1,721,049 research outputs found

    USP8, a regulator of endosomal sorting, is involved in mouse acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules

    No full text
    Ubiquitin-specific peptidase 8 (USP8) is a deubiquitinating enzyme that works as a regulator of endosomal sorting and vesicle morphology in cultured cells. Its function in vivo is, however, unknown as USP8 gene deletion leads to embryonic lethality. Previously, we have shown that USP8 is highly expressed in male germ cells. These cells develop a peculiar acidic vesicle that is indispensable for fertilization, the acrosome; USP8 might be involved in vivo in acrosomogenesis. The objective of this study was to test this hypothesis by determining if selective components of the early endosomal machinery interact functionally with USP8 during acrosomogenesis using protein-protein interaction assays and double/triple immunolabeling. Moreover, by exploiting the characteristic of USP8 that exhibits a microtubule interacting and trafficking/transport (MIT) domain, we verified whether USP8 effectively associates with spermatid microtubules by microtubule cosedimentation and binding assays. USP8 was able to interact with spermatid ESCRT-0 (endosomal-sorting complex required for transport-0) and microtubule structures; USP8/ESCRT-0-labeled vesicles, monitored by fluorescence microscopy, were found to contribute to acrosome formation while USP8 can directly link, via its MIT domain, the labeled vesicles/developing acrosome to microtubules, which could favor both acrosome assembly and shaping. VPS54, the vacuolar-sorting protein responsible for early endocytic retrograde transport, was here detected for the first time in male germ cells; VPS54 followed the intracellular route of USP8/ESCRT-0-labeled vesicles during acrosomogenesis. We concluded that in vivo USP8 has a role strongly associated with acrosome biogenesis and that the early endosome pathway is significantly involved in the process, which suggests that the acrosome could be a novel lysosomerelated organelle

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

    Full text link
    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

    Full text link
    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    AMALPI trek: a geocultural trail from Maloja to St. Gotthard to increase the awareness of natural hazard in mountain settings

    Full text link
    The AMALPI Trek takes its name from the A.M.AL.PI.18 Project [1], which is the Italian acronymous for “Moving Alps, and Movements in the Alps”, developed in the framework of the European funded Interreg Italy-Switzerland Cooperation Program V-A 2014-2020. The project aims to encourage an innovative strategy for the promotion of natural and cultural heritage in the Alpine area from Maloja to St. Gotthard (through Val Bregaglia, Valchiavenna, Regione Moesa and Alto Ticino), even by the creation of a cross-border geo-cultural trail connecting sites which have experienced important geomorphological and anthropic changes due to the occurrence of landslides of great social impact. The trail is addressed to a scientific-cultural and educational tourism, to raise the perception of landscape components in the framework of the “total history”, composed by the geo(morpho)logical, bioecological and historic-cultural heritages. Placed in a central position, the AMALPI Center (scheduled to open mid-2023 in Chiavenna), will be a study and research hub on large landslides, reference for school activities and promotion events. In addition, an open access hiking guidebook and map will lead the trekker to discover tools and methods that allow the comprehension of past and ongoing processes, with the help of illustrative panels describing the main patrimonial aspects of the territory, which is rich in historical palaces, archaeological sites, and natural monuments. The AMALPI Trek runs through 10 Alpine valleys and crosses 7 mountain passes, for a total of about 150 km, plus several thematic itineraries that branch out of the main trail. Along the way, 19 large landslides of different age and type are touched. In many segments, the AMALPI trek follows historical trade routes, used in the past for the exchange of silk and soapstone products. There are some links between large landslides and stone resources typical of these mountains. A striking example are the “crotti”, natural caves used as cellars, perfect places for the storage of foods and other goods, and the “trone”, local soapstone caves, both generated by the gravitational accumulation of cyclopean boulders. The petrographic features of soapstone outcropping rock offer then a good workability, but locally they become weakness planes predisposing sliding. Looking at the causes and effects of landslide events, the trekker accrues the perception of human vulnerability to natural hazard, but it is also invited to discover how to prevent, mitigate, and manage hillslope dynamic to develop a sustainable and fulfilling life in mountain areas. [1] Interreg V-A Italy-Switzerland 2014-2020 Cooperation Program, Axis II “Cultural and natural enhancement”). Project ID 594274, “A.M.AL.PI. 2018 – Alpi in Movimento, Movimento nelle Alpi. Piuro1618–2018”. https://progetti.interreg-italiasvizzera.eu/it/b/78/alpiinmovimentomovimentonellealpipiur

