A wide range of cell types depend on mechanically induced signals to enable appropriate physiological responses. The skeleton is particularly dependent on mechanical information to guide the resident ...cell population towards adaptation, maintenance and repair. Research at the organ, tissue, cell and molecular levels has improved our understanding of how the skeleton can recognize the functional environment, and how these challenges are translated into cellular information that can site-specifically alter phenotype. This review first considers those cells within the skeleton that are responsive to mechanical signals, including osteoblasts, osteoclasts, osteocytes and osteoprogenitors. This is discussed in light of a range of experimental approaches that can vary parameters such as strain, fluid shear stress, and pressure. The identity of mechanoreceptor candidates is approached, with consideration of integrins, pericellular tethers, focal adhesions, ion channels, cadherins, connexins, and the plasma membrane including caveolar and non-caveolar lipid rafts and their influence on integral signaling protein interactions. Several mechanically regulated intracellular signaling cascades are detailed including activation of kinases (Akt, MAPK, FAK), β-catenin, GTPases, and calcium signaling events. While the interaction of bone cells with their mechanical environment is complex, an understanding of mechanical regulation of bone signaling is crucial to understanding bone physiology, the etiology of diseases such as osteoporosis, and to the development of interventions to improve bone strength.
► A thorough review of mechanical signaling pathways related to bone biology. ► Covers signaling events regulating functions in cells influencing bone formation. ► Details the various mechanical loading parameters influencing signaling pathways.
Conventional progressive concentric strengthening exercise (CSE) to improve bone mineral density (BMD) and bone mineral content (BMC) may not be feasible for populations with chronic musculoskeletal ...and/or metabolic conditions, such as osteoporosis or obesity. Muscle lengthening exercise, also known as an eccentric strengthening exercise (ESE), may have a special utility for those populations due to greater force generation versus CSE. In fact, greater mechanical loading can be induced on bone at lower resistance levels with ESE. However, effects of ESE on BMD and BMC are unclear. Thus, the purpose of this review was to interrogate the effects of ESE on BMD and BMC.
A literature review was conducted between January 1995 and April 2022 focusing on randomized controlled trials investigating the effects of ESE on BMD and/or BMC in humans. Terms covering the domains of exercise, bone, and populations were searched on PubMed, CINAHL, and Scopus. The methodological quality of each interventional study was rated using Physiotherapy Evidence Database (PEDro) scale. Cohen's d was calculated to determine the magnitude of the effects of ERE on site-specific outcome measures of BMD and/or BMC.
Out of 1,182 articles initially found, a total of seven full length articles met our inclusion criteria. Of the seven studies, most of the interventions were performed in young (n = 5, PEDro = 5-7) versus middle-aged (n = 1, PEDro = 4) or older (n = 1, PEDro = 6) adults. BMD and BMC generally improved due to ESE; however the effects of ESE on BMD and BMC were non-homogenous. Effect size (d) ranged from 0.10-0.87 in young adults while it was 1.16 in older adults. Effect size (d) could not be calculated for the middle-aged adult study due to critical methodological limitations of the intervention.
Large variability exists for the effectiveness of ESE on BMD/BMC across the human life spectrum. The benefits of ESE on BMD holds promise but rigorous studies are lacking. Further research is needed to examine if the dose, mode, age, and sex-specificity dictate effects of ESE on BMD/BMC.
Neonicotinoid insecticides are widely used in both urban and agricultural settings around the world. Historically, neonicotinoid insecticides have been viewed as ideal replacements for more toxic ...compounds, like organophosphates, due in part to their perceived limited potential to affect the environment and human health. This critical review investigates the environmental fate and toxicity of neonicotinoids and their metabolites and the potential risks associated with exposure. Neonicotinoids are found to be ubiquitous in the environment, drinking water, and food, with low-level exposure commonly documented below acceptable daily intake standards. Available toxicological data from animal studies indicate possible genotoxicity, cytotoxicity, impaired immune function, and reduced growth and reproductive success at low concentrations, while limited data from ecological or cross-sectional epidemiological studies have identified acute and chronic health effects ranging from acute respiratory, cardiovascular, and neurological symptoms to oxidative genetic damage and birth defects. Due to the heavy use of neonicotinoids and potential for cumulative chronic exposure, these insecticides represent novel risks and necessitate further study to fully understand their risks to humans.
Beyond clay Rasmussen, Craig; Heckman, Katherine; Wieder, William R. ...
Biogeochemistry,
02/2018, Letnik:
137, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Improved quantification of the factors controlling soil organic matter (SOM) stabilization at continental to global scales is needed to inform projections of the largest actively cycling terrestrial ...carbon pool on Earth, and its response to environmental change. Biogeochemical models rely almost exclusively on clay content to modify rates of SOM turnover and fluxes of climate-active CO₂ to the atmosphere. Emerging conceptual understanding, however, suggests other soil physicochemical properties may predict SOM stabilization better than clay content. We addressed this discrepancy by synthesizing data from over 5,500 soil profiles spanning continental scale environmental gradients. Here, we demonstrate that other physicochemical parameters are much stronger predictors of SOM content, with clay content having relatively little explanatory power. We show that exchangeable calcium strongly predicted SOM content in water-limited, alkaline soils, whereas with increasing moisture availability and acidity, iron- and aluminum-oxyhydroxides emerged as better predictors, demonstrating that the relative importance of SOM stabilization mechanisms scales with climate and acidity. These results highlight the urgent need to modify biogeochemical models to better reflect the role of soil physicochemical properties in SOM cycling.
