If, as previously hypothesized, the effective elastic response of the lithosphere is sensitive to the imposed stress regime, then it may vary in time and produce distinctive geomorphic responses. ...Such effects will be at their most crucial in landscapes of low relief. Motivated by the existence of numerous small endorheic (internally‐drained) basins in central Australia, we examine the influence of changing elastic response in the presence of large embedded loads in the lithosphere underlying stable continental interiors. Focusing on the western Lake Eyre Basin and adjoining Lake Lewis basin—an area with a close correlation between drainage pattern and extreme Bouguer gravity anomalies—we devise a set of numerical simulations that incorporate the flexural response to time‐transient horizontal stresses. The simulations demonstrate that transient changes in the effective elastic thickness can drive topographic changes in low‐relief landscapes, including drainage capture and the development of endorheic basins, consistent with field observations.
Plain Language Summary
Extreme density anomalies in central Australia suggest the presence of significant stress within the lithosphere, even though the region lies far from any tectonic plate boundaries. This in situ stress probably dates back to a mountain‐building period in the Paleozoic. The density anomalies correlate closely with drainage patterns and a set of internally‐drained catchments, suggesting an important relationship exists between the deep‐earth and landscape‐forming processes. We propose the driving mechanism is the result of changes in the rigidity of the lithosphere, which in the presence of in situ stress lead to surface uplift or subsidence. We use a landscape evolution model to show that topography similar to field observations can be simulated by imposing cycles of uplift and subsidence brought about by these changes in lithospheric rigidity over tens of millions of years. In consequence, the lithosphere must have fairly low rigidity counter to previously held ideas about continental interiors.
Key Points
Loads embedded within the central Australian lithosphere produce large flexural responses that may evolve cyclically over time
Surface deflections induced by transient lithospheric rigidity can explain endorheic basins formed at wavelengths of order 100 km
Cyclical behavior in lithospheric rigidity is consistent with the observed geomorphic record of erosion and deposition
The major genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is a C9orf72 G
C
repeat expansion
. Proposed mechanisms by which the expansion causes c9FTD/ALS ...include toxicity from repeat-containing RNA and from dipeptide repeat proteins translated from these transcripts. To investigate the contribution of poly(GR) dipeptide repeat proteins to c9FTD/ALS pathogenesis in a mammalian in vivo model, we generated mice that expressed GFP-(GR)
in the brain. GFP-(GR)
mice developed age-dependent neurodegeneration, brain atrophy, and motor and memory deficits through the accumulation of diffuse, cytoplasmic poly(GR). Poly(GR) co-localized with ribosomal subunits and the translation initiation factor eIF3η in GFP-(GR)
mice and, of importance, in c9FTD/ALS patients. Combined with the differential expression of ribosome-associated genes in GFP-(GR)
mice, these findings demonstrate poly(GR)-mediated ribosomal distress. Indeed, poly(GR) inhibited canonical and non-canonical protein translation in HEK293T cells, and also induced the formation of stress granules and delayed their disassembly. These data suggest that poly(GR) contributes to c9FTD/ALS by impairing protein translation and stress granule dynamics, consequently causing chronic cellular stress and preventing cells from mounting an effective stress response. Decreasing poly(GR) and/or interrupting interactions between poly(GR) and ribosomal and stress granule-associated proteins may thus represent potential therapeutic strategies to restore homeostasis.
The human genome contains "dark" gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations ...within these gene regions that may be relevant to human disease. Here, we identify regions with few mappable reads that we call dark by depth, and others that have ambiguous alignment, called camouflaged. We assess how well long-read or linked-read technologies resolve these regions.
Based on standard whole-genome Illumina sequencing data, we identify 36,794 dark regions in 6054 gene bodies from pathways important to human health, development, and reproduction. Of these gene bodies, 8.7% are completely dark and 35.2% are ≥ 5% dark. We identify dark regions that are present in protein-coding exons across 748 genes. Linked-read or long-read sequencing technologies from 10x Genomics, PacBio, and Oxford Nanopore Technologies reduce dark protein-coding regions to approximately 50.5%, 35.6%, and 9.6%, respectively. We present an algorithm to resolve most camouflaged regions and apply it to the Alzheimer's Disease Sequencing Project. We rescue a rare ten-nucleotide frameshift deletion in CR1, a top Alzheimer's disease gene, found in disease cases but not in controls.
