Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: Involvement of src family protein kinases

The increased production of amyloid beta -peptide (A beta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to A beta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to A beta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar A beta (25-35) and A beta (1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-( 4-chlorophenyl)- 7(t-butyl) pyrazol(3,4-D) pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from A beta (25-35)-treated neurons showed an increased association of Fyn with FAK. A beta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in A beta -treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to A beta exposure and may be critical for subsequent neurodegenerative changes

Bifurcations in annular electroconvection with an imposed shear

We report an experimental study of the primary bifurcation in electrically-driven convection in a freely suspended film. A weakly conducting, submicron thick smectic liquid crystal film was supported by concentric circular electrodes. It electroconvected when a sufficiently large voltage $V$ was applied between its inner and outer edges. The film could sustain rapid flows and yet remain strictly two-dimensional. By rotation of the inner electrode, a circular Couette shear could be independently imposed. The control parameters were a dimensionless number ${\cal R}$, analogous to the Rayleigh number, which is $\propto V^2$ and the Reynolds number ${\cal R}e$ of the azimuthal shear flow. The geometrical and material properties of the film were characterized by the radius ratio $\alpha$, and a Prandtl-like number ${\cal P}$. Using measurements of current-voltage characteristics of a large number of films, we examined the onset of electroconvection over a broad range of $\alpha$, ${\cal P}$ and ${\cal R}e$. We compared this data quantitatively to the results of linear stability theory. This could be done with essentially no adjustable parameters. The current-voltage data above onset were then used to infer the amplitude of electroconvection in the weakly nonlinear regime by fitting them to a steady-state amplitude equation of the Landau form. We show how the primary bifurcation can be tuned between supercritical and subcritical by changing $\alpha$ and ${\cal R}e$.Comment: 17 pages, 12 figures. Submitted to Phys. Rev. E. Minor changes after refereeing. See also http://mobydick.physics.utoronto.c

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Seasonal Spatial Segregation in Blue Sharks (Prionace glauca) by Sex and Size Class in the Northeast Pacific Ocean

Aim: Animal tracking can provide unique insights into the ecology and conservation of marine species, such as the partitioning of habitat, including differences between life history stages or sexes, and can inform fisheries stock assessments, bycatch reduction and spatial management such as dynamic management. Location: Northeast Pacific Ocean. Methods: We used satellite tracking data from 47 blue sharks (Prionace glauca) from the Northeast Pacific to determine movements and home range along the west coast of North America, and sex–size class (immature females, mature males) specific habitat preferences using boosted regression trees. Using a suite of static and dynamic environmental variables, we determined distribution and habitat preferences across summer and fall for each sex–size class. Results: We found that there was spatial segregation between sex–size classes particularly in the summer months with immature females found largely north of 33°N, and males south of 35°N. In fall, females travelled south, resulting in an overlap in distributions south of 37°N. Sea surface temperature (SST), latitude and longitude were top predictors. However, immature females and adult males demonstrated unique habitat preferences including SST, with immature females preferring cooler temperatures (SST \u3c 15°C) than adult males in summer, and a broader band of SST than adult males in fall. All models performed well, explaining 50%–67% of deviance, and 23%–41% of deviance when predictions were cross‐validated. Main conclusions: We provide first insights into coastal movements and habitat preferences of blue sharks in the Northeast Pacific. We found that immature females undergo a seasonal southward migration in this more coastal habitat, similar to patterns observed in the North Atlantic. We also found some overlap between adult males and immature females in fall months, suggesting the importance of more coastal habitat in managing this species, particularly in determining population structure for blue shark stock assessments, and reducing blue shark bycatch

Nonlinear regularization techniques for seismic tomography

The effects of several nonlinear regularization techniques are discussed in the framework of 3D seismic tomography. Traditional, linear, $\ell_2$ penalties are compared to so-called sparsity promoting $\ell_1$ and $\ell_0$ penalties, and a total variation penalty. Which of these algorithms is judged optimal depends on the specific requirements of the scientific experiment. If the correct reproduction of model amplitudes is important, classical damping towards a smooth model using an $\ell_2$ norm works almost as well as minimizing the total variation but is much more efficient. If gradients (edges of anomalies) should be resolved with a minimum of distortion, we prefer $\ell_1$ damping of Daubechies-4 wavelet coefficients. It has the additional advantage of yielding a noiseless reconstruction, contrary to simple $\ell_2$ minimization (`Tikhonov regularization') which should be avoided. In some of our examples, the $\ell_0$ method produced notable artifacts. In addition we show how nonlinear $\ell_1$ methods for finding sparse models can be competitive in speed with the widely used $\ell_2$ methods, certainly under noisy conditions, so that there is no need to shun $\ell_1$ penalizations.Comment: 23 pages, 7 figures. Typographical error corrected in accelerated algorithms (14) and (20

