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The underlying disease mechanisms of neurodevelopmental disorders (NDDs) have been investigated in this thesis by applying a multilevel phenotyping approach of mouse models. We generated and characterized several valid mouse models for NDDs, namely Stxbp1+/- mice (on four different genetic backgrounds), Stxbp1+/-Snap25+/- mice, Stxbp1+/+Snap25+/- mice and Dpp10 transgenic mice. The underlying disease mechanisms have been investigated on the cellular, network, system and behavioural level. In Chapter 2, we studied how heterozygous mutations in the STXBP1 gene leads to early infantile epileptic encephalopathy. We showed that decreased protein stability, STXBP1 haploinsufficiency and imbalanced excitation in the cortex explain STXBP1-encephalopathy and that Stxbp1+/- mice represent a valid mouse model with construct, face and predictive validity. In Chapter 3, we investigated the phenotypic diversity of SNAREopathies by studying gene interactions between two SNARE genes, namely Stxbp1 and Snap25. This study demonstrated that haploinsufficiency at two interacting loci at cellular and/or network level can explain deviation and severity of the epileptic phenotype in double Stxbp1/Snap25 mice and that atypical cortical development of GABA-ergic inhibition can contribute to the cognitive and behavioural impairments. Findings from this chapter provide a proof of concept for how modifying genes in the patient genome may enhance phenotypic diversity in human patient population. In Chapter 4, we studied the link between aberrant behavioural phenotypes observed in Dpp10null mice generated using insertional mutagenesis, and the functional consequences of gene inactivation on the cellular level. We showed that lack of Dpp10 expression affects inhibitory neuron branching and synapse number, neuronal excitability and leads to acoustic hypersensitivity, hyperactivity and impaired working memory in mice. Taken together, the data acquired in this thesis provide novel insights into the neurobiological basis of NDDs and their phenotypic diversity using transgenic mouse models.

Listeria monocytogenes is a significant concern for the produce industry; however, there is limited information to support the practical decision-making to mitigate this risk. This study investigated the prevalence of Listeria spp. and L. monocytogenes in seven produce handling and processing (PHP) facilities in the Pacific Northwest. PHP facilities were defined as facilities that receive raw agricultural commodities and further handle, pack, wash, or process prior to distribution into the retail sector. Environmental swabs (n = 50/facility) were collected in high-risk areas (e.g., near raw product entry points) from seven PHP facilities over two visits. Listeria spp. were isolated using modified ISO 11290-1 method and speciated with Microgen® Listeria-ID. Listeria spp., including L. monocytogenes, were found in 5/7 PHP. Prevalence of Listeria spp. ranged from 2% to 26% in these five facilities. Drains, entry areas, and portable equipment consistently tested positive for Listeria spp. during active production. Two additional sampling rounds (n = 50/round) were conducted in the highest prevalence facility (Facility #1). Overall, Listeria spp. were detected in 44/150 (29.3%) swabs collected from Facility #1. This study demonstrated the high prevalence of Listeria spp. near raw product entry points across PHP facilities.

In the context of closed inbound innovation, as a form of open innovation practice, the quality of coordination among employees takes an important place. Innovative ideas can appear at any moment of the numerous formal and informal conversations. Concept generation is a key moment of upstream innovation processes. Thanks to internal web-platforms, in many organizations employees are integrated within the innovation processes and often, community discussions are organized on-line. We carry an empirical exploration by analyzing on-line, innovation-oriented, web community discussions that we have had the opportunity to co-animate throughout collaboration with a consulting firm. The innovation-oriented online discussions were launched in the context of an online community of employees to allow its members to go beyond daily discussions and further explore one trend or opportunity for the group. In this dissertation, we explore the dynamic of online collaborative concept generation at ideation stage. Therefore, we present three sets of results: firstly, we describe the general conversational dynamics of online innovation-oriented discussions, secondly contextualized community management practices, then the collaborative dynamics of concept generation. Finally, we try to establish a general framework enabling the analysis of an online innovation-oriented conversation. This research leads us to further discuss the links between open innovation platforms and the innovation organization.; Dans le contexte de closed inbound innovation, comme une des pratiques de l'innovation ouverte, la qualité de la coordination informelle des salariées prend une place importante. Des idées innovantes peuvent apparaître à tout moment lors de nombreuses conversations formelles et informelles. La génération de concepts est un moment clé de processus d'innovation. De plus en plus d'entreprises impliquent ses salariées dans leurs processus d’innovation et, dans un certain nombre d’eux, les discussions entre les salariées sont organisées en ligne, grâce à des plateformes internes. Nous proposons ici d'explorer les discussions en ligne orientées innovation, que nous avons eu l'occasion de co-animé à travers la collaboration avec un cabinet de conseil. Les discussions en ligne orientées innovation ont été lancés dans le cadre d'une communauté en ligne des salariées afin de permettre à ses membres d'aller au-delà des discussions quotidiennes et d’explorer davantage une tendance ou une opportunité pour le groupe. Ce projet nous amène à étudier la dynamique d'une génération collaborative de concepts en ligne à l'étape d'idéation. Par conséquent, nous présentons trois séries de résultats: d’abord, nous décrivons la dynamique générale des discussions en ligne orientées innovation, ensuite les pratiques de Community Management dans le contexte, et enfin les caractéristiques de la dynamique collaborative de la génération de concepts. De plus, nous essayons d'établir un cadre général permettant l'analyse d'une conversation orientée innovation en ligne pour les chercheurs académiques. Cette recherche nous amène à discuter davantage des liens entre les plateformes d'innovation ouverte et l'organisation de l'innovation.

The presence of Listeria spp. and L. monocytogenes (Lm) was investigated in provincially inspected food processing and retail facilities in British Columbia. Lm (n=56) was recovered in food processing environment (FPE) of dairy, meat and fish facilities, and in ready-to-eat fish products. The majority of Lm belonged to listeriosis causing serotypes 1/2a and 4b. Isolate fingerprinting revealed 14 sequence types, and 38 pulsotypes, with 66% of Lm possessing the full-length inlA, a causally linked virulence determinant. Unexpectedly, 4b serotypes more readily acquired point mutations leading to rifampicin resistance compared to other serotypes (p

Sustainable open innovation often has idea generation as a key step. When faced with challenge of stimulating ideation, organizations have few things they are sure about. An experiment was conducted to identify what type of stimulating written communication yields the biggest number of submitted ideas from students as users of educational services from their university. Results show that users generate more ideas when they are presented with specific problems that need solution than when they are generally asked to give any ideas for improvement they have. These results are discussed in the context of stimulating ideation through open innovation software platforms. This research tried to examine possible communication stimuli that may lead to bigger number of submitted ideas by users. In conclusion, the results of this research are applied to the field of open innovation software.