How do engineering materials deform when bearing mechanical loads? To answer this crucial question, the book bridges the gap between continuum mechanics and materials science. The different kinds of ...material deformation are explained in detail.
Background Plants that accumulate metal and metalloid trace elements to extraordinarily high concentrations in their living biomass have inspired much research worldwide during the last decades. ...Hyperaccumulators have been recorded and experimentally confirmed for elements such as nickel, zinc, cadmium, manganese, arsenic and selenium. However, to date, hyperaccumulation of lead, copper, cobalt, chromium and thallium remain largely unconfirmed. Recent uses of the term in relation to rare-earth elements require critical evaluation. Scope Since the mid-1970s the term 'hyperaccumulator' has been used millions of times by thousands of people, with varying degrees of precision, aptness and understanding that have not always corresponded with the views of the originators of the terminology and of the present authors. There is therefore a need to clarify the circumstances in which the term 'hyperaccumulator' is appropriate and to set out the conditions that should be met when the terms are used. We outline here the main considerations for establishing metal or metalloid hyperaccumulation status of plants, (re) defme some of the terminology and note potential pitfalls. Conclusions Unambiguous communication will require the international scientific community to adopt standard terminology and methods for confirming the reliability of analytical data in relation to metal and metalloid hyperaccumulators.
•One principal regulator of circulating estrogens is the gut microbiome.•Disruption in the gut microbiome results in decreased circulating estrogens.•Alterations in the estrobolome can drive ...estrogen-mediated pathologies.•Bariatric surgery, fecal-microbiome transplant and metformin alter gut microbiota composition.•Interventions that alter gut microbiome diversity impact estrogen-mediated disease.
Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women’s health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development of conditions discussed herein: obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study.
Much of our understanding of the biological mechanisms that underlie cellular functions, such as migration, differentiation and force-sensing has been garnered from studying cells cultured on ...two-dimensional (2D) glass or plastic surfaces. However, more recently the cell biology field has come to appreciate the dissimilarity between these flat surfaces and the topographically complex, three-dimensional (3D) extracellular environments in which cells routinely operate in vivo. This has spurred substantial efforts towards the development of in vitro 3D biomimetic environments and has encouraged much cross-disciplinary work among biologists, material scientists and tissue engineers. As we move towards more-physiological culture systems for studying fundamental cellular processes, it is crucial to define exactly which factors are operative in 3D microenvironments. Thus, the focus of this Commentary will be on identifying and describing the fundamental features of 3D cell culture systems that influence cell structure, adhesion, mechanotransduction and signaling in response to soluble factors, which - in turn - regulate overall cellular function in ways that depart dramatically from traditional 2D culture formats. Additionally, we will describe experimental scenarios in which 3D culture is particularly relevant, highlight recent advances in materials engineering for studying cell biology, and discuss examples where studying cells in a 3D context provided insights that would not have been observed in traditional 2D systems.
Hyperaccumulator plants are the material basis for phytoextraction research and for practical applications in decontaminating polluted soils and industrial wastes. China’s high biodiversity and ...substantial mineral resources make it a global hotspot for hyperaccumulator plant species. Intensive screening efforts over the past 20 years by researchers working in China have led to the discovery of many different hyperaccumulators for a range of elements. In this review, we present the state of knowledge on all currently reported hyperaccumulator species from China, including Cardamine hupingshanensis (selenium, Se), Dicranopteris dichotoma (rare earth elements, REEs), Elsholtzia splendens (copper, Cu), Phytolacca americana (manganese, Mn), Pteris vittata (arsenic, As), Sedum alfredii, and Sedum plumbizincicola (cadmium/zinc, Cd/Zn). This review covers aspects of the ecophysiology and molecular biology of tolerance and hyperaccumulation for each element. The major scientific advances resulting from the study of hyperaccumulator plants in China are summarized and synthesized.
We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression.
