3]) during its previous apparition in 1998. We observed similarly high CH3OH/C2H6, and also similar rotational temperature to that measured for 21 P, in Comet 8P/Tuttle [4,5]. We used our (higher signal-to-noise) NIRSPEC observations of 8P to produce effective (empirical) CH3OH g-factors for several lines in the v2 band. These will be presented together with interpretation of our results, including constraints on the spin temperature of water. We acknowledge support from the NASA Planetary Atmospheres, Planetary Astronomy, and Astrobiology Programs and from the NSF Astronomy and Astrophysics Research Grants Program.

Bismuth heterocycles based on a diphenyl sulfone scaffold: synthesis and substituent effect on the antifungal activity against Saccharomyces cerevisiae.

PubMed

Murafuji, Toshihiro; Fujiwara, Yudai; Yoshimatsu, Daisuke; Miyakawa, Isamu; Migita, Kouto; Mikata, Yuji

2011-02-01

A series of heterocyclic organobismuth(III) compounds 2 [ClBi(5-R-C6H(3)-2-SO2C6H(4)-1'-): R=Me, Ph, MeO, Cl, H, t-Bu, CF3, F, Me2N] was synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae. A clear structure-activity relationship between the size of the inhibition zone and the value of ClogP was found for 2. These results suggest that the higher the lipophilicity, the lower the antifungal activity. Thus, 2e (R=H) and 2h (R=F), which had ClogP values of 1.18 and 1.45, respectively, were most active. In contrast, 2b (R=Ph) and 2f (R=t-Bu) had ClogP values of 3.06 and 3.00, respectively, and exhibited no antifungal activity. Compound 6b ClBi[5-(OH)C6H(3)-2-SO(2)-5'-(OH)C6H(3)-1'-] had an estimated ClogP value of 0.81 but exhibited only low activity in spite of its low ClogP value, suggesting that such a considerable decrease in lipophilicity lowers inhibition activity. Bismuth carboxylate 7b derived from p-nitrobenzoic acid and 2e exhibited inhibition activity comparable to those of 2e and 2h despite its higher lipophilicity (ClogP=2.68). Copyright © 2010 Elsevier Masson SAS. All rights reserved.

[Influence of nutrition on hormone secretion. I. Study in Agua Preta (author's transl)].

PubMed

Chaves, N; Guimarães, E D; Aguiar, F; Viana, T; Matos, E; Basto de Medeiros, R; Martins, G C; Bazante, M O; Pimenta, P P

1975-01-01

A positive correlation between the circulating growth hormone levels and the nutritional status was reported in 9 children of both sexes, aged 1 to 6 years, suffering from 2nd degree malnutrition. The mean serum insulin levels, the mean urinary 17-KS and 17-OHCS levels were low before the dietary therapy. No significant correlation between the levels of these hormones and the nutritional status was found. The hormone levels gradually returned to normal after the dietary therapy and the nutritional status of the children improved, according to the observed biochemical, clinical and anthropometric data.

Toxic Accumulation of LPS Pathway Intermediates Underlies the Requirement of LpxH for Growth of Acinetobacter baumannii ATCC 19606

PubMed Central

Richie, Daryl L.; Takeoka, Kenneth T.; Bojkovic, Jade; Metzger, Louis E.; Rath, Christopher M.; Sawyer, William S.; Wei, Jun-Rong; Dean, Charles R.

2016-01-01

The lipid A moiety of lipopolysaccharide (LPS) is the main constituent of the outer leaflet of the Gram-negative bacterial outer membrane (OM) and is essential in many Gram-negative pathogens. An exception is Acinetobacter baumannii ATCC 19606, where mutants lacking enzymes occurring early in lipid A biosynthesis (LpxA, LpxC or LpxD), and correspondingly lacking LPS, can grow. In contrast, we show here that LpxH, an enzyme that occurs downstream of LpxD in the lipid A biosynthetic pathway, is essential for growth in this strain. Multiple attempts to disrupt lpxH on the genome were unsuccessful, and when LpxH expression was controlled by an isopropyl β-d-1-thiogalactopyranoside (IPTG) inducible promoter, cell growth under typical laboratory conditions required IPTG induction. Mass spectrometry analysis of cells shifted from LpxH-induced to uninduced (and whose growth was correspondingly slowing as LpxH was depleted) showed a large cellular accumulation of UDP-2,3-diacyl-GlcN (substrate of LpxH), a C14:0(3-OH) acyl variant of the LpxD substrate (UDP-3-O-[(R)-3-OH-C14]-GlcN), and disaccharide 1-monophosphate (DSMP). Furthermore, the viable cell counts of the LpxH depleted cultures dropped modestly, and electron microscopy revealed clear defects at the cell (inner) membrane, suggesting lipid A intermediate accumulation was toxic. Consistent with this, blocking the synthesis of these intermediates by inhibition of the upstream LpxC enzyme using CHIR-090 abrogated the requirement for IPTG induction of LpxH. Taken together, these data indicate that LpxH is essential for growth in A. baumannii ATCC19606, because, unlike earlier pathway steps like LpxA or LpxC, blockage of LpxH causes accumulation of detergent-like pathway intermediates that prevents cell growth. PMID:27526195

d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

PubMed Central

Kirkwood, Nerissa K.; O'Reilly, Molly; Derudas, Marco; Kenyon, Emma J.; Huckvale, Rosemary; van Netten, Sietse M.; Ward, Simon E.; Richardson, Guy P.; Kros, Corné J.

2017-01-01

Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical transducer (MET) channels located at the tips of the hair cell's stereocilia. d-Tubocurarine (dTC) is a MET channel blocker that reduces the loading of gentamicin-Texas Red (GTTR) into rat cochlear hair cells and protects them from gentamicin treatment. Berbamine is a structurally related alkaloid that reduces GTTR labeling of zebrafish lateral-line hair cells and protects them from aminoglycoside-induced cell death. Both compounds are thought to reduce aminoglycoside entry into hair cells through the MET channels. Here we show that dTC (≥6.25 μM) or berbamine (≥1.55 μM) protect zebrafish hair cells in vivo from neomycin (6.25 μM, 1 h). Protection of zebrafish hair cells against gentamicin (10 μM, 6 h) was provided by ≥25 μM dTC or ≥12.5 μM berbamine. Hair cells in mouse cochlear cultures are protected from longer-term exposure to gentamicin (5 μM, 48 h) by 20 μM berbamine or 25 μM dTC. Berbamine is, however, highly toxic to mouse cochlear hair cells at higher concentrations (≥30 μM) whilst dTC is not. The absence of toxicity in the zebrafish assays prompts caution in extrapolating results from zebrafish neuromasts to mammalian cochlear hair cells. MET current recordings from mouse outer hair cells (OHCs) show that both compounds are permeant open-channel blockers, rapidly and reversibly blocking the MET channel with half-blocking concentrations of 2.2 μM (dTC) and 2.8 μM (berbamine) in the presence of 1.3 mM Ca2+ at −104 mV. Berbamine, but not dTC, also blocks the hair cell's basolateral K+ current, IK,neo, and modeling studies indicate that berbamine permeates the MET channel more readily than dTC. These studies reveal key properties of MET-channel blockers required for the future design of successful otoprotectants. PMID:28928635

Physical and Chemical Characterization Of Greater Yam (Dioscorea Alata) And Jack Bean (Canavalia Ensiformis) - Based Composite Flour

NASA Astrophysics Data System (ADS)

Affandi, D. R.; Praseptiangga, D.; Nirmala, F. S.; Sigit Amanto, B.; Atmaka, W.

2017-04-01

Indonesia is a tropical country that has great potential in agriculture. Tubers and legumes as examples of the potential commodities are needed to be more developed. Flour production is one of the best alternatives to be chosen as the downstream stage of the tubers and legumes utilization. Greater yam (Dioscorea alata) and jack bean (Canavalia ensiformis) were used in this study. This study was conducted to determine best formula of composite flour based on physical, chemical, and functional characterization of composite flour produced. Variations of formula used was the ratio of greater yam flour and jack bean flour, which were 85:15 (F1), 70:30 (F2), 55:45 (F3), respectively, and this study was conducted using completely randomized design (CRD). The formula variations didn’t show any significant effect on the water absorption capability, water holding capacity (WHC), oil holding capacity (OHC), swelling power, and starch content of the composite flour. However, the formula variations had a significant influence on the colour, proximate parameters, amylose and amylopectin content, resistant starch content, dietary fibre, total phenol, and antioxidant activity of the composite flour produced. Considering the results of physical, chemical, and functional characteristics of composite flour, formula (F1) was selected as the best composite flour developed from greater yam and jack bean flours.

Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature

PubMed Central

2014-01-01

Background Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Discussion Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Mechanism Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of ‘immunosterol’ 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. Summary We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology. PMID:24656052

Systematic review: Factors associated with return to work in burnout.

PubMed

Kärkkäinen, R; Saaranen, T; Hiltunen, S; Ryynänen, O P; Räsänen, K

2017-08-01

Professional burnout predicts sick leave and even permanent withdrawal from the labour force. However, knowledge of the barriers to and facilitators of return to work (RTW) in such burnout is limited. To identify factors associated with RTW of burned-out individuals to inform occupational health care (OHC) RTW policy. A systematic search of peer-reviewed quantitative and mixed-method studies published from January 2005 to July 2016 in English and Finnish in ARTO, CINAHL (EBSCO), Medic, PsycINFO (ProQuest), PubMed, Scopus and Web of Science databases, followed by a manual search. We included studies that identify burnout with valid burnout measures and measure the degree of RTW or sick leave as outcomes. We excluded studies with heterogeneous samples without subgroup analyses of RTW in burnout cases. We included 10 studies (three experimental and seven observational) of the initial 1345 identified. The studies reported work-related factors; enhanced communication (positive association) and low control at work (negative association) and individual-related factors; male gender (positive association), covert coping (negative association), high over-commitment to work (positive association) and burnout-related factors; unimpaired sleep (positive association), duration of sick leave over 6 months (negative association) and part-time sick leave (positive association) associated with RTW in burnout. Associations between burnout rehabilitation and RTW, and the level of symptoms and cognitive impairment and RTW remained unclear. Few quantitative studies, of varied methodological quality, explore factors associated with RTW in burnout. Further research is needed to build an evidence base and develop guidelines for supportive OHC actions. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature.

PubMed

Lathe, Richard; Sapronova, Alexandra; Kotelevtsev, Yuri

2014-03-21

Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of 'immunosterol' 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology.

N-acyl-homoserine lactone-mediated quorum-sensing in Azospirillum: an exception rather than a rule.

PubMed

Vial, Ludovic; Cuny, Caroline; Gluchoff-Fiasson, Katia; Comte, Gilles; Oger, Phil M; Faure, Denis; Dessaux, Yves; Bally, René; Wisniewski-Dyé, Florence

2006-11-01

Forty Azospirillum strains were tested for their ability to synthesize N-acyl-homoserine lactones (AHLs). AHL production was detected for four strains belonging to the lipoferum species and isolated from a rice rhizosphere. AHL molecules were structurally identified for two strains: Azospirillum lipoferum TVV3 produces 3O,C(8)-HSL (N-3-oxo-octanoyl-homoserine-lactone), C(8)-HSL (N-3-octanoyl-homoserine-lactone), 3O,C(10)-HSL (N-3-oxo-decanoyl-homoserine-lactone), 3OH,C(10)-HSL (N-3-hydroxy-decanoyl-homoserine-lactone) and C(10)-HSL (N-3-decanoyl-homoserine-lactone), whereas A. lipoferum B518 produced 3O,C(6)-HSL (N-3-oxo-hexanoyl-homoserine-lactone), C(6)-HSL (N-3-hexanoyl-homoserine-lactone), 3O,C(8)-HSL, 3OH,C(8)-HSL and C(8)-HSL. Genes involved in AHL production were characterized for A. lipoferum TVV3 by generating a genomic library and complementing an AHL-deficient strain with sensor capabilities. Those genes, designated alpI and alpR, were found to belong to the luxI and luxR families, respectively. When cloned in a suitable heterologous host, alpI and alpR could direct the synthesis of the five cognate AHLs present in A. lipoferum TVV3. These two adjacent genes were found to be located on a 85 kb plasmid. Southern hybridization experiments with probes alpI/R indicated that genes involved in AHL production in the three other AHL-producing strains were not closely related to alpI and alpR. This study demonstrates that AHL-based quorum-sensing is not widespread among the genus Azospirillum and could be found only in some A. lipoferum strains.

Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men.

PubMed

Ribel-Madsen, Amalie; Ribel-Madsen, Rasmus; Brøns, Charlotte; Newgard, Christopher B; Vaag, Allan A; Hellgren, Lars I

2016-10-01

We hypothesized that an increased, incomplete fatty acid beta-oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5-day high-fat, high-calorie diet. We demonstrated that LBW men had higher C2 and C4-OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta-oxidation relative to the tricarboxylic acid cycle flux. Also, they had higher C6-DC, C10-OH/C8-DC, and total hydroxyl-/dicarboxyl-acylcarnitine levels, which may suggest an increased fatty acid omega-oxidation in the liver. Furthermore, LBW and NBW men decreased several acylcarnitine levels in response to overfeeding, which is likely a result of an upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10-OH/C8-DC and total hydroxyl-/dicarboxyl-acylcarnitine levels tended to be negatively associated with the serum insulin level, and the total hydroxyl-/dicarboxyl-acylcarnitine level additionally tended to be negatively associated with the hepatic insulin resistance index. This indicates that an increased fatty acid omega-oxidation could be a compensatory mechanism to prevent an accumulation of lipid species that impair insulin signaling. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Noise alters guinea pig's blood-labyrinth barrier ultrastructure and permeability along with a decrease of cochlear Claudin-5 and Occludin.

PubMed

Wu, Yong-Xiang; Zhu, Guo-Xia; Liu, Xin-Qin; Sun, Fei; Zhou, Ke; Wang, Shuang; Wang, Chun-Mei; Jia, Jin-Wen; Song, Jian-Tao; Lu, Lian-Jun

2014-12-24

Noise exposure (NE) is a severe modern health hazard that induces hearing impairment. However, the noise-induced ultrastructural changes of blood-labyrinth barrier (BLB) and the potential involvements of tight junction proteins (TJP) remain inconclusive. We investigated the effects of NE on not only the ultrastructure of cochlea and permeability of BLB but also the expression of TJP within the guinea pig cochlea. Male albino guinea pigs were exposed to white noise for 4 h or 2 consecutive days (115 dB sound pressure level, 6 hours per day) and the hearing impairments and light microscopic change of BLB were evaluated with auditory brainstem responses (ABR) and the cochlear sensory epithelia surface preparation, respectively. The cochlear ultrastructure and BLB permeability after NE 2d were revealed with transmission electron microscope (TEM) and lanthanum nitrate-tracing techniques, respectively. The potential alterations of TJPs Claudin-5 and Occludin were quantified with immunohistochemistry and western blot. NE induced significant hearing impairment and NE 2d contributed to significant outer hair cell (OHC) loss that is most severe in the first row of outer hair cells. Furthermore, the loosen TJ and an obvious leakage of lanthanum nitrate particles beneath the basal lamina were revealed with TEM. Moreover, a dose-dependent decrease of Claudin-5 and Occludin was observed in the cochlea after NE. All these findings suggest that both decrease of Claudin-5 and Occludin and increased BLB permeability are involved in the pathologic process of noise-induced hearing impairment; however, the causal relationship and underlying mechanisms should be further investigated.

Difference in Perseverative Errors during a Visual Attention Task with Auditory Distractors in Alpha-9 Nicotinic Receptor Subunit Wild Type and Knock-Out Mice.

PubMed

Jorratt, Pascal; Delano, Paul H; Delgado, Carolina; Dagnino-Subiabre, Alexies; Terreros, Gonzalo

2017-01-01

The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through olivocochlear (OC) neurons. Medial OC neurons make cholinergic synapses with outer hair cells (OHCs) through nicotinic receptors constituted by α9 and α10 subunits. One of the physiological functions of the α9 nicotinic receptor subunit (α9-nAChR) is the suppression of auditory distractors during selective attention to visual stimuli. In a recent study we demonstrated that the behavioral performance of alpha-9 nicotinic receptor knock-out (KO) mice is altered during selective attention to visual stimuli with auditory distractors since they made less correct responses and more omissions than wild type (WT) mice. As the inhibition of the behavioral responses to irrelevant stimuli is an important mechanism of the selective attention processes, behavioral errors are relevant measures that can reflect altered inhibitory control. Errors produced during a cued attention task can be classified as premature, target and perseverative errors. Perseverative responses can be considered as an inability to inhibit the repetition of an action already planned, while premature responses can be considered as an index of the ability to wait or retain an action. Here, we studied premature, target and perseverative errors during a visual attention task with auditory distractors in WT and KO mice. We found that α9-KO mice make fewer perseverative errors with longer latencies than WT mice in the presence of auditory distractors. In addition, although we found no significant difference in the number of target error between genotypes, KO mice made more short-latency target errors than WT mice during the presentation of auditory distractors. The fewer perseverative error made by α9-KO mice could be explained by a reduced motivation for reward and an increased impulsivity during decision making with auditory distraction in KO mice.

[Morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise].

