Fragile X syndrome (FXS), the most common cause of inherited mental impairment, is caused by the loss of expression of the fragile X mental retardation protein (FMRP). As an RNA binding protein, FMRP has been proposed to regulate the transport and translation of specific message RNA (mRNA). It has been reported that FMRP uses its RGG box domain to bind mRNA targets that form a G-quadruplex structure, structure believed to be important for FMRP recognition of at least a subclass of its mRNA targets. We have hypothesized that the interaction of FMRP with selected relevant mRNA targets occurs in a G-quadruplex dependent manner. By analyzing the structure of two FMRP in vivo mRNA targets, Shank1 mRNA and BASP1 mRNA, and their interactions with FMRP, we showed a high-affinity interaction between Shank1 RNA G-quadruplex and FMRP. The other G-quadruplex forming mRNA BASP1, however, interacts with FMRP using other structural elements. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences; / Pharmaceutics / MS; / Thesis;

This research has investigated marine biofouling and its influence on the durability of concrete sea defences using on-site and laboratory-based studies. The study was divided into three main phases namely: the surface analysis of armour concrete, the study of algal colonisation within the matrix and investigations into the presence of a bacterial biofilm within freshly hardened armour concrete. The effectiveness of photocatalytic coatings as a non-toxic anti-fouling strategy and cell attachment to synthetic fibres was also studied. It was found that algal growth quickly developed at the interface of inclusions within the matrix and that power washing with the use of Dairy Hypochlorite to remove this accelerated wear, leading to significant mass loss. It was also observed that bacterial growth within local beach sand, which was used in the production of the revetment armour units, survived the concrete manufacturing process. Bacteria were cultured from the sand and were found to match the Actinomycete like growth in the freshly hardened matrix of armour concrete. This thesis proposes a holistic model for biofouling of fibre reinforced marine concrete in which algal growth around inclusions facilitates a complex process of biodeterioration. Bacterial filamentous growth around and through synthetic fibres embedded in the new concrete mix, appears to be detrimental to the long term durability of synthetic fibres. Subsequent algal colonisation on the surface of newly placed units appeared to quickly penetrate the surface through exposed fibres and percolated interfaces of inclusions, subsequently weakening their bond. During the manufacture of the armour units, aggregate segregation in the 90° corners in the bottom of the form created a weaker matrix in the surface region most exposed to biodeterioration, the full force of wave action and power washing. The main conclusions from this study are: • Synthetic fibres used at the study site are inappropriate for marine concrete, particularly in algal rich waters, within the inter-tidal zone where beach sand is used in the concrete mix. Amendments to Concrete Society Technical Report No. 65: Guidance on the use of Macro-synthetic-fibre-reinforced concrete have been recommended. • Bacterial loaded beach sand is detrimental to the durability of marine concrete in the inter-tidal zone and amendments are recommended to PD 6682-1:2013 Aggregates for concrete (BSI, 2013a) in order to highlight this concern. This UK guidance suggests limiting values for aggregate properties within the ranges permitted in BS EN 12620 (BSI, 2013) but does not place any limits on microorganisms present in beach sand. Further work is needed into the susceptibility of synthetic fibres to crystal growth. Alterations in the manufacture of armour units have been recommended by this author.

