Actin turnover is required to prevent axon retraction driven by endogenous actomyosin contractility

Growth cone motility and guidance depend on the dynamic reorganization of filamentous actin (F-actin). In the growth cone, F-actin undergoes turnover, which is the exchange of actin subunits from existing filaments. However, the function of F-actin turnover is not clear. We used jasplakinolide (jasp), a cell-permeable macrocyclic peptide that inhibits F-actin turnover, to study the role of F-actin turnover in axon extension. Treatment with jasp caused axon retraction, demonstrating that axon extension requires F-actin turnover. The retraction of axons in response to the inhibition of F-actin turnover was dependent on myosin activity and regulated by RhoA and myosin light chain kinase. Significantly, the endogenous myosin-based contractility was sufficient to cause axon retraction, because jasp did not alter myosin activity. Based on these observations, we asked whether guidance cues that cause axon retraction (ephrin-A2) inhibit F-actin turnover. Axon retraction in response to ephrin-A2 correlated with decreased F-actin turnover and required RhoA activity. These observations demonstrate that axon extension depends on an interaction between endogenous myosin-driven contractility and F-actin turnover, and that guidance cues that cause axon retraction inhibit F-actin turnover

Influence of gender and age on cognitive inhibition in late-onset depression: a case-control study

ObjectiveTo compare cognitive inhibition performance between people with early-onset (EOD) or late-onset depression (LOD) and controls, and between women and men with LOD.MethodsOn the basis of a case-control design, global executive performance (Frontal Assessment Battery); verbal (Hayling), attention (Stroop), and motor (Go/No-Go) components of cognitive inhibition; mental shifting (Trail Making Test parts A and B); and updating in working memory (Wechsler Adult Intelligence Scale) were assessed in 40 participants (10 depressed women with LOD (i.e., 60years old), 10 depressed women with EOD (i.e., <60years old), 10 healthy women and 10 depressed men with LOD (i.e., 60years old)). ResultsOlder depressed women, irrespective of age of depression onset, had greater cognitive inhibition impairments (attention and verbal component) compared with healthy women. LOD was significantly associated with the attention component of cognitive inhibition impairment, unlike EOD (p=0.026). No executive differences were found regarding age of first-onset depression in older depressed women, and between women and men with LOD. ConclusionCognitive inhibition impairment, and more specifically its attention component, was the main characteristic of depression in the studied sample of older adults, independently of gender and age of depression onset. It is essential to perform similar studies in both genders in view of future tailor-made therapeutic modalities. Copyright (c) 2013 John Wiley & Sons, Ltd

Recent developments on micrometric fission chambers for high neutron fluxes

ISBN 9781424452071International audiencewith the development of innovative nuclear systems and new generation neutron sources, the nuclear instrumentation should be adapted. Since several years, we developed microscopic fission chambers to study the transmutation of minor actinides in high thermal-neutron fluxes. The recent developments done to fulfill the drastic conditions of irradiations are described in this paper together with the feedback from the measurements. Two installations were used: the HFR of the ILL for its highest thermal neutron flux of the world and the MEGAPIE target which was the first 1 MW liquid Pb-Bi spallation target in the world

Variability in spine radiosurgery treatment planning - results of an international multi-institutional study

Background: The aim of this study was to quantify the variability in spinal radiosurgery (SRS) planning practices between five international institutions, all member of the Elekta Spine Radiosurgery Research Consortium. Methods: Four institutions provided one representative patient case each consisting of the medical history, CT and MR imaging. A step-wise planning approach was used where, after each planning step a consensus was generated that formed the basis for the next planning step. This allowed independent analysis of all planning steps of CT-MR image registration, GTV definition, CTV definition, PTV definition and SRS treatment planning. In addition, each institution generated one additional SRS plan for each case based on intra-institutional image registration and contouring, independent of consensus results. Results: Averaged over the four cases, image registration variability ranged between translational 1.1 mm and 2.4 mm and rotational 1.1° and 2.0° in all three directions. GTV delineation variability was 1.5 mm in axial and 1.6 mm in longitudinal direction averaged for the four cases. CTV delineation variability was 0.8 mm in axial and 1.2 mm in longitudinal direction. CTV-to-PTV margins ranged between 0 mm and 2 mm according to institutional protocol. Delineation variability was 1 mm in axial directions for the spinal cord. Average PTV coverage for a single fraction18 Gy prescription was 87 ± 5 %; Dmin to the PTV was 7.5 ± 1.8 Gy averaged over all cases and institutions. Average Dmax to the PRV_SC (spinal cord + 1 mm) was 10.5 ± 1.6 Gy and the average Paddick conformity index was 0.69 ± 0.06. Conclusions: Results of this study reflect the variability in current practice of spine radiosurgery in large and highly experienced academic centers. Despite close methodical agreement in the daily workflow, clinically significant variability in all steps of the treatment planning process was demonstrated. This may translate into differences in patient clinical outcome and highlights the need for consensus and established delineation and planning criteria

