An ESCRT module is required for neuron pruning

Neural circuits are refined by both functional and structural changes. Structural remodeling by large-scale pruning occurs where relatively long neuronal branches are cut away from their parent neuron and removed by local degeneration. Until now, the molecular mechanisms executing such branch severing events have remained poorly understood. Here, we reveal a role for the Endosomal Sorting Complex Required for Transport (ESCRT) machinery during neuronal remodeling. Our data show that a specific ESCRT pruning module, including members of the ESCRT-I and ESCRT-III complexes, but not ESCRT-0 or ESCRT-II, are required for the neurite scission event during pruning. Furthermore we show that this ESCRT module requires a direct, in vivo, interaction between Shrub/CHMP4B and the accessory protein Myopic/HD-PTP

Techniques for an image space occlusion culling engine

In this work we present several techniques applied to implement an Image Space Software Occlusion Culling Engine to increase the speed of rendering general dynamic scenes with high depth complexity. This conservative culling method is based on a tiled Occlusion Map that is updated only when needed, deferring and even avoiding the expensive per pixel rasterization process. We show how the tiles become a useful way to increase the speed of visibility tests. Finally we describe how different parts of the engine were parallelized using OpenMP directives and SIMD instructions.Eje: Workshop Computación gráfica, imágenes y visualización (WCGIV)Red de Universidades con Carreras en Informática (RedUNCI

Detección de indicadores de seguridad de pacientes (PSI-Patient Safety Indicators) en un estudio multi-céntrico de carga de enfermedad y resultados de la atención

La calidad/ seguridad de la atención médica se puede estimar analizando los registros de egresos de hospitales generales de agudos (HGA). Se obtuvieron indicadores de seguridad de los pacientes (PSI), que detectan eventos adversos en la atención médica (EAs). En un estudio multi-céntrico se adecuó un método para obtener los PSI en la Argentina basado en codificaciones diagnosticas primarias (Dx1) y secundarias (Dx2) y codificaciones de procedimientos (Px1 y Px 2). La estandarización de los diagnósticos y de los procedimientos permitió realizar la plataforma del estudio Utilización de Servicios, Costos y Resultados en Argentina (USCR-A). Se obtienen los EAs definidos por los PSI #3, #7 y #13. El objetivo de este trabajo es presentar los resultados cuali y cuantitativos de una aplicación de los PSI en el contexto del trabajo y registro del estudio multi-céntrico en Utilización de Servicios, Costos y Resultados en Argentina (USCR-A).Sociedad Argentina de Informática e Investigación Operativ

Very early Guillain-Barré syndrome: A clinical-electrophysiological and ultrasonographic study

Objectives: Using recent optimized electrodiagnostic criteria sets, we primarily aimed at verifying the accuracy of the initial electrophysiological test in very early Guillain-Barré syndrome (VEGBS), ?4 days of onset, compared with the results of serial electrophysiology. Our secondary objective was to correlate early electrophysiological results with sonographic nerve changes. Methods: This is a retrospective study based on consecutive VEGBS patients admitted to the hospital. Each patient had serial nerve conduction studies (NCS) in at least 4 nerves. Initial NCS were done within 4 days after onset, and serial ones from the second week onwards. Electrophysiological recordings of each case were re-evaluated, GBS subtype being established accordingly. Nerve ultrasonography was almost always performed within 2 weeks after onset. Results: Fifteen adult VEGBS patients were identified with a mean age of 57.8 years. At first NCS, VEGBS sub-typing was only possible in 3 (20%) cases that showed an axonal pattern, the remaining patterns being mixed (combining axonal and demyelinating features) in 6 (40%), equivocal in 5 (33.3%), and normal in 1 (6.7%). Upon serial NCS, 7 (46.7%) cases were categorized as acute demyelinating polyneuropathy, 7 (46.7%) as axonal GBS, and 1 (6.6%) as unclassified syndrome. Antiganglioside reactivity was detected in 5 out of the 7 axonal cases. Nerve US showed that lesions mainly involved the ventral rami of scanned cervical nerves. Conclusions: Serial electrophysiological evaluation is necessary for accurate VEGBS subtype classification. Ultrasonography helps delineate the topography of nerve changes. Significance: We provide new VEGBS pathophysiological insights into nerve conduction alterations within the first 4 days of the clinical course.Acknowledgement: This paper was supported by IDIVAL (ID APG/11) and CIBERNED. The authors are most grateful to Mrs Marta de la Fuente for secretarial assistance

Implementing software occlusion culling for real-time applications

The visualization of complex virtual scenes can be significantly accelerated by applying Occlusion Culling. In this work we introduce a variant of the Hierarchical Occlusion Map method to be used in Real-Time applications. To avoid using real objects geometry we generate specialized conservative Occluders based on Axis Aligned Bounding Boxes which are converted into coplanar quads and then rasterized in CPU using a downscaled Depth Buffer. We implement this method in a 3D scene using a software occlusion map rasterizer module specifically optimized to rasterize Occluder quads into a Depth Buffer. We demonstrate that this approach effectively increases the number of occluded objects without generating significant runtime overhead.Eje: Workshop Computación gráfica, imágenes y visualización (WCGIV)Red de Universidades con Carreras en Informática (RedUNCI

Techniques for an image space occlusion culling engine

In this work we present several techniques applied to implement an Image Space Software Occlusion Culling Engine to increase the speed of rendering general dynamic scenes with high depth complexity. This conservative culling method is based on a tiled Occlusion Map that is updated only when needed, deferring and even avoiding the expensive per pixel rasterization process. We show how the tiles become a useful way to increase the speed of visibility tests. Finally we describe how different parts of the engine were parallelized using OpenMP directives and SIMD instructions.Eje: Workshop Computación gráfica, imágenes y visualización (WCGIV)Red de Universidades con Carreras en Informática (RedUNCI

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Targeting of Sna3p to the Endosomal Pathway Depends on Its Interaction with Rsp5p and Multivesicular Body Sorting on Its Ubiquitylation

Rsp5p is an ubiquitin (Ub)-protein ligase of the Nedd4 family that carries WW domains involved in interaction with PPXY-containing proteins. It plays a key role at several stages of intracellular trafficking, such as Ub-mediated internalization of endocytic cargoes and Ub-mediated sorting of membrane proteins to internal vesicles of multivesicular bodies (MVBs), a process that is crucial for their subsequent targeting to the vacuolar lumen. Sna3p is a membrane protein previously described as an Ub-independent MVB cargo, but proteomic studies have since shown it to be an ubiquitylated protein. Sna3p carries a PPXY motif. We observed that this motif mediates its interaction with Rsp5p WW domains. Mutation of either the Sna3p PPXY motif or the Rsp5p WW3 domain or reduction in the amounts of Rsp5 results in the mistargeting of Sna3p to multiple mobile vesicles and prevents its sorting to the endosomal pathway. This sorting defect appears to occur prior to the defect displayed in rsp5 mutants by other MVB cargoes, which are correctly sorted to the endosomal pathway but missorted to the vacuolar membrane instead of the vacuolar lumen. Sna3p is polyubiquitylated on one target lysine, and a mutant Sna3p lacking its target lysine displays defective MVB sorting. Sna3p undergoes Rsp5-dependent polyubiquitylation, with K63-linked Ub chains