Abstract The relationship between depression and dementia is complex and still not well understood. A number of different views exist regarding how the two conditions are linked as well as the ...underlying neurobiological mechanisms at work. This narrative review examined longitudinal and cross sectional studies in the existing literature and determined the evidence supporting depression being a risk factor, a prodrome, a consequence, or an independent comorbidity in dementia. Overall there is convincing evidence to support both the notion that early life depression can act as a risk factor for later life dementia, and that later life depression can be seen as a prodrome to dementia. There is also evidence to support both conditions showing similar neurobiological changes, particularly white matter disease, either indicating shared risk factors or a shared pattern of neuronal damage. These findings highlight the need to examine if effective treatment of depressive episodes has any effect in reducing the prevalence of dementia, as well as clinicians being vigilant for late life depression indicating the incipient development of dementia, and therefore carefully following up these individuals for future cognitive impairment.
1. In the context of ongoing climatic warming, forest landscapes face increasing risk of conversion to non-forest vegetation through alteration of their fire regimes and their post-fire recovery ...dynamics. However, this pressure could be amplified or dampened, depending on how fire-driven changes to vegetation feed back to alter the extent or behaviour of subsequent fires. 2. Here we develop a mathematical model to formalize understanding of how firevegetation feedbacks and the time to forest recovery following high-severity (i.e. stand-replacing) fire affect the extent and stability of forest cover across landscapes facing altered fire regimes. We evaluate responses to increasing burn rates while varying the direction (negative vs. positive) of fire-vegetation feedbacks under a continuum of values for feedback strength and post-fire recovery time. In doing so, we determine how interactions among these variables produce thresholds and tipping points in landscape responses to changing fire regimes. 3. Where the early-seral vegetation was less fire-prone than older forests, negative feedbacks limited the reductions in forest cover in response to higher fire frequency or slower forest recovery. By contrast, positive feedbacks (more flammable early-seral vegetation) produced a tipping point beyond which increases in burn rates or a slowing of forest recovery drove extensive forest loss. 4. With negative feedbacks, the rates of forest loss and expansion in response to variation in fire frequency were similar. However, where feedbacks were positive, the conversion from predominantly forested to non-forested conditions in response to increasing fire frequency was faster than the re-expansion of forest cover following a return to the initial burn rate. Strengthening the positive feedbacks increased this asymmetry. 5. Synthesis. Our analyses elucidate how fire-vegetation feedbacks and post-fire recovery rates interact to affect the trajectories and rates of landscape response to altered fire regimes. We illustrate the vulnerability of ecosystems with positive fire-vegetation feedbacks to climate change-driven increases in fire activity, especially where post-fire recovery is slow. Although negative feedbacks initially provide resistance to forest loss with increasing burn rates, this resistance is eventually overwhelmed with sufficient increases to burn rates relative to recovery times.
Abstract
The MEROPS database (http://www.ebi.ac.uk/merops/) is an integrated source of information about peptidases, their substrates and inhibitors. The hierarchical classification is: ...protein-species, family, clan, with an identifier at each level. The MEROPS website moved to the EMBL-EBI in 2017, requiring refactoring of the code-base and services provided. The interface to sequence searching has changed and the MEROPS protein sequence libraries can be searched at the EMBL-EBI with HMMER, FastA and BLASTP. Cross-references have been established between MEROPS and the PANTHER database at both the family and protein-species level, which will help to improve curation and coverage between the resources. Because of the increasing size of the MEROPS sequence collection, in future only sequences of characterized proteins, and from completely sequenced genomes of organisms of evolutionary, medical or commercial significance will be added. As an example, peptidase homologues in four proteomes from the Asgard superphylum of Archaea have been identified and compared to other archaean, bacterial and eukaryote proteomes. This has given insights into the origins and evolution of peptidase families, including an expansion in the number of proteasome components in Asgard archaeotes and as organisms increase in complexity. Novel structures for proteasome complexes in archaea are postulated.
