Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1

Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

Open Personalization: Involving Third Parties in Improving the User Experience of Websites

Traditional software development captures the user needs during the requirement analysis. The Web makes this endeavour even harder due to the difficulty to determine who these users are. In an attempt to tackle the heterogeneity of the user base, Web Personalization techniques are proposed to guide the users’ experience. In addition, Open Innovation allows organisations to look beyond their internal resources to develop new products or improve existing processes. This thesis sits in between by introducing Open Personalization as a means to incorporate actors other than webmasters in the personalization of web applications. The aim is to provide the technological basis that builds up a trusty environment for webmasters and companion actors to collaborate, i.e. "an architecture of participation". Such architecture very much depends on these actors’ profile. This work tackles three profiles (i.e. software partners, hobby programmers and end users), and proposes three "architectures of participation" tuned for each profile. Each architecture rests on different technologies: a .NET annotation library based on Inversion of Control for software partners, a Modding Interface in JavaScript for hobby programmers, and finally, a domain specific language for end-users. Proof-of-concept implementations are available for the three cases while a quantitative evaluation is conducted for the domain specific language.

Self-reported sitting time and physical activity: interactive associations with mental well-being and productivity in office employees

Background: Little is known about how sitting time, alone or in combination with markers of physical activity (PA), influences mental well-being and work productivity. Given the need to develop workplace PA interventions that target employees' health related efficiency outcomes; this study examined the associations between self-reported sitting time, PA, mental well-being and work productivity in office employees. Methods: Descriptive cross-sectional study. Spanish university office employees (n = 557) completed a survey measuring socio-demographics, total and domain specific (work and travel) self-reported sitting time, PA (International Physical Activity Questionnaire short version), mental well-being (Warwick-Edinburg Mental Well-Being Scale) and work productivity (Work Limitations Questionnaire). Multivariate linear regression analyses determined associations between the main variables adjusted for gender, age, body mass index and occupation. PA levels (low, moderate and high) were introduced into the model to examine interactive associations. Results: Higher volumes of PA were related to higher mental well-being, work productivity and spending less time sitting at work, throughout the working day and travelling during the week, including the weekends (p < 0.05). Greater levels of sitting during weekends was associated with lower mental well-being (p < 0.05). Similarly, more sitting while travelling at weekends was linked to lower work productivity (p < 0.05). In highly active employees, higher sitting times on work days and occupational sitting were associated with decreased mental well-being (p < 0.05). Higher sitting times while travelling on weekend days was also linked to lower work productivity in the highly active (p < 0.05). No significant associations were observed in low active employees. Conclusions: Employees' PA levels exerts different influences on the associations between sitting time, mental well-being and work productivity. The specific associations and the broad sweep of evidence in the current study suggest that workplace PA strategies to improve the mental well-being and productivity of all employees should focus on reducing sitting time alongside efforts to increase PA.

Discriminating languages in bilingual contexts: the impact of orthographic markedness

Does language-specific orthography help language detection and lexical access in naturalistic bilingual contexts? This study investigates how L2 orthotactic properties influence bilingual language detection in bilingual societies and the extent to which it modulates lexical access and single word processing. Language specificity of naturalistically learnt L2 words was manipulated by including bigram combinations that could be either L2 language-specific or common in the two languages known by bilinguals. A group of balanced bilinguals and a group of highly proficient but unbalanced bilinguals who grew up in a bilingual society were tested, together with a group of monolinguals (for control purposes). All the participants completed a speeded language detection task and a progressive demasking task. Results showed that the use of the information of orthotactic rules across languages depends on the task demands at hand, and on participants' proficiency in the second language. The influence of language orthotactic rules during language detection, lexical access and word identification are discussed according to the most prominent models of bilingual word recognition.

Phosphorylation of the carboxy-terminal domain of histone H1: effects on secondary structure and DNA condensation

Linker histone H1 plays an important role in chromatin folding. Phosphorylation by cyclin-dependent kinases is the main post-translational modification of histone H1. We studied the effects of phosphorylation on the secondary structure of the DNA-bound H1 carboxy-terminal domain (CTD), which contains most of the phosphorylation sites of the molecule. The effects of phosphorylation on the secondary structure of the DNA-bound CTD were site-specific and depended on the number of phosphate groups. Full phosphorylation significantly increased the proportion of -structure and decreased that of -helix. Partial phosphorylation increased the amount of undefined structure and decreased that of -helix without a significant increase in -structure. Phosphorylation had a moderate effect on the affinity of the CTD for the DNA, which was proportional to the number of phosphate groups. Partial phosphorylation drastically reduced the aggregation of DNA fragments by the CTD, but full phosphorylation restored to a large extent the aggregation capacity of the unphosphorylated domain. These results support the involvement of H1 hyperphosphorylation in metaphase chromatin condensation and of H1 partial phosphorylation in interphase chromatin relaxation. More generally, our results suggest that the effects of phosphorylation are mediated by specific structural changes and are not simply a consequence of the net charge.

Processing Facilitation Strategies in OV and VO Languages: A Corpus Study

The present corpus study aimed to examine whether Basque (OV) resorts more often than Spanish (VO) to certain grammatical operations, in order to minimi ze the number of arguments to be processed before the verb. Ueno & Polinsky (2009) argue that VO/OV languages use certain grammatical resources with different frequencies in order to facilitate real-time processing. They observe that both OV and VO languages in their sample (Japanese, Turkish and Spanish) have a similar frequency of use of subject pro-drop; however, they find that OV languages (Japanese, Turkish) use more intransitive sentences than VO languages (English, Spanish), and conclude this is an OV-specific strategy to facilitate processing. We conducted a comparative corpus study of Spanish (VO) and Basque (OV). Results show (a) that the fre- quency of use of subject pro-drop is higher in Basque than in Spanish; and (b) Basque does not use more intransitive sentences than Spanish; both languages have a similar frequency of intransitive sentences. Based on these findings, we conclude that the frequency of use of grammatical resources to facilitate the processing does not depend on a single typological trait (VO/OV) but it is modulated by the concurrence of other grammatical feature.