Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity

<p>Abstract</p> <p>Background</p> <p>The balance between muscle regeneration and ongoing degeneration is a relationship that greatly influences the progression of muscular dystrophy. Numerous factors may influence the muscle regeneration, but more information about the relationship between genotype, clinical severity and the ability to regenerate is needed.</p> <p>Methods</p> <p>Muscle biopsies were obtained from the tibialis anterior muscle, and frozen sections were stained for general histopathological and immunohistological evaluation. Differences between groups were considered statistical significant at <it>P </it>< 0.05 using Student's unpaired <it>t</it>-test.</p> <p>Results</p> <p>We found that all patients with limb-girdle muscular dystrophy type 2I (LGMD2I) had a large number of internally nucleated fibers, a sign of previous regeneration. The level of expression of muscle-specific developmental proteins, such as neonatal myosin heavy chain (nMHC) and myogenin, was related to the clinical severity. Additionally, we found that the majority of nMHC-positive fibers did not stain positively for utrophin in patients who were compound heterozygous for the L276I mutation, suggesting that the predominant form of regeneration in these patients is fiber repair rather than formation of new fibers. Double staining showed that many smaller nMHC-positive fibers were positive for antibodies against the glycosylation on α-dystroglycan, suggesting that such glycosylation may be a result of muscle regeneration.</p> <p>Conclusion</p> <p>Severely affected patients with LGMD2I have a high level of muscle degeneration, which leads to a high rate of regeneration, but this is insufficient to change the imbalance between degeneration and regeneration, ultimately leading to progressive muscle wasting. Detailed information regarding the level and rate of muscle regeneration and potential obstructions of the regenerative pathway should be of use for future therapies involving satellite-cell activation.</p

Exploring Approaches for Blended Learning in Life Sciences

Digital tools and platforms offer new solutions to design and conduct university teaching. This case illustrates how such digital solutions may be utilized in problem-based learning programmes within life science educations. Specifically, the case evaluated the use of live-streamed and recorded lectures, the incorporation of digital formative assessment in lectures, and the use of a digital platform to support experimental project work in a research laboratory. We find that digital solutions provide flexibility for both lecturers and students, advantageous options for collecting and sharing information, and for engaging students in their learning process. However, digital tools cannot replace all aspects of traditional in-person teaching, such as social interactions. Rather, when blended with in-person teaching, digital solutions have a large potential for supporting new forms of and approaches to both theoretical and experimental university teaching

Reconciling behavioral, bioenergetic, and oceanographic views of bowhead whale predation on overwintering copepods at an Arctic hotspot (Disko Bay, Greenland)

Bowhead whales (Balaena mysticetus) visit Disko Bay, West Greenland in winter and early spring to feed on Calanus spp., at a time of year when the copepods are still mostly in diapause and concentrated in near-bottom patches. Combining past observations of copepod abundance and distribution with detailed observations of bowhead whale foraging behaviour from telemetry suggests that if the whales target the highest-density patches, they likely consume 26–75% of the Calanus standing stock annually. A parallel bioenergetic calculation further suggests that the whales’ patch selection must be close to optimally efficient at finding hotspots of high density copepods near the sea floor in order for foraging in Disko Bay to be a net energetic gain. Annual Calanus consumption by bowhead whales is similar to median estimates of consumption by each of three zooplankton taxa (jellies, chaetognaths, and predatory copepods), and much greater than the median estimate of consumption by fish larvae, as derived from seasonal abundance and specific ingestion rates from the literature. The copepods’ self-concentration during diapause, far from providing a refuge from predation, is the behaviour that makes this strong trophic link possible. Because the grazing impact of the whales comes 6–10 months later than the annual peak in primary production, and because Disko Bay sits at the end of rapid advective pathways (here delineated by a simple numerical particle-tracking experiment), it is likely that these Calanus populations act in part as a long-distance energetic bridge between the whales and primary production hundreds or thousands of km away

Energetic and physical limitations on the breaching performance of large whales

The considerable power needed for large whales to leap out of the water may represent the single most expensive burst maneuver found in nature. However, the mechanics and energetic costs associated with the breaching behaviors of large whales remain poorly understood. In this study we deployed whale-borne tags to measure the kinematics of breaching to test the hypothesis that these spectacular aerial displays are metabolically expensive. We found that breaching whales use variable underwater trajectories, and that high-emergence breaches are faster and require more energy than predatory lunges. The most expensive breaches approach the upper limits of vertebrate muscle performance, and the energetic cost of breaching is high enough that repeated breaching events may serve as honest signaling of body condition. Furthermore, the confluence of muscle contractile properties, hydrodynamics, and the high speeds required likely impose an upper limit to the body size and effectiveness of breaching whales

