Trees affected by mass movements record the evidence of geomorphic disturbance in the growth-ring series, and thereby provide a precise geochronological tool for the reconstruction of past activity ...of mass movement. The identification of past activity of processes was typically based on the presence of growth anomalies in affected trees and focused on the presence of scars, tilted or buried trunks, as well as on apex decapitation. For the analyses and interpretation of disturbances in tree-ring records, in contrast, clear guidelines have not been established, with largely differing or no thresholds used to distinguish signal from noise. At the same time, processes with a large spatial footprint (e.g., snow avalanches, landslides, or floods) will likely leave growth anomalies in a large number of trees, whereas a falling rock would only cause scars in one or a few trees along its trajectory.
Based on the above considerations, we examine issues relating to the interpretation and dendrogeomorphic dating of mass movements. Particular attention is drawn to sampling in terms of sample distribution across a study site, the actual selection of trees as well as to sample size (i.e., number of trees sampled). Based on case studies from snow avalanche, debris flow, and landslide sites, we demonstrate that thresholds can indeed improve dating quality and, at the same time, minimize noise in time series. We also conclude that different thresholds need to be used for different processes and different periods of the reconstruction, especially for the early stages of the reconstruction when the number of potentially responding trees will be much smaller. This paper seeks to set standards for dendrogeomorphic fieldwork, analysis, and interpretation for different processes of mass movements.
► Sample depth and thresholds chiefly influence the quality of dendrogeomorphic time series. ► Growth disturbance and index values need to be flexible and adjusted over time. ► Processes with a large spatial fingerprint can be reconstructed with fewer trees. ► Discrete processes, such as rockfalls, need more samples to be reconstructed properly. ► A good mixture of different species and age classes of trees yields the best results.
The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood. Here we map the transcriptional ...landscape of mouse bone marrow vascular, perivascular and osteoblast cell populations at single-cell resolution, both at homeostasis and under conditions of stress-induced haematopoiesis. This analysis revealed previously unappreciated levels of cellular heterogeneity within the bone marrow niche and resolved cellular sources of pro-haematopoietic growth factors, chemokines and membrane-bound ligands. Our studies demonstrate a considerable transcriptional remodelling of niche elements under stress conditions, including an adipocytic skewing of perivascular cells. Among the stress-induced changes, we observed that vascular Notch delta-like ligands (encoded by Dll1 and Dll4) were downregulated. In the absence of vascular Dll4, haematopoietic stem cells prematurely induced a myeloid transcriptional program. These findings refine our understanding of the cellular architecture of the bone marrow niche, reveal a dynamic and heterogeneous molecular landscape that is highly sensitive to stress and illustrate the utility of single-cell transcriptomic data in evaluating the regulation of haematopoiesis by discrete niche populations.
This study aimed to shed light on contradictory associations of alcohol intake with waist circumference (WC) and body mass index (BMI) by examining 5-yr changes in alcohol intake in relation to 5-yr ...WC and BMI changes.
This prospective study included 4,355 participants (1,974 men and 2,381 women) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study at baseline (1985-1986) and followed over 25 years (2010-2011). Longitudinal random effects linear regression models were used to test whether changes in drinking (defined categorically) as starting to drink, increasing, decreasing, stable drinking or stopping drinking (versus stable non-drinking) over a series of 5-yr periods were associated with corresponding 5-yr WC and BMI changes. Associations with 5-yr changes (defined categorically as starting, stable or stopping) in drinking level (i.e., light/moderate and excessive) and 5-yr changes (defined categorically as increasing, no change, or decreasing) by beverage type (i.e., beer, wine and liquor/mixed drinks) were also examined.
In men, compared to stable non-drinking, decreasing total alcohol intake was associated with lower 5-yr WC (β:-0.62 cm; 95% CI: -1.09, -0.14 cm) and BMI gains (β:-0.20 kg/m2; 95% CI: -0.30, -0.03 kg/m2) and stopping excessive drinking was associated with lower 5-yr WC gains (β:-0.77 cm; 95% CI: -1.51, -0.03 cm). In women, compared to those with stable non-drinking habits, starting light/moderate drinking was associated with lower 5-yr WC (β: -0.78 cm; 95% CI: -1.29, -0.26 cm) and BMI gains (β:-0.42 kg/m2; 95% CI: -0.64, -0.20 kg/m2). Increasing wine intake was associated with a lower 5-yr BMI gain (β:-0.27 kg/m2; 95% CI: -0.51, -0.03 kg/m2). Decreasing liquor/mixed drink (β:-0.33 kg/m2; 95% CI: -0.56, -0.09 kg/m2) intake was associated with lower 5-yr WC (β:-0.88 cm; 95% CI: -1.43, -0.34 cm) and BMI (β:-0.33 kg/m2; 95% CI: -0.56, -0.09 kg/m2) gains.