While we could not formally assess the association of the CR1 frameshift mutation with Alzheimer's disease due to insufficient sample-size, we believe it merits investigating in a larger cohort. There remain thousands of potentially important genomic regions overlooked by short-read sequencing that are largely resolved by long-read technologies.
Reliable quantitative information about sediment sources is a key requirement for river catchment management, especially in settings with high sediment loads. This study explores the potential for ...using source fingerprinting techniques to establish the relative contribution of three sub-basins to the sediment deposited in a reservoir impounded by an earth dam located at the outlet of the Lavar watershed, in Hormozgan Province, southern Iran. The three sub-basins feeding the reservoir are characterized by complex topography and underlying geology. The source material and target sediment samples were analyzed for 53 potential geochemical tracers, including trace elements and rare earth elements (REEs) and their ratios. Stepwise discriminant function analysis (DFA) was applied to select optimum composite fingerprints from those fingerprint properties passing the range test and we compared two different modelling procedures to estimate the relative contribution of the three sub-basins to the sediment deposited in the reservoir. The first involves a Bayesian mixing model within a Markov Chain Monte Carlo framework (BM) and, the second, an un-mixing model within a Monte Carlo simulation framework (UM). The latter model permits the use of ratio properties, which represents a novel aspect of our study. Particular attention was directed to the uncertainty associated with the source contribution estimates provided by the two models. A goodness of fit estimator was employed to evaluate the results of the UM. Both modelling procedures demonstrated that the southern sub-basin was the main source of the majority of samples we collected from the reservoir. The BM model indicated that the central sub-basin was the dominant source of two samples (S6 and S8). Overall, the results provided by the BM model for the source of seven sediment samples (S1, S2, S3, S4, S5, S7 and S9) are compatible with those provided by the UM model and the central sub-basin was recognized as the most important source supplying sediment in the study area. Both approaches offer potential for using geochemical fingerprinting to quantify spatial sediment source contributions and the uncertainty associated with those estimates.
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•This study demonstrates the successful use of two different modelling approaches to estimate the source contribution of sediment deposited in an earth dam reservoir.•The REE ratio tracers applied in the UM model.•The central sub-basin (Ss) recognized as the main source supplying sediment in the study area by both modelling approaches.
To investigate the impact of evolving International Commission on Radiological Protection (ICRP) recommendations concerning calculation of effective dose (E) and compare updated typical UK values for ...common CT examinations with previous data.
Monte Carlo simulations have provided normalized organ doses relating to 15 CT scanner models and 5 virtual reference adults. Series of representative E/dose-length product (DLP) coefficients were derived for common examinations on the separate bases of not only older stylized mathematical phantoms and voxel phantoms presently recommended by ICRP, but also the 1977, 1990 and 2007 formulations for E. Updated E/DLP coefficients were applied to typical values of DLP from the 2011 UK survey.
Changes in ICRP recommendations that have arisen from improving evidence on stochastic risk, influence values of E by up to a factor two for CT examinations of the head and neck, although differences for the trunk typically amount to ±10%. Adoption of the voxel rather than the mathematical phantoms used previously can lead to further changes in E by a few tens of percent. Updated typical values of E for UK CT examinations range from 2 to 20 mSv. Increases by 20-400% since 2003 arise not only from increases by 30-160% in typical values of DLP, but also increases by 30-90% in relation to E/DLP coefficients for examinations of the trunk.
Values of E, including updated typical data for UK CT, should be compared with caution in relation to their purpose and underlying factors concerning their calculation.
Updated E/DLP coefficients and typical values of E for UK CT, and an appreciation of factors influencing these data.
