The MMS22L-TONSL complex mediates recovery from replication stress and homologous recombination

Genome integrity is jeopardized each time DNA replication forks stall or collapse. Here we report the identification of a complex composed of MMS22L (C6ORF167) and TONSL (NFKBIL2) that participates in the recovery from replication stress. MMS22L and TONSL are homologous to yeast Mms22 and plant Tonsoku/Brushy1, respectively. MMS22L-TONSL accumulates at regions of ssDNA associated with distressed replication forks or at processed DNA breaks, and its depletion results in high levels of endogenous DNA double-strand breaks caused by an inability to complete DNA synthesis after replication fork collapse. Moreover, cells depleted of MMS22L are highly sensitive to camptothecin,?a topoisomerase I poison that impairs DNA replication progression. Finally, MMS22L and TONSL are necessary for the efficient formation of RAD51 foci after DNA damage, and their depletion impairs homologous recombination. These results indicate that MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks.     

Seasonal Variation in Seed Dispersal by Tamarins Alters Seed Rain in a Secondary Rain Forest

Reduced dispersal of large seeds into degraded areas is one of the major factors limiting rain forest regeneration, as many seed dispersers capable of transporting large seeds avoid these sites with a limited forest cover. However, the small size of tamarins allows them to use small trees, and hence to disperse seeds into young secondary forests. Seasonal variations in diet and home range use might modify their contribution to forest regeneration through an impact on the seed rain. For a 2-yr period, we followed a mixed-species group of tamarins in Peru to determine how their role as seed dispersers in a 9-yr-old secondary-growth forest varied across seasons. These tamarins dispersed small to large seeds of 166 tree species, 63 of which were into a degraded area. Tamarins’ efficiency in dispersing seeds from primary to secondary forest varied across seasons. During the late wet season, high dietary diversity and long forays in secondary forest allowed them to disperse large seeds involved in later stages of regeneration. This occurred precisely when tamarins spent a more equal amount of time eating a high diversity of fruit species in primary forest and pioneer species in secondary forest. We hypothesized that well-balanced fruit availability induced the movement of seed dispersers between these 2 habitats. The noteworthy number of large-seeded plant species dispersed by such small primates suggests that tamarins play an important, but previously neglected, role in the regeneration and maintenance of forest structure.     

Complex patterns of hybridization between exotic and native North American poplar species

? Premise of the study: Poplars and their hybrids are seen as important candidates for bioenergy initiatives. However, many concerns have been raised about large-scale plantations of new poplar cultivars. The deployment of such plants with novel traits brings the risk of potential spread of novel genome regions (including exotic genes, transgenes, or other heritable modifications) into natural populations of related species. The possibility of introgression is especially high in poplars because reproductive barriers between species are weak. Knowledge of the frequency of hybridization between cultivated trees and natural populations is one important step in the risk-assessment process. ? Methods: We studied the rate of spontaneous hybridization from two sexually mature poplar plantations into adjacent natural populations of Populus deltoides and P. balsamifera. The two plantations, both in eastern Canada, contain many different complex hybrid clones with components from exotic species, mostly P. nigra, P. trichocarpa, and P. maximowiczii. We analyzed 12 species-specific single nucleotide polymorphisms from six different genes in 5373 offspring sampled from the natural populations. ? Results: Contributions from all three exotics were found in the offspring, confirming low reproductive barriers among poplar species in these sections. The frequency of hybrid offspring varied among pollen donors, recipient populations, and years. ? Conclusions: The remarkably high rate of hybridization that was found in the smallest natural population sampled suggests that small peripheral populations carry a higher risk of introgression. These results could be used as a starting point for developing regulatory guidelines for the introduction of plants with novel traits.     

Influence of Density and Climate on Population Dynamics of a Large Herbivore Under Harsh Environmental Conditions

ABSTRACT Dynamics of herbivore populations can be influenced both by density-dependent processes and climate. We used age-at-harvest data for adult female white-tailed deer (Odocoileus virginianus) collected over 23 years to estimate survival and reproduction by age class and to identify effects of environmental factors. The study population was located on Anticosti Island (QC, Canada), at the northern limit of the species' range; the population was at high density, and the landscape had scarce forage and abundant snow during winter. Despite severe environmental conditions, population growth apparently increased during the study; adult survival was similar to other populations, although reproduction appeared lower. Winter severity was not related to survival, but density affected adult female survival. Density at estrus was the main factor influencing reproduction of 2- and 3–4-year-olds and also affected reproduction of prime-aged females (5–9-yr-olds), but not of older females. Reproductive rate of younger females was influenced by environmental conditions in autumn, such as high density or snow conditions that limited forage availability. Reproductive success of 5–9- and ≥10-year-old females appeared dependent on spring conditions favoring high-quality forage, probably through effects on neonatal survival. Relative to other studies on northern ungulates, demographic processes in our study appeared to be more affected by autumn and spring climate, in addition to population density, than by winter climate. We thus propose that population density, as well as autumn and spring climate, should be considered in management strategies. Harvest data offered a unique opportunity to study forest ungulates, for which individual monitoring is rarely possible.     

Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study

Introduction  

The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares.     

Autotransporter-encoding sequences are phylogenetically distributed among Escherichia coli clinical isolates and reference strains

Autotransporters are secreted bacterial proteins exhibiting diverse virulence functions. Various autotransporters have been identified among Escherichia coli associated with intestinal or extraintestinal infections; however, the specific distribution of autotransporter sequences among a diversity of E. coli strains has not been investigated. We have validated the use of a multiplex PCR assay to screen for the presence of autotransporter sequences. Herein, we determined the presence of 13 autotransporter sequences and five allelic variants of antigen 43 (Ag43) among 491 E. coli isolates from human urinary tract infections, diarrheagenic E. coli, and avian pathogenic E. coli (APEC) and E. coli reference strains belonging to the ECOR collection. Clinical isolates were also classified into established phylogenetic groups. The results indicated that Ag43 alleles were significantly associated with clinical isolates (93%) compared to commensal isolates (56%) and that agn43K12 was the most common and widely distributed allele. agn43 allelic variants were also phylogenetically distributed. Sequences encoding espC, espP, and sepA and agn43 alleles EDL933 and RS218 were significantly associated with diarrheagenic E. coli strains compared to other groups. tsh was highly associated with APEC strains, whereas sat was absent from APEC. vat, sat, and pic were associated with urinary tract isolates and were identified predominantly in isolates belonging to either group B2 or D of the phylogenetic groups based on the ECOR strain collection. Overall, the results indicate that specific autotransporter sequences are associated with the source and/or phylogenetic background of strains and suggest that, in some cases, autotransporter gene profiles may be useful for comparative analysis of E. coli strains from clinical, food, and environmental sources.     

The checkpoint Saccharomyces cerevisiae Rad9 protein contains a tandem tudor domain that recognizes DNA

DNA damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. At the site of DNA damage, ‘mediator’ proteins are in charge of recruiting ‘signal transducers’ to molecules ‘sensing’ the damage. Budding yeast Rad9, fission yeast Crb2 and metazoan 53BP1 are presented as mediators involved in the activation of checkpoint kinases. Here we show that, despite low sequence conservation, Rad9 exhibits a tandem tudor domain structurally close to those found in human/mouse 53BP1 and fission yeast Crb2. Moreover, this region is important for the resistance of Saccharomyces cerevisiae to different genotoxic stresses. It does not mediate direct binding to a histone H3 peptide dimethylated on K79, nor to a histone H4 peptide dimethylated on lysine 20, as was demonstrated for 53BP1. However, the tandem tudor region of Rad9 directly interacts with single-stranded DNA and double-stranded DNAs of various lengths and sequences through a positively charged region absent from 53BP1 and Crb2 but present in several yeast Rad9 homologs. Our results argue that the tandem tudor domains of Rad9, Crb2 and 53BP1 mediate chromatin binding next to double-strand breaks. However, their modes of chromatin recognition are different, suggesting that the corresponding interactions are differently regulated.     

Visualization of ribonucleotide reductase catalytic oxidation establishes thioredoxins as its major reductants in yeast

Thioredoxins and/or glutaredoxins assist ribonucleotide reductase, and other such enzymes that require disulfide bond reduction during their catalytic cycle. In Saccharomyces cerevisiae, the presence of either pathway is essential but which of these pathways operates in ribonucleotide reductase reduction and how this function contributes to the pathways' essential nature have not been definitively established. We have identified two in vivo redox forms of the S. cerevisiae ribonucleotide reductase R1 subunit, which correspond to catalytically reduced or oxidized enzymes. Cells lacking thioredoxins, which exhibit an elongated S phase, accumulate R1 in its oxidized form and also contain significantly decreased deoxyribonucleotide levels during the S phase. Overexpressing R1 in these cells increases both the amount of the R1 reduced form and the concentrations of deoxyribonucleotides and accelerates DNA replication. These results establish thioredoxins as the major RNR reducing system in yeast and indicate that impaired RNR reduction accounts for the S phase defects of thioredoxin-deficient cells.