User experience with immersive and interactive media = Experiencia de usuario en entornos 3D inmersivos e interactivos

Estudios recientes promueven la integración de estímulos multisensoriales en activos multimedia con el fin de mejorar la experiencia de usuario mediante la estimulación de nuevos sentidos, más allá de la tradicional experiencia audiovisual. Del mismo modo, varios trabajos proponen la introducción de componentes de interacción capaces de complementar con nuevas características, funcionalidades y/o información la experiencia multimedia. Efectos sensoriales basados en el uso de nuevas técnicas de audio, olores, viento, vibraciones y control de la iluminación, han demostrado tener un impacto favorable en la sensación de Presencia, en el disfrute de la experiencia multimedia y en la calidad, relevancia y realismo de la misma percibidos por el usuario. Asimismo, los servicios basados en dos pantallas y la manipulación directa de (elementos en) la escena de video tienen el potencial de mejorar la comprensión, la concentración y la implicación proactiva del usuario en la experiencia multimedia. El deporte se encuentra entre los géneros con mayor potencial para integrar y explotar éstas soluciones tecnológicas. Trabajos previos han demostrado asimismo la viabilidad técnica de integrar éstas tecnologías con los estándares actualmente adoptados a lo largo de toda la cadena de transmisión de televisión. De este modo, los sistemas multimedia enriquecidos con efectos sensoriales, los servicios interactivos multiplataforma y un mayor control del usuario sobre la escena de vídeo emergen como nuevas formas de llevar la multimedia immersiva e interactiva al mercado de consumo de forma no disruptiva. Sin embargo, existen numerosas interrogantes relativas a los efectos sensoriales y/o soluciones interactivas más adecuadas para complementar un contenido audiovisual determinado o a la mejor manera de de integrar y combinar dichos componentes para mejorar la experiencia de usuario de un segmento de audiencia objetivo. Además, la evidencia científica sobre el impacto de factores humanos en la experiencia de usuario con estas nuevas formas de immersión e interacción en el contexto multimedia es aún insuficiente y en ocasiones, contradictoria. Así, el papel de éstos factores en el potencial de adopción de éstas tecnologías ha sido amplia-mente ignorado. La presente tesis analiza el impacto del audio binaural, efectos sensoriales (de iluminación y olfativos), interacción con objetos 3D integrados en la escena de vídeo e interacción con contenido adicional utilizando una segunda pantalla en la experiencia de usuario con contenidos de deporte. La posible influencia de dichos componentes en las variables dependientes se explora tanto a nivel global (efecto promedio) como en función de las características de los usuarios (efectos heterogéneos). Para ello, se ha llevado a cabo un experimento con usuarios orientado a explorar la influencia de éstos componentes immersivos e interactivos en dos grandes dimensiones de la experiencia multimedia: calidad y Presencia. La calidad de la experiencia multimedia se analiza en términos de las posibles variaciones asociadas a la calidad global y a la calidad del contenido, la imagen, el audio, los efectos sensoriales, la interacción con objetos 3D y la interacción con la segunda pantalla. El posible impacto en la Presencia considera dos de las dimensiones definidas por el cuestionario ITC-SOPI: Presencia Espacial (Spatial Presence) e Implicación (Engagement). Por último, los individuos son caracterizados teniendo en cuenta los siguientes atributos afectivos, cognitivos y conductuales: preferencias y hábitos en relación con el contenido, grado de conocimiento de las tecnologías integradas en el sistema, tendencia a involucrarse emocionalmente, tendencia a concentrarse en una actividad bloqueando estímulos externos y los cinco grandes rasgos de la personalidad: extroversión, amabilidad, responsabilidad, inestabilidad emocional y apertura a nuevas experiencias. A nivel global, nuestro estudio revela que los participantes prefieren el audio binaural frente al sistema estéreo y que los efectos sensoriales generan un aumento significativo del nivel de Presencia Espacial percibido por los usuarios. Además, las manipulaciones experimentales realizadas permitieron identificar una gran variedad de efectos heterogéneos. Un resultado interesante es que dichos efectos no se encuentran distribuidos de forma equitativa entre las medidas de calidad y Presencia. Nuestros datos revelan un impacto generalizado del audio binaural en la mayoría de las medidas de calidad y Presencia analizadas. En cambio, la influencia de los efectos sensoriales y de la interacción con la segunda pantalla se concentran en las medidas de Presencia y calidad, respectivamente. La magnitud de los efectos heterogéneos identificados está modulada por las siguientes características personales: preferencias en relación con el contenido, frecuencia con la que el usuario suele ver contenido similar, conocimiento de las tecnologías integradas en el demostrador, sexo, tendencia a involucrarse emocionalmente, tendencia a a concentrarse en una actividad bloqueando estímulos externos y niveles de amabilidad, responsabilidad y apertura a nuevas experiencias. Las características personales consideradas en nuestro experimento explicaron la mayor parte de la variación en las variables dependientes, confirmando así el importante (y frecuentemente ignorado) papel de las diferencias individuales en la experiencia multimedia. Entre las características de los usuarios con un impacto más generalizado se encuentran las preferencias en relación con el contenido, el grado