Modern pollen rain predicts shifts in plant trait composition but not plant diversity along the Andes–Amazon elevational gradient

This is the final version. Available on open access from Wiley via the DOI in this record. Aims: Terrestrial ecosystems are changing in biodiversity, species composition and functional trait composition. To understand the underlying causes of these changes and predict the long-term resilience of the ecosystem to withstand future disturbances, we can evaluate changes in diversity and composition from fossil pollen records. Although diversity can be well estimated from pollen in temperate ecosystems, this is less clear for the hyperdiverse tropics. Moreover, it remains unknown whether functional composition of plant assemblages can be accurately predicted from pollen assemblage composition. Here, we evaluate how community-weighted mean (CWM) traits and diversity indices change along elevation. Location: Amazon–Andes elevation gradient in Peru. Methods: We used 82 modern pollen samples and 59 vegetation plots along the elevation gradient, and calculated CWM traits and diversity indices for each pollen sample and vegetation plot. We also quantified the degree to which taxa are over- or underrepresented by their pollen, by dividing the relative pollen abundance by the relative basal area abundance in the nearby vegetation survey plots (i.e. the R-rel values). Results: We found that CWM wood density increased, and CWM adult height and leaf area decreased with elevation. This change was well predicted by pollen assemblages, indicating that CWM trait–environment relationships based on pollen abundance data provide meaningful results. Diversity (richness, Shannon and Simpson) decreased with elevation for vegetation plots, but these trends could not be observed from pollen assemblages. Conclusions: Our results demonstrate that more research is needed to develop methods that lead to accurate diversity estimates from pollen data in these tropical ecosystems, but that CWM traits can be calculated from pollen data to assess spatial shifts in functional composition. This opens opportunities to calculate CWM traits from fossil pollen data sets in the tropics, with broad implications for improving our understanding and predictions of forest dynamics, functioning and resilience through time.Nederlandse Organisatie voor Wetenschappelijk Onderzoe

Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection

Background: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. Methodology/Principal Findings: We present the cellular immunology profile in the blood, and detailed clinical (and postmortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. Conclusion/Significance: Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype

Explanatory pluralism in the medical sciences: theory and practice

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise

Genome modeling system: A knowledge management platform for genomics

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

Warming, drought, and disturbances lead to shifts in functional composition: a millennial‐scale analysis for Amazonian and Andean sites

Tropical forests are changing in composition and productivity, probably in response to changes in climate and disturbances. The responses to these multiple environmental drivers, and the mechanisms underlying the changes, remain largely unknown. Here, we use a functional trait approach on timescales of 10,000 years to assess how climate and disturbances influence the community-mean adult height, leaf area, seed mass, and wood density for eight lowland and highland forest landscapes. To do so, we combine data of eight fossil pollen records with functional traits and proxies for climate (temperature, precipitation, and El Niño frequency) and disturbances (fire and general disturbances). We found that temperature and disturbances were the most important drivers of changes in functional composition. Increased water availability (high precipitation and low El Niño frequency) generally led to more acquisitive trait composition (large leaves and soft wood). In lowland forests, warmer climates decreased community-mean height probably because of increased water stress, whereas in highland forests warmer climates increased height probably because of upslope migration of taller species. Disturbance increased the abundance of acquisitive, disturbance-adapted taxa with small seeds for quick colonization of disturbed sites, large leaves for light capture, and soft wood to attain fast height growth. Fire had weak effects on lowland forests but led to more stress-adapted taxa that are tall with fast life cycles and small seeds that can quickly colonize burned sites. Site-specific analyses were largely in line with cross-site analyses, except for varying site-level effects of El Niño frequency and fire activity, possibly because regional patterns in El Niño are not a good predictor of local changes, and charcoal abundances do not reflect fire intensity or severity. With future global changes, tropical Amazonian and Andean forests may transition toward shorter, drought- and disturbance-adapted forests in the lowlands but taller forests in the highlands

Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease

The Origin and Evolution of Mutations in Acute Myeloid Leukemia

SummaryMost mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is “captured” as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse