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1.
Res Sq ; 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37886550

ABSTRACT

Intermediate wheatgrass (IWG, Thinopyrum intermedium [Host] Barkworth & D. R. Dewey) has been developed as a perennial grain crop to provide ecosystem services, environmental benefits, and human food. Grain and products derived from IWG varieties improved for food production have been marketed under the registered trademark, Kernza. In the 1980s, a joint breeding effort between the Rodale Institute (RI) and the Big Flats Plant Material Center used IWG plant introductions (PI) from the National Plant Germplasm System (NPGS) and recurrent phenotypic selection to improve populations of IWG with the goal of developing a perennial grain. Initial selections were provided to The Land Institute where they were subsequently improved for grain production, yet the identity of the founder material of improved, food-grade IWG has not been publicly documented. Recently recovered original documents have been used to reconstruct the early breeding program to identify the most likely 20 PIs that form the founders of modern food-grade IWG. Molecular data using genotyping-by-sequencing in current elite breeding material, remnant seed from the initial RI selections, and preserved sample material have provided supporting evidence for the historical records. The genetic origin for food-grade IWG is focused between the Black Sea and Caspian Sea in the Stavropol region of Russia, with smaller contributions likely from collections as distant as Kazakhstan in the east to Turkey in the west. This work connects the flow of germplasm and utility of NPGS PIs to present day IWG grain cultivars being developed in multiple breeding programs around the world.

2.
Sci Total Environ ; 895: 164975, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37336402

ABSTRACT

Perennial grains have potential to contribute to ecological intensification of food production by enabling the direct harvest of human-edible crops without requiring annual cycles of disturbance and replanting. Studies of prototype perennial grains and other herbaceous perennials point to the ability of agroecosystems including these crops to protect water quality, enhance wildlife habitat, build soil quality, and sequester soil carbon. However, genetic improvement of perennial grain candidates has been hindered by limited investment due to uncertainty about whether the approach is viable. As efforts to develop perennial grain crops have expanded in past decades, critiques of the approach have arisen. With a recent report of perennial rice producing yields equivalent to those of annual rice over eight consecutive harvests, many theoretical concerns have been alleviated. Some valid questions remain over the timeline for new crop development, but we argue these may be mitigated by implementation of recent technological advances in crop breeding and genetics such as low-cost genotyping, genomic selection, and genome editing. With aggressive research investment in the development of new perennial grain crops, they can be developed and deployed to provide atmospheric greenhouse gas reductions.


Subject(s)
Agriculture , Plant Breeding , Humans , Edible Grain , Crops, Agricultural , Soil
3.
ACS Earth Space Chem ; 6(5): 1321-1330, 2022 May 19.
Article in English | MEDLINE | ID: mdl-36275877

ABSTRACT

Armor-penetrating projectiles and fragments of depleted uranium (DU) have been deposited in soils at weapon-tested sites. Soil samples from these military facilities were analyzed by inductively coupled plasma-optical emission spectroscopy and X-ray diffraction to determine U concentrations and transport across an arid ecosystem. Under arid conditions, both vertical transport driven by evaporation (upward) and leaching (downward) and horizontal transport of U driven by surface runoff in the summer were observed. Upward vertical transport was simulated and confirmed under laboratory-controlled conditions, to be leading to the surface due to capillary action via evaporation during alternating wetting and drying conditions. In the field, the 92.8% of U from DU penetrators and fragments remained in the top 5 cm of soil and decreased to background concentrations in less than 20 cm. In locations prone to high amounts of water runoff, U concentrations were reduced significantly after 20 m from the source due to high surface runoff. Uranium was also transported throughout the ecosystem via plant uptake and wild animal consumption between trophic levels, but with limited accumulation in edible portions in plants and animals.

4.
Theor Appl Genet ; 135(8): 2769-2784, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35763029

ABSTRACT

KEY MESSAGE: Analysis of multi-year breeding program data revealed that the genetic architecture of an intermediate wheatgrass population was highly polygenic for both domestication and agronomic traits, supporting the use of genomic selection for new crop domestication. Perennial grains have the potential to provide food for humans and decrease the negative impacts of annual agriculture. Intermediate wheatgrass (IWG, Thinopyrum intermedium, Kernza®) is a promising perennial grain candidate that The Land Institute has been breeding since 2003. We evaluated four consecutive breeding cycles of IWG from 2016 to 2020 with each cycle containing approximately 1100 unique genets. Using genotyping-by-sequencing markers, quantitative trait loci (QTL) were mapped for 34 different traits using genome-wide association analysis. Combining data across cycles and years, we found 93 marker-trait associations for 16 different traits, with each association explaining 0.8-5.2% of the observed phenotypic variance. Across the four cycles, only three QTL showed an FST differentiation > 0.15 with two corresponding to a decrease in floret shattering. Additionally, one marker associated with brittle rachis was 216 bp from an ortholog of the btr2 gene. Power analysis and quantitative genetic theory were used to estimate the effective number of QTL, which ranged from a minimum of 33 up to 558 QTL for individual traits. This study suggests that key agronomic and domestication traits are under polygenic control and that molecular methods like genomic selection are needed to accelerate domestication and improvement of this new crop.


Subject(s)
Agropyron , Quantitative Trait Loci , Agropyron/genetics , Domestication , Edible Grain/genetics , Genome-Wide Association Study , Humans , Plant Breeding/methods , Selection, Genetic
5.
Plant Cell Physiol ; 63(11): 1624-1640, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-35583202

ABSTRACT

Sustainable agriculture in the future will depend on crops that are tolerant to biotic and abiotic stresses, require minimal input of water and nutrients and can be cultivated with a minimal carbon footprint. Wild plants that fulfill these requirements abound in nature but are typically low yielding. Thus, replacing current high-yielding crops with less productive but resilient species will require the intractable trade-off of increasing land area under cultivation to produce the same yield. Cultivating more land reduces natural resources, reduces biodiversity and increases our carbon footprint. Sustainable intensification can be achieved by increasing the yield of underutilized or wild plant species that are already resilient, but achieving this goal by conventional breeding programs may be a long-term prospect. De novo domestication of orphan or crop wild relatives using mutagenesis is an alternative and fast approach to achieve resilient crops with high yields. With new precise molecular techniques, it should be possible to reach economically sustainable yields in a much shorter period of time than ever before in the history of agriculture.


Subject(s)
Domestication , Plant Breeding , Crops, Agricultural/genetics , Agriculture , Biodiversity
6.
Plant Genome ; 14(3): e20145, 2021 11.
Article in English | MEDLINE | ID: mdl-34626160

ABSTRACT

Perennial grain crops have the potential to improve agricultural sustainability but few existing species produce sufficient grain yield to be economically viable. The outcrossing, allohexaploid, and perennial forage species intermediate wheatgrass (IWG) [Thinopyrum intermedium (Host) Barkworth & D. R. Dewey] has shown promise in undergoing direct domestication as a perennial grain crop using phenotypic and genomic selection. However, decades of selection will be required to achieve yields on par with annual small-grain crops. Marker-aided selection could accelerate progress if important genomic regions associated with domestication were identified. Here we use the IWG nested association mapping (NAM) population, with 1,168 F1 progeny across 10 families to dissect the genetic control of brittle rachis, floret shattering, and threshability. We used a genome-wide association study (GWAS) with 8,003 single nucleotide polymorphism (SNP) markers and linkage mapping-both within-family and combined across families-with a robust phenotypic dataset collected from four unique year-by-location combinations. A total of 29 quantitative trait loci (QTL) using GWAS and 20 using the combined linkage analysis were detected, and most large-effect QTL were in common across the two analysis methods. We reveal that the genetic control of these traits in IWG is complex, with significant QTL across multiple chromosomes, sometimes within and across homoeologous groups and effects that vary depending on the family. In some cases, these QTL align within 216 bp to 31 Mbp of BLAST hits for known domestication genes in related species and may serve as precise targets of selection and directions for further study to advance the domestication of IWG.