Scaling of swimming performance in baleen whales

The scale dependence of locomotor factors has long been studied in comparative biomechanics, but remains poorly understood for animals at the upper extremes of body size. Rorqual baleen whales include the largest animals, but we lack basic kinematic data about their movements and behavior below the ocean surface. Here, we combined morphometrics from aerial drone photogrammetry, whale-borne inertial sensing tag data and hydrodynamic modeling to study the locomotion of five rorqual species. We quantified changes in tail oscillatory frequency and cruising speed for individual whales spanning a threefold variation in body length, corresponding to an order of magnitude variation in estimated body mass. Our results showed that oscillatory frequency decreases with body length (proportional to length(-0.5)(3)) while cruising speed remains roughly invariant (proportional to length(0.08)) at 2 m s(-1). We compared these measured results for oscillatory frequency against simplified models of an oscillating cantilever beam (proportional to length(-1)) and an optimized oscillating Strouhal vortex generator (proportional to length(-1)). The difference between our length-scaling exponent and the simplified models suggests that animals are often swimming non-optimally in order to feed or perform other routine behaviors. Cruising speed aligned more closely with an estimate of the optimal speed required to minimize the energetic cost of swimming (proportional to length(-1)). Our results are among the first to elucidate the relationships between both oscillatory frequency and cruising speed and body size for free-swimming animals at the largest scale

Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality:a cluster-randomized clinical trial (TRIAGE III)

Abstract Background Risk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients. Methods The TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality. Results The trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group. The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results. Conclusions The TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice. Trial registration clinicaltrials.gov, NCT02643459. Registered 31 December 2015

High source levels and small active space of high-pitched song in bowhead whales (Balaena mysticetus)

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Public Library of Science, doi:10.1371/journal.pone.0052072.The low-frequency, powerful vocalizations of blue and fin whales may potentially be detected by conspecifics across entire ocean basins. In contrast, humpback and bowhead whales produce equally powerful, but more complex broadband vocalizations composed of higher frequencies that suffer from higher attenuation. Here we evaluate the active space of high frequency song notes of bowhead whales (Balaena mysticetus) in Western Greenland using measurements of song source levels and ambient noise. Four independent, GPS-synchronized hydrophones were deployed through holes in the ice to localize vocalizing bowhead whales, estimate source levels and measure ambient noise. The song had a mean apparent source level of 185±2 dB rms re 1 µPa @ 1 m and a high mean centroid frequency of 444±48 Hz. Using measured ambient noise levels in the area and Arctic sound spreading models, the estimated active space of these song notes is between 40 and 130 km, an order of magnitude smaller than the estimated active space of low frequency blue and fin whale songs produced at similar source levels and for similar noise conditions. We propose that bowhead whales spatially compensate for their smaller communication range through mating aggregations that co-evolved with broadband song to form a complex and dynamic acoustically mediated sexual display.This work was funded by the Oticon Foundation (grant # 08-3469 to Arctic Station, OT). OT and MC were additionally funded by AP Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal, MS by a PhD scholarship from the Oticon Foundation, FHJ by a Danish Council for Independent Research, Natural Sciences post-doctoral grant, SEP by a grant from the U.S. Office of Naval Research, and PTM by frame grants from the Danish Natural Science Research Council

Don’t forget the porpoise: acoustic monitoring reveals fine scale temporal variation between bottlenose dolphin and harbour porpoise in Cardigan Bay SAC

Populations of bottlenose dolphin and harbour porpoise inhabit Cardigan Bay, which was designated a Special Area of Conservation (SAC), with bottlenose dolphin listed as a primary feature for its conservation status. Understanding the abundance, distribution and habitat use of species is fundamental for conservation and the implementation of management. Bottlenose dolphin and harbour porpoise usage of feeding sites within Cardigan Bay SAC was examined using passive acoustic monitoring. Acoustic detections recorded with calibrated T-PODs (acoustic data loggers) indicated harbour porpoise to be present year round and in greater relative abundance than bottlenose dolphin. Fine-scale temporal partitioning between the species occurred at three levels: (1) seasonal differences, consistent between years, with porpoise detections peaking in winter months and dolphin detections in summer months; (2) diel variation, consistent across sites, seasons and years, with porpoise detections highest at night and dolphin detections highest shortly after sunrise; and (3) tidal variation was observed with peak dolphin detections occurring during ebb at the middle of the tidal cycle and before low tide, whereas harbour porpoise detections were highest at slack water, during and after high water with a secondary peak recorded during and after low water. General Additive Models (GAMs) were applied to better understand the effects of each covariate. The reported abundance and distribution of the two species, along with the temporal variation observed, have implications for the design and management of protected areas. Currently, in the UK, no SACs have been formally designated for harbour porpoise while three exist for bottlenose dolphins. Here, we demonstrate a need for increased protection and species-specific mitigation measures for harbour porpoise