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Introduction: Asymmetrical sensorimotor function after stroke creates unique challenges for bipedal tasks such as walking or perturbation-induced reactive stepping. Preference for initiating steps with the less-involved (preferred) leg after a perturbation has been reported with limited information on the stepping response of the more-involved (non-preferred) leg. Understanding the capacity of both legs to respond to a perturbation would enhance the design of future treatment approaches. This pilot study investigated the difference in perturbation-induced stepping between legs in stroke participant and non-impaired controls. We hypothesized that stepping performance will be different between groups as well as between legs for post-stroke participants.Methods: Thirty-six participants (20 persons post-stroke, 16 age matched controls) were given an anterior perturbation from three stance positions: symmetrical (SS), preferred asymmetrical (PAS−70% body weight on the preferred leg), and non-preferred asymmetrical (N-PAS−70% body weight on the non-preferred leg). Kinematic and kinetic data were collected to measure anticipatory postural adjustment (APA), characteristics of the first step (onset, length, height, duration), number of steps, and velocity of the body at heel strike. Group differences were tested using the Mann-Whitney U-test and differences between legs tested using the Wilcoxon signed-rank test with an alpha level of 0.05.Results: Stepping with the more-involved leg increased from 11.5% of trials in SS and N-PAS up to 46% in PAS stance position for participants post-stroke. Post-stroke participants had an earlier APA and always took more steps than controls to regain balance. However, differences between post-stroke and control participants were mainly found when stance position was modified. Compare to controls, steps with the preferred leg (N-PAS) were earlier and shorter (in time and length), whereas steps with the non-preferred leg (PAS) were also shorter but took longer. For post-stroke participants, step duration was longer and utilized more steps when stepping with the more-involved leg compared to the less-involved leg.Conclusions: Stepping with the more-involved leg can be facilitated by unweighting the leg. The differences between groups, and legs in post-stroke participants illustrate the simultaneous bipedal role (support and stepping) both legs have in reactive stepping and should be considered for reactive balance training.

We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5' UTRs that stall and repress the enzymatic activity of the cellular 5'-3' exoribonuclease XRN1, resulting in dramatic changes in the stability of cellular mRNAs. We used biochemical assays, virus infections, and transfection of the HCV and BVDV 5' untranslated regions in the absence of other viral gene products to directly demonstrate the existence and mechanism of this novel host-virus interaction. In the context of HCV infection, we observed globally increased stability of mRNAs resulting in significant increases in abundance of normally short-lived mRNAs encoding a variety of relevant oncogenes and angiogenesis factors. These findings suggest that non-coding regions from multiple genera of the Flaviviridae interfere with XRN1 and impact post-transcriptional processes, causing global dysregulation of cellular gene expression which may promote cell growth and pathogenesis.

Mutations in the LRRK2 gene, coding for dardarin, cause dominantly inherited Parkinson's disease (PD). Dardarin is a large protein, and mutations are found throughout the gene including the kinase domain. However, it is not clear if kinase activity is important for the damaging effects of pathogenic mutations. In this study, we noted two cellular phenotypes associated with mutant dardarin. First, pathogenic mutations increase the tendency of dardarin to form inclusion bodies. Secondly, neurons and neuronal cell lines undergo cell death after expression of mutant protein. Manipulating activity by replacing the kinase domain with a ‘kinase-dead’ version blocks inclusion body formation and strongly delays cell death. This predicts that kinase inhibitors will be useful therapeutic agents in patients with LRRK2 mutations and, perhaps, in sporadic PD. We also show that dardarin protein is expressed within human midbrain neurons and that C-terminal epitopes are also found in some Lewy bodies.