PubMed

2017-06-18

To observe the morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise and to investigate the different changes in three turns of hair cells. Thirty-two healthy SD rats, all males, were randomly divided into four groups: control group, weightlessness group, noise group and weightlessness+noise groups (n=8). Then rats were exposed to -30° head down tilt as simulated weightlessness and inboard noise including steady-state noise which was (72±2) dB SPL and impulse noise up to 160 dB SPL in spaceship environment. The control group was kept in normal condition for 8 weeks. Bilateral auditory brainstem response (ABR) thresholds were tested before and after exposure respectively, and immunofluorescence staining and scanning electron microscopy (SEMs) of basilar membrane were applied after exposure. ABR threshold shifts of each group were higher after exposure. There was difference between ABRs of the experiment groups before and after exposure (P<0.05). IF showed that the inner hair cells (IHCs) missing was the main damage in the basal turn of weightlessness group, the hair cells in the middle turn were swell and in the top turn, the hair cells were not clear. In noise group, the main loss happened in the outer hair cells (OHCs) of the outermost layer. In weightlessness+noise group, the nuclear missing in the basal turn was apparent, and mainly happened at the outermost layer. Meanwhile, the missing of hair cells in the middle turn and top turn was seen at the innermost layer. SEM showed that the cilia in the basal turn of weightlessness group were serious lodging, and occasional absence. Furthermore, the basal cilia in noise group became lodged and absent, and the other two turns were seriously missing. And in weightlessness+noise group, the cilia missing in the basal turn was apparently seen. The damage degree of the four groups: weightlessness+noise group>noise group>weightlessness group>control group and the damage degree of the four turns of hair cells: basal turn>mid turn>top turn. The rats exposed to the above environment for 2 weeks displayed obvious changes in cochlea morphology, and the weightlessness +noise group had the most obvious damage.

Hormonal responses of pilots flying high-performance aircraft during seven repetitive flight missions.

PubMed

Tarui, H; Nakamura, A

1991-12-01

Hormonal responses during seven repetitive flight missions (7RFM) were evaluated on F-4EJ fighter pilots. The following biochemical constituents were measured: 1) cortisol in saliva; 2) 17-OHCS; 3) unbound cortisol; 4) catecholamines in urine; and 5) electrolytes in urine. Samples were collected at about 30 min before the mission, 20 min after each flight, and in a nonflight day for control. The levels of saliva and urine corticosteroids slightly increased during 7RFM when compared with controls. The concentrations of urine catecholamines during 7RFM were significantly higher than those of preflight and control. These data suggest that flight stresses were moderate for the pilots flying 7RFM.

Periods of sensitivity to thyroid hormone during the development of the organ of Corti.

PubMed

Uziel, A

1986-01-01

Cochlear structures are sensitive to the morphogenetic effect of thyroid hormone during the whole duration of maturation. For each structure, there exists a period of maximal sensitivity to thyroid hormone which corresponds to the period of development during which the structure of interest undergoes its main morphological changes (6 to 13 days for the inner sulcus epithelium, 6 to 10 days for the pillars, the 2nd and a part of the 3rd postnatal week for OHCs and their efferent innervation in rats). These periods of sensitivity can be considered as critical periods because cochlear structures are maximally vulnerable to thyroid deficiency during these periods.

Long term effects of BAPTA in scala media on cochlear function.

PubMed

Sellick, Peter M

2007-09-01

BAPTA was iontophoresed or allowed to diffuse into the scala media of the first turn of the guinea pig cochlea via pipettes inserted through the round window and basilar membrane. Cochlear action potential (CAP) thresholds for basal turn frequencies were elevated, scala media cochlear microphonic in response to a 207Hz tone were drastically reduced and the distortion products 2f1-f2 and f2-f2 in response to primaries set at 18 and 21.6kHz were eliminated or severely reduced. The animals were recovered and the above measurements repeated between 24 and 240h after the application of BAPTA. In all animals thresholds for basal turn frequencies remained elevated, and the distortion components were severely reduced. The endolymphatic potential (EP), measured through the basilar membrane on recovery, was not significantly different from the values measured before BAPTA was applied. If the effect of BAPTA, in lowering endolymphatic Ca(2+) concentration, is restricted to the destruction of tip links, as has been shown in many other preparations, then these results suggest that this effect has permanent consequences, either because the tip links failed to regenerate or because their destruction precipitated the degeneration of OHCs. These results may have a bearing on the mechanisms behind permanent threshold shift.

Altered vitamin D status in liver tissue and blood plasma from Greenland sledge dogs (Canis familiaris) dietary exposed to organohalogen contaminated minke whale (Balaenoptera acuterostrata) blubber.

PubMed

Sonne, Christian; Kirkegaard, Maja; Jakobsen, Jette; Jenssen, Bjørn Munro; Letcher, Robert J; Dietz, Rune

2014-06-01

This study compared vitamin D3 (vitD3) and 25-OH vitamin D3 (25OHD3) status in Greenland sledge dogs (Canis familiaris) given either minke whale (Balaenoptera acuterostrata) blubber high in organohalogen contaminants (OHCs) or clean porcine (Suis scrofa) fat for up to 636 days. A group of six exposed and six control sister bitches (maternal generation) and their three exposed and four control pups, respectively, were daily fed 112g whale blubber (193µg ∑PCB/day) or porcine fat (0.17µg ∑PCB/day). Mean level of ∑PCB in adipose tissue of exposed bitches and their pups was 3106 and 2670ng/g lw, respectively, which was significantly higher than the mean concentration of 53ng/g lw for all controls (p<0.001). The vitamin analyses showed that 25OHD3 in liver of maternal exposed bitches were significantly lower than in controls (p=0.004) while vitD3 was significantly highest in liver of exposed pups (p<0.003). Regarding blood plasma concentrations, exposed F generation pups had significantly higher concentrations of 25OHD3 than controls (p=0.009). Correlation analyses showed that blood 25OHD3 decreased significantly with increased adipose tissue concentrations of ∑PCB in exposed dogs (R(2)=0.64, p=0.005) and a similar trend was found for liver 25OHD3 (R(2)=0.32, p=0.08). The results indicate that the homeostasis and metabolism of vitamin D compounds may respond differently to the dietary composition of fatty acids and OHC exposure. It is unknown if the lower level of 25OHD3 in the liver of exposed dogs would have any negative effects on immunity and reproduction and more focus should be conducted on this compound in Arctic wildlife. Copyright © 2014 Elsevier Inc. All rights reserved.

Elevated Temperature, Notched Compression Performance of Out of Autoclave Processed Composites

NASA Technical Reports Server (NTRS)

Grimsley, Brian W.; Sutter, James K.; Dixon, Genevieve D.; Smeltzer, Satn S.

2013-01-01

Curved honeycomb sandwich panels composed of carbon fiber reinforced toughened-epoxy polymer facesheets are being evaluated for potential use as payload fairing components on the NASA heavy-lift space launch system (HL-SLS). These proposed composite sandwich panels provide the most efficient aerospace launch structures, and offer mass and thermal advantages when compared with existing metallic payload fairing structures. NASA and industry are investigating recently developed carbon fiber epoxy prepreg systems which can be fabricated using out-of autoclave (OOA) processes. Specifically, OOA processes using vacuum pressure in an oven and thereby significantly reducing the cost associated with manufacturing large (up to 10 m diameter) composite structures when compared with autoclave. One of these OOA composite material systems, CYCOM(R) 5320-1, was selected for manufacture of a 1/16th scale barrel portion of the payload fairing; such that, the system could be compared with the well-characterized prepreg system, CYCOM(R) 977-3, typically processed in an autoclave. Notched compression coupons for each material were obtained from the minimum-gauge flat laminate [60/-60/0]S witness panels produced in this manufacturing study. The coupons were also conditioned to an effective moisture equilibrium point and tested according to ASTM D6484M-09 at temperatures ranging from 25 C up to 177 C. The results of this elevated temperature mechanical characterization study demonstrate that, for thin coupons, the OHC strength of the OOA laminate was equivalent to the flight certified autoclave processed composite laminates; the limitations on the elevated temperature range are hot-wet conditions up to 163 C and are only within the margins of testing error. At 25 C, both the wet and dry OOA material coupons demonstrated greater OHC failure strengths than the autoclave processed material laminates. These results indicate a substantial improvement in OOA material development and processing since previous studies have consistently reported OOA material strengths on par or below those of autoclave processed composite laminates.

A dominant variant in the PDE1C gene is associated with nonsyndromic hearing loss.

PubMed

Wang, Li; Feng, Yong; Yan, Denise; Qin, Litao; Grati, M'hamed; Mittal, Rahul; Li, Tao; Sundhari, Abhiraami Kannan; Liu, Yalan; Chapagain, Prem; Blanton, Susan H; Liao, Shixiu; Liu, Xuezhong

2018-06-02

Identification of genes with variants causing non-syndromic hearing loss (NSHL) is challenging due to genetic heterogeneity. The difficulty is compounded by technical limitations that in the past prevented comprehensive gene identification. Recent advances in technology, using targeted capture and next-generation sequencing (NGS), is changing the face of gene identification and making it possible to rapidly and cost-effectively sequence the whole human exome. Here, we characterize a five-generation Chinese family with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining population-specific mutation arrays, targeted deafness genes panel, whole exome sequencing (WES), we identified PDE1C (Phosphodiesterase 1C) c.958G>T (p.A320S) as the disease-associated variant. Structural modeling insights into p.A320S strongly suggest that the sequence alteration will likely affect the substrate-binding pocket of PDE1C. By whole-mount immunofluorescence on postnatal day 3 mouse cochlea, we show its expression in outer (OHC) and inner (IHC) hair cells cytosol co-localizing with Lamp-1 in lysosomes. Furthermore, we provide evidence that the variant alters the PDE1C hydrolytic activity for both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Collectively, our findings indicate that the c.958G>T variant in PDE1C may disrupt the cross talk between cGMP-signaling and cAMP pathways in Ca 2+ homeostasis.

On the stability and compressive nonlinearity of a physiologically based model of the cochlea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nankali, Amir; Grosh, Karl; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan

Hearing relies on a series of coupled electrical, acoustical (fluidic) and mechanical interactions inside the cochlea that enable sound processing. A positive feedback mechanism within the cochlea, called the cochlear amplifier, provides amplitude and frequency selectivity in the mammalian auditory system. The cochlear amplifier and stability are studied using a nonlinear, micromechanical model of the Organ of Corti (OoC) coupled to the electrical potentials in the cochlear ducts. It is observed that the mechano-electrical transduction (MET) sensitivity and somatic motility of the outer hair cell (OHC), control the cochlear stability. Increasing MET sensitivity beyond a critical value, while electromechanical couplingmore » coefficient is within a specific range, causes instability. We show that instability in this model is generated through a supercritical Hopf bifurcation. A reduced order model of the system is approximated and it is shown that the tectorial membrane (TM) transverse mode effect on the dynamics is significant while the radial mode can be simplified from the equations. The cochlear amplifier in this model exhibits good agreement with the experimental data. A comprehensive 3-dimensional model based on the cross sectional model is simulated and the results are compared. It is indicated that the global model qualitatively inherits some characteristics of the local model, but the longitudinal coupling along the cochlea shifts the stability boundary (i.e., Hopf bifurcation point) and enhances stability.« less

Physicochemical properties of water-soluble polysaccharides from black cumin seeds.

PubMed

Trigui, Ines; Yaich, Héla; Sila, Assaâd; Cheikh-Rouhou, Salma; Bougatef, Ali; Blecker, Christophe; Attia, Hamadi; Ayadi, M A

2018-06-01

In the present work, water-soluble polysaccharides were isolated from black cumin seeds. Polysaccharides were characterized by their carbohydrate composition, molecular weight, thermal stability and by FTIR, NMR spectroscopy and X-ray diffraction. The surface, the functional and the antioxidant properties of black cumin water-soluble polysaccharides (BCWSP) were also investigated. BCWSP consisted mainly of galacturonic acid (30.20%), glucuronic acid (17.66%) and neutral sugar (22.99%). BCWSP was composed of high peak molecular weight. The FTIR spectrum obtained for BCWSP showed two most important absorptions, at 1659 and 1085 cm -1 , which corresponded to COO - of uronic acids and pyranose form, respectively. NMR spectroscopy data suggested that the BCWSP is probably a rhamnogalacturonan backbone with galactan and arabinan side chains. X-ray pattern revealed the semi-crystalline behavior of BCWSP. WHC and OHC of BCWSP were relatively high and varied with temperatures. The polysaccharide zeta potential was greatly affected by pH. Results indicated that the decrease of surface tension has influenced foaming and emulsifying capacities. The DPPH radical scavenging activity of the BCWSP was 63.25% at 1 mg/mL. The BCWSP displayed moderate reductive, β carotene bleaching and chelating abilities. Overall, our results suggested that BCWSP could be used as alternative additives in food and non-food products. Copyright © 2017. Published by Elsevier B.V.

An Economic Feasibility Study on the Space-Based Production of Methane Gas from Human Waste through Aerobic Digestion for Use as an Orbit Maintenance Propellant.

DTIC Science & Technology

1985-12-01

TEMP, PEOPLE / It VoaeSolids Inese Volume I l Retention Time[ Methane Generated (Eqns 1 r 2, Figure 61 k,_:E OHC Convert, zFgu 9 MethIne Vol 4to Mas...other in the event of a system failure. Table III reflects the redundancy in the’U equipment and additional spare components. 6..1 ’,t 61 TABLE III Cost...1.09 4.00 27.7q D!ESTE ’JLUME 57.748 9.473 41,27 71.16 4.08 78.62 107 , ji * *0 e e .4 S.\\ * ’’ TEMP 35C PqEg;l I -0 D , D, m :𔃻,𔄁 I JM jM T’ P

Charge-transfer state excitation as the main mechanism of the photodarkening process in ytterbium-doped aluminosilicate fibres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bobkov, K K; Rybaltovsky, A A; Vel'miskin, V V

2014-12-31

We have studied photodarkening in ytterbium-doped fibre preforms with an aluminosilicate glass core. Analysis of their absorption and luminescence spectra indicates the formation of stable Yb{sup 2+} ions in the glass network under IR laser pumping at a wavelength λ = 915 nm and under UV irradiation with an excimer laser (λ = 193 nm). We have performed comparative studies of the luminescence spectra of the preforms and crystals under excitation at a wavelength of 193 nm. The mechanism behind the formation of Yb{sup 2+} ions and aluminium – oxygen hole centres (Al-OHCs), common to ytterbium-doped YAG crystals and aluminosilicatemore » glass, has been identified: photoinduced Yb{sup 3+} charge-transfer state excitation. (optical fibres)« less

TectaY1870C/+ mice with alterations in the structure and porosity of the tectorial membrane display large numbers of spontaneous emissions

NASA Astrophysics Data System (ADS)

Cheatham, M. A.; Ahmad, A.; Dallos, P.; Richardson, G. P.

2018-05-01

Spontaneous otoacoustic emissions (SOAEs) are a signature of cochlear amplification, a process associated with outer hair cell (OHC) function and required for the sensitivity and frequency selectivity of cochlear responses. Although normal mice rarely exhibit these signals, those with mutations that influence the structure of the tectorial membrane (TM) show a greater incidence of these phenomena. In this report, we study mouse models with mutations affecting the striated-sheet matrix that forms the body of this accessory structure. In addition to CEACAM16, the matrix is composed of both α- and β-tectorin (TECTA and TECTB respectively) and these latter two noncollagenous proteins are the focus of this study. Of all the mutants tested to date, mice heterozygous (het) for a missense mutation (c.5609A>G, p.Tyr1870Cys) in Tecta (TectaY1870C/+ mice) are prolific emitters with an average of ˜7 SOAEs per cochlea, which is higher than in the very few normal mice with SOAEs where the average is 2-3 per cochlea. A small number of homozygous Tectb-/- mice lacking TECTB are also emitters, but they produce only one SOAE in any given ear. Although both mouse mutants have hearing loss, SOAE frequencies coincide with frequency regions where some degree of amplification is retained. The larger number of SOAEs in TectaY1870C/+ mice appears to correlate with an increase in porosity (1), which controls the spread of excitation of tectorial membrane traveling waves. Sellon and colleagues reported that this change in the material properties of the TM was associated with the larger size of nanoscale pores linked to the Y1870C missense mutation in TECTA. In mice lacking Tectb, where porosity is wild-type like, the number of SOAEs per cochlea is small and only a few of these animals present with this phenomenon. Characterization of traveling-wave properties in other emitting TM mutants will be required to know if the correlation between increased porosity and increased numbers of SOAEs reliably causes the change in phenotype.

Solid lipid nanoparticles loaded with edaravone for inner ear protection after noise exposure.

PubMed

Gao, Gang; Liu, Ya; Zhou, Chang-Hua; Jiang, Ping; Sun, Jian-Jun

2015-01-20

Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO 3 ) staining at 1, 4, and 6 days. The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

Solid Lipid Nanoparticles Loaded with Edaravone for Inner Ear Protection After Noise Exposure

PubMed Central

Gao, Gang; Liu, Ya; Zhou, Chang-Hua; Jiang, Ping; Sun, Jian-Jun

2015-01-01

Background: Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. Methods: SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25–4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO3) staining at 1, 4, and 6 days. Results: The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Conclusions: Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL). PMID:25591563

Ab initio and density functional study on the mechanism of the C2H2++methanol reaction

NASA Astrophysics Data System (ADS)

Irle, Stephan; Morokuma, Keiji

1999-09-01

High level ab initio (G2MS and CASSCF) and density functional (B3LYP) calculations were carried out to study the mechanism of the ion-molecule reaction C2H2++CH3OH for four reaction channels: hydride abstraction from methanol (HA), proton transfer from acetylene cation (PT), charge transfer (CT), and covalent complex formation (CC) channel. For the CT channel, two pathways have been found: a usual nonadiabatic pathway via A'/A″ seam of crossing, and a low-energy adiabatic pathway through an initial intermediate; the latter may be the dominant process with favorable energies and a large impact parameter. The HA process involves a low-energy direct intermediate and a very low barrier to form C2H3+CH2OH+ and is also energetically favorable. The PT processes require passage over a high-energy transition state (TS) and are not important. One of the experimentally unobserved CC channels, formation of the COCC skeleton, is energetically favorable and there is no energetic reason for it not to take place; a "dynamic bottleneck" argument may have to be invoked to explain the experiment. The increase in reaction efficiency with the C-C stretch excitation may be justified by considering the TSs for two CT pathways, where the C-C distance changed substantially from that in the reactant C2H2+. Very qualitatively, the C2H2++CH3OH potential energy surface looks more like that of the C2H2++NH3 system than the C2H2++CH4 system, because of the differences in the ionization potentials: NH3˜CH3OH

Promoting walking among office employees ― evaluation of a randomized controlled intervention with pedometers and e-mail messages

PubMed Central

2012-01-01

Background The purpose of the study was to evaluate a 6-month intervention to promote office-employees’ walking with pedometers and e-mail messages. Methods Participants were recruited by 10 occupational health care units (OHC) from 20 worksites with 2,230 employees. Voluntary and insufficiently physically active employees (N = 241) were randomized to a pedometer (STEP, N = 123) and a comparison group (COMP, N = 118). STEP included one group meeting, log-monitored pedometer-use and six e-mail messages from OHC. COMP participated in data collection. Reach, effectiveness, adoption, implementation, maintenance (RE-AIM) and costs were assessed with questionnaires (0, 2, 6, 12 months), process evaluation and interviews (12 months). Results The intervention reached 29% (N = 646) of employees in terms of participation willingness. Logistic regression showed that the proportion of walkers tended to increase more in STEP than in COMP at 2 months in “walking for transportation” (Odds ratio 2.12, 95%CI 0.94 to 4.81) and at 6 months in “walking for leisure” (1.86, 95%CI 0.94 to 3.69). Linear model revealed a modest increase in the mean duration of “walking stairs” at 2 and 6 months (Geometric mean ratio 1.26, 95%CI 0.98 to 1.61; 1.27, 0.98 to 1.64). Adoption and implementation succeeded as intended. At 12 months, some traces of the intervention were sustained in 15 worksites, and a slightly higher number of walkers in STEP in comparison with COMP was observed in “walking stairs” (OR 2.24, 95%CI 0.94 to 5.31) and in “walking for leisure” (2.07, 95%CI 0.99 to 4.34). The direct costs of the intervention were 43 Euros per participant. Conclusions The findings indicate only modest impact on some indicators of walking. Future studies should invest in reaching the employees, minimizing attrition rate and using objective walking assessment. Trial registeration ISRCTN79432107 PMID:22672576

Ocean Observing Public-Private Collaboration to Improve Tropical Storm and Hurricane Predictions in the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Perry, R.; Leung, P.; McCall, W.; Martin, K. M.; Howden, S. D.; Vandermeulen, R. A.; Kim, H. S. S.; Kirkpatrick, B. A.; Watson, S.; Smith, W.

2016-02-01

In 2008, Shell partnered with NOAA to explore opportunities for improving storm predictions in the Gulf of Mexico. Since, the collaboration has grown to include partners from Shell, NOAA National Data Buoy Center and National Center for Environmental Information, National Center for Environmental Prediction, University of Southern Mississippi, and the Gulf of Mexico Coastal Ocean Observing System. The partnership leverages complementary strengths of each collaborator to build a comprehensive and sustainable monitoring and data program to expand observing capacity and protect offshore assets and Gulf communities from storms and hurricanes. The program combines in situ and autonomous platforms with remote sensing and numerical modeling. Here we focus on profiling gliders and the benefits of a public-private partnership model for expanding regional ocean observing capacity. Shallow and deep gliders measure ocean temperature to derive ocean heat content (OHC), along with salinity, dissolved oxygen, fluorescence, and CDOM, in the central and eastern Gulf shelf and offshore. Since 2012, gliders have collected 4500+ vertical profiles and surveyed 5000+ nautical miles. Adaptive sampling and mission coordination with NCEP modelers provides specific datasets to assimilate into EMC's coupled HYCOM-HWRF model and 'connect-the-dots' between well-established Eulerian metocean measurements by obtaining (and validating) data between fixed stations (e.g. platform and buoy ADCPs) . Adaptive sampling combined with remote sensing provides satellite-derived OHC validation and the ability to sample productive coastal waters advected offshore by the Loop Current. Tracking coastal waters with remote sensing provides another verification of estimate Loop Current and eddy boundaries, as well as quantifying productivity and analyzing water quality on the Gulf coast, shelf break and offshore. Incorporating gliders demonstrates their value as tools to better protect offshore oil and gas assets and the greater Gulf coast communities from storms and hurricanes. Data collected under the collaboration, along with deployment of gliders, will have long-term benefits in helping to understand the ecological and environmental health of the Gulf by monitoring real-time annual and seasonal physical variability.

PubMed Central

RALLI, M.; TROIANI, D.; PODDA, M.V.; PACIELLO, F.; ERAMO, S.L.M.; DE CORSO, E.; SALVI, R.; PALUDETTI, G.; FETONI, A.R.

2014-01-01

SUMMARY Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The present study confirms the role of cochlear NMDA receptors in the induction of salicylate-induced tinnitus. PMID:24882929

Fimbriiglobus ruber gen. nov., sp. nov., a Gemmata-like planctomycete from Sphagnum peat bog and the proposal of Gemmataceae fam. nov.

PubMed

Kulichevskaya, Irina S; Ivanova, Anastasia A; Baulina, Olga I; Rijpstra, W Irene C; Sinninghe Damsté, Jaap S; Dedysh, Svetlana N

2017-02-01

An aerobic, budding, dark pink to red-pigmented bacterium was isolated from an acidic boreal Sphagnum peat bog and designated strain SP5T. Cells of this strain were non-motile spheres that were uniformly covered with crateriform pits and fimbria, and tended to form aggregates during growth in liquid media. Strain SP5T was capable of growth between pH 4.0 and pH 6.8 (optimum at pH 5.5-6.0) and at temperatures between 10 and 30 °C (optimum at 20-25 °C). The preferred growth substrates were sugars and some heteropolysaccharides. The major fatty acids were C20 : 1ω9c, C16 : 1ω9c and C16 : 0, and the major polar lipid was trimethylornithine. Cells contained also significant amounts of bound (ω-1)OH-C30 : 1 fatty acid. The quinone was menaquinone-6, and the G+C content of the DNA was 60.7 mol%. Strain SP5T was a member of the order Planctomycetales and belonged to the phylogenetic lineage defined by the genus Gemmata. It displayed 88 and 89 % 16S rRNA gene sequence similarity to Gemmata obscuriglobusUQM 2246T and 'Gemmata massiliana' IIL30, 89 % to Zavarzinella formosa A10T and 86 % to Telmatocola sphagniphila SP2T. However, strain SP5T differed from members of these genera by cell morphology, substrate utilization pattern and fatty acid composition. Based on these data, the novel isolate should be considered as representing a novel species of a new genus of planctomycetes, for which the name Fimbriiglobus ruber gen. nov., sp. nov, is proposed. The type strain is SP5T (=LMG 29572T=VKM B-3045T). We also suggest the establishment of a novel family, Gemmataceaefam. nov., which includes the phylogenetically related genera Gemmata, Zavarzinella, Telmatocola and Fimbriiglobus.

Frequency specificity and left-ear advantage of medial olivocochlear efferent modulation: a study based on stimulus frequency otoacoustic emission.

PubMed

Xing, Dongjia; Gong, Qin

2017-09-06

The medial olivocochlear (MOC) bundle is an auditory nucleus that projects efferent nerve fibers to the outer hair cells (OHCs) for synaptic innervation. The aim of the present study was to investigate the possible existence of frequency and ear specificity in MOC efferent modulation, as well as how MOC activation influences cochlear tuning. Stimulus frequency otoacoustic emissions (SFOAEs) were used to study MOC efferent modulation. Therefore, the current experiment was designed to compare the degree of SFOAE suppression in the both ears of 20 individuals at 1, 2, 4, and 8 kHz. We also compared changes in Q10 values of SFOAE suppression tuning curves at 1, 2, and 4 kHz under contralateral acoustic stimulation (CAS) and no-CAS conditions. We observed a significant reduction in SFOAE magnitude in the CAS condition compared with the no-CAS condition at 1 and 2 kHz in the left ear. A significant difference in CAS suppression was also found between the left and right ears at 1 and 2 kHz, with larger CAS suppression in the left ear. CAS further produced a statistically significant increase in the Q10 value at 1 kHz and a significant reduction in Q10 values at 2 and 4 kHz. These findings suggest a left-ear advantage in terms of CAS-induced MOC efferent SFOAE suppression, with larger MOC efferent modulation for lower frequencies, and cochlear tuning was sharpened by means of MOC activation at lower frequencies and broadened at higher frequencies.

Lelliottia aquatilis sp. nov., isolated from drinking water.

PubMed

Kämpfer, Peter; Glaeser, Stefanie P; Packroff, Gabriele; Behringer, Katja; Exner, Martin; Chakraborty, Trinad; Schmithausen, Ricarda M; Doijad, Swapnil

2018-06-22

Five beige-pigmented, oxidase-negative bacterial isolates, 6331-17 T , 6332-17, 6333-17, 6334-17 and 9827-07, isolated either from a drinking water storage reservoir or drinking water in 2006 and 2017 in Germany, were examined in detail applying by a polyphasic taxonomic approach. Cells of the isolates were rod-shaped and Gram-stain-negative. Comparison of the 16S rRNA gene sequences of these five isolates showed highest sequence similarities to Lelliottia amnigena (99.98 %) and Lelliottia nimipressuralis (99.99 %). Multilocus sequence analyses based on concatenated partial rpoB, gyrB, infB and atpD sequences confirmed the clustering of these isolates with Lelliottia species, but also revealed a clear distinction to the closest related type strains. Analysis of the genome sequences of these isolates indicated >70 % in silico DNA-DNA hybridization and high average nucleotide identities between strains. Nevertheless, they showed only <70 and <95 % similarity to the type strains of these two Lelliottia species. The fatty acid profiles of these isolates were very similar and consisted of the major fatty acids C16:0, C17 : 0cyclo, C15 : 0iso 2-OH/C16 : 1ω7c and C18 : 1ω7c. In addition, physiological/biochemical tests revealed high phenotypic similarity to each other. These cumulative data indicate that these isolates represent a novel Lelliottia species, for which the name Lelliottia aquatilis sp. nov. is proposed, with strain 6331-17 T (=CCM 8846 T =CIP 111609 T =LMG 30560 T ) as the type strain.

First-order wetting transition at a liquid-vapor interface

NASA Technical Reports Server (NTRS)

Schmidt, J. W.; Moldover, M. R.

1983-01-01

Evidence from reflectance and contact angle measurements is presented that three-phase mixtures of i-C3H7OH-C7F14 exhibit a first-order wetting phase transition at the liquid-vapor interface at 38 C. Equilibration phenomena support this interpretation. Ellipsometry was used to measure the apparent thickness of the intruding layer in the three-phase mixture. At temperatures slightly above the wetting temperature T(w), the intruding layer's thickness is several hundred angstroms and its variation with temperature is extremely weak. Below T(w), three-phase contact can occur between the vapor and both the upper and lower liquid phases; one of the angles which characterizes this contact has a very simple temperature dependence. The thickness of the intruding layer, monitored as the solutions approached equilibrium, is found to depend quite weakly on the height spanned by the upper liquid phase in the vicinity of a first-order wetting transition.

A two-dimensional ZnII coordination polymer constructed from benzene-1,2,3-tricarboxylic acid and N,N'-bis[(pyridin-4-yl)methylidene]hydrazine.

PubMed

Wang, Xiangfei; Yang, Fang; Tang, Meng; Yuan, Limin; Liu, Wenlong

2015-07-01

The hydrothermal synthesis of the novel complex poly[aqua(μ4-benzene-1,2,3-tricarboxylato)[μ2-4,4'-(hydrazine-1,2-diylidenedimethanylylidene)dipyridine](μ3-hydroxido)dizinc(II)], [Zn(C9H3O6)(OH)(C12H10N4)(H2O)]n, is described. The benzene-1,2,3-tricarboxylate ligand connects neighbouring Zn4(OH)2 secondary building units (SBUs) producing an infinite one-dimensional chain. Adjacent one-dimensional chains are connected by the N,N'-bis[(pyridin-4-yl)methylidene]hydrazine ligand, forming a two-dimensional layered structure. Adjacent layers are stacked to generate a three-dimensional supramolecular architecture via O-H...O hydrogen-bond interactions. The thermal stability of this complex is described and the complex also appears to have potential for application as a luminescent material.

Acyl-Homoserine Lactone Production in Nitrifying Bacteria of the Genera Nitrosospira, Nitrobacter, and Nitrospira Identified via a Survey of Putative Quorum-Sensing Genes.

PubMed

Mellbye, Brett L; Spieck, Eva; Bottomley, Peter J; Sayavedra-Soto, Luis A

2017-11-15

The genomes of many bacteria that participate in nitrogen cycling through the process of nitrification contain putative genes associated with acyl-homoserine lactone (AHL) quorum sensing (QS). AHL QS or bacterial cell-cell signaling is a method of bacterial communication and gene regulation and may be involved in nitrogen oxide fluxes or other important phenotypes in nitrifying bacteria. Here, we carried out a broad survey of AHL production in nitrifying bacteria in three steps. First, we analyzed the evolutionary history of AHL synthase and AHL receptor homologs in sequenced genomes and metagenomes of nitrifying bacteria to identify AHL synthase homologs in ammonia-oxidizing bacteria (AOB) of the genus Nitrosospira and nitrite-oxidizing bacteria (NOB) of the genera Nitrococcus , Nitrobacter , and Nitrospira Next, we screened cultures of both AOB and NOB with uncharacterized AHL synthase genes and AHL synthase-negative nitrifiers by a bioassay. Our results suggest that an AHL synthase gene is required for, but does not guarantee, cell density-dependent AHL production under the conditions tested. Finally, we utilized mass spectrometry to identify the AHLs produced by the AOB Nitrosospira multiformis and Nitrosospira briensis and the NOB Nitrobacter vulgaris and Nitrospira moscoviensis as N -decanoyl-l-homoserine lactone (C 10 -HSL), N -3-hydroxy-tetradecanoyl-l-homoserine lactone (3-OH-C 14 -HSL), a monounsaturated AHL (C 10:1 -HSL), and N -octanoyl-l-homoserine lactone (C 8 -HSL), respectively. Our survey expands the list of AHL-producing nitrifiers to include a representative of Nitrospira lineage II and suggests that AHL production is widespread in nitrifying bacteria. IMPORTANCE Nitrification, the aerobic oxidation of ammonia to nitrate via nitrite by nitrifying microorganisms, plays an important role in environmental nitrogen cycling from agricultural fertilization to wastewater treatment. The genomes of many nitrifying bacteria contain genes associated with bacterial cell-cell signaling or quorum sensing (QS). QS is a method of bacterial communication and gene regulation that is well studied in bacterial pathogens, but less is known about QS in environmental systems. Our previous work suggested that QS might be involved in the regulation of nitrogen oxide gas production during nitrite metabolism. This study characterized putative QS signals produced by different genera and species of nitrifiers. Our work lays the foundation for future experiments investigating communication between nitrifying bacteria, the purpose of QS in these microorganisms, and the manipulation of QS during nitrification. Copyright © 2017 American Society for Microbiology.

Estimating TCR using an integrated model-observation framework that accounts for spatio-temporal variability and pre-industrial radiative imbalances.

NASA Astrophysics Data System (ADS)

Haustein, K.; Schurer, A. P.; Venema, V.

2016-12-01

Apart from a few exceptions (e.g. Aldrin et al. 2012, Skeie et al. 2013) TCR estimates with EBMs are based on global data. Since these estimates don't represent the true spatial-temporal behaviour for observed temperature as well as external forcing (Marvel et al. 2015), we have developed a two-box EBM framework that accounts for these effects. In addition, external forcing from anthropogenic aerosol and GHGs tends to have different response times in comparison to volcanic stratospheric aerosols. Using PMIP3 and an extended ensemble of HadCM3 simulations (Euro500; Schurer et al. 2014) GCM simulations for the pre-industrial period, we obtain the fast and slow response time constants required in the EBM. With the most recent anthropogenic and natural forcing estimates, we test a range of TCR values against observations. The TCR/ECS ratio necessary to achieve that goal is taken from CMIP5 as observationally OHC-based estimates are notoriously unreliable. Given that observed and modelled OHC estimates are in agreement (Cheng et al. 2016), we argue that this should be the standard procedure the make inferences about ECS. Alternatively, it should be distinguished between equilibrium and effective climate sensitivity. The preliminary best estimate for TCR is 1.6K (1.1-2.2K) with an associated ECS value of 2.9K (2.0-4.0K). This is in good agreement with other D&A techniques that do use spatio-temporal patterns as well (e.g. Jones et al. 2016, Gillet et al. 2013). Correcting for natural ENSO variability and tas/tos-related inaccuracies (Richardson et al. 2016) further increases the robustness of the estimated sensitivity range. Our results also indicate that the small radiative imbalance caused by the period of very strong volcanic eruptions just before the CMIP5 historical period starts (1809-1840) has noteworthy implications for the response to later volcanic eruptions and the temperature evolution after 1850. Simply put, CMIP5-type simulations are slightly more sensitive to volcanic eruptions than PMIP3-type simulations. This has been pointed out in the literature before (e.g. Gleckler et al. 2006, Stenchikov et al. 2009, Gregory et al. 2010). We therefore argue that more PMIP3-type of experiments are needed to factor in the planetary energy imbalance caused by earlier volcanic eruptions.

Intervention mapping for development of a participatory return-to-work intervention for temporary agency workers and unemployed workers sick-listed due to musculoskeletal disorders

PubMed Central

Vermeulen, Sylvia J; Anema, Johannes R; Schellart, Antonius JM; van Mechelen, Willem; van der Beek, Allard J

2009-01-01

Background In the past decade in activities aiming at return-to-work (RTW), there has been a growing awareness to change the focus from sickness and work disability to recovery and work ability. To date, this process in occupational health care (OHC) has mainly been directed towards employees. However, within the working population there are two vulnerable groups: temporary agency workers and unemployed workers, since they have no workplace/employer to return to, when sick-listed. For this group there is a need for tailored RTW strategies and interventions. Therefore, this paper aims to describe the structured and stepwise process of development, implementation and evaluation of a theory- and practise-based participatory RTW program for temporary agency workers and unemployed workers, sick-listed due to musculoskeletal disorders (MSD). This program is based on the already developed and cost-effective RTW program for employees, sick-listed due to low back pain. Methods The Intervention Mapping (IM) protocol was used to develop a tailor-made RTW program for temporary agency workers and unemployed workers, sick-listed due to MSD. The Attitude-Social influence-self-Efficacy (ASE) model was used as a theoretical framework for determinants of behaviour regarding RTW of the sick-listed worker and development of the intervention. To ensure participation and facilitate successful adoption and implementation, important stakeholders were involved in all steps of program development and implementation. Results of semi-structured interviews and 'fine-tuning' meetings were used to design the final participatory RTW program. Results A structured stepwise RTW program was developed, aimed at making a consensus-based RTW implementation plan. The new program starts with identifying obstacles for RTW, followed by a brainstorm session in which the sick-listed worker and the labour expert of the Social Security Agency (SSA) formulate solutions/possibilities for suitable (therapeutic) work. This process is guided by an independent RTW coordinator to achieve consensus. Based on the resulting RTW implementation plan, to create an actual RTW perspective, a vocational rehabilitation agency is assigned to find a matching (therapeutic) workplace. The cost-effectiveness of this participatory RTW program will be evaluated in a randomised controlled trial. Conclusion IM is a promising tool for the development of tailor-made OHC interventions for the vulnerable working population. PMID:19573229

Contralateral Inhibition of Click- and Chirp-Evoked Human Compound Action Potentials

PubMed Central

Smith, Spencer B.; Lichtenhan, Jeffery T.; Cone, Barbara K.

2017-01-01

Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit provides the neural substrate for the MOC reflex, which inhibits cochlear amplifier gain and is believed to play a role in listening in noise and protection from acoustic overexposure. The human MOC reflex has been studied extensively using otoacoustic emissions (OAE) paradigms; however, these measurements are insensitive to subsequent “downstream” efferent effects on the neural ensembles that mediate hearing. In this experiment, click- and chirp-evoked auditory nerve compound action potential (CAP) amplitudes were measured electrocochleographically from the human eardrum without and with MOC reflex activation elicited by contralateral broadband noise. We hypothesized that the chirp would be a more optimal stimulus for measuring neural MOC effects because it synchronizes excitation along the entire length of the basilar membrane and thus evokes a more robust CAP than a click at low to moderate stimulus levels. Chirps produced larger CAPs than clicks at all stimulus intensities (50–80 dB ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low stimulus levels when quantified both in terms of amplitude reduction and effective attenuation. Effective attenuation was larger for chirp- and click-evoked CAPs than for click-evoked OAEs measured from the same subjects. Our results suggest that the chirp is an optimal stimulus for evoking CAPs at low stimulus intensities and for assessing MOC reflex effects on the auditory nerve. Further, our work supports previous findings that MOC reflex effects at the level of the auditory nerve are underestimated by measures of OAE inhibition. PMID:28420960

Enterobacter muelleri sp. nov., isolated from the rhizosphere of Zea mays.

PubMed

Kämpfer, Peter; McInroy, John A; Glaeser, Stefanie P

2015-11-01

A beige-pigmented, oxidase-negative bacterial strain (JM-458T), isolated from a rhizosphere sample, was studied using a polyphasic taxonomic approach. Cells of the isolate were rod-shaped and stained Gram-negative. A comparison of the 16S rRNA gene sequence of strain JM-458T with sequences of the type strains of closely related species of the genus Enterobacter showed that it shared highest sequence similarity with Enterobacter mori (98.7 %), Enterobacter hormaechei (98.3 %), Enterobacter cloacae subsp. dissolvens, Enterobacter ludwigii and Enterobacter asburiae (all 98.2 %). 16S rRNA gene sequence similarities to all other Enterobacter species were below 98 %. Multilocus sequence analysis based on concatenated partial rpoB, gyrB, infB and atpD gene sequences showed a clear distinction of strain JM-458T from its closest related type strains. The fatty acid profile of the strain consisted of C16 : 0, C17 : 0 cyclo, iso-C15 : 0 2-OH/C16 : 1ω7c and C18 : 1ω7c as major components. DNA-DNA hybridizations between strain JM-458T and the type strains of E. mori, E. hormaechei and E. ludwigii resulted in relatedness values of 29 % (reciprocal 25 %), 24 % (reciprocal 43 %) and 16 % (reciprocal 17 %), respectively. DNA-DNA hybridization results together with multilocus sequence analysis results and differential biochemical and chemotaxonomic properties showed that strain JM-458T represents a novel species of the genus Enterobacter, for which the name Enterobacter muelleri sp. nov. is proposed. The type strain is JM-458T ( = DSM 29346T = CIP 110826T = LMG 28480T = CCM 8546T).

Child protection services and parents with intellectual and developmental disabilities.

PubMed

LaLiberte, Traci; Piescher, Kristine; Mickelson, Nicole; Lee, Mi Hwa

2017-05-01

Information about parents with intellectual and developmental disabilities (IDD) in the child protection system (CPS) continues to evolve. This study examined characteristics, experiences and representation of parents with IDD across three CPS decision points, as compared to parents with other disabilities and parents without disabilities in the United States. The sample consisted of 303,039 individuals: 2,081 were individuals identified as parents in a CPS investigation; 1,101 had children in out-of-home care (OHC); and 308 experienced termination of parental rights (TPR). Descriptive statistics, chi-square analysis, disparity indices and logistic regression were employed. Parents with IDD were significantly more likely than parents without disabilities (but not significantly more likely than parents with other types of disabilities) to experience disproportionately representation. Parents with IDD are generally over-represented within CPS; however, this representation is dependent upon the comparison group utilized and other risk factors. CPS system-level changes are necessary. © 2016 John Wiley & Sons Ltd.

Effects of high-speed homogenization and high-pressure homogenization on structure of tomato residue fibers.

PubMed

Hua, Xiao; Xu, Shanan; Wang, Mingming; Chen, Ying; Yang, Hui; Yang, Ruijin

2017-10-01

Tomato residue fibers obtained after derosination and deproteinization were processed by high-speed homogenization (HSH) and high-pressure homogenization (HPH), and their effects on fiber structure was investigated, respectively. Characterizations including particle size distribution, SEM, TEM and XRD were performed. HSH could break raw fibers to small particles of around 60μm, while HPH could reshape fibers to build network structure. Microfibrils were released and their nanostructure consisting of elementary fibrils was observed by TEM. XRD patterns indicated both HSH and HPH could hardly alter the nanostructure of the fibers. Physicochemical properties including expansibility, WHC and OHC were determined. Both HSH and HPH could increase the soluble fiber content by about 8%, but HSH-HPH combined processing did not show better result. Acid (4mol/L HCl) was used in replacement of water medium and the acidic degradation of fibers could be promoted by high speed shearing or high pressure processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Short-term effects of air temperature on plasma metabolite concentrations in patients undergoing cardiac catheterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hampel, Regina, E-mail: regina.hampel@helmholtz-mu

Background: Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease. Objectives: To investigate short-term temperature effects on metabolites related to cardiovascular disease. Methods: Concentrations of 45 acylcarnitines, 15 amino acids, ketone bodies and total free fatty acids were available in 2869 participants from the CATHeterization GENetics cohort recruited at the Duke University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten metabolites were selected based on quality criteria and cluster analysis. Daily averages of meteorological variables were obtained from the North American Regionalmore » Reanalysis project. Immediate, lagged, and cumulative temperature effects on metabolite concentrations were analyzed using (piecewise) linear regression models. Results: Linear temperature effects were found for glycine, C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5 °C increase in temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%] increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1-DC (lag of four days), and a −1.4% [−2.4%; −0.3%] decrease in aspartic acid/asparagine (lag of two days). Non-linear temperature effects were observed for alanine and total ketone bodies with breakpoint of 4 °C and 20 °C, respectively. Both a 5 °C decrease in temperature on colder days (<4 °C)and a 5 °C increase in temperature on warmer days (≥4 °C) were associated with a four day delayed increase in alanine by 6.6% [11.7; 1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate (0-day lag) increases of 4.2% [−0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated with 5 °C decreases on colder (<20 °C) days and 5 °C increases on warmer days (≥20 °C), respectively. Conclusions: We observed multiple effects of air temperature on metabolites several of which are reported to be involved in cardiovascular disease. Our findings might help to understand the link between air temperature and cardiovascular disease. - Highlights: • Certain metabolites are assumed to be novel biomarkers for cardiovascular disease. • First study investigating associations between air temperature and metabolites. • Short-term effects of temperature on amino acids, ketone bodies and acylcarnitines. • Our findings may help to understand the link between temperature and cardiovascular disease.« less

Tracking ocean heat uptake during the surface warming hiatus

DOE PAGES

Liu, Wei; Xie, Shang -Ping; Lu, Jian

2016-03-30

Ocean heat uptake is observed to penetrate deep during the recent hiatus1,2,3 of global warming in the Atlantic and Southern Ocean. This has been suggested to indicate that the two regions are the driver of the surface warming hiatus4. We show that the deep heat penetration in the Atlantic and Southern Ocean is not unique to the hiatus but common to the past four decades including the 1970s-90s epoch of accelerated surface warming. Our analyses of a large ensemble simulation5 confirm the deep heat penetration in the Atlantic and Southern Ocean in ensemble members with or without surface warming hiatusmore » in the early 21th century. During the past four decades, the global ocean heat content (OHC) of upper 1500m is dominated by a warming trend, and the depth of anthropogenic heat penetration merely reflects the depth of the mean meridional overturning circulation in the basin. Furthermore, the heat penetration depth is not a valid basis to infer the hiatus mechanism.« less

The significance of cholesterol and its metabolite, 27-hydroxycholesterol in breast cancer.

PubMed

Nelson, Erik R

2018-05-05

Although significant advances in the treatment of breast cancer have been made, in particular in the use of endocrine therapy, de novo and aquired resistance to therapy, and metastatic recurrence continue to be major clinical problems. Given the high prevalence of breast cancer, new life-style or chemotherapeutic approaches are required. In this regard, cholesterol has emerged as a risk factor for the onset of breast cancer, and elevated cholesterol is associated with a poor prognosis. While treatment with cholesterol lowering medication is not associated with breast cancer risk, it does appear to be protective against recurrence. Importantly, the cholesterol axis represents a potential target for both life-style and pharmacological intervention. This review will outline the clinical and preclinical data supporting a role for cholesterol in breast cancer pathophysiology. Specific focus is given to 27-hydroxycholesterol (27-OHC; (3β,25R)-Cholest-5-ene-3,26-diol)), a primary metabolite of cholesterol that has recently been defined as an endogenous Selective Estrogen Receptor Modulator. Future perspectives and directions are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of RTM370 Polyimide Composites by Resin Film Infusion (RFI)

NASA Technical Reports Server (NTRS)

Chuang, Kathy C.; Yip, Thomas A.; Kollmansberger, Ronald B.; Tsotsis, Thomas K.

2014-01-01

RTM370 imide oligomer based on 2,3,3',4'-biphenyl dianhydride (a-BPDA), 3,4'-oxydianiline (3,4'-ODA) and terminated with the 4-phenylethynylphthalic (PEPA) endcap has been shown to exhibit a low melt viscosity (10-30 poise) at 280 C with a pot-life of 1-2 h and a high cured glass-transition temperature (Tg) of 370 C. RTM370 resin has been successfully infused into fiberglass-stitched T650-35 carbon-fabric preforms (ranged from 3- to 6-mm thick) by resin film infusion (RFI). The resulting composite panels were inspected by ultrasonic C-scan and by photomicrographs before and after post-curing as a quality control. Mechanical tests such as unnotched compression (UNC), open-hole compression (OHC), and short-beam shear strength (SBS) at ambient and elevated temperatures were performed before and after isothermal aging at 288 C for 1000 h to assess high-temperature performance. Thermal cycling of RTM370 stitched composites was also conducted from -54 C to 288 C for up to 1600 cycles to evaluate the microcrack resistance of RTM370 polyimide composites fabricated by RFI.

Synthesis, Structure and Thermal Behavior of Oxalato-Bridged Rb+ and H3O+ Extended Frameworks with Different Dimensionalities

PubMed Central

Kherfi, Hamza; Hamadène, Malika; Guehria-Laïdoudi, Achoura; Dahaoui, Slimane; Lecomte, Claude

2010-01-01

Correlative studies of three oxalato-bridged polymers, obtained under hydrothermal conditions for the two isostructural compounds {Rb(HC2O4)(H2C2O4)(H2O)2}∞1, 1, {H3O(HC2O4)(H2C2O4).2H2O}∞1, 2, and by conventional synthetic method for {Rb(HC2O4)}∞3, 3, allowed the identification of H-bond patterns and structural dimensionality. Ferroïc domain structures are confirmed by electric measurements performed on 3. Although 2 resembles one oxalic acid sesquihydrate, its structure determination doesn’t display any kind of disorder and leads to recognition of a supramolecular network identical to hybrid s-block series, where moreover, unusual H3O+ and NH4+ similarity is brought out. Thermal behaviors show that 1D frameworks with extended H-bonds, whether with or without a metal center, have the same stability. Inversely, despite the dimensionalities, the same metallic intermediate and final compounds are obtained for the two Rb+ ferroïc materials.

Tracking ocean heat uptake during the surface warming hiatus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei; Xie, Shang -Ping; Lu, Jian

Ocean heat uptake is observed to penetrate deep during the recent hiatus1,2,3 of global warming in the Atlantic and Southern Ocean. This has been suggested to indicate that the two regions are the driver of the surface warming hiatus4. We show that the deep heat penetration in the Atlantic and Southern Ocean is not unique to the hiatus but common to the past four decades including the 1970s-90s epoch of accelerated surface warming. Our analyses of a large ensemble simulation5 confirm the deep heat penetration in the Atlantic and Southern Ocean in ensemble members with or without surface warming hiatusmore » in the early 21th century. During the past four decades, the global ocean heat content (OHC) of upper 1500m is dominated by a warming trend, and the depth of anthropogenic heat penetration merely reflects the depth of the mean meridional overturning circulation in the basin. Furthermore, the heat penetration depth is not a valid basis to infer the hiatus mechanism.« less

[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].

PubMed

Notsu, K; Takagi, C; Umaki, I

1995-03-20

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

Ablation of the auditory cortex results in changes in the expression of neurotransmission-related mRNAs in the cochlea.

PubMed

Lamas, Verónica; Juiz, José M; Merchán, Miguel A

2017-03-01

The auditory cortex (AC) dynamically regulates responses of the Organ of Corti to sound through descending connections to both the medial (MOC) and lateral (LOC) olivocochlear efferent systems. We have recently provided evidence that AC has a reinforcement role in the responses to sound of the auditory brainstem nuclei. In a molecular level, we have shown that descending inputs from AC are needed to regulate the expression of molecules involved in outer hair cell (OHC) electromotility control, such as prestin and the α10 nicotinic acetylcholine receptor (nAchR). In this report, we show that descending connections from AC to olivocochlear neurons are necessary to regulate the expression of molecules involved in cochlear afferent signaling. RT-qPCR was performed in rats at 1, 7 and 15 days after unilateral ablation of the AC, and analyzed the time course changes in gene transcripts involved in neurotransmission at the first auditory synapse. This included the glutamate metabolism enzyme glutamate decarboxylase 1 (glud1) and AMPA glutamate receptor subunits GluA2-4. In addition, gene transcripts involved in efferent regulation of type I spiral ganglion neuron (SGN) excitability mediated by LOC, such as the α7 nAchR, the D2 dopamine receptor, and the α1, and γ2 GABAA receptor subunits, were also investigated. Unilateral AC ablation induced up-regulation of GluA3 receptor subunit transcripts, whereas both GluA2 and GluA4 mRNA receptors were down-regulated already at 1 day after the ablation. Unilateral removal of the AC also resulted in up-regulation of the transcripts for α7 nAchR subunit, D2 dopamine receptor, and α1 GABAA receptor subunit at 1 day after the ablation. Fifteen days after the injury, AC ablations induced an up-regulation of glud1 transcripts. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Functional recovery in the avian ear after hair cell regeneration.

PubMed

Smolders, J W

1999-01-01

Trauma to the inner ear in birds, due to acoustic overstimulation or ototoxic aminoglycosides, can lead to hair cell loss which is followed by regeneration of new hair cells. These processes are paralleled by hearing loss followed by significant functional recovery. After acoustic trauma, functional recovery is rapid and nearly complete. The early and major part of functional recovery after sound trauma occurs before regenerated hair cells become functional. Even very intense sound trauma causes loss of only a proportion of the hair cell population, mainly so-called short hair cells residing on the abneural mobile part of the avian basilar membrane. Uncoupling of the tectorial membrane from the hair cells during sound overexposure may serve as a protection mechanism. The rapid functional recovery after sound trauma appears not to be associated with regeneration of the lost hair cells, but with repair processes involving the surviving hair cells. Small residual functional deficits after recovery are most likely associated with the missing upper fibrous layer of the tectorial membrane which fails to regenerate after sound trauma. After aminoglycoside trauma, functional recovery is slower and parallels the structural regeneration more closely. Aminoglycosides cause damage to both types of hair cells, starting at the basal (high frequency) part of the basilar papilla. However, functional hearing loss and recovery also occur at lower frequencies, associated with areas of the papilla where hair cells survive. Functional recovery in these low frequency areas is complete, whereas functional recovery in high frequency areas with complete hair cell loss is incomplete, despite regeneration of the hair cells. Permanent residual functional deficits remain. This indicates that in low frequency regions functional recovery after aminoglycosides involves repair of nonlethal injury to hair cells and/or hair cell-neural synapses. In the high frequency regions functional recovery involves regenerated hair cells. The permanent functional deficits after the regeneration process in these areas are most likely associated with functional deficits in the regenerated hair cells or shortcomings in the synaptic reconnections of nerve fibers with the regenerated hair cells. In conclusion, the avian inner ear appears to be much more resistant to trauma than the mammalian ear and possesses a considerable capacity for functional recovery based on repair processes along with its capacity to regenerate hair cells. The functional recovery in areas with regenerated hair cells is considerable but incomplete.

[The cell theory. Progress in studies on cell-cell communications].

PubMed

Brodskiĭ, V Ia

2009-01-01

Current data confirm the fundamental statement of the cell theory concerning the cell reproduction in a series of generations (omnis cellula e cellula). Cell communities or ensembles integrated by the signaling systems established in prokaryotes and protists and functioning in multicellular organisms including mammals are considered as the structural and functional unit of a multicellular organism. The cell is an elementary unit of life and basis of organism development and functioning. At the same time, the adult organism is not just a totality of cells. Multinucleated cells in some tissues, syncytial structure, and structural-functional units of organs are adaptations for optimal functioning of the multicellular organism and manifestations of cell-cell communications in development and definitive functioning. The cell theory was supplemented and developed by studies on cell-cell communications; however, these studies do not question the main generalizations of the theory.

Single-cell-type Proteomics: Toward a Holistic Understanding of Plant Function*

PubMed Central

Dai, Shaojun; Chen, Sixue

2012-01-01

Multicellular organisms such as plants contain different types of cells with specialized functions. Analyzing the protein characteristics of each type of cell will not only reveal specific cell functions, but also enhance understanding of how an organism works. Most plant proteomics studies have focused on using tissues and organs containing a mixture of different cells. Recent single-cell-type proteomics efforts on pollen grains, guard cells, mesophyll cells, root hairs, and trichomes have shown utility. We expect that high resolution proteomic analyses will reveal novel functions in single cells. This review provides an overview of recent developments in plant single-cell-type proteomics. We discuss application of the approach for understanding important cell functions, and we consider the technical challenges of extending the approach to all plant cell types. Finally, we consider the integration of single-cell-type proteomics with transcriptomics and metabolomics with the goal of providing a holistic understanding of plant function. PMID:22982375

Development and modification of a single overhead camshaft 4-valve 4-stroke 135 cc formula varsity race car engine

NASA Astrophysics Data System (ADS)

Abdullah, M. A.; Tamaldin, N.; Rusnandi, H.; Manoharan, T.; Samsir, M. A.

2013-12-01

The engine that was chosen to be developed and modified is Yamaha LC 135 Single Overhead Camshaft (SOHC) 4-valve 4-stroke 135cc liquid-cooled engine. The engine selection is based on the specification, rule and regulation in UTeM Formula Varsity 2012 (FV 2012). The engine performance is determined by engine operating characteristics. The engine air flow affects the filtration, intake and exhaust systems. The heat from the engine rejected to the surrounding through the active cooling system which has radiator and fan. The selection of the engine is based on weighted decision matrix which consists of reliability, operating and maintenance cost, fuel consumption and weight. The score of the matrix is formulated based on relative weighted factor among the selections. It been compared between Yamaha LC 135 Single Overhead Camshaft (SOHC) 4-valve 4-stroke 135cc liquid-cooled engine, Honda Wave 125 X Air Cooled, 4 Cycle Engine Overhead Camshaft (OHC) and Suzuki Shogun RR 4 stroke air cooled Single Overhead Camshaft (SOHC). The modification is applied to the engine through the simulation and tuning of Capacitor Discharge Ignition (CDI).

Parapedobacter koreensis gen. nov., sp. nov.

PubMed

Kim, Myung Kyum; Na, Ju-Ryun; Cho, Dong Ha; Soung, Nak-Kyun; Yang, Deok-Chun

2007-06-01

Strain Jip14(T), a Gram-negative, non-spore-forming, rod-shaped, non-motile bacterium, was isolated from dried rice straw and characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain Jip14(T) belongs to the family Sphingobacteriaceae, and the highest degree of sequence similarity was determined to be to Pedobacter saltans DSM 12145(T) (88.5 %), Pedobacter africanus DSM 12126(T) (87.6 %), Pedobacter heparinus DSM 2366(T) (87.1 %) and Pedobacter caeni LMG 22862(T) (86.9 %). Chemotaxonomic data revealed that strain Jip14(T) possesses menaquinone MK-7 and the predominant fatty acids C(15 : 0) iso, C(16 : 0), C(16 : 0) 10-methyl, C(17 : 0) iso 3-OH and summed feature 3 (C(15 : 0) iso 2-OH/C(16 : 1)omega7c). The results of physiological and biochemical tests clearly demonstrated that strain Jip14(T) represents a distinct species. Based on these data, Jip14(T) should be classified within a novel genus and species, for which the name Parapedobacter koreensis gen. nov., sp. nov. is proposed. The type strain of Parapedobacter koreensis is Jip14(T) (=KCTC 12643(T)=LMG 23493(T)).

T Cell Receptor Signaling in the Control of Regulatory T Cell Differentiation and Function

PubMed Central

Li, Ming O.; Rudensky, Alexander Y.

2016-01-01

Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self-tolerance and inflammatory responses. Recent studies have revealed a discrete mode of TCR signaling that regulates Treg cell differentiation, maintenance and function and that impacts on gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of Treg cells in the context of their function in health and disease. PMID:27026074

Effects of DDT and Triclosan on Tumor-cell Binding Capacity and Cell-Surface Protein Expression of Human Natural Killer Cells

PubMed Central

Hurd-Brown, Tasia; Udoji, Felicia; Martin, Tamara; Whalen, Margaret M.

2012-01-01

1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) and triclosan (TCS) are organochlorine (OC) compounds that contaminate the environment, are found in human blood, and have been shown to decrease the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. They bind to these targets, utilizing a variety of cell surface proteins. This study examined concentrations of DDT and TCS that decrease lytic function for alteration of NK binding to tumor targets. Levels of either compound that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. NK cells exposed to 2.5 μM DDT for 24 h (which caused a greater than 55% loss of lytic function) showed a decrease in NK binding function of about 22%, and a decrease in CD16 cell-surface protein of 20%. NK cells exposed to 5 μM TCS for 24 h showed a decrease in ability to bind tumor cells of 37% and a decrease in expression of CD56 of about 34%. This same treatment caused a decrease in lytic function of greater than 87%. These results indicated that only a portion of the loss of NK lytic function seen with exposures to these compounds could be accounted for by loss of binding function. They also showed that loss of binding function is accompanied by a loss cell-surface proteins important in binding function. PMID:22729613

Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity.

PubMed

Gerriets, Valerie A; Danzaki, Keiko; Kishton, Rigel J; Eisner, William; Nichols, Amanda G; Saucillo, Donte C; Shinohara, Mari L; MacIver, Nancie J

2016-08-01

Upon activation, T cells require energy for growth, proliferation, and function. Effector T (Teff) cells, such as Th1 and Th17 cells, utilize high levels of glycolytic metabolism to fuel proliferation and function. In contrast, Treg cells require oxidative metabolism to fuel suppressive function. It remains unknown how Teff/Treg-cell metabolism is altered when nutrients are limited and leptin levels are low. We therefore examined the role of malnutrition and associated hypoleptinemia on Teff versus Treg cells. We found that both malnutrition-associated hypoleptinemia and T cell-specific leptin receptor knockout suppressed Teff-cell number, function, and glucose metabolism, but did not alter Treg-cell metabolism or suppressive function. Using the autoimmune mouse model EAE, we confirmed that fasting-induced hypoleptinemia altered Teff-cell, but not Treg-cell, glucose metabolism, and function in vivo, leading to decreased disease severity. To explore potential mechanisms, we examined HIF-1α, a key regulator of Th17 differentiation and Teff-cell glucose metabolism, and found HIF-1α expression was decreased in T cell-specific leptin receptor knockout Th17 cells, and in Teff cells from fasted EAE mice, but was unchanged in Treg cells. Altogether, these data demonstrate a selective, cell-intrinsic requirement for leptin to upregulate glucose metabolism and maintain function in Teff, but not Treg cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hollow fibers - Their applications to the study of mammalian cell function

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Angeline, M.; Harkness, J.; Chu, M.; Grindleland, R.

1984-01-01

The use of hollow fiber technology in cell culture and transplantation is examined. The morphologies of encapsulated pituitary cells before and after implantation into the rat are defined. Implantation experiments using hollow fibers to study mammalian cell functions are described. Consideration is given to examining somatotroph, prolactin, prostrate, fibroblast, and retinal cell functions. These experiments demonstrate that hollow fiber technology is applicable for studying mammalian cell functions.

An evolving new paradigm: endothelial cells – conditional innate immune cells

PubMed Central

2013-01-01

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies. PMID:23965413

An evolving new paradigm: endothelial cells--conditional innate immune cells.

PubMed

Mai, Jietang; Virtue, Anthony; Shen, Jerry; Wang, Hong; Yang, Xiao-Feng

2013-08-22

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies.

[Influence of Cx26/Cx32 gap junction channel on antineoplastic effect of etoposide in Hela cells].

PubMed

Tong, Xu-Hui; Dong, Shu-Ying; Jiang, Guo-Jun; Fan, Gao-Fu

2012-03-01

To observe the influence of Cx26/Cx32 gap junction channel on the antineoplastic effect of etoposide in Hela cervical cancer cells. Fluorescence trace was used to assay the gap junction intercellular communication mediated by Cx26/Cx32 in Hela cells and its functional modulation by the pharmacological agents (oleamide, retinoid acid). A standard colony-forming assay was applied to determine the cell growth-inhibiting effect of etoposide in Hela cells with functional modulation of the gap junction. Hoechst 33258 staining was used to assess the changes in etoposide-induced apoptosis of Hela cells with altered gap junction functions. Oleamide markedly decreased while retinoid acid obviously increased the gap junction function in Hela cells. Standard colony-forming assay showed that etoposide produced a lowered antiproliferative effect in Hela cells with reduced gap junction and an increased antiproliferative effect in cells with enhanced gap junction function. In cells with a reduced gap junction function, etoposide induced a lowered apoptosis rate, which increased obviously in cells with an enhanced gap junction function. The antineoplastic effect of etoposide is reduced in Hela cells with a decreased gap junction intercellular communication mediated by Cx26/Cx32 and is enhanced in cells with an increased gap junction intercellular communication.

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Cantarovich, Marcelo; Lipman, Mark; Tchervenkov, Jean I; Paraskevas, Steven

2016-02-01

Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI. In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture. The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality. Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

Antioxidants Complement the Requirement for Protein Chaperone Function to Maintain β-Cell Function and Glucose Homeostasis

PubMed Central

Han, Jaeseok; Song, Benbo; Kim, Jiun; Kodali, Vamsi K.; Pottekat, Anita; Wang, Miao; Hassler, Justin; Wang, Shiyu; Pennathur, Subramaniam; Back, Sung Hoon; Katze, Michael G.

2015-01-01

Proinsulin misfolding in the endoplasmic reticulum (ER) initiates a cell death response, although the mechanism(s) remains unknown. To provide insight into how protein misfolding may cause β-cell failure, we analyzed mice with the deletion of P58IPK/DnajC3, an ER luminal co-chaperone. P58IPK−/− mice become diabetic as a result of decreased β-cell function and mass accompanied by induction of oxidative stress and cell death. Treatment with a chemical chaperone, as well as deletion of Chop, improved β-cell function and ameliorated the diabetic phenotype in P58IPK−/− mice, suggesting P58IPK deletion causes β-cell death through ER stress. Significantly, a diet of chow supplemented with antioxidant dramatically and rapidly restored β-cell function in P58IPK−/− mice and corrected abnormal localization of MafA, a critical transcription factor for β-cell function. Antioxidant feeding also preserved β-cell function in Akita mice that express mutant misfolded proinsulin. Therefore defective protein folding in the β-cell causes oxidative stress as an essential proximal signal required for apoptosis in response to ER stress. Remarkably, these findings demonstrate that antioxidant feeding restores cell function upon deletion of an ER molecular chaperone. Therefore antioxidant or chemical chaperone treatment may be a promising therapeutic approach for type 2 diabetes. PMID:25795214

Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets

PubMed Central

2011-01-01

Background It is well established that PD-1 is expressed by follicular T cells but its function in regulation of human T helper cells has been unclear. We investigated the expression modality and function of PD-1 expressed by human T cells specialized in helping B cells. Results We found that PD-1-expressing T cells are heterogeneous in PD-1 expression. We identified three different PD-1-expressing memory T cell subsets (i.e. PD-1low (+), PD-1medium (++), and PD-1high (+++) cells). PD-1+++ T cells expressed CXCR5 and CXCR4 and were localized in the rim of germinal centers. PD-1+ or PD-1++ cells expressed CCR7 and were present mainly in the T cell area or other parts of the B cell follicles. Utilizing a novel antigen density-dependent magnetic sorting (ADD-MS) method, we isolated the three T cell subsets for functional characterization. The germinal center-located PD-1+++ T cells were most efficient in helping B cells and in producing IL-21 and CXCL13. Other PD-1-expressing T cells, enriched with Th1 and Th17 cells, were less efficient than PD-1+++ T cells in these capacities. PD-1+++ T cells highly expressed Ki-67 and therefore appear active in cell activation and proliferation in vivo. IL-2 is a cytokine important for proliferation and survival of the PD-1+++ T cells. In contrast, IL-21, while a major effector cytokine produced by the PD-1-expressing T helper cells, had no function in generation, survival, or proliferation of the PD-1-expressing helper T cells at least in vitro. PD-1 triggering has a suppressive effect on the proliferation and B cell-helping function of PD-1+++ germinal center T cells. Conclusion Our results revealed the phenotype and effector function of PD-1-expressing T helper cell subsets and indicate that PD-1 restrains the B cell-helping function of germinal center-localized T cells to prevent excessive antibody response. PMID:21914188

Regulation of Satellite Cell Function in Sarcopenia

PubMed Central

Alway, Stephen E.; Myers, Matthew J.; Mohamed, Junaith S.

2014-01-01

The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function. PMID:25295003

Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.

PubMed

Milasta, Sandra; Dillon, Christopher P; Sturm, Oliver E; Verbist, Katherine C; Brewer, Taylor L; Quarato, Giovanni; Brown, Scott A; Frase, Sharon; Janke, Laura J; Perry, S Scott; Thomas, Paul G; Green, Douglas R

2016-01-19

The role of apoptosis inducing factor (AIF) in promoting cell death versus survival remains controversial. We report that the loss of AIF in fibroblasts led to mitochondrial electron transport chain defects and loss of proliferation that could be restored by ectopic expression of the yeast NADH dehydrogenase Ndi1. Aif-deficiency in T cells led to decreased peripheral T cell numbers and defective homeostatic proliferation, but thymic T cell development was unaffected. In contrast, Aif-deficient B cells developed and functioned normally. The difference in the dependency of T cells versus B cells on AIF for function and survival correlated with their metabolic requirements. Ectopic Ndi1 expression rescued homeostatic proliferation of Aif-deficient T cells. Despite its reported roles in cell death, fibroblasts, thymocytes and B cells lacking AIF underwent normal death. These studies suggest that the primary role of AIF relates to complex I function, with differential effects on T and B cells. Copyright © 2016 Elsevier Inc. All rights reserved.

T cell fates ‘zipped up’: how the Bach2 basic leucine zipper transcriptional repressor directs T cell differentiation and function1

PubMed Central

Richer, Martin J.; Lang, Mark L.; Butler, Noah S.

2016-01-01

Recent data illustrate a key role for the transcriptional regulator Bach2 in orchestrating T cell differentiation and function. Although Bach2 has a well-described role in B cell differentiation, emerging data show that Bach2 is a prototypical member of a novel class of transcription factors that regulates transcriptional activity in T cells at super enhancers, or regions of high transcriptional activity. Accumulating data demonstrate specific roles for Bach2 in favoring regulatory T cell generation, restraining effector T cell differentiation and potentiating memory T cell development. Evidence suggests that Bach2 regulates various facets of T cell function by repressing other key transcriptional regulator such as Blimp-1. This review examines our current understanding of the role of Bach2 in T cell function and highlights the growing evidence that this transcriptional repressor functions as a key regulator involved in maintenance of T cell quiescence, T cell subset differentiation and memory T cell generation. PMID:27496973

Cryopreservation has no effect on function of natural killer cells differentiated in vitro from umbilical cord blood CD34(+) cells.

PubMed

Domogala, Anna; Madrigal, J Alejandro; Saudemont, Aurore

2016-06-01

Natural killer (NK) cells offer the potential for a powerful cellular immunotherapy because they can target malignant cells without being direct effectors of graft-versus-host disease. We have previously shown that high numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34(+) cells. To develop a readily available, off-the-shelf cellular product, it is essential that NK cells differentiated in vitro can be frozen and thawed while maintaining the same phenotype and functions. We evaluated the phenotype and function of fresh and frozen NK cells differentiated in vitro. We also assessed whether the concentration of NK cells at the time of freezing had an impact on cell viability. We found that cell concentration of NK cells at the time of freezing did not have an impact on their viability and on cell recovery post-thaw. Moreover, freezing of differentiated NK cells in vitro did not affect their phenotype, cytotoxicity and degranulation capacity toward K562 cells, cytokine production and proliferation. We are therefore able to generate large numbers of functional NK cells from CB CD34(+) cells that maintain the same phenotype and function post-cryopreservation, which will allow for multiple infusions of a highly cytotoxic NK cell product. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Development of Nano/Micro Probes for Femtoliter Volume and Single Cell Measurements

NASA Astrophysics Data System (ADS)

Gao, Yang

Single cell analysis has recently emerged as an important field of biomedical re- search. It is now clear that heterogeneity of cell metabolism functions in complex biological systems is correlated to changes in biological function and disease processes. A variety of nano/micro probes were developed to enable investigation of cells properties such as membrane stiffness, pH value. However, very few designs were focused on single cell metabolic function studies. There is a critical need for technologies that provide analysis of heterogeneity of cell metabolic functions, especially on metabolism. Nevertheless, the few existing approaches suffer from fundamental defects and need to be improved. This work focused on developing nano/micro probes that are suitable for single cell functionality investigation. Both types of probes are designed to measure cell-to-cell/time-to-time heterogeneity in metabolic functions over a long period of time. Lab-made carbon nanoprobes were developed especially for electro-physiological measurement. The unique structure of the carbon nanoprobes makes them suitable for important intracellular applications like trans-membrane potential measurements and various electrochemical measurement for cell function studies. While it is important of have ability to carry out intracellular measure, there are also occasions where the information of a cell as a whole is collected. One of the most important indicator of a cells metabolic functions is cell respiration rate/oxygen consumption rate. A micro-perfusion based multi-functional single cell sensing probe was the developed to carry out measurements on cell as a whole. Formed by a double-barrel theta pipette, the perfusion flow enables the direct measurement of the metabolic flux for example oxygen consumption rate. In conclusion, this work developed nano/micro-probes as novel single cell investigation tools. The data acquired from these tools could provide valuable assistance on applications including cell metabolism studies, cancer diagnoses, and therapy evaluations.

