Biological age is typically estimated using biomarkers whose states have been observed to correlate with chronological age. A persistent limitation of such aging clocks is that it is difficult to establish how the biomarker states are related to the mechanisms of aging. Somatic mutations could potentially form the basis for a more fundamental aging clock since the mutations are both markers and drivers of aging and have a natural timescale. Cell lineage trees inferred from these mutations reflect the somatic evolutionary process, and thus, it has been conjectured, the aging status of the body. Such a timer has been impractical thus far, however, because detection of somatic variants in single cells presents a significant technological challenge. Here, we show that somatic mutations detected using single-cell RNA sequencing (scRNA-seq) from thousands of cells can be used to construct a cell lineage tree whose structure correlates with chronological age. De novo single-nucleotide variants (SNVs) are detected in human peripheral blood mononuclear cells using a modified protocol. A default model based on penalized multiple regression of chronological age on 31 metrics characterizing the phylogenetic tree gives a Pearson correlation of 0.81 and a median absolute error of ~4 years between predicted and chronological ages. Testing of the model on a public scRNA-seq dataset yields a Pearson correlation of 0.85. In addition, cell tree age predictions are found to be better predictors of certain clinical biomarkers than chronological age alone, for instance glucose, albumin levels, and leukocyte count. The geometry of the cell lineage tree records the structure of somatic evolution in the individual and represents a new modality of aging timer. In addition to providing a numerical estimate of "cell tree age," it unveils a temporal history of the aging process, revealing how clonal structure evolves over life span. Cell Tree Rings complements existing aging clocks and may help reduce the current uncertainty in the assessment of geroprotective trials.

• MeSH
• biologické markery MeSH
• dlouhověkost MeSH
• fylogeneze MeSH
• leukocyty mononukleární * MeSH
• lidé MeSH
• stárnutí * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Large genomic rearrangements (LGR) represent substantial proportion of pathogenic mutations in the BRCA1 gene, whereas the frequency of rearrangements in the BRCA2 gene is low in many populations. We screened for LGRs in BRCA1 and BRCA2 genes by multiplex ligation-dependent probe amplification (MLPA) in 521 unrelated patients negative for BRCA1/2 point mutations selected from 655 Czech high-risk breast and/or ovarian cancer patients. Besides long range PCR, a chromosome 17-specific oligonucleotide-based array comparative genomic hybridization (aCGH) was used for accurate location of deletions. We identified 14 patients carrying 8 different LGRs in BRCA1 that accounted for 12.3% of all pathogenic BRCA1 mutations. No LGRs were detected in the BRCA2 gene. In a subgroup of 239 patients from high-risk families, we found 12 LGRs (5.0%), whereas two LGRs were revealed in a subgroup of 282 non-familial cancer cases (0.7%). Five LGRs (deletion of exons 1-17, 5-10, 13-19, 18-22 and 21-24) were novel; two LGRs (deletion of exons 5-14 and 21-22) belong to the already described Czech-specific mutations; one LGR (deletion of exons 1-2) was reported from several countries. The deletions of exons 1-17 and 5-14, identified each in four families, represented Czech founder mutations. The present study indicates that screening for LGRs in BRCA1 should include patients from breast or ovarian cancer families as well as high-risk patients with non-familial cancer, in particular cases with early-onset breast or ovarian cancer. On the contrary, our analyses do not support the need to screen for LGRs in the BRCA2 gene. Implementation of chromosome-specific aCGH could markedly facilitate the design of primers for amplification and sequence analysis of junction fragments, especially in deletions overlapping gene boundaries.

• MeSH
• bodová mutace MeSH
• body zlomu chromozomu MeSH
• dospělí MeSH
• exony MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• genová přestavba MeSH
• haplotypy MeSH
• hodnocení rizik MeSH
• introny MeSH
• inzerční mutageneze MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• mutační analýza DNA MeSH
• nádory prsu genetika   MeSH
• nádory vaječníků genetika   MeSH
• plošný screening metody   MeSH
• polymerázová řetězová reakce MeSH
• prediktivní hodnota testů MeSH
• protein BRCA1 MeSH
• protein BRCA2 genetika   MeSH
• rizikové faktory MeSH
• rodokmen MeSH
• sekvence nukleotidů MeSH
• sekvenční delece MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• hodnocení rizik MeSH
• lidé MeSH
• modely genetické MeSH
• mutace MeSH
• nádory prsu genetika   MeSH
• odds ratio MeSH
• plošný screening metody   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• regulace genové exprese u nádorů MeSH
• rizikové faktory MeSH
• rodokmen MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