Chemokine-induced macrophage recruitment into the vascular wall is an early pathological event in the progression of atherosclerosis. Macrophage activation and chemotaxis during cell recruitment are mediated by chemokine ligation of multiple G- protein coupled receptors. The Regulator of G-Protein Signalling-l (RGS-l) acts to down-regulate the response to sustained chemokine stimulation. Studies in this laboratory have shown Rgsl is up-regulated in atherosclerotic ApoE1- mice in association with atherosclerotic plaque progression and published findings have reported that RGS 1 is highly expressed in leukocytes. However an in vivo role for RGS-l in macrophage function or in atherosclerosis has not been investigated. This thesis aimed to address the hypothesis that RGS 1 has an important role in atherosclerosis and modulates the inflammatory response by controlling chemokine signalling and macrophage chemotaxis to atherosclerotic plaques. To investigate the role of RGS 1 in macrophage function and the development of atherosclerosis, Rgsrl- mice were characterised on the ApoE1- background. Flow cytometric analysis of leukocytes in blood, spleen and bone marrow indicated Rgsrl- ApoE1- mice had no significant differences in the numbers of monocytes or lymphocytes compared to ApoE1- mice. Rgsl was found to be highly expressed in macrophages from ApoE1- mice compared to B-Iymphocytes, where it has a non-redundant role, and other cells involved in plaque formation. Furthermore, Rgsl is up-regulated with monocyte- macrophage activation by innate stimuli. For the first time, RGS 1 'was shown to affect chemokine receptor signalling in macrophages in vitro. RgsrlApoE1- macrophages showed significantly enhanced chemotaxis to CCL2, CCL3 and CCLS and impaired homologous desensitisation to the chemokine CCLS in comparison to ApoE1- cells. To determine the role of RGS-l in leukocyte trafficking and atherosclerosis, a detailed atherosclerosis study was carried out. RgsrlApoE1- mice had significantly less lesion formation in the aortic roots at 9-weeks and in the aorta at 16-weeks on a chow diet in comparison to ApoE1- mice. This was accompanied with decreased macrophage content in the aortic root at 9-weeks. To further investigate aortic leukocyte recruitment, an Angiotensin IT-induced model of acute vascular inflammation was used. At 9 weeks of age, Rgsrl-ApoE1- mice had significantly less aortic CD4S+ leukocytes and cons' myeloid cells recruited to the aorta in comparison to ApoE1- mice. Collectively, these findings identify a new role for RGS-l in macrophage function and support a role for RGS-l in leukocyte recruitment and retention in the initial stages of atherosclerotic plaque formation. These results identify RGS 1 as a novel target for the treatment of acute vascular inflammation and early atherosclerosis.

Droughts are one of the most widespread and complex natural hazards, and remain poorly understood in the context of the United Kingdom. Although the UK is perceived as a relatively water rich country, droughts are a recurrent feature of its climate, causing widespread and serious environmental and economic impacts. Current understanding of drought risk is often based on relatively short records, and/or a small number of specific contemporary case study events from the last couple of decades (e.g. 1976). This study addresses this problem through the development of long (>150 year) meteorological drought records reconstructed using the self-calibrating Palmer Drought Severity Index (scPDSI). The index was calculated using long duration temperature and rainfall records. New rainfall series were generated for Carlisle and Chatsworth, existent rainfall series were extended for Kew, Spalding, Manchester, Edinburgh and Oxford. Additional rainfall series were kindly provided for Appleby and Durham. Temperature series for the Lancashire Plain, Oxford, Edinburgh and Durham were also extended. Where appropriate the newly developed and existing series were evaluated and tested to ensure homogeneity. The drought reconstructions identify multiple drought-rich periods, particularly in the eighteenth and twentieth centuries, with an increasing tendency towards more severe droughts during the latter period. Prolonged rainfall deficiencies are found to be the primary cause of severe droughts, with rising temperatures exacerbating the rainfall conditioned drought pattern. Cycles at the 6-10 year period identify a sub-decadal to decadal signal during the more drought-rich periods, which can be interpreted as reflecting large scale modes of climate variability. Analysis of the spatial variability of droughts finds that whilst severe events predominantly display spatial coherence, there are notable variations in drought characteristics (severity and duration) that reflect intra- and interregional variability in drought behaviour. In part this can be attributed to localised variations in rainfall and distance between sites. This study extends the temporal range of previous drought studies and places recent drought events in a longer context, improving upon existing ‘benchmark’ drought analyses; with far-reaching implications for local, national and continental scale reduction of drought vulnerability and risk.

La aplicación de estrategias, que permiten la mejora continua de las organizaciones, obliga a éstas a realizar la búsqueda de alternativas, que mejor se adecuen a sus necesidades, tomando en cuenta el avance en el desarrollo de tecnologías de información, las cuales permiten generar un flujo más rápido de la información; contribuyendo así a minimizar los costos, a tener un proceso productivo más eficiente que ayude a tener un mejor control de las actividades en todos los niveles de una empresa y a agilizar la toma de decisiones, para esto es necesario aplicar estrategias como la Reingeniería de Procesos, Rediseño o Mejora de procesos para que posteriormente pueda ser apoyado mediante un sistema de información.El presente estudio fue realizado a la empresa T&G Informática, la cual se dedica a brindar soluciones tecnológicas. Al realizar las respectivas reuniones, se detectó como problemática, falta de conocimiento integral de sus procesos y su interacción con las demás áreas de la empresa, provocando retrasos en el flujo principal del proceso, causados al ser ejecutados sin la información debida, ni en los tiempos adecuados, y por no contar con un sistema de información que sirva de apoyo para la integración de sus actividades. Por ello, nuestra tesis se centra principalmente, en el rediseño de procesos de la empresa T&G Informática para implementar un sistema ERP que comunique sus procesos principales.