The response of soil microbial communities following changes in land-use is governed by multiple factors. The objectives of this study were to investigate (i) whether soil microbial communities track ...the changes in aboveground vegetation during succession; and (ii) whether microbial communities return to their native state over time. Two successional gradients with different vegetation were studied at the W. K. Kellogg Biological Station, Michigan. The first gradient comprised a conventionally tilled cropland (CT), mid-succession forest (SF) abandoned from cultivation prior to 1951, and native deciduous forest (DF). The second gradient comprised the CT cropland, early-succession grassland (ES) restored in 1989, and long-term mowed grassland (MG). With succession, the total microbial PLFAs and soil microbial biomass C consistently increased in both gradients. While bacterial rRNA gene diversity remained unchanged, the abundance and composition of many bacterial phyla changed significantly. Moreover, microbial communities in the relatively pristine DF and MG soils were very similar despite major differences in soil properties and vegetation. After >50 years of succession, and despite different vegetation, microbial communities in SF were more similar to those in mature DF than in CT. In contrast, even after 17 years of succession, microbial communities in ES were more similar to CT than endpoint MG despite very different vegetation between CT and ES. This result suggested a lasting impact of cultivation history on the soil microbial community. With conversion of deciduous to conifer forest (CF), there was a significant change in multiple soil properties that correlated with changes in microbial biomass, rRNA gene diversity and community composition. In conclusion, history of land-use was a stronger determinant of the composition of microbial communities than vegetation and soil properties. Further, microbial communities in disturbed soils apparently return to their native state with time.
► We study microbial communities of cultivated soils developing into grassland and forest. ► After >50 years of succession, communities were more similar to native forest. ► Even after 17-years grassland establishment, communities were more similar to cropland. ► Mostly, soil microbial communities did not follow changes in aboveground vegetation. ► Effect of land-use history is strong, but with time microbial communities return to native state.
Interferometric synthetic aperture sonar (InSAS) systems produce high resolution seafloor imagery and 3‐D bathymetry by exploiting the phase differences between image pairs formed from data collected ...by vertically separated arrays. This process is non‐trivial due to the inherent ambiguity of interferometric phase estimates, and the effect of layover, where the response of multiple scatterers with different positions are mapped onto the same pixel during imaging. These effects are particularly problematic for complex scenes with strong bathymetry, such as ship wrecks. This is an unsolved problem and improved algorithms for InSAS bathymetry estimation are needed. However, developing and assessing such algorithms using data from fielded InSAS systems is difficult because of a lack of accurate ground truth for the platform motion and the true 3‐D shape of the scene. This paper presents an openly available synthetic data set as an alternative to field‐collected data for use by InSAS algorithm developers. The dataset is derived from a high‐resolution 3‐D photogrammetry scan of the SS Thistlegorm wreck. It was produced by a point‐based diffraction model using parameters similar to the Minehunting UUV for Shallow water Covert Littoral Expeditions (MUSCLE) InSAS.
This paper introduces an openly available synthetic dataset for the future development, assessment, comparison, and benchmarking of interferometric synthetic aperture sonar (InSAS) algorithms. The simulated InSAS data is from the SS Thistlegorm ship wreck. It has been produced using a 3‐D photogrammetry model of the wreck and a point‐based diffraction model for the coherent underwater acoustics. It presents a significant challenge due to its strong bathymetry and complex layover.
To investigate the feasibility and value of positron emission tomography and computed tomography (PET/CT) for treatment verification after proton radiotherapy.
This study included 9 patients with ...tumors in the cranial base, spine, orbit, and eye. Total doses of 1.8-3 GyE and 10 GyE (for an ocular melanoma) per fraction were delivered in 1 or 2 fields. Imaging was performed with a commercial PET/CT scanner for 30 min, starting within 20 min after treatment. The same treatment immobilization device was used during imaging for all but 2 patients. Measured PET/CT images were coregistered to the planning CT and compared with the corresponding PET expectation, obtained from CT-based Monte Carlo calculations complemented by functional information. For the ocular case, treatment position was approximately replicated, and spatial correlation was deduced from reference clips visible in both the planning radiographs and imaging CT. Here, the expected PET image was obtained from an analytical model.
Good spatial correlation and quantitative agreement within 30% were found between the measured and expected activity. For head-and-neck patients, the beam range could be verified with an accuracy of 1-2 mm in well-coregistered bony structures. Low spine and eye sites indicated the need for better fixation and coregistration methods. An analysis of activity decay revealed as tissue-effective half-lives of 800-1,150 s.
This study demonstrates the feasibility of postradiation PET/CT for in vivo treatment verification. It also indicates some technological and methodological improvements needed for optimal clinical application.
The structure and flow of water inside 75 and 150 nm-long carbon nanotubes with diameters ranging from 0.83 to 1.66 nm are examined using molecular dynamics simulation. The flow rate enhancement, ...defined as the ratio of the observed flow rate to that predicted from the no-slip Poiseuille relation, is calculated for each tube and the liquid structure is examined using an axial distribution function. The relationship between the intermolecular water structure and water flow is quantified and differences between continuum and subcontinuum flow are discussed.
