btn1, the Schizosaccharomyces pombe homologue of the human Batten disease gene CLN3, regulates vacuole homeostasis

International audienc

MAARS: a novel high-content acquisition software for the analysis of mitotic defects in fission yeast

Faithful segregation of chromosomes during cell division relies on multiple processes such as chromosome attachment and correct spindle positioning. Yet mitotic progression is defined by multiple parameters, which need to be quantitatively evaluated. To study the spatiotemporal control of mitotic progression, we developed a high-content analysis (HCA) approach that combines automated fluorescence microscopy with real-time quantitative image analysis and allows the unbiased acquisition of multiparametric data at the single-cell level for hundreds of cells simultaneously. The Mitotic Analysis and Recording System (MAARS) provides automatic and quantitative single-cell analysis of mitotic progression on an open-source platform. It can be used to analyze specific characteristics such as cell shape, cell size, metaphase/anaphase delays, and mitotic abnormalities including spindle mispositioning, spindle elongation defects, and chromosome segregation defects. Using this HCA approach, we were able to visualize rare and unexpected events of error correction during anaphase in wild-type or mutant cells. Our study illustrates that such an expert system of mitotic progression is able to highlight the complexity of the mechanisms required to prevent chromosome loss during cell division

A WORLDWIDE 3D GCP DATABASE INHERITED FROM 20 YEARS OF MASSIVE MULTI-SATELLITE OBSERVATIONS

Abstract. High location accuracy is a major requirement for satellite image users. Target performance is usually achieved thanks to either specific on-board satellite equipment or an auxiliary registration reference dataset. Both methods may be expensive and with certain limitations in terms of performance. The Institut national de l'information géographique et forestière (IGN) and Airbus Defence and Space (ADS) have worked together for almost 20 years, to build reference data for improving image location using multi-satellite observations. The first geometric foundation created has mainly used SPOT 5 High Resolution Stereoscopic (HRS) imagery, ancillary Ground Control Points (GCP) and Very High Resolution (VHR) imagery, providing a homogenous location accuracy of 10m CE90 almost all over the world in 2010.Space Reference Points (SRP) is a new worldwide 3D GCP database, built from a plethoric SPOT 6/7 multi-view archive, largely automatically processed, with cloud-based technologies. SRP aims at providing a systematic and reliable solution for image location (Unmanned Aerial Vehicle, VHR satellite imagery, High Altitudes Pseudo-Satellite…) and similar topics thanks to a high-density point distribution with a 3m CE90 accuracy.This paper describes the principle of SRP generation and presents the first validation results. A SPOT 6/7 smart image selection is performed to keep only relevant images for SRP purpose. The location of these SPOT 6/7 images is refined thanks to a spatiotriangulation on the worldwide geometric foundation, itself improved where needed. Points making up the future SRP database are afterward extracted thanks to classical feature detection algorithms and with respect to the expected density. Different filtering methods are applied to keep the best candidates. The last step of the processing chain is the formatting of the data to the delivery format, including metadata. An example of validation of SRP concept and specification on two tests sites (Spain and China) is then given. As a conclusion, the on-going production is shortly presented

Treatment of Low-flow Vascular Malformations by Ultrasound-guided Sclerotherapy with Polidocanol Foam: 24 Cases and Literature Review

AbstractObjectivesTreatment by sclerotherapy has been suggested as a first-line treatment of low-flow vascular malformations. This study reports our experience in treating low-flow vascular malformations by ultrasound-guided sclerosis with polidocanol foam at the Vascular Medicine Department in Grenoble, France.DesignRetrospective single-centre consecutive series.Materials and methodsBetween January 2006 and December 2009, we analysed the complete records of patients with symptomatic low-flow vascular malformations of venous, lymphatic or complex type (Klippel–Trenaunay syndrome, KTS) treated by ultrasound-guided sclerosis. The therapeutic indication was always validated by the Consultative Committee for vascular malformations of the University Hospital of Grenoble. All vascular malformations were classified according to the Hamburg Classification. The sclerosing agent was polidocanol used as foam.ResultsA total of 24 patients between 7 and 78 years were treated (19 venous malformations, three KTSs and two venous-lymphatic malformations). The concentrations of polidocanol used ranged from 0.25% to 3%. The average number of sessions was 2.3 (1–16). After a median follow-up at 5 months after the last session, 23 out of 24 patients reported a decrease in pain; in nine cases (37.5%), over 50% reduction in size was observed, and in 14 cases (58.3%), a reduction of less than 50% of the original size was obtained. Two minor side effects were reported.ConclusionsTreatment by ultrasound-guided sclerosis using polidocanol foam seems to be well tolerated and can improve the symptoms of low-flow malformations without the risks of more aggressive sclerosing agents, such as ethanol

