DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose

Macroautophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. The process operates under basal conditions as a mechanism to turnover damaged or misfolded proteins and organelles. As a result, it has a major role in preserving cellular integrity and viability. In addition to this basal function, macroautophagy can also be modulated in response to various forms of cellular stress, and the rate and cargoes of macroautophagy can be tailored to facilitate appropriate cellular responses in particular situations. The macroautophagy machinery is regulated by a group of evolutionarily conserved autophagy-related (ATG) proteins and by several other autophagy regulators, which either have tissue-restricted expression or operate in specific contexts. We report here the characterization of a novel autophagy regulator that we have termed DRAM-3 due to its significant homology to damage-regulated autophagy modulator (DRAM-1). DRAM-3 is expressed in a broad spectrum of normal tissues and tumor cells, but different from DRAM-1, DRAM-3 is not induced by p53 or DNA-damaging agents. Immunofluorescence studies revealed that DRAM-3 localizes to lysosomes/autolysosomes, endosomes and the plasma membrane, but not the endoplasmic reticulum, phagophores, autophagosomes or Golgi, indicating significant overlap with DRAM-1 localization and with organelles associated with macroautophagy. In this regard, we further proceed to show that DRAM-3 expression causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Reciprocally, CRISPR/Cas9-mediated disruption of DRAM-3 impairs autophagic flux confirming that DRAM-3 is a modulator of macroautophagy. As macroautophagy can be cytoprotective under starvation conditions, we also tested whether DRAM-3 could promote survival on nutrient deprivation. This revealed that DRAM-3 can repress cell death and promote long-term clonogenic survival of cells grown in the absence of glucose. Interestingly, however, this effect is macroautophagy-independent. In summary, these findings constitute the primary characterization of DRAM-3 as a modulator of both macroautophagy and cell survival under starvation conditions

Toxicological screening and DNA sequencing detects contamination and adulteration in regulated herbal medicines and supplements for diet, weight loss and cardiovascular health

Use of herbal medicines and supplements by consumers to prevent or treat disease, particularly chronic conditions continues to grow, leading to increased awareness of the minimal regulation standards in many countries. Fraudulent, adulterated and contaminated herbal and traditional medicines and dietary supplements are a risk to consumer health, with adverse effects and events including overdose, drug-herb interactions and hospitalisation. The scope of the risk has been difficult to determine, prompting calls for new approaches, such as the combination of DNA metabarcoding and mass spectrometry used in this study. Here we show that nearly 50% of products tested had contamination issues, in terms of DNA, chemical composition or both. Two samples were clear cases of pharmaceutical adulteration, including a combination of paracetamol and chlorpheniramine in one product and trace amounts of buclizine, a drug no longer in use in Australia, in another. Other issues include the undeclared presence of stimulants such as caffeine, synephrine or ephedrine. DNA data highlighted potential allergy concerns (nuts, wheat), presence of potential toxins (Neem oil) and animal ingredients (reindeer, frog, shrew), and possible substitution of bird cartilage in place of shark. Only 21% of the tested products were able to have at least one ingredient corroborated by DNA sequencing. This study demonstrates that, despite current monitoring approaches, contaminated and adulterated products are still reaching the consumer. We suggest that a better solution is stronger pre-market evaluation, using techniques such as that outlined in this study

A Search for Propylene Oxide and Glycine in Sagittarius B2 (LMH) and Orion

We have used the Mopra Telescope to search for glycine and the simple chiral molecule propylene oxide in the Sgr B2 (LMH) and Orion KL, in the 3-mm band. We have not detected either species, but have been able to put sensitive upper limits on the abundances of both molecules. The 3-sigma upper limits derived for glycine conformer I are 3.7 x 10^{14} cm^{-2} in both Orion-KL and Sgr B2 (LMH), comparable to the reported detections of conformer I by Kuan et al. However, as our values are 3-sigma upper limits rather than detections we conclude that this weighs against confirming the detection of Kuan et al. We find upper limits for the glycine II column density of 7.7 x 10^{12} cm^{-2} in both Orion-KL and Sgr B2 (LMH), in agreement with the results of Combes et al. The results presented here show that glycine conformer II is not present in the extended gas at the levels detected by Kuan et al. for conformer I. Our ATCA results (Jones et al.) have ruled out the detection of glycine (both conformers I and II) in the compact hot core of the LMH at the levels reported, so we conclude that it is unlikely that Kuan et al. have detected glycine in either Sgr B2 or Orion-KL. We find upper limits for propylene oxide abundance of 3.0 x 10^{14} cm^{-2} in Orion-KL and 6.7 x 10^{14} cm^{-2} in Sgr B2 (LMH). We have detected fourteen features in Sgr B2 and four features in Orion-KL which have not previously been reported in the ISM, but have not be able to plausibly assign these transitions to any carrier.Comment: 12 pages, 3 figures. Accepted by MNRAS 12th January 200

Toxicological screening and DNA sequencing detects contamination and adulteration in regulated herbal medicines and supplements for diet, weight loss and cardiovascular health

Use of herbal medicines and supplements by consumers to prevent or treat disease, particularly chronic conditions continues to grow, leading to increased awareness of the minimal regulation standards in many countries. Fraudulent, adulterated and contaminated herbal and traditional medicines and dietary supplements are a risk to consumer health, with adverse effects and events including overdose, drug-herb interactions and hospitalisation. The scope of the risk has been difficult to determine, prompting calls for new approaches, such as the combination of DNA metabarcoding and mass spectrometry used in this study. Here we show that nearly 50% of products tested had contamination issues, in terms of DNA, chemical composition or both. Two samples were clear cases of pharmaceutical adulteration, including a combination of paracetamol and chlorpheniramine in one product and trace amounts of buclizine, a drug no longer in use in Australia, in another. Other issues include the undeclared presence of stimulants such as caffeine, synephrine or ephedrine. DNA data highlighted potential allergy concerns (nuts, wheat), presence of potential toxins (Neem oil) and animal ingredients (reindeer, frog, shrew), and possible substitution of bird cartilage in place of shark. Only 21% of the tested products were able to have at least one ingredient corroborated by DNA sequencing. This study demonstrates that, despite current monitoring approaches, contaminated and adulterated products are still reaching the consumer. We suggest that a better solution is stronger pre-market evaluation, using techniques such as that outlined in this study

Gas Accretion in Star-Forming Galaxies

Cold-mode gas accretion onto galaxies is a direct prediction of LCDM simulations and provides galaxies with fuel that allows them to continue to form stars over the lifetime of the Universe. Given its dramatic influence on a galaxy's gas reservoir, gas accretion has to be largely responsible for how galaxies form and evolve. Therefore, given the importance of gas accretion, it is necessary to observe and quantify how these gas flows affect galaxy evolution. However, observational data have yet to conclusively show that gas accretion ubiquitously occurs at any epoch. Directly detecting gas accretion is a challenging endeavor and we now have obtained a significant amount of observational evidence to support it. This chapter reviews the current observational evidence of gas accretion onto star-forming galaxies.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springer. This chapter includes 22 pages with 7 Figure

Mapping as a knowledge translation tool for Ontario Early Years Centres: views from data analysts and managers

<p>Abstract</p> <p>Background</p> <p>Local Ontario Early Years Centres (OEYCs) collect timely and relevant local data, but knowledge translation is needed for the data to be useful. Maps represent an ideal tool to interpret local data. While geographic information system (GIS) technology is available, it is less clear what users require from this technology for evidence-informed program planning. We highlight initial challenges and opportunities encountered in implementing a mapping innovation (software and managerial decision-support) as a knowledge translation strategy.</p> <p>Methods</p> <p>Using focus groups, individual interviews and interactive software development events, we taped and transcribed verbatim our interactions with nine OEYCs in Ontario, Canada. Research participants were composed of data analysts and their managers. Deductive analysis of the data was based on the Ottawa Model of Research Use, focusing on the innovation (the mapping tool and maps), the potential adopters, and the environment.</p> <p>Results</p> <p>Challenges associated with the innovation included preconceived perceptions of a steep learning curve with GIS software. Challenges related to the potential adopters included conflicting ideas about tool integration into the organization and difficulty with map interpretation. Lack of funds, lack of availability of accurate data, and unrealistic reporting requirements represent environmental challenges.</p> <p>Conclusion</p> <p>Despite the clear need for mapping software and maps, there remain several challenges to their effective implementation. Some can be modified, while other challenges might require attention at the systemic level. Future research is needed to identify barriers and facilitators related to using mapping software and maps for decision-making by other users, and to subsequently develop mapping best practices guidelines to assist community-based agencies in circumventing some challenges, and support information equity across a region.</p

Observational Diagnostics of Gas Flows: Insights from Cosmological Simulations

Galactic accretion interacts in complex ways with gaseous halos, including galactic winds. As a result, observational diagnostics typically probe a range of intertwined physical phenomena. Because of this complexity, cosmological hydrodynamic simulations have played a key role in developing observational diagnostics of galactic accretion. In this chapter, we review the status of different observational diagnostics of circumgalactic gas flows, in both absorption (galaxy pair and down-the-barrel observations in neutral hydrogen and metals; kinematic and azimuthal angle diagnostics; the cosmological column density distribution; and metallicity) and emission (Lya; UV metal lines; and diffuse X-rays). We conclude that there is no simple and robust way to identify galactic accretion in individual measurements. Rather, progress in testing galactic accretion models is likely to come from systematic, statistical comparisons of simulation predictions with observations. We discuss specific areas where progress is likely to be particularly fruitful over the next few years.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dave, to be published by Springer. Typos correcte

The Circumgalactic Medium in Massive Halos

This chapter presents a review of the current state of knowledge on the cool (T ~ 1e4 K) halo gas content around massive galaxies at z ~ 0.2-2. Over the last decade, significant progress has been made in characterizing the cool circumgalactic gas in massive halos of Mh ~ 1e12-1e14 Msun at intermediate redshifts using absorption spectroscopy. Systematic studies of halo gas around massive galaxies beyond the nearby universe are made possible by large spectroscopic samples of galaxies and quasars in public archives. In addition to accurate and precise constraints for the incidence of cool gas in massive halos, detailed characterizations of gas kinematics and chemical compositions around massive quiescent galaxies at z ~ 0.5 have also been obtained. Combining all available measurements shows that infalling clouds from external sources are likely the primary source of cool gas detected at d >~ 100 kpc from massive quiescent galaxies. The origin of the gas closer in is currently less certain, but SNe Ia driven winds appear to contribute significantly to cool gas found at d < 100 kpc. In contrast, cool gas observed at d <~ 200 kpc from luminous quasars appears to be intimately connected to quasar activities on parsec scales. The observed strong correlation between cool gas covering fraction in quasar host halos and quasar bolometric luminosity remains a puzzle. Combining absorption-line studies with spatially-resolved emission measurements of both gas and galaxies is the necessary next step to address remaining questions.Comment: 29 pages, 7 figures, invited review to appear in "Gas Accretion onto Galaxies", Astrophysics and Space Science Library, eds. A. Fox & R. Dave, to be published by Springe

Towards an Airframe Noise Prediction Methodology: Survey of Current Approaches

In this paper, we present a critical survey of the current airframe noise (AFN) prediction methodologies. Four methodologies are recognized. These are the fully analytic method, CFD combined with the acoustic analogy, the semi-empirical method and fully numerical method. It is argued that for the immediate need of the aircraft industry, the semi-empirical method based on recent high quality acoustic database is the best available method. The method based on CFD and the Ffowcs William- Hawkings (FW-H) equation with penetrable data surface (FW-Hpds ) has advanced considerably and much experience has been gained in its use. However, more research is needed in the near future particularly in the area of turbulence simulation. The fully numerical method will take longer to reach maturity. Based on the current trends, it is predicted that this method will eventually develop into the method of choice. Both the turbulence simulation and propagation methods need to develop more for this method to become useful. Nonetheless, the authors propose that the method based on a combination of numerical and analytical techniques, e.g., CFD combined with FW-H equation, should also be worked on. In this effort, the current symbolic algebra software will allow more analytical approaches to be incorporated into AFN prediction methods