Mycobacterium tuberculosis (Mtb) encodes five type VII secretion systems (T7SS), designated ESX-1–ESX-5, that are critical for growth and pathogenesis. The best characterized is ESX-1, which ...profoundly impacts host cell interactions. In contrast, the ESX-3 T7SS is implicated in metal homeostasis, but efforts to define its function have been limited by an inability to recover deletion mutants. We overcame this impediment using medium supplemented with various iron complexes to recover mutants with deletions encompassing select genes within esx-3 or the entire operon. The esx-3 mutants were defective in uptake of siderophore-bound iron and dramatically accumulated cell-associated mycobactin siderophores. Proteomic analyses of culture filtrate revealed that secretion of EsxG and EsxH was codependent and that EsxG–EsxH also facilitated secretion of several members of the proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) protein families (named for conserved PE and PPE N-terminal motifs). Substrates that depended on EsxG–EsxH for secretion included PE5, encoded within the esx-3 locus, and the evolutionarily related PE15–PPE20 encoded outside the esx-3 locus. In vivo characterization of the mutants unexpectedly showed that the ESX-3 secretion system plays both iron-dependent and -independent roles in Mtb pathogenesis. PE5–PPE4 was found to be critical for the siderophore-mediated iron-acquisition functions of ESX-3. The importance of this iron-acquisition function was dependent upon host genotype, suggesting a role for ESX-3 secretion in counteracting host defense mechanisms that restrict iron availability. Further, we demonstrate that the ESX-3 T7SS secretes certain effectors that are important for iron uptake while additional secreted effectors modulate virulence in an iron-independent fashion.
Depolymerization of the actin cytoskeleton induces nuclear trafficking of regulatory proteins and global effects on gene transcription. We here show that in mesenchymal stem cells (MSCs), ...cytochalasin D treatment causes rapid cofilin-/importin-9-dependent transfer of G-actin into the nucleus. The continued presence of intranuclear actin, which forms rod-like structures that stain with phalloidin, is associated with induction of robust expression of the osteogenic genes osterix and osteocalcin in a Runx2-dependent manner, and leads to acquisition of osteogenic phenotype. Adipogenic differentiation also occurs, but to a lesser degree. Intranuclear actin leads to nuclear export of Yes-associated protein (YAP); maintenance of nuclear YAP inhibits Runx2 initiation of osteogenesis. Injection of cytochalasin into the tibial marrow space of live mice results in abundant bone formation within the space of 1 week. In sum, increased intranuclear actin forces MSC into osteogenic lineage through controlling Runx2 activity; this process may be useful for clinical objectives of forming bone.
Summary Background Little is known about the amount and availability of surgical care globally. We estimated the number of major operations undertaken worldwide, described their distribution, and ...assessed the importance of surgical care in global public-health policy. Methods We gathered demographic, health, and economic data for 192 member states of WHO. Data for the rate of surgery were sought from several sources including governmental agencies, statistical and epidemiological organisations, published studies, and individuals involved in surgical policy initiatives. We also obtained per-head total expenditure on health from analyses done in 2004. Major surgery was defined as any intervention occurring in a hospital operating theatre involving the incision, excision, manipulation, or suturing of tissue, usually requiring regional or general anaesthesia or sedation. We created a model to estimate rates of major surgery for countries for which such data were unavailable, then used demographic information to calculate the total worldwide volume of surgery. Findings We obtained surgical data for 56 (29%) of 192 WHO member states. We estimated that 234·2 (95% CI 187·2–281·2) million major surgical procedures are undertaken every year worldwide. Countries spending US$100 or less per head on health care have an estimated mean rate of major surgery of 295 (SE 53) procedures per 100 000 population per year, whereas those spending more than $1000 have a mean rate of 11 110 (SE 1300; p<0·0001). Middle-expenditure ($401–1000) and high-expenditure (>$1000) countries, accounting for 30·2% of the world's population, provided 73·6% (172·3 million) of operations worldwide in 2004, whereas poor-expenditure (≤$100) countries account for 34·8% of the global population yet undertook only 3·5% (8·1 million) of all surgical procedures in 2004. Interpretation Worldwide volume of surgery is large. In view of the high death and complication rates of major surgical procedures, surgical safety should now be a substantial global public-health concern. The disproportionate scarcity of surgical access in low-income settings suggests a large unaddressed disease burden worldwide. Public-health efforts and surveillance in surgery should be established. Funding WHO.
ABSTRACT
We present the first 3D hydrodynamics simulations of the excitation and propagation of internal gravity waves (IGWs) in the radiative interiors of low-mass stars on the red giant branch ...(RGB). We use the ppmstar explicit gas dynamics code to simulate a portion of the convective envelope and all the radiative zone down to the hydrogen-burning shell of a $1.2\, {\rm M}_{\odot }$ upper RGB star. We perform simulations for different grid resolutions (7683, 15363, and 28803), a range of driving luminosities, and two different stratifications (corresponding to the bump luminosity and the tip of the RGB). Our RGB tip simulations can be directly performed at the nominal luminosity, circumventing the need for extrapolations to lower luminosities. A rich, continuous spectrum of IGWs is observed, with a significant amount of total power contained at high wavenumbers. By following the time evolution of a passive dye in the stable layers, we find that IGW mixing in our simulations is weaker than predicted by a simple analytical prescription based on shear mixing and not efficient enough to explain the missing RGB extra mixing. However, we may be underestimating the efficiency of IGW mixing given that our simulations include a limited portion of the convective envelope. Quadrupling its radial extent compared to our fiducial set-up increases convective velocities by up to a factor 2 and IGW velocities by up to a factor 4. We also report the formation of a $\sim 0.2\, H_P$ penetration zone and evidence that IGWs are excited by plumes that overshoot into the stable layers.
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