A shared mechanism of muscle wasting in cancer and Huntington's disease.

Skeletal muscle loss and dysfunction in aging and chronic diseases is one of the major causes of mortality in patients, and is relevant for a wide variety of diseases such as neurodegeneration and cancer. Muscle loss is accompanied by changes in gene expression and metabolism that lead to contractile impairment and likely affect whole-body metabolism and function. The changes may be caused by inactivity, inflammation, age-related factors or unbalanced nutrition. Although links with skeletal muscle loss have been found in diseases with disparate aetiologies, for example both in Huntingtons disease (HD) and cancer cachexia, the outcome is a similar impairment and mortality. This short commentary aims to summarize recent achievements in the identification of common mechanisms leading to the skeletal muscle wasting syndrome seen in diseases as different as cancer and HD. The latter is the most common hereditary neurodegenerative disorder and muscle wasting is an important component of its pathology. In addition, possible therapeutic strategies for anti-cachectic treatment will be also discussed in the light of their translation into possible therapeutic approaches for HD

New Deterministic Algorithms for Solving Parity Games

We study parity games in which one of the two players controls only a small number $k$ of nodes and the other player controls the $n-k$ other nodes of the game. Our main result is a fixed-parameter algorithm that solves bipartite parity games in time $k^{O(\sqrt{k})}\cdot O(n^3)$, and general parity games in time $(p+k)^{O(\sqrt{k})} \cdot O(pnm)$, where $p$ is the number of distinct priorities and $m$ is the number of edges. For all games with $k = o(n)$ this improves the previously fastest algorithm by Jurdzi{\'n}ski, Paterson, and Zwick (SICOMP 2008). We also obtain novel kernelization results and an improved deterministic algorithm for graphs with small average degree

Imitation in Large Games

In games with a large number of players where players may have overlapping objectives, the analysis of stable outcomes typically depends on player types. A special case is when a large part of the player population consists of imitation types: that of players who imitate choice of other (optimizing) types. Game theorists typically study the evolution of such games in dynamical systems with imitation rules. In the setting of games of infinite duration on finite graphs with preference orderings on outcomes for player types, we explore the possibility of imitation as a viable strategy. In our setup, the optimising players play bounded memory strategies and the imitators play according to specifications given by automata. We present algorithmic results on the eventual survival of types

Symmetric Strategy Improvement

Symmetry is inherent in the definition of most of the two-player zero-sum games, including parity, mean-payoff, and discounted-payoff games. It is therefore quite surprising that no symmetric analysis techniques for these games exist. We develop a novel symmetric strategy improvement algorithm where, in each iteration, the strategies of both players are improved simultaneously. We show that symmetric strategy improvement defies Friedmann's traps, which shook the belief in the potential of classic strategy improvement to be polynomial

Structural abnormalities of the optic nerve and retina in Huntington’s disease pre-clinical and clinical settings

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies

Blackwell-Optimal Strategies in Priority Mean-Payoff Games

We examine perfect information stochastic mean-payoff games - a class of games containing as special sub-classes the usual mean-payoff games and parity games. We show that deterministic memoryless strategies that are optimal for discounted games with state-dependent discount factors close to 1 are optimal for priority mean-payoff games establishing a strong link between these two classes

Regular Strategies in Pushdown Reachability Games

International audienceWe show that positional winning strategies in pushdown reachability games can be implemented by deterministic finite state au-tomata of exponential size. Such automata read the stack and control state of a given pushdown configuration and output the set of winning moves playable from that position. This result can originally be attributed to Kupferman, Piterman and Vardi using an approach based on two-way tree automata. We present a more direct approach that builds upon the popular saturation technique. Saturation for analysing pushdown systems has been successfully implemented by Moped and WALi. Thus, our approach has the potential for practical applications to controller-synthesis problems

Management practices, and not surrounding habitats, drive bird and arthropod biodiversity within vineyards

Agrochemical use and habitat loss associated with agriculture are drivers of biodiversity loss worldwide, and biodiversity-friendly farming practices, including organic management, are increasingly promoted by policy and industry in an attempt to offset this. Grapes are an important perennial crop globally, and in the UK, viticulture is the fastest growing agricultural sector and sustainable vineyard management is promoted by the Sustainable Wines of Great Britain ‘SWGB’ scheme. Here, we performed the first assessment of the simultaneous effects of surrounding habitats and vineyard management practices on bird and arthropod biodiversity across 22 English vineyards (10 certified-organic, 11 SWGB-accredited, and 3 both). We surveyed birds using point counts and arthropods with pitfall traps, and used linear mixed modelling to relate diversity and abundance to habitat and management predictors at landscape and local scales. We show that arthropod abundance is significantly higher on organic vineyards, whilst bird diversity is significantly lower on SWGB-accredited vineyards, but we find no other significant effects of organic certification or SWGB-accreditation on biodiversity. We also find no significant effects of the surrounding habitat structure on the biodiversity of birds and arthropods. Instead, we show that ecotoxicity scores derived from agrochemical use data have a significant negative impact on bird diversity, and on arthropod abundance and diversity. Organic status predicts a significant reduction in ecotoxicity scores, but only when application frequency is not considered, and contradictorily, SWGB-accredited vineyards have higher ecotoxicity scores than those without accreditation. Ground vegetation cover has a consistent, positive effect on bird and arthropod diversity, with model predicted diversity increasing 1.5 and 2.5-fold, respectively, in vineyards with the highest vegetation cover, and herbicide use has a negative effect on the vegetation cover. Our research demonstrates that individual management practices have a stronger effect on vineyard biodiversity than the habitat context, overall management regime or certification. Our study sets an important baseline for vineyard management and accreditation schemes and generates key recommendations for improvement. To benefit biodiversity within vineyards, we recommend that sustainability accreditation schemes include requirements to reduce the ecotoxicity of used agrochemicals, and promote higher ground vegetation cover and height by reducing herbicide use