Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium

The social amoebozoan Dictyostelium discoideum undergoes a developmental sequence wherein an extracellular matrix (ECM) sheath surrounds a group of differentiating cells. This sheath is comprised of proteins and carbohydrates, like the ECM of mammalian tissues. One of the characterized ECM proteins is the cysteine-rich, EGF-like (EGFL) repeat-containing, calmodulin (CaM)-binding protein (CaMBP) CyrA. The first EGFL repeat of CyrA increases the rate of random cell motility and cyclic AMP-mediated chemotaxis. Processing of full-length CyrA (~63 kDa) releases two major EGFL repeat-containing fragments (~45 kDa and ~40 kDa) in an event that is developmentally regulated. Evidence for an EGFL repeat receptor also exists and downstream intracellular signaling pathways involving CaM, Ras, protein kinase A and vinculin B phosphorylation have been characterized. In total, these results identify CyrA as a true matricellular protein comparable in function to tenascin C and other matricellular proteins from mammalian cells. Insight into the regulation and processing of CyrA has also been revealed. CyrA is the first identified extracellular CaMBP in this eukaryotic microbe. In keeping with this, extracellular CaM (extCaM) has been shown to be present in the ECM sheath where it binds to CyrA and inhibits its cleavage to release the 45 kDa and 40 kDa EGFL repeat-containing fragments. The presence of extCaM and its role in regulating a matricellular protein during morphogenesis extends our understanding of CaM-mediated signal transduction in eukaryotes

Cortical lamina-dependent blood volume changes in human brain at 7T

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8–1.6 mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans

Loss of Cln3 Function in the Social Amoeba Dictyostelium discoideum Causes Pleiotropic Effects That Are Rescued by Human CLN3

The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL) is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3− cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3− cells was precocious and cln3− slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3− cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3− cells, strongly supports the use of this new model for JNCL research

Geometric inequalities from phase space translations

We establish a quantum version of the classical isoperimetric inequality relating the Fisher information and the entropy power of a quantum state. The key tool is a Fisher information inequality for a state which results from a certain convolution operation: the latter maps a classical probability distribution on phase space and a quantum state to a quantum state. We show that this inequality also gives rise to several related inequalities whose counterparts are well-known in the classical setting: in particular, it implies an entropy power inequality for the mentioned convolution operation as well as the isoperimetric inequality, and establishes concavity of the entropy power along trajectories of the quantum heat diffusion semigroup. As an application, we derive a Log-Sobolev inequality for the quantum Ornstein-Uhlenbeck semigroup, and argue that it implies fast convergence towards the fixed point for a large class of initial states.Comment: 37 pages; updated to match published versio

Human-Robot Control Strategies for the NASA/DARPA Robonaut

The Robotic Systems Technology Branch at the NASA Johnson Space Center (JSC) is currently developing robot systems to reduce the Extra-Vehicular Activity (EVA) and planetary exploration burden on astronauts. One such system, Robonaut, is capable of interfacing with external Space Station systems that currently have only human interfaces. Robonaut is human scale, anthropomorphic, and designed to approach the dexterity of a space-suited astronaut. Robonaut can perform numerous human rated tasks, including actuating tether hooks, manipulating flexible materials, soldering wires, grasping handrails to move along space station mockups, and mating connectors. More recently, developments in autonomous control and perception for Robonaut have enabled dexterous, real-time man-machine interaction. Robonaut is now capable of acting as a practical autonomous assistant to the human, providing and accepting tools by reacting to body language. A versatile, vision-based algorithm for matching range silhouettes is used for monitoring human activity as well as estimating tool pose

Nd Isotopic Structure of the Pacific Ocean 70-30 and Numerical Evidence for Vigorous Ocean Circulation and Ocean Heat Transport in a Greenhouse World

The oceanic meridional overturning circulation (MOC) is a crucial component of the climate system, impacting heat and nutrient transport, and global carbon cycling. Past greenhouse climate intervals present a paradox because their weak equator-to-pole temperature gradients imply a weaker MOC, yet increased poleward oceanic heat transport appears to be required to maintain these weak gradients. To investigate the mode of MOC that operated during the early Cenozoic, we compare new Nd isotope data with Nd tracer-enabled numerical ocean circulation and coupled climate model simulations. Assimilation of new Nd isotope data from South Pacific Deep Sea Drilling Project and Ocean Drilling Program Sites 323, 463, 596, 865, and 869 with previously published data confirm the hypothesized MOC characterized by vigorous sinking in the South and North Pacific ~70 to 30 Ma. Compilation of all Pacific Nd isotope data indicates vigorous, distinct, and separate overturning circulations in each basin until ~40 Ma. Simulations consistently reproduce South Pacific and North Pacific deep convection over a broad range of conditions, but cases using strong deep ocean vertical mixing produced the best data-model match. Strong mixing, potentially resulting from enhanced abyssal tidal dissipation, greater interaction of wind-driven internal wave activity with submarine plateaus, or higher than modern values of the geothermal heat flux enable models to achieve enhanced MOC circulation rates with resulting Nd isotope distributions consistent with the proxy data. The consequent poleward heat transport may resolve the paradox of warmer worlds with reduced temperature gradients

Enhancing the Care Navigation Model: Potential Roles for Health Sciences Librarians

This study analyzed the overlap between roles and activities that health care navigators perform and competencies identified by the Medical Library Association\u27s (MLA\u27s) educational policy statement. Roles and activities that health care navigators perform were gleaned from published literature. Once common roles and activities that health care navigators perform were identified, MLA competencies were mapped against those roles and activities to identify areas of overlap. The greatest extent of correspondence occurred in patient empowerment and support. Further research is warranted to determine the extent to which health sciences librarians might assume responsibility for roles and activities that health care navigators perform

A Hydrologic Model of the Bear River Basin

As demands upon available water supplies increase, there is an accompanying increase in the need to assess downstream consequences resulting from changes at specific locations within a hydrologic system. The problem is approached in this study by hybrid computer simulation of the hydrologic system. Modeling concepts are based upon the development of basic relationships which describe the various hydrologic processes. Within a system these relationships are linked by the continuity-of-mass priciple which requires a hydrologic balance at all points. Spatial resolution is achieved by considering the modeled areas as a series of subbasins. The time increment adopted for the model is one month, so taht time varying quantities are expressed in terms of mean monthly values. The model is general in nature and in applied to a partifular hydrologic system through a programmed verification procedure whereby model coefficients are evaluated for the particular system. In this study the model was synthesized on a hybrid computer and applied to the Bear River basin of western Wyoming, southern Idaho, and northern Utah. Comparisons between observed and comptued outflow hydrographs for each subbasin are shown. The utility of the model for predicting the effects of various possible water resources management alternatives is demonstrated for the number 1, or Evanston subbasin. The hybrid computer is very efficient for model development, and the verified model can be readily programmed on the all-digital computer