Archaeaphage therapy to control rumen methanogens

Phage therapy is becoming increasingly important as a means of eradicating or controlling microbial populations and has been raised as a potential strategy to reduce methane emissions from ruminants. To date, very little is currently known about phages which may infect the methane-producing archaeal strains (methanogens) dominant within the rumen of Australian cattle, such as the Methanobrevibacter ruminantium. This project aimed to assemble a collection of phages to be employed in phage therapy. A range of animal-derived and environmental source samples were tested using culture-based methodology, however no lytic phages of methanogens were isolated. Given the dearth of knowledge regarding phages of rumen methanogens, this project established that these naturally-occurring phages may be present in very low concentrations within the rumen and this will need to be considered in future methanogen-phage isolation investigations. The project has begun the process of developing and adapting new methodologies for detecting and examining these phages

Using genomic data to make indirect (and unauthorized) estimates of disease risk

The number of genetic factors associated with common human traits and disease is increasing rapidly, and the general public is utilizing affordable, direct-to-consumer genetic tests. The results of these tests are often in the public domain. A combination of factors has increased the potential for the indirect estimation of an individual's risk for a particular trait. Here we explain the basic principals underlying risk estimation which allowed us to test the ability to make an indirect risk estimation from genetic data by imputing Dr. James Watson's redacted apolipoprotein E gene (APOE) information. The principles underlying risk prediction from genetic data have been well known and applied for many decades, however, the recent increase in genomic knowledge, and advances in mathematical and statistical techniques and computational power, make it relatively easy to make an accurate but indirect estimation of risk. There is a current hazard for indirect risk estimation that is relevant not only to the subject but also to individuals related to the subject; this risk will likely increase as more detailed genomic data and better computational tools become available.

Age-related changes in hepatic function: An update on implications for drug therapy

The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.

A market assessment and evaluation of structural roundwood products from hardwood pulp plantations.

Roundwood structures have always been used for temporary and low cost shelters and other fleeting structures. Novel concepts for the use of plantation hardwoods in roundwood form in construction were developed and circulated along with an electronic questionnaire to stakeholders representing growers, designers and users of hardwood. Responses indicate that there is a high level of interest in developing products from the emerging small roundwood resource and a detailed program of research was supported and recommended by the majority of participants in the survey. These results indicate a high level of support for further investigation into the use of plantation hardwood for roundwood components. Respondents representing a wide range of stakeholders have indicated that to gain benefit from a detailed project they would require solutions for connection systems and protection from pests and weathering, indications of cost and assurance of ongoing supply for niche applications, data for strength, acoustic dampening and thermal insulation properties, acceptance by regulatory authorities and training for on-site construction.

Adenoviral gene therapy for non-small cell lung cancer

Adenoviral gene therapy is an experimental approach to cancer refractory to standard cancer therapies. Adenoviruses can be utilized as vectors to deliver therapeutic transgenes into cancer cells, while gene therapy with oncolytic adenoviruses exploits the lytic potential of viruses to kill tumor cells. Although adenoviruses demonstrate several advantages over other vectors - such as the unparalleled transduction efficacy and natural tropism to a wide range of tissues - the gene transfer efficacy to cancer cells has been limited, consequently restricting the therapeutic effect. There are, however, several approaches to circumvent this problem. We utilized different modified adenoviruses to obtain information on adenovirus tropism towards non-small cell lung cancer (NSCLC) cells. To enhance therapeutic outcome, oncolytic adenoviruses were evaluated. Further, to enhance gene delivery to tumors, we used mesenchymal stem cells (MSCs) as carriers. To improve adenovirus specificity, we investigated whether widely used cyclooxygenase 2 (Cox-2) promoter is induced by adenovirus infection in nontarget cells and whether selectivity can be retained by the 3 untranslated region (UTR) AU-rich elements. In addition, we investigated whether switching adenovirus fiber can retain gene delivery in the presence of neutralizing antibodies. Our results show that adenoviruses, whose capsids were modified with arginine-glycine-aspartatic acid (RGD-4C), the serotype 3 knob, or polylysins displayed enhanced gene transfer into NSCLC cell lines and fresh clinical specimens from patients. The therapeutic efficacy was further improved by using respective oncolytic adenoviruses with isogenic 24bp deletion in the E1A gene. Cox-2 promoter was also shown to be induced in normal and tumor cells following adenovirus infection, but utilization of 3 UTR elements can increase the tumor specificity of the promoter. Further, the results suggested that use of MSCs could enhance the bioavailability and delivery of adenoviruses into human tumors, although cells had no tumor tropism per se. Finally, we demonstrated that changing adenovirus fiber can allow virus to escape from existing neutralizing antibodies when delivered systemically. In conclusion, these results reveal that adenovirus gene transfer and specificity can be increased by using modified adenoviruses and MSCs as carriers, and fiber modifications simultaneously decrease the effect of neutralizing antibodies. This promising data suggest that these approaches could translate into clinical testing in patients with NSCLC refractory to current modalities.