Aktivierte G-Protein gekoppelte Rezeptoren aktivieren heterotrimere GProteine, in dem sie den Austausch von GDP zu GTP am G-Protein katalysieren. Theoretische Untersuchungen mittels eines vereinfachten kinetischen Modells des Gi/o-Protein Zyklus legen nahe, dass nicht nur GDP-,sondern auch GTP-gebundene Gi/o-Proteine mit aktivierten α2A-adrenergen Rezeptoren (α2A-AR) interagieren können. Demgemäß sollten aktivierte Gi/o-Proteine mit aktivierten α2A-AR vermehrt interagieren, wenn mehr α2A-AR aktiviert werden als für eine maximale G-Protein Aktivierung nötig sind. Dies sollte zu einer paradoxen Deaktivierung von Gi/o-Proteinen und deren Effektorproteinen, z.B. dem G-Protein gekoppelten, einwärtsgleichrichtenden Kaliumkanal (GIRK-Kanal) führen. Mittels FRET lässt sich in lebenden und in permeabilisierten Zellen unter Kontrolle der intrazellulären Nukleotide die Aktivierung von α2A-AR, die Interaktion von Gi/o-Proteinen mit α2A-AR und die Aktivierung von Gi/o-Proteinen bestimmen. Die Arbeit zeigt auf mehreren Ebenen, dass Go-Proteine mit aktivierten α2A-AR interagieren und im nukleotidfreiem Zustand sequestriert werden können: (I) Go-Proteine,irreversibel durch GTPγS aktiviert werden abhängig von der Rezeptor Aktivierung in Abwesenheit von Nukleotiden deaktiviert, (II) Go-Proteine interagieren in Gegenwart niedriger Nukleotidkonzentrationen in wesentlich größer Fraktion mit aktivierten α2A-AR als in Gegenwart hoher Nukleotidkonzentrationen, (III) Go Proteine können in Gegenwart niedriger GTP und GTPγS-Konzentrationen bei Aktivierung des α2A-AR inaktiviert werden. Die Arbeit zeigt exemplarisch an der Signalkaskade des α2A-AR und Go, dass der G-Protein Zyklus in lebenden Zellen reversibel ist, woraus eine Deaktivierung aktivierter G-Proteine und aktivierter G-Protein Effektoren resultieren kann. Dies erklärt paradoxe Befunde zur Deaktivierung von GIRK-Kanälen in Myozyten durch A1-Rezeptoren. / G protein coupled receptors activate heterotrimeric G proteins by catalyzing the exchange of GDP with GTP at the Gα subunit. Kinetic modelling of the Gi/o protein cycle suggests, that both GDP- and GTP-bound Gi/o proteins interact with activated α2A-adrenergic receptors (α2A-AR). Consequently, upon activating more α2A-AR then required for maximal Gi/o protein activation, the interaction of activated Gi/o proteins with activated α2A-AR will become incresingly prominent and ultimately lead to a paradoxic deactivation of Gi/o proteins and their effectors such as G protein coupled inwardly rectifying potassium channels. Using means of FRET allows the detection of the receptor activation, receptor/G protein interaction and G protein activation in single living cells and in single permeabilized cells while controlling the intracellular nucleotide composition.Data suggest, that activated Go proteins may be sequestrated at activated α2A-AR in their nucleotide-free state: (I) Go proteins irreversibly activated by GTPγS become inactivated upon receptor stimulation in the absence of nucleotides, (II) Go proteins interact with activated α2A-AR to a large extent in the presence of low concentrations of nucleotide, (III) Go proteins may be inactivated upon activation of α2A-AR in the presence of low concentrations of GTP or GTPγS. Taken together, the data demonstrate the reversibility of the G protein cycle in living cells for the paradigm α2A-AR/Go pathway. The data thereby explain the paradoxic inactivation of G protein coupled inwardly rectifying potassium channels in myocytes upon activation of adenosine A1 receptors.

