1,942 research outputs found
ATP hydrolysis is critically required for function of Ca<sub>V</sub>1.3 channels in cochlear inner hair cells via fueling Ca<sup>2+</sup> clearance
Sound encoding is mediated by Ca2+ influx-evoked release of glutamate at the ribbon synapse of inner hair cells. Here we studied the role of ATP in this process focusing on Ca2+ current through CaV1.3 channels and Ca2+ homeostasis in mouse inner hair cells. Patch-clamp recordings and Ca2+ imaging demonstrate that hydrolyzable ATP is essential to maintain synaptic Ca2+ influx in inner hair cells via fueling Ca2+-ATPases to avoid an increase in cytosolic [Ca2+] and subsequent Ca2+/calmodulin-dependent inactivation of CaV1.3 channels.</p
Concurrent maturation of inner hair cell synaptic Ca2+ influx and auditory nerve spontaneous activity around hearing onset in mice
Hearing over a wide range of sound intensities is thought to require complementary coding by functionally diverse spiral ganglion neurons (SGNs), each changing activity only over a subrange. The foundations of SGN diversity are not well understood but likely include differences among their inputs: the presynaptic active zones (AZs) of inner hair cells (IHCs). Here we studied one candidate mechanism for causing SGN diversity-heterogeneity of Ca2+ influx among the AZs of IHCs-during postnatal development of the mouse cochlea. Ca2+ imaging revealed a change from regenerative to graded synaptic Ca2+ signaling after the onset of hearing, when in vivo SGN spike timing changed from patterned to Poissonian. Furthermore, we detected the concurrent emergence of stronger synaptic Ca2+ signals in IHCs and higher spontaneous spike rates in SGNs. The strengthening of Ca2+ signaling at a subset of AZs primarily reflected a gain of Ca2+ channels. We hypothesize that the number of Ca2+ channels at each IHC AZ critically determines the firing properties of its corresponding SGN and propose that AZ heterogeneity enables IHCs to decompose auditory information into functionally diverse SGNs
Alice and Cliff Donahue
Photograph - Friends of Alice B. and William Clifford Donahue, Athabasca, Alberta. Seated, left to right: Cliff Donahue, Joe Mikkelsen, Beryl Mikkelsen, and Marge Logan. Standing, left to right: Don Logan, Alice B. Donahue, Aaron Jones, Lorene Jones, and Beatrice Par
The curricular content of primary education in developing countries
This paper examines the curriculum policies for primary schools in a wide range of developing countries in the 1980s and, to a lesser extent, the 1960s. The research covers what subjects are taught, what percentage of instructional time is allocated to each subject, and how much instructional time is available overall in primary education. The results indicate that there is little international debate about primary school curricula. The curricula of mass education systems are increasingly alike all over the world, with surprisingly little regional and national variation. Almost all national educational systems emphasize certain core subjects: language (35%), math (18%), science (8%), and social science (9%).Curriculum&Instruction,Teaching and Learning,Primary Education,Gender and Education,ICT Policy and Strategies
The costs associated with prosecuting crime in Oregon
prepared by: Master of Public Administration capstone team: Heidi Blaine, Megan Entwistle, Mark Nystrom, B. Aaron Weaver ; prepared for: Oregon Criminal Justice Commission.Title from PDF cover (viewed on February 10, 2020).This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (page 15).Mode of access: Internet from the Oregon Government Publications Collection.Text in English
Aaron Burr as his contemporaries saw him : senior honors thesis [(HONRS 499)]
It is the author's purpose in this presentation to discuss Aaron Burr as he was seen by his own period of history and his own world. This objective shall be accomplished by examining sources contemporary to Burr and relevant to the three major areas of his life: the man, the politician, and the conspirator. This division of discussion has been chosen because the author feels that almost every part of Aaron Burr's life can be adapted to one of these three areas. The author has also found that any matter which cannot be suited to one of these three areas is but incidental commentary and has little importance for the subject at hand.Thesis (B.?.)Honors Colleg
A new probe for super-resolution imaging of membranes elucidates trafficking pathways
The molecular composition of the organelles involved in membrane recycling is difficult to establish as a result of the absence of suitable labeling tools. We introduce in this paper a novel probe, named membrane-binding fluorophore-cysteine-lysine-palmitoyl group (mCLING), which labels the plasma membrane and is taken up during endocytosis. It remains attached to membranes after fixation and permeabilization and can therefore be used in combination with immunostaining and super-resolution microscopy. We applied mCLING to mammalian-cultured cells, yeast, bacteria, primary cultured neurons, Drosophila melanogaster larval neuromuscular junctions, and mammalian tissue. mCLING enabled us to study the molecular composition of different trafficking organelles. We used it to address several questions related to synaptic vesicle recycling in the auditory inner hair cells from the organ of Corti and to investigate molecular differences between synaptic vesicles that recycle actively or spontaneously in cultured neurons. We conclude that mCLING enables the investigation of trafficking membranes in a broad range of preparations
Rescue of placental phenotype in a mechanistic model of Beckwith-Wiedemann syndrome
Background:
Several imprinted genes have been implicated in the process of placentation. The distal region of mouse chromosome 7 (Chr 7) contains at least ten imprinted genes, several of which are expressed from the maternal homologue in the placenta. The corresponding paternal alleles of these genes are silenced in cis by an incompletely understood mechanism involving the formation of a repressive nuclear compartment mediated by the long non-coding RNA Kcnq1ot1 initiated from imprinting centre 2 (IC2). However, it is unknown whether some maternally expressed genes are silenced on the paternal homologue via a Kcnq1ot1-independent mechanism. We have previously reported that maternal inheritance of a large truncation of Chr7 encompassing the entire IC2-regulated domain (DelTel7 allele) leads to embryonic lethality at mid-gestation accompanied by severe placental abnormalities. Kcnq1ot1 expression can be abolished on the paternal chromosome by deleting IC2 (IC2KO allele). When the IC2KO mutation is paternally inherited, epigenetic silencing is lost in the region and the DelTel7 lethality is rescued in compound heterozygotes, leading to viable DelTel7/IC2KO mice.
Results:
Considering the important functions of several IC2-regulated genes in placentation, we set out to determine whether these DelTel7/IC2KO rescued conceptuses develop normal placentae. We report no abnormalities with respect to the architecture and vasculature of the DelTel7/IC2KO rescued placentae. Imprinted expression of several of the IC2-regulated genes critical to placentation is also faithfully recapitulated in DelTel7/IC2KO placentae.
Conclusion:
Taken together, our results demonstrate that all the distal chromosome 7 imprinted genes implicated in placental function are silenced by IC2 and Kcnq1ot1 on the paternal allele. Furthermore, our results demonstrate that the methylated maternal IC2 is not required for the regulation of nearby genes. The results show the potential for fully rescuing trans placental abnormalities that are caused by imprinting defects.Medical Genetics, Department ofMedicine, Faculty ofOther UBCNon UBCReviewedFacult
Author Correction: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps
Correction to: Nature Genetics https://doi.org/10.1038/ng.3668, published online 26 September 2016.
In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs
The 5E model as a framework for facilitating multiple teacher education outcomes : a secondary science methods course in Australia
Australia is a large country geographically with a relatively small population of approximately twenty four million people. Like many countries, the health of the economy fluctuates over time, but Australia has enjoyed a mostly healthy and stable trajectory of economic output over the last forty years. There is now a strong push to develop STEM education throughout the country, not only due to the need for more students to enter into STEM professions, but also due to concerns about science and mathematics literacy (Australian Council of Learned Academies, 2013). This chapter describes preparing grade 7–10 science teachers at Western Sydney University in Australia using an approach based on the 5E learning cycle (Bybee et al., 2006). The author focuses on teacher discourse practices as his signature lesson, and has students develop their own 5E lesson plan as a summative assessment in the course
- …
