Kinesin-1 transports various cargos along the axon, while the light chain subunits play a role in selecting the types of cargos to transport. However, the mechanisms of cargo recognition and interaction have yet to be characterized. Both c-Jun kinase-interacting protein-1 (JIP1) and alcadein-1 (ALC1) are kinesin-1 cargos and compete with each other for the axonal transport machinery. I identified two polar patches of KLC1 that play a role in the interactions with JIP1 and ALC1, respectively. The main components of these two polar patches are asparagine “clamps” surrounded by positively charged lysines. Consistent with this finding, negatively charged residues of JIP1 and ALC1 are required to interact with KLC1. By structural modeling, I narrowed down the possible key residues of KLC1 that are required for interaction with c-Jun kinase interacting protein-3 (JIP3). Together, these findings reveal the versatility of KLC in the mode of interaction with many different cargos.

Kinesin-1 transports various cargos along the axon, while the light chain subunits play a role in selecting the types of cargos to transport. However, the mechanisms of cargo recognition and interaction have yet to be characterized. Both c-Jun kinase-interacting protein-1 (JIP1) and alcadein-1 (ALC1) are kinesin-1 cargos and compete with each other for the axonal transport machinery. I identified two polar patches of KLC1 that play a role in the interactions with JIP1 and ALC1, respectively. The main components of these two polar patches are asparagine “clamps” surrounded by positively charged lysines. Consistent with this finding, negatively charged residues of JIP1 and ALC1 are required to interact with KLC1. By structural modeling, I narrowed down the possible key residues of KLC1 that are required for interaction with c-Jun kinase interacting protein-3 (JIP3). Together, these findings reveal the versatility of KLC in the mode of interaction with many different cargos.

Interaction between bovine serum albumin (BSA) and thimerosal (TM), organic mercury compound, was investigated by spectroscopic methods. The results, by molecular fluorescence, show that the interaction takes place by static quenching with electrostatic forces spontaneously (ΔG = - 4.40 kJ mol-1 at 30°C). The binding constant (Kb) was 3.24 ± 0.01x103 L mol-1 (30°C) is considered a moderate interaction. Fluorescence in three dimensions revealed that TM causes structural involving the the polypeptide chain BSA changes in the polarity of the tryptophan and tyrosine residues confirmed by circular dichroism (CD) showed an increase in α-helix content after interaction with TM. In addition, the TM decreases the surface hydrophobicity of the protein. Bilirubin was used as a marker for the subdomain IB, confirming that TM interacts in this region of the protein. The study of the interaction mechanism proposed that TM is reacted with BSA through the free cysteine residue, forming the adduct BSA-HgEt release of thiosalicylic acid (ATS), which interacts with amino acids with side chain positive. Besides, it was seen that TM accelerates the protein fibrillation kinetics by 42%, with a possible indication of the toxicity of this compound in biological systems. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A interação entre albumina do soro bovino (BSA) e timerosal (TM), composto orgânico de mercúrio, foi investigada utilizando métodos espectroscópicos. Os resultados, por fluorescência molecular, evidenciam que a interação acontece por quenching estático através de forças eletrostáticas de forma espontânea (ΔG = - 4,40 kJ mol-1 a 30ºC). A constante de ligação (Kb) foi de 3,24 ± 0,01x103 L mol-1 (30ºC) sendo considerada uma interação moderada. A fluorescência em três dimensões revelou que TM causa mudanças estruturais envolvendo a cadeia polipeptídica da BSA assim como altera a polaridade dos resíduos de triptofano e tirosina, confirmada por dicroísmo circular (DC) que evidenciou aumento no conteúdo de α-hélice após interação com TM. Além disto, TM diminui a hidrofobicidade superficial da proteína. Bilirrubina foi utilizada como marcador para o subdomínio IB, confirmando que TM interage nesta região da proteína. O estudo do mecanismo de interação propôs que TM reage com BSA através do resíduo de cisteína livre, formando o aduto BSA-HgEt com liberação de ácido tiosalicílico (ATS), que interage com os aminoácidos com cadeia lateral positiva. Por fim, foi visto que TM acelera a cinética de fibrilação proteica em 42%, sendo um possível indício da toxicidade deste composto em sistemas biológicos.

Parental monitoring of settings is not always relevant for the prevention of adolescent crime because adolescents with strong personal moral rules and the ability to exercise self control are unlikely to offend even when they are unsupervised and know that their parents have little knowledge about their activities. Parental monitoring, commonly operationalised as parental supervision or parental knowledge, is often shown to have a negative relationship with crime involvement. However, research often ignores both the mechanism by which these relationships occur and the conditions under which they might (and might not) be found. This thesis uses specialist Space-Time Budget data (from the Peterborough Adolescent and Young Adult Development Study) to allow the comparison of adolescent crime rates in settings characterised by the of convergence of i) the physical presence or absence of parents and other guardians, ii) the psychological presence or absence of parents (represented by adolescent-perceived generalised parental knowledge of the circumstances of unsupervised activity) and iii) personal crime propensity (moral rules and ability to exercise self control). The conclusion derived from the results is that the physical presence of parents and other guardians in settings reduces the rate of adolescent crime committed in those settings; and the psychological presence of parents reduces the criminogenic impact of unsupervised time. Crucially however, these effects of parental monitoring are almost irrelevant for adolescents with a lower personal crime propensity, who are not likely to offend in settings irrespective of the physical or psychological absence of parents and other guardians. These findings provide support for person-environment interactions inherent in the causal model of Situational Action Theory, and provide a novel addition to evidence that could be used in future to inform policy-relevant recommendations concerning parenting behaviour and adolescent offending. Although this thesis provides new evidence about the relationship between parental monitoring and crime, the bulk of its contribution is relevant to a much wider audience. It contributes to the debate on approaches to the study of crime and crime prevention, adds clarity to key concepts and develops theoretical arguments in the field of parental monitoring and crime, develops a novel application of Situational Action Theory, extends theoretical and methodological discussions surrounding situational analysis, applies novel data and analytical methods to the study of the psychological and physical presence of guardians, generates and situates unique findings about the situational role of aspects of parental monitoring and crime, and makes some policy recommendations and suggestions about the nature and direction of future research.