Alternative splicing by hnRNP L as a new modulator of hematopoietic cell differentiation, survival and migration

Les modifications post-transcriptionnelles de l’ARN messager (ARNm), comme l’épissage alternatif, jouent un rôle important dans la régulation du développement embryonnaire, de la fonction cellulaire et de l’immunité. De nouvelles évidences révèlent que l’épissage alternatif serait également impliqué dans la régulation de la maturation et de l’activation des cellules du système hématopoïétique. Le facteur hnRNP L a été identifié comme étant le principal régulateur de l’épissage alternatif du gène codant pour le récepteur CD45 in vitro. Le récepteur CD45 est une tyrosine phosphatase exprimée par toutes les cellules du système hématopoïétique qui contrôle le développement et l’activation des lymphocytes T. Dans un premier temps, nous avons étudié la fonction du facteur hnRNP L dans le développement des lymphocytes T et dans l’épissage de l’ARNm de CD45 in vivo en utilisant des souris dont le gène de hnRNP L a été supprimé spécifiquement dans les cellules T. La délétion de hnRNP L dans les thymocytes résulte en une expression aberrante des différents isoformes de CD45 avec une prédominance de l'isoforme CD45RA qui est généralement absent dans le thymus. Une conséquence de la délétion de hnRNP L est une diminution de la cellularité du thymus causée par un blocage partiel du développement des cellules pré-T au stade DN4. Cette réduction du nombre de cellules dans le thymus n’est pas liée à une hausse de la mort cellulaire. Les thymocytes déficients pour hnRNP L démontrent plutôt une prolifération augmentée comparée aux thymocytes sauvages due à une hyper-activation des kinases Lck, Erk1/2 et Akt. De plus, la délétion de hnRNP L dans le thymus cause une perte des cellules T en périphérie. Les résultats des expériences in vitro suggèrent que cette perte est principalement due à un défaut de migration des thymocytes déficients pour hnRNP L du thymus vers la périphérie en réponse aux chimiokines. L’épissage alternatif de CD45 ne peut expliquer ce phénotype mais l’identification de cibles par RNA-Seq a révélé un rôle de hnRNP L dans la régulation de l’épissage alternatif de facteurs impliqués dans la polymérisation de l’actine. Dans un second temps, nous avons étudié le rôle de hnRNP L dans l’hématopoïèse en utilisant des souris dont la délétion de hnRNP L était spécifique aux cellules hématopoïétiques dans les foies fœtaux et la moelle osseuse. L’ablation de hnRNP L réduit le nombre de cellules progénitrices incluant les cellules progénitrices lymphocytaires (CLPs), myéloïdes (CMPs, GMPs) et mégakaryocytes-érythrocytaires (MEPs) et une perte des cellules hématopoïétiques matures. À l’opposé des cellules progénitrices multipotentes (MPPs) qui sont affectées en absence de hnRNP L, la population de cellules souches hématopoïétiques (HSCs) n’est pas réduite et prolifère plus que les cellules contrôles. Cependant, les HSCs n’exprimant pas hnRNP L sont positives pour l'Annexin V et expriment CD95 ce qui suggère une mort cellulaire prononcée. Comme pour les thymocytes, une analyse par RNA-Seq des foies fœtaux a révélé différents gènes cibles de hnRNP L appartenant aux catégories reliées à la mort cellulaire, la réponse aux dommages à l’ADN et à l’adhésion cellulaire qui peuvent tous expliquer le phénotype des cellules n’exprimant pas le gène hnRNP L. Ces résultats suggèrent que hnRNP L et l’épissage alternatif sont essentiels pour maintenir le potentiel de différenciation des cellules souches hématopoïétiques et leur intégrité fonctionnelle. HnRNP L est aussi crucial pour le développement des cellules T par la régulation de l’épissage de CD45 ainsi que pour leur migration.

The effects of group-based psychosocial therapy on conversational fluency and communication handicap

This paper studies whether a combination of group rehabilitation in conjunction with psychosocial therapy enhances conversational fluency and diminishes communication handicap in cochlear implant recipients.