Remote sensing of specific climatic and biogeographical parameters is an effective means of evaluating the large-scale desertification status of drylands affected by negative human impacts. Here, we ...identify and analyze desertification trends in Iran for the period 2001-2015 via a combination of three indices for vegetation (NPP-net primary production, NDVI-normalized difference vegetation index, LAI-leaf area index) and two climate indices (LST-land surface temperature, P-precipitation). We combine these indices to identify and map areas of Iran that are susceptible to land degradation. We then apply a simple linear regression method, the Mann-Kendall non-parametric test, and the Theil-Sen estimator to identify long-term temporal and spatial trends within the data. Based on desertification map, we find that 68% of Iran shows a high to very high susceptibility to desertification, representing an area of 1.1 million km
(excluding 0.42 million km
classified as unvegetated). Our results highlight the importance of scale in assessments of desertification, and the value of high-resolution data, in particular. Annually, no significant change is evident within any of the five indices, but significant changes (some positive, some negative) become apparent on a seasonal basis. Some observations follow expectations; for instance, NDVI is strongly associated with cooler, wet spring and summer seasons, and milder winters. Others require more explanation; for instance, vegetation appears decoupled from climatic forcing during autumn. Spatially, too, there is much local and regional variation, which is lost when the data are considered only at the largest nationwide scale. We identify a northwest-southeast belt spanning central Iran, which has experienced significant vegetation decline (2001-2015). We tentatively link this belt of land degradation with intensified agriculture in the hinterlands of Iran's major cities. The spatial and temporal trends identified with the three vegetation and two climate indices afford a cost-effective framework for the prediction and management of future environmental trends in developing regions at risk of desertification.
The blocking of river courses by mass movements is very common in mountainous areas with deep and narrow valleys. Landslide dams may pose serious threats to people and their livelihoods downstream in ...the case of abrupt dam failure. Since the publication of benchmark reviews of Costa and Schuster (1988) and Korup (2002), there is a growing number of studies focusing on the formation, stability, and short-term impacts of landslide dams. This review combines the insights of all these studies, builds on current concepts of landslide dams, and suggests ways to unify terminologies and classifications. We furthermore present a new worldwide database compiled from literature data. It contains 410 landslide dams >1 million m3 in volume that were formed since 1900 since these have the most complete data entries. These data show that dam longevity is, among other factors, correlated with the type of landslide forming the dam. Those formed by rock/debris avalanches and rockslides have longest lifespans. However, the influence of landslide type or material on dam longevity decreases with time after dam formation. To ensure consistency in the next database generation, we suggest guidelines for data collection to provide a solid basis for evaluating dam stability and governing factors. A preliminary classification matrix for landslide dam stability that combines topographic setting and the internal structure of the dam body is another outcome of our review. Furthermore, an evaluation of the various geomorphic stability indices proposed in the literature regarding their suitability and limitations in assessing dam formation and stability shows that they predict the probability of dam formation reasonably well, but that their application to longevity estimates requires further assessment. The geomorphic impacts of landslide dams in the short-, medium- and long-term are summarized and illustrated with key examples. Finally, for a better understanding of the factors controlling dam stability, we recommend to (1) include dam composition and sedimentary structures in future case studies, (2) maintain and update the worldwide database for sound statistical analyses, (3) refine landslide dam stability indices and test them for different landslide types, and (4) study hazard cascades related to multiple dams in one watershed. For long-term landscape evolution studies, we suggest to (5) quantify terrestrial sediment flux related to landslide dams, (6) detect ancient landslide dams in river profiles, and (7) further exploit the sediment archives in former impoundment areas.
•Compilation of a new worldwide database of 410 landslide dams and design of a template for future data collection.•Preliminary classification matrix for landslide dam stability combining topographic setting and sedimentological features.•Comprehensive review and evaluation of landslide dam stability criteria and geomorphic indices.•Landscape impacts of landslide dams discussed on different time scales.