Subject(s)
Hordeum , Oryza , Genome, Plant , Genome-Wide Association Study , Hordeum/genetics , Humans , Oryza/genetics , Plant Breeding , Quantitative Trait Loci , Seeds , Triticum/genetics
7.
ACS Earth Space Chem ; 5(2): 356-364, 2021 Feb 18.
Article in English | MEDLINE | ID: mdl-34337281

ABSTRACT

Uranium is a chemically toxic and radioactive heavy metal. Depleted uranium (DU) is the byproduct of the uranium enrichment process, with a majority of U as uranium-238, and a lower content of the fissile isotope uranium-235 than natural uranium. Uranium-235 is mainly used in nuclear reactors and in the manufacture of nuclear weapons. Exposure is likely to have an impact on humans or the ecosystem where military operations have used DU. Yuma Proving Ground in Arizona, USA has been using depleted uranium ballistics for 36 years. At a contaminated site in the Proving Grounds, soil samples were collected from the flat, open field and lower elevated trenches that typically collect summer runoff. Spatial distribution and fractionation of uranium in the fields were analyzed with total acid digestion and selective sequential dissolution with eight operationally defined solid-phase fractions. In addition to uranium, other trace elements (As, Ba, Co, Cr, Cu, Hg, Mo, Nb, Pd, Pb, V, Zn, Zr) were also assessed. Results show that the trench area in the testing site had a higher accumulation of total U (12.4%) compared to the open-field soil with 279 mg/kg U. Among the eight solid-phase components in the open-field samples, U demonstrated stronger affinities for the amorphous iron-oxide bound, followed by the carbonate bound, and the residual fractions. However, U in the trench area had a stronger binding to the easily reducible oxide bound fraction, followed by the carbonate-bound and amorphous iron-oxide-bound fractions. Among other trace elements, Nb, As, and Zr exhibited the strongest correlations with U distribution among solid-phase components. This study indicates a significant spatial variation of U distribution in the shooting range site. Fe/Mn oxides and carbonate were the major solid-phase components for binding U in the weapon test site.

8.
Nat Commun ; 12(1): 4669, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34344873

ABSTRACT

Diseases are a manifestation of how thousands of proteins interact. In several diseases, such as cancer and Alzheimer's disease, proteome-wide disturbances in protein-protein interactions are caused by alterations to chaperome scaffolds termed epichaperomes. Epichaperome-directed chemical probes may be useful for detecting and reversing defective chaperomes. Here we provide structural, biochemical, and functional insights into the discovery of epichaperome probes, with a focus on their use in central nervous system diseases. We demonstrate on-target activity and kinetic selectivity of a radiolabeled epichaperome probe in both cells and mice, together with a proof-of-principle in human patients in an exploratory single group assignment diagnostic study (ClinicalTrials.gov Identifier: NCT03371420). The clinical study is designed to determine the pharmacokinetic parameters and the incidence of adverse events in patients receiving a single microdose of the radiolabeled probe administered by intravenous injection. In sum, we introduce a discovery platform for brain-directed chemical probes that specifically modulate epichaperomes and provide proof-of-principle applications in their use in the detection, quantification, and modulation of the target in complex biological systems.


Subject(s)
Central Nervous System/metabolism , Molecular Chaperones/metabolism , Protein Interaction Mapping/instrumentation , Proteome/metabolism , Animals , Biomarkers, Tumor/metabolism , Blood-Brain Barrier/metabolism , Brain Neoplasms/diagnosis , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Cell Survival/drug effects , Central Nervous System/drug effects , Glioblastoma/diagnosis , Glioblastoma/metabolism , HSP90 Heat-Shock Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/chemistry , HSP90 Heat-Shock Proteins/metabolism , Humans , Mice , Molecular Probes/chemistry , Molecular Probes/pharmacokinetics , Molecular Probes/pharmacology , Molecular Probes/therapeutic use , Positron-Emission Tomography
9.
J Nucl Med ; 62(8): 1133-1139, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33277396

ABSTRACT

In 2018, the National Cancer Institute and NRG Oncology partnered for the first time to host a joint workshop on systemic radiopharmaceutical therapy (RPT) to specifically address dosimetry issues and strategies for future clinical trials. The workshop focused on current dosimetric approaches for clinical trials, strategies under development that would optimize dose reporting, and future desired or optimized approaches for novel emerging radionuclides and carriers in development. In this article, we review the main approaches that are applied clinically to calculate the absorbed dose. These include absorbed doses calculated over a variety of spatial scales, including whole body, organ, suborgan, and voxel, the last 3 of which are achievable within the MIRD schema (S value) and can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This article will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biologic effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We also briefly discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.