Equilibrium configurations of two charged masses in General Relativity

An asymptotically flat static solution of Einstein-Maxwell equations which describes the field of two non-extreme Reissner - Nordstr\"om sources in equilibrium is presented. It is expressed in terms of physical parameters of the sources (their masses, charges and separating distance). Very simple analytical forms were found for the solution as well as for the equilibrium condition which guarantees the absence of any struts on the symmetry axis. This condition shows that the equilibrium is not possible for two black holes or for two naked singularities. However, in the case when one of the sources is a black hole and another one is a naked singularity, the equilibrium is possible at some distance separating the sources. It is interesting that for appropriately chosen parameters even a Schwarzschild black hole together with a naked singularity can be "suspended" freely in the superposition of their fields.Comment: 4 pages; accepted for publication in Phys. Rev.

The History of Makassan Trepang Fishing and Trade

The Malayan term trepang describes a variety of edible holothurians commonly known as sea cucumbers. Although found in temperate and tropical marine waters all over the world, the centre of species diversity and abundance are the shallow coastal waters of Island Southeast Asia. For at least 300 years, trepang has been a highly priced commodity in the Chinese market. Originally, its fishing and trade was a specialized business, centred on the town of Makassar in South Sulawesi (Indonesia). The rise of trepang fishing in the 17th century added valuable export merchandize to the rich shallow seas surrounding the islands of Southeast Asia. This enabled local communities to become part of large trading networks and greatly supported their economic development. In this article, we follow Makassan trepang fishing and trading from its beginning until the industrialization of the fishery and worldwide depletion of sea cucumbers in the 20th century. Thereby, we identify a number of characteristics which trepang fishing shares with the exploitation of other marine resources, including (1) a strong influence of international markets, (2) the role of patron-client relationships which heavily influence the resource selection, and (3) the roving-bandit-syndrome, where fishermen exploit local stocks of valuable resources until they are depleted, and then move to another area. We suggest that understanding the similarities and differences between historical and recent exploitation of marine resources is an important step towards effective management solutions

The place and barriers of evidence based practice: knowledge and perceptions of medical, nursing and allied health practitioners in malaysia

<p>Abstract</p> <p>Background</p> <p>Despite a recent increase in activities to promote evidence-based practice (EBP), it was unclear how Malaysian hospital practitioners received this new approach in medicine. This study examines their confidence and perceptions on EBP.</p> <p>Findings</p> <p>We conducted cross-sectional surveys using a self-administered questionnaire during two EBP training courses in two Malaysian hospitals in January and June 2007. Our subjects (n = 144) were doctors and nursing and allied health staff (NAH) participating in the EBP courses. Our questionnaire covered three domains: confidence and understanding (six items), attitude (five items) and barriers to practice (four items). We presented simple descriptive statistics, including the sum ratings and the proportions with different responses for each item, and compared different groups using Mann-Whitney U test for scaled ratings and Chi-square test for dichotomous responses.</p> <p>Ninety-two doctors and 52 NAH staff completed the surveys. Overall, doctors expressed slightly higher confidence on EBP compared to NAH staff. Out of a maximum sum rating of 27 over six items, doctors reported an average of 18.3 (SD 3.2) and NAH staff reported an average of 16.0 (SD 3.4), p = 0.002. Doctors were also more positive in their views on EBP. For example, 67.4% of doctors disagreed, but 61% of NAH staff agreed that "the importance of EBP in patient care is exaggerated", and 79.3% of doctors disagreed, but 46.2% of NAH staff agreed that "EBP is too tedious and impractical". Similar responses were observed for other items in the domain.</p> <p>Doctors and NAH staff shared similar concerns on barriers to evidence-based practice. The highest proportions considered poor facilities to access evidence a barrier (76% of doctors and 90% of NAH), followed by poor awareness of evidence (62% of doctors and 70% of NAH) and time constraints (63% of doctors and 68% of NAH), p = 0.09 for the combined rating of four items in the domain.</p> <p>Conclusions</p> <p>The findings of our survey suggest a need for greater efforts in promoting EBP among Malaysian hospital practitioners especially for NAH staff. From the responses based on the barriers to EBP, improving facilities for accessing evidence and promoting more user-friendly resources to address time constraints appear to be the priorities.</p