Calcium Signals: STIM Dynamics Mediate Spatially Unique Oscillations

SummaryReceptor-induced Ca2+ oscillations provide ‘digitized’ signals that confer precise activation of downstream targets. New studies reveal that STIM proteins — sensors of endoplasmic reticulum Ca2+ levels — cyclically translocate during oscillations, transiently coupling to activate cell-surface Ca2+ entry channels, resulting in a spatially unique signal that selectively triggers immediate-early gene expression

Store-Operated Ca2+ Entry Evidence for a Secretion-like Coupling Model

AbstractThe elusive coupling between endoplasmic reticulum (ER) Ca2+ stores and plasma membrane (PM) “store-operated” Ca2+ entry channels was probed through a novel combination of cytoskeletal modifications. Whereas coupling was unaffected by disassembly of the actin cytoskeleton, in situ redistribution of F-actin into a tight cortical layer subjacent to the PM displaced cortical ER and prevented coupling between ER and PM Ca2+ entry channels, while not affecting inositol 1,4,5-trisphosphate-mediated store release. Importantly, disassembly of the induced cortical actin layer allowed ER to regain access to the PM and reestablish coupling of Ca2+ entry channels to Ca2+ store depletion. Coupling is concluded to be mediated by a physical “secretion-like” mechanism involving close but reversible interactions between the ER and the PM

Wheat hay for livestock

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Cognitive Information Processing

Contains reports on three research projects.National Science Foundation (Grant GP-2495)National Institutes of Health (Grant MH-04737-04)National Aeronautics and Space Administration (Grant NsG-496

Observer Dependent Horizon Temperatures: a Coordinate-Free Formulation of Hawking Radiation as Tunneling

We reformulate the Hamilton-Jacobi tunneling method for calculating Hawking radiation in static, spherically-symmetric spacetimes by explicitly incorporating a preferred family of frames. These frames correspond to a family of observers tied to a locally static timelike Killing vector of the spacetime. This formulation separates the role of the coordinates from the choice of vacuum and thus provides a coordinate-independent formulation of the tunneling method. In addition, it clarifies the nature of certain constants and their relation to these preferred observers in the calculation of horizon temperatures. We first use this formalism to obtain the expected temperature for a static observer at finite radius in the Schwarzschild spacetime. We then apply this formalism to the Schwarzschild-de Sitter spacetime, where there is no static observer with 4-velocity equal to the static timelike Killing vector. It is shown that a preferred static observer, one whose trajectory is geodesic, measures the lowest temperature from each horizon. Furthermore, this observer measures horizon temperatures corresponding to the well-known Bousso-Hawking normalization.Comment: 11 pages, 1 2-part figure, references added, appendix added, discussion streamline

An Analysis of Private School Closings

We add to the small literature on private school supply by exploring exits of K-12 private schools. We find that the closure of private schools is not an infrequent event, and use national survey data from the National Center for Education Statistics to study closures of private schools. We assume that the probability of an exit is a function of excess supply of private schools over the demand, as well as the school's characteristics such as age, size, and religious affiliation. Our empirical results generally support the implications of the model. Working Paper 07-0

Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides

MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca^(2+) Stress

Mitochondria shape cytosolic calcium ([Ca^(2+)]_c) transients and utilize the mitochondrial Ca_2^+ ([Ca^(2+)]_m) in exchange for bioenergetics output. Conversely, dysregulated [Ca^(2+)]_c causes [Ca^(2+)]_m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca^(2+) uptake exhibited elevated [Ca^(2+)]_c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca^(2+)-induced shape change that is distinct from mitochondrial fission and swelling. [Ca^(2+)]_c elevation, but not MCU-mediated Ca^(2+) uptake, appears to be essential for the process we term mitochondrial shape transition (MiST). MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca^(2+)-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca^(2+) sensor that decodes metazoan Ca^(2+) signals as MiST

Decoherence, the measurement problem, and interpretations of quantum mechanics

Environment-induced decoherence and superselection have been a subject of intensive research over the past two decades, yet their implications for the foundational problems of quantum mechanics, most notably the quantum measurement problem, have remained a matter of great controversy. This paper is intended to clarify key features of the decoherence program, including its more recent results, and to investigate their application and consequences in the context of the main interpretive approaches of quantum mechanics.Comment: 41 pages. Final published versio