de conocimiento de las tecnologías integradas en el sistema y la tendencia a involucrarse emocionalmente. En particular, los primeros dos factores parecen generar un conflicto de atención hacia el contenido versus las características/elementos técnicos del sistema, respectivamente. Asimismo, la experiencia multimedia de los fans del fútbol parece estar modulada por procesos emociona-les, mientras que para los no-fans predominan los procesos cognitivos, en particular aquellos directamente relacionados con la percepción de calidad. Abstract Recent studies encourage the integration of multi-sensorial stimuli into multimedia assets to enhance the user experience by stimulating other senses beyond sight and hearing. Similarly, the introduction of multi-modal interaction components complementing with new features, functionalities and/or information the multimedia experience is promoted. Sensory effects as odor, wind, vibration and light effects, as well as an enhanced audio quality, have been found to favour media enjoyment and to have a positive influence on the sense of Presence and on the perceived quality, relevance and reality of a multimedia experience. Two-screen services and a direct manipulation of (elements in) the video scene have the potential to enhance user comprehension, engagement and proactive involvement of/in the media experience. Sports is among the genres that could benefit the most from these solutions. Previous works have demonstrated the technical feasibility of implementing and deploying end-to-end solutions integrating these technologies into legacy systems. Thus, sensorially-enhanced media, two-screen services and an increased user control over the displayed scene emerge as means to deliver a new form of immersive and interactive media experiences to the mass market in a non-disruptive manner. However, many questions remain concerning issues as the specific interactive solutions or sensory effects that can better complement a given audiovisual content or the best way in which to integrate and combine them to enhance the user experience of a target audience segment. Furthermore, scientific evidence on the impact of human factors on the user experience with these new forms of immersive and interactive media is still insufficient and sometimes, contradictory. Thus, the role of these factors on the potential adoption of these technologies has been widely ignored. This thesis analyzes the impact of binaural audio, sensory (light and olfactory) effects, interaction with 3D objects integrated into the video scene and interaction with additional content using a second screen on the sports media experience. The potential influence of these components on the dependent variables is explored both at the overall level (average effect) and as a function of users’ characteristics (heterogeneous effects). To these aims, we conducted an experimental study exploring the influence of these immersive and interactive elements on the quality and Presence dimensions of the media experience. Along the quality dimension, we look for possible variations on the quality scores as-signed to the overall media experience and to the media components content, image, audio, sensory effects, interaction with 3D objects and interaction using the tablet device. The potential impact on Presence is analyzed by looking at two of the four dimensions defined by the ITC-SOPI questionnaire, namely Spatial Presence and Engagement. The users’ characteristics considered encompass the following personal affective, cognitive and behavioral attributes: preferences and habits in relation to the content, knowledge of the involved technologies, tendency to get emotionally involved and tendency to get absorbed in an activity and block out external distractors and the big five personality traits extraversion, agreeableness, conscientiousness, neuroticism and openness to experience. At the overall level, we found that participants preferred binaural audio than standard stereo audio and that sensory effects increase significantly the level of Spatial Presence. Several heterogeneous effects were also revealed as a result of our experimental manipulations. Interestingly, these effects were not equally distributed across the quality and Presence measures analyzed. Whereas binaural audio was foud to have an influence on the majority of the quality and Presence measures considered, the effects of sensory effects and of interaction with additional content through the tablet device concentrate mainly on the dimensions of Presence and on quality measures, respectively. The magnitude of these effects was modulated by individual’s characteristics, such as: preferences in relation to the content, frequency of viewing similar content, knowledge of involved technologies, gender, tendency to get emotionally involved, tendency to absorption and levels of agreeableness, conscientiousness and openness to experience. The personal characteristics collected in our experiment explained most of the variation in the dependent variables, confirming the frequently neglected role of individual differences on the media experience. Preferences in relation to the content, knowledge of involved technologies and tendency to get emotionally involved were among the user variables with the most generalized influence. In particular, the former two features seem to present a conflict in the allocation of attentional resources towards the media content versus the technical features of the system, respectively. Additionally, football fans’ experience seems to be modulated by emotional processes whereas for not fans, cognitive processes (and in particular those related to quality judgment) prevail.

