A Case of Isolated Palsy of the Eight External Rectus.

n/

Missense mutations in the perforin (PRF1) gene as a cause of hereditary cancer predisposition

Perforin, a pore-forming toxin released from secretory granules of NK cells and CTLs, is essential for their cytotoxic activity against infected or cancerous target cells. Bi-allelic loss-of-function mutations in the perforin gene are invariably associated with a fatal immunoregulatory disorder, familial haemophagocytic lymphohistiocytosis type 2 (FHL2), in infants. More recently, it has also been recognized that partial loss of perforin function can cause disease in later life, including delayed onset FHL2 and haematological malignancies. Herein we report a family in which a wide range of systemic inflammatory and neoplastic manifestations have occurred across three generations. We found that disease was linked to two missense perforin gene mutations (encoding A91V, R410W) that cause protein misfolding and partial loss of activity. These cases link the partial loss of perforin function with some solid tumours that are known to be controlled by the immune system, as well as haematological cancers. Our findings also demonstrate that perforin gene mutations can contribute to hereditary cancer predisposition

Biomechanical analysis of walking gait when simulating the use of an Ilizarov external fixator

The Ilizarov frame is an external fixation device, primarily used for the treatment of complex fractures. The authors postulate that the size and weight of the frame may lead to biomechanical adaptations to gait, independent to any injury. Temporospatial characteristics, kinetics and kinematics were assessed when simulating the use of an Ilizarov frame. Fifteen healthy participants performed walking trials, with and without the simulated frame. Significant changes to temporospatial characteristics were identified, with a decreased mean walking speed (with: 1.24 m s⁻¹; without: 1.29 m s⁻¹) and increased mean step width (with: 0.14 m; without: 0.11 m). The push-off phase of gait differed significantly between test conditions with mean increases in ankle dorsiflexion angles (with: 90.4°; without: 89.0°) and extension moments (proportional to body weight or P BWT) at the knee and ankle (knee with: 0.8 P BWT·m; without: 0.7 P BWT·m; ankle with: 1.6 P BWT·m; without: 1.6 P BWT·m). Although changes were small and likely to be clinically insignificant, the size and weight of the frame led to adaptations which may be magnified for patient groups with associated injury and pain at the lower limb. Results provide an argument for the potential redesign of the frame

Exploring Canadian Echinoderm Diversity through DNA Barcodes

Funding: This research was funded, in part, by the Natural Sciences and Engineering Research Council (NSERC) through a Discovery Grant to PDNH and a postgraduate scholarship to EAC. Sequence analysis was enabled by funding from the government of Canada through Genome Canada and the Ontario Genomics Institute in support of the International Barcode of Life Project (OGI-036). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Bridgette Clarkston, Christina Carr, Claudia Hand, Jeremy deWaard, Jim Boutillier, Katy Hind, Robert Frank, Sandra McCubbin, Tanya Brown, Tom Sheldon, and Victoria Frank for contributing specimens and aiding in collections. Kelly Sendall kindly provided access to the echinoderm collections at the Royal British Columbia Museum while we deeply appreciate the help that Chris Mah, Melissa Frey, and Phil Lambert provided with identifications. We also thank staff at the Canadian Centre for DNA Barcoding in the CBG for their aid in sequence acquisition. Lastly, we thank O.S. Klanten and two anonymous reviewers for their helpful suggestions on earlier versions of this manuscript.Peer reviewedPublisher PD

Bifurcation study of blood flow control in the kidney.

Renal blood flow is maintained within a narrow window by a set of intrinsic autoregulatory mechanisms. Here, a mathematical model of renal hemodynamics control in the rat kidney is used to understand the interactions between two major renal autoregulatory mechanisms: the myogenic response and tubuloglomerular feedback. A bifurcation analysis of the model equations is performed to assess the effects of the delay and sensitivity of the feedback system and the time constants governing the response of vessel diameter and smooth muscle tone. The results of the bifurcation analysis are verified using numerical simulations of the full nonlinear model. Both the analytical and numerical results predict the generation of limit cycle oscillations under certain physiologically relevant conditions, as observed in vivo

Characteristics of hip joint reaction forces during a range of activities

The paper reports the characteristics of joint forces for 9 activities in 18 normal healthy subjects. Activities included Walk, Walk Turn, Stand to Sit, Sit to Stand, Squat, Stand Reach, Kneel Reach, Lunge, and Golf Swing. Within the cohort ∼30% variability occurred in the manner in which each activity was completed. Within the activities the average maximum load characteristics varied in magnitude (0.5–6.4 ρBWT) and also in duration (0.96–5.89 s.) when compared to walking (3.1 ρBWT,1.1 s.). The corresponding impulse ranged from 1.6 during the Walk to 6.7 ρ.BWT.s for the Golf Swing . As high loads with low sliding velocities have been shown in the literature to be damaging to the tribology of compliant contact surfaces the findings are postulated by the authors to be specifically important for the pre-clinical testing of cartilage substitutional materials. Note: Force was normalized to body weight (ρBWT) throughout the study

Factors affecting follower responses to movement calls in cooperatively breeding dwarf mongooses

In social species, individuals maximize the benefits of group living by remaining cohesive and coordinating their actions. Communication is key to collective action, including ensuring that group members move together; individuals often produce signals when attempting to lead a group to a new area. However, the function of these signals, and how responses to them are affected by intrinsic characteristics of the caller and extrinsic factors, has rarely been experimentally tested. We conducted a series of field-based playback experiments with habituated wild dwarf mongooses, Helogale parvula, a cooperatively breeding and territorial species, to investigate follower responses to movement calls. In our first experiment, we found that focal individuals were more likely to respond to playback of ‘movement calls’ than control ‘close calls’, indicating movement calls function as recruitment signals. In a second experiment, we found that focal individuals responded similarly to the movement calls of dominant and subordinate groupmates, suggesting that dominance status (an intrinsic factor) does not influence receiver responses. In a final experiment, we found that individuals responded to the simulated presence of a rival group, but that this outgroup conflict (an extrinsic factor) did not affect responses to movement calls compared to a control situation. This may be because attention is instead focused on the potential presence of an imminent threat. By using playbacks to isolate the acoustic signal from physical movement cues, our results provide experimental evidence of how movement calls help leaders to attract followers and thus adds to our understanding of recruitment signals more generally

Salford postgraduate annual research conference (SPARC) 2012 proceedings

These proceedings bring together a selection of papers from the 2012 Salford Postgraduate Annual Research Conference (SPARC). They reflect the breadth and diversity of research interests showcased at the conference, at which over 130 researchers from Salford, the North West and other UK universities presented their work. 21 papers are collated here from the humanities, arts, social sciences, health, engineering, environment and life sciences, built environment and business