Somatostatin ist ein regulatorisches Peptid, das eine Vielzahl von biologischen Prozessen innerhalb des Körpers beeinflußt. Die Wirkung von Somatostatin wird auf zellulärer Ebene über eine Familie von fünf G-Protein-gekoppelten Rezeptoren vermittelt, die entweder in G Protein-abhängiger Weise oder vermutlich auch über andere interagierende intrazelluläre Proteine auf nachgeschaltete Signaltransduktionswege wirken. Der Somatostatinrezeptor Subtyp 4 (SSTR4) wird hauptsächlich im Gehirn exprimiert und wirkt dort inhibierend auf die exzitatorische Signalweiterleitung. Es sind aber auch stimulierende Effekte des SSTR4 bekannt. Um das subtypspezifische Signalverhalten des SSTR4 weiter zu untersuchen, wurden im Rahmen dieser Arbeit Proteine gesucht, die intrazellulär mit dem SSTR4 interagieren und so seine physiologischen Effekte beeinflussen. In einem ersten Ansatz konnten drei mögli-che Interaktionspartner mit Hilfe des Hefe-Zwei-Hybrid-Systems identifiziert werden, die aber in nachfolgenden Untersuchungen als unpezifisch eingestuft wurden. Mit Hilfe einer Affinitätschromatografie wurden dann zwei Proteine identifiziert, die spezifisch mit dem SSTR4 interagieren. Sowohl PSD-95 als auch PSD-93 (Postsynaptic density protein of 95 kDa bzw. 93kDa) wurden mit einem immobilisierten Peptid präzipitiert, das die neun C-terminalen Aminosäuren des SSTR4 enthält. Die Interaktion des SSTR4 mit PSD 95 wurde im Weiteren näher charakterisiert. In einem Bindungsexperiment mit rekombinaten Proteinen konnte gezeigt werden, dass die Interaktion durch die 1. und 2. PDZ-Domäne von PSD-95 vermittelt wird. In humanen embryonalen Nieren-Zellen (HEK293), die den SSTR4 stabil exprimieren, konnte PSD-95 mit dem Rezeptor koimmunpräzipitiert werden. Nach Koexpression von PSD-95 und SSTR4 findet man eine partielle Kolokalisierung beider Proteine an der Zellmembran, wobei aber der Großteil des PSD-95 weiterhin eine diffuse zytoplasmatische Verteilung zeigt. Die Interaktion wurde in vivo sowohl immunhistochemisch in kultivierten Hippocampus-Neuronen als auch durch Koimmunpräzipitation beider Proteine aus Rattengehirn-Lysaten nachgewiesen. Die Interaktion von PSD-95 mit dem SSTR4 beeinflußt weder die Agonisten-induzierte Internalisierung des Rezeptors in HEK293-Zellen, noch die Kopplung des Rezeptors an einen G-Protein-gekoppelten einwärtsgleichrichtenden Kaliumkanal in Oozyten des afrikanischen Krallenfrosches Xenopus laevis. Durch die Interaktion mit PSD-95 wird der SSTR4 in physikalische Nähe zu bestimmten Zielproteinen gebracht, über die nachfolgend die Somatostatineffekte weitervermittelt werden. So ermöglicht die Interaktion vermutlich eine Integration des SSTR4 in den postsynaptischen Komplex aus PSD-95 und Glutamatrezeptoren, wo der SSTR4 die bereits beschrieben regulatorischen Effekte auf die Glutamat-vermittelte exzitatorische Signaltransduktion ausüben kann. / Somatostatin is a regulatory peptid, which affects a multiplicity of biological processes within the body. The effects of Somatostatin are mediated by a family of five G-protein-coupled receptors, which act on several downstream signaltransduction pathways either in a G-protein-dependent way or probably in a G-protein-independent manner via intracellular interacting proteins. The somatostatin receptor subtype 4 (SSTR4) is mainly expressed in brain, where it inhibits the excitatory neurotransmission. In addition, excitatory effects of SSTR4 have also been published. In order to examine the subtype specific signalling of SSTR4, I tried to identify intracellular proteins which interact directly with the SSTR4 and affect its physiological effects. Using the yeast two-hybrid system I identified three possible interaction partners for SSTR4, which were however classified as non-specific in subsequent experiments. In a second approach two proteins which interact with SSTR4 could be identified by affinity-chromatography. Both proteins PSD-95 and PSD-93 (Postsynaptic density protein of 95 kDa and 93kDa) were precipitated specifically with an immobilized peptid that contains the nine C-terminal amino acids of SSTR4. The interaction of the SSTR4 with PSD-95 was further characterized. In a binding experiment with recombinant proteins I could show that the interaction is mediated by the 1st and 2nd PDZ-domain of PSD-95. In human embryonic kidney cells (HEK293) which stably express SSTR4, PSD-95 could be coprecipitated with the receptor. After coexpression of PSD-95 and SSTR4 both proteins are partially colocalized at the plasma membrane. The majority of the PSD-95 however shows a diffuse cytoplasmic distribution. The in vivo interaction was proven by immunohistochemistry on cultivated hippocampal neurons and by coimmunoprecipitation of both proteins from rat brain lysates. The interaction of PSD-95 with SSTR4 affected neither the agonist induced internalisation of the receptor in HEK293 cells, nor the coupling of the receptor to a G-protein-coupled inwardly-rectifying potassium channel in oocytes obtained from the african clawed frog Xenopus laevis. By the interaction with PSD-95, SSTR4 is brought into physical proximity to certain target proteins which mediate the effects of somatostatin. Thus the interaction probably allows an integration of SSTR4 into the postsynaptic complex of PSD-95 and glutamergic receptors, where SSTR4 could regulate the glutamat-mediated excitatory signaltransduction.

1 Summary The first part of this thesis is preoccupied with the identification of protein alterations in the membrane fraction of HEK293-E2M11 cells after prolonged TRH treatment. The isolated membrane fraction enriched in plasma membranes contained markedly increased the amount of Na,K-ATPase, TRH receptor and G-proteins compared to the postnuclear supernatant. By using 2D electrophoresis and mass spectrometry, the levels of 42 proteins were identified to be altered in samples of PM- enriched fractions from TRH-treated (16 h; 10 μM) cells. Out of these proteins only ezrin and stomatin-like 2 are known to be localized in the plasma membrane. Five proteins (mitofilin, MTHSP75, prohibitin, stomatin like-2, peroxiredoxin III) whose levels were increased after the prolonged TRH treatment represent proteins localized in mitochondria. All of them are important for proper structure and function of mitochondria. The ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax was markedly higher in cells treated with TRH than in control untreated cells. Hence, it can be concluded that prolonged TRH treatment may significantly affect mitochondrial membrane and function of mitochondria. The second part of this thesis deals with the identification of molecular protein complexes of TRH-R and/or Gq/11 protein. The presumed...

O diabetes mellitus tipo 1A (DM1) é uma doença crônica caracterizada pela destruição imunológica das células ? do pâncreas e pela incapacidade de seu portador produzir insulina. Nas últimas décadas foram descritos vários aspectos sobre a fisiopatologia do DM1 e identificado um aumento de sua incidência mundial. Entretanto, na literatura há lacunas a serem respondidas envolvendo a etiologia e a imunopatologia desta doença. No presente trabalho, foi analisado o impacto de duas moléculas endógenas imunoregulatórias, Antígeno Leucocitário Humano-G (HLA-G) e Galectina-1 (GAL-1), no DM1 humano e experimental. Para tanto, as formas recombinantes de HLA-G (-G5 e -G6) e seus respectivos anticorpos foram produzidos e/ou bioquimicamente caracterizados. A partir de amostras de pacientes diagnosticados com DM1 ou de indivíduos controle foi feita uma análise comparativa envolvendo o perfil de expressão do HLA-G e da GAL-1 e a identificação de microRNAs (miRNAs) associados a estas duas moléculas. Camundongos Lgals-/- ou não para o gene da GAL-1 foram tratados com estreptozotocina (STZ) para indução do DM1 experimental. As duas formas recombinantes do HLA-G foram produzidas, mas apenas o HLA-G6 foi caracterizado como uma solução polidispersa contendo um componente majoritário (99,2%) com massa molecular de 23.603,766 Da, raio hidrodinâmico de 6,0 ± 2,0 nm e imunoreatividade para diferentes anticorpos anti-HLA-G comerciais ou produzidos no laboratório. Os níveis transcricional e proteico do HLA-G e da GAL-1 não foram diferentes entre os grupos de indivíduos estudados. A análise comparativa de miRNAs mostrou que a elevada indução do miRNA modulador negativo da expressão do HLA-G (hsa-miR-16-5p) nos controles em relação aos pacientes foi a única associação robusta com a patogenia do DM1. Curiosamente, os animais selvagens apresentam maior suscetilibilidade à indução de DM1 por STZ, uma vez que os indicadores desta doença como o grau de insulite, a taxa de migração de linfócitos T CD4 e T CD8 para os linfonodos pancreáticos, o nível de redução de insulina no pâncreas e a taxa glicêmica estavam aumentados nesses animais em relação aos nocautes para GAL-1. Finalmente, este conjunto de resultados sugere que possa ocorrer uma regulação positiva da expressão de transcritos do HLA-G em pacientes com DM1 e que a presença de GAL-1 endógena pode favorecer o DM1 experimental. Estes dados abrem novas perspectivas para o melhor entendimento da imunopatologia do DM-1 / Diabetes Mellitus type 1A (DM1) is a chronic disease characterized by the immune destruction of pancreatic beta cells and by the consequent inability of its bearer to produce insulin. For the last decades, several aspects of the pathophysiology of DM1 were described and an increase on its worldwide incidence has been