Differential Response of Bacterial Microdiversity to Simulated Global Change

ACKNOWLEDGMENTS UC Irvine and the LRGCE are located on the ancestral homelands of the Indigenous Kizh and Acjachemen nations. We thank Alejandra Rodriguez Verdugo, Katrine Whiteson, Kendra Walters, Cynthia Rodriguez, Kristin Barbour, Alberto Barron Sandoval, Joanna Wang, Joia Kai Capocchi, Pauline Uyen Phuong Nguyen, Khanh Thuy Huynh, and Clara Barnosky for their input on analyses and previous drafts and for laboratory help. This work was supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research grants DE-SC0016410 and DE-SC0020382.Peer reviewedPublisher PD

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

Tyrosine Phosphorylation of Tau by the Src Family Kinases Lck and Fyn

<p>Abstract</p> <p>Background</p> <p>Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.</p> <p>Results</p> <p>In this study we show that Lck is a tau kinase. <it>In vitro</it>, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.</p> <p>Conclusions</p> <p>Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.</p

Positive youth development in swimming: clarification and consensus of key psychosocial assets

The purpose of this study was to gain a more cohesive understanding of the assets considered necessary to develop in young swimmers to ensure both individual and sport specific development. This two stage study involved (a) a content analysis of key papers to develop a list of both psychosocial skills for performance enhancement and assets associated with positive youth development, and (b) in-depth interviews involving ten expert swim coaches, practitioners and youth sport scholars. Five higher order categories containing seventeen individual assets emerged. These results are discussed in relation to both existing models of positive youth development and implications for coaches, practitioners and parents when considering the psychosocial development of young British swimmers

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

Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

Nature-Based Tourism and Neoliberalism: Concealing Contradictions

This paper demonstrates how tourism, including nature based tourism, simultaneously produces and conceals the contradictions of capitalism; this is because it relies on creating attractions, or new sources of accumulation from the very crises it produces. Nature-based tourism is promoted as a ‘win-win’ that can resolve the contradiction between continual economic growth and finite natural resources (Fletcher, 2011; O’Connor, 1988). This is made possible via a process of neoliberalising nature, which cuts the threads that bind ecosystems together, so that the constituent parts can be transformed into new commodities (Büscher et al, 2012; Castree, 2009; Heynen et al, 2007; McCarthy and Prudham, 2004: 275-277; Peck and Theodore, 2007). To draw out these broad arguments, this paper firstly examines the claims around tourism as ‘Green Economy’ – which proponents claim can produce environmentally sustainable economic growth – a benefit also associated with nature-based tourism. I also show that this can be regarded as simply the latest version of an existing debate rather than offering a new intepretation. This is explored further via a comparative analysis of how tourism neoliberalises nature at the scales of the individual animal (elephant trekking in Thailand) and the landscape (by global networks of NGOs operating in Madagascar). In the case of neoliberalisation of nature at the individual animal scale, the notion of bodily fix is also important. It is not just the elephants that are primed for commodity capture, it is the emotional experience of close interactions with elephants which is commodified (Fletcher, 2014: 185; Fletcher and Neves, 2013). Such changes reshape societal relations with nature, but in uneven and incomplete ways. This is underlined by a discussion of the case of the Durban Vision Initiative in Madagascar – which reveals how neoliberalisation was incomplete as a result of its encounter with local level materialities

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

A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial

<p>Abstract</p> <p>Background</p> <p>Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay.</p> <p>Methods and design</p> <p>This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes.</p> <p>Discussion</p> <p>Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00683683">NCT00683683</a></p