Entertainment education theory and practice in HIV/AIDS communication: a South Africa / United Kingdom comparison

Within development communication, gaps remain in theory and practice: communication innovations are taking place which either do not incorporate theory or fail to challenge the assumptions of development communication and HIV/AIDS theory. This can lead to the implementation of unsuccessful interventions that lack theoretical frameworks or to uninformed practice, making it difficult to replicate. Further, research has demonstrated that Entertainment Education (EE) interventions have a measurable impact on behaviour in areas such as HIV/AIDS prevention. Given the transitions in EE practice and evidence of its impact, EE theory and practice can contribute insight into these challenges. A pilot study investigated these dilemmas within the context of the monitoring and evaluation of development communication. Framing this discussion is the concept of South-North dialogue, using comparative analysis of EE interventions to distil lessons through contrasting experiences in two diverse settings. It holds as a principle that lessons from the experience of EE in the Southern context can inform lessons for the North. Further, comparison of the case studies can generate insights for the broader development communication field. We present four case studies, informed by key informant interviews, of EE interventions in the UK and South Africa. We address how communication is defined in planning, implementation and evaluation, highlighting how it often misses the importance of 'listening'. The case studies show that HIV/AIDS communication, and development communication more broadly, has not internalised ideas of evaluation and listening in communication. Successes in the case studies can be partially attributed to responsiveness and context-specificity rather than following rigid planning templates, such as those found in some development communication literature. This indicates the importance of flexibility and responsiveness to context for both development communication and HIV/AIDS communication.

Consumers' attitudes, trust and willingness to pay for food information

Market failure can be corrected using different regulatory approaches ranging from high to low intervention. Recently, classic regulations have been criticized as costly and economically irrational and thus policy makers are giving more consideration to soft regulatory techniques such as information remedies. However, despite the plethora of food information conveyed by different media there appears to be a lack of studies exploring how consumers evaluate this information and how trust towards publishers influence their choices for food information. In order to fill such a gap, this study investigates questions related to topics which are more relevant to consumers, who should disseminate trustful food information, and how communication should be conveyed and segmented. Primary data were collected both through qualitative (in depth interviews and focus groups) and quantitative research (web and mail surveys). Attitudes, willingness to pay for food information and trust towards public and private sources conveying information through a new food magazine were assessed using both multivariate statistical methods and econometric analysis. The study shows that consumer attitudes towards food information topics can be summarized along three cognitive-affective dimensions: the agro-food system, enjoyment and wellness. Information related to health risks caused by nutritional disorders and food safety issues caused by bacteria and chemical substances is the most important for about 90% of respondents. Food information related to regulations and traditions is also considered important for more than two thirds of respondents, while information about food production and processing techniques, life style and food fads are considered less important by the majority of respondents. Trust towards food information disseminated by public bodies is higher than that observed for private bodies. This behavior directly affects willingness to pay (WTP) for food information provided by public and private publishers when markets are shocked by a food safety incident. WTP for consumer association (€ 1.80) and the European Food Safety Authority (€ 1.30) are higher than WTP for the independent and food industry publishers which cluster around zero euro. Furthermore, trust towards the type of publisher also plays a key role in food information market segmentation together with socio-demographic and economic variables such as gender, age, presence of children and income. These findings invite policy makers to reflect on the possibility of using information remedies conveyed using trusted sources of information to specific segments of consumers as an interesting soft alternative to the classic way of regulating modern food markets.

Molecular and phenotypic characterization of the alternative seasonal growth habit and flowering time in barley (Hordeum vulgare ssp. vulgare L.)

Barley can be classified into three major agronomic types, based on its seasonal growth habit (SGH): spring, winter and alternative. Winter varieties require exposure to vernalization to promote subsequent flowering and are autumn-sown. Spring varieties proceed to flowering in the absence of vernalization and are sown in the spring. The ‘alternative’ (also known as ‘facultative’) SGH is only loosely defined and can be sown in autumn or spring. Here, we investigate the molecular genetic basis of alternative barley. Analysis of the major barley vernalization (VRN-H1, VRN-H2) and photoperiod (PPD-H1, PPD-H2) response genes in a collection of 386 varieties found alternative SGH to be characterized by specific allelic combinations. Spring varieties possessed spring loci at one or both of the vernalization response loci, combined with long-day non-responsive ppd-H1 alleles and wild-type alleles at the short-day photoperiod response locus, PPD-H2. Winter varieties possessed winter alleles at both vernalization loci, in combination with the mutant ppd-H2 allele conferring delayed flowering under short-day photoperiods. In contrast, all alternative varieties investigated possessed a single spring allele (either at VRN-H1 or at VRN-H2) combined with mutant ppd-H2 alleles. This allelic combination is found only in alternative types and is diagnostic for alternative SGH in the collection studied. Analysis of flowering time under controlled environment found alternative varieties flowered later than spring control lines, with the difference most pronounced under short-day photoperiods. This work provides genetic characterization of the alternative SGH phenotype, allowing precise manipulation of SGH and flowering time within breeding programmes, and provides the molecular tools for classification of all three SGH categories within national variety registration processes.

