Synthesis and cellular uptake of neutral rhenium(I) morpholine complexes.

Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules which have several shortcomings including small Stokes shifts, short emission lifetimes, and susceptibility to photobleaching. To explore alternative lysosome targeting imaging agents we have used a rhenium based phosphorescent platform which has been previously demonstrated to have an improved Stokes shift, a long lifetime emission, and is highly photostable.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients.

Rhenium(I) conjugates as tools for tracking cholesterol in cells.

Cholesterol is vital to control membrane integrity and fluidity, but is also a precursor to produce steroid hormones, bile acids, and vitamin D. Consequently, altered cholesterol biology has been linked to many diseases, including metabolic syndromes and cancer. Defining the intracellular pools of cholesterol and its trafficking within cells is essential to understand both normal cell physiology and mechanisms of pathogenesis.

Fluorescence Microscopy-An Outline of Hardware, Biological Handling, and Fluorophore Considerations.

Fluorescence microscopy has become a critical tool for researchers to understand biological processes at the cellular level. Micrographs from fixed and live-cell imaging procedures feature in a plethora of scientific articles for the field of cell biology, but the complexities of fluorescence microscopy as an imaging tool can sometimes be overlooked or misunderstood. This review seeks to cover the three fundamental considerations when designing fluorescence microscopy experiments: (1) hardware availability; (2) amenability of biological models to fluorescence microscopy; and (3) suitability of imaging agents for intended applications.

Neutral Re(I) Complex Platform for Live Intracellular Imaging.

Luminescent metal complexes are a valuable platform for the generation of cell imaging agents. However, many metal complexes are cationic, a factor that can dominate the intracellular accumulation to specific organelles. Neutral Re(I) complexes offer a more attractive platform for the development of bioconjugated imaging agents, where charge cannot influence their intracellular distribution.

Detecting metabolic differences in fetal and adult sheep adipose and skeletal muscle tissues.

The primary metabolic pathway required to produce ATP differs as a result of tissue type, developmental stage and substrate availability. We utilized molecular and histological techniques to define the metabolic status in foetal and adult, adipose and skeletal muscle tissues. Redox ratios of these tissues were also determined optically by two-photon microscopy.

Lipid profiles of prostate cancer cells.

Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a).

Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane.

The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion.

Mitochondrial imaging in live or fixed tissues using a luminescent iridium complex.

Mitochondrial morphology is important for the function of this critical organelle and, accordingly, altered mitochondrial structure is exhibited in many pathologies. Imaging of mitochondria can therefore provide important information about disease presence and progression. However, mitochondrial imaging is currently limited by the availability of agents that have the capacity to image mitochondrial morphology in both live and fixed samples.

Label-free imaging of redox status and collagen deposition showing metabolic differences in the heart.

The heart has high metabolic demand to maintain function. The primary source of energy supply to support correct contractile muscle function differs between a fetus and an adult. In fetal life, ATP is primarily generated by glycolysis and lactate oxidation, whereas following birth, there is a shift towards a reliance on mitochondrial metabolism and fatty acid oxidation.

Synthesis, photophysical and cellular characterisation of folate and methotrexate labelled luminescent lanthanide complexes.

In this work we have developed a series of highly emissive europium(III) and terbium(III) complexes tethered to either folic acid (FA) or methotrexate (MTX), with the aim of developing visual probes that enable the imaging of folate receptors in cancer cells. The synthesis, photophysical properties and cellular behaviour are reported for four new lanthanide Ln(III) complexes, where either FA or MTX are tethered to 1,4,7-tris(carbonylmethyl)-10-(4'-quinolineacetic acid, (7'-acetamido)-1',2'-dihydro-2'-oxo)-1,4,7,10-tetraazacyclododecane Ln(III) complex, and Ln(III)=Eu(III) or Tb(III); herein referred to as Eu-FA, Eu-MTX, Tb-FA or Tb-MTX. All four complexes were found to be sensitive to the presence of the folate receptor in a range of cell lines.

Investigating Intracellular Localisation and Cytotoxicity Trends for Neutral and Cationic Iridium Tetrazolato Complexes in Live Cells.

A family of five neutral cyclometalated iridium(III) tetrazolato complexes and their methylated cationic analogues have been synthesised and characterised. The complexes are distinguished by variations of the substituents or degree of π conjugation on either the phenylpyridine or tetrazolato ligands. The photophysical properties of these species have been evaluated in organic and aqueous media, revealing predominantly a solvatochromic emission originating from mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity.

Label-free imaging of healthy and infarcted fetal sheep hearts by two-photon microscopy.

Coronary heart disease is one of the largest causes of death worldwide, making this a significant health care issue. A critical problem for the adult human heart is that it does not undergo effective repair in response to damage, leaving patients with a poor prognosis. Unlike the adult, fetal hearts have the ability to repair after myocardial damage.

Proteome Analysis of Drosophila Mutants Identifies a Regulatory Role for 14-3-3ε in Metabolic Pathways.

The evolutionary conserved family of 14-3-3 proteins appears to have a role in integrating numerous intracellular pathways, including signal transduction, intracellular trafficking, and metabolism. However, little is known about how this interactive network might be affected by the direct abrogation of 14-3-3 function. The loss of Drosophila 14-3-3ε resulted in reduced survival of mutants during larval-to-adult transition, which is known to depend on an energy supply coming from the histolysis of fat body tissue.

A Molecular Probe for the Detection of Polar Lipids in Live Cells.

Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, obesity, heart disease, immune disorders and cancers, which commonly display altered lipid transport and metabolism. However, the investigation of these important cellular processes has been limited by the availability of specific tools to visualise lipids in live cells.

Imaging nuclear, endoplasmic reticulum and plasma membrane events in real time.

Live cell imaging can provide important information on cellular dynamics; however, the full utilisation of this technology has been hampered by the limitations of imaging reagents. Metal-based complexes have the potential to overcome many of the issues common to many current imaging agents. The rhenium (I)-based complex fac-[Re(CO)3 (1,10-phenanthroline)(4-pyridyltetrazolate)], herein referred to as ReZolve-ER(™) , shows promise as a live cell imaging agent with rapid cell uptake, low cytotoxicity, resistance to photobleaching and compatibility with multicolour imaging.

Adult mosquito trap sensitivity for detecting exotic mosquito incursions and eradication: a study using EVS traps and the Australian southern saltmarsh mosquito, Aedes camptorhynchus.

Adult mosquito traps are commonly used in biosecurity surveillance for the detection of exotic mosquito incursions or for the demonstration of elimination. However, traps are typically deployed without knowledge of how many are required for detecting differing numbers of the target species. The aim of this study was to determine the sensitivity (i.

The extinction of dengue through natural vulnerability of its vectors.

Background: Dengue is the world's most important mosquito-borne viral illness. Successful future management of this disease requires an understanding of the population dynamics of the vector, especially in the context of changing climates. Our capacity to predict future dynamics is reflected in our ability to explain the significant historical changes in the distribution and abundance of the disease and its vector.