Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin

Neocortical neurons have highly branched dendritic trees that are essential for their function. Indeed, defects in dendritic arborization are associated with human neurodevelopmental disorders. The molecular mechanisms regulating dendritic arbor complexity, however, are still poorly understood. Here, we uncover the molecular basis for the regulation of dendritic branching during cortical development. We show that during development, dendritic branching requires post-mitotic suppression of the RhoGTPase Cdc42. By generating genetically modified mice, we demonstrate that this is catalyzed in vivo by the novel Cdc42-GAP NOMA-GAP. Loss of NOMA-GAP leads to decreased neocortical volume, associated specifically with profound oversimplification of cortical dendritic arborization and hyperactivation of Cdc42. Remarkably, dendritic complexity and cortical thickness can be partially restored by genetic reduction of post-mitotic Cdc42 levels. Furthermore, we identify the actin regulator cofilin as a key regulator of dendritic complexity in vivo. Cofilin activation during late cortical development depends on NOMA-GAP expression and subsequent inhibition of Cdc42. Strikingly, in utero expression of active cofilin is sufficient to restore postnatal dendritic complexity in NOMA-GAP-deficient animals. Our findings define a novel cell-intrinsic mechanism to regulate dendritic branching and thus neuronal complexity in the cerebral cortex

Deuterium and impurity contamination of divertor tiles and collector probes of asdex-upgrade

The uptake and release of hydrogen isotopes at the plasma-facing components in magnetic, confinement fusion devices affects the working gas recycling, the plasma behaviour and the tritium inventory [1]. This attracts considerable interest in the investigation of hydrogen trapping during plasma exposure. The most intensive plasma material interaction occurs on limiters and divertor plates. Post-mortem analysis of such components gives information on the total amount of hydrogen isotopes retained in the material after plasma exposure. Recent investigations of divertor tiles of ASDEX-UPGRADE have shown that the dominant trapped deuterium amount is contained in the deposited material at the surface [2]. This surface contamination consists mainly of carbon, boron and the hydrogenic isotopes. Movable collector probes have been applied to investigate the hydrogen trapping and impurity deposition under specific plasma conditions. In the present paper results on the impurity and deuterium contamination at the surface of collector samples are presented and compared with corresponding results from the divertor tiles. The collector samples were exposed to the scrape-off plasma of the main chamber (SOL-probe) and to the divertor plasma (DIV-probe

Counting valence quarks at RHIC and LHC

We consider the Nuclear Modification Ratios in heavy ion collisions, R_CP and R_AA, in the region of intermediate transverse momentum, and study the dependency upon the constituent quark composition of the observed hadron. Adopting a two component recombination/fragmentation model, validated by experimental information from STAR and PHENIX, we show that a clear distinction is predicted for the f0(980) between the assumptions of $s\bar s$ or diquark-antidiquark content.Comment: 14 pages, 11 eps figures, added figures and minor corrections, to appear in Phys. Lett.

Fermionic R-Operator and Algebraic Structure of 1D Hubbard Model: Its application to quantum transfer matrix

The algebraic structure of the 1D Hubbard model is studied by means of the fermionic R-operator approach. This approach treats the fermion models directly in the framework of the quantum inverse scattering method. Compared with the graded approach, this approach has several advantages. First, the global properties of the Hamiltonian are naturally reflected in the algebraic properties of the fermionic R-operator. We want to note that this operator is a local operator acting on fermion Fock spaces. In particular, SO(4) symmetry and the invariance under the partial particle hole transformation are discussed. Second, we can construct a genuinely fermionic quantum transfer transfer matrix (QTM) in terms of the fermionic R-operator. Using the algebraic Bethe Ansatz for the Hubbard model, we diagonalize the fermionic QTM and discuss its properties.Comment: 22 pages, no figure

Tenacidad a la fractura de compuestos cermets 3Al2O3*2SiO2/Ag manufacturados por molienda de alta energía

