Seasonal snowcover dynamics beneath boreal forest canopies

The accurate simulation of snowpack deposition and ablation beneath forested areas is confounded by the fact that the vegetation canopy strongly affects the snow surface energy balance. The canopy alters the radiation balance of the snowcover, and reduces the wind speed at the snow surface. Data collected as part of the BOREAS experiment are used to analyze the effects of a variety of forest canopies on the climate at the snow surface. Simple algorithms are developed and used to adjust climate data collected above forest canopies to the snow surface. A 2-layer coupled energy- and mass-balance snowmelt model is used to simulate the deposition and ablation of the snowpack at five forested sites within the Canadian boreal forest for the 1994-1995 snow season. Results of the snowcover simulations indicate that the net snowcover energy balance remains close to zero for the winter months, but exhibits a sharp increase in the spring months. The rapid energy gain in the spring is strongly controlled by canopy cover, and is dominated by net radiation fluxes, with minor contributions from sensible, latent, soil, and advected energy fluxes. Net snowcover irradiance dominates during the spring months due to increased solar intensity and longer day lengths, coupled with increased radiation transmission through canopies at high sun angles, and reduced snowcover albedo resulting from the deposition of fine organic debris. Turbulent (sensible and latent) energy fluxes comprise a relatively minor portion of the net snowcover energy exchange, indicating that the sub-canopy snowcover is relatively insensitive to the meteorological parameters controlling these fluxes. The low thermal conductivity of organic-rich boreal soils must be considered for studies focusing on snowcover development when soil heat flux comprises a large portion of the snowcover energy balance. Model outputs at all sites generally show good agreement with measured snow depths, indicating that the techniques used in these investigations accurately simulate both the deposition and ablation of seasonal snowcovers. Results indicate that snowcovers in the boreal environment may be more sensitive to land-use transitions, rather than climate shifts, due to the strong control exerted by vegetation canopies on radiation transfer processes. The results also suggest that simple canopy adjustment algorithms may be effectively applied to spatially distributed snowcover simulations. More data is required to evaluate the accuracy of these methods for computing energy transfer within canopies having significantly different structures than the sites used in this study

Simulation of Water and Energy Fluxes in an Old-Growth Seasonal Temperate Rain Forest Using the Simultaneous Heat and Water (SHAW) Model

In the Pacific Northwest (PNW), concern about the impacts of climate and land cover change on water resources and flood-generating processes emphasizes the need for a mechanistic understanding of the interactions between forest canopies and hydrologic processes. Detailed measurements during the 1999 and 2000 hydrologic years were used to modify the Simultaneous Heat and Water (SHAW) model for application in forested systems. Major changes to the model include improved representation of rainfall interception and stomatal conductance dynamics. The model was developed for the 1999 hydrologic year and tested for the 2000 hydrologic year without modification of the site parameters. The model effectively simulated throughfall, soil water content profiles, and shallow soil temperatures for both years. The largest discrepancies between soil moisture and temperature were observed during periods of discontinuous snow cover due to spatial variability that was not explicitly simulated by the model. Soil warming at bare locations was delayed until most of the snow cover ablated because of the large heat sink associated with the residual snow patches. During the summer, simulated transpiration decreased from a maximum monthly mean of 2.2 mm day⁻¹ in July to 1.3 mm day⁻¹ in September as a result of decreasing soil moisture and declining net radiation. The results indicate that a relatively simple representation of the vegetation canopy can accurately simulate seasonal hydrologic fluxes in this environment, except during periods of discontinuous snow cover

Genetic and transcriptional contributions to relapse in normal karyotype acute myeloid leukemia

To better understand clonal and transcriptional adaptations after relapse in patients with acute myeloid leukemia (AML), we collected presentation and relapse samples from six normal karyotype AML cases. We performed enhanced whole-genome sequencing to characterize clonal evolution, and deep-coverage single-cell RNA sequencing on the same samples, which yielded 142,642 high-quality cells for analysis. Identifying expressed mutations in individual cells enabled us to discriminate between normal and AML cells, to identify coordinated changes in the genome and transcriptome, and to identify subclone-specific cell states. We quantified the coevolution of genetic and transcriptional heterogeneity during AML progression, and found that transcriptional changes were significantly correlated with genetic changes. However, transcriptional adaptation sometimes occurred independently, suggesting that clonal evolution does not represent all relevant biological changes. In three cases, we identified cells at diagnosis that likely seeded the relapse. Finally, these data revealed a conserved relapse-enriched leukemic cell state bearing markers of stemness, quiescence, and adhesion. SIGNIFICANCE: These data enabled us to identify a relapse-enriched leukemic cell state with distinct transcriptional properties. Detailed case-by-case analyses elucidated the complex ways in which the AML genome, transcriptome, and immune microenvironment interact to evade chemotherapy. These analyses provide a blueprint for evaluating these factors in larger cohorts

Forage fish interactions: A symposium on creating the tools for ecosystem-based management of marine resources

