The Hercules-Lyra Association revisited New age estimation and multiplicity study

The Her-Lyr assoc., a nearby young MG, contains a few tens of ZAMS stars of SpT F to M. The existence and the properties of the Her-Lyr assoc. are controversial and discussed in the literature. The present work reassesses properties and the member list of Her-Lyr assoc., based on kinematics and age. Many objects form multiple systems or have low-mass companions and so we need to account for multiplicity. We use our own new imaging obs. and archival data to identify multiple systems. The colors and magnitudes of kinematic candidates are compared to isochrones. We derive further information on the age based on Li depletion, rotation, and coronal and chromospheric activity. A set of canonical members is identified to infer mean properties. Membership criteria are derived from the mean properties and used to discard non-members. The candidates selected from the literature belong to 35 stellar systems, 42.9% of which are multiple. Four multiple systems are confirmed in this work by common proper motion. An orbital solution is presented for the binary system HH Leo B and C. Indeed, a group of candidates displays signatures of youth. 7 canonical members are identified. The distribution of EWLi of canonical Her-Lyr members is spread widely and is similar to that of the Pleiades and the UMa group. Gyrochronology gives an age of 257+-46 Myr which is in between the ages of the Pleiades and the Ursa Major group. The measures of chromospheric and coronal activity support the young age. Four membership criteria are presented based on kinematics, EWLi, chromospheric activity, and gyro. age. In total, 11 stars are identified as certain members including co-moving objects plus additional 23 possible members while 14 candidates are doubtful or can be rejected. A comparison to the mass function, however, indicates the presence of a large number of additional unidentified low-mass members.Comment: 19 pages 16 figure

Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short telomeres, and 80 genes that confer long telomeres relative to those of wild-type yeast. Among identified genes, 88 have not been previously implicated in telomere length control. Genes that regulate telomere length span a variety of functions that can be broadly separated into telomerase-dependent and telomerase-independent pathways. We also found 39 genes that have an important role in telomere maintenance or cell proliferation in the absence of telomerase, including genes that participate in deoxyribonucleotide biosynthesis, sister chromatid cohesion, and vacuolar protein sorting. Given the large number of loci identified, we investigated telomere lengths in 13 wild yeast strains and found substantial natural variation in telomere length among the isolates. Furthermore, we crossed a wild isolate to a laboratory strain and analyzed telomere length in 122 progeny. Genome-wide linkage analysis among these segregants revealed two loci that account for 30%–35% of telomere length-variation between the strains. These findings support a general model of telomere length-variation in outbred populations that results from polymorphisms at a large number of loci. Furthermore, our results laid the foundation for studying genetic determinants of telomere length-variation and their roles in human disease

Astrometric confirmation of young low-mass binaries and multiple systems in the Chamaeleon star-forming regions

The star-forming regions in Chamaeleon are one of the nearest (distance ~165 pc) and youngest (age ~2 Myrs) conglomerates of recently formed stars and the ideal target for population studies of star formation. We investigate a total of 16 Cha targets, which have been suggested, but not confirmed as binaries or multiple systems in previous literature. We used the adaptive optics instrument Naos-Conica (NACO) at the Very Large Telescope Unit Telescope 4 of the Paranal Observatory, at 2-5 different epochs, in order to obtain relative and absolute astrometric measurements, as well as differential photometry in the J, H, and K band. On the basis of known proper motions and these observations, we analyse the astrometric results in our "Proper Motion Diagram" (PMD: angular separation / position angle versus time), to eliminate possible (non-moving) background stars, establish co-moving binaries and multiples, and search for curvature as indications for orbital motion. All previously suggested close components are co-moving and no background stars are found. The angular separations range between 0.07 and 9 arcseconds, corresponding to projected distances between the components of 6-845 AU. Thirteen stars are at least binaries and the remaining three (RX J0919.4-7738, RX J0952.7-7933, VW Cha) are confirmed high-order multiple systems with up to four components. In 13 cases, we found significant slopes in the PMDs, which are compatible with orbital motion whose periods range from 60 to 550 years. However, in only four cases there are indications of a curved orbit, the ultimate proof of a gravitational bond. Massive primary components appear to avoid the simultaneous formation of equal-mass secondary components. (abridged)Comment: 33 pages, 22 figures, accepted for publication in A&A, 2nd version: typos and measurement unit added in Table