La fabricación de materiales compuestos de matriz cerámica reforzados con partículas metálicas han propiciado la formación de nuevos materiales conocidos como compuestos CERMETS, materiales que debido a sus elementos precursores poseen propiedades distintas a las de los materiales convencionales. En este trabajo se establece la ruta de fabricación de materiales compuestos cermets base 3Al2O3*2SiO2 reforzados con partículas metálicas de Ag a partir de la formación de la composición química en peso de polvos de 3Al2O3*2SiO2 / 1% Ag en busca de un aumento en la tenacidad a la fractura con respecto al cerámico base. La composición química de polvos es sometida a un proceso de mezcla molienda de alta energía en seco en un molino tipo planetario por 2 horas a 200 rpm. Los polvos posteriormente son conformados en muestras cilíndricas de 20 mm de diámetro y 3 mm de espesor mediante la aplicación de carga uniaxial en frío de 200 MPa. Las muestras son sinterizadas a 1500°C y 1600°C por una y dos horas en un horno de resistencia eléctrica en atmósfera controlada de gas nitrógeno. Los compuestos fabricados son analizados microestructuralmente por microscopia óptica y electrónica de barrido. Se determina la densidad y las propiedades mecánicas de dureza y tenacidad a la fractura, las dos últimas por el método de indentación. Los resultados muestran la viabilidad de fabricación de materiales compuestos cermets así como los cambios en la densidad, la dureza y la tenacidad a la fractura, con respecto al cerámico 3Al2O3*2SiO2 sin refuerzo metálico

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells

Vascular Endothelial Protein Tyrosine Phosphatase (VE-PTP) is an endothelial-specific phosphatase that stabilizes Vascular Endothelial (VE)-cadherin junctions. Although studies have focused on the role of VE-PTP in dephosphorylating VE-cadherin in the activated endothelium, little is known of VE-PTP’s role in the quiescent endothelial monolayer. Here we used the photo-convertible fluorescent protein, VE-cadherin-Dendra2, to monitor VE-cadherin dynamics at AJs in confluent endothelial monolayers. We discovered that VE-PTP stabilizes VE-cadherin junctions by reducing the rate of VE-cadherin internalization independently of its phosphatase activity. VE-PTP serves as an adaptor protein which through binding and inhibiting the RhoGEF, GEF-H1 modulates RhoA activity and tension across VE-cadherin junctions. Overexpression of VE-PTP cytosolic domain mutant interacting with GEF-H1 in VE-PTP-depleted endothelial cells reduced GEF-H1 activity and restored VE-cadherin dynamics at AJs. Thus, VE-PTP stabilizes VE-cadherin junctions and restricts endothelial permeability through inhibiting GEF-H1, and thereby limits RhoA signaling at AJs and reduces the VE-cadherin internalization rate

Distinct mPTP activation mechanisms in ischaemia-reperfusion: contributions of Ca2+, ROS, pH, and inorganic polyphosphate

Aims: The mitochondrial permeability transition pore (mPTP) plays a central role for tissue damage and cell death during ischaemia–reperfusion (I/R). We investigated the contribution of mitochondrial inorganic polyphosphate (polyP), a potent activator of Ca2+-induced mPTP opening, towards mPTP activation and cardiac cell death in I/R. Methods and results: A significant increase in mitochondrial free calcium concentration ([Ca2+]m), reactive oxygen species (ROS) generation, mitochondrial membrane potential depolarization (ΔΨm), and mPTP activity, but no cell death, was observed after 20 min of ischaemia. The [Ca2+]m increase during ischaemia was partially prevented by the mitochondrial Ca2+ uniporter (MCU) inhibitor Ru360 and completely abolished by the combination of Ru360 and the ryanodine receptor type 1 blocker dantrolene, suggesting two complimentary Ca2+ uptake mechanisms. In the absence of Ru360 and dantrolene, mPTP closing by polyP depletion or CSA decreased mitochondrial Ca2+ uptake, suggesting that during ischaemia Ca2+ can enter mitochondria through mPTP. During reperfusion, a burst of endogenous polyP production coincided with a decrease in [Ca2+]m, a decline in superoxide generation, and an acceleration of hydrogen peroxide (H2O2) production. An increase in H2O2 correlated with restoration of mitochondrial pHm and an increase in cell death. mPTP opening and cell death on reperfusion were prevented by antioxidants Trolox and MnTBAP [Mn (III) tetrakis (4-benzoic acid) porphyrin chloride]. Enzymatic polyP depletion did not affect mPTP opening during reperfusion, but increased ROS generation and cell death, suggesting that polyP plays a protective role in cellular stress response. Conclusions: Transient Ca2+/polyP-mediated mPTP opening during ischaemia may serve to protect cells against cytosolic Ca2+ overload, whereas ROS/pH-mediated sustained mPTP opening on reperfusion induces cell death