Huntington disease is a fatal neurodegenerative disorder caused by expansion of a polyglutamine tract in the protein huntingtin (Htt), which leads to its aggregation in nuclear and cytoplasmic inclusion bodies. We recently identified 52 loss-of-function mutations in yeast genes that enhance the toxicity of a mutant Htt fragment. Here we report the results from a genome-wide loss-of-function suppressor screen in which we identified 28 gene deletions that suppress toxicity of a mutant Htt fragment. The suppressors are known or predicted to have roles in vesicle transport, vacuolar degradation, transcription and prion-like aggregation. Among the most potent suppressors was Bna4 (kynurenine 3-monooxygenase), an enzyme in the kynurenine pathway of tryptophan degradation that has been linked directly to the pathophysiology of Huntington disease in humans by a mechanism that may involve reactive oxygen species. This finding is suggestive of a conserved mechanism of polyglutamine toxicity from yeast to humans and identifies new candidate therapeutic targets for the treatment of Huntington disease.

Abstract. This paper could have been given the title: "How to positively and implicitly solve Euler equations using only linear scalar advections." The new relaxation method we propose is able to solve Euler-like systems-as well as initial and boundary value problems-with real state laws at very low cost, using a hybrid explicit-implicit time integration associated with the Arbitrary Lagrangian-Eulerian formalism. Furthermore, it possesses many attractive properties, such as: (i) the preservation of positivity for densities; (ii) the guarantee of min-max principle for mass fractions; (iii) the satisfaction of entropy inequality, under an expressible bound on the CFL ratio. The main feature that will be emphasized is the design of this optimal time-step, which takes into account data not only from the inner domain but also from the boundary conditions.

We present a dynamical-mass measurement of the supermassive black hole (SMBH) in the nearby double-barred spiral galaxy NGC 3504 as part of the Measuring Black Holes in Below Milky Way (M ⋆) mass galaxies (MBHBM ⋆) Project. Our analysis is based on Atacama Large Millimeter/submillimeter Array (ALMA) Cycle-5 observations of the 12 CO(2 − 1) emission line. These observations probe NGC 3504's circumnuclear gas disk (CND). Our dynamical model of the CND simultaneously constrains a black hole (BH) mass of 1.6 +0.6 −0.4 × 10 7 M ⊙ , which is consistent with the empirical BH-galaxy scaling relations, and a mass-to-light ratio in H-band of 0.44 ± 0.12 (M ⊙ /L ⊙). This measurement also relies on our new distant estimation to the galaxy of 32.4 ± 2.1 Mpc using the surface brightness fluctuation method (SBF), which is much further than the existing distant estimates. Additionally, our observations detect a central deficit in the 12 CO(2 − 1) integrated intensity map with a diameter of 6.3 pc at the putative position of the SMBH. However, we find a dense gas tracer CS(5 − 4) peaks at the galaxy center, filling in the 12 CO(2 − 1)-attenuated hole. Holes like this one are observed in other galaxies, and our observations suggest these may be caused by changing excitation conditions rather than a true absence of molecular gas around the nucleus.