Conditioning with Treosulfan and Fludarabine followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

In this prospective study 60 patients of median age 46 (range: 5-60 years), with acute myelogenous leukemia (AML; n = 44), acute lymphoblastic leukemia (ALL; n = 3), or myelodysplastic syndrome (MDS; n = 13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine (Flu) combination. Most patients were considered at high risk for relapse or nonrelapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m2/day (n = 5) or 14 g/m2/day (n = 55) on days −6 to −4, and Flu (30 mg/m2/day) on days −6 to −2, followed by infusion of marrow (n = 7) or peripheral blood stem cells (n = 53) from HLA-identical siblings (n = 30) or unrelated donors (n = 30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival (RFS) for all patients was 58% and 88% for patients without high-risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/Flu regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/Flu to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients

Genetic Variation Shapes Protein Networks Mainly through Non-transcriptional Mechanisms

Variation in the levels of co-regulated proteins that function within networks in an outbred yeast population is not driven by variation in the corresponding transcripts

Natural Polymorphism in BUL2 Links Cellular Amino Acid Availability with Chronological Aging and Telomere Maintenance in Yeast

Aging and longevity are considered to be highly complex genetic traits. In order to gain insight into aging as a polygenic trait, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard strain RM11 and a laboratory strain S288c, to identify quantitative trait loci that control chronological lifespan. Among the major loci that regulate chronological lifespan in this cross, one genetic linkage was found to be congruent with a previously mapped locus that controls telomere length variation. We found that a single nucleotide polymorphism in BUL2, encoding a component of an ubiquitin ligase complex involved in trafficking of amino acid permeases, controls chronological lifespan and telomere length as well as amino acid uptake. Cellular amino acid availability changes conferred by the BUL2 polymorphism alter telomere length by modulating activity of a transcription factor Gln3. Among the GLN3 transcriptional targets relevant to this phenotype, we identified Wtm1, whose upregulation promotes nuclear retention of ribonucleotide reductase (RNR) components and inhibits the assembly of the RNR enzyme complex during S-phase. Inhibition of RNR is one of the mechanisms by which Gln3 modulates telomere length. Identification of a polymorphism in BUL2 in this outbred yeast population revealed a link among cellular amino acid availability, chronological lifespan, and telomere length control

Replicative Age Induces Mitotic Recombination in the Ribosomal RNA Gene Cluster of Saccharomyces cerevisiae

Somatic mutations contribute to the development of age-associated disease. In earlier work, we found that, at high frequency, aging Saccharomyces cerevisiae diploid cells produce daughters without mitochondrial DNA, leading to loss of respiration competence and increased loss of heterozygosity (LOH) in the nuclear genome. Here we used the recently developed Mother Enrichment Program to ask whether aging cells that maintain the ability to produce respiration-competent daughters also experience increased genomic instability. We discovered that this population exhibits a distinct genomic instability phenotype that primarily affects the repeated ribosomal RNA gene array (rDNA array). As diploid cells passed their median replicative life span, recombination rates between rDNA arrays on homologous chromosomes progressively increased, resulting in mutational events that generated LOH at >300 contiguous open reading frames on the right arm of chromosome XII. We show that, while these recombination events were dependent on the replication fork block protein Fob1, the aging process that underlies this phenotype is Fob1-independent. Furthermore, we provide evidence that this aging process is not driven by mechanisms that modulate rDNA recombination in young cells, including loss of cohesion within the rDNA array or loss of Sir2 function. Instead, we suggest that the age-associated increase in rDNA recombination is a response to increasing DNA replication stress generated in aging cells