Genetic association studies in forest trees would greatly benefit from information on the response of trees to environmental stressors over time, which can be provided by dendroecological analysis. Here, we jointly analysed dendroecological and genetic data of surviving silver fir trees to explore the genetic basis of their response to the iconic stress episode of the 1970s and 1980s that led to large-scale forest dieback in Central Europe and has been attributed to air pollution. Specifically, we derived dendrophenotypic measures from 190 trees in the Bavarian Forest that characterize the resistance, resilience and recovery during this growth depression, and in the drought year in 1976. By focusing on relative growth changes of trees and by standardizing the dendrophenotypes within stands, we accounted for variation introduced by micro- and macroscale environmental differences. We associated the dendrophenotypes with single nucleotide polymorphisms (SNPs) in candidate genes using general linear models (GLMs) and the machine learning algorithm random forest with subsequent feature selection. Most trees at our study sites experienced a severe growth decline from 1974 until the mid-1980s with minimum values during the drought year. Fifteen genes were associated with the dendrophenotypes, including genes linked to photosynthesis and drought stress. With our study, we show that dendrophenotypes can be a powerful resource for genetic association studies that permit to account for micro- and macroenvironmental variation when data are derived from natural populations. We call for a wider collaboration of dendroecologists and forest geneticists to integrate individual tree-level dendrophenotypes in genetic association studies.

• MeSH
• ekologie MeSH
• fyziologická adaptace genetika   MeSH
• fyziologický stres genetika   MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• jedle genetika   růst a vývoj   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• období sucha MeSH
• podnebí MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In coppice-with-standards, once a common type of management in Central European lowland forests, selected trees (standards) were left to grow mature among the regularly harvested coppice stools to obtain construction wood. After the underwood was harvested, the forest canopy opened rapidly, giving standard trees an opportunity to benefit from reduced competition. Although this silvicultural system virtually disappeared after WWII, historical management cycles can still be traced in the tree-rings of remaining standards. Our research aims at answering the question whether tree-ring series of standard trees can be used to reconstruct past management practices. The study was carried out on 117 oak standard trees from five sites situated in formerly coppiced calcareous oak-hornbeam and acidophilous oak forests in the Bohemian Karst Protected Landscape Area, Czech Republic. The evaluation was based on the analysis of growth releases representing the response of the standards to coppicing events, and comparison to the archival records of coppice events. Our results showed that coppicing events can be successfully detected by tree-ring analysis, although there are some limitations. Altogether 241 releases were identified (49% of major releases). Large number of releases could be related to historical records, with the major ones giving better results. The overall probability of correct detection (positive predictive power) was 58%, ranging from 50 to 67%, probability for major releases was 78%, ranging from 63 to 100% for different sites. The ability of individual trees to mirror past coppice events was significantly affected by competition from neighboring trees (their number and the sum of distance-weighted basal areas). A dendro-ecological approach to the study of forest management history can serve as an input for current attempts of coppice reintroduction and for conservation purposes.

• MeSH
• dub (rod) chemie   růst a vývoj   MeSH
• ekosystém * MeSH
• lesy MeSH
• zachování přírodních zdrojů * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Trees with hollows are key features sustaining biodiversity in wooded landscapes. They host rich assemblages of often highly specialised organisms. Hollow trees, however, have become rare and localised in Europe. Many of the associated biota is thus declining or endangered. The challenge of its conservation, therefore, is to safeguard the presence of hollow trees in sufficient numbers. Populations of numerous species associated with tree hollows and dead wood are often found in habitats that were formed by formerly common traditional silvicultural practices such as coppicing, pollarding or pasture. Although it has been occasionally mentioned that such practices increase the formation of hollows and the availability of often sun-exposed dead wood, their effect has never been quantified. Our study examined the hollow incidence in pollard and non-pollard (unmanaged) willows and the effect of pollarding on incremental growth rate by tree ring analysis. The probability of hollow occurrence was substantially higher in pollard than in non-pollard trees. Young pollards, especially, form hollows much more often than non-pollards; for instance, in trees of 50 cm DBH, the probability of hollow ocurrence was ∼0.75 in pollards, but only ∼0.3 in non-pollards. No difference in growth rate was found. Pollarding thus leads to the rapid formation of tree hollows, a habitat usually associated with old trees. It is therefore potentially a very important tool in the restoration of saproxylic habitats and conservation of hollow-dependent fauna. If applied along e.g. roads and watercourses, pollarding could also be used to increase landscape connectivity for saproxylic organisms. In reserves where pollarding was formerly practiced, its restoration would be necessary to prevent loss of saproxylic biodiversity. Our results point to the importance of active management measures for maintaining availability, and spatial and temporal continuity of deadwood microhabitats.