Platelet FcγRIIA-induced serotonin release exacerbates the severity of Transfusion-Related Acute Lung Injury in mice

Transfusion-related acute lung injury (TRALI) remains a major cause of transfusion-related fatalities. The mechanism of human antibody-mediated TRALI, especially the involvement of the Fcγ receptors, is not clearly established. Contrary to mice, human platelets are unique in their expression of the FcγRIIA/CD32A receptor, suggesting that our understanding of the pathogenesis of antibody-mediated TRALI is partial, as the current murine models incompletely recapitulate the human immunology. We evaluated the role of FcγRIIA/CD32A in TRALI using a humanized mouse model expressing the FcγRIIA/CD32A receptor. When challenged with a recombinant chimeric human immunoglobulin G1/mouse anti–major histocompatibility complex class I monoclonal antibody, these mice exhibited exacerbated alveolar edema and higher mortality compared with wild-type (WT) mice. Unlike in WT mice, monocytes/macrophages in CD32A(+) mice were accessory for TRALI initiation, indicating the decisive contribution of another cell type. Platelet activation was dramatically increased in CD32A(+) animals, resulting in their increased consumption and massive release of their granule contents. Platelet depletion prevented the exacerbation of TRALI in CD32A(+) mice but did not affect TRALI in WT animals. By blocking platelet serotonin uptake with fluoxetine, we showed that the severity of TRALI in CD32A(+) mice resulted from the serotonin released by the activated platelets. Furthermore, inhibition of 5-hydroxytryptamine 2A serotonin receptor with sarpogrelate, before or after the induction of TRALI, abolished the aggravation of lung edema in CD32A(+) mice. Our findings show that platelet FcγRIIA/CD32A activation exacerbates antibody-mediated TRALI and provide a rationale for designing prophylactic and therapeutic strategies targeting the serotonin pathway to attenuate TRALI in patients

Experiencias y comprensiones sobre violencias contra mujeres jóvenes : relatos de mujeres entre 18 y 29 años en la ciudad de Bogotá

