Mechanisms of ATF4-mediated neuronal apoptosis

Abstract to be provide

THE ROLE OF THE P53 FAMILY IN PUMA INDUCTION DURING NEURONAL CELL DEATH

Oxidative stress and ER dysfunction have been implicated as key triggers of neuronal apoptosis in acute and chronic neurodegenerative conditions. In the present study we demonstrate that oxidative- and ER-stressors induce PUMA expression and neuronal cell death through a p53-independent mechanism. Since the p53 family members, p63 and p73, can transactivate certain p53-responsive genes, we examined the possibility that these family members might co-operate with p53 or compensate for its loss in this context. Wildtype and p63-deficient cortical neurons exhibited similar levels of PUMA induction and neuronal apoptosis in response to oxidative and ER-stress. Furthermore, attenuation of p53 family activity via adenoviral transduction of Ad- ANp73a did not confer protection against ER-stress mediated apoptosis. Taken together, these results indicate that the p53-independent pathway regulating PUMA expression during ER-stress is not coordinated by the p53 family members, p63 or p73. Therefore, we have proposed two putative upstream regulators, ATF4 and CHOP, as potential regulators of PUMA induction via ER dysfunction

Idempotent ideals and non-finitely generated projective modules over integral group rings of polycyclic-by-finite groups

We prove that every non-finitely generated projective module over the integral group ring of a polycyclic-by-finite group G is free if and only if G is polycyclic.Comment: 15 pages, to appear in J. Algebr

Harnessing the Melanocortin System in the control of food intake and glucose homeostasis

The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.</p

Thermal processing of thermogelling nanoemulsions as a route to tune material properties

Many soft matter systems have properties which depend on their processing history. It is generally accepted that material properties can be finely tuned by carefully directing self-assembly. However, for gelling colloidal systems, it is difficult to characterize such path-dependent effects since the colloidal attraction is often provided by adding another component to the system such as salts or depletants. Therefore, studies of and an understanding of the role of processing on the material properties of attractive colloidal systems are largely lacking. In this work, we systematically studied how processing greatly influences the properties and the microstructures of model attractive colloidal systems. We perform experiments using a thermogelling nanoemulsion as a model system where the isotropic attraction can be precisely tuned via the temperature. The effects of processing conditions on gel formation and properties is tested by performing well-designed sequential temperature jumps. By properly controlling the thermal history, we demonstrate that properties of colloidal gels can be beyond the limit set by direct quenching, which has been a major focus in literature, and that otherwise slow aging of the system associated with a decrease in elasticity can be prevented. Our results provide new experimental evidence of path-dependent rheology and associated microstructures in attractive colloidal systems and provide guidance to future applications in manufacturing complex colloid-based materials.National Science Foundation (U.S.) (DMR – 1419807)Think Global Education Trust (Taiwan) (scholarship

Planetesimals at DZ stars I: chondritic compositions and a massive accretion event

There is a wealth of evidence to suggest that planetary systems can survive beyond the main sequence. Most commonly, white dwarfs are found to be accreting material from tidally disrupted asteroids, whose bulk compositions are reflected by the metals polluting the stellar photospheres. While many examples are known, most lack the deep, high-resolution data required to detect multiple elements, and thus characterise the planetesimals that orbit them. Here, spectra of seven DZ white dwarfs observed with Keck HIRES are analysed, where up to nine metals are measured per star. Their compositions are compared against those of solar system objects, working in a Bayesian framework to infer or marginalise over the accretion history. All of the stars have been accreting primitive material, similar to chondrites, with hints of a Mercury-like composition at one star. The most polluted star is observed several Myr after its last major accretion episode, in which a Moon-sized object met its demise.Comment: Accepted to MNRAS. 18 pages, 9 figure

Planetesimals at DZ stars – I. Chondritic compositions and a massive accretion event

There is a wealth of evidence to suggest that planetary systems can survive beyond the main sequence. Most commonly, white dwarfs are found to be accreting material from tidally disrupted asteroids, whose bulk compositions are reflected by the metals polluting the stellar photospheres. While many examples are known, most lack the deep, high-resolution data required to detect multiple elements, and thus characterize the planetesimals that orbit them. Here, spectra of seven DZ white dwarfs observed with Keck High Resolution Echelle Spectrometer (HIRES) are analysed, where up to nine metals are measured per star. Their compositions are compared against those of Solar system objects, working in a Bayesian framework to infer or marginalize over the accretion history. All of the stars have been accreting primitive material, similar to chondrites, with hints of a Mercury-like composition at one star. The most polluted star is observed several Myr after its last major accretion episode, in which a Moon-sized object met its demise