A sudden drop in river base-level can trigger a knickpoint that propagates throughout the fluvial network causing a transient state in the landscape. Knickpoint retreat has been confirmed in large ...fluvial settings (drainage areas >100km2) and field data suggest that the same applies to the case of small bedrock river catchments (drainage areas <100km2). Nevertheless, knickpoint recession on resistant lithologies with structure that potentially affects the retreat rate needs to be confirmed with field-based data. Moreover, it remains unclear whether small bedrock rivers can absorb base-level fall via knickpoint retreat. Here we evaluate the response of small bedrock rivers to base-level fall on the isle of Jura in western Scotland (UK), where rivers incise into dipping quartzite. The mapping of raised beach deposits and strath terraces, and the analysis of stream long profiles, were used to identify knickpoints that had been triggered by base-level fall. Our results indicate that the distance of knickpoint retreat scales to the drainage area in a power law function irrespective of structural setting. On the other hand, local channel slope and basin size influence the vertical distribution of knickpoints. As well, at low drainage areas (~4km2) rivers are unable to absorb the full amount of base-level fall and channel reach morphology downstream of the knickpoint tends towards convexity. The results obtained here confirm that knickpoint retreat is mostly controlled by stream discharge, as has been observed for other transient landscapes. Local controls, reflecting basin size and channel slope, have an effect on the vertical distribution of knickpoints; such controls are also related to the ability of rivers to absorb the base-level fall.
A G
C
hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease ...mechanisms underlying c9FTD/ALS include toxicity from sense G
C
and antisense G
C
repeat-containing RNA, and from dipeptide repeat (DPR) proteins unconventionally translated from these RNA products.
Intracerebroventricular injections with adeno-associated virus (AAV) encoding 2 or 149 G
C
repeats were performed on postnatal day 0, followed by assessment of behavioral and neuropathological phenotypes.
Relative to control mice, gliosis and neurodegeneration accompanied by cognitive and motor deficits were observed in (G
C
)
mice by 6 months of age. Recapitulating key pathological hallmarks, we also demonstrate that sense and antisense RNA foci, inclusions of poly(GA), poly(GP), poly(GR), poly(PR), and poly(PA) DPR proteins, and inclusions of endogenous phosphorylated TDP-43 (pTDP-43) developed in (G
C
)
mice but not control (G
C
)
mice. Notably, proteins that play a role in the regulation of stress granules - RNA-protein assemblies that form in response to translational inhibition and that have been implicated in c9FTD/ALS pathogenesis - were mislocalized in (G
C
)
mice as early as 3 months of age. Specifically, we observed the abnormal deposition of stress granule components within inclusions immunopositive for poly(GR) and pTDP-43, as well as evidence of nucleocytoplasmic transport defects.
Our in vivo model of c9FTD/ALS is the first to robustly recapitulate hallmark features derived from both sense and antisense C9orf72 repeat-associated transcripts complete with neurodegeneration and behavioral impairments. More importantly, the early appearance of persistent pathological stress granules prior to significant pTDP-43 deposition implicates an aberrant stress granule response as a key disease mechanism driving TDP-43 proteinopathy in c9FTD/ALS.
Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein ...(RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown or knockout inhibits tau misfolding and associated toxicity in cultured hippocampal neurons, while overexpressing TIA1 induces tau misfolding and stimulates neurodegeneration. Pharmacological interventions that prevent SG formation also inhibit tau pathophysiology. These studies suggest that the pathophysiology of tauopathy requires an intimate interaction with RNA-binding proteins.
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•Tau is required for normal interactions of RNA binding proteins in brain tissue•Tau promotes stress granules, while TIA1 promotes tau misfolding and insolubility•TIA1 knockdown or knockout inhibits tau pathology and toxicity•TIA1 and tau act synergistically to modulate degeneration of cultured neurons
Vanderweyde et al. show that the interaction of microtubule associated protein tau with the RNA binding protein (RBP) TIA1 regulates stress granule (SG) formation as well as misfolding and aggregation of tau. TIA1 knockdown prevents tau misfolding and tau-mediated toxicity, which points to RBPs as potential targets for therapy of tauopathies.
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