Subject(s)
National Cancer Institute (U.S.) , Radiometry , Neoplasms , United States
10.
Theor Appl Genet ; 133(11): 3217-3233, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32785739

ABSTRACT

KEY MESSAGE: Paternity assignment and genome-wide association analyses for fertility were applied to a Thinopyrum intermedium breeding program. A lack of progeny between combinations of parents was associated with loci near self-incompatibility genes. In outcrossing species such as intermediate wheatgrass (IWG, Thinopyrum intermedium), polycrossing is often used to generate novel recombinants through each cycle of selection, but it cannot track pollen-parent pedigrees and it is unknown how self-incompatibility (SI) genes may limit the number of unique crosses obtained. This study investigated the potential of using next-generation sequencing to assign paternity and identify putative SI loci in IWG. Using a reference population of 380 individuals made from controlled crosses of 64 parents, paternity was assigned with 92% agreement using Cervus software. Using this approach, 80% of 4158 progeny (n = 3342) from a polycross of 89 parents were assigned paternity. Of the 89 pollen parents, 82 (92%) were represented with 1633 unique full-sib families representing 42% of all potential crosses. The number of progeny per successful pollen parent ranged from 1 to 123, with number of inflorescences per pollen parent significantly correlated to the number of progeny (r = 0.54, p < 0.001). Shannon's diversity index, assessing the total number and representation of families, was 7.33 compared to a theoretical maximum of 8.98. To test our hypothesis on the impact of SI genes, a genome-wide association study of the number of progeny observed from the 89 parents identified genetic effects related to non-random mating, including marker loci located near putative SI genes. Paternity testing of polycross progeny can impact future breeding gains by being incorporated in breeding programs to optimize polycross methodology, maintain genetic diversity, and reveal genetic architecture of mating patterns.


Subject(s)
Plant Breeding , Poaceae/genetics , Pollen/genetics , Self-Incompatibility in Flowering Plants/genetics , Crosses, Genetic , Fertility/genetics , Genes, Plant , Genetic Association Studies , Genetic Markers , Genotype , Pedigree
11.
Genome ; 63(9): 445-457, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32384249

ABSTRACT

Bluebunch wheatgrass (referred to as BBWG) [Pseudoroegneria spicata (Pursh) Á. Löve] is an important rangeland Triticeae grass used for forage, conservation, and restoration. This diploid has the basic St genome that occurs also in many polyploid Triticeae species, which serve as a gene reservoir for wheat improvement. Until now, the St genome in diploid species of Pseudoroegneria has not been mapped. Using a double-cross mapping populations, we mapped 230 expressed sequence tag derived simple sequence repeat (EST-SSR) and 3468 genotyping-by-sequencing (GBS) markers to 14 linkage groups (LGs), two each for the seven homologous groups of the St genome. The 227 GBS markers of BBWG that matched those in a previous study helped identify the unclassified seven LGs of the St sub-genome among 21 LGs of Thinopyrum intermedium (Host) Barkworth & D.R. Dewey. Comparisons of GBS sequences in BBWG to whole-genome sequences in bread wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) revealed that the St genome shared a homology of 35% and 24%, a synteny of 86% and 84%, and a collinearity of 0.85 and 0.86, with ABD and H, respectively. This first-draft molecular map of the St genome will be useful in breeding cereal and forage crops.


Subject(s)
Chromosome Mapping , Genomics , Hordeum/genetics , Poaceae/genetics , Triticum/genetics , Chromosomes, Plant , Diploidy , Expressed Sequence Tags , Genetic Linkage , Genetic Markers , Genome, Plant , Microsatellite Repeats , Polyploidy , Synteny
12.
Trends Plant Sci ; 25(6): 525-537, 2020 06.
Article in English | MEDLINE | ID: mdl-32407693

ABSTRACT

Shifting the life cycle of grain crops from annual to perennial would usher in a new era of agriculture that is more environmentally friendly, resilient to climate change, and capable of soil carbon sequestration. Despite decades of work, transforming the annual grain crop wheat (Triticum aestivum) into a perennial has yet to be realized. Direct domestication of wild perennial grass relatives of wheat, such as Thinopyrum intermedium, is an alternative approach. Here we highlight protein coding sequences in the recently released T. intermedium genome sequence that may be orthologous to domestication genes identified in annual grain crops. Their presence suggests a roadmap for the accelerated domestication of this plant using new breeding technologies.


