Orthogonal biofunctionalization of magnetic nanoparticles via ``clickable'' poly(ethylene glycol) silanes: a ``universal ligand'' strategy to design stealth and target-specific nanocarriers

The present work demonstrates a novel strategy to synthesize orthogonally bio-engineered magnetonanohybrids (MNPs) through the design of versatile, biocompatible linkers whose structure includes: (i) a robust anchor to bind with metal-oxide surfaces; (ii) tailored surface groups to act as spacers and (iii) a general method to implement orthogonal functionalizations of the substrate via ``click chemistry''. Ligands that possess the synthetic generality of features (i)-(iii) are categorized as ``universal ligands''. Herein, we report the synthesis of a novel, azido-terminated poly(ethylene glycol) (PEG) silane that can easily self-assemble on MNPs through hetero-condensation between surface hydroxyl groups and the silane end of the ligand, and simultaneously provide multiple clickable sites for high density, chemoselective bio-conjugation. To establish the universal-ligand-strategy, we clicked alkyl-functionalized folate onto the surface of PEGylated MNPs. By further integrating a near-infrared fluorescent (NIRF) marker (Alexa-Fluor 647) with MNPs, we demonstrated their folate-receptor mediated internalization inside cancer cells and subsequent translocation into lysosomes and mitochondria. Ex vivo NIRF imaging established that the azido-PEG-silane developed in course of the study can effectively reduce the sequestration of MNPs by macrophage organs (viz. liver and spleen). These folate-PEG-MNPs were not only stealth and noncytotoxic but their dual optical and magnetic properties aided in tracking their whereabouts through combined magnetic resonance and optical imaging. Together, these results provided a strong motivation for the future use of the ``universal ligand'' strategy towards development of ``smart'' nanohybrids for theragnostic applications.

Développement d'une sonde fluorescente bioactivable pour l'étude du rôle in vitro et in vivo des protéases dégradant l’apolipoprotéine A-I.

Les effets bénéfiques des lipoprotéines de haute densité (HDL) contre l'athérosclérose ont été attribués, en grande partie, à leur composante protéique majeure, l'apolipoprotéine A-I (apoA-I). Cependant, il y a des indications que l'apoA-I peut être dégradée par des protéases localisées dans les plaques athérosclérotiques humaines, ce qui pourrait réduire l'efficacité des thérapies basées sur les HDL sous certaines conditions. Nous décrivons ici le développement et l'utilisation d'une nouvelle sonde bioactivatable fluorescente dans le proche infrarouge, apoA-I-Cy5.5, pour l'évaluation des activités protéolytiques spécifiques qui dégradent l'apoA-I in vitro, in vivo et ex vivo. La fluorescence basale de la sonde est inhibée par la saturation du fluorophore Cy5.5 sur la protéine apoA-I, et la fluorescence émise par le Cy5.5 (proche infrarouge) est révélée après clivage de la sonde. La protéolyse in vitro de l'apoA-I par des protéases a montré une augmentation de la fluorescence allant jusqu'à 11 fois (n=5, P ≤ 0.05). En utilisant notre nouvelle sonde apoA-I-Cy5.5 nous avons pu quantifier les activités protéolytiques d'une grande variété de protéases, incluant des sérines (chymase), des cystéines (cathepsine S), et des métalloprotéases (MMP-12). En outre, nous avons pu détecter l'activation de la sonde apoA-I-Cy5.5 sur des sections d'aorte de souris athérosclérotiques par zymographie in situ et avons observé qu'en présence d'inhibiteurs de protéases à large spectre, la sonde pourrait être protégée des activités protéolytiques des protéases (-54%, n=6, P ≤ 0,001). L'infusion in vivo de la sonde apoA-I-Cy5.5 dans les souris athérosclérotiques (Ldlr -/--Tg (apoB humaine)) a résulté en utilisant un système d'imagerie moléculaire combinant la fluorescence moléculaire tomographique et la résonance magnétique,en un signal de fluorescence dans l'aorte plus important que celui dans les aortes des souris de type sauvage C57Bl/6J (CTL). Les mesures in vivo ont été confirmées par l'imagerie ex vivo de l'aorte qui a indiqué une augmentation de 5 fois du signal fluorescent dans l'aorte des souris ATX (n=5) par rapport à l'aorte des souris (n=3) CTL (P ≤ 0,05). L'utilisation de cette sonde pourrait conduire à une meilleure compréhension des mécanismes moléculaires qui sous-tendent le développement et la progression de l'athérosclérose et l'amélioration des stratégies thérapeutiques à base de HDL.

The Euro-American psyche and the imaging of Samoa in the early 20th century

Drawing on English language sources and material from Western Samoa (now Samoa), this examination of photographically illustrated serial encyclopaedia and magazines proposes an alternative historical analysis of the colonial photographs of Samoa, the most extensively covered field in Oceanic photographic studies. Photographs published between the 1890s and World War II were not necessarily from that era, and despite claims in the text of illustrated publications of an unchanged, enduring, archaic tradition in Samoa, the amazing variety of content and subject matter often offered contradictory evidence, depicting a modern, adaptive and progressive Samoa. Contrary to orthodox historical analysis, the images of Samoa in illustrated magazines and encyclopaedia were not limited to a small, repetitive gallery of partially clothed women and costumed chiefs.

Re-imagining and re-imaging the nation through the history curriculum.

Nationalism is not a naturally occurring sentiment, but rather needs to be carefully nurtured and sustained in the social imaginary through the production and circulation of unifying narratives that invoke the nation’s imagined community. The school curriculum is crucial in this process, legitimating and disseminating selected narratives while de-legitimating and marginalising other accounts and their voices. Certain watershed events in nations’ histories have always posed political problems in history curricula (Cajani & Ross, 2007) –however the pressures and concerns of current times now suggest political solutions in history curricula. This paper briefly examines recent political debates in Australia to argue that the school history curriculum has become a site of increasing interest for the exercise of official forms of nationalism and the production of a nostalgic, celebratory national biography. The public debates around school history curriculum are theorised as nostalgic re-nationalising efforts in response to the march of cultural globalisation and its attendant uncertainties.

Quantifying the volume fraction and texture of cancellous bone using 3.0 Tesla magnetic resonance imaging

Introduction: 3.0 Tesla MRI offers the potential to quantify the volume fraction and structural texture of cancellous bone, along with quantification of marrow composition, in a single non-invasive examination. This study describes our preliminary investigations to identify parameters which describe cancellous bone structure including the relationships between texture and volume fraction.

Prehistoric hand stencils at Fern Cave, North Queensland (Australia): environmental and chronological implications of Raman spectroscopy and FT-IR imaging results

Raman spectroscopy and FT-IR imaging analyses of cave wall pigment samples from north Queensland (Australia) indicate that some hand stencils were undertaken during a dry environmental phase indicating late Holocene age. Other, earlier painting episodes also took place during dry environmental periods of the terminal Pleistocene and/or early Holocene. These results represent a rare opportunity to attain chronological information for rock art in conditions where insufficient carbon is present for radiocarbon dating.

Repeatability and validity of lens densitometry measured with Scheimpflug imaging

Purpose To assess the repeatability and validity of lens densitometry derived from the Pentacam Scheimpflug imaging system. Setting Eye Clinic, Queensland University of Technology, Brisbane, Australia. Methods This prospective cross-sectional study evaluated 1 eye of subjects with or without cataract. Scheimpflug measurements and slitlamp and retroillumination photographs were taken through a dilated pupil. Lenses were graded with the Lens Opacities Classification System III. Intraobserver and interobserver reliability of 3 observers performing 3 repeated Scheimpflug lens densitometry measurements each was assessed. Three lens densitometry metrics were evaluated: linear, for which a line was drawn through the visual axis and a mean lens densitometry value given; peak, which is the point at which lens densitometry is greatest on the densitogram; 3-dimensional (3D), in which a fixed, circular 3.0 mm area of the lens is selected and a mean lens densitometry value given. Bland and Altman analysis of repeatability for multiple measures was applied; results were reported as the repeatability coefficient and relative repeatability (RR). Results Twenty eyes were evaluated. Repeatability was high. Overall, interobserver repeatability was marginally lower than intraobserver repeatability. The peak was the least reliable metric (RR 37.31%) and 3D, the most reliable (RR 5.88%). Intraobserver and interobserver lens densitometry values in the cataract group were slightly less repeatable than in the noncataract group. Conclusion The intraobserver and interobserver repeatability of Scheimpflug lens densitometry was high in eyes with cataract and eyes without cataract, which supports the use of automated lens density scoring using the Scheimpflug system evaluated in the study