Hybrid cell adhesive material for instant dielectrophoretic cell trapping and long-term cell function assessment.

PubMed

Reyes, Darwin R; Hong, Jennifer S; Elliott, John T; Gaitan, Michael

2011-08-16

Dielectrophoresis (DEP) for cell manipulation has focused, for the most part, on approaches for separation/enrichment of cells of interest. Advancements in cell positioning and immobilization onto substrates for cell culture, either as single cells or as cell aggregates, has benefited from the intensified research efforts in DEP (electrokinetic) manipulation. However, there has yet to be a DEP approach that provides the conditions for cell manipulation while promoting cell function processes such as cell differentiation. Here we present the first demonstration of a system that combines DEP with a hybrid cell adhesive material (hCAM) to allow for cell entrapment and cell function, as demonstrated by cell differentiation into neuronlike cells (NLCs). The hCAM, comprised of polyelectrolytes and fibronectin, was engineered to function as an instantaneous cell adhesive surface after DEP manipulation and to support long-term cell function (cell proliferation, induction, and differentiation). Pluripotent P19 mouse embryonal carcinoma cells flowing within a microchannel were attracted to the DEP electrode surface and remained adhered onto the hCAM coating under a fluid flow field after the DEP forces were removed. Cells remained viable after DEP manipulation for up to 8 d, during which time the P19 cells were induced to differentiate into NLCs. This approach could have further applications in areas such as cell-cell communication, three-dimensional cell aggregates to create cell microenvironments, and cell cocultures.

Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells

PubMed Central

2012-01-01

Background Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata. Results Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI) nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells. Conclusions PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations. PMID:22686683

ICAM-1 (CD54) expression on B lymphocytes is associated with their costimulatory function and can be increased by coactivation with IL-1 and IL-7.

PubMed

Dennig, D; Lacerda, J; Yan, Y; Gasparetto, C; O'Reilly, R J

1994-07-01

Recent studies have demonstrated that acute lymphoblastic leukemia-derived pre-B cell lines are deficient in their costimulatory function for T cell proliferation in response to the mitogen Con A and the superantigens TSST-1 and SEB. Stimulation of these pre-B cells with IL-7 increased their costimulatory function which involved the B7/CD28 pathway. In the present study, we stimulated T cells with Con A, TSST-1, and SEB in the presence of peripheral blood B lineage cells that do not constitutively express B7/BB1 on their surface and investigated whether their costimulatory function could also be enhanced by IL-7. We found that, in the presence of IL-1, stimulation with IL-7 increased the costimulatory function of B cells and their surface expression level of ICAM-1 (CD54). We then investigated whether costimulatory B cell function could be inhibited by blocking the ICAM-1/LFA-1 pathway. Addition of anti-ICAM-1 mAb to the coculture of T and B cells inhibited T cell proliferation by approximately 20%. In contrast, addition of anti-LFA-1 beta (CD18) mAb, directed against the T cell ligand of ICAM-1, inhibited T cell proliferation almost completely. To determine the role of ICAM-1 in costimulatory B cell function, we sorted B cells into ICAM-1low-and ICAM-1high-expressing populations. We found that B cells expressing high levels of surface ICAM-1 elicited significantly higher T cell responses than those with low levels, suggesting that the expression level of ICAM-1 on peripheral blood B cells correlates with their costimulatory function.

Glutathione diminishes Dibutyltin- and tributyltin-induced loss of lytic function in human natural killer cells

PubMed Central

Powell, Jeralyn J.; Davis, McLisa V.; Whalen, Margaret M.

2008-01-01

This study investigated whether reduced glutathione (GSH) was able to alter the negative effects of tributyltin (TBT) or dibutyltin (DBT) on the lytic function of human natural killer (NK) cells. NK cells are an intital immune defense against the development of tumors or viral infections. TBT and DBT are widespread environmental contaminants, due to their various industrial applications. Both TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor cells (lytic function). The results indicated that the presence of GSH during exposure of NK cells to TBT or DBT diminished the negative effect of the BT on the lytic function of NK cells. This suggests that interaction TBT and DBT with functionally relevant sulfhydryl groups in NK cells may be part of the mechanism by which they decrease NK lytic function. PMID:18821099

Glutathione diminishes tributyltin- and dibutyltin-induced loss of lytic function in human natural killer cells.

PubMed

Powell, Jeralyn J; Davis, McLisa V; Whalen, Margaret M

2009-01-01

This study investigated whether reduced glutathione (GSH) was able to alter the negative effects of tributyltin (TBT) or dibutyltin (DBT) on the lytic function of human natural killer (NK) cells. NK cells are an initial immune defense against the development of tumors or viral infections. TBT and DBT are widespread environmental contaminants, due to their various industrial applications. Both TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor cells (lytic function). The results indicated that the presence of GSH during the exposure of NK cells to TBT or DBT diminished the negative effect of the butyltin on the lytic function of NK cells. This suggests that the interaction of TBT and DBT with functionally relevant sulfhydryl groups in NK cells may be part of the mechanism by which they decrease NK lytic function.

Associations of smoking and alcohol consumption with impaired β-cell function in Chinese men.

PubMed

Xu, Min; Zhou, Yulin; Xu, Baihui; Sun, Jichao; Wang, Tiange; Lu, Jieli; Lai, Shenghan; Bi, Yufang; Wang, Weiqing; Ning, Guang

2016-05-01

The aims of the present study were to examine the association of cigarette smoking and alcohol consumption with impaired β-cell function in Chinese men, particularly the interaction of smoking and alcohol consumption on impaired insulin secretion. A population-based cross-sectional study was performed in 3957 Chinese men aged ≥40 years. The homeostatic model assessment of β-cell function (HOMA-β) was calculated, and impaired β-cell function was defined as less than the lowest quartile HOMA-βcut-off point. The prevalence of impaired β-cell function in current smokers and heavy drinkers (≥200 g/week) was significantly higher than in non-smokers and non-drinkers, respectively. Compared with non-smoking, current smoking had an exacerbating relationship with impaired β-cell function (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.47-2.15; P < 0.001). No significant association was found between impaired β-cell function and former smoking (P = 0.21), although low and heavy drinking were associated with an increased risk of impaired β-cell function (OR 1.40 [95% CI 1.07-1.81] and 2.14 [95% CI 1.77-2.58], respectively) compared with non-drinking. The combination of current smoking and heavy drinking was associated with the highest risk of impaired β-cell function (OR 3.16; 95% CI 2.43-4.12; P < 0.0001) after adjustment for confounders. We did not detect an additive interaction between current smoking and heavy drinking on the association with impaired β-cell function. Cigarette smoking and alcohol consumption were significantly and independently associated with impaired β-cell function in Chinese men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Variation is function: Are single cell differences functionally important?: Testing the hypothesis that single cell variation is required for aggregate function.

PubMed

Dueck, Hannah; Eberwine, James; Kim, Junhyong

2016-02-01

There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single-cell molecular variation per se might be crucial for population-level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of identical cells, and this functional diversity facilitates collective behavior that would be inaccessible to a homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population-level function. We consider several possible methods to further pursue the hypothesis that variation is function through the use of comparative analysis and novel experimental techniques. © 2015 The Authors. BioEssays published by WILEY Periodicals, Inc.

IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function.

PubMed

Orange, Jordan S; Roy-Ghanta, Sumita; Mace, Emily M; Maru, Saumya; Rak, Gregory D; Sanborn, Keri B; Fasth, Anders; Saltzman, Rushani; Paisley, Allison; Monaco-Shawver, Linda; Banerjee, Pinaki P; Pandey, Rahul

2011-04-01

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency associated with an increased susceptibility to herpesvirus infection and hematologic malignancy as well as a deficiency of NK cell function. It is caused by defective WAS protein (WASp). WASp facilitates filamentous actin (F-actin) branching and is required for F-actin accumulation at the NK cell immunological synapse and NK cell cytotoxicity ex vivo. Importantly, the function of WASp-deficient NK cells can be restored in vitro after exposure to IL-2, but the mechanisms underlying this remain unknown. Using a WASp inhibitor as well as cells from patients with WAS, we have defined a direct effect of IL-2 signaling upon F-actin that is independent of WASp function. We found that IL-2 treatment of a patient with WAS enhanced the cytotoxicity of their NK cells and the F-actin content at the immunological synapses formed by their NK cells. IL-2 stimulation of NK cells in vitro activated the WASp homolog WAVE2, which was required for inducing WASp-independent NK cell function, but not for baseline activity. Thus, WAVE2 and WASp define parallel pathways to F-actin reorganization and function in human NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2. These results demonstrate how overlapping cytoskeletal activities can utilize immunologically distinct pathways to achieve synonymous immune function.

IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function

PubMed Central

Orange, Jordan S.; Roy-Ghanta, Sumita; Mace, Emily M.; Maru, Saumya; Rak, Gregory D.; Sanborn, Keri B.; Fasth, Anders; Saltzman, Rushani; Paisley, Allison; Monaco-Shawver, Linda; Banerjee, Pinaki P.; Pandey, Rahul

2011-01-01

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency associated with an increased susceptibility to herpesvirus infection and hematologic malignancy as well as a deficiency of NK cell function. It is caused by defective WAS protein (WASp). WASp facilitates filamentous actin (F-actin) branching and is required for F-actin accumulation at the NK cell immunological synapse and NK cell cytotoxicity ex vivo. Importantly, the function of WASp-deficient NK cells can be restored in vitro after exposure to IL-2, but the mechanisms underlying this remain unknown. Using a WASp inhibitor as well as cells from patients with WAS, we have defined a direct effect of IL-2 signaling upon F-actin that is independent of WASp function. We found that IL-2 treatment of a patient with WAS enhanced the cytotoxicity of their NK cells and the F-actin content at the immunological synapses formed by their NK cells. IL-2 stimulation of NK cells in vitro activated the WASp homolog WAVE2, which was required for inducing WASp-independent NK cell function, but not for baseline activity. Thus, WAVE2 and WASp define parallel pathways to F-actin reorganization and function in human NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2. These results demonstrate how overlapping cytoskeletal activities can utilize immunologically distinct pathways to achieve synonymous immune function. PMID:21383498

Environmental Impact on Intestinal Stem Cell Functions in Mucosal Homeostasis and Tumorigenesis.

PubMed

Augenlicht, Leonard H

2017-05-01

Multiple cell compartments at or near the base of the intestinal crypt have been identified as contributing intestinal stem cells for homeostasis of the rapidly turning over intestinal mucosa and cells that can initiate tumor development upon appropriate genetic changes. There is a strong literature establishing the importance of the frequently dividing Lgr5+ crypt base columnar cells as the fundamental cell in providing these stem cell-associated functions, but there are also clear data that more quiescent cells from other compartments can be mobilized to provide these stem cell functions upon compromise of Lgr5+ cells. We review the data that vitamin D, a pleiotropic hormone, is essential for Lgr5 stem cell functions by signaling through the vitamin D receptor. Moreover, we discuss the implications of this role of vitamin D and its impact on relatively long-lived stem cells in regards to the fact that virtually all the data on normal functioning of mouse Lgr5 stem cells is derived from mice exposed to vitamin D levels well above those that characterize the human population. Thus, there are still many questions regarding how dietary and environmental factors influence the complement of cells providing stem cell functions and the mechanisms by which this is determined, and the importance of this in human colorectal tumor development. J. Cell. Biochem. 118: 943-952, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fish T cells: recent advances through genomics

USGS Publications Warehouse

Laing, Kerry J.; Hansen, John D.

2011-01-01

This brief review is intended to provide a concise overview of the current literature concerning T cells, advances in identifying distinct T cell functional subsets, and in distinguishing effector cells from memory cells. We compare and contrast a wealth of recent progress made in T cell immunology of teleost, elasmobranch, and agnathan fish, to knowledge derived from mammalian T cell studies. From genome studies, fish clearly have most components associated with T cell function and we can speculate on the presence of putative T cell subsets, and the ability to detect their differentiation to form memory cells. Some recombinant proteins for T cell associated cytokines and antibodies for T cell surface receptors have been generated that will facilitate studying the functional roles of teleost T cells during immune responses. Although there is still a long way to go, major advances have occurred in recent years for investigating T cell responses, thus phenotypic and functional characterization is on the near horizon.

Engineering of Surface Functionality onto Polystyrene Microcarriers for the Attachment and Growth of Human Endothelial Cells

NASA Astrophysics Data System (ADS)

Xiong, Gordon M.; Foord, John S.; Griffiths, Jon-Paul; Parker, Emily M.; Moloney, Mark G.; Choong, Cleo

2014-08-01

This work reports the effects of introducing diverse chemical functionalities onto the surface of polystyrene microcarrier beads on their ability to function as injectable cell carriers. Cellular adhesion and proliferation, as well as cellular outgrowths from microcarrier surfaces, using human umbilical vein endothelial cells (HUVECs), were examined in detail. It was observed that initial cell adhesion appeared to be most significantly decreased by hydrophobicity, whilst cell proliferation appeared to be improved in most chemical functional groups over unmodified polystyrene. Overall, our study highlights the importance of surface chemistry in directing the growth and function of human endothelial cells.

Gammadelta T cells: functional plasticity and heterogeneity.

PubMed

Carding, Simon R; Egan, Paul J

2002-05-01

Gammadelta T cells remain an enigma. They are capable of generating more unique antigen receptors than alphabeta T cells and B cells combined, yet their repertoire of antigen receptors is dominated by specific subsets that recognize a limited number of antigens. A variety of sometimes conflicting effector functions have been ascribed to them, yet their biological function(s) remains unclear. On the basis of studies of gammadelta T cells in infectious and autoimmune diseases, we argue that gammadelta T cells perform different functions according to their tissue distribution, antigen-receptor structure and local microenvironment; we also discuss how and at what stage of the immune response they become activated.

Evaluation of accessory cell heterogeneity. III. Role of dendritic cells in the in vitro activation of the antibody response to soluble antigens.

PubMed

Erb, P; Ramila, G; Sklenar, I; Kennedy, M; Sunshine, G H

1985-05-01

Dendritic cells and macrophages obtained from spleen and peritoneal exudate were tested as accessory cells for the activation of lymphokine production by T cells, for supporting T-B cooperation and for the induction of antigen-specific T helper cells. Dendritic cells as well as macrophages were able to activate T cells for interleukin-2 secretion and functioned as accessory cells in T-B cooperation, but only macrophages induced T helper cells, which cooperate with B cells by a linked recognition interaction, to soluble antigens. Dendritic cell- and antigen-activated T cells also did not help B cells in the presence of Con A supernatants which contained various T cell- and B cell-stimulatory factors. The failure of dendritic cells to differentiate memory into functional T helper cells, but their efficient accessory cell function in T-B cooperation, where functional T helper cells are already present, can be best explained by a differential accessory cell requirement for T helper cell activation dependent on the differentiation stage of the T helper cell.

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets

PubMed Central

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-01-01

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms. PMID:24903657

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.

PubMed

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-06-06

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms.

B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients.

PubMed

Marasco, Emiliano; Farroni, Chiara; Cascioli, Simona; Marcellini, Valentina; Scarsella, Marco; Giorda, Ezio; Piano Mortari, Eva; Leonardi, Lucia; Scarselli, Alessia; Valentini, Diletta; Cancrini, Caterina; Duse, Marzia; Grimsholm, Ola; Carsetti, Rita

2017-01-01

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system. © 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer

PubMed Central

Felices, M.; Chu, S.; Kodal, B.; Bendzick, L.; Ryan, C.; Lenvik, A.J.; Boylan, K.L.M.; Wong, H.C.; Skubitz, A.P.N.; Miller, J.S.; Geller, M.A.

2017-01-01

Objective Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. Methods NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays +/− ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. Results ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. Conclusions ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK-cell-based immunotherapeutic approaches for the treatment of ovarian cancer. PMID:28236454

A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

EPA Science Inventory

Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

Quantitative and Functional Requirements for Bioluminescent Cancer Models.

PubMed

Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vermeulen, Stefan; Vandesompele, J O; Vanderheyden, Katrien; Messens, Kathy; Bracke, Marc; De Wever, Olivier

2016-01-01

Bioluminescent cancer models are widely used but detailed quantification of the luciferase signal and functional comparison with a non-transfected control cell line are generally lacking. In the present study, we provide quantitative and functional tests for luciferase-transfected cells. We quantified the luciferase expression in BLM and HCT8/E11 transfected cancer cells, and examined the effect of long-term luciferin exposure. The present study also investigated functional differences between parental and transfected cancer cells. Our results showed that quantification of different single-cell-derived populations are superior with droplet digital polymerase chain reaction. Quantification of luciferase protein level and luciferase bioluminescent activity is only useful when there is a significant difference in copy number. Continuous exposure of cell cultures to luciferin leads to inhibitory effects on mitochondrial activity, cell growth and bioluminescence. These inhibitory effects correlate with luciferase copy number. Cell culture and mouse xenograft assays showed no significant functional differences between luciferase-transfected and parental cells. Luciferase-transfected cells should be validated by quantitative and functional assays before starting large-scale experiments. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A critical role for transcription factor Smad4 in T cell function independent of transforming growth factor beta receptor signaling

PubMed Central

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A.; Wan, Yisong Y.

2014-01-01

Summary Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. While Smad4 was dispensable for T cell generation, homeostasis and effector function, it was essential for T cell proliferation following activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity and anti-tumor immunity. PMID:25577439

A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor β receptor signaling.

PubMed

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A; Wan, Yisong Y

2015-01-20

Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

Human Naive T Cells Express Functional CXCL8 and Promote Tumorigenesis.

PubMed

Crespo, Joel; Wu, Ke; Li, Wei; Kryczek, Ilona; Maj, Tomasz; Vatan, Linda; Wei, Shuang; Opipari, Anthony W; Zou, Weiping

2018-05-25

Naive T cells are thought to be functionally quiescent. In this study, we studied and compared the phenotype, cytokine profile, and potential function of human naive CD4 + T cells in umbilical cord and peripheral blood. We found that naive CD4 + T cells, but not memory T cells, expressed high levels of chemokine CXCL8. CXCL8 + naive T cells were preferentially enriched CD31 + T cells and did not express T cell activation markers or typical Th effector cytokines, including IFN-γ, IL-4, IL-17, and IL-22. In addition, upon activation, naive T cells retained high levels of CXCL8 expression. Furthermore, we showed that naive T cell-derived CXCL8 mediated neutrophil migration in the in vitro migration assay, supported tumor sphere formation, and promoted tumor growth in an in vivo human xenograft model. Thus, human naive T cells are phenotypically and functionally heterogeneous and can carry out active functions in immune responses. Copyright © 2018 by The American Association of Immunologists, Inc.

Liver-enriched transcription factors uncoupled from expression of hepatic functions in hepatoma cell lines.

PubMed Central

Chaya, D; Fougère-Deschatrette, C; Weiss, M C

1997-01-01

Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver. PMID:9343392

Liver-enriched transcription factors uncoupled from expression of hepatic functions in hepatoma cell lines.

PubMed

Chaya, D; Fougère-Deschatrette, C; Weiss, M C

1997-11-01

Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver.

An essential role for IL-2 receptor in regulatory T cell function

PubMed Central

Levine, Andrew G; Fan, Xiying; Klein, Ulf; Zheng, Ye; Gasteiger, Georg; Feng, Yongqiang; Fontenot, Jason D.; Rudensky, Alexander Y.

2016-01-01

Regulatory T (Treg) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage specification factor Foxp3, confounding experimental efforts to understand the role of IL-2R expression and signaling in Treg suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4+ T cells, but is important for limiting CD8+ T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in Treg cell suppressor function separable from T cell receptor signaling. PMID:27595233

Expression of checkpoint molecules on myeloid-derived suppressor cells.

PubMed

Ballbach, Marlene; Dannert, Angelika; Singh, Anurag; Siegmund, Darina M; Handgretinger, Rupert; Piali, Luca; Rieber, Nikolaus; Hartl, Dominik

2017-12-01

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population expanded in cancer, infection and autoimmunity capable of suppressing T-cell functions. Checkpoint inhibitors have emerged as a key therapeutic strategy in immune-oncology. While checkpoint molecules were initially associated with T cell functions, recent evidence suggests a broader expression and function in innate myeloid cells. Previous studies provided first evidence for a potential role for checkpoints on MDSCs, yet the human relevance remained poorly understood. Therefore, we investigated the expression and functional relevance of checkpoint molecules in human MDSC-T-cell interactions. Our studies demonstrate that programmed death-ligand 1 (PD-L1) is expressed on granulocytic MDSCs upon co-culture with T cells. Transwell experiments showed that cell-to-cell contact was required for MDSC-T-cell interactions and antibody blocking studies showed that targeting PD-L1 partially impaired MDSC-mediated T-cell suppression. Collectively, these studies suggest a role for PD-L1 in human MDSC function and thereby expand the functionality of this checkpoint beyond T cells, which could pave the way for further understanding and therapeutic targeting of PD-1/PD-L1 in innate immune-mediated diseases. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function.

PubMed

Alimperti, Stella; Mirabella, Teodelinda; Bajaj, Varnica; Polacheck, William; Pirone, Dana M; Duffield, Jeremy; Eyckmans, Jeroen; Assoian, Richard K; Chen, Christopher S

2017-08-15

The integrity of the endothelial barrier between circulating blood and tissue is important for blood vessel function and, ultimately, for organ homeostasis. Here, we developed a vessel-on-a-chip with perfused endothelialized channels lined with human bone marrow stromal cells, which adopt a mural cell-like phenotype that recapitulates barrier function of the vasculature. In this model, barrier function is compromised upon exposure to inflammatory factors such as LPS, thrombin, and TNFα, as has been observed in vivo. Interestingly, we observed a rapid physical withdrawal of mural cells from the endothelium that was accompanied by an inhibition of endogenous Rac1 activity and increase in RhoA activity in the mural cells themselves upon inflammation. Using a system to chemically induce activity in exogenously expressed Rac1 or RhoA within minutes of stimulation, we demonstrated RhoA activation induced loss of mural cell coverage on the endothelium and reduced endothelial barrier function, and this effect was abrogated when Rac1 was simultaneously activated. We further showed that N -cadherin expression in mural cells plays a key role in barrier function, as CRISPR-mediated knockout of N -cadherin in the mural cells led to loss of barrier function, and overexpression of N -cadherin in CHO cells promoted barrier function. In summary, this bicellular model demonstrates the continuous and rapid modulation of adhesive interactions between endothelial and mural cells and its impact on vascular barrier function and highlights an in vitro platform to study the biology of perivascular-endothelial interactions.

Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion

PubMed Central

Becker, Silke; Eastlake, Karen; Jayaram, Hari; Jones, Megan F.; Brown, Robert A.; McLellan, Gillian J.; Charteris, David G.; Khaw, Peng T.

2016-01-01

Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection. PMID:26718648

Increased curvature of hollow fiber membranes could up-regulate differential functions of renal tubular cell layers.

PubMed

Shen, Chong; Meng, Qin; Zhang, Guoliang

2013-08-01

Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices. Copyright © 2013 Wiley Periodicals, Inc.

In vitro effects of 4-hydroperoxycyclophosphamide on human immunoregulatory T subset function. I. Selective effects on lymphocyte function in T-B cell collaboration.

PubMed

Ozer, H; Cowens, J W; Colvin, M; Nussbaum-Blumenson, A; Sheedy, D

1982-01-01

The alkylating agent cyclophosphamide may suppress or enhance immune responses in vivo but is inactive in vitro unless metabolized by microsomal enzyme activation. 4-hydroperoxycyclophosphamide (4-HC) is a synthetic compound that is spontaneously converted in aqueous solution to the active metabolites. In this report, we examined the in vitro sensitivity of functional human T cell subsets to 4-HC in a polyclonal B cell differentiation assay and in the generation of mitogen-induced suppressor cells for effector B cell function. Con A-induced T suppression of B cell differentiation is completely abrogated by a 1-h pretreatment of T cells at very low concentrations of between 10(-2) and 20 nmol/ml, whereas inducer T cell function is sensitive only to concentrations in greater than 40 nmol/ml. The effects of 4-HC on suppressor T cells appear to occur at concentrations that do not result in DNA cross-linking or decreased blastogenesis. Con A-induced T suppressors are generated from within the OKT4+, OKT8- subset and are sensitive to low-dose 4-HC only before activation, whereas differentiated suppressor cells are resistant to concentrations in greater than 80 nmol/ml. Low-dose 4-HC pretreatment of the B cell population results in abrogation of immunoglobulin secretion when treated B cells are cocultured with unfractionated T cells, however, this effect is completely reversible if pretreated B cells are cocultured with T cells devoid of suppressor activity. These results demonstrate that human presuppressor cells for B-effector function differentiate in response to Con A from the OKT4+, OKT8- subset and are exquisitely sensitive to low concentrations of CYP whereas mature suppressor and inducer functions are resistant to all but very high concentrations in vitro. The differential sensitivity of functional T and B cell subsets to 4-HC in vitro can be a very useful probe in dissecting immunoregulatory interactions with man.

[Functional properties of taste bud cells. Mechanisms of afferent neurotransmission in Type II taste receptor cells].

PubMed

Romanov, R A

2013-01-01

Taste Bud cells are heterogeneous in their morphology and functionality. These cells are responsible for sensing a wide variety of substances and for associating detected compounds with a different taste: bitter, sweet, salty, sour and umami. Today we know that each of the five basic tastes corresponds to distinct cell populations organized into three basic morpho-functional cell types. In addition, some receptor cells of the taste bud demonstrate glia-related functions. In this article we expand on some properties of these three morphological receptor cell types. Main focus is devoted to the Type II cells and unusual mechanism for afferent neurotransmission in these cells. Taste cells of the Type II consist of three populations detecting bitter, sweet and umami tastes, and, thus, evoke a serious scientific interest.

Unhole and open hole compressive behaviours of hybrid Kevlar/glass fibre reinforced silica nanocomposites

NASA Astrophysics Data System (ADS)

Shaari, Norazean; Jumahat, Aidah

2018-06-01

The paper presents the effects of hybridization and silica nanoparticles on unhole and open hole compressive behaviours of woven Kevlar/glass fibre hybrid composite laminates. Residual compressive strength and stiffness were determined from an open hole compression (OHC) test conducted according to ASTM D6484-09, whereas the fractured surface behaviour was observed under scanning electron microscope (SEM). Silica nanoparticles were mixed into the epoxy resins using vacuum mechanical stirrer. Then, composite laminates were prepared using vacuum bagging method. Three different silica nanoparticles contents (5 wt%, 13 wt% and 25 wt%) were incorporated into the resin system with three different hybrid system (20:80, 50:50 and 80:20 of Kevlar fibres to glass fibres ratio). Results showed that the lowest compressive strength was observed in Kevlar fibre reinforced polymer. Therefore, hybridization of glass fibres with Kevlar fibres reduced the compressive strength of hybrid composites. However, the incorporation of silica nanoparticles into the epoxy resins improved the compressive properties of the hybrid composites. From the observation of the fractured surface, different fracture behaviours were observed in both Kevlar fibre and glass fibre composites. Fibre barrelling and crimping was observed in Kevlar fibres while glass fibres showed a fibre fracture with serrated and rough surfaces.

Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression.

PubMed

Wang, Rui; Wan, Qi; Kozhaya, Lina; Fujii, Hodaka; Unutmaz, Derya

2008-07-16

Regulatory T (T(reg)) cells control immune activation and maintain tolerance. How T(regs) mediate their suppressive function is unclear. Here we identified a cell surface molecule, called GARP, (or LRRC32), which within T cells is specifically expressed in T(regs) activated through the T cell receptor (TCR). Ectopic expression of GARP in human naïve T (T(N)) cells inhibited their proliferation and cytokine secretion upon TCR activation. Remarkably, GARP over-expression in T(N) cells induced expression of T(reg) master transcription factor Foxp3 and endowed them with a partial suppressive function. The extracellular but not the cytoplasmic region of GARP, was necessary for these functions. Silencing Foxp3 in human T(reg) cells reduced expression of GARP and attenuated their suppressive function. However, GARP function was not affected when Foxp3 was downregulated in GARP-overexpressing cells, while silencing GARP in Foxp3-overexpressing cells reduced their suppressive activity. These findings reveal a novel cell surface molecule-mediated regulatory mechanism, with implications for modulating aberrant immune responses.

B cell biology: implications for treatment of systemic lupus erythematosus.

PubMed

Anolik, J H

2013-04-01

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.

An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells

NASA Astrophysics Data System (ADS)

Nilsson, Peter; Magnusson, Karin; Appelqvist, Hanna; Cieslar-Pobuda, Artur; Bäck, Marcus; Kågedal, Bertil; Jonasson, Jon; Los, Marek

2015-10-01

Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

Functional defect in regulatory T cells in myasthenia gravis

PubMed Central

Thiruppathi, Muthusamy; Rowin, Julie; Jiang, Qin Li; Sheng, Jian Rong; Prabhakar, Bellur S.; Meriggioli, Matthew N.

2012-01-01

Forkhead box P3 (FOXP3)+ is a transcription factor necessary for the function of regulatory T cells (Treg cells). Treg cells maintain immune homeostasis and self-tolerance, and play an important role in the prevention of autoimmune disease. Here, we discuss the role of Treg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in Treg cell in vitro suppressive function exists in MG patients, without an alteration in circulating frequency. This functional defect is associated with a reduced expression of key functional molecules such as FOXP3 on isolated Treg cells and appears to be more pronounced in immunosuppression-naive MG patients. In vitro administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the suppressive function of Treg cells and up-regulated FOXP3 expression. These findings indicate a clinically relevant Treg cell–intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target. PMID:23252899

Extracellular hemoglobin: the case of a friend turned foe

PubMed Central

Quaye, Isaac K.

2015-01-01

Hemoglobin (Hb) is a highly conserved molecule present in all life forms and functionally tied to the complexity of aerobic organisms on earth in utilizing oxygen from the atmosphere and delivering to cells and tissues. This primary function sustains the energy requirements of cells and maintains cellular homeostasis. Decades of intensive research has presented a paradigm shift that shows how the molecule also functions to facilitate smooth oxygen delivery through the cardiovascular system for cellular bioenergetic homeostasis and signaling for cell function and defense. These roles are particularly highlighted in the binding of Hb to gaseous molecules carbon dioxide (CO2), nitric oxide (NO) and carbon monoxide (CO), while also serving indirectly or directly as sources of these signaling molecules. The functional activities impacted by Hb outside of bioenergetics homeostasis, include fertilization, signaling functions, modulation of inflammatory responses for defense and cell viability. These activities are efficiently executed while Hb is sequestered safely within the confines of the red blood cell (rbc). Outside of rbc confines, Hb disaggregates and becomes a danger molecule to cell survival. In these perpectives, Hb function is broadly dichotomous, either a friend in its natural environment providing and facilitating the means for cell function or foe when dislocated from its habitat under stress or pathological condition disrupting cell function. The review presents insights into how this dichotomy in function manifests. PMID:25941490

Kupffer Cell Metabolism and Function

PubMed Central

Nguyen-Lefebvre, Anh Thu; Horuzsko, Anatolij

2015-01-01

Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions. PMID:26937490

Transcription Factor Foxo1 Is a Negative Regulator of NK Cell Maturation and Function

PubMed Central

Deng, Youcai; Kerdiles, Yann; Chu, Jianhong; Yuan, Shunzong; Wang, Youwei; Chen, Xilin; Mao, Hsiaoyin; Zhang, Lingling; Zhang, Jianying; Hughes, Tiffany; Deng, Yafei; Zhang, Qi; Wang, Fangjie; Zou, Xianghong; Liu, Chang-Gong; Freud, Aharon G.; Li, Xiaohui; Caligiuri, Michael A; Vivier, Eric; Yu, Jianhua

2015-01-01

SUMMARY Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes through upregulating CD62L expression, and impaired late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21+/− mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions. PMID:25769609

Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis.

PubMed

Zhao, Dejian; Lin, Mingyan; Pedrosa, Erika; Lachman, Herbert M; Zheng, Deyou

2017-11-10

Monoallelic expression of autosomal genes has been implicated in human psychiatric disorders. However, there is a paucity of allelic expression studies in human brain cells at the single cell and genome wide levels. In this report, we reanalyzed a previously published single-cell RNA-seq dataset from several postmortem human brains and observed pervasive monoallelic expression in individual cells, largely in a random manner. Examining single nucleotide variants with a predicted functional disruption, we found that the "damaged" alleles were overall expressed in fewer brain cells than their counterparts, and at a lower level in cells where their expression was detected. We also identified many brain cell type-specific monoallelically expressed genes. Interestingly, many of these cell type-specific monoallelically expressed genes were enriched for functions important for those brain cell types. In addition, function analysis showed that genes displaying monoallelic expression and correlated expression across neuronal cells from different individual brains were implicated in the regulation of synaptic function. Our findings suggest that monoallelic gene expression is prevalent in human brain cells, which may play a role in generating cellular identity and neuronal diversity and thus increasing the complexity and diversity of brain cell functions.

Conjunctival Goblet Cell Function: Effect of Contact Lens Wear and Cytokines

PubMed Central

García-Posadas, Laura; Contreras-Ruiz, Laura; Soriano-Romaní, Laura; Dartt, Darlene A.; Diebold, Yolanda

2015-01-01

This review focuses on conjunctival goblet cells and their essential function in the maintenance of eye health. The main function of goblet cells is to produce and secrete mucins that lubricate the ocular surface. An excess or a defect in those mucins leads to several alterations that makes goblet cells central players in maintaining the proper mucin balance and ensuring the correct function of ocular surface tissues. A typical pathology that occurs with mucous deficiency is dry eye disease, whereas the classical example of mucous hyperproduction is allergic conjunctivitis. In this review we analyze how goblet cell number and function can be altered in these diseases and in contact lens wearers. We found that most published studies focused exclusively on goblet cell number. However, recent advances have demonstrated that, along with mucin secretion, goblet cells are also able to secrete cytokines and respond to them. We describe the effect of different cytokines on goblet cell proliferation and secretion. We conclude that it is important to further explore the effect of contact lens wear and cytokines on conjunctival goblet cell function. PMID:26067396

Human Cells Display Reduced Apoptotic Function Relative to Chimpanzee Cells

PubMed Central

McDonald, John F.

2012-01-01

Previously published gene expression analyses suggested that apoptotic function may be reduced in humans relative to chimpanzees and led to the hypothesis that this difference may contribute to the relatively larger size of the human brain and the increased propensity of humans to develop cancer. In this study, we sought to further test the hypothesis that humans maintain a reduced apoptotic function relative to chimpanzees by conducting a series of apoptotic function assays on human, chimpanzee and macaque primary fibroblastic cells. Human cells consistently displayed significantly reduced apoptotic function relative to the chimpanzee and macaque cells. These results are consistent with earlier findings indicating that apoptotic function is reduced in humans relative to chimpanzees. PMID:23029431

Changes in Nutritional Status Impact Immune Cell Metabolism and Function.