Combined external-endonasal approach for complete excision of the lacrimal drainage apparatus

Purpose: The purpose of this study was to describe a new surgical technique for the complete excision of the lacrimal drainage apparatus (LDA) that combines external and endoscopic approaches. Methods: This study involved a noncomparative, retrospective chart review of the clinical and pathological findings of four patients presenting with LDA papillomas who underwent a combined open and endonasal excision of the lacrimal system. Results. Of the four patients, three were male. The mean age at referral was 41 years, and all cases were unilateral. Histopathology revealed two transitional cell papillomas, one squamous cell papilloma, and one combined transitional/squamous papilloma. Epiphora and an external lesion were the main complaints at presentation. Nasolacrimal duct obstruction was present in all four patients. Papilloma virus infection was suggested in two cases and was confirmed in the only patient who had recurrence. CT identified a solid enhancing mass in two cases. The surgical approach in all cases was performed with the patient under general anesthetic supplemented with infiltration of local anesthesia with vasoconstriction. The lacrimal sac was exposed as per an external dacryocystorhinostomy with biopsy collection from the lacrimal sac lumen to confirm the diagnosis prior LDA excision. The superior aspect of the LDA was isolated by using lacrimal probes in each canaliculus to stabilized parallel incisions and careful dissection toward the common canaliculus until they met the medial aspect of the lacrimal sac. The sac was then separated from the periosteum from the medial orbital wall, using sharp dissection. Finally, an endoscopic dissection of the lower end of the nasolacrimal duct released the most inferior aspect of the LDA, allowing the surgeon to pull and excise the complete system from the external wound. Conclusions: Extensive LDA papillomas required complete excision of the drainage system to prevent recurrence and/or malignant transformation. The use of a combined approach through an open excision of the superior part of the LDA in conjunction with the direct manipulation of the nasolacrimal duct guided by the nasal endoscope facilitates the complete excision of the system for extensive benign lesions.

Fabric and greasy wool handle, their importance to the Australian wool industry: a review

Handle-related properties of woollen fabrics have been demonstrated to be major factors affecting consumer buying attitudes. Handle is the combination of both textural and compressional attributes. Compressional handle has demonstrated processing advantages in woven and knitted fabrics. The handle of processing lots can be manipulated using a variety of technologies but direct manipulation of textural greasy wool handle pre-processing is still crude. On-farm, there is documented evidence that including handle assessment in a selection index provides additional improvements in genetic gain. However, the assessment of greasy wool handle is based on a tactile evaluation of the wool staple by sheep and wool classers, and its application is affected by a lack of framework that instructs assessors on a standard method of assessment. Once a reliable and repeatable protocol is developed, further understanding of the effect greasy wool handle has on final garment quality will be possible.