Selection of Corymbia citriodora for pulp productivity

Evaluation of a series of spotted gum (Corymbia citirodora) progeny trials, established in the subtropical region of Queensland, Australia, was undertaken to provide information for the development of advanced-generation breeding populations suitable for pulp production. Measurements of growth at two ages were combined with assessments of wood density and pulp yield from a selected sample of provenances to provide comparisons between provenances, to generate genetic parameter estimates and to predict genetic gain potential. Although growth at this age was moderate relative to other eucalypts, the near-infrared predictions of average wood density of 756 kg m(-3) and pulp yield of 55% indicate the species has considerable potential as a pulpwood crop. A pulp productivity breeding objective was used to identify production populations using a range of selection trait weightings to determine potential genetic gain for pulp productivity. Genetic parameters indicated (1) levels of genetic control were moderate for all traits and higher for wood property traits, (2) genetic improvements could be achieved by selection among and within provenances with greater levels of improvement available from selection within populations, (3) genotype by environment interactions were negligible, (4) genetic correlations between traits were favourable, and (5) selection of volume production alone would maximise improvements in pulp productivity.

Association genetics in Corymbia citriodora subsp variegata identifies single nucleotide polymorphisms affecting wood growth and cellulosic pulp yield

Wood is an important biological resource which contributes to nutrient and hydrology cycles through ecosystems, and provides structural support at the plant level. Thousands of genes are involved in wood development, yet their effects on phenotype are not well understood. We have exploited the low genomic linkage disequilibrium (LD) and abundant phenotypic variation of forest trees to explore allelic diversity underlying wood traits in an association study. Candidate gene allelic diversity was modelled against quantitative variation to identify SNPs influencing wood properties, growth and disease resistance across three populations of Corymbia citriodora subsp. variegata, a forest tree of eastern Australia. Nine single nucleotide polymorphism (SNP) associations from six genes were identified in a discovery population (833 individuals). Associations were subsequently tested in two smaller populations (130160 individuals), validating our findings in three cases for actin 7 (ACT7) and COP1 interacting protein 7 (CIP7). The results imply a functional role for these genes in mediating wood chemical composition and growth, respectively. A flip in the effect of ACT7 on pulp yield between populations suggests gene by environment interactions are at play. Existing evidence of gene function lends strength to the observed associations, and in the case of CIP7 supports a role in cortical photosynthesis.

Reliability and validity of objective measures of physical activity in youth with cerebral palsy who are ambulatory