Alternative splicing and genetic diversity: silencers are more frequently modified by SNVs associated with alternative exon/intron borders

With the availability of a large amount of genomic data it is expected that the influence of single nucleotide variations (SNVs) in many biological phenomena will be elucidated. Here, we approached the problem of how SNVs affect alternative splicing. First, we observed that SNVs and exonic splicing regulators (ESRs) independently show a biased distribution in alternative exons. More importantly, SNVs map more frequently in ESRs located in alternative exons than in ESRs located in constitutive exons. By looking at SNVs associated with alternative exon/intron borders (by their common presence in the same cDNA molecule), we observed that a specific type of ESR, the exonic splicing silencers (ESSs), are more frequently modified by SNVs. Our results establish a clear association between genetic diversity and alternative splicing involving ESSs.

Developing a Communication link between Agents and cross Platform IDE

The main objective of this thesis work is to develop communication link between Runrev Revolution (IDE) and JADE (Multi-Agent System) through Socket programming using TCP/IP layer. These two independent platforms are connected using socket programming technique. Socket programming is considered to be newly emerging technology among these two platforms, the work done in this thesis work is considered to be a prototype.A Graphical simulation model is developed by salixphere (Company in Hedemora) to simulate logistic problems using Runrev Revolution (IDE). The simulation software/program is called “BIOSIM”. The logistic problems are complex, and conventional optimization techniques are unlikely very successful. “BIOSIM” can demonstrate the graphical representation of logistic problems depending upon the problem domains. As this simulation model is developed in revolution programming language (Transcript) which is dynamically typed and English-like language, it is quite slow compared to other high level programming languages. The object of this thesis work is to add intelligent behaviour in graphical objects and develop communication link between Runrev revolution (IDE) and JADE (Multi-Agent System) using TCP/IP layers.The test shows the intelligent behaviour in the graphical objects and successful communication between Runrev Revolution (IDE) and JADE (Multi-Agent System).

Processes of feelings in a society with a violent past : A qualitative study of the communication for Societal healing in the Truth Commissions in East Timor, Sri Lanka and Ghana between 2002-2011

The research investigates in what extent and how communication for meeting feelings is provided in Truth Commission work. It examines if and in what way feelings are addressed in the communication officially published by the Truth Commissions in East Timor, Ghana and Sri Lanka, occurring between 2002-2011. The research is also looking at the healing processes in a time perspective to find out if there is a communication for Societal healing to be continued in a longer term. My conclusion is that two cases of three in my research, the TRCs in Ghana and East Timor, have communication clearly directed to meet feelings caused by the war. One of the three cases (East Timor) has a communication with a clear ambition to heal over a longer period, to continue after the existence of the Truth Commission. The research suggests that communication with a clear ambition to reach out widely in the society, a communication directed to meet and process feelings over a longer period, can make Societal healing more effective. It also concludes that, in the future, Societal healing, as a field in conflict resolution, will be more based on representational media than today, provided through web communication.

Interações comunicativas entre uma professora e um aluno com transtorno invasivo do desenvolvimento na escola regular

Inclusion of students with autism in regular education settings is a topic that has not been much explored by the national scientific literature. This matter is complex and, due to the extent of various aspects involved, it is essential to delimitate a focus of investigation. The direction taken by this study was to evaluate the effects of an intervention program in the communicative interactions between a student with autism and his teacher in a regular classroom. Data were collected in an elementary private school, located in the city of Natal, Rio Grande do Norte during the 2010 academic school year. The study included a teacher and a non-vocal, 10-year-old student diagnosed with autism. A quasi-experimental A-B research design was employed. During the intervention program the teacher was trained to use Naturalistic Teaching Strategies and Alternative and Augmentative Communication (AAC) resources to increase the frequency of interactions with the student during three classroom routines (entry time, snack and pedagogical activity). The results indicated qualitative and quantitative changes in the interactions of the dyad after the implementation of the intervention program. The student began to use pictograms to communicate with the teacher in two of the three routines investigated. The frequency of AAC use was also observed in the teacher‟s repertoire, especially when the student failed to understand gestures and words. The teacher positively evaluated the intervention program

Alternative low doses and routes of administering a prostaglandin F2 alpha analogue to induce luteolysis in Nelore cows