Fifteen men ...(21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of ring-13C6 phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition.
These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.
Molecular dynamics simulations are well established for the study of biomolecular systems. Within these simulations, energy functions known as force fields are used to determine the forces acting on ...atoms and molecules. While these force fields have been very successful, they contain a number of approximations, included to overcome limitations in computing power. One of the most important of these approximations is the omission of polarizability, the process by which the charge distribution in a molecule changes in response to its environment. Since polarizability is known to be important in many biochemical situations, and since advances in computer hardware have reduced the need for approximations within force fields, there is major interest in the use of force fields that include an explicit representation of polarizability. As such, a number of polarizable force fields have been under development: these have been largely experimental, and their use restricted to specialized researchers. This situation is now changing. Parameters for fully optimized polarizable force fields are being published, and associated code incorporated into standard simulation software. Simulations on the hundred‐nanosecond timescale are being reported, and are now within reach of all simulation scientists. In this overview, I examine the polarizable force fields available for the simulation of biomolecules, the systems to which they have been applied, and the benefits and challenges that polarizability can bring. In considering future directions for development of polarizable force fields, I examine lessons learnt from non‐polarizable force fields, and highlight issues that remain to be addressed. WIREs Comput Mol Sci 2015, 5:241–254. doi: 10.1002/wcms.1215
This article is categorized under:
Structure and Mechanism > Computational Biochemistry and Biophysics
Molecular and Statistical Mechanics > Molecular Mechanics
Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods
The extracellular, matrix-modifying enzyme lysyl oxidase (LOX) has recently been linked to colorectal cancer (CRC) progression, in particular to the stages of invasion and metastasis. In this report, ...we use cell lines expressing a catalytically inactive mutant form of LOX to show that catalytic activity is required for LOX-mediated effects on proliferation and invasion in both in vitro and in vivo models of CRC. Furthermore, we use rheology to measure the relative stiffness of modified collagen matrices and subcutaneous tumors, and show that LOX-induced collagen cross-linking results in stiffening of the matrix both in vitro and in vivo. We observe a strong association between matrix stiffness and activation of the FAK (focal adhesion kinase)/SRC-signaling pathway, with a stiffer environment resulting in increased FAK/SRC phosphorylation and a more proliferative and invasive phenotype. We are the first to show a direct relationship between LOX enzymatic activity and tissue stiffness, and to demonstrate a role for stiffness in driving CRC progression. Our findings provide significant evidence to suggest that therapeutic inhibition of LOX activity may provide a novel effective treatment option for patients with metastatic CRC.
Neural ensembles are found throughout the brain and are believed to underlie diverse cognitive functions including memory and perception. Methods to activate ensembles precisely, reliably, and ...quickly are needed to further study the ensembles' role in cognitive processes. Previous work has found that ensembles in layer 2/3 of the visual cortex (V1) exhibited pattern completion properties: ensembles containing tens of neurons were activated by stimulation of just two neurons. However, methods that identify pattern completion neurons are underdeveloped. In this study, we optimized the selection of pattern completion neurons in simulated ensembles. We developed a computational model that replicated the connectivity patterns and electrophysiological properties of layer 2/3 of mouse V1. We identified ensembles of excitatory model neurons using K-means clustering. We then stimulated pairs of neurons in identified ensembles while tracking the activity of the entire ensemble. Our analysis of ensemble activity quantified a neuron pair's power to activate an ensemble using a novel metric called pattern completion capability (PCC) based on the mean pre-stimulation voltage across the ensemble. We found that PCC was directly correlated with multiple graph theory parameters, such as degree and closeness centrality. To improve selection of pattern completion neurons in vivo, we computed a novel latency metric that was correlated with PCC and could potentially be estimated from modern physiological recordings. Lastly, we found that stimulation of five neurons could reliably activate ensembles. These findings can help researchers identify pattern completion neurons to stimulate in vivo during behavioral studies to control ensemble activation.
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