Medical imaging has become a central component of patient care to ensure early and accurate diagnosis. Unfortunately, many imaging modalities use ionizing radiation to generate images. Ionizing ...radiation even in low doses can cause direct DNA damage and generate reactive oxygen species and free radicals, leading to DNA, protein, and lipid membrane damage. This cell damage can lead to apoptosis, necrosis, teratogenesis, or carcinogenesis. As many as 2% of cancers (and an associated 15,000 deaths annually) can be linked to computed tomography exposure alone. Radioprotective agents have been investigated using various models including cells, animals, and recently humans. The data suggest that radioprotective agents working through a variety of mechanisms have the potential to decrease free radical damage produced by ionizing radiation. Radioprotective agents may be useful as an adjunct to medical imaging to reduced patient morbidity and mortality due to ionizing radiation exposure. Some radioprotective agents can be found in high quantities in antioxidant rich foods, suggesting that a specific diet recommendation could be beneficial in radioprotection.
This paper reports the development of a ∼30 m resolution two‐dimensional hydrodynamic model of the conterminous U.S. using only publicly available data. The model employs a highly efficient numerical ...solution of the local inertial form of the shallow water equations which simulates fluvial flooding in catchments down to 50 km2 and pluvial flooding in all catchments. Importantly, we use the U.S. Geological Survey (USGS) National Elevation Dataset to determine topography; the U.S. Army Corps of Engineers National Levee Database to explicitly represent known flood defenses; and global regionalized flood frequency analysis to characterize return period flows and rainfalls. We validate these simulations against the complete catalogue of Federal Emergency Management Agency (FEMA) Special Flood Hazard Area (SFHA) maps and detailed local hydraulic models developed by the USGS. Where the FEMA SFHAs are based on high‐quality local models, the continental‐scale model attains a hit rate of 86%. This correspondence improves in temperate areas and for basins above 400 km2. Against the higher quality USGS data, the average hit rate reaches 92% for the 1 in 100 year flood, and 90% for all flood return periods. Given typical hydraulic modeling uncertainties in the FEMA maps and USGS model outputs (e.g., errors in estimating return period flows), it is probable that the continental‐scale model can replicate both to within error. The results show that continental‐scale models may now offer sufficient rigor to inform some decision‐making needs with dramatically lower cost and greater coverage than approaches based on a patchwork of local studies.
Key Points
A 30 m resolution flood hazard model of the entire conterminous United States is built using publicly available data
Delineations of flood hazard are comprehensively validated against United States government agency benchmarks
Model performance is largely comparable to quality local models, offering cheaper hazard information with complete spatial coverage
The deep sea, the largest ecosystem on Earth and one of the least studied, harbours high biodiversity and provides a wealth of resources. Although humans have used the oceans for millennia, ...technological developments now allow exploitation of fisheries resources, hydrocarbons and minerals below 2000 m depth. The remoteness of the deep seafloor has promoted the disposal of residues and litter. Ocean acidification and climate change now bring a new dimension of global effects. Thus the challenges facing the deep sea are large and accelerating, providing a new imperative for the science community, industry and national and international organizations to work together to develop successful exploitation management and conservation of the deep-sea ecosystem. This paper provides scientific expert judgement and a semi-quantitative analysis of past, present and future impacts of human-related activities on global deep-sea habitats within three categories: disposal, exploitation and climate change. The analysis is the result of a Census of Marine Life--SYNDEEP workshop (September 2008). A detailed review of known impacts and their effects is provided. The analysis shows how, in recent decades, the most significant anthropogenic activities that affect the deep sea have evolved from mainly disposal (past) to exploitation (present). We predict that from now and into the future, increases in atmospheric CO(2) and facets and consequences of climate change will have the most impact on deep-sea habitats and their fauna. Synergies between different anthropogenic pressures and associated effects are discussed, indicating that most synergies are related to increased atmospheric CO(2) and climate change effects. We identify deep-sea ecosystems we believe are at higher risk from human impacts in the near future: benthic communities on sedimentary upper slopes, cold-water corals, canyon benthic communities and seamount pelagic and benthic communities. We finalise this review with a short discussion on protection and management methods.
Background:
Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and ...old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown.
Purpose:
The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health.
Methods:
Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-ring-13C6phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention.
Results:
Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates.
Conclusion:
The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.
Muscle hypertrophy following resistance training (RT) involves activation of myofibrillar protein synthesis (MPS) to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, ...however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE) in untrained men (n = 23) and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index = 26.4±0.9 kg•m²) underwent a primed constant infusion of L-ring-¹³C₆ phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (P<0.001) above rest 60-180 min post-exercise and 184±28% (P = 0.037) 180-360 min post exercise. Quadriceps volume increased 7.9±1.6% (-1.9-24.7%) (P<0.001) after training. There was no correlation between changes in quadriceps muscle volume and acute rates of MPS measured over 1-3 h (r = 0.02), 3-6 h (r = 0.16) or the aggregate 1-6 h post-exercise period (r = 0.10). Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05) with phosphorylation of 4E-BP1(Thr37/46) at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.
