Elements and evolutionary determinants of genomic divergence between paired primary and metastatic tumors

Can metastatic-primary (M-P) genomic divergence measured from next generation sequencing reveal the natural history of metastatic dissemination? This remains an open question of utmost importance in facilitating a deeper understanding of metastatic progression, and thereby, improving its prevention. Here, we utilize mathematical and computational modeling to tackle this question as well as to provide a framework that illuminates the fundamental elements and evolutionary determinants of M-P divergence. Our framework facilitates the integration of sequencing detectability of somatic variants, and hence, paves the way towards bridging the measurable between-tumor heterogeneity with analytical modeling and interpretability. We show that the number of somatic variants of the metastatic seeding cell that are experimentally undetectable in the primary tumor, can be characterized as the path of the phylogenetic tree from the last appearing variant of the seeding cell back to the most recent detectable variant. We find that the expected length of this path is principally determined by the decay in detectability of the variants along the seeding cell’s lineage; and thus, exhibits a significant dependence on the underlying tumor growth dynamics. A striking implication of this fact, is that dissemination from an advanced detectable subclone of the primary tumor can lead to an abrupt drop in the expected measurable M-P divergence, thereby breaking the previously assumed monotonic relation between seeding time and M-P divergence. This is emphatically verified by our single cell-based spatial tumor growth simulation, where we find that M-P divergence exhibits a non-monotonic relationship with seeding time when the primary tumor grows under branched and linear evolution. On the other hand, a monotonic relationship holds when we condition on the dynamics of progressive diversification, or by restricting the seeding cells to always originate from undetectable subclones. Our results highlight the fact that a precise understanding of tumor growth dynamics is the sine qua non for exploiting M-P divergence to reconstruct the chronology of metastatic dissemination. The quantitative models presented here enable further careful evaluation of M-P divergence in association with crucial evolutionary and sequencing parameters.

ASPECTS CONCERNING PEANUTS CROPS ON SANDY SOILS IN SOUTHERN OLTENIA

"For the capitalization of the climate and soil conditions for the sandy soil region in Southern Oltenia by cultivating peanuts it is necessary to use varieties with large production abilities and proper technology for the crops. In view of its cultivation on south Oltenia sandy soils, there were carried out in the period 2004-2006, at the Plants Crops Research and Development Station on Sandy Soils Dabuleni, experiments have been set regarding aspects such as: the optimal seeding period, the recommendation varieties with high yield potential and balanced composition. The research was conducted under irrigation conditions, in a three-year rotation of wheat, peanut, maize. Along with erect growth type varieties, known for their short vegetation period, rising and creeping growth type varieties can also be used; these varieties have a great production potential in our country`s conditions. Establishing the proper time for seeding is espe since sandy soils are heating quickly but are also cooling quickly, the best seeding time is between the end of April- the beginning of May, depending on the date when the seeding depth has a steady temperature, minimal required for the seed to germinate."

Elements and Evolutionary Determinants of Genomic Divergence Between Paired Primary and Metastatic Tumors

ABSTRACTCan metastatic-primary (M-P) genomic divergence measured from next generation sequencing reveal the natural history of metastatic dissemination? This remains an open question of utmost importance in facilitating a deeper understanding of metastatic progression, and thereby, improving its prevention. Here, we utilize mathematical and computational modeling to tackle this question as well as to provide a framework that illuminates the fundamental elements and evolutionary determinants of M-P divergence. Our framework facilitates the integration of sequencing detectability of somatic variants, and hence, paves the way towards bridging the measurable between-tumor heterogeneity with analytical modeling and interpretability. We show that the number of somatic variants of the metastatic seeding cell that are experimentally undetectable in the primary tumor, can be characterized as the path of the phylogenetic tree from the last appearing variant of the seeding cell back to the most recent detectable variant. We find that the expected length of this path is principally determined by the decay in detectability of the variants along the seeding cell’s lineage; and thus, exhibits a significant dependence on the underlying tumor growth dynamics. A striking implication of this fact, is that dissemination from an advanced detectable subclone of the primary tumor can lead to an abrupt drop in the expected measurable M-P divergence, thereby breaking the previously assumed monotonic relation between seeding time and M-P divergence. This is emphatically verified by our single cell-based spatial tumor growth simulation, where we find that M-P divergence exhibits a non-monotonic relationship with seeding time when the primary tumor grows under branched and linear evolution. On the other hand, a monotonic relationship holds when we condition on the dynamics of progressive diversification, or by restricting the seeding cells to always originate from undetectable subclones. Our results highlight the fact that a precise understanding of tumor growth dynamics is the sine qua non for exploiting M-P divergence to reconstruct the chronology of metastatic dissemination. The quantitative models presented here enable further careful evaluation of M-P divergence in association with crucial evolutionary and sequencing parameters.Graphical AbstractHighlightsDepth of most recent detectable variant characterizes Metastatic-Primary divergenceDecay in variant detectability determines the expected M-P divergenceDissemination from late detectable subclone leads to an abrupt drop in M-P divergenceSpatial model verifies growth mode governs M-P divergence dependency on seeding time

