Adaptation of the Transverse Carpal Ligament Associated with Repetitive Hand Use in Pianists

The transverse carpal ligament (TCL) plays a critical role in carpal tunnel biomechanics through interactions with its surrounding tissues. The purpose of this study was to investigate the in vivo adaptations of the TCL’s mechanical properties in response to repetitive hand use in pianists using acoustic radiation force impulse (ARFI) imaging. It was hypothesized that pianists, in comparison to non-pianists, would have a stiffer TCL as indicated by an increased acoustic shear wave velocity (SWV). ARFI imagining was performed for 10 female pianists and 10 female non-pianists. The median SWV values of the TCL were determined for the entire TCL, as well as for its radial and ulnar portions, rTCL and uTCL, respectively. The TCL SWV was significantly increased in pianists relative to non-pianists (p < 0.05). Additionally, the increased SWV was location dependent for both pianist and non-pianist groups (p < 0.05), with the rTCL having a significantly greater SWV than the uTCL. Between groups, the rTCL SWV of pianists was 22.2% greater than that of the non-pianists (p < 0.001). This localized increase of TCL SWV, i.e. stiffening, may be primarily attributable to focal biomechanical interactions that occur at the radial TCL aspect where the thenar muscles are anchored. Progressive stiffening of the TCL may become constraining to the carpal tunnel, leading to median nerve compression in the tunnel. TCL maladaptation helps explain why populations who repeatedly use their hands are at an increased risk of developing musculoskeletal pathologies, e.g. carpal tunnel syndrome.     

Elevated p16ink4a Expression in Human Labial Salivary Glands as a Potential Correlate of Cognitive Aging in Late Midlife

Background

The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase inhibitor, p16^ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a) locus on chromosome 9q21. Up-regulation of p16^ink4a has been linked to cellular senescence, and findings from studies on different mammalian tissues suggest that p16^ink4a may be a biomarker of organismal versus chronological age.

Objective

The aim of this study was to examine the immunolocalization pattern of p16^ink4a in human labial salivary gland (LSG) tissue, and to analyze whether its expression level in LSGs is a peripheral correlate of cognitive decline in late midlife.

Methods

The present study was a part of a study of causes and predictors of cognitive decline in middle-aged men in a Danish birth cohort. It is based on data from 181 male participants from the Danish Metropolit birth cohort, born in 1953, who were examined for age-associated alterations in cognition, dental health, and morphological and autonomic innervation characteristics of the LSGs. The participants were allocated to two groups based on the relative change in cognitive performance from young adulthood to late midlife. LSG biopsies were analyzed by qRT-PCR for the expression level of p16^ink4a. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of LSGs.

Results

p16^ink4a immunoreactivity was observed in LSG ductal, myoepithelial, and stromal cells, but not in acinar cells. The mean relative expression of p16^ink4a in LSGs was higher in the group of participants with decline in cognitive performance. A logistic regression analysis revealed that the relative p16 expression was predictive of the participant’s group assignment. A negative correlation was found between relative p16^ink4a expression and the participant’s standardized regression residuals from early adulthood to late midlife cognitive performance scores.

Conclusions

p16^ink4a expression in human LSGs may constitute a potential peripheral correlate of cognitive decline. Human labial salivary glands seem suitable for studies on organismal as opposed to chronological age.     

Construction and Rescue of a Molecular Clone of Deformed Wing Virus (DWV)

European honey bees are highly important in crop pollination, increasing the value of global agricultural production by billions of dollars. Current knowledge about virulence and pathogenicity of Deformed wing virus (DWV), a major factor in honey bee colony mortality, is limited. With this study, we close the gap between field research and laboratory investigations by establishing a complete in vitro model for DWV pathogenesis. Infectious DWV was rescued from a molecular clone of a DWV-A genome that induces DWV symptoms such as crippled wings and discoloration. The expression of DWV proteins, production of infectious virus progeny, and DWV host cell tropism could be confirmed using newly generated anti-DWV monoclonal antibodies. The recombinant RNA fulfills Koch’s postulates circumventing the need of virus isolation and propagation of pure virus cultures. In conclusion, we describe the development and application of a reverse genetics system for the study of DWV pathogenesis.     

TMEM45A Is Dispensable for Epidermal Morphogenesis,Keratinization and Barrier Formation

TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.     

Molecular phylogeny of Harpactorinae and Bactrodinae uncovers complex evolution of sticky trap predation in assassin bugs (Heteroptera: Reduviidae)

Sticky trap predation, the use of adhesive substances to trap and capture prey, is an intriguing yet poorly studied predatory strategy. Unique among known sticky trap predators, assassin bugs (Reduviidae) have evolved both exogenous and endogenous sticky trap predatory mechanisms: some trap their prey with sticky plant resins, some scavenge insects entrapped by sticky plant trichomes and others self‐produce sticky secretions. The evolution of these different strategies in assassin bugs is poorly understood due to the lack of comprehensive phylogenies. We reconstruct a phylogeny of Reduviidae (141 taxa; > 5000 bp) focusing on the Harpactorinae and Bactrodinae that engage in sticky trap predation. Ancestral state reconstruction, and temporal and geographical divergence analyses show that sticky trap predation techniques in assassin bugs evolved at least seven times independently since the late Cretaceous: use of sticky plant trichomes evolved as many as four times, resin‐use twice independently and once as a transition from trichome use, and ‘self‐stickiness’ once. Exogenous and endogenous sticky traps first appeared in the Neotropics, with the two exogenous mechanisms (resin and trichome use) subsequently evolving independently in the Old World. This study illustrates, for the first time, the complex evolutionary pattern of sticky trap predation within assassin bugs.     

The P2-receptor-mediated Ca2+ signalosome of the human pulmonary endothelium - implications for pulmonary arterial hypertension

Purinergic Signalling - Dysfunction of the pulmonary endothelium is associated with most lung diseases. Extracellular nucleotides modulate a plethora of endothelial functions in the lung such as...     

Modeling population dynamics in a microbial consortium under control of a synthetic pheromone‐mediated communication system

Microbial consortia can be used to catalyze complex biotransformations. Tools to control the behavior of these consortia in a technical environment are currently lacking. In the present study, a synthetic biology approach was used to build a model consortium of two Saccharomyces cerevisiae strains where growth and expression of the fluorescent marker protein EGFP by the receiver strain is controlled by the concentration of α‐factor pheromone, which is produced by the emitter strain. We have developed a quantitative experimental and theoretical framework to describe population dynamics in the model consortium. We measured biomass growth and metabolite production in controlled bioreactor experiments, and used flow cytometry to monitor changes of the subpopulations and protein expression under different cultivation conditions. This dataset was used to parameterize a segregated mathematical model, which took into account fundamental growth processes, pheromone‐induced growth arrest and EGFP production, as well as pheromone desensitization after extended exposure. The model was able to predict the growth dynamics of single‐strain cultures and the consortium quantitatively and provides a basis for using this approach in actual biotransformations.