Isolation of Bioactive Compounds That Relate to the Anti-Platelet Activity of Cymbopogon ambiguus

Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, eugenol methylether and trans-isoelemicin. While both eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC50 value of 46.6 μM, in comparison to aspirin, with an IC50 value of 46.1 μM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of headache and inflammatory conditions

The Response of Selected Temperate Forages to Increasing Summer Drought Conditions and High Summer Temperatures in Northern Victoria, Australia

In the dairy region of northern Victoria, Australia, the performance of temperate perennial dairy pastures is often poor over summer due to a combination of high temperatures and limited water availability that can restrict dry matter production and plant survival. A series of field experiments examined the effects of heat and restricted irrigation (as a consequence of drought) on the growth and nutritive characteristics of selected forage species, and whether survival under experimental conditions was influenced by plant genotype, irrigation and grazing management strategies, as well as endophyte presence. The major focus was on perennial ryegrass. Detailed sampling of perennial ryegrass (Lolium perenne L.), lucerne (Medicago sativa L.) and tall fescue (Festuca arundinacea Schreb) pastures on commercial farms during five extreme heat events (\u3e 35 oC) over summer 2018/2019, highlighted the impact of high temperatures on pasture nutritive parameters. In vitro dry matter digestibility and water soluble carbohydrate concentrations decreased by 0.2% units per degree rise in average maximum daily temperature from 23 to 40 ºC and neutral detergent fibre and acid detergent fibre concentrations increased by 0.2% and 0.15% units per degree, respectively. When a range of perennial ryegrass cultivars, hybrid ryegrasses and tall fescue cultivars were evaluated under full and restricted irrigation and two grazing strategies, few differences in net pasture accumulation over summer or survival were observed. The research highlighted the importance of maintaining plant density during periods of restricted irrigation to ensure plant recovery once irrigation or rainfall becomes available. No endophyte-ryegrass combinations were found to be better adapted to restricted water and high temperature conditions. The incidences of extreme heat events and low water availability are increasing in northern Victoria and this research will assist farmers to identify strategies to mitigate the negative effect of these conditions on the production and feed quality of perennial ryegrass-based pastures

COVID-19 and OD: Unplanned Disruption and the Opportunity for Planned Talent Development

COVID-19 created an unprecedented global health crisis and caused a rapid, global economic meltdown. Organizations of all sizes are scrambling to salvage workforces and adopting policies to protect employees from the virus. Talent development practices face new challenges as the world reckons with our altered COVID-19 pandemic reality. Organization leaders must think creatively to design the employment practices of the future. In this article, we consider how changes in work environments affect employees and organization performance, examine how recruitment, training, onboarding, and developing talent present complex challenges that must be addressed for sustainability, and consider how talent development principles can enhance OD practices. Finally, we offer perspectives on employing OD principles and practices to facilitate workforce changes to maximize productivity and performance

New procedures for testing whether stock price processes are martingales

We propose procedures for testing whether stock price processes are martingales based on limit order type betting strategies. We first show that the null hypothesis of martingale property of a stock price process can be tested based on the capital process of a betting strategy. In particular with high frequency Markov type strategies we find that martingale null hypotheses are rejected for many stock price processes

Pluronic F127 thermosensitive injectable smart hydrogels for controlled drug delivery system development

YesUnderstanding structure-property relationships is critical for the development of new drug delivery systems. This study investigates the properties of Pluronic smart hydrogel formulations for future use as injectable controlled drug carriers. The smart hydrogels promise to enhance patient compliance, decrease side effects and reduce dose and frequency. Pharmaceutically, these systems are attractive due to their unique sol-gel phase transition in the body, biocompatibility, safety and injectability as solutions before transforming into gel matrices at body temperature. We quantify the structural changes of F127 systems under controlled temperature after flow, as experienced during real bodily injection. Empirical formulae combining the coupled thermal and shear dependency are produced to aid future application of these systems. Induced structural transitions measured in-situ by small angle x-ray and neutron scattering reveal mixed oriented structures that can be exploited to tailor the drug release profile

ConCap: Designing to Empower Individual Reflection on Chronic Conditions using Mobile Apps

The world is faced with a growing number of people who live with chronic medical conditions. There have been numerous digital interventions into personal management of these diseases in recent years, yet gaps remain in the HCI literature. In particular, we lack a systematic understanding of user requirements in tools that support independent management while away from external influences. This paper presents a first investigation into low-intervention support for self-management. A mobile application enabled individuals to capture contextual information related to their health in the form of photographs. Through a month-long user study, we identify four management trends amongst our participants and describe their influence on mobile application adoption

The evolution of azole resistance in Candida albicans sterol 14α-demethylase (CYP51) through incremental amino acid substitutions

Recombinant Candida albicans CYP51 (CaCYP51) proteins containing 23 single and 5 double amino acid substitutions found in clinical strains and the wild-type enzyme were expressed in Escherichia coli and purified by Ni2+-nitrilotriacetic acid agarose chromatography. Catalytic tolerance to azole antifungals was assessed by determination of the concentration causing 50% enzyme inhibition (IC50) using CYP51 reconstitution assays. The greatest increase in the IC50 compared to that of the wild-type enzyme was observed with the five double substitutions Y132F+K143R (15.3-fold), Y132H+K143R (22.1-fold), Y132F+F145L (10.1-fold), G307S+G450E (13-fold), and D278N+G464S (3.3-fold). The single substitutions K143R, D278N, S279F, S405F, G448E, and G450E conferred at least 2-fold increases in the fluconazole IC50, and the Y132F, F145L, Y257H, Y447H, V456I, G464S, R467K, and I471T substitutions conferred increased residual CYP51 activity at high fluconazole concentrations. In vitro testing of select CaCYP51 mutations in C. albicans showed that the Y132F, Y132H, K143R, F145L, S405F, G448E, G450E, G464S, Y132F+K143R, Y132F+F145L, and D278N+G464S substitutions conferred at least a 2-fold increase in the fluconazole MIC. The catalytic tolerance of the purified proteins to voriconazole, itraconazole, and posaconazole was far lower and limited to increased residual activities at high triazole concentrations for certain mutations rather than large increases in IC50 values. Itraconazole was the most effective at inhibiting CaCYP51. However, when tested against CaCYP51 mutant strains, posaconazole seemed to be the most resistant to changes in MIC as a result of CYP51 mutation compared to itraconazole, voriconazole, or fluconazole

Loss of Upc2p-Inducible ERG3 Transcription Is Sufficient To Confer Niche-Specific Azole Resistance without Compromising Candida albicans Pathogenicity

Inactivation of sterol Δ5,6-desaturase (Erg3p) in the prevalent fungal pathogen Candida albicans is one of several mechanisms that can confer resistance to the azole antifungal drugs. However, loss of Erg3p activity is also associated with deficiencies in stress tolerance, invasive hyphal growth, and attenuated virulence in a mouse model of disseminated infection. This may explain why relatively few erg3-deficient strains have been reported among azole-resistant clinical isolates. In this study, we examined the consequences of Erg3p inactivation upon C. albicans pathogenicity and azole susceptibility in mouse models of mucosal and disseminated infection. While a C. albicans erg3Δ/Δ mutant was unable to cause lethality in the disseminated model, it induced pathology in a mouse model of vaginal infection. The erg3Δ/Δ mutant was also more resistant to fluconazole treatment than the wild type in both models of infection. Thus, complete loss of Erg3p activity confers azole resistance but also niche-specific virulence deficiencies. Serendipitously, we discovered that loss of azole-inducible ERG3 transcription (rather than complete inactivation) is sufficient to confer in vitro fluconazole resistance, without compromising C. albicans stress tolerance, hyphal growth, or pathogenicity in either mouse model. It is also sufficient to confer fluconazole resistance in the mouse vaginal model, but not in the disseminated model of infection, and thus confers niche-specific azole resistance without compromising C. albicans pathogenicity at either site. Collectively, these results establish that modulating Erg3p expression or activity can have niche-specific consequences on both C. albicans pathogenicity and azole resistanc