• MeSH
• biodiverzita * MeSH
• dřevo fyziologie   MeSH
• lesnictví metody   MeSH
• pravděpodobnost MeSH
• Salix anatomie a histologie   růst a vývoj   fyziologie   MeSH
• stromy anatomie a histologie   růst a vývoj   fyziologie   MeSH
• zachování přírodních zdrojů * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-continental tree-ring width database from sites where both dead and living trees were sampled (2970 dead and 4224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca. 84% of the mortality events. The extent and duration of these reductions were highly variable (1-100 years in 96% of events) due to the complex interactions among study species and the source(s) of mortality. Strong and long-lasting declines were found for gymnosperms, shade- and drought-tolerant species, and trees that died from competition. Angiosperms and trees that died due to biotic attacks (especially bark-beetles) typically showed relatively small and short-term growth reductions. Our analysis did not highlight any universal trade-off between early growth and tree longevity within a species, although this result may also reflect high variability in sampling design among sites. The intersite and interspecific variability in growth patterns before mortality provides valuable information on the nature of the mortality process, which is consistent with our understanding of the physiological mechanisms leading to mortality. Abrupt changes in growth immediately before death can be associated with generalized hydraulic failure and/or bark-beetle attack, while long-term decrease in growth may be associated with a gradual decline in hydraulic performance coupled with depletion in carbon reserves. Our results imply that growth-based mortality algorithms may be a powerful tool for predicting gymnosperm mortality induced by chronic stress, but not necessarily so for angiosperms and in case of intense drought or bark-beetle outbreaks.

• MeSH
• brouci * MeSH
• fyziologický stres MeSH
• období sucha * MeSH
• stromy růst a vývoj   MeSH
• uhlík MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.

• MeSH
• dějiny středověku MeSH
• epidemický výskyt choroby dějiny   MeSH
• lidé MeSH
• mor epidemiologie   přenos   MeSH
• podnebí * MeSH
• Check Tag
• dějiny středověku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: The detailed knowledge of plant anatomical characters and their variation among closely related taxa is key to understanding their evolution and function. We examined anatomical variation in 46 herbaceous taxa from the subfamily Campanuloideae (Campanulaceae) to link this information with their phylogeny, ecology and comparative material of 56 woody tropical taxa from the subfamily Lobelioideae. The species studied covered major environmental gradients from Mediterranean to Arctic zones, allowing us to test hypotheses on the evolution of anatomical structure in relation to plant competitive ability and ecological preferences. METHODOLOGY/PRINCIPAL FINDINGS: To understand the evolution of anatomical diversity, we reconstructed the phylogeny of studied species from nucleotide sequences and examined the distribution of anatomical characters on the resulting phylogenetic tree. Redundancy analysis, with phylogenetic corrections, was used to separate the evolutionary inertia from the adaptation to the environment. A large anatomical diversity exists within the Campanuloideae. Traits connected with the quality of fibres were the most congruent with phylogeny, and the Rapunculus 2 ("phyteumoid") clade was especially distinguished by a number of characters (absence of fibres, pervasive parenchyma, type of rays) from two other clades (Campanula s. str. and Rapunculus 1) characterized by the dominance of fibres and the absence of parenchyma. Septate fibres are an exclusive trait in the Lobelioideae, separating it clearly from the Campanuloideae where annual rings, pervasive parenchyma and crystals in the phellem are characteristic features. CONCLUSIONS/SIGNIFICANCE: Despite clear phylogenetic inertia in the anatomical features studied, the ecological attributes and plant height had a significant effect on anatomical divergence. From all three evolutionary clades, the taller species converged towards similar anatomical structure, characterized by a smaller number of early wood vessels of large diameter, thinner cell-walls and alternate intervessel pits, while the opposite trend was found in small Arctic and alpine taxa. This supports the existing generalization that narrower vessels allow plants to grow in colder places where they can avoid freezing-induced embolism, while taller plants have wider vessels to minimize hydraulic resistance with their greater path lengths.

• MeSH
• Bayesova věta MeSH
• biologická adaptace genetika   fyziologie   MeSH
• biologická evoluce * MeSH
• Campanulaceae anatomie a histologie   MeSH
• druhová specificita MeSH
• ekosystém * MeSH
• fylogeneze * MeSH
• modely genetické MeSH
• stonky rostlin anatomie a histologie   MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH