Analysis and exploitation of AHFCA-dependent signalling systems in Streptomyces bacteria

From genome sequencing and analyses, Streptomyces bacteria are predicted to produce hundreds of bioactive metabolite compounds; however, the products of some of these cryptic biosynthetic gene clusters are most often silent or produced in very small quantities in laboratory conditions. The AHFCA-dependent signalling system is an example of a regulatory systems that tightly control expression of cryptic biosynthetic gene clusters in Streptomyces bacteria. Bioinformatic analyses, using MEME and FIMO, were able to successfully reveal TetR repressor binding sites to gain insights into complex regulatory networks. The S. avermitilis cryptic biosynthetic gene cluster, which is proposed to be under the control of an AHFCA-dependent signalling system, has not been investigated before and genome mining predictions suggest the biosynthetic gene cluster could be involved in the biosynthesis of novel azoxy compounds. The 50 kb predicted azoxy biosynthetic gene cluster was captured using pESAC13A PAC technologies and introduced into S. coelicolor M1152 and S. lividans TK24 heterologous hosts. Comparative metabolic profiling successfully identified the predicted azoxy compounds in S. coelicolor M1152 by LC-MS and identification of the azoxy compounds were supported by UHPLC-ESI-TOF-MS analysis and incorporation of isotope-labelled L-serine. Consistent with the model of transcriptional regulation, exploitation of the S. avermitilis AHFCA-dependent signalling system through the inactivation of sav_2268 transcriptional repressor in S. lividans TK24 heterologous hosts unlocked the production of azoxy compounds and AHFCA signalling molecules

EXPLAINING SUSTAINABILITY IN HEALTHCARE - A PRELIMINARY STUDY OF AN AGED CARE ORGANISATION IN AUSTRALIA

IT initiatives in healthcare often promise much but fail to deliver. As with IT projects in any other industry, healthcare projects may be abandoned before delivery, or if delivered, they may lack adoption or fail to deliver continuous use over a sustained period of time. Failure factors typically discussed in the IS literature fail to fully explain why sustainability is such an issue in the healthcare industry. Healthcare systems are technically complex to begin with. They involve a large number of stakeholders. Therefore their implementation process involves more planning and forethoughts. This paper focuses on the sustainability issues of healthcare information systems (HIS) implementation. We reviewed a broad array of literature to try to clarify the concept of sustainability within the defined context. We arrived at a broad framework for defining different types of sustainability for HIS. We propose they must all be considered for every sustainable healthcare IS implementation. Then using a successful aged care organisation in Australia, we explain the relevance of each type of sustainability defined. We conclude with some discussions of future work

Overproduction and identification of butyrolactones SCB1-8 in the antibiotic production superhost Streptomyces M1152

Gamma-butyrolactones (GBLs) are signalling molecules that control antibiotic production in Streptomyces bacteria. The genetically engineered strain S. coelicolor M1152 was found to overproduce GBLs SCB1-3 as well as five novel GBLs named SCB4-8. Incorporation experiments using isotopically-labelled precursors confirmed the chemical structures of SCB1-3 and established those of SCB4-8

Implications of Therapy-Induced Selective Autophagy on Tumor Metabolism and Survival

Accumulating evidence indicates that therapies designed to trigger apoptosis in tumor cells cause mitochondrial depolarization, nuclear damage, and the accumulation of misfolded protein aggregates, resulting in the activation of selective forms of autophagy. These selective forms of autophagy, including mitophagy, nucleophagy, and ubiquitin-mediated autophagy, counteract apoptotic signals by removing damaged cellular structures and by reprogramming cellular energy metabolism to cope with therapeutic stress. As a result, the efficacies of numerous current cancer therapies may be improved by combining them with adjuvant treatments that exploit or disrupt key metabolic processes induced by selective forms of autophagy. Targeting these metabolic irregularities represents a promising approach to improve clinical responsiveness to cancer treatments given the inherently elevated metabolic demands of many tumor types. To what extent anticancer treatments promote selective forms of autophagy and the degree to which they influence metabolism are currently under intense scrutiny. Understanding how the activation of selective forms of autophagy influences cellular metabolism and survival provides an opportunity to target metabolic irregularities induced by these pathways as a means of augmenting current approaches for treating cancer

The Orbital Structure of Triaxial Galaxies with Figure Rotation

We survey the properties of all orbit families in the rotating frame of a family of realistic triaxial potentials with central supermassive black holes (SMBHs). In such galaxies, most regular box orbits (vital for maintaining triaxiality) are associated with resonances which occupy two-dimensional surfaces in configuration space. For slow figure rotation all orbit families are largely stable. At intermediate pattern speeds a significant fraction of the resonant box orbits as well as inner long-axis tubes are destabilized by the "envelope doubling" that arises from the Coriolis forces and are driven into the destabilizing center. Thus, for pattern rotation periods .2 Gyr < Tp < 5 Gyr, the two orbit families that are most important for maintaining triaxiality are highly chaotic. As pattern speed increases there is also a sharp decrease in the overall fraction of prograde short-axis tubes and a corresponding increase in the retrograde variety. At the highest pattern speeds (close to that of triaxial bars), box-like orbits undergo a sudden transition to a new family of stable retrograde loop-like orbits, which resemble orbits in three-dimensional bars, and circulate about the short axis. Our analysis implies that triaxial systems (with central cusps and SMBHs) can either have high pattern speeds like fast bars or low patten speeds like triaxial elliptical galaxies or dark matter halos found in N-body simulations. Intermediate pattern speeds produce a high level of stochasticity in both the box and inner long-axis tube orbit families implying that stable triaxial systems are unlikely to have such pattern speeds.Comment: Version accepted for publication in ApJ, Vol 727, Feb. 1 issue, 201

Encapsulated bacteria deform lipid vesicles into flagellated swimmers

We study a synthetic system of motile Escherichia coli bacteria encapsulated inside giant lipid vesicles. Forces exerted by the bacteria on the inner side of the membrane are sufficient to extrude membrane tubes filled with one or several bacteria. We show that a physical coupling between the membrane tube and the flagella of the enclosed cells transforms the tube into an effective helical flagellum propelling the vesicle. We develop a simple theoretical model to estimate the propulsive force from the speed of the vesicles and demonstrate the good efficiency of this coupling mechanism. Together, these results point to design principles for conferring motility to synthetic cells

Anisotropic dynamics and kinetic arrest of dense colloidal ellipsoids in the presence of an external field studied by differential dynamic microscopy

Anisotropic dynamics on the colloidal length scale is ubiquitous in nature. Of particular interest is the dynamics of systems approaching a kinetically arrested state. The failure of classical techniques for investigating the dynamics of highly turbid suspensions has contributed toward the limited experimental information available up until now. Exploiting the recent developments in the technique of differential dynamic microscopy (DDM), we report the first experimental study of the anisotropic collective dynamics of colloidal ellipsoids with a magnetic hematite core over a wide concentration range approaching kinetic arrest. In addition, we have investigated the effect of an external magnetic field on the resulting anisotropic collective diffusion. We combine DDM with small-angle x-ray scattering and rheological measurements to locate the glass transition and to relate the collective short- and long-time diffusion coefficients to the structural correlations and the evolution of the zero shear viscosity as the system approaches an arrested state