M8R tropomyosin mutation disrupts actin binding and filament regulation: The beginning affects the middle and end

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin''s reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T''s N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.     

Integrating multiple data sources to assess the distribution and abundance of bottlenose dolphins Tursiops truncatus in Scottish waters

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A layover stop in the African American great migration: identity,ruination, and memory

Gone Home challenges dominant representations of Appalachia as white, placing in the foreground the life histories of African Americans who hail from the coalfields of eastern Kentucky. The book reveals how mass migration shapes subjectivities, examining two generations of African Americans who migrated into and out of the coalfields between 1910 and 1970. The coalfields were a layover stop in an intergenerational migration from the rural South to urban centres in the North, Midwest, and West. This review reflects on the significance of the layover stop, both empirically and conceptually. One of the key contributions of Gone Home is to show how the layover stop was important not only in terms of time and place, but also in terms of collective identity. The review concludes by reflecting on interconnected themes of industrial ruination and intergenerational memory.     

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A forceful upper jaw facilitates picking-based prey capture: biomechanics of feeding in a butterflyfish,Chaetodon trichrous

Biomechanical models of feeding mechanisms elucidate how animals capture food in the wild, which, in turn, expands our understanding of their fundamental trophic niche. However, little attention has been given to modeling the protrusible upper jaw apparatus that characterizes many teleost species. We expanded existing biomechanical models to include upper jaw forces using a generalist butterflyfish, Chaetodon trichrous (Chaetodontidae) that produces substantial upper jaw protrusion when feeding on midwater and benthic prey. Laboratory feeding trials for C. trichrous were recorded using high-speed digital imaging; from these sequences we quantified feeding performance parameters to use as inputs for the biomechanical model. According to the model outputs, the upper jaw makes a substantial contribution to the overall forces produced during mouth closing in C. trichrous. Thus, biomechanical models that only consider lower jaw closing forces will underestimate total bite force for this and likely other teleost species. We also quantified and subsequently modeled feeding events for C. trichrous consuming prey from the water column versus picking attached prey from the substrate to investigate whether there is a functional trade-off between prey capture modes. We found that individuals of C. trichrous alter their feeding behavior when consuming different prey types by changing the timing and magnitude of upper and lower jaw movements and that this behavioral modification will affect the forces produced by the jaws during prey capture by dynamically altering the lever mechanics of the jaws. In fact, the slower, lower magnitude movements produced during picking-based prey capture should produce a more forceful bite, which will facilitate feeding on benthic attached prey items, such as corals. Similarities between butterflyfishes and other teleost lineages that also employ picking-based prey capture suggest that a suite of key behavioral and morphological innovations enhances feeding success for benthic attached prey items.