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Concept: Tissues


Ancient human mobility at the individual level is conventionally studied by the diverse application of suitable techniques (e.g. aDNA, radiogenic strontium isotopes, as well as oxygen and lead isotopes) to either hard and/or soft tissues. However, the limited preservation of coexisting hard and soft human tissues hampers the possibilities of investigating high-resolution diachronic mobility periods in the life of a single individual. Here, we present the results of a multidisciplinary study of an exceptionally well preserved circa 3.400-year old Danish Bronze Age female find, known as the Egtved Girl. We applied biomolecular, biochemical and geochemical analyses to reconstruct her mobility and diet. We demonstrate that she originated from a place outside present day Denmark (the island of Bornholm excluded), and that she travelled back and forth over large distances during the final months of her life, while consuming a terrestrial diet with intervals of reduced protein intake. We also provide evidence that all her garments were made of non-locally produced wool. Our study advocates the huge potential of combining biomolecular and biogeochemical provenance tracer analyses to hard and soft tissues of a single ancient individual for the reconstruction of high-resolution human mobility.

Concepts: Tissues, Copper, Tin, Denmark, Danish language, Geochemistry, Mesopotamia, Isotope geochemistry


Heterochronic parabiosis rejuvenates the performance of old tissue stem cells at some expense to the young, but whether this is through shared circulation or shared organs is unclear. Here we show that heterochronic blood exchange between young and old mice without sharing other organs, affects tissues within a few days, and leads to different outcomes than heterochronic parabiosis. Investigating muscle, liver and brain hippocampus, in the presence or absence of muscle injury, we find that, in many cases, the inhibitory effects of old blood are more pronounced than the benefits of young, and that peripheral tissue injury compounds the negative effects. We also explore mechanistic explanations, including the role of B2M and TGF-beta. We conclude that, compared with heterochronic parabiosis, heterochronic blood exchange in small animals is less invasive and enables better-controlled studies with more immediate translation to therapies for humans.

Concepts: Blood, Heart, Liver, Organ, Tissues, Tissue


Protein timing is a popular dietary strategy designed to optimize the adaptive response to exercise. The strategy involves consuming protein in and around a training session in an effort to facilitate muscular repair and remodeling, and thereby enhance post-exercise strength- and hypertrophy-related adaptations. Despite the apparent biological plausibility of the strategy, however, the effectiveness of protein timing in chronic training studies has been decidedly mixed. The purpose of this paper therefore was to conduct a multi-level meta-regression of randomized controlled trials to determine whether protein timing is a viable strategy for enhancing post-exercise muscular adaptations. The strength analysis comprised 478 subjects and 96 ESs, nested within 41 treatment or control groups and 20 studies. The hypertrophy analysis comprised 525 subjects and 132 ESs, nested with 47 treatment or control groups and 23 studies. A simple pooled analysis of protein timing without controlling for covariates showed a small to moderate effect on muscle hypertrophy with no significant effect found on muscle strength. In the full meta-regression model controlling for all covariates, however, no significant differences were found between treatment and control for strength or hypertrophy. The reduced model was not significantly different from the full model for either strength or hypertrophy. With respect to hypertrophy, total protein intake was the strongest predictor of ES magnitude. These results refute the commonly held belief that the timing of protein intake in and around a training session is critical to muscular adaptations and indicate that consuming adequate protein in combination with resistance exercise is the key factor for maximizing muscle protein accretion.

Concepts: Metabolism, Energy, Muscle, Physical exercise, Actin, Tissues, Muscular system, Exercise physiology


During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.

Concepts: Inflammation, Atherosclerosis, Heart, Blood vessel, Capillary, Tissues, Endothelium, Vein


Intracellular concentrations of adenosine-5'-triphosphate (ATP) are many times greater than extracellular concentrations (1-10 mM versus 10-100 nM, respectively) and cellular release of ATP is tightly controlled. Transient rises in extracellular ATP and its metabolite adenosine have important signaling roles; and acting through purinergic receptors, can increase blood flow and oxygenation of tissues; and act as neurotransmitters. Increased blood flow not only increases substrate availability but may also aid in recovery through removal of metabolic waste products allowing muscles to accomplish more work with less fatigue. The objective of the present study was to determine if supplemental ATP would improve muscle torque, power, work, or fatigue during repeated bouts of high intensity resistance exercise.

Concepts: Metabolism, Energy, Muscle, Tissues, Lactic acid, Exercise physiology, Power, Waste


Cycling has been shown to confer considerable benefits in terms of health, leading to reductions in death rates principally due to cardiovascular improvements and adaptation. Given the disparity between the benefits of cycling on cardiovascular fitness and previous research finding that cycling may not be beneficial for bone health, Hugo Olmedillas and colleagues performed a systematic review of the literature. They concluded that road cycling does not appear to confer any significant osteogenic benefit. They postulate that the cause of this is that, particularly at a competitive level, riders spend long periods of time in a weight-supported position on the bike. Training programs may be supplemented with impact loading to preserve bone health; however, the small increased risk of soft tissue injury must also be considered. See related research article

Concepts: Academic publishing, Research, Tissues, Cycling, Soft tissue, Position, Employee benefit, Soft tissue injury


Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM) homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young’s modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA) stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF)) were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in designing hydrogel substrates with physiologically relevant stiffness to dynamically redirect cell fate in vitro.

Concepts: Bone, Wound healing, Collagen, Extracellular matrix, Muscle, Tissues, Connective tissue, Young's modulus


The gluteus medius muscle is essential for gait and hip stability. Changes that occur in the gluteus medius muscles in patients with developmental dysplasia of the hip (DDH) are not well understood. A better understanding of DDH related changes will have positive repercussions toward hip soft tissue reconstruction.

Concepts: Tissues, Gluteus medius muscle


Human subcutaneous (SQ) white adipose tissue (WAT) can vary according to its anatomical location, with subsequent differences in its proteomic profile.

Concepts: Adipose tissue, Tissues, Brown adipose tissue, White adipose tissue


Mechanics is an important component in the regulation of cell shape, proliferation, migration and differentiation during normal homeostasis and disease states. Biomaterials that match the elastic modulus of soft tissues have been effective for studying this cell mechanobiology, but improvements are needed in order to investigate a wider range of physicochemical properties in a controlled manner. We hypothesized that polydimethylsiloxane (PDMS) blends could be used as the basis of a tunable system where the elastic modulus could be adjusted to match most types of soft tissue. To test this we formulated blends of two commercially available PDMS types, Sylgard 527 and Sylgard 184, which enabled us to fabricate substrates with an elastic modulus anywhere from 5 kPa up to 1.72 MPa. This is a three order-of-magnitude range of tunability, exceeding what is possible with other hydrogel and PDMS systems. Uniquely, the elastic modulus can be controlled independently of other materials properties including surface roughness, surface energy and the ability to functionalize the surface by protein adsorption and microcontact printing. For biological validation, PC12 (neuronal inducible-pheochromocytoma cell line) and C2C12 (muscle cell line) were used to demonstrate that these PDMS formulations support cell attachment and growth and that these substrates can be used to probe the mechanosensitivity of various cellular processes including neurite extension and muscle differentiation.

Concepts: Muscle, Cellular differentiation, Cell culture, Tissues, Materials science, Tissue, Soft tissue, Young's modulus