Opening the black box of outer space: the case of Jason-3

If you look at a rendering of planet Earth from a bird's eye view, you will see satellites orbiting the planet like electrons, each one a testament to humanity's expansion beyond Earth's atmosphere. It begs the question: what is this new humanized landscape? The dominant voice that has attempted to answer this question is the realist one, which has led the charge of academic inquiry into outer space since the fateful launch of the Sputnik in 1957. Though enlightening in some respects, the realist perspective oftentimes obscures the heterogeneous complexity of the actors, actions, limits and possibilities that have constructed this very humanized outer space. This paper looks at the humanization of outer space through the lens of JASON-3, an internationally collaborative satellite designed primarily to measure the topography of the Earth's oceans. A vast number of actors collaborated to enact the network that created JASON-3, including bureaucratic agencies, academics, private contractors, political bodies, other satellites, the sun and even gravity. This paper will focus on these actors and the work that they did to form the network, showing a glimpse of the entangled connections that eventually produced JASON-3. Through telling this story, I argue: (1) outer space is more complex than state-level relations and (2) critical geography -- with its insight into relational spaces and deconstructing power structures -- has a unique place to fill in outer space literature

Spallation Neutron Production by 0.8, 1.2 and 1.6 GeV Protons on various Targets

Spallation neutron production in proton induced reactions on Al, Fe, Zr, W, Pb and Th targets at 1.2 GeV and on Fe and Pb at 0.8, and 1.6 GeV measured at the SATURNE accelerator in Saclay is reported. The experimental double-differential cross-sections are compared with calculations performed with different intra-nuclear cascade models implemented in high energy transport codes. The broad angular coverage also allowed the determination of average neutron multiplicities above 2 MeV. Deficiencies in some of the models commonly used for applications are pointed out.Comment: 20 pages, 32 figures, revised version, accepted fpr publication in Phys. Rev.

SPIRAL II Project (electron option) - Preliminary Design Study

This document presents a Preliminary Design Study (PDS) of the electron option of the SPIRAL II project

Exploring the effectiveness of the output-based aid voucher program to increase uptake of gender-based violence recovery services in Kenya: a qualitative evaluation

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Few studies in Africa have explored in detail the ability of output-based aid (OBA) voucher programs to increase access to gender-based violence recovery (GBVR) services. Methods: A qualitative study was conducted in 2010 and involved: (i) in-depth interviews (IDIs) with health managers, service providers, voucher management agency (VMA) managers and (ii) focus group discussions (FGDs) with voucher users, voucher non-users, voucher distributors and opinion leaders drawn from five program sites in Kenya. Results: The findings showed promising prospects for the uptake of OBA GBVR services among target population. However, a number of factors affect the uptake of the services. These include lack of general awareness of the GBVR services vouchers, lack of understanding of the benefit package, immediate financial needs of survivors, as well as stigma and cultural beliefs that undermine reporting of cases or seeking essential medical services. Moreover, accreditation of only hospitals to offer GBVR services undermines access to the services in rural areas. Poor responsiveness from law enforcement agencies and fear of reprisal from perpetrators also undermine treatment options and access to medical services. Low provider knowledge on GBVR services and lack of supplies also affect effective provision and management of GBVR services. Conclusions: The above findings suggest that there is a need to build the capacity of health care providers and police officers, strengthen the community strategy component of the OBA program to promote the GBVR services voucher, and conduct widespread community education programs aimed at prevention, ensuring survivors know how and where to access services and addressing stigma and cultural barriers.The Bill and Melinda Gates Foundatio

Families of superintegrable Hamiltonians constructed from exceptional polynomials

We introduce a family of exactly-solvable two-dimensional Hamiltonians whose wave functions are given in terms of Laguerre and exceptional Jacobi polynomials. The Hamiltonians contain purely quantum terms which vanish in the classical limit leaving only a previously known family of superintegrable systems. Additional, higher-order integrals of motion are constructed from ladder operators for the considered orthogonal polynomials proving the quantum system to be superintegrable

Angioimmunoblastic T-cell lymphoma and Kaposi sarcoma: A fortuitous collision?

Follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic-type (AITL), one of the most prevalent T-cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein-Barr virus-positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. Three male patients aged 49-76 years, HIV-negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10 <sup>+</sup> (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31 <sup>+</sup> and/or CD34 <sup>+</sup> , HHV8+ spindle cells. High-throughput sequencing showed AITL-associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open