Enzymes fold into unique three-dimensional structures, which underlie their remarkable catalytic properties. The requirement to adopt a stable, folded conformation is likely to contribute to their ...relatively large size (>10,000 Da). However, much shorter peptides can achieve well-defined conformations through the formation of amyloid fibrils. To test whether short amyloid-forming peptides might in fact be capable of enzyme-like catalysis, we designed a series of seven-residue peptides that act as Zn(2+)-dependent esterases. Zn(2+) helps stabilize the fibril formation, while also acting as a cofactor to catalyse acyl ester hydrolysis. These results indicate that prion-like fibrils are able to not only catalyse their own formation, but they can also catalyse chemical reactions. Thus, they might have served as intermediates in the evolution of modern-day enzymes. These results also have implications for the design of self-assembling nanostructured catalysts including ones containing a variety of biological and non-biological metal ions.
We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor ...prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.
Terrestrial primary production is a fundamental ecological process and a crucial component in understanding the flow of energy through trophic levels. The global MODIS gross primary production (GPP) ...and net primary production (NPP) products (MOD17) are widely used for monitoring GPP and NPP at coarse resolutions across broad spatial extents. The coarse input datasets and global biome‐level parameters, however, are well‐known limitations to the applicability of the MOD17 product at finer scales. We addressed these limitations and created two improved products for the conterminous United States (CONUS) that capture the spatiotemporal variability in terrestrial production. The MOD17 algorithm was utilized with medium resolution land cover classifications and improved meteorological data specific to CONUS in order to produce: (a) Landsat derived 16‐day GPP and annual NPP at 30 m resolution from 1986 to 2016 (GPPL30 and NPPL30, respectively); and (b) MODIS derived 8‐day GPP and annual NPP at 250 m resolution from 2001 to 2016 (GPPM250 and NPPM250 respectively). Biome‐specific input parameters were optimized based on eddy covariance flux tower‐derived GPP data from the FLUXNET2015 database. We evaluated GPPL30 and GPPM250 products against the standard MODIS GPP product utilizing a select subset of representative flux tower sites, and found improvement across all land cover classes except croplands. We also found consistent interannual variability and trends across NPPL30, NPPM250, and the standard MODIS NPP product. We highlight the application potential of the production products, demonstrating their improved capacity for monitoring terrestrial production at higher levels of spatial detail across broad spatiotemporal scales.
We produced two higher resolution primary production datasets, using better input data than currently existing datasets. These products more closely match the scale of many ecological processes and management activities, and will facilitate better understandings of production dynamics. Our products correspond well with other production datasets at multiple scales. The products fill a critical gap in our ability to monitor and assess terrestrial production dynamics in relation to many ecological processes and land use change. As production is a foundational ecological process and ecosystem service, understanding these dynamics is critical for environmental sustainability.
Current methods to repair ablation-type peripheral nerve injuries (PNIs) using peripheral nerve allografts (PNAs) often result in poor functional recovery due to immunological rejection as well as to ...slow and inaccurate outgrowth of regenerating axonal sprouts. In contrast, ablation-type PNIs repaired by PNAs, using a multistep protocol in which one step employs the membrane fusogen polyethylene glycol (PEG), permanently restore sciatic-mediated behaviors within weeks. Axons and cells within PEG-fused PNAs remain viable, even though outbred host and donor tissues are neither immunosuppressed nor tissue matched. PEG-fused PNAs exhibit significantly reduced T cell and macrophage infiltration, expression of major histocompatibility complex I/II and consistently low apoptosis. In this study, we analyzed the coding transcriptome of PEG-fused PNAs to examine possible mechanisms underlying immunosuppression.
Ablation-type sciatic PNIs in adult Sprague-Dawley rats were repaired using PNAs and a PEG-fusion protocol combined with neurorrhaphy. Electrophysiological and behavioral tests confirmed successful PEG-fusion of PNAs. RNA sequencing analyzed differential expression profiles of protein-coding genes between PEG-fused PNAs and negative control PNAs (not treated with PEG) at 14 days PO, along with unoperated control nerves. Sequencing results were validated by quantitative reverse transcription PCR (RT-qPCR), and in some cases, immunohistochemistry.
PEG-fused PNAs display significant downregulation of many gene transcripts associated with innate and adaptive allorejection responses. Schwann cell-associated transcripts are often upregulated, and cellular processes such as extracellular matrix remodeling and cell/tissue development are particularly enriched. Transcripts encoding several potentially immunosuppressive proteins (e.g., thrombospondins 1 and 2) also are upregulated in PEG-fused PNAs.
This study is the first to characterize the coding transcriptome of PEG-fused PNAs and to identify possible links between alterations of the extracellular matrix and suppression of the allorejection response. The results establish an initial molecular basis to understand mechanisms underlying PEG-mediated immunosuppression.
This review addresses the accumulating evidence that live (not decellularized) allogeneic peripheral nerves are functionally and immunologically peculiar in comparison with many other transplanted ...allogeneic tissues. This is relevant because live peripheral nerve allografts are very effective at promoting recovery after segmental peripheral nerve injury via axonal regeneration and axon fusion. Understanding the immunological peculiarities of peripheral nerve allografts may also be of interest to the field of transplantation in general. Three topics are addressed: The first discusses peripheral nerve injury and the potential utility of peripheral nerve allografts for bridging segmental peripheral nerve defects via axon fusion and axon regeneration. The second reviews evidence that peripheral nerve allografts elicit a more gradual and less severe host immune response allowing for prolonged survival and function of allogeneic peripheral nerve cells and structures. Lastly, potential mechanisms that may account for the immunological differences of peripheral nerve allografts are discussed.
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