Comparative Severity Analysis of Asian Soybean Rust in Soybean Farms Sown in December and February in Mato Grosso, 2018/19 Growing Season

The objective of this work was to compare the leaflet severity of Asian soybean rust in farms sown in December and February in the state of Mato Grosso. In the survey, 28 fields were sampled in 14 counties in the North, West and South regions of the state. A total of 40 leaflets were collected per plot, in randomized treatments with four replication and three crop phenological stages. Leaflet severity was assessed according to a diagrammatic scale. The data were expressed as leaflet severity, submitted to linear regression analysis, calculated the area under the disease progress curve (AUDPC) considering the three phenological stages sampled, and the means compared by the Tukey’s test. Leaflet severity was significantly higher in the fields sown in December than in February, as well the number of fungicides sprayings. Our results indicate that the proposed change in seeding time from December to February can be implemented by significantly reducing risks and in compliance with the principles of IN 002/2015.

Seeding Time Affects Bermudagrass Establishment in the Transition Zone Environment

Bermudagrass is becoming increasingly popular in the Mediterranean transition zone of Europe for establishing new sports and recreational turfgrasses. In these regions, the quality and winter hardiness of bermudagrass turf is influenced by the establishment. It has been demonstrated that an early establishment of bermudagrass results in a longer growing season with a greater stolon and rhizome production, which favors cold hardiness and a quicker green up after the first winter. Dormant seeding is reported to be beneficial for an early establishment. However, the response to early seeding depends on local environmental conditions. A field study was conducted in northeastern Italy during spring 2018 and 2019. Four bermudagrass cultivars (“Transcontinental”, “Jackpot”, “SR9554”, and “La Paloma”) were compared under three seeding times from March to May to evaluate whether early spring seeding allows anticipating the establishment of bermudagrass compared with late spring seeding which generally benefits of better temperatures for germination and growth. The number of days from seeding to the emergence and from seeding to the full establishment were determined, and the number of seedlings was counted in each plot. Late March seeding assured the earliest establishment. This result could be due to the quick lateral spreading of seedlings as the emergence occurred about 15 days later in the late March seeding compared with April and May seedings. Results also displayed that the speed of establishment was positively related to the number of emerged seedlings. “Transcontinental”, “Jackpot”, and “SR9554” performed similarly, whereas “Jackpot” showed a slower establishment.

Variation of Seed Components According to Sowing Date and Variety of Sprout Soybean in the Mid-Northern Region in Korea

Objectives Soybean(Glycine max L.) sprouts are widely used in Korea as main and sub materials in various dishes such as stew, ‘Bibimbap’, ‘Haejangguk’, and seasoned bean sprouts. The purpose of this study was to investigate the variations of general compositions and antioxidant properties in sprout soybean seed according to varieties and sowing dates in the central region of Korea, and to utilize the basic data for stable supply of raw soybeans in response to the changes in production environment. Methods Sprout soybean were produced from the experimental field of Department of Central Area Crop Science of the National Institute of Crop Science (NICS), located in Suwon, Gyeonggi-do. The sowing dates were on June 30th, July 10th and July 20th in 2018 respectively. Planting and cultivation were followed by standard soybean cultivation methods of NICS. The harvested raw sprout soybean seeds at each seeding time were ground for the general compositions analysis. Antioxidant capacity was measured with total polyphenol contents and DPPH and ABTS radical scavenging activity. Results Approximate compositions of sprout soybean seed showed significant differences according to varieties and sowing date. Moisture, crude fat, and crude protein were the highest in the first sowing date, and tended to decrease in most varieties as the seeding time was delayed, whereas carbohydrate content increased at late sowing time. DPPH radical scavenging activity showed the highest tendency in second seeding. ABTS radical scavenging activity decreased as the seeding time was delayed in the most varieties, but ‘Soyeon’ and ‘Aram’ increased in second seeding. Conclusions Taken the above results together, the significant differences in the approximate compositions and antioxidant capacities recognized due to varieties and sowing dates. Therefore, it was considered that the selection of proper varieties and sowing date should be considered carefully when growing raw sprout soybean grains in the central region in Korea. Funding Sources This study was supported by the RDA Agenda Project (project number: PJ01251603).