BACKGROUND Physical therapy for youth with cerebral palsy (CP) who are ambulatory includes interventions to increase functional mobility and participation in physical activity (PA). Thus, reliable and valid measures are needed to document PA in youth with CP. OBJECTIVE The purpose of this study was to evaluate the inter-instrument reliability and concurrent validity of 3 accelerometer-based motion sensors with indirect calorimetry as the criterion for measuring PA intensity in youth with CP. METHODS Fifty-seven youth with CP (mean age=12.5 years, SD=3.3; 51% female; 49.1% with spastic hemiplegia) participated. Inclusion criteria were: aged 6 to 20 years, ambulatory, Gross Motor Function Classification System (GMFCS) levels I through III, able to follow directions, and able to complete the full PA protocol. Protocol activities included standardized activity trials with increasing PA intensity (resting, writing, household chores, active video games, and walking at 3 self-selected speeds), as measured by weight-relative oxygen uptake (in mL/kg/min). During each trial, participants wore bilateral accelerometers on the upper arms, waist/hip, and ankle and a portable indirect calorimeter. Intraclass coefficient correlations (ICCs) were calculated to evaluate inter-instrument reliability (left-to-right accelerometer placement). Spearman correlations were used to examine concurrent validity between accelerometer output (activity and step counts) and indirect calorimetry. Friedman analyses of variance with post hoc pair-wise analyses were conducted to examine the validity of accelerometers to discriminate PA intensity across activity trials. RESULTS All accelerometers exhibited excellent inter-instrument reliability (ICC=.94-.99) and good concurrent validity (rho=.70-.85). All accelerometers discriminated PA intensity across most activity trials. LIMITATIONS This PA protocol consisted of controlled activity trials. CONCLUSIONS Accelerometers provide valid and reliable measures of PA intensity among youth with CP.

Phage therapy in livestock methane amelioration

Viruses of prokaryotes (phages) are obligate microbial pathogens that can, in the lytic phase of development, infect and lyse their respective bacterial or archaeal hosts. As such, these viruses can reduce the population density of their hosts rapidly, and have been viewed as possible agents of biological control (phage therapy). Phage therapy is becoming increasingly important as a means of eradicating or controlling microbial populations as the use of antibiotics and chemical treatments becomes both less effective and less publicly acceptable. Phage therapy has therefore been raised as a potential strategy to reduce methane (CH 4) emissions from ruminants, providing an innovative biological approach, harnessing the potent, yet targeted, biocidal attributes of these naturally occurring microbial predators.

Phage therapy in livestock methane amelioration.

Viruses of prokaryotes (phages) are obligate microbial pathogens that can, in the lytic phase of development, infect and lyse their respective bacterial or archaeal hosts. As such, these viruses can reduce the population density of their hosts rapidly, and have been viewed as possible agents of biological control (phage therapy). Phage therapy is becoming increasingly important as a means of eradicating or controlling microbial populations as the use of antibiotics and chemical treatments becomes both less effective and less publicly acceptable. Phage therapy has therefore been raised as a potential strategy to reduce methane (CH4) emissions from ruminants, providing an innovative biological approach, harnessing the potent, yet targeted, biocidal attributes of these naturally occurring microbial predators.

Soil N availability, rather than N deposition, controls indirect N2O emissions

Ammonia volatilised and re-deposited to the landscape is an indirect N2O emission source. This study established a relationship between N2O emissions, low magnitude NH4 deposition (0–30  kg N ha − 1 ), and soil moisture content in two soils using in-vessel incubations. Emissions from the clay soil peaked ( < 0.002 g N [ g soil ] − 1 min − 1 ) from 85 to 93% WFPS (water filled pore space), increasing to a plateau as remaining mineral-N increased. Peak N2O emissions for the sandy soil were much lower ( < 5 × 10 − 5 μg N [ g soil ] − 1 min − 1 ) and occurred at about 60% WFPS, with an indistinct relationship with increasing resident mineral N due to the low rate of nitrification in that soil. Microbial community and respiration data indicated that the clay soil was dominated by denitrifiers and was more biologically active than the sandy soil. However, the clay soil also had substantial nitrifier communities even under peak emission conditions. A process-based mathematical denitrification model was well suited to the clay soil data where all mineral-N was assumed to be nitrified ( R 2 = 90 % ), providing a substrate for denitrification. This function was not well suited to the sandy soil where nitrification was much less complete. A prototype relationship representing mineral-N pool conversions (NO3− and NH4+) was proposed based on time, pool concentrations, moisture relationships, and soil rate constants (preliminary testing only). A threshold for mineral-N was observed: emission of N2O did not occur from the clay soil for mineral-N <70 mg ( kg of soil ) − 1 , suggesting that soil N availability controls indirect N2O emissions. This laboratory process investigation challenges the IPCC approach which predicts indirect emissions from atmospheric N deposition alone.