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

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

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Functionalized Congeners of P2Y 1 Receptor Antagonists: 2-Alkynyl ( N )-Methanocarba 2′-Deoxyadenosine 3′,5′-Bisphosphate Analogues and Conjugation to a Polyamidoamine (PAMAM) Dendrimer Carrier

The P2Y1 receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3′,5′-bisphosphate antagonists of the P2Y1 receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N6-methyl-(N)-methanocarba-2′-deoxyadenosine-3′,5′-bisphosphates containing extended 2-alkynyl chains was designed and binding affinity at the human (h) P2Y1 receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (Ki 23 nM) and extended amine congener 15 (Ki 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended ε-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y1 receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y1 receptor modeling and ligand docking. Attempted P2Y1 antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM dendrimer to produce a multivalent conjugate exhibiting a desired biological effect, i.e. antithrombotic action