A three-nucleotide mutation altering the Maize streak virus Rep pRBR-interaction motif reduces symptom severity in maize and partially reverts at high frequency without restoring pRBR-Rep binding

Geminivirus infectivity is thought to depend on interactions between the virus replication-associated proteins Rep or RepA and host retinoblastoma-related proteins (pRBR), which control cell-cycle progression. It was determined that the substitution of two amino acids in the Maize streak virus (MSV) RepA pRBR-interaction motif (LLCNE to LLCLK) abolished detectable RepA-pRBR interaction in yeast without abolishing infectivity in maize. Although the mutant virus was infectious in maize, it induced less severe symptoms than the wild-type virus. Sequence analysis of progeny viral DNA isolated from infected maize enabled detection of a high-frequency single-nucleotide reversion of C(601)A in the 3 nt mutated sequence of the Rep gene. Although it did not restore RepA-pRBR interaction in yeast, sequence-specific PCR showed that, in five out of eight plants, the C(601)A reversion appeared by day 10 post-inoculation. In all plants, the C(601)A revertant eventually completely replaced the original mutant population, indicating a high selection pressure for the single-nucleotide reversion. Apart from potentially revealing an alternative or possibly additional function for the stretch of DNA that encodes the apparently non-essential pRBR-interaction motif of MSV Rep, the consistent emergence and eventual dominance of the C(601)A revertant population might provide a useful tool for investigating aspects of MSV biology, such as replication, mutation and evolution rates, and complex population phenomena, such as competition between quasispecies and population turnover. © 2005 SGM.

Dry powder inhaler formulations : effect of carrier size on the drug dispersion

Background: The size of the carrier influences drug aerosolization from a dry powder inhaler (DPI) formulation. Lactose particles with irregular shape and rough surface in a variety of sizes are additionally used as carriers; however, contradictory reports exist regarding the effect of carrier size on the dispersion of drug. We examined the influence of the spherical particle size of the biodegradable polylactide-co-glycolide (PLGA) carrier on the aerosolization of a model drug, salbutamol sulphate (SS). Methods: Four different sizes (20-150 µm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were determined by laser diffraction and SEM, respectively. Results: The FPF was found to increase from 5.6% to 21.3% with increasing carrier sizeup to150 µm. Conclusions: The aerosolization of drug increased linearly with the size of polymer carriers. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Dry powder inhaler formulations-effect of polymer carrier size on the drug dispersion

Background The size of the carrier influences the aerosolization of drug from a dry powder inhaler (DPI) formulation. Currently, lactose monohydrate particles in a variety of sizes are preferably used in carrier based DPI formulations of various drugs; however, contradictory reports exist regarding the effect of the size of the carrier on the dispersion of drug. In this study we examined the influence of the intrinsic particle size of the polymeric carrier on the aerosolization of a model drug salbutamol sulphate (SS). Methods Four different sizes (20–150 lm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS particles from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were by laser diffraction and SEM, respectively. Results The FPF from these carriers was found to be increasing from 5.6% to 21.3% with increasing the carrier size. The FPF was found to be greater (21%) with the highest particle size of the carrier (150 lm). Conclusions The aerosolization of drug was dependent on the size of polymer carriers. The smaller size of the carrier resulted in lower FPF which was increased with increasing the carrier size. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Effect of chemical conjugation of L-leucine to chitosan on the dispersibility and drug release of a dry powder inhaler nanoparticle formulation

Purpose: This study investigated the effect of chemical conjugation of the amino acid L-leucine to the polysaccharide chitosan on the dispersibility and drug release pattern of a polymeric nanoparticle (NP)-based controlled release dry powder inhaler (DPI) formulation. Methods: A chemical conjugate of L-leucine with chitosan was synthesized and characterized by Infrared (IR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis and X-ray Photoelectron Spectroscopy (XPS). Nanoparticles of both chitosan and its conjugate were prepared by a water-in-oil emulsification – glutaraldehyde cross-linking method using the antihypertensive agent, diltiazem (Dz) hydrochloride as the model drug. The surface morphology and particle size distribution of the nanoparticles were determined by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The dispersibility of the nanoparticle formulation was analysed by a Twin Stage Impinger (TSI) with a Rotahaler as the DPI device. Deposition of the particles in the different stages was determined by gravimetry and the amount of drug released was analysed by UV spectrophotometry. The release profile of the drug was studied in phosphate buffered saline at 37 ⁰C and analyzed by UV spectrophotometry. Results: The TSI study revealed that the fine particle fractions (FPF), as determined gravimetrically, for empty and drug-loaded conjugate nanoparticles were significantly higher than for the corresponding chitosan nanoparticles (24±1.2% and 21±0.7% vs 19±1.2% and 15±1.5% respectively; n=3, p<0.05). The FPF of drug-loaded chitosan and conjugate nanoparticles, in terms of the amount of drug determined spectrophotometrically, had similar values (21±0.7% vs 16±1.6%). After an initial burst, both chitosan and conjugate nanoparticles showed controlled release that lasted about 8 to 10 days, but conjugate nanoparticles showed twice as much total drug release compared to chitosan nanoparticles (~50% vs ~25%). Conjugate nanoparticles also showed significantly higher dug loading and entrapment efficiency than chitosan nanoparticles (conjugate: 20±1% & 46±1%, chitosan: 16±1% & 38±1%, n=3, p<0.05). Conclusion: Although L-leucine conjugation to chitosan increased dispersibility of formulated nanoparticles, the FPF values are still far from optimum. The particles showed a high level of initial burst release (chitosan, 16% and conjugate, 31%) that also will need further optimization.

Dry tropics water smart : a community based approach to residential outdoor water consumption

This paper discusses the Townsville City Council Dry Tropics Water Smart (DTWS) initiative, developed by TCC Integrated Sustainability Services (ISS) and Townsville Water, and informed by The University of Adelaide. The program draws on many years of experience by the TCC team to blend key community-based research approaches in order to develop this residential outdoor water conservation program. Several community pilots have been conducted to test different behaviour change strategies and messages. This paper outlines recent steps taken to develop the community trials, as guided by a combination of behaviour change theories including community-based social marketing and thematic communications methods. Some preliminary results are outlined focused on community uptake of different strategies, community perceptions of communication materials, and some insights into the effectiveness of outdoor water hardware.

Preparation and in vitro evaluation of a polymer based controlled release dry powder inhaler formulation for pulmonary delivery

This thesis described the synthesis of an L-leucine conjugate of the biodegradable polymer, chitosan and its potential application for the development of controlled release nanoparticulate dry powder inhaler (DPI) formulations. The study demonstrated that the physicochemical properties of conjugated chitosan nanoparticles had favourable effects on the dispersibility and controlled release profile of a model drug. The toxicity profile of the nanoparticulate formulation revealed promising outcome for its use in pulmonary delivery. The chitosan conjugate produced in this project would be useful for the application of polymer nanoparticulate systems for efficient lung delivery of drugs.

Terrestrial invertebrates of dry river beds are not simply subsets of riparian assemblages

Dry river beds are common worldwide and are rapidly increasing in extent due to the effects of water management and prolonged drought periods due to climate change. While attention has been given to the responses of aquatic invertebrates to drying rivers, few studies exist on the terrestrial invertebrates colonizing dry river beds. Dry river beds are physically harsh and they often differ substantially in substrate, topography, microclimate and inundation frequency from adjacent riparian zones. Given these differences, we predicted that dry river beds provide a unique habitat for terrestrial invertebrates, and that their assemblage composition differs from that in adjacent riparian zones. Dry river beds and riparian zones in Australia and Italy were sampled for terrestrial invertebrates with pitfall traps. Sites differed in substrate type, climate and flow regime. Dry river beds contained diverse invertebrate assemblages and their composition was consistently different from adjacent riparian zones, irrespective of substrate, climate or hydrology. Although some taxa were shared between dry river beds and riparian zones, 66 of 320 taxa occurred only in dry river beds. Differences were due to species turnover, rather than shifts in abundance, indicating that dry river bed assemblages are not simply subsets of riparian assemblages. Some spatial patterns in invertebrate assemblages were associated with environmental variables (irrespective of habitat type), but these associations were statistically weak. We suggest that dry river beds are unique habitats in their own right. We discuss potential human stressors and management issues regarding dry river beds and provide recommendations for future research.

RAD51-associated Protein 1 (RAD51AP1) Interacts with the Meiotic Recombinase DMC1 through a Conserved Motif

Homologous recombination (HR) reactions mediated by the RAD51 recombinase are essential for DNA and replication fork repair, genome stability, and tumor suppression. RAD51-associated protein 1 (RAD51AP1) is an important HR factor that associates with and stimulates the recombinase activity of RAD51. We have recently shown that RAD51AP1 also partners with the meiotic recombinase DMC1, displaying isoform-specific interactions with DMC1. Here, we have characterized the DMC1 interaction site in RAD51AP1 by a series of truncations and point mutations to uncover a highly conserved WVPP motif critical for DMC1 interaction but dispensable for RAD51 association. This RAD51AP1 motif is reminiscent of the FVPP motif in the tumor suppressor protein BRCA2 that mediates DMC1 interaction. These results further implicate RAD51AP1 in meiotic HR via RAD51 and DMC1.

Unusually cold and dry winters increase mortality in Australia

Seasonal patterns in mortality have been recognised for decades, with a marked excess of deaths in winter, yet our understanding of the causes of this phenomenon is not yet complete. Research has shown that low and high temperatures are associated with increased mortality independently of season; however, the impact of unseasonal weather on mortality has been less studied. In this study, we aimed to determine if unseasonal patterns in weather were associated with unseasonal patterns in mortality. We obtained daily temperature, humidity and mortality data from 1988 to 2009 for five major Australian cities with a range of climates. We split the seasonal patterns in temperature, humidity and mortality into their stationary and non-stationary parts. A stationary seasonal pattern is consistent from year-to-year, and a non-stationary pattern varies from year-to-year. We used Poisson regression to investigate associations between unseasonal weather and an unusual number of deaths. We found that deaths rates in Australia were 20–30% higher in winter than summer. The seasonal pattern of mortality was non-stationary, with much larger peaks in some winters. Winters that were colder or drier than a typical winter had significantly increased death risks in most cities. Conversely summers that were warmer or more humid than average showed no increase in death risks. Better understanding the occurrence and cause of seasonal variations in mortality will help with disease prevention and save lives.

Pt(II) bipyridyl complexes bearing substituted fluorenyl motif on the bipyridyl and acetylide ligands : synthesis, photophysics, and reverse saturable absorption

A series of Pt(II) diimine complexes bearing benzothiazolylfluorenyl (BTZ-F8), diphenylaminofluorenyl (NPh2- F8), or naphthalimidylfluorenyl (NI-F8) motifs on the bipyridyl or acetylide ligands (Pt-4−Pt-8), (i.e., {4,4′-bis[7-R1-F8-(≡)n-]bpy}Pt(7- R2-F8- ≡ -)2, where F8 = 9,9′-di(2-ethylhexyl)fluorene, bpy = 2,2′- bipyridine, Pt-4: R1 = R2 = BTZ, n = 0; Pt-5: R1 = BTZ, R2 = NI, n = 0; Pt-6: R1 = R2 = BTZ, n = 1; Pt-7: R1 = BTZ, R2 = NPh2, n = 1; Pt- 8: R1 = NPh2, R2 = BTZ, n = 1) were synthesized. Their ground-state and excited-state properties and reverse saturable absorption performances were systematically investigated. The influence of these motifs on the photophysics of the complexes was investigated by spectroscopic methods and simulated by time-dependent density functional theory (TDDFT). The intense absorption bands below 410 nm for these complexes is assigned to predominantly 1π,π* transitions localized on either the bipyridine or the acetylide ligands; while the broad low-energy absorption bands between 420 and 575 nm are attributed to essentially 1MLCT (metal-to-ligand charge transfer)/ 1LLCT (ligand-to-ligand charge transfer) transitions, likely mixed with some 1ILCT (intraligand charge transfer) transition for Pt-4−Pt-7, and predominantly 1ILCT transition admixing with minor 1MLCT/1LLCT characters for Pt-8. The different substituents on the acetylide and bipyridyl ligands, and the degrees of π-conjugation in the bipyridyl ligand influence both the 1π,π* and charge transfer transitions pronouncedly. All complexes are emissive at room temperature. Upon excitation at their respective absorption band maxima, Pt-4, Pt-6, and Pt-8 exhibit acetylide ligand localized 1π,π* fluorescence and 3MLCT/3LLCT phosphorescence in CH2Cl2, while Pt-5 manifests 1ILCT fluorescence and 3ILCT phosphorescence. However, only 1LLCT fluorescence was observed for Pt-7 at room temperature. The nanosecond transient absorption study was carried out for Pt-4−Pt-8 in CH3CN. Except for Pt-7 that contains NPh2 at the acetylide ligands, Pt-4−Pt-6 and Pt-8 all exhibit weak to moderate excited-state absorption in the visible spectral region. Reverse saturable absorption (RSA) of these complexes was demonstrated at 532 nm using 4.1 ns laser pulses in a 2 mm cuvette. The strength of RSA follows this trend: Pt-4 > Pt-5 > Pt-7 > Pt-6 > Pt-8. Incorporation of electron-donating substituent NPh2 on the bipyridyl ligand significantly decreases the RSA, while shorter π-conjugation in the bipyridyl ligand increases the RSA. Therefore, the substituent at either the acetylide ligands or the bipyridyl ligand could affect the singlet and triplet excited-state characteristics significantly, which strongly influences the RSA efficiency.

Mark Shorter : Dry Gulch

This is a catalogue essay for Mark Shorter's exhibition "Dry Gulch" held at Boxcopy, Brisbane, in 2014. "Dry Gulch is a durational performance and installation in which the artist, Mark Shorter, occupies the pitch-­‐black gallery space for the opening hours of the exhibition. While drawing on the vocabulary of 1970s conceptual performance art (think Vito Acconci, Chris Burden, Marina Abramovic et al.), it is also an exhibition specifically of its time and its place. It probes and, at times, illuminates (pun intended) some of the dark corners of subjective experiences in a contemporary context typically swamped by distractions and saturated with templates for self-­‐actualisation...."

Analysis of arm elevation muscle activity through different movement planes and speeds during in-water and dry-land exercise

Objective The objectives of this cross-sectional, analytical inference analysis were to compare shoulder muscle activation at arm elevations of 0° to 90° through different movement planes and speeds during in-water and dry-land exercise and to extrapolate this information to a clinical rehabilitation model. Methods Six muscles of right-handed adult subjects (n = 16; males/females: 50%; age: 26.1 ± 4.5 years) were examined with surface electromyography during arm elevation in water and on dry land. Participants randomly performed 3 elevation movements (flexion, abduction, and scaption) through 0° to 90°. Three movement speeds were used for each movement as determined by a metronome (30°/sec, 45°/sec, and 90°/sec). Dry-land maximal voluntary contraction tests were used to determine movement normalization. Results Muscle activity levels were significantly lower in water compared with dry land at 30°/sec and 45°/sec but significantly higher at 90°/sec. This sequential progressive activation with increased movement speed was proportionally higher on transition from gravity-based on-land activity to water-based isokinetic resistance. The pectoralis major and latissimus dorsi muscles showed higher activity during abduction and scaption. Conclusions These findings on muscle activation suggest protocols in which active flexion is introduced first at low speeds (30°/sec) in water, then at medium speeds (45°/sec) in water or on dry land, and finally at high speeds (90°/sec) on dry land before in water. Abduction requires higher stabilization, necessitating its introduction after flexion, with scaption introduced last. This model of progressive sequential movement ensures that early active motion and then stabilization are appropriately introduced. This should reduce rehabilitation time and improve therapeutic goals without compromising patient safety or introducing inappropriate muscle recruitment or movement speed.

Analysis of the neuromuscular activity during rising from a chair in water and on dry land

PURPOSE: The purpose of the present study was to analyze the neuromuscular responses during the performance of a sit to stand [STS] task in water and on dry land. SCOPE: 10 healthy subjects, five males and five females were recruited for study. Surface electromyography sEMG was used for lower limb and trunk muscles maximal voluntarty contraction [MVC] and during the STS task. RESULTS: Muscle activity was significantly higher on dry land than in water normalized signals by MVC from the quadriceps-vastus medialis [17.3%], the quadriceps - rectus femoris [5.3%], the long head of the biceps femoris [5.5%], the tibialis anterior [13.9%], the gastrocnemius medialis [3.4%], the soleus [6.2%]. However, the muscle activity was higher in water for the rectus abdominis [-26.6%] and the erector spinae [-22.6%]. CONCLUSIONS: This study for the first time describes the neuromuscular responses in healthy subjects during the performance of the STS task in water. The differences in lower limb and trunk muscle activity should be considered when using the STS movement in aquatic rehabilitation.