Lipofuscin and melanolipofuscin organelles in retinal pigment epithelium (RPE) cells are signal sources for clinical fundus autofluorescence (AF). To elucidate the subcellular basis of AF imaging, we ...identified, characterized, and quantified the frequency of RPE morphology and AF phenotypes in donor eyes with age-related macular degeneration (AMD).
In 25 RPE-Bruch's membrane flat mounts from 25 eyes, we analyzed 0.4-μm z-stack epifluorescence images of RPE stained with phalloidin for actin cytoskeleton. Using a custom ImageJ plugin, we classified cells selected in a systematic unbiased fashion in six phenotypes representing increasing degrees of pathology. For each cell, area, AF intensity, and number of Voronoi neighbors were compared with phenotype 1 (uniform AF, polygonal morphology) via generalized estimating equations. We also analyzed each cell's neighborhood.
In 29,323 cells, compared with phenotype 1, all other phenotypes, in order of increasing pathology, had significantly larger area, reduced AF, and more variable number of neighbors. Neighborhood area and AF showed similar, but subtler, trends. Cells with highly autofluorescent granule aggregates are no more autofluorescent than others and are in fact lower overall in AF. Pre-aggregates were found in phenotype 1. Phenotype 2, which exhibited degranulation despite normal cytoskeleton, was the most numerous nonhealthy phenotype (16.23%).
Despite aggregation of granules that created hyperAF aggregates within cells, overall AF on a per cell basis decreased with increasing severity of dysmorphia (abnormal shape). Data motivate further development of subcellular resolution in clinical fundus AF imaging and inform an ongoing reexamination of the role of lipofuscin in AMD.
In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects ...adaptive immune responses and combinatorial efficacy of radiotherapy with immune checkpoint blockade (ICB).
We developed a preclinical model to compare stereotactic radiotherapy (Tumor RT) with or without ENI to examine immunologic differences between radiotherapy techniques that spare or irradiate the DLN.
Tumor RT was associated with upregulation of an intratumoral T-cell chemoattractant chemokine signature (CXCR3, CCR5-related) that resulted in robust infiltration of antigen-specific CD8
effector T cells as well as FoxP3
regulatory T cells (Tregs). The addition of ENI attenuated chemokine expression, restrained immune infiltration, and adversely affected survival when combined with ICB, especially with anti-CLTA4 therapy. The combination of stereotactic radiotherapy and ICB led to long-term survival in a subset of mice and was associated with favorable CD8 effector-to-Treg ratios and increased intratumoral density of antigen-specific CD8
T cells. Although radiotherapy technique (Tumor RT vs. ENI) affected initial tumor control and survival, the ability to reject tumor upon rechallenge was partially dependent upon the mechanism of action of ICB; as radiotherapy/anti-CTLA4 was superior to radiotherapy/anti-PD-1.
Our results highlight that irradiation of the DLN restrains adaptive immune responses through altered chemokine expression and CD8
T-cell trafficking. These data have implications for combining radiotherapy and ICB, long-term survival, and induction of immunologic memory. Clinically, the immunomodulatory effect of the radiotherapy strategy should be considered when combining stereotactic radiotherapy with immunotherapy.
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Background Abdominal aortic aneurysm (AAA) disease is an insidious condition with an 85% chance of death after rupture. Ultrasound screening can reduce mortality, but its use is advocated only for a ...limited subset of the population at risk. Methods We used data from a retrospective cohort of 3.1 million patients who completed a medical and lifestyle questionnaire and were evaluated by ultrasound imaging for the presence of AAA by Life Line Screening in 2003 to 2008. Risk factors associated with AAA were identified using multivariable logistic regression analysis. Results We observed a positive association with increasing years of smoking and cigarettes smoked and a negative association with smoking cessation. Excess weight was associated with increased risk, whereas exercise and consumption of nuts, vegetables, and fruits were associated with reduced risk. Blacks, Hispanics, and Asians had lower risk of AAA than whites and Native Americans. Well-known risk factors were reaffirmed, including male gender, age, family history, and cardiovascular disease. A predictive scoring system was created that identifies aneurysms more efficiently than current criteria and includes women, nonsmokers, and individuals aged <65 years. Using this model on national statistics of risk factors prevalence, we estimated 1.1 million AAAs in the United States, of which 569,000 are among women, nonsmokers, and individuals aged <65 years. Conclusions Smoking cessation and a healthy lifestyle are associated with lower risk of AAA. We estimated that about half of the patients with AAA disease are not eligible for screening under current guidelines. We have created a high-yield screening algorithm that expands the target population for screening by including at-risk individuals not identified with existing screening criteria.
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