Subject(s)
Domestication , Edible Grain , Agriculture , Breeding , Crops, Agricultural/genetics , Edible Grain/genetics
13.
Theor Appl Genet ; 132(8): 2325-2351, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31172227

ABSTRACT

Allohexaploid (2n = 6x = 42) intermediate wheatgrass (Thinopyrum intermedium), abbreviated IWG, is an outcrossing perennial grass belonging to the tertiary gene pool of wheat. Perenniality would be valuable option for grain production, but attempts to introgress this complex trait from wheat-Thinopyrum hybrids have not been commercially successful. Efforts to breed IWG itself as a dual-purpose forage and grain crop have demonstrated useful progress and applications, but grain yields are significantly less than wheat. Therefore, genetic and physical maps have been developed to accelerate domestication of IWG. Herein, these maps were used to identify quantitative trait loci (QTLs) and candidate genes associated with IWG grain production traits in a family of 266 full-sib progenies derived from two heterozygous parents, M26 and M35. Transgressive segregation was observed for 17 traits related to seed size, shattering, threshing, inflorescence capacity, fertility, stem size, and flowering time. A total of 111 QTLs were detected in 36 different regions using 3826 genotype-by-sequence markers in 21 linkage groups. The most prominent QTL had a LOD score of 15 with synergistic effects of 29% and 22% over the family means for seed retention and percentage of naked seeds, respectively. Many QTLs aligned with one or more IWG gene models corresponding to 42 possible domestication orthogenes including the wheat Q and RHT genes. A cluster of seed-size and fertility QTLs showed possible alignment to a putative Z self-incompatibility gene, which could have detrimental grain-yield effects when genetic variability is low. These findings elucidate pathways and possible hurdles in the domestication of IWG.


Subject(s)
Agropyron/genetics , Chromosome Mapping , Domestication , Quantitative Trait Loci/genetics , Quantitative Trait, Heritable , Base Sequence , Chromosomes, Plant/genetics , Genetic Linkage , Genetic Markers , Genome, Plant , Genotype , Lod Score , Phenotype
14.
Evol Appl ; 11(10): 2025-2039, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30459846

ABSTRACT

A species' population structure and history are critical pieces of information that can help guide the use of available native plant materials in restoration treatments and decide what new native plant materials should be developed to meet future restoration needs. In the western United States, Pseudoroegneria spicata (bluebunch wheatgrass; Poaceae) is an important component of grassland and shrubland plant communities and commonly used for restoration due to its drought resistance and competitiveness with exotic weeds. We used next-generation sequencing data to investigate the processes that shaped P. spicata's geographic pattern of genetic variation across the Intermountain West. Pseudoroegneria spicata's genetic diversity is partitioned into populations that likely differentiated since the Last Glacial Maximum. Adjacent populations display varying magnitudes of historical gene flow, with migration rates ranging from multiple migrants per generation to multiple generations per migrant. When considering the commercial germplasm sources available for restoration, genetic identities remain representative of the wildland localities from which germplasm sources were originally developed, and they maintain high levels of heterozygosity and nucleotide diversity. However, the commercial germplasm sources represent a small fraction of the overall genetic diversity of P. spicata in the Intermountain West. Given the low migration rates and long divergence times between some pairs of P. spicata populations, using commercial germplasm sources could facilitate undesirable restoration outcomes when used in certain geographic areas, even if the environment in which the commercial materials thrive is similar to that of the restoration site. As such, population structure and history can be used to provide guidance on what geographic areas may need additional native plant materials so that restoration efforts support species and community resilience and improve outcomes.

15.
Plant Direct ; 2(6): e00065, 2018 Jun.
Article in English | MEDLINE | ID: mdl-31245728

ABSTRACT

Rhizomes facilitate the wintering and vegetative propagation of many perennial grasses. Sorghum halepense (johnsongrass) is an aggressive perennial grass that relies on a robust rhizome system to persist through winters and reproduce asexually from its rootstock nodes. This study aimed to sequence and assemble expressed transcripts within the johnsongrass rhizome. A de novo transcriptome assembly was generated from a single johnsongrass rhizome meristem tissue sample. A total of 141,176 probable protein-coding sequences from the assembly were identified and assigned gene ontology terms using Blast2GO. Estimated expression analysis and BLAST results were used to reduce the assembly to 64,447 high-confidence sequences. The johnsongrass assembly was compared to Sorghum bicolor, a related nonrhizomatous species, along with an assembly of similar rhizome tissue from the perennial grain crop Thinopyrum intermedium. The presence/absence analysis yielded a set of 98 expressed johnsongrass contigs that are likely associated with rhizome development.

16.
Genome ; 60(6): 530-536, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28235186

ABSTRACT

Simple sequence repeat technology based on expressed sequence tag (EST-SSR) is a useful genomic tool for genome mapping, characterizing plant species relationships, elucidating genome evolution, and tracing genes on alien chromosome segments. EST-SSR primers developed from three perennial diploid species of Triticeae, Pseudoroegneria spicata (Pursh) Á. Löve (having St genome), Thinopyrum bessarabicum (Savul. & Rayss) Á. Löve (Jb = Eb = J), and Thinopyrum elongatum (Host) D.R. Dewey (Je = Ee = E), were used to produce amplicons in these three species to (i) assess relative transferability, (ii) identify polymorphic species-specific markers, and (iii) determine genome relationships among the three species. Because of the close relationship between Jb and Je genomes, EST-SSR primers derived from Th. bessarabicum and Th. elongatum had greater transferability to each other than those derived from the St-genome P. spicata. A large number of polymorphic species- and genome-specific EST-SSR amplicons were identified that will be used for construction of genetic maps of these diploid species, and tracing economically useful genes in breeding or gene transfer programs in various species of Triticeae.


Subject(s)
DNA Primers/genetics , Elymus/genetics , Microsatellite Repeats/genetics , Chromosome Mapping/methods , Chromosomes, Plant/genetics , Diploidy , Expressed Sequence Tags , Genome, Plant/genetics , Phylogeny
17.
J Nucl Med ; 58(5): 717-722, 2017 05.
Article in English | MEDLINE | ID: mdl-27738010

ABSTRACT

The optimal management of radioactive iodine (RAI) treatment in patients with metastatic thyroid cancer (TC) is still a matter of debate. Methods: We retrospectively analyzed 352 patients with RAI-avid metastatic well-differentiated TC treated with 131I by an empiric fixed activity of 3.7 GBq at Gustave Roussy (GR, n = 231) or by personalized activity (2.7-18.6 GBq) based on whole-body/-blood clearance (WB/BC) dosimetry at Memorial Sloan Kettering Cancer Center (MSKCC, n = 121). The primary endpoint was to compare overall survival (OS) in the 2 groups of patients by log-rank test. Results: Patients received a median cumulative activity of 14.8 GBq at GR and 24.2 GBq at MSKCC (P < 0.0001). The median follow-up after the diagnosis of metastases was 7.2 y (0.4-31 y). Five-year OS was 86.8% and 78.8% for patients treated at GR and at MSKCC, respectively (P < 0.01). However, there was no statistical difference in OS after correction for sex, age at the diagnosis of distant metastases, metastases site, and metastases extension between the 2 centers (P = 0.16). OS at 5 y was 96% and 96% for patients younger than 40 y with micrometastases, 70% and 65% for patients older than 40 y with macrometastases or multiple metastases, and 92% and 87% for younger patients with macrometastases or older patients with micrometastases treated at GR and MSKCC, respectively (P = not significant). Conclusion: Routine use of WB/BC dosimetry without lesional dosimetry provided no OS advantage when compared with empiric fixed RAI activity in the management of thyroid cancer patients with RAI-avid distant metastases.


Subject(s)
Iodine Radioisotopes/therapeutic use , Radiation Exposure/statistics & numerical data , Radiotherapy, Conformal/mortality , Thyroid Neoplasms/mortality , Thyroid Neoplasms/radiotherapy , Whole-Body Counting/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Dose-Response Relationship, Radiation , France/epidemiology , Humans , Male , Metabolic Clearance Rate , Middle Aged , Neoplasm Metastasis , Prevalence , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome , Whole-Body Counting/methods , Young Adult
18.
Theor Appl Genet ; 130(1): 137-150, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27738715