identified.Nevertheless, there are gaps in the literature related to aspects of its etiology and immunopathology to be filled.In the present work, the impact of two endogenous immunoregulatory molecules, Human Leukocyte Antigen-G (HLA-G) and Galectin-1 (GAL-1), was analyzed on human and experimental DM1.To do so, the recombinant forms of HLA-G (-G5 and - G6) and its respective antibodies were produced and/or biochemically characterized. A comparative analysis involving the expression profile of HLA-G and GAL-1 and the identification of microRNAs (miRNAs) associated with these two molecules was made from samples of patients diagnosed with DM1, or control subjects. Mice deficient or not for the GAL-1 gene were treated with streptozotocin (STZ) for the induction of experimental DM1.Both recombinant forms of HLA-G were produced, but only HLA-G6 was characterized as a polydisperse solution containing a major component (99.2%), with molecular mass of 23,603,766 Da, hydrodynamic radius of 6.0 ± 2.0 nm, and immunoreactivity for different commercial or lab produced anti-HLA-G antibodies HLA-G and GAL-1. The transcriptional and protein levels were not different between the groups of subjects studied. High induction of the negative modulator miRNA expression of HLA-G (hsa-miR-16-5p) in the controls compared to the patients was the only robust association found with the pathogenesis of DM1.Interestingly, wild type animals presented more susceptibility to the induction of DM1 by STZ, once the indicators of this disease such as the degree of insulin, the migration rate of CD4 T and CD8 T lymphocytes to pancreatic lymph nodes, the level of insulin reduction in the pancreas and the glycemic rate were increased in wild type mice (Lgals-1+/+) when compared to GAL-1-knock out mice (Lgals-1-/-). Finally, this set of results suggests that a positive regulation of the expression of HLA-G transcripts may occur in patients with DM1 and that the presence of endogenous GAL-1 may favor the experimental DM1. These data open new perspectives for a better understanding of the immunopathology of DM-1

Anthropogenic impact, through animal trade, climate change, habitat fragmentation and globalisation, is a principal cause of global species redistributions and community rearrangements. Species introduced accidently or intentionally to non-native ranges may adapt to survive and proliferate, and native species threatened by environmental change may need to adapt in situ, or track more tolerable conditions through extra-range dispersal. Under both scenarios, we must facilitate greater understanding of the mechanisms that underlie adaptation within a complexity of ecosystem dynamics, which in turn will inform management strategies for both introduced species, and preserving biodiversity. Here, I explore mechanisms that support adaptive potential to rapid environmental change across taxa, and model them to the introduced ringneck parakeet Psittacula krameri. This species has recently successfully traversed extensive climate gradients in establishing introduced global populations. Some of this success may be attributable to morphological, behavioural, physiological or phenological adaptations, and therefore the species represents an opportunity for exploring rapid adaptation. I initially review the navigation of dispersal and invasive pathways, and the importance of specific character traits toward adaptive potential, before identifying genetic and non-genetic adaptive mechanisms (pertinent across taxa) that may help explain observed establishment and population growth of the ringneck parakeet. Mutations as the basis for an evolutionary adaptive response are examined, alongside the significance that the origin and extent of such polymorphisms may have toward a rapid adaptive response. I consider the role of selective sweeps and polygenic models as genetic processes for an adaptive response, alongside non-genetic mechanisms such as phenotypic plasticity and epigenetics that may better support rapid adaptation. Finally, I assess avian literature to interpret genetic and plastic responses as explanations for adaptive potential.