Associations of alcohol intake with obesity measures are complex. In women, wine and liquor/mixed drink intakes had contrasting associations with WC and BMI change. In men, decreasing weekly alcoholic beverage intake with an emphasis on stopping excessive consumption may be beneficial in managing WC and BMI gains.
Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, ...indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced. Signatures of discontinued exposures, including tobacco smoke and ultraviolet light, were not generated in vitro. Signatures of normal and defective DNA repair and replication continued to be generated at roughly stable mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing exhibited substantial fluctuations in mutation rate over time with episodic bursts of mutations. The initiating factors for the bursts are unclear, although retrotransposon mobilization may contribute. The examined cell lines constitute a resource of live experimental models of mutational processes, which potentially retain patterns of activity and regulation operative in primary human cancers.
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•Annotation of mutational signatures across 1,001 cancer cell lines and 577 PDXs•Activities of mutational processes determined over time in cancer cell lines•APOBEC-associated mutagenesis is often ongoing and can be episodic•Detection of mutational signatures by single-cell sequencing
An analysis of 1,001 human cancer cell lines and 577 xenografts shows that mutagenesis associated with the cytodine deaminase APOBEC occurs in episodic bursts in contrast to mutation signatures associated with DNA replication and repair.
Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. ...However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity.
Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio OR = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency.
In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.
Cryptococcal meningitis is common in sub-Saharan Africa. Given the need for data for a rapid, point-of-care cryptococcal antigen (CRAG) lateral flow immunochromatographic assay (LFA), we assessed ...diagnostic performance of cerebrospinal fluid (CSF) culture, CRAG latex agglutination, India ink microscopy, and CRAG LFA for 832 HIV-infected persons with suspected meningitis during 2006-2009 (n = 299) in Uganda and during 2010-2012 (n = 533) in Uganda and South Africa. CRAG LFA had the best performance (sensitivity 99.3%, specificity 99.1%). Culture sensitivity was dependent on CSF volume (82.4% for 10 μL, 94.2% for 100 μL). CRAG latex agglutination test sensitivity (97.0%-97.8%) and specificity (85.9%-100%) varied between manufacturers. India ink microscopy was 86% sensitive. Laser thermal contrast had 92% accuracy (R = 0.91, p<0.001) in quantifying CRAG titers from 1 LFA strip to within <1.5 dilutions of actual CRAG titers. CRAG LFA is a major advance for meningitis diagnostics in resource-limited settings.
The Anthropocene: A Special Issue Butler, David R.
Annals of the American Association of Geographers,
04/2021, Letnik:
111, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This special issue of the Annals of the American Association of Geographers is devoted to the Anthropocene, the period of unprecedented human impacts on Earth's environmental systems. The articles ...contained in this special issue illustrate that geographers have a diverse perspective on what the Anthropocene is and represents. The articles also show that geographers do not feel it necessary to identify only one starting point for the temporal onset of the Anthropocene. Several starting points are suggested, and some authors support the concept of a time-transgressive Anthropocene. Articles in this issue are organized into six sections, but many of them transcend easy categorization and could easily have fit into two or even three different sections. Geographers embrace the concept of the Anthropocene while defining it and studying it in a variety of ways that clearly show the breadth and diversity of the discipline.
Antony R. Orme’s Ireland (1970) Butler, David R
Progress in physical geography,
10/2020, Letnik:
44, Številka:
5
Journal Article
Recenzirano
Antony R. “Tony” Orme passed away on 30 May 2020. Professor Orme was one of the US’ most distinguished geomorphologists and physical geographers. This Classics Revisited piece honors the memory of ...Professor Tony Orme and examines his classic book Ireland, an outstanding example of a regional geography book with a strong foundation in physical geography.
Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of ...AML and informs clinical practice.
We enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes.
We identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNA-splicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2(R172) mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co-occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials.
The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT00146120.).
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