Ancient DNA reveals the timing and persistence of organellar genetic bottlenecks over 3,000 years of sunflower domestication and improvement

Here, we report a comprehensive paleogenomic study of archaeological and ethnographic sunflower remains that provides significant new insights into the process of domestication of this important crop. DNA from both ancient and historic contexts yielded high proportions of endogenous DNA, and although archaeological DNA was found to be highly degraded, it still provided sufficient coverage to analyze genetic changes over time. Shotgun sequencing data from specimens from the Eden's Bluff archaeological site in Arkansas yielded organellar DNA sequence from specimens up to 3,100 years old. Their sequences match those of modern cultivated sunflowers and are consistent with an early domestication bottleneck in this species. Our findings also suggest that recent breeding of sunflowers has led to a loss of genetic diversity that was present only a century ago in Native American landraces. These breeding episodes also left a profound signature on the mitochondrial and plastid haplotypes in cultivars, as two types were intentionally introduced from other Helianthus species for crop improvement. These findings gained from ancient and historic sunflower specimens underscore how future in-depth gene-based analyses can advance our understanding of the pace and targets of selection during the domestication of sunflower and other crop species

Recognizing Treelike k-Dissimilarities

A k-dissimilarity D on a finite set X, |X| >= k, is a map from the set of size k subsets of X to the real numbers. Such maps naturally arise from edge-weighted trees T with leaf-set X: Given a subset Y of X of size k, D(Y) is defined to be the total length of the smallest subtree of T with leaf-set Y . In case k = 2, it is well-known that 2-dissimilarities arising in this way can be characterized by the so-called "4-point condition". However, in case k > 2 Pachter and Speyer recently posed the following question: Given an arbitrary k-dissimilarity, how do we test whether this map comes from a tree? In this paper, we provide an answer to this question, showing that for k >= 3 a k-dissimilarity on a set X arises from a tree if and only if its restriction to every 2k-element subset of X arises from some tree, and that 2k is the least possible subset size to ensure that this is the case. As a corollary, we show that there exists a polynomial-time algorithm to determine when a k-dissimilarity arises from a tree. We also give a 6-point condition for determining when a 3-dissimilarity arises from a tree, that is similar to the aforementioned 4-point condition.Comment: 18 pages, 4 figure

New SPB stars in the field of the young open cluster NGC 2244 discovered by the MOST photometric satellite

During two weeks of nearly continuous optical photometry of the young open cluster NGC 2244 obtained by the MOST satellite, we discovered two new SPB stars, GSC 00154-00785 and GSC 00154-01871. We present frequency analyses of the MOST light curves of these stars, which reveal two oscillation frequencies (0.61 and 0.71 c/d) in GSC 00154-00785 and two (0.40 and 0.51 c/d) in GSC 00154-01871. These frequency ranges are consistent with g-modes of $\ell \leq 2$ excited in models of main-sequence or pre-main-sequence (PMS) stars of masses 4.5 - 5 $M_{\odot}$ and solar composition $(X, Z)= (0.7, 0.02)$. Published proper motion measurements and radial velocities are insufficient to establish unambiguously cluster membership for these two stars. However, the PMS models which fit best their eigenspectra have ages consistent with NGC 2244. If cluster membership can be confirmed, these would be the first known PMS SPB stars, and would open a new window on testing asteroseismically the interior structures of PMS stars.Comment: accepted for publication in MNRA

Plasmas and Controlled Nuclear Fusion

Contains research objectives and reports on four research projects.National Science Foundation (Grant GK-614)National Science Foundation (Grant GK-57

Three-way symbolic tree-maps and ultrametrics

Three-way dissimilarities are a generalization of (two-way) dissimilarities which can be used to indicate the lack of homogeneity or resemblance between any three objects. Such maps have applications in cluster analysis and have been used in areas such as psychology and phylogenetics, where three-way data tables can arise. Special examples of such dissimilarities are three-way tree-metrics and ultrametrics, which arise from leaf-labelled trees with edges labelled by positive real numbers. Here we consider three-way maps which arise from leaf-labelled trees where instead the interior vertices are labelled by an arbitrary set of values. For unrooted trees, we call such maps three-way symbolic tree-maps; for rooted trees, we call them three-way symbolic ultrametrics since they can be considered as a generalization of the (two-way) symbolic ultrametrics of Bocker and Dress. We show that, as with two- and three-way tree-metrics and ultrametrics, three-way symbolic tree-maps and ultrametrics can be characterized via certain k-point conditions. In the unrooted case, our characterization is mathematically equivalent to one presented by Gurvich for a certain class of edge-labelled hypergraphs. We also show that it can be decided whether or not an arbitrary three-way symbolic map is a tree-map or a symbolic ultrametric using a triplet-based approach that relies on the so-called BUILD algorithm for deciding when a set of 3-leaved trees or triplets can be displayed by a single tree. We envisage that our results will be useful in developing new approaches and algorithms for understanding 3-way data, especially within the area of phylogenetics

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer

What, if anything, are hybrids: enduring truths and challenges associated with population structure and gene flow

Hybridization is a potent evolutionary process that can affect the origin, maintenance, and loss of biodiversity. Because of its ecological and evolutionary consequences, an understanding of hybridization is important for basic and applied sciences, including conservation biology and agriculture. Herein, we review and discuss ideas that are relevant to the recognition of hybrids and hybridization. We supplement this discussion with simulations. The ideas we present have a long history, particularly in botany, and clarifying them should have practical consequences for managing hybridization and gene flow in plants. One of our primary goals is to illustrate what we can and cannot infer about hybrids and hybridization from molecular data; in other words, we ask when genetic analyses commonly used to study hybridization might mislead us about the history or nature of gene flow and selection. We focus on patterns of variation when hybridization is recent and populations are polymorphic, which are particularly informative for applied issues, such as contemporary hybridization following recent ecological change. We show that hybridization is not a singular process, but instead a collection of related processes with variable outcomes and consequences. Thus, it will often be inappropriate to generalize about the threats or benefits of hybridization from individual studies, and at minimum, it will be important to avoid categorical thinking about what hybridization and hybrids are. We recommend potential sampling and analytical approaches that should help us confront these complexities of hybridization

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 × 107 transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n=19, P=0.002, r=0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients