C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten.

Amyotrophic lateral sclerosis (ALS) is a devastating and incurable neurodegenerative disease, characterised by progressive failure of the neuromuscular system. A (G4C2)n repeat expansion in C9ORF72 is the most common genetic cause of ALS and frontotemporal dementia (FTD). To date, the balance of evidence indicates that the (G4C2)n repeat causes toxicity and neurodegeneration via a gain-of-toxic function mechanism; either through direct RNA toxicity or through the production of toxic aggregating dipeptide repeat proteins. Here, we have generated a stable and isogenic motor neuronal NSC34 cell model with inducible expression of a (G4C2)102 repeat, to investigate the gain-of-toxic function mechanisms. The expression of the (G4C2)102 repeat produces RNA foci and also undergoes RAN translation. In addition, the expression of the (G4C2)102 repeat shows cellular toxicity. Through comparison of transcriptomic data from the cellular model with laser-captured spinal motor neurons from C9ORF72-ALS cases, we also demonstrate that the PI3K/Akt cell survival signalling pathway is dysregulated in both systems. Furthermore, partial knockdown of Pten rescues the toxicity observed in the NSC34 (G4C2)102 cellular gain-of-toxic function model of C9ORF72-ALS. Our data indicate that PTEN may provide a potential therapeutic target to ameliorate toxic effects of the (G4C2)n repeat

Assistive Arm Exosleleton

The Assistive Arm Exoskeleton aims to assist those in need of support when trying to perform daily tasks. The need for independence during eating by those afflicted by Muscular Dystrophy was specifically targeted. In order to accomplish this, a motorized linkage system capable of supporting a person’s arm proof of concept was developed. In implementation, the device would be attached to the user’s battery powered wheelchair, and be available to them whenever needed. The system uses a collection of force sensing devices in order to detect user intent. With the information gathered by this sensor interface, the system can position the linkage, and subsequently the user’s arm, anywhere within the work space, thus enabling the user to have independent control of their arm once again

Transforming Transportation

Moscow has fallen behind the world’s push for alternative fuel development, due to a nearly ubiquitous use of gasoline vehicles. Our project seeks to determine the most economically feasible alternative fuel for Moscow’s present and future vehicle economy. To accomplish this goal we conducted a life-cycle cost analysis on three vehicles selected to represent the Moscow consumer’s buying preferences. We concluded that, at present, electric vehicles are non-viable in Moscow, while natural gas powered vehicles are practical, economical, sustainable, and take advantage of both the existing infrastructure and Russia’s enormous natural gas reserves

Osmium carbonyl clusters containing labile ligands hyperstabilize microtubules

10.1021/tx900056aChemical Research in Toxicology2261116-1122CRTO

Ecological insights from three decades of animal movement tracking across a changing Arctic

The Arctic is entering a new ecological state, with alarming consequences for humanity. Animal-borne sensors offer a window into these changes. Although substantial animal tracking data from the Arctic and subarctic exist, most are difficult to discover and access. Here, we present the new Arctic Animal Movement Archive (AAMA), a growing collection of more than 200 standardized terrestrial and marine animal tracking studies from 1991 to the present. The AAMA supports public data discovery, preserves fundamental baseline data for the future, and facilitates efficient, collaborative data analysis. With AAMA-based case studies, we document climatic influences on the migration phenology of eagles, geographic differences in the adaptive response of caribou reproductive phenology to climate change, and species-specific changes in terrestrial mammal movement rates in response to increasing temperature.</p