The present study was conducted in order to verify the efficacy of lower doses and alternative routes of a prostaglandin F2 alpha analogue, luprostiol (PGF), for the induction of luteolysis and the precipitation of estrus in nonlactating Nelore cows (Bos taurus indicus). A conventional dose (15 mg) of PGF was compared to doses lower than the conventional dose, which ranges from 10 to 50%, that were administered intramuscularly (IM), intravulvosubmucosally (IVSM), or in the Bai-hui acupuncture site located within the lumbosacral area. The cows were administered PGF 8 day after estrus in the presence of a corpus luteum, and randomly assigned to the following groups: G1 (positive control), 15 mg, IM (n = 23); G2, 7.5 mg, IM (n = 23); G3, 3.75 mg, I M (n = 24); G4, 7.5 mg, IVSM (n = 25); G5, 3.75 mg, Bai-hui acupoint (n = 24); and G6, 1.5 mg, Bai-hui acupoint (n = 25). The results indicated that 50% of a conventional dose of PGF (7.5 mg) resulted in a complete luteal regression (plasma progesterone < 1 ng/ml) at Hour 48, and hastened estrus, regardless of whether or not PGF was administered IM or IVSM. Comparatively, 10 or 25% of the conventional dose, even when administered to the Bai-hui acupoint, resulted in an initial reduction in the concentration of progesterone at Hour 24, followed by an increase observed at Hour 48. In conclusion, 25% of a conventional PGF dose administered via the Bai-hui acupoint proved inadequate to induce a complete luteal regression, whereas 50% of a conventional dose administered IM or IVSM was found to be the minimal dose required to induce effectively a complete luteal regression, and to precipitate the onset of estrus in nonlactating Nelore cows.

Alcohol Impairs Predation Risk Response and Communication in Zebrafish

The effects of ethanol exposure on Danio rerio have been studied from the perspectives of developmental biology and behavior. However, little is known about the effects of ethanol on the prey-predator relationship and chemical communication of predation risk. Here, we showed that visual contact with a predator triggers stress axis activation in zebrafish. We also observed a typical stress response in zebrafish receiving water from these conspecifics, indicating that these fish chemically communicate predation risk. Our work is the first to demonstrate how alcohol effects this prey-predator interaction. We showed for the first time that alcohol exposure completely blocks stress axis activation in both fish seeing the predator and in fish that come in indirect contact with a predator by receiving water from these conspecifics. Together with other research results and with the translational relevance of this fish species, our data points to zebrafish as a promising animal model to study human alcoholism. © 2013 Oliveira et al.

Estudo de vocábulos para proposta de instrumento de avaliação do vocabulário de crianças não-oralizadas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Organizational communication and innovation in micro and small companies: a study on the application of the Innovation Radar

This paper is a study on corporate communication and the ability to innovate in small businesses. The guiding question seeks to respond whether organizational communication is able to make progress and / or support innovation in micro and small companies, and the main objective is to analyze the relationship between innovation and organizational communication. It was applied the case study method and document research for interpreting a diagnosis instru- ment called “Innovation Radar” in a small business company located in the countryside of São Paulo state. The diagnosis is made based on assessment dimensions aimed at checking the maturity and the degree of innovation in micro and small companies. By evaluating these di- mensions it was possible to build analytical frameworks and highlight the influence of corporate communication in promoting innovation. The results indicate that every dimension of the “In- novation Radar” can improve their performance by means of corporate communication.

Higher-Order Concurrency: Expressiveness and Decidability Results

Higher-order process calculi are formalisms for concurrency in which processes can be passed around in communications. Higher-order (or process-passing) concurrency is often presented as an alternative paradigm to the first order (or name-passing) concurrency of the pi-calculus for the description of mobile systems. These calculi are inspired by, and formally close to, the lambda-calculus, whose basic computational step ---beta-reduction--- involves term instantiation. The theory of higher-order process calculi is more complex than that of first-order process calculi. This shows up in, for instance, the definition of behavioral equivalences. A long-standing approach to overcome this burden is to define encodings of higher-order processes into a first-order setting, so as to transfer the theory of the first-order paradigm to the higher-order one. While satisfactory in the case of calculi with basic (higher-order) primitives, this indirect approach falls short in the case of higher-order process calculi featuring constructs for phenomena such as, e.g., localities and dynamic system reconfiguration, which are frequent in modern distributed systems. Indeed, for higher-order process calculi involving little more than traditional process communication, encodings into some first-order language are difficult to handle or do not exist. We then observe that foundational studies for higher-order process calculi must be carried out directly on them and exploit their peculiarities. This dissertation contributes to such foundational studies for higher-order process calculi. We concentrate on two closely interwoven issues in process calculi: expressiveness and decidability. Surprisingly, these issues have been little explored in the higher-order setting. Our research is centered around a core calculus for higher-order concurrency in which only the operators strictly necessary to obtain higher-order communication are retained. We develop the basic theory of this core calculus and rely on it to study the expressive power of issues universally accepted as basic in process calculi, namely synchrony, forwarding, and polyadic communication.