Biological insights in the pathogenesis of hypermobile Ehlers-Danlos syndrome from proteome profiling of patients' dermal myofibroblasts

Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS nosology. Moreover, the hEDS phenotypic spectrum is wide-ranging and comprises multiple associated signs and symptoms shared with other heritable or acquired connective tissue disorders and chronic inflammatory diseases. In this complex scenario, we previously demonstrated that hEDS patients' skin fibroblasts show phenotypic features of myofibroblasts, widespread extracellular matrix (ECM) disarray, perturbation of ECM-cell contacts, and dysregulated expression of genes involved in connective tissue architecture and related to inflammatory and pain responses. Herein, the cellular proteome of 6 hEDS dermal myofibroblasts was compared to that of 12 control fibroblasts to deepen the knowledge on mechanisms involved in the disease pathogenesis. Qualitative and quantitative differences were assessed based on top-down and bottom-up approaches and some differentially expressed proteins were proofed by biochemical analyses. Proteomics disclosed the differential expression of proteins principally implicated in cytoskeleton organization, energy metabolism and redox balance, proteostasis, and intracellular trafficking. Our findings offer a comprehensive view of dysregulated protein networks and related pathways likely associated with the hEDS pathophysiology. The present results can be regarded as a starting point for future in-depth investigations aimed to decipher the functional impact of potential bioactive molecules for the development of targeted management and therapies.     

Genetic and ecological consequences of recent habitat fragmentation in a narrow endemic plant species within an urban context

Understanding the timescales that shape spatial genetic structure is pivotal to ascertain the impact of habitat fragmentation on the genetic diversity and reproductive viability of long-lived plant populations. Combining genetic and ecological information with current and past fragmentation conditions allows the identification of the main drivers important in shaping population structure and declines in reproduction, which is crucial for informing conservation strategies. Using historic aerial photographs, we defined the past fragmentation conditions for the shrub Conospermum undulatum, a species now completely embedded in an urban area. We explored the impact of current and past conditions on its genetic layout and assessed the effects of genetic and environmental factors on its reproduction. The historically high structural connectivity was evident in the genetics of the species. Despite the current intense fragmentation, we found similar levels of genetic diversity across populations and a weak spatial genetic structure. Historical connectivity was negatively associated with genetic differentiation among populations and positively related to within-population genetic diversity. Variation partitioning of reproductive performance explained?~?66% of the variance, showing significant influences for genetic (9%), environmental (15%), and combined (42%) fractions. Our study highlights the importance of considering the historical habitat dynamics when investigating fragmentation consequences in long-lived plants. A detailed characterization of fragmentation from 1953 has shown how low levels of genetic fixation are due to extensive gene flow through the non-fragmented landscape. Moreover, knowledge of the relationships between genetic and environmental variation and reproduction can help to implement effective conservation strategies, particularly in highly dynamic landscapes.

     

Invading parasites: spillover of an alien nematode reduces survival in a native species

Biological Invasions - It is widely assumed that spillover of alien parasites to native host species severely impacts naïve populations, ultimately conferring a competitive advantage to...     

What shapes the range edge of a dominant African savanna tree,Colophospermum mopane? A demographic approach

Climate is widely assumed to be the primary process that limits the distribution ranges of plants. Yet, savannas have vegetation not at equilibrium with climate, instead its structure and function are shaped by interactions between fire, herbivory, climate, and vegetation. I use the rich literature of a dominant African savanna woody plant, Colophospermum mopane, to demonstrate that climate and disturbance interact with each demographic stage to shape this species range limits. This synthesis highlights that climate‐based predictions for the range of C. mopane inadequately represents the processes that shape its distribution. Instead, seed bank depletion and rainfall limitation create a demographic bottleneck at the early seedling stage. The legacy of top‐kill from disturbance changes tree stand architecture causing a critical limitation in seed supply. Exposure to top‐kill at all demographic stages causes a vigorous resprouting response and shifts tree architecture from that of 1–2 stemmed tall trees to that of a short multi‐stemmed shrub. The shorter, multi‐stemmed shrubs are below the height threshold (4 m) at which they can produce seeds, resulting in shrub‐dominated landscapes that are effectively sterile. This effect is likely most pronounced at the range edge where top‐kill‐inducing disturbances increase in frequency. The proposed mechanistic, demographic‐based understanding of C. mopane''s range limits highlights the complexity of processes that interact to shape its range edges. This insight serves as a conceptual model for understanding the determinants of range limits of other dominant woody savannas species living in disturbance limited ecosystems.     

Massage and stretching reduce spinal reflex excitability without affecting twitch contractile properties

Both stretching and massage can increase range of motion. Whereas the stretching-induced increases in ROM have been attributed to changes in neural and muscle responses, there is no literature investigating the ROM mechanisms underlying the interaction of stretch and massage. The objective of this paper was to evaluate changes in neural and evoked muscle responses with two types of massage and static stretching. With this repeated measures design, 30 s of plantar flexors musculotendinous junction (MTJ) and tapotement (TAP) massage were implemented either with or without 1 min of concurrent stretching as well as a control condition. Measures included the soleus maximum H-reflex/M-wave (H/M) ratio, as well as electromechanical delay (EMD), and evoked contractile properties of the triceps surae. With the exception of EMD, massage and stretch did not significantly alter triceps surae evoked contractile properties. Massage with and without stretching decreased the soleus H/M ratio. Both TAP conditions provided greater H/M ratio depression than MTJ massage while the addition of stretch provided the greatest inhibition. Both massage types when combined with stretching increased the duration of the EMD. In conclusion, MTJ and TAP massage as well as stretching decreased spinal reflex excitability, with TAP providing the strongest suppression. While static stretching prolongs EMD, massage did not affect contractile properties.