    Composition, components and sources of fine aerosol fractions using multielemental EDXRF analysis

    No full text
    The extensive characterization of the elemental composition of some important components and of major sources of participate matter PM10 and PM2.5, sampled in parallel three times per week in Milan, for the whole year 2001 is described. More than 250 PM samples were analysed and major, minor and trace element concentrations were obtained by EDXRF. A strong seasonal modulation of particulate matter and element concentrations and an important contribution to PM from secondary compounds originating from gaseous precursors were observed. The main sources and their contribution were obtained by the application of absolute principal factor analysis to the large data set of elemental concentration. Copyrigh

    The deubiquitinating enzyme UBPy/USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells

    No full text
    The tropomyosin-relatedkinase (Trk) family of receptor tyrosine kinases controls synaptic function, plasticity and sustains differentiation, morphology,and neuronal cell survival. UnderstandingTrk receptors down-regulation and recycling is a crucial step to point out sympathetic and sensory neuron function and survival. PC12 cells derived from pheochromocytoma of the rat adrenal medulla have been widely used as a model system for studies of neuronal differentiation as they respond to nerve growth factor (NGF) with a dramatic change in phenotype and acquire a number of properties characteristic of sympathetic neurons. In this study we demonstrated that in PC12 cells theTrkA receptor interacts with the deubiquitinating enzyme USP8/UBPy in a NGF-dependent manner and that it is deubiquitinated in vivo and in vitro by USP8. USP8overexpressionblockedNGF-inducedneuritesoutgrowthwhilethe overexpressionofthecatalyticallyinactivemutantUSP8/UBPyC748A causedamarkedincreaseofcell differentiation.LocalizationandbiochemicalexperimentshavepointoutthatUSP8andTrkApartially co-localizeinendosomesafterNGFstimulation.FinallywehavestudiedtheroleplayedbyUSP8on TrkAturnover;usingspecific siRNAforUSP8wefoundthatUSP8knockdownincreasesTrkAhalf-life, suggestingthatthedeubiquitinatingactivityofUSP8promotesTrkAdegradation

    Impaired fertility and spermiogenetic disorders with loss of cell adhesion in male mice expressing an interfering Rap1 mutant

    No full text
    The guanosine trisphosphatase Rap1 serves as a critical player in signal transduction, somatic cell proliferation and differentiation, and cell–cell adhesion by acting through distinct mechanisms. During mouse spermiogenesis, Rap1 is activated and forms a signaling complex with its effector, the serine-threonine kinase B-Raf. To investigate the functional role of Rap1 in male germ cell differentiation, we generated transgenic mice expressing an inactive Rap1 mutant selectively in differentiating spermatids. This expression resulted in a derailment of spermiogenesis due to an anomalous release of immature round spermatids from the seminiferous epithelium within the tubule lumen and in low sperm counts. These spermiogenetic disorders correlated with impaired fertility, with the transgenic males being severely subfertile. Because mutant testis exhibited perturbations in ectoplasmic specializations (ESs), a Sertoli–germ cell-specific adherens junction, we searched for expression of vascular endothelial cadherin (VE-cadherin), an adhesion molecule regulated by Rap1, in spermatogenic cells of wild-type and mutant mice. We found that germ cells express VE-cadherin with a timing strictly related to apical ES formation and function; immature, VE-cadherin–positive spermatids were, however, prematurely released in the transgenic testis. In conclusion, interfering with Rap1 function during spermiogenesis leads to reduced fertility by impairment of germ–Sertoli cell contacts; our transgenic mouse provides an in vivo model to study the regulation of ES dynamics
    corecore