Forage fish (FF) have a unique position within marine foodwebs and the development of sustainable harvest strategies for FF will be a critical step in advancing and implementing the broader, ecosystem-based management of marine systems. In all, 70 scientists from 16 nations gathered for a symposium on 12–14 November 2012 that was designed to address three key questions regarding the effective management of FF and their ecosystems: (i) how do environmental factors and predator–prey interactions drive the productivity and distribution of FF stocks across ecosystems worldwide, (ii) what are the economic and ecological costs and benefits of different FF management strategies, and (iii) do commonalities exist across ecosystems in terms of the effective management of FF exploitation

Clonal architecture of secondary acute myeloid leukemia defined by single-cell sequencing

Next-generation sequencing has been used to infer the clonality of heterogeneous tumor samples. These analyses yield specific predictions-the population frequency of individual clones, their genetic composition, and their evolutionary relationships-which we set out to test by sequencing individual cells from three subjects diagnosed with secondary acute myeloid leukemia, each of whom had been previously characterized by whole genome sequencing of unfractionated tumor samples. Single-cell mutation profiling strongly supported the clonal architecture implied by the analysis of bulk material. In addition, it resolved the clonal assignment of single nucleotide variants that had been initially ambiguous and identified areas of previously unappreciated complexity. Accordingly, we find that many of the key assumptions underlying the analysis of tumor clonality by deep sequencing of unfractionated material are valid. Furthermore, we illustrate a single-cell sequencing strategy for interrogating the clonal relationships among known variants that is cost-effective, scalable, and adaptable to the analysis of both hematopoietic and solid tumors, or any heterogeneous population of cells

Next-generation sequencing identifies the natural killer cell microRNA transcriptome

Natural killer (NK) cells are innate lymphocytes important for early host defense against infectious pathogens and surveillance against malignant transformation. Resting murine NK cells regulate the translation of effector molecule mRNAs (e.g., granzyme B, GzmB) through unclear molecular mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate the translation of their mRNA targets, and are therefore candidates for mediating this control process. While the expression and importance of miRNAs in T and B lymphocytes have been established, little is known about miRNAs in NK cells. Here, we used two next-generation sequencing (NGS) platforms to define the miRNA transcriptomes of resting and cytokine-activated primary murine NK cells, with confirmation by quantitative real-time PCR (qRT-PCR) and microarrays. We delineate a bioinformatics analysis pipeline that identified 302 known and 21 novel mature miRNAs from sequences obtained from NK cell small RNA libraries. These miRNAs are expressed over a broad range and exhibit isomiR complexity, and a subset is differentially expressed following cytokine activation. Using these miRNA NGS data, miR-223 was identified as a mature miRNA present in resting NK cells with decreased expression following cytokine activation. Furthermore, we demonstrate that miR-223 specifically targets the 3′ untranslated region of murine GzmB in vitro, indicating that this miRNA may contribute to control of GzmB translation in resting NK cells. Thus, the sequenced NK cell miRNA transcriptome provides a valuable framework for further elucidation of miRNA expression and function in NK cell biology

Clonal architecture of secondary acute myeloid leukemia

BACKGROUND: The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. METHODS: We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. RESULTS: Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast count. The secondary-AML samples contained mutations in 11 recurrently mutated genes, including 4 genes that have not been previously implicated in the myelodysplastic syndromes or AML. In every case, progression to acute leukemia was defined by the persistence of an antecedent founding clone containing 182 to 660 somatic mutations and the outgrowth or emergence of at least one subclone, harboring dozens to hundreds of new mutations. All founding clones and subclones contained at least one mutation in a coding gene. CONCLUSIONS: Nearly all the bone marrow cells in patients with myelodysplastic syndromes and secondary AML are clonally derived. Genetic evolution of secondary AML is a dynamic process shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent gene mutations are found in both founding clones and daughter subclones. (Funded by the National Institutes of Health and others.

Genomic landscape of TP53-mutated myeloid malignancies

TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants, which complicates detailed genomic analysis by conventional clinical techniques. We performed whole-genome sequencing (WGS) of 42 acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) cases with paired normal tissue to better characterize the genomic landscape of TP53-mutated AML/MDS. WGS accurately determines TP53 allele status, a key prognostic factor, resulting in the reclassification of 12% of cases from monoallelic to multihit. Although aneuploidy and chromothripsis are shared with most TP53-mutated cancers, the specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. ETV6 expression is reduced in nearly all cases of TP53-mutated AML/MDS, either through gene deletion or presumed epigenetic silencing. Within the AML cohort, mutations of NF1 are highly enriched, with deletions of 1 copy of NF1 present in 45% of cases and biallelic mutations in 17%. Telomere content is increased in TP53-mutated AMLs compared with other AML subtypes, and abnormal telomeric sequences were detected in the interstitial regions of chromosomes. These data highlight the unique features of TP53-mutated myeloid malignancies, including the high frequency of chromothripsis and structural variation, the frequent involvement of unique genes (including NF1 and ETV6) as cooperating events, and evidence for altered telomere maintenance