Background: Current neuroscience has identified rehabilitation approaches with the potential to stimulate adaptive changes in the brains of persons with hemiparesis. These approaches include, intensive task-oriented training, bimanual activities and balancing proximal and distal upper extremity interventions to reduce competition between these segments for neural territory.

Ethanol production from lignocellulosic biomass holds promise as an alternative fuel. However, industrial stresses, including ethanol stress, limit microbial fermentation and thus prevent cost competitiveness with fossil fuels. To identify novel engineering targets for increased ethanol tolerance, we took advantage of natural diversity in wild Saccharomyces cerevisiae strains. We previously showed that an S288c-derived lab strain cannot acquire higher ethanol tolerance after a mild ethanol pretreatment, which is distinct from other stresses. Here, we measured acquired ethanol tolerance in a large panel of wild strains and show that most strains can acquire higher tolerance after pretreatment. We exploited this major phenotypic difference to address the mechanism of acquired ethanol tolerance, by comparing the global gene expression response to 5% ethanol in S288c and two wild strains. Hundreds of genes showed variation in ethanol-dependent gene expression across strains. Computational analysis identified several transcription factor modules and known coregulated genes as differentially expressed, implicating genetic variation in the ethanol signaling pathway. We used this information to identify genes required for acquisition of ethanol tolerance in wild strains, including new genes and processes not previously linked to ethanol tolerance, and four genes that increase ethanol tolerance when overexpressed. Our approach shows that comparative genomics across natural isolates can quickly identify genes for industrial engineering while expanding our understanding of natural diversity.

This paper presents preliminary results from a virtual reality (VR)-based system for hand rehabilitation that uses a CyberGlove and a Rutgers Master II-ND haptic glove. This computerized system trains finger range of motion, finger flexion speed, independence of finger motion, and finger strength using specific VR simulation exercises. A remote Web-based monitoring station was developed to allow telerehabilitation interventions. The remote therapist observes simplified versions of the patient exercises that are updated in real time. Patient data is stored transparently in an Oracle database, which is also Web accessible through a portal GUI. Thus the remote therapist or attending physician can graph exercise outcomes and thus evaluate patient outcomes at a distance. Data from the VR simulations is complemented by clinical measurements of hand function and strength. Eight chronic post-stroke subjects participated in a pilot study of the above system. In keeping with variability in both their lesion size and site and in their initial upper extremity function, each subject showed improvement on a unique combination of movement parameters in VR training. Importantly, these improvements transferred to gains on clinical tests, as well as to significant reductions in task-completion times for the prehension of real objects. These results are indicative of the potential feasibility of this exercise system for rehabilitation in patients with hand dysfunction resulting from neurological impairment.

Natural variation in gene expression is pervasive within and between species, and it likely explains a significant fraction of phenotypic variation between individuals. Phenotypic variation in acute systemic responses can also be leveraged to reveal physiological differences in how individuals perceive and respond to environmental perturbations. We previously found extensive variation in the transcriptomic response to acute ethanol exposure in two wild isolates and a common laboratory strain of Saccharomyces cerevisiae. Many expression differences persisted across several modules of coregulated genes, implicating trans-acting systemic differences in ethanol sensing and/or response. Here, we conducted expression QTL mapping of the ethanol response in two strain crosses to identify the genetic basis for these differences. To understand systemic differences, we focused on "hotspot" loci that affect many transcripts in trans. Candidate causal regulators contained within hotspots implicate upstream regulators as well as downstream effectors of the ethanol response. Overlap in hotspot targets revealed additive genetic effects of trans-acting loci as well as "epihotspots," in which epistatic interactions between two loci affected the same suites of downstream targets. One epi-hotspot implicated interactions between Mkt1p and proteins linked to translational regulation, prompting us to show that Mkt1p localizes to P bodies upon ethanol stress in a strain-specific manner. Our results provide a glimpse into the genetic architecture underlying natural variation in a stress response and present new details on how yeast respond to ethanol stress. N ATURAL variation in gene expression is hypothesized to be a major source of phenotypic variation between individuals (King and Wilson 1975;Oleksiak et al. 2002). Gene expression variation underlies differences in susceptibility to infectious disease (Li et al. 2010;Barreiro et al. 2012), drug sensitivity (Fay et al. 2004;Kvitek et al. 2008;Maranville et al. 2011;Hodgins-Davis et al. 2012;Chang et al. 2013), inflammation (Gargalovic et al. 2006Orozco et al. 2012), cardiovascular disease (Romanoski et al. 2010), metabolism (Fraser et al. 2010Rossouw et al. 2012;Skelly et al. 2013), morphology (Yvert et al. 2003Chin et al. 2012;Skelly et al. 2013), and even behavior (Ziebarth et al. 2012). Still, identifying the genetic and molecular mechanisms that underlie the expression variation is a major challenge.Expression quantitative trait loci (eQTL) mapping (reviewed in Gilad et al. 2008) is a powerful approach to dissect the genetic basis of expression differences. Transcript abundance is treated as a quantitative trait whose genetic determinants can be implicated by well-established linkage mapping techniques. The first eQTL studies in yeast illuminated the genetic landscape of gene expression-variation determinants under standard growth conditions (Brem et al. 2002;Yvert et al. 2003). Subsequent eQTL studies surveyed the genetic control of transcript abundance in Arabidopsi...