Oral History Interview with John Niland: Conceptualising SMU

This is an abridged version of the original interview. Please contact the Library at [email protected] for access to the full version of the transcript and/or audio recording.</p

ND4 samples information

Table with information regarding all samples sequenced with mitochondrial gene ND4

Scripts and datasets used in this study

This is a compressed zip file of scripts to process the raw data and datasets used in analyses for this study

Sample Information

Information and results (microsatellite data analyses and control region - CR - haplotypes) for the samples analysed in the study and respective GenBank Accession Numbers for mtDNA data

Cyclic α,β-Tetrapeptoids: Sequence-Dependent Cyclization and Conformational Preference

The presence of at least one <i>N</i>-Cα branched side chain is crucial for successful cyclization of α,β-tetrapeptoids. The <i>ctct</i> amide sequence revealed in the crystal structure of the 14-membered cyclotetrapeptoid <b>8</b> is also the most populated conformation in solution and is reminiscent of the predominant amide arrangement of the 12-membered cyclic tetrapeptides (CTPs)

Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation

Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor used as adjuvant therapy in Parkinson’s disease. However, it has a highly hepatotoxic profile, as recognized by the U.S. Food and Drug Administration. As a possible solution, nanoscience brought us several tools in the development of new functional nanomaterials with tunable physicochemical properties, which can be part of a solution to solve several drawbacks, including drug’s short half-life and toxicity. This work aims to use PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a stable carrier with lower hydrodynamic size and polydispersity to encapsulate tolcapone in order to overcome its therapeutic drawbacks. Using the nanoprecipitation method, tolcapone-loaded nanoparticles with a DLC% of 5.7% were obtained (EE% of 47.0%) and subjected to a lyophilization optimization process to obtain a final shelf-stable formulation. Six different cryoprotectants in concentrations up to 10% (w/v) were tested. A formulation of PLGA nanoparticles with 3% hydroxypropyl-β-cyclodextrin (HPβCD) as a cryoprotectant (PLGA-HP@Tolc), presenting sub-200 nm sizes and low polydispersity (PdI < 0.200) was selected. Cytotoxicity assays, namely, MTT and SRB, were used to study the metabolic activity and cell density of tolcapone and PLGA-HP@Tolc-treated cells. In both assays, a hepatocarcinoma cell line (HepG2) growing in glucose or glucose-free media (galactose-supplemented medium) was used. The results demonstrated that the treatment with the PLGA-HP@Tolc formulation led to a decrease in cytotoxicity in comparison to free tolcapone-treated cells in both media tested. Moreover, the elected formulation also counteracted ATP-depletion and excessive ROS production induced by tolcapone. The results suggest that HPβCD might have a dual function in the formulation: cryoprotectant and anticytotoxic agent, protecting cells from tolcapone-induced damage. Using an in vitro COMT inhibition assay, the PLGA-HP@Tolc formulation demonstrated to inhibit COMT as efficiently as free tolcapone. Overall, the results suggest that tolcapone-loaded PLGA NPs could be an interesting alternative to free tolcapone, demonstrating the same in vitro efficacy in inhibiting COMT but with a safer cytotoxic profile

Cyclic α,β-Tetrapeptoids: Sequence-Dependent Cyclization and Conformational Preference

The presence of at least one <i>N</i>-Cα branched side chain is crucial for successful cyclization of α,β-tetrapeptoids. The <i>ctct</i> amide sequence revealed in the crystal structure of the 14-membered cyclotetrapeptoid <b>8</b> is also the most populated conformation in solution and is reminiscent of the predominant amide arrangement of the 12-membered cyclic tetrapeptides (CTPs)

Microsatellite Dataset

Microsatellite dataset used in the study. Genotypes recovered for 302 samples analysed for 11 microsatellite loci

Cluster membership and genetic structure of red fox individuals in Portugal as inferred by the uncorrelated frequency model in GENELAND and sPCA.

<p>On the left, cluster membership of red fox individuals with a membership probability ≥ 0.9 by the uncorrelated frequency model in GENELAND (the River Tagus is indicated by a dashed arrow); On the middle and right, genetic structure as assessed by sPCA; shown are the first Principal Component (PC) and the respective mapping of cluster membership. Lines in both maps represent country borders and main watercourses.</p

Cluster membership of stone marten individuals.

<p>Cluster membership of stone marten individuals with a membership probability ≥ 0.9 in the best run of, respectively from left to right, BAPS (K = 3), TESS with no admixture (K = 3) and GENELAND for the uncorrelated frequency model (K = 3). Stars represent non-assigned individuals (i.e., with membership coefficients < 0.9). Lines represent country borders and main watercourses.</p