PubMed

Alwarawrah, Yazan; Kiernan, Kaitlin; MacIver, Nancie J

2018-01-01

Immune cell function and metabolism are closely linked. Many studies have now clearly demonstrated that alterations in cellular metabolism influence immune cell function and that, conversely, immune cell function determines the cellular metabolic state. Less well understood, however, are the effects of systemic metabolism or whole organism nutritional status on immune cell function and metabolism. Several studies have demonstrated that undernutrition is associated with immunosuppression, which leads to both increased susceptibility to infection and protection against several types of autoimmune disease, whereas overnutrition is associated with low-grade, chronic inflammation that increases the risk of metabolic and cardiovascular disease, promotes autoreactivity, and disrupts protective immunity. Here, we review the effects of nutritional status on immunity and highlight the effects of nutrition on circulating cytokines and immune cell populations in both human studies and mouse models. As T cells are critical members of the immune system, which direct overall immune response, we will focus this review on the influence of systemic nutritional status on T cell metabolism and function. Several cytokines and hormones have been identified which mediate the effects of nutrition on T cell metabolism and function through the expression and action of key regulatory signaling proteins. Understanding how T cells are sensitive to both inadequate and overabundant nutrients may enhance our ability to target immune cell metabolism and alter immunity in both malnutrition and obesity.

Quantification of endocytosis using a folate functionalized silica hollow nanoshell platform

PubMed Central

Sandoval, Sergio; Mendez, Natalie; Alfaro, Jesus G.; Yang, Jian; Aschemeyer, Sharraya; Liberman, Alex; Trogler, William C.; Kummel, Andrew C.

2015-01-01

Abstract. A quantification method to measure endocytosis was designed to assess cellular uptake and specificity of a targeting nanoparticle platform. A simple N-hydroxysuccinimide ester conjugation technique to functionalize 100-nm hollow silica nanoshell particles with fluorescent reporter fluorescein isothiocyanate and folate or polyethylene glycol (PEG) was developed. Functionalized nanoshells were characterized using scanning electron microscopy and transmission electron microscopy and the maximum amount of folate functionalized on nanoshell surfaces was quantified with UV-Vis spectroscopy. The extent of endocytosis by HeLa cervical cancer cells and human foreskin fibroblast (HFF-1) cells was investigated in vitro using fluorescence and confocal microscopy. A simple fluorescence ratio analysis was developed to quantify endocytosis versus surface adhesion. Nanoshells functionalized with folate showed enhanced endocytosis by cancer cells when compared to PEG functionalized nanoshells. Fluorescence ratio analyses showed that 95% of folate functionalized silica nanoshells which adhered to cancer cells were endocytosed, while only 27% of PEG functionalized nanoshells adhered to the cell surface and underwent endocytosis when functionalized with 200 and 900  μg, respectively. Additionally, the endocytosis of folate functionalized nanoshells proved to be cancer cell selective while sparing normal cells. The developed fluorescence ratio analysis is a simple and rapid verification/validation method to quantify cellular uptake between datasets by using an internal control for normalization. PMID:26315280

Experimental demonstration of programmable multi-functional spin logic cell based on spin Hall effect

NASA Astrophysics Data System (ADS)

Zhang, X.; Wan, C. H.; Yuan, Z. H.; Fang, C.; Kong, W. J.; Wu, H.; Zhang, Q. T.; Tao, B. S.; Han, X. F.

2017-04-01

Confronting with the gigantic volume of data produced every day, raising integration density by reducing the size of devices becomes harder and harder to meet the ever-increasing demand for high-performance computers. One feasible path is to actualize more logic functions in one cell. In this respect, we experimentally demonstrate a prototype spin-orbit torque based spin logic cell integrated with five frequently used logic functions (AND, OR, NOT, NAND and NOR). The cell can be easily programmed and reprogrammed to perform desired function. Furthermore, the information stored in cells is symmetry-protected, making it possible to expand into logic gate array where the cell can be manipulated one by one without changing the information of other undesired cells. This work provides a prospective example of multi-functional spin logic cell with reprogrammability and nonvolatility, which will advance the application of spin logic devices.

Lidocaine Stimulates the Function of Natural Killer Cells in Different Experimental Settings.

PubMed

Cata, Juan P; Ramirez, Maria F; Velasquez, Jose F; Di, A I; Popat, Keyuri U; Gottumukkala, Vijaya; Black, Dahlia M; Lewis, Valerae O; Vauthey, Jean N

2017-09-01

One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery. NK cells from healthy donors and 43 patients who had undergone surgery for cancer were isolated. The function of NK cells was measured by lactate dehydrogenase release assay. NK cells were incubated with clinically relevant concentrations of lidocaine. By flow cytometry, we determined the impact of lidocaine on the expression of galactosylgalactosylxylosylprotein3-beta-glucuronosytranferase 1, marker of cell maturation (CD57), killer cell lectin like receptor A, inhibitory (NKG2A) receptors and killer cell lectin like receptor D, activation (NKG2D) receptors of NK cells. Differences in expression at p<0.05 were considered statistically significant. Lidocaine increased the expression of NKG2D receptors and stimulated the function of NK cells against ovarian, pancreatic and ovarian cancer cell lines. Lidocaine also increased the cytolytic activity of NK cells from patients who underwent oncological surgery, except for those who had orthopedic procedures. Lidocaine showed an important stimulatory activity on NK cells. Our findings suggest that lidocaine might be used perioperatively to minimize the impact of surgery on NK cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Molecular and functional characterization of CD133+ stem/progenitor cells infused in patients with end-stage liver disease reveals their interplay with stromal liver cells.

PubMed

Catani, Lucia; Sollazzo, Daria; Bianchi, Elisa; Ciciarello, Marilena; Antoniani, Chiara; Foscoli, Licia; Caraceni, Paolo; Giannone, Ferdinando Antonino; Baldassarre, Maurizio; Giordano, Rosaria; Montemurro, Tiziana; Montelatici, Elisa; D'Errico, Antonia; Andreone, Pietro; Giudice, Valeria; Curti, Antonio; Manfredini, Rossella; Lemoli, Roberto Massimo

2017-12-01

Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133 + stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133 + cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133 + and LX-2 hepatic stellate cells. We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133 + SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133 + SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. We demonstrated that the interaction between CD133 + SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Shape functions for velocity interpolation in general hexahedral cells

USGS Publications Warehouse

Naff, R.L.; Russell, T.F.; Wilson, J.D.

2002-01-01

Numerical methods for grids with irregular cells require discrete shape functions to approximate the distribution of quantities across cells. For control-volume mixed finite-element (CVMFE) methods, vector shape functions approximate velocities and vector test functions enforce a discrete form of Darcy's law. In this paper, a new vector shape function is developed for use with irregular, hexahedral cells (trilinear images of cubes). It interpolates velocities and fluxes quadratically, because as shown here, the usual Piola-transformed shape functions, which interpolate linearly, cannot match uniform flow on general hexahedral cells. Truncation-error estimates for the shape function are demonstrated. CVMFE simulations of uniform and non-uniform flow with irregular meshes show first- and second-order convergence of fluxes in the L2 norm in the presence and absence of singularities, respectively.

[Advances in the research of function of Merkel cells in tactile formation of skin].

PubMed

You, X; Wei, Z R

2018-01-20

Skin is the largest sense organ of human, with many mechanoreceptor cells under epidermis or dermis of skin and Merkel cell is one of them. It has been confirmed that Merkel cells play an important role in the process of mechanical transmission of mammalian soft tactile stimulation. Researches showed that Merkel cells had close relation to tactile formation and functioned by Merkel cell-neurite complexes and ion channels Piezo2. This article reviews Merkel cells and the function, problem and prospect of Merkel cells in tactile formation.

Newtonian cell interactions shape natural killer cell education.

PubMed

Goodridge, Jodie P; Önfelt, Björn; Malmberg, Karl-Johan

2015-09-01

Newton's third law of motion states that for every action on a physical object there is an equal and opposite reaction. The dynamic change in functional potential of natural killer (NK) cells during education bears many features of such classical mechanics. Cumulative physical interactions between cells, under a constant influence of homeostatic drivers of differentiation, lead to a reactive spectrum that ultimately shapes the functionality of each NK cell. Inhibitory signaling from an array of self-specific receptors appear not only to suppress self-reactivity but also aid in the persistence of effector functions over time, thereby allowing the cell to gradually build up a functional potential. Conversely, the frequent non-cytolytic interactions between normal cells in the absence of such inhibitory signaling result in continuous stimulation of the cells and attenuation of effector function. Although an innate cell, the degree to which the fate of the NK cell is predetermined versus its ability to adapt to its own environment can be revealed through a Newtonian view of NK cell education, one which is both chronological and dynamic. As such, the development of NK cell functional diversity is the product of qualitatively different physical interactions with host cells, rather than simply the sum of their signals or an imprint based on intrinsically different transcriptional programs. © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy

PubMed Central

Wang, Yichuan; Solaymani-Mohammadi, Shahram; Frey, Blake; Kulkarni, Shweta; Andersen, Peter; Agger, Else Marie; Sui, Yongjun

2017-01-01

T cells with high functional avidity can sense and respond to low levels of cognate Ag, a characteristic that is associated with more potent responses against tumors and many infections, including HIV. Although an important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of high functional avidity through vaccination. Attempts to induce high-avidity T cells by low-dose in vivo vaccination failed because this strategy simply gave no response. Instead, selective induction of high-avidity T cells has required in vitro culturing of specific T cells with low Ag concentrations. In this study, we combined low vaccine Ag doses with a novel potent cationic liposomal adjuvant, cationic adjuvant formulation 09, consisting of dimethyldioctadecylammonium liposomes incorporating two immunomodulators (monomycolyl glycerol analog and polyinosinic-polycytidylic acid) that efficiently induces CD4 Th cells, as well as cross-primes CD8 CTL responses. We show that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. Importantly, CD4 T cells of higher functional avidity induced by low-dose vaccinations showed higher cytokine release per cell and lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) compared with their lower-avidity CD4 counterparts. Notably, increased functional CD4 T cell avidity improved antiviral efficacy of CD8 T cells. These data suggest that potent adjuvants, such as cationic adjuvant formulation 09, render low-dose vaccination a feasible and promising approach for generating high-avidity T cells through vaccination. PMID:28348274

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normalmore » glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.« less

Glycoconjugates and methods

DOEpatents

Bertozzi, Carolyn C [Albany, CA; Yarema, Kevin J [Albany, CA; Mahal, Lara K [Berkeley, CA

2008-04-01

Methods for making the functionalized glycoconjugates include (a) contacting a cell with a first monosaccharide, and (b) incubating the cell under conditions whereby the cell (i) internalizes the first monosaccharide, (ii) biochemically processes the first monosaccharide into a second saccharide, (iii) conjugates the saccharide to a carrier to form a glycoconjugate, and (iv) extracellularly expresses the glycoconjugate to form an extracellular glycoconjugate comprising a selectively reactive functional group. Methods for forming products at a cell further comprise contacting the functional group of the extracellularly expressed glycoconjugate with an agent which selectively reacts with the functional group to form a product. Subject compositions include cyto-compatible monosaccharides comprising a nitrogen or ether linked functional group selectively reactive at a cell surface and compositions and cells comprising such saccharides.

Requirements of transcription factor Smad-dependent and -independent TGF-β signaling to control discrete T-cell functions.

PubMed

Gu, Ai-Di; Wang, Yunqi; Lin, Lin; Zhang, Song S; Wan, Yisong Y

2012-01-17

TGF-β modulates immune response by suppressing non-regulatory T (Treg) function and promoting Treg function. The question of whether TGF-β achieves distinct effects on non-Treg and Treg cells through discrete signaling pathways remains outstanding. In this study, we investigated the requirements of Smad-dependent and -independent TGF-β signaling for T-cell function. Smad2 and Smad3 double deficiency in T cells led to lethal inflammatory disorder in mice. Non-Treg cells were spontaneously activated and produced effector cytokines in vivo on deletion of both Smad2 and Smad3. In addition, TGF-β failed to suppress T helper differentiation efficiently and to promote induced Treg generation of non-Treg cells lacking both Smad2 and Smad3, suggesting that Smad-dependent signaling is obligatory to mediate TGF-β function in non-Treg cells. Unexpectedly, however, the development, homeostasis, and function of Treg cells remained intact in the absence of Smad2 and Smad3, suggesting that the Smad-independent pathway is important for Treg function. Indeed, Treg-specific deletion of TGF-β-activated kinase 1 led to failed Treg homeostasis and lethal immune disorder in mice. Therefore, Smad-dependent and -independent TGF-β signaling discretely controls non-Treg and Treg function to modulate immune tolerance and immune homeostasis.

Functional analysis of HPV-like particle-activated Langerhans cells in vitro.

PubMed

Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin

2015-01-01

Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.

GATA-3 function in innate and adaptive immunity.

PubMed

Tindemans, Irma; Serafini, Nicolas; Di Santo, James P; Hendriks, Rudi W

2014-08-21

The zinc-finger transcription factor GATA-3 has received much attention as a master regulator of T helper 2 (Th2) cell differentiation, during which it controls interleukin-4 (IL-4), IL-5, and IL-13 expression. More recently, GATA-3 was shown to contribute to type 2 immunity through regulation of group 2 innate lymphoid cell (ILC2) development and function. Furthermore, during thymopoiesis, GATA-3 represses B cell potential in early T cell precursors, activates TCR signaling in pre-T cells, and promotes the CD4(+) T cell lineage after positive selection. GATA-3 also functions outside the thymus in hematopoietic stem cells, regulatory T cells, CD8(+) T cells, thymic natural killer cells, and ILC precursors. Here we discuss the varied functions of GATA-3 in innate and adaptive immune cells, with emphasis on its activity in T cells and ILCs, and examine the mechanistic basis for the dose-dependent, developmental-stage- and cell-lineage-specific activity of this transcription factor. Copyright © 2014 Elsevier Inc. All rights reserved.

Drug screens based on the newly found role of dystroglycan proteolysis and restoration of dystroglycan function thereof

DOEpatents

Bissell, Mina J.; Muschler, John L.

2010-02-23

The present invention provides methods and compositions for the diagnosis and treatment of cells lacking normal growth arresting characteristic. The present invention demonstrates that many tumor cells lack normal cell surface .alpha.-dystroglycan and thereby lack dystroglycan function. Dystroglycan can be lost from the cell surface by proteolytic shedding of a fragment of .alpha.-dystroglycan into the surrounding medium. Upon restoration of dystroglycan function and over-expression of the dystroglycan gene, the once tumorigenic cells revert to non-tumorigenic cells which polarize and arrest cell growth in the presence of basement membrane proteins, demonstrating that dystroglycan functions as a tumor marker and suppressor.

Leptin Directly Promotes T Cell Glycolytic Metabolism to Drive Effector T cell Differentiation in Autoimmunity

PubMed Central

Gerriets, Valerie A.; Danzaki, Keiko; Kishton, Rigel J.; Eisner, William; Nichols, Amanda G.; Saucillo, Donte C.; Shinohara, Mari L.; MacIver, Nancie J.

2016-01-01

Upon activation, T cells require energy for growth, proliferation and function. Effector T cells (Teff), such as Th1 and Th17, utilize high levels of glucose uptake and glycolysis to fuel proliferation and function. In contrast, Treg instead require oxidative metabolism to fuel suppressive function. It remains unknown how Teff/Treg metabolism is altered in settings of malnutrition, when nutrients are limited and circulating leptin levels are low. We therefore examined the role of malnutrition and associated hypoleptinemia on Teff versus Treg. We found that both malnutrition-associated hypoleptinemia and T cell-specific leptin receptor knockout suppressed Teff number, function, and glucose metabolism, but did not alter Treg metabolism or suppressive function. Using the autoimmune model EAE, we confirmed that fasting-induced hypoleptinemia altered Teff, but not Treg, glucose metabolism and function in vivo, leading to decreased disease severity. To explore potential mechanisms, we examined HIF-1α, a key regulator of Th17 differentiation and Teff glucose metabolism, and found HIF-1α expression was decreased in T cell-specific leptin receptor knockout Th17 cells, and in Teff cells from fasted EAE mice, but was unchanged in Treg. Altogether, these data demonstrate a selective, cell-intrinsic requirement for leptin to upregulate glucose metabolism and maintain function in Teff, but not Treg. PMID:27222115

Autoreactive T effector memory differentiation mirrors β-cell function in type 1 diabetes.

PubMed

Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana; Lorenc, Anna; Eichmann, Martin; Pujol-Autonell, Irma; Melchiotti, Rossella; Skowera, Ania; Fidanis, Efthymios; Dolton, Garry M; Tungatt, Katie; Sewell, Andrew K; Heck, Susanne; Saxena, Alka; Beam, Craig A; Peakman, Mark

2018-05-31

In type 1 diabetes, cytotoxic CD8 T cells with specificity for β-cell autoantigens are found in the pancreatic islets where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β-cell-reactive CD8 T cells that are detectable in the circulation, and their relationship to β-cell function, are not known. Here, we tracked multiple, circulating β-cell-reactive CD8 T cell subsets and measured β-cell function longitudinally for two years, starting immediately after diagnosis of type 1 diabetes. We found that change in β-cell-specific effector memory CD8 T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8 T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer specific protein 37 and CD16, and reduced expression of CD28) compared with their CD57-negative counterparts, and network association modelling indicated that the dynamics of β-cell-reactive CD57+ effector memory CD8 T cell subsets were strongly linked. Thus, coordinated changes in circulating β-cell-specific CD8 T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

The structure and function of fungal cells

NASA Technical Reports Server (NTRS)

Nozawa, Y.

1984-01-01

The structure and function of fungal cell walls were studied with particular emphasis on dermatophytes. Extraction, isolation, analysis, and observation of the cell wall structure and function were performed. The structure is described microscopically and chemically.