ABSTRACT

KEY MESSAGE: Development of the first consensus genetic map of intermediate wheatgrass gives insight into the genome and tools for molecular breeding. Intermediate wheatgrass (Thinopyrum intermedium) has been identified as a candidate for domestication and improvement as a perennial grain, forage, and biofuel crop and is actively being improved by several breeding programs. To accelerate this process using genomics-assisted breeding, efficient genotyping methods and genetic marker reference maps are needed. We present here the first consensus genetic map for intermediate wheatgrass (IWG), which confirms the species' allohexaploid nature (2n = 6x = 42) and homology to Triticeae genomes. Genotyping-by-sequencing was used to identify markers that fit expected segregation ratios and construct genetic maps for 13 heterogeneous parents of seven full-sib families. These maps were then integrated using a linear programming method to produce a consensus map with 21 linkage groups containing 10,029 markers, 3601 of which were present in at least two populations. Each of the 21 linkage groups contained between 237 and 683 markers, cumulatively covering 5061 cM (2891 cM--Kosambi) with an average distance of 0.5 cM between each pair of markers. Through mapping the sequence tags to the diploid (2n = 2x = 14) barley reference genome, we observed high colinearity and synteny between these genomes, with three homoeologous IWG chromosomes corresponding to each of the seven barley chromosomes, and mapped translocations that are known in the Triticeae. The consensus map is a valuable tool for wheat breeders to map important disease-resistance genes within intermediate wheatgrass. These genomic tools can help lead to rapid improvement of IWG and development of high-yielding cultivars of this perennial grain that would facilitate the sustainable intensification of agricultural systems.


Subject(s)
Agropyron/genetics , Chromosome Mapping , Genome, Plant , Genotyping Techniques , Gene Library , Genetic Linkage , Genetic Markers , Genotype , Hordeum/genetics , Plant Breeding , Polyploidy , Synteny
19.
Genome ; 58(2): 63-70, 2015 Feb.
Article in English | MEDLINE | ID: mdl-26000870

ABSTRACT

Intermediate wheatgrass (Thinopyrum intermedium (Host) Barkworth & D.R. Dewey), a segmental autoallohexaploid (2n = 6x = 42), is not only an important forage crop but also a valuable gene reservoir for wheat (Triticum aestivum L.) improvement. Throughout the scientific literature, there continues to be disagreement as to the origin of the different genomes in intermediate wheatgrass. Genotypic data obtained from newly developed EST-SSR primers derived from the putative progenitor diploid species Pseudoroegneria spicata (Pursh) Á. Löve (St genome), Thinopyrum bessarabicum (Savul. & Rayss) Á. Löve (J = J(b) = E(b)), and Thinopyrum elongatum (Host) D. Dewey (E = J(e) = E(e)) indicate that the V genome of Dasypyrum (Coss. & Durieu) T. Durand is not one of the three genomes in intermediate wheatgrass. Based on all available information in the literature and findings in this study, the genomic designation of intermediate wheatgrass should be changed to J(vs)J(r)St, where J(vs) and J(r) represent ancestral genomes of present-day J(b) of Th. bessarabicum and J(e) of Th. elongatum, with J(vs) being more ancient. Furthermore, the information suggests that the St genome in intermediate wheatgrass is most similar to the present-day St found in diploid species of Pseudoroegneria from Eurasia.


Subject(s)
Evolution, Molecular , Expressed Sequence Tags , Genome, Plant , Microsatellite Repeats , Poaceae/genetics , Cluster Analysis , DNA, Plant/genetics , Diploidy , Genetic Markers , Genotype , Poaceae/classification , Sequence Analysis, DNA
20.
Nature ; 518(7537): 74-6, 2015 Feb 05.
Article in English | MEDLINE | ID: mdl-25561176

ABSTRACT

Quasars have long been known to be variable sources at all wavelengths. Their optical variability is stochastic and can be due to a variety of physical mechanisms; it is also well-described statistically in terms of a damped random walk model. The recent availability of large collections of astronomical time series of flux measurements (light curves) offers new data sets for a systematic exploration of quasar variability. Here we report the detection of a strong, smooth periodic signal in the optical variability of the quasar PG 1302-102 with a mean observed period of 1,884 ± 88 days. It was identified in a search for periodic variability in a data set of light curves for 247,000 known, spectroscopically confirmed quasars with a temporal baseline of about 9 years. Although the interpretation of this phenomenon is still uncertain, the most plausible mechanisms involve a binary system of two supermassive black holes with a subparsec separation. Such systems are an expected consequence of galaxy mergers and can provide important constraints on models of galaxy formation and evolution.

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