The supporting-cell antigen: a receptor-like protein tyrosine phosphatase expressed in the sensory epithelia of the inner ear

After noise- or drug-induced hair-cell loss, the sensory epithelia of the avian inner ear can regenerate new hair cells. Few molecular markers are available for the supporting-cell precursors of the hair cells that regenerate, and little is known about the signaling mechanisms underlying this regenerative response. Hybridoma methodology was used to obtain a monoclonal antibody (mAb) that stains the apical surface of supporting cells in the sensory epithelia of the inner ear. The mAb recognizes the supporting-cell antigen (SCA), a protein that is also found on the apical surfaces of retinal Müller cells, renal tubule cells, and intestinal brush border cells. Expression screening and molecular cloning reveal that the SCA is a novel receptor-like protein tyrosine phosphatase (RPTP), sharing similarity with human density-enhanced phosphatase, an RPTP thought to have a role in the density-dependent arrest of cell growth. In response to hair-cell damage induced by noise in vivo or hair-cell loss caused by ototoxic drug treatment in vitro, some supporting cells show a dramatic decrease in SCA expression levels on their apical surface. This decrease occurs before supporting cells are known to first enter S-phase after trauma, indicating that it may be a primary rather than a secondary response to injury. These results indicate that the SCA is a signaling molecule that may influence the potential of nonsensory supporting cells to either proliferate or differentiate into hair cell

Effects of Perinatal Oxycodone Exposure on the Cardiovascular Response to Acute Stress in Male Rats at Weaning and in Young Adulthood

Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress. Objectives: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood. Methods: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males were fitted with BP telemetry units. Offspring were classically conditioned by following a pulsed tone (CS+) with tail shock. A steady tone (CS-) was not followed by shock. BP and HR were recorded during resting periods and conditioning. Changes in BP, HR from composite analysis were compared. The paradigm was repeated on PD 75. Results: At PD 40, OXY rats had a lower baseline mean BP (OXY: 114.8 ± 1.0 vs. CON: 118.3 ± 1.0 mm Hg; mean ± SEM) but larger amplitude of the conditional BP increase during the stress response (OXY: +3.9 ± 0.4 vs. CON: +1.7 ± 0.4 mm Hg). Both OXY and CON rats were able to discriminate between CS+ and CS-. At PD 75, the effects of OXY on the increased amplitude of the conditional BP had dissipated (CON: +3.4 ± 2.3 vs. OXY: +4.5 ± 1.4 mm Hg). BP responses to the stress and non-stress stimuli did not differ in the OXY group, suggesting that OXY may have decreased the ability of the offspring to discriminate (OXY: CS+: 147.1 ± 1.6, CS-: 145.9 ± 1.6 mm Hg vs. CON: CS+: 155.4 ± 2.7, CS-: 147.8 ± 2.7 mm Hg). Conclusion: POE is associated with subtle alterations in stress CV responses in weanling rats which dissipate when the conditioning is repeated at an early adult age. Although POE effect on the ability to discriminate at weanling age could not be detected, POE may impair retention of this ability in adulthood

Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domain-specific structural phenotypes in the tectorial membrane

Tecta is a modular, non-collagenous protein of the tectorial membrane, an extracellular matrix of the cochlea essential for normal hearing. Missense mutations in Tecta cause dominant forms of nonsyndromic deafness and a genotype-phenotype correlation has been reported in humans, with mutations in different Tecta domains causing mid- or high-frequency hearing impairments that are either stable or progressive. Three mutant mice were created as models for human Tecta mutations; the TectaL1820F, G1824D/+ mouse for zona pellucida (ZP) domain mutations causing stable mid-frequency hearing loss in a Belgian family, the TectaC1837G/+ mouse for a ZP-domain mutation underlying progressive mid-frequency hearing loss in a Spanish family, and the TectaC1619S/+ mouse for a zonadhesin-like (ZA) domain mutation responsible for progressive, high-frequency hearing loss in a French family. Mutations in the ZP and ZA domains generate distinctly different changes in the structure of the tectorial membrane. ABR thresholds in the 8-40 kHz range are elevated by 30-40 dB in the ZP-domain mutants, whilst those in the ZA-domain mutant are elevated by 20-30 dB. The phenotypes are stable and no evidence has been found for a progressive deterioration in tectorial membrane structure or auditory function. Despite elevated auditory thresholds, the Tecta mutant mice all exhibit an enhanced tendency to have audiogenic seizures in response to white noise stimuli at low sound pressure levels (≤84 dB SPL), revealing a previously unrecognised consequence of Tecta mutations. These results, together with those from previous studies, establish an allelic series for Tecta unequivocally demonstrating an association between genotype and phenotype

The very large G-protein coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles

The photoneuroendocrine control of seasonal breeding in the ewe

The major environmental parameter controlling seasonal breeding in ewes is photoperiod. Short days stimulate, and long days inhibit breeding activity. One of the more intriguing enigmas of neuroendocrinology is the endocrine mechanism whereby a mere change in daylength initiates or prevents estrous cycles. Recent experiments have begun to solve this problem by demonstrating that in ewes, photoperiod governs response of the hypothalamo-pituitary axis to the negative feedback action of estradiol. In long days, estradiol is a potent inhibitor of gonadotropin secretion, whereas in short days it is relatively ineffective in this regard. These photoperiod-induced changes in estradiol feedback are proposed to permit or prevent estrous cycles by controlling the occurrence of a crucial step in the sequence of events leading to ovulation, namely a sustained, preovulatory rise in LH. Thus, estrous cycles cease in long days because an increase in estradiol negative feedback prevents the sustained rise in LH. In short days, estrous cycles resume because a decrease in estradiol feedback permits the sustained rise in LH required for ovulation. Even more puzzling, at present, than the mechanism of transduction of photoperiodic information into an endocrine event controlling seasonal breeding is the problem of transmission of photoperiodic information from the environment to the hypothalamo-pituitary axis. In sheep, early investigations of the transmission pathway have elicited provocative results, only some of which are similar to those obtained in other species. Among the questions which remain to be answered are: what is the location of the photoreceptors, and what, if any, are the roles of the suprachiasmatic nuclei and the pineal in photoperiodic control of seasonal breeding? These issues promise to provide a tantalizing challenge for future investigations into the photoneuroendocrine control of seasonal breeding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24213/1/0000472.pd

Channeling and Volume Reflection Based Crystal Collimation of Tevatron Circulating Beam Halo (T-980)

The T980 crystal collimation experiment is underway at the Tevatron to determine if this technique could increase 980 GeV beam-halo collimation efficiency at high-energy hadron colliders such as the Tevatron and the LHC. T980 also studies various crystal types and parameters. The setup has been substantially enhanced during the Summer 2009 shutdown by installing a new O-shaped crystal in the horizontal goniometer, as well as adding a vertical goniometer with two alternating crystals (O-shaped and multi-strip) and additional beam diagnostics. First measurements with the new system are quite encouraging, with channeled and volume-reflected beams observed on the secondary collimators as predicted. Investigation of crystal collimation efficiencies with crystals in volume reflection and channeling modes are described in comparison with an amorphous primary collimator. Results on the system performance are presented for the end-of-store studies and for entire collider stores. The first investigation of colliding beam collimation simultaneously using crystals in both the vertical and horizontal plane has been made in the regime with horizontally channeled and vertically volume-reflected beams. Planning is underway for significant hardware improvements during the FY10 summer shutdown and for dedicated studies during the final year of Tevatron operation and also for a "post-collider beam physics running" period.Comment: 3 pp. 1st International Particle Accelerator Conference: IPAC'10, 23-28 May 2010: Kyoto, Japa

Enhancement of PCA-based fault detection system through utilising dissimilarity matrix for continuous-based process

This research is about enhancement of PCA-based fault detection system through utilizing dissimilarity matrix. Nowadays, the chemical process industry is highly based on the non-linear relationships between measured variables. However, the conventional PCA-based MSPC is no longer effective because it only valid for the linear relationships between measured variables. Due in order to solve this problem, the technique of dissimilarity matrix is used in multivariate statistical process control as alternative technique which models the non-linear process and can improve the process monitoring performance. The conventional PCA system was run and the dissimilarity system was developed and lastly the monitoring performance in each technique were compared and analysed to achieve aims of this research. This research is to be done by using Matlab software. The findings of this study are illustrated in the form of Hotelling’s T2 and Squared Prediction Errors (SPE) monitoring statistics to be analysed. As a conclusion, the dissimilarity system is comparable to the conventional method. Thus can be the other alternative ways in the process monitoring performance. Finally, it is recommended to use data from other chemical processing systems for more concrete justification of the new technique

The Effects of Perinatal Oxycodone Exposure on Behavioral Outcome in a Rodent Model

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic–pituitary–adrenal axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy; however, limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant effects of POE were detected on isolation-induced ultrasonic vocalizations in the early postnatal period or on learning and memory in the water maze in adult offspring. Our findings are consistent with hyperactivity problems identified in children exposed to opiates in utero