Stereociliary Myosin-1c Receptors Are Sensitive to Calcium Chelation and Absent from Cadherin 23 Mutant Mice

The identities of some of the constituents of the hair-cell transduction apparatus have been elucidated only recently. The molecular motor myosin-1c (Myo1c) functions in adaptation of the hair-cell response to sustained mechanical stimuli and is therefore an integral part of the transduction complex. Recent data indicate that Myo1c interacts in vitro with two other molecules proposed to be important for transduction: cadherin 23 (Cdh23), a candidate for the stereociliary tip link, and phosphatidylinositol 4,5-bisphosphate (PIP2), which is abundant in the membranes of hair-cell stereocilia. It is not known, however, whether these interactions occur in hair cells. Using an in situ binding assay on saccular hair cells, we demonstrated previously that Myo1c interacts with molecules at stereociliary tips, the site of transduction, through sequences contained within its calmodulin (CaM)-binding neck domain, which can bind up to four CaM molecules. In the current study, we identify the second CaM-binding IQ domain as a region of Myo1c that mediates CaM-sensitive binding to stereociliary tips and to PIP2 immobilized on a solid support. Binding of Myo1c to stereociliary tips of cochlear and vestibular hair cells is disrupted by treatments that break tip links. In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP2 in the stereociliary membranes. Collectively, our data suggest that Myo1c and Cdh23 interact at the tips of hair-cell stereocilia and that this interaction is modulated by CaM

Hsp70 in mitochondrial biogenesis

The family of hsp70 (70 kilodalton heat shock protein) molecular chaperones plays an essential and diverse role in cellular physiology, Hsp70 proteins appear to elicit their effects by interacting with polypeptides that present domains which exhibit non-native conformations at distinct stages during their life in the cell. In this paper we review work pertaining to the functions of hsp70 proteins in chaperoning mitochondrial protein biogenesis. Hsp70 proteins function in protein synthesis, protein translocation across mitochondrial membranes, protein folding and finally the delivery of misfolded proteins to proteolytic enzymes in the mitochondrial matrix

Time Variations in Elemental Abundances in Solar Energetic Particle Events

The Solar Isotope Spectrometer (SIS) on-board the Advanced Composition Explorer has a large collection power and high telemetry rate, making it possible to study elemental abundances in large solar energetic particle (SEP) events as a function of time. Results have now been obtained for more than 25 such events. Understanding the causes of these variations is key to obtaining reliable solar elemental abundances and to understanding solar acceleration processes. Such variations have been previously attributed to two models: (1) a mixture of an initial impulsive phase having enhanced heavy element abundances with a longer gradual phase with coronal abundances and (2) rigidity dependent escape from CME-driven shocks through plasma waves generated by wave-particle interactions. In this second model the injected abundances are assumed to be coronal. Both these models can be expected to depend upon solar longitude since impulsive events are associated with flares at longitudes well-connected magnetically to the observer, and shock properties and connection of the observer to the shock are also longitude dependent. We present results on temporal variations from event to event and within events and show that they appear to have a longitude dependence. We show that the events which have been well-explained by model (2) tend to be near central meridian or the west limb. In addition, we show that there are events with little time variation and heavy element enhancements similar to those of impulsive events. These events seem to be better explained by model (1) with only an impulsive phase

Étude de la précocité sexuelle et de certaines caractéristiques de l'éjaculat chez des verrats appartenant a 5 types génétiques: premiers résultats

International audienc

Expansion of magnetic clouds in the outer heliosphere

A large amount of magnetized plasma is frequently ejected from the Sun as coronal mass ejections (CMEs). Some of these ejections are detected in the solar wind as magnetic clouds (MCs) that have flux rope signatures. Magnetic clouds are structures that typically expand in the inner heliosphere. We derive the expansion properties of MCs in the outer heliosphere from one to five astronomical units to compare them with those in the inner heliosphere. We analyze MCs observed by the Ulysses spacecraft using insitu magnetic field and plasma measurements. The MC boundaries are defined in the MC frame after defining the MC axis with a minimum variance method applied only to the flux rope structure. As in the inner heliosphere, a large fraction of the velocity profile within MCs is close to a linear function of time. This is indicative of} a self-similar expansion and a MC size that locally follows a power-law of the solar distance with an exponent called zeta. We derive the value of zeta from the insitu velocity data. We analyze separately the non-perturbed MCs (cases showing a linear velocity profile almost for the full event), and perturbed MCs (cases showing a strongly distorted velocity profile). We find that non-perturbed MCs expand with a similar non-dimensional expansion rate (zeta=1.05+-0.34), i.e. slightly faster than at the solar distance and in the inner heliosphere (zeta=0.91+-0.23). The subset of perturbed MCs expands, as in the inner heliosphere, at a significantly lower rate and with a larger dispersion (zeta=0.28+-0.52) as expected from the temporal evolution found in numerical simulations. This local measure of the expansion also agrees with the distribution with distance of MC size,mean magnetic field, and plasma parameters. The MCs interacting with a strong field region, e.g. another MC, have the most variable expansion rate (ranging from compression to over-expansion)

Ticagrelor versus clopidogrel in patients with acute coronary syndromes and chronic obstructive pulmonary disease: An analysis from the platelet inhibition and patient outcomes (PLATO) trial

Background Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients. Methods and Results In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1‐year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO‐defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non‐COPD patients (HR=1.85). No COPD status‐by‐treatment interactions were found, showing consistency with the main trial results. Conclusions In this post‐hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit‐risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872

The Grizzly, February 12, 1982

Administration Keeping an Eye on Pledging • Housing System Under One Roof • Sororities Dance for Charity • UC College Bowl Impressive at Moravian • Comment: A Letter to Dr. Kane • USGA Notes • Legend Behind Lorelei • FCA Marathon for Special Olympics • Winterfest Tickets Available for Students • Forum on Rising Medical Costs • President\u27s Corner: The Biologist and the Poet • Concert Review: JT, Somehow Perfect; Cars, Shakin\u27 It Up • Vanities Auditions • Soft Core Culture • Frats Converge for Bid Day • Sports Briefs: W\u27s Swimming Gets Revenge; Aquabears Down Swarthmore; Dreamers and Jamas Undefeated • Matmen Run With Streak to Six • Women Crush Cabrini, 78-62 • Men\u27s B-Ball Takes Twohttps://digitalcommons.ursinus.edu/grizzlynews/1072/thumbnail.jp

Space Weather Application Using Projected Velocity Asymmetry of Halo CMEs

Halo coronal mass ejections (HCMEs) originating from regions close to the center of the Sun are likely to be responsible for severe geomagnetic storms. It is important to predict geo-effectiveness of HCMEs using observations when they are still near the Sun. Unfortunately, coronagraphic observations do not provide true speeds of CMEs due to the projection effects. In the present paper, we present a new technique allowing estimate the space speed and approximate source location using projected speeds measured at different position angles for a given HCME (velocity asymmetry). We apply this technique to HCMEs observed during 2001-2002 and find that the improved speeds are better correlated with the travel times of HCMEs to Earth and with the magnitudes ensuing geomagnetic storms.Comment: accepted for [publication in Solar Physic

Europe as a multilevel federation

Peer reviewedPublisher PD