A reflective characterization of occasional user

This work revisits established user classifications and aims to characterise a historically unspecified user category, the Occasional User (OU). Three user categories, novice, intermediate and expert, have dominated the work of user interface (UI) designers, researchers and educators for decades. These categories were created to conceptualise user's needs, strategies and goals around the 80s. Since then, UI paradigm shifts, such as direct manipulation and touch, along with other advances in technology, gave new access to people with little computer knowledge. This fact produced a diversification of the existing user categories not observed in the literature review of traditional classification of users. The findings of this work include a new characterisation of the occasional user, distinguished by user's uncertainty of repetitive use of an interface and little knowledge about its functioning. In addition, the specification of the OU, together with principles and recommendations will help UI community to informatively design for users without requiring a prospective use and previous knowledge of the UI. The OU is an essential type of user to apply user-centred design approach to understand the interaction with technology as universal, accessible and transparent for the user, independently of accumulated experience and technological era that users live in.

Avaliação da sensibilidade ao latex em profissionais de saúde num hospital do norte alentejano

Nos profissionais de saúde a alergia ao látex representa um importante problema de saúde ocupacional. Em contexto hospitalar, a principal fonte de exposição alergénica é a utilização de luvas látex empoadas e a inalação dos bioaerossóis que se formam pela manipulação das mesmas. Mediante consentimento informado, os participantes preencheram um inquérito de resposta fechada e realizaram os testes cutâneos (TC). Aqueles que apresentaram reacção foram encaminhados para a consulta de imunoalergologia e realizaram TC para alimentos, doseamentos séricos de imunoglobulinas (lgE total e específica). Foram incluídos no estudo 44 dos 48 participantes (a=0.1). A sensibilidade ao látex foi posta em evidência em 15 dos elementos da amostra, seis dos quais reagem ao extracto de látex utilizado nos TC. A alergia ao látex foi diagnosticada em duas pessoas. A aplicação de questionários na avaliação sensibilização ocupacional ao látex pode vir a constituir ferramenta válida de auscultação deste problema nas instituições prestadoras de cuidados de saúde. ABSTRACT: Latex allergy is a major occupational disease among health care workers. ln hospitals, the main source of allergen exposure is the powdered latex gloves latex and the inhalation of the aerosols formed by its direct manipulation. By means of informed assent, the participants filled an inquiry and carried out the SPT. Those with cutaneous reaction to the latex extract went to an immunoallergology appointment. SPT for fruit and pollen with cross reactivity to latex allergens where performed, and blood levels of total and specific lgE where determined. The study group included 44 of the 48 participants (a=0.1). Fifteen elements showed latex sensitization and six of them had cutaneous reaction to the latex extract used in the SPT. Latex allergy was found in two health care professionals. Questionnaires may provide a reliability tool to access the sensitization due to natural rubber products and the symptoms more commonly associated with it, in health care facilities.

Heavy tools manipulation by low powered direct-drive five-bar parallel robot

This paper presents a simple and available system for manipulation of heavy tools by low powered manipulator for industrial applications. In the heavy manufacturing industries, sometimes, heavy tools are employed for different types of work. But the application of robots with heavy tools is not possible due to the limited torque limits of actuators. Suspended tool systems (STS) have been proposed to manipulate heavy tools by low powered robot-arm for this purpose. A low powered five-bar direct-drive parallel manipulator is designed and constructed to manipulate heavy tools suspended from a spring balancer. The validity, usefulness, and effectiveness of the suspended tool system are shown by experimental results.

Endosperm balance number manipulation for direct in vivo germplasm introgression to potato from a sexually isolated relative (Solanum commersonii Dun.)

