TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension.

Microarchitectural cues drive aligned fibrillar collagen deposition in vivo and in biomaterial scaffolds, but the cell-signaling events that underlie this process are not well understood. Utilizing a multicellular patterning model system that allows for observation of intracellular signaling events during collagen matrix assembly, we investigated the role of calcium (Ca2+) signaling in human mesenchymal stem cells (MSCs) during this process. We observed spontaneous Ca2+ oscillations in MSCs during fibrillar collagen assembly, and hypothesized that the transient receptor potential vanilloid 4 (TRPV4) ion channel, a mechanosensitive Ca2+-permeable channel, may regulate this signaling. Inhibition of TRPV4 nearly abolished Ca2+ signaling at initial stages of collagen matrix assembly, while at later times had reduced but significant effects. Importantly, blocking TRPV4 activity dramatically reduced aligned collagen fibril assembly; conversely, activating TRPV4 accelerated aligned collagen formation. TRPV4-dependent Ca2+ oscillations were found to be independent of pattern shape or subpattern cell location, suggesting this signaling mechanism is necessary for aligned collagen formation but not sufficient in the absence of physical (microarchitectural) cues that force multicellular alignment. As cell-generated mechanical forces are known to be critical to the matrix assembly process, we examined the role of TRPV4-mediated Ca2+ signaling in force generated across the load-bearing focal adhesion protein vinculin within MSCs using an FRET-based tension sensor. Inhibiting TRPV4 decreased tensile force across vinculin, whereas TRPV4 activation caused a dynamic unloading and reloading of vinculin. Together, these findings suggest TRPV4 activity regulates forces at cell-matrix adhesions and is critical to aligned collagen matrix assembly by MSCs.

Genetic variation in horizontally transmitted fungal endophytes of pine needles reveals population structure in cryptic species.

UNLABELLED: • PREMISE OF THE STUDY: Fungal endophytes comprise one of the most ubiquitous groups of plant symbionts, inhabiting healthy leaves and stems of all major lineages of plants. Together, they comprise immense species richness, but little is known about the fundamental processes that generate their diversity. Exploration of their population structure is needed, especially with regard to geographic distributions and host affiliations.• METHODS: We take a multilocus approach to examine genetic variation within and among populations of Lophodermium australe, an endophytic fungus commonly associated with healthy foliage of pines in the southeastern United States. Sampling focused on two pine species ranging from montane to coastal regions of North Carolina and Virginia.• KEY RESULTS: Our sampling revealed two genetically distinct groups within Lophodermium australe. Our analysis detected less than one migrant per generation between them, indicating that they are distinct species. The species comprising the majority of isolates (major species) demonstrated a panmictic structure, whereas the species comprising the minority of isolates (cryptic species) demonstrated isolation by distance. Distantly related pine species hosted the same Lophodermium species, and host species did not influence genetic structure.• CONCLUSIONS: We present the first evidence for isolation by distance in a foliar fungal endophyte that is horizontally transmitted. Cryptic species may be common among microbial symbionts and are important to delimit when exploring their genetic structure and microevolutionary processes. The hyperdiversity of endophytic fungi may be explained in part by cryptic species without apparent ecological and morphological differences as well as genetic diversification within rare fungal species across large spatial scales.

A novel portable and cost-efficient wheelchair training roller for persons with disabilities in economically disadvantaged settings: the EasyRoller.

PURPOSE: Stationary training rollers enable wheelchair users to maintain physical health and train as athletes, which serves to treat and prevent immobility-associated chronic disease and improve cardiorespiratory fitness required for sports performance. However, conventional exercise equipment is largely inaccessible for persons with disabilities in low-resource areas, primarily due to cost. The aim of this study was to prototype, develop, and test a portable, cost-efficient stationary training device for wheelchair users in low-resource settings - The EasyRoller. MATERIALS AND METHODS: Stakeholder input from wheelchair athletes, trainers, and potential commercial manufacturers was solicited and utilized to conceptualize The EasyRoller design. The device was constructed from easily sourced, low cost components, following which it was user-tested with Para athletes. Feedback was analysed and incorporated into newer versions of the prototype.Results and conclusions: The EasyRoller creatively combines easily-sourced components to significantly cut down cost and ease both manufacture and repair for use in low-resource settings. The device is portable with a total weight of 34 pounds and total size of 42 linear inches while also affordable with a total cost of USD$199. Hereby, The EasyRoller has the potential to increase physical activity participation in populations with impairment who live in socioeconomically deprived world regions.Implications for rehabilitationExercise and physical activity are key aspects of health and quality of life for persons with disabilitiesStationary training rollers, devices that enable wheelchair users to train, are often bulky and expensive and therefore inaccessible for populations in socio-economically disadvantaged settingsThe EasyRoller is a portable and affordable training device that increases access to exercise and physical activity for these populations.