The serum small non-coding RNA (SncRNA) landscape as a molecular biomarker of age associated muscle dysregulation and insulin resistance in older adults.

Small noncoding RNAs (sncRNAs) are implicated in age-associated pathologies, including sarcopenia and insulin resistance (IR). As potential circulating biomarkers, most studies have focussed on microRNAs (miRNAs), one class of sncRNA. This study characterized the wider circulating sncRNA transcriptome of older individuals and associations with sarcopenia and IR.

DNA methylation of insulin signaling pathways is associated with HOMA2-IR in primary myoblasts from older adults.

Background: While ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.

Methods: We measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.

Adiposity is associated with widespread transcriptional changes and downregulation of longevity pathways in aged skeletal muscle.

Background: Amongst healthy older people, a number of correlates of impaired skeletal muscle mass and function have been defined. Although the prevalence of obesity is increasing markedly in this age group, information is sparse about the particular impacts of obesity on ageing skeletal muscle or the molecular mechanisms that underlie this and associated disease risk.

Methods: Here, we examined genome-wide transcriptional changes using RNA sequencing in muscle biopsies from 40 older community-dwelling men from the Hertfordshire Sarcopenia Study with regard to obesity (body mass index [BMI] >30 kg/m , n = 7), overweight (BMI 25-30, n = 19), normal weight (BMI < 25, n = 14), and per cent and total fat mass.

The effect of oxygen concentration on the speciation of laser ablated uranium.

In order to model the fate and transport of particles following a nuclear explosion, there must first be an understanding of individual physical and chemical processes that affect particle formation. One interaction pertinent to fireball chemistry and resultant debris formation is that between uranium and oxygen. In this study, we use laser ablation of uranium metal in different concentrations of oxygen gas, either O or O, to determine the influence of oxygen on rapidly cooling uranium.

Epigenome-wide association study of sarcopenia: findings from the Hertfordshire Sarcopenia Study (HSS).

Background: Sarcopenia is the age-related loss of muscle mass, strength, and function. Epigenetic processes such as DNA methylation, which integrate both genetic and environmental exposures, have been suggested to contribute to the development of sarcopenia. This study aimed to determine whether differences in the muscle methylome are associated with sarcopenia and its component measures: grip strength, appendicular lean mass index (ALMi), and gait speed.

Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice.

Folic acid (FA) intake has been associated with increased breast cancer risk in some studies. Although underlying mechanisms are unknown, epigenetic modifications that persistently alter transcription have been suggested. We tested the hypothesis that high FA (HFA) intake alters the adult mammary transcriptome in a manner consistent with increased potential for carcinogenesis, detectable beyond the period of intake.

The ground state of KO revisited: the millimeter and submillimeter spectrum of potassium oxide.

The millimeter/sub-millimeter spectrum of the KO radical has been recorded in the frequency range 90-534 GHz using direct absorption methods. The radical was synthesized by reacting potassium vapor, produced with a Broida-type oven, with either N2O or O2 mixed in argon carrier gas. Twenty-seven rotational transitions of KO were measured, each exhibiting a doublet structure with a relatively small splitting (∼100-200 MHz) that increased noticeably with frequency.

Nutritional modulation of the epigenome and its implication for future health.

Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression.

Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome.

Down syndrome (DS, trisomy 21) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21) encoding the Alzheimer's disease (AD) amyloid precursor protein (APP). Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Abeta), early-onset AD neuropathology, and age-dependent cognitive sequelae.

The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.

Background: The amyloid beta-protein (Abeta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, Abeta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities.

Rural oral health workforce issues in NSW and the Charles Sturt University Dentistry Program.

Adequate numbers of dental, medical and allied health professionals in rural and regional areas of NSW are vital for the health of these populations and supporting local community structures and economies. Well-documented shortages of health professionals are a major social and political issue in rural and regional communities and this workforce shortfall is recognised by both the NSW Government State Plan and the State Health Plan. This paper outlines rural and regional dental workforce shortages in NSW and describes current rural oral health workforce initiatives, including the new Charles Sturt University Dentistry Program.

Pre-treatment with a non-therapeutic dose of cisplatin increases solid tumour response to liposomal-p53 gene therapy- An in vivo study.

Successful liposomal-mediated gene therapy is often limited by poor transfection efficiencies. One method previously shown to increase the efficiency of liposomal gene delivery is through the administration of a non-therapeutic dose of the chemotherapeutic drug cisplatin prior to lipofection. The currents study aims to utilise this method to deliver lipoplexes containing the p53 tumour suppressor gene with the aim of increasing therapeutic effect of the p53 gene on a solid tumour in vivo.

Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE.

Unlabelled: We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined.

Development of polysaccharide gel coated pellets for oral administration 1. Physico-mechanical properties.

Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets.

Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro.

Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting.

Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro.

Adenoviral vectors have been commonly used in gene therapy protocols but the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced, which limits further administration. This study examines the effectiveness of a novel combination of microspheres and liposomes for the shielding of adenovirus from neutralising antibodies in an in-vitro setting.

Respiratory function testing: the impact of respiratory scientists on the training and support of primary health care providers.

Objective: In rural Australia access to doctors is limited, access to respiratory physicians even more so and these are the traditional sources of lung function testing. The aim of this study was to assess the feasibility of training and supporting existing rural primary healthcare providers in lung function testing as a screening and monitoring mechanism due to the shortage of healthcare professionals capable of providing such a service.

Methodology: As pharmacists are readily accessible healthcare professionals, they were trained in spirometry measurement and supported with ongoing quality assurance by respiratory scientists.

In-vitro evaluation of ion-exchange microspheres for the sustained release of liposomal-adenoviral conjugates.

This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify the net charge of the AL complexes by varying the concentrations of adenovirus to liposomes. The modification of the net charge resulted in altered binding and release characteristics.

Modified microplex vector enhances transfection of cells in culture while maintaining tumour-selective gene delivery in-vivo.

A non-commercial liposome (dimethyl dioctadecyl ammonium bromide:dioleoyl phosphatidylethanolamine) was compared with a commercial variety (Lipofectamine) for transfection of cultured rat adenocarcinoma cells and in an in-vivo kidney tumour model. Transfection of the cells in culture and in tumours in-vivo was variable with both types of liposomes. A high-dose microplex (lipoplex-microsphere) vector enhanced liposome-mediated transfection of cells in culture.

A model for evaluating selective delivery of plasmid DNA to tumours via the vasculature.

A comparative study of plasmid DNA delivery in a newly established rat renal solid tumour model was undertaken. Free plasmid, plasmids bound to microspheres, and plasmids complexed with liposomes were selectively delivered to tumours via arterial catheterisation. Forty-eight hours post delivery, tumour to normal kidney tissue chloramphenicol acetyltransferase expression ratios were as follows: free (1.

Liposomes containing cationic dimethyl dioctadecyl ammonium bromide: formulation, quality control, and lipofection efficiency.

This article describes a novel, simple, and relatively inexpensive method to prepare cationic liposomes using an ethanol injection/pressure extrusion method. The study also demonstrated that binding erythrosine dye to cationic liposomes results in a shift of the absorption maximum of the dye from 528 nm to 549 nm at pH 4.25, allowing quantification and visualization of these vesicles.