Diploid (2n = 2x = 24) Solanum species with endosperm balance number (EBN) = 1 are sexually isolated from diploid 2EBN species and both tetraploid (2n = 4x = 48, 4EBN) and haploid (2n = 2x = 24, 2EBN) S. tuberosum Group Tuberosum. To sexually overcome these crossing barriers in the diploid species S. commersonii (1EBN), the manipulation of the EBN was accomplished by scaling up and down ploidy levels. Triploid F1 hybrids between an in vitro-doubled clone of S. commersonii (2n = 4x = 48, 2EBN) and diploid 2EBN clones were successfully used in 3x × 4x crosses with S. tuberosum Group Tuberosum, resulting in pentaploid/near pentaploid BC1 progenies. This provided evidence of 2n (3x) egg formation in the triploid female parents. Two selected BC1 pentaploid hybrids were successfully backcrossed both as male and as female parents with S. tuberosum Group Tuberosum. The somatic chromosome number varied greatly among the resulting BC2 progenies, which included hyperaneuploids, but also a number (4.8%) of 48-chromosome plants. The introgression of S. commersonii genomes was confirmed by the presence of S. commersonii-specific randomly amplified polymorphic DNA markers in the BC2 population analyzed. The results clearly demonstrate the feasibility of germplasm introgression from sexually isolated diploid 1EBN species into the 4x (4EBN) gene pool of the cultivated potato using sexual hybridization. Based on the amount and type of genetic variation generated, cumbersomeness, general applicability, costs, and other factors, it would be interesting to compare the approach reported here with other in vitro or in vivo, direct or indirect, approaches previously reported.

Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify a Critical Role for Leading-Edge Calcium Flux.

Calcium signaling has long been associated with key events of immunity, including chemotaxis, phagocytosis, and activation. However, imaging and manipulation of calcium flux in motile immune cells in live animals remain challenging. Using light-sheet microscopy for in vivo calcium imaging in zebrafish, we observe characteristic patterns of calcium flux triggered by distinct events, including phagocytosis of pathogenic bacteria and migration of neutrophils toward inflammatory stimuli. In contrast to findings from ex vivo studies, we observe enriched calcium influx at the leading edge of migrating neutrophils. To directly manipulate calcium dynamics in vivo, we have developed transgenic lines with cell-specific expression of the mammalian TRPV1 channel, enabling ligand-gated, reversible, and spatiotemporal control of calcium influx. We find that controlled calcium influx can function to help define the neutrophil's leading edge. Cell-specific TRPV1 expression may have broad utility for precise control of calcium dynamics in other immune cell types and organisms.

Direct somatic embroygenesis from immature embryos of rosewood (Dalbergia latifolia Roxb.)

Direct regeneration of somatic embryos was obtained from immature zygotic embryos of Dalbergia latifolia. Immature embryos dissected from green pods 90 d after flowering gave the highest frequency of somatic embryo formation. Preculture on high 2,4-D medium for 4 weeks induced direct somatic embryogenesis, which was expressed during the second culture phase in the presence of low 2,4-D along with a high sucrose concentration. Embryos were separated and transferred to the maturation medium containing MS + 0.5-1.0 mg/L BAP, where embryos developed into plantlets. Somatic embryos failed to convert into complete plants without BAP treatment. This method of direct regeneration of somatic embryos without a callus phase has direct application for genetic manipulation studies.

Direct Measurement of Three-Dimensional Forces in Atomic Force Microscopy

Direct measurement of three-dimensional (3-D) forces between an atomic force microscope (AFM) probe and the sample benefits diverse applications of AFM, including force spectroscopy, nanometrology, and manipulation. This paper presents the design and evaluation of a measurement system, wherein the deflection of the AFM probe is obtained at two points to enable direct measurement of all the three components of 3-D tip-sample forces in real time. The optimal locations for measurement of deflection on the probe are derived for a conventional AFM probe. Further, a new optimal geometry is proposed for the probe that enables measurement of 3-D forces with identical sensitivity and nearly identical resolution along all three axes. Subsequently, the designed measurement system and the optimized AFM probe are both fabricated and evaluated. The evaluation demonstrates accurate measurement of tip-sample forces with minimal cross-sensitivities. Finally, the real-time measurement system is employed as part of a feedback control system to regulate the normal component of the interaction force, and to perform force-controlled scribing of a groove on the surface of polymethyl methacrylate.

