245 research outputs found
A mixed methods study exploring older womens\u27 attitudes toward osteoporosis medications: Adapting a health communication framework
Redundant Mechanisms for Regulation of Midline Crossing in Drosophila
During development, all neurons have to decide on whether to cross the longitudinal midline to project on the contralateral side of the body. In vertebrates and invertebrates regulation of crossing is achieved by interfering with Robo signalling either through sorting and degradation of the receptor, in flies, or through silencing of its repulsive activity, in vertebrates. Here I show that in Drosophila a second mechanism of regulation exists that is independent from sorting. Using in vitro and in vivo assays I mapped the region of Robo that is sufficient and required for its interaction with Comm, its sorting receptor. By modifying that region, I generated new forms of Robo that are insensitive to Comm sorting in vitro and in vivo, yet still able to normally translate repulsive activity in vivo. Using gene targeting by homologous recombination I created new conditional alleles of robo that are sorting defective (roboSD). Surprisingly, expression of these modified proteins results in phenotypically normal flies, unveiling a sorting independent mechanism of regulation
Epigenetic Regulation of Learning and Memory by Drosophila EHMT/G9a
Behavioral phenotyping and genome-wide profiling of the histone modifier EHMT in Drosophila reveals a mechanism through which an epigenetic writer may control cognition
Genetics of intellectual disability in consanguineous families
Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence
Arc magmas sourced from melange diapirs in subduction zones
Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 862-867, doi:10.1038/ngeo1634.At subduction zones, crustal material is recycled back into the mantle. A certain proportion, however, is returned to the overriding
plate via magmatism. The magmas show a characteristic range of compositions that have been explained by three-component
mixing in their source regions: hydrous fluids derived from subducted altered oceanic crust and components derived from the thin
sedimentary veneer are added to the depleted peridotite in the mantle beneath the volcanoes. However, currently no uniformly
accepted model exists for the physical mechanism that mixes the three components and transports them from the slab to the
magma source.
Here we present an integrated physico-chemical model of subduction zones that emerges from a review of the combined findings
of petrology, modelling, geophysics, and geochemistry: Intensely mixed metamorphic rock formations, so-called mélanges, form
along the slab-mantle interface and comprise the characteristic trace-element patterns of subduction-zone magmatic rocks. We
consider mélange formation the physical mixing process that is responsible for the geochemical three-component pattern of the
magmas. Blobs of low-density mélange material, so-called diapirs, rise buoyantly from the surface of the subducting slab and
provide a means of transport for well-mixed materials into the mantle beneath the volcanoes, where they produce melt. Our model
provides a consistent framework for the interpretation of geophysical, petrological and geochemical data of subduction zones.H.M. was funded
by the J. LamarWorzel Assistant Scientist Fund and the
Penzance Endowed Fund in Support of Assistant Scientists.
Funding from NSF grant #1119403 (G. Harlow)
is acknowledged.2013-05-1
A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion
Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor.National Institutes of Health (U.S.) (Grant F32-CA165700)National Institutes of Health (U.S.) (Grant R01-GM068678)National Institutes of Health (U.S.) (Grant P30-CA014051
Roles of the Drosophila SK Channel (dSK) in Courtship Memory
A role for SK channels in synaptic plasticity has been very well-characterized. However, in the absence of simple genetic animal models, their role in behavioral memory remains elusive. Here, we take advantage of Drosophila melanogaster with its single SK gene (dSK) and well-established courtship memory assay to investigate the contribution of this channel to memory. Using two independent dSK alleles, a null mutation and a dominant negative subunit, we show that while dSK negatively regulates the acquisition of short-term memory 30 min after a short training session, it is required for normal long-term memory 24 h after extended training. These findings highlight important functions for dSK in courtship memory and suggest that SK channels can mediate multiple forms of behavioral plasticity
The Evolution of Religion: How Cognitive By-Products, Adaptive Learning Heuristics, Ritual Displays, and Group Competition Generate Deep Commitments to Prosocial Religio
Understanding religion requires explaining why supernatural beliefs, devotions, and rituals are both universal and variable across cultures, and why religion is so often associated with both large-scale cooperation and enduring group conflict. Emerging lines of research suggest that these oppositions result from the convergence of three processes. First, the interaction of certain reliably developing cognitive processes, such as our ability to infer the presence of intentional agents, favors—as an evolutionary by-product—the spread of certain kinds of counterintuitive concepts. Second, participation in rituals and devotions involving costly displays exploits various aspects of our evolved psychology to deepen people's commitment to both supernatural agents and religious communities. Third, competition among societies and organizations with different faith-based beliefs and practices has increasingly connected religion with both within-group prosociality and between-group enmity. This connection has strengthened dramatically in recent millennia, as part of the evolution of complex societies, and is important to understanding cooperation and conflict in today's world
A comparative analysis of body psychotherapy and dance movement psychotherapy from a European perspective
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