La violencia contra mujeres jóvenes es una problemática social que ha incrementado en los últimos años, ya que las mujeres entre los 18 y 29 años son las víctimas más frecuentes de violencia basada en género. Para el año 2013, en Colombia el más alto número de mujeres asesinadas se encontraban entre los 15 y 29 años. Sin embargo, es notable el bajo índice de denuncia de hechos de violencia contra mujeres en esta etapa del ciclo vital. Por tanto, esta investigación indaga sobre experiencias y comprensiones relativas a las violencias contra las mujeres relatadas por mujeres jóvenes entre 18 y 29 años en la ciudad de Bogotá. Para el análisis de los relatos se acude a la perspectiva de género y a categorías como subjetividad femenina, violencia contra mujeres y ámbito público-privado. Se utiliza una metodología con enfoque cualitativo y se diseña un cuestionario con 24 preguntas que fue aplicado a 40 mujeres de todos los estratos socioeconómicos, divididas en dos rangos de edades: entre 18 y 23 años, y entre 24 y 29 años, posteriormente, se realizó un grupo focal con seis mujeres. Se identifica que los tipos de violencia psicológica, sexual y física son las que más afectan a las mujeres jóvenes. Igualmente se hace evidente que, si bien las jóvenes reconocen y son conscientes sobre situaciones y tipos de violencias en lugares públicos y privados en los que se sienten o están efectivamente en riesgo, la persistencia de roles estereotipados de género coexisten con discursos contradictorios de contenido relativamente emancipatorio respecto a condiciones históricas y culturales que configuran sus subjetividades, lo cual incide de manera negativa respecto a prácticas de autoprotección y de denuncia.Violence against young women is a social issue that has increased in the last few years, women between the ages of 18 and 29 are the most frequent victims of gender-based violence. In 2013, the highest number of murdered women in Colombia was between the ages of 15 and 29. However the report rate of these violent crimes against women at this stage of their life cycle is notably low. Therefore, this investigation is about experiences related to violence against women, described by young women between the ages of 18 and 29 in the city of Bogota. For the analysis of the stories, we resort to gender perspective and categories like feminine subjectivity, violence against women, and the public-private sector. We opted for a method with a qualitative focus and designed a questionnaire with 24 questions that was presented to 40 women of all the socioeconomic levels, divided in two age groups: between 18 and 23, and between 24 and 29, afterwards we formed a focal group of six women. We identified that the types of violence that most affects young women are psychological, sexual, and physical. Likewise, it s evident that if young women recognize and are conscious about situations and types of violence in public and private places in which they feel or are in fact at risk, the persistence of stereotypical gender roles coexist with contradictory speeches of relatively emancipatory content regarding historical and cultural conditions that configure their subjectivity, which influences them in a negative way regarding practices of autoprotection and reporting of crimes.Psicólogo (a)Pregrad

The ATP-gated P2X1 ion channel contributes to the severity of antibody-mediated Transfusion-Related Acute Lung Injury in mice

The biological responses that control the development of Transfusion-Related Acute Lung Injury (TRALI), a serious post-transfusion respiratory syndrome, still need to be clarified. Since extracellular nucleotides and their P2 receptors participate in inflammatory processes as well as in cellular responses to stress, we investigated the role of the ATP-gated P2X1 cation channel in antibody-mediated TRALI. The effects of NF449, a selective P2X1 receptor (P2RX1) antagonist, were analyzed in a mouse two-hit model of TRALI. Mice were primed with lipopolysaccharide (LPS) and 24 h later challenged by administrating an anti-MHC I antibody. The selective P2RX1 antagonist NF449 was administrated before the administration of LPS and/or the anti-MHC I antibody. When given before antibody administration, NF449 improved survival while maximal protection was achieved when NF449 was also administrated before the sensitization step. Under this later condition, protein contents in bronchoalveolar lavages were dramatically reduced. Cell depletion experiments indicated that monocytes/macrophages, but not neutrophils, contribute to this effect. In addition, the reduced lung periarteriolar interstitial edemas in NF449-treated mice suggested that P2RX1 from arteriolar smooth muscle cells could represent a target of NF449. Accordingly, inhibition of TRPC6, another cation channel expressed by smooth muscle cells, also reduced TRALI-associated pulmonary interstitial and alveolar edemas. These data strongly suggest that cation channels like P2RX1 or TRPC6 participate to TRALI pathological responses

Aortic thrombus in a patient with myeloproliferative thrombocytosis, successfully treated by pharmaceutical therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Thrombosis in myeloproliferative thrombocytosis occurs usually in the microvessels and medium-sized arteries and veins and only rarely in the aorta. Aortic thrombosis is usually treated with thrombectomy. Reported here is a rare case that was treated pharmacologically.</p> <p>Case presentation</p> <p>A 60-year-old Japanese woman presented with numbness of both lower extremities. Her platelet count was 1787 × 10³/μl. Through bone marrow examination, we diagnosed her condition as myelodysplastic and/or myeloproliferative disorder-unclassifiable. Abdominal ultrasonography and computed tomographic scan revealed aortic thrombosis. Her platelet count was controlled with hydroxyurea and ranimustine. Aspirin and ticlopidine improved the numbness in both lower limbs on the second day. Aortic thrombosis was not observed in a computed tomographic scan on the seventh day.</p> <p>Conclusion</p> <p>For aortic thrombosis, surgical management is usually adopted, but pharmacological management is also an option because of its immediate curative effects.</p