Increasing the open-circuit voltage of photoprotein-based photoelectrochemical cells by manipulation of the vacuum potential of the electrolytes.

The innately highly efficient light-powered separation of charge that underpins natural photosynthesis can be exploited for applications in photoelectrochemistry by coupling nanoscale protein photoreaction centers to man-made electrodes. Planar photoelectrochemical cells employing purple bacterial reaction centers have been constructed that produce a direct current under continuous illumination and an alternating current in response to discontinuous illumination. The present work explored the basis of the open-circuit voltage (V(OC)) produced by such cells with reaction center/antenna (RC-LH1) proteins as the photovoltaic component. It was established that an up to ~30-fold increase in V(OC) could be achieved by simple manipulation of the electrolyte connecting the protein to the counter electrode, with an approximately linear relationship being observed between the vacuum potential of the electrolyte and the resulting V(OC). We conclude that the V(OC) of such a cell is dependent on the potential difference between the electrolyte and the photo-oxidized bacteriochlorophylls in the reaction center. The steady-state short-circuit current (J(SC)) obtained under continuous illumination also varied with different electrolytes by a factor of ~6-fold. The findings demonstrate a simple way to boost the voltage output of such protein-based cells into the hundreds of millivolts range typical of dye-sensitized and polymer-blend solar cells, while maintaining or improving the J(SC). Possible strategies for further increasing the V(OC) of such protein-based photoelectrochemical cells through protein engineering are discussed.

Control of material transport through pulse shape manipulation-a development toward designer pulses

The variety of laser systems available to industrial laser users is growing and the choice of the correct laser for a material target application is often based on an empirical assessment. Industrial master oscillator power amplifier systems with tuneable temporal pulse shapes have now entered the market, providing enormous pulse parameter flexibility in an already crowded parameter space. In this paper, an approach is developed to design interaction parameters based on observations of material responses. Energy and material transport mechanisms are studied using pulsed digital holography, post process analysis techniques and finite-difference modelling to understand the key response mechanisms for a variety of temporal pulse envelopes incident on a silicon (1/1/1) substrate. The temporal envelope is shown to be the primary control parameter of the source term that determines the subsequent material response and the resulting surface morphology. A double peak energy-bridged temporal pulse shape designed through direct application of holographic imaging data is shown to substantially improve surface quality. © 2014 IEEE.

Sexual selections in the northern fall field cricket, Gryllus pennsylvanicus: a manipulation of the adult sex ratio

The operational sex ratio has long been considered an important constraint on the structure of mating systems. The effects of an experimentally manipulated sex ratio on mating behavior and selection were investigated in a polygynous species, Gryllus pennsylvanicus, where the potential exists for spatial/temporal fluctuations in sex ratio of field populations. Four different sex ratios (males: females, 5:0, 5:2, 5:5, 5:10) were investigated. Observations were conducted in late summer over two field seasons, from 2400 h , to 1000 h EST. Several male characters thought to be associated with male reproduc.tive success were studied: calling duration, searching distance, weight, fighting behavior, courtship frequency, and mating success. Variance in male mating success was used as the indicator for the opportunity for sexual selection. Total selection was estimated as the univariate regression coefficient between relative fitness and the character of interest, while direct selection was estimated as standardized partial regression coefficients generated from a multiple regression of relative fitness on each character. The opportunity for sexual selection was highest at 5:2 and lowest at 5:10. The frequency of fighting behavior was highest at 5:2 and 5:5. Fighting ability (% wins) was determined to be an important correlate of male body weight. Direct selection for increased male body weight was detected at 5:2, while total selection for body weight was seen at 5:5. Selection on male body weight was not detected at 5: 10. Calling duration decreased as sex ratio became more female-biased. Total and direct selection were detected for increased calling at 5:2, only total selection for calling was seen at 5:5, whereas direct selection against calling was detected at 5: 10. Searching distance also decreased as sex ratio became more female-biased, however no form of selection was detected for searching at any of the sex ratios. Data are discussed in terms of sexual selection on male reproductive tactics, the mating system and maintenance of genetic variation in male reproductive behavior.

Manipulation of the ubiquitin-proteasome system by HIV-1 : role of the accessory protein Vpr

Le virus de l’immunodéficience humaine de type 1 (VIH-1), l’agent étiologique du SIDA, est un rétrovirus complexe arborant plusieurs protéines accessoires : Nef, Vif, Vpr, et Vpu. Celles-ci sont impliquées dans la modulation de la réplication virale, dans l’évasion immunitaire et dans la progression de la pathogenèse du SIDA. Dans ce contexte, il a été démontré que la protéine virale R (Vpr) induit un arrêt de cycle cellulaire en phase G2. Le mécanisme par lequel Vpr exerce cette fonction est l’activation, ATR (Ataxia telangiectasia and Rad3 related)-dépendante, du point de contrôle de dommage à l’ADN, mais les facteurs et mécanismes moléculaires directement impliqués dans cette activité demeurent inconnus. Afin d’identifier de nouveaux facteurs cellulaires interagissant avec Vpr, nous avons utilisé une purification d’affinité en tandem (TAP) pour isoler des complexes protéiques natifs contenant Vpr. Nous avons découvert que Vpr s’associait avec CRL4A(VprBP), un complexe cellulaire d’E3 ubiquitine ligase, comprenant les protéines Cullin 4A, DDB1 (DNA damage-binding protein 1) et VprBP (Vpr-binding protein). Nos études ont mis en évidence que le recrutement de la E3 ligase par Vpr était nécessaire mais non suffisant pour l’induction de l’arrêt de cycle cellulaire en G2, suggérant ainsi que des événements additionnels seraient impliqués dans ce processus. À cet égard, nous apportons des preuves directes que Vpr détourne les fonctions de CRL4A(VprBP) pour induire la polyubiquitination de type K48 et la dégradation protéosomale de protéines cellulaires encore inconnues. Ces événements d’ubiquitination induits par Vpr ont été démontrés comme étant nécessaire à l’activation d’ATR. Finalement, nous montrons que Vpr forme des foyers ancrés à la chromatine co-localisant avec VprBP ainsi qu’avec des facteurs impliqués dans la réparation de l’ADN. La formation de ces foyers représente un événement essentiel et précoce dans l’induction de l’arrêt de cycle cellulaire en G2. Enfin, nous démontrons que Vpr est capable de recruter CRL4A(VprBP) au niveau de la chromatine et nous apportons des preuves indiquant que le substrat inconnu ciblé par Vpr est une protéine associée à la chromatine. Globalement, nos résultats révèlent certains des ménanismes par lesquels Vpr induit des perturbations du cycle cellulaire. En outre, cette étude contribue à notre compréhension de la modulation du système ubiquitine-protéasome par le VIH-1 et son implication fonctionnelle dans la manipulation de l’environnement cellulaire de l’hôte.

Direct experimental evidence that early-life farm environment influences regulation of immune responses

Background: In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment. Methods: Piglets were nursed by their mother on a commercial farm, while isolatorreared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. Results: There was more CD4+ and CD4+CD25+ effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4+CD25+Foxp3+ regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to-effector ratio in the farm animals. Consistent with these findings, isolator-reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets. Conclusion: Here, we provide the first direct evidence, derived from intervention, that components of the early-life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.