1,965 research outputs found

    A Genetic Screen Identifies New Steps In Oocyte Maturation That Enhance Proteostasis In The Immortal Germ Lineage

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    Somatic cells age and die, but the germ-cell lineage is immortal. In Caenorhabditis elegans, germline immortality involves proteostasis renewal at the beginning of each new generation, when oocyte maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen. Oocyte maturation signals are known to trigger protein-aggregate removal via lysosome acidification. Our findings suggest that lysosomes are acidified as a consequence of changes in endoplasmic reticulum activity that permit assembly of the lysosomal V-ATPase, which in turn allows lysosomes to clear the aggregates via microautophagy. We define two functions for mitochondria, both of which appear to be independent of ATP generation. Many genes from the screen also regulate lysosome acidification and age-dependent protein aggregation in the soma, suggesting a fundamental mechanistic link between proteostasis renewal in the germline and somatic longevity

    Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant Acinetobacter baumannii global clone 1.

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    The majority of Acinetobacter baumannii isolates that are multiply, extensively and pan-antibiotic resistant belong to two globally disseminated clones, GC1 and GC2, that were first noticed in the 1970s. Here, we investigated microevolution and phylodynamics within GC1 via analysis of 45 whole-genome sequences, including 23 sequenced for this study. The most recent common ancestor of GC1 arose around 1960 and later diverged into two phylogenetically distinct lineages. In the 1970s, the main lineage acquired the AbaR resistance island, conferring resistance to older antibiotics, via a horizontal gene transfer event. We estimate a mutation rate of ∼5 SNPs genome- 1 year- 1 and detected extensive recombination within GC1 genomes, introducing nucleotide diversity into the population at >20 times the substitution rate (the ratio of SNPs introduced by recombination compared with mutation was 22). The recombination events were non-randomly distributed in the genome and created significant diversity within loci encoding outer surface molecules (including the capsular polysaccharide, the outer core lipooligosaccharide and the outer membrane protein CarO), and spread antimicrobial resistance-conferring mutations affecting the gyrA and parC genes and insertion sequence insertions activating the ampC gene. Both GC1 lineages accumulated resistance to newer antibiotics through various genetic mechanisms, including the acquisition of plasmids and transposons or mutations in chromosomal genes. Our data show that GC1 has diversified into multiple successful extensively antibiotic-resistant subclones that differ in their surface structures. This has important implications for all avenues of control, including epidemiological tracking, antimicrobial therapy and vaccination

    The clearing of discs around late type T Tauri stars: constraints from the infrared two colour plane

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    We have undertaken SED modeling of discs around low mass T Tauri stars in order to delineate regions of the infrared two colour plane (K - [8] versus K - [24]) that correspond to discs in different evolutionary stages. This provides a ready tool for classifying the nature of star-disc systems based on infrared photometry. In particular we demonstrate the distinct loci followed by discs that undergo `uniform draining' (reduction in surface density by a spatially uniform factor) from those that clear from the inside out. We draw attention to the absence of objects on this `draining locus' in those star forming regions where the 24um sensitivity would permit their detection, as compared with the ~20 objects in these regions with colours suggestive of inner holes. We thus conclude that discs predominantly clear from the inside out. We also apply our classification of the infrared two colour plane to stars of spectral type M3-M5 in the IC 348 cluster and show that some of its members (dubbed `weak excess' sources by Muzerolle et al 2010) that had previously been assumed to be in a state of clearing are instead likely to be optically thick discs in which the dust is well settled towards the mid-plane. Nevertheless, there are many discs in a state of partial clearing in IC 348, with their abundance (relative to the total population of disc bearing stars) being around four times higher than for comparable stars in Taurus. However, the number of partially cleared discs relative to the total number of late type stars is similarly low in both regions (10 and 20 % respectively). We therefore conclude that IC 348 represents a more evolved version of the Taurus population (with more of its discs being highly settled or partially cleared) but that the timescale for clearing is similarly short (a few times 10^5 years) in both cases.Comment: 9 pages, 6 figures, accepted, MNRA

    Debris discs in binaries: a numerical study

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    Debris disc analysis and modelling provide crucial information about the structure and the processes at play in extrasolar planetary systems. In binary systems, this issue is more complex because the disc should in addition respond to the companion star's perturbations. We explore the dynamical evolution of a collisionally active debris disc for different initial parent body populations, diverse binary configurations and optical depths. We focus on the radial extent and size distribution of the disc at a stationary state. We numerically follow the evolution of 10510^{5} massless small grains, initially produced from a circumprimary disc of parent bodies following a size distribution in dNs3.5dN \propto s^{-3.5}ds . Grains are submitted to both stars' gravity as well as radiation pressure. In addition, particles are assigned an empirically derived collisional lifetime. For all the binary configurations the disc extends far beyond the critical semimajor axis acrita_crit for orbital stability. This is due to the steady production of small grains, placed on eccentric orbits reaching beyond acrita_crit by radiation pressure. The amount of matter beyond acrit depends on the balance between collisional production and dynamical removal rates: it increases for more massive discs as well as for eccentric binaries. Another important effect is that, in the dynamically stable region, the disc is depleted from its smallest grains. Both results could lead to observable signatures. We have shown that a companion star can never fully truncate a collisionally active disc. For eccentric companions, grains in the unstable regions can significantly contribute to the thermal emission in the mid-IR. Discs with sharp outer edges, especially bright ones such as HR4796A, are probably shaped by other mechanisms.Comment: accepted for publication in A&

    Identification of Acinetobacter baumannii loci for capsular polysaccharide (KL) and lipooligosaccharide outer core (OCL) synthesis in genome assemblies using curated reference databases compatible with Kaptive.

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    Multiply antibiotic-resistant Acinetobacter baumannii infections are a global public health concern and accurate tracking of the spread of specific lineages is needed. Variation in the composition and structure of capsular polysaccharide (CPS), a critical determinant of virulence and phage susceptibility, makes it an attractive epidemiological marker. The outer core (OC) of lipooligosaccharide also exhibits variation. To take better advantage of the untapped information available in whole genome sequences, we have created a curated reference database of 92 publicly available gene clusters at the locus encoding proteins responsible for biosynthesis and export of CPS (K locus), and a second database for 12 gene clusters at the locus for outer core biosynthesis (OC locus). Each entry has been assigned a unique KL or OCL number, and is fully annotated using a simple, transparent and standardized nomenclature. These databases are compatible with Kaptive, a tool for in silico typing of bacterial surface polysaccharide loci, and their utility was validated using (a) >630 assembled A. baumannii draft genomes for which the KL and OCL regions had been previously typed manually, and (b) 3386 A. baumannii genome assemblies downloaded from NCBI. Among the previously typed genomes, Kaptive was able to confidently assign KL and OCL types with 100?% accuracy. Among the genomes retrieved from NCBI, Kaptive detected known KL and OCL in 87 and 90?% of genomes, respectively, indicating that the majority of common KL and OCL types are captured within the databases; 13 of the 92 KL in the database were not detected in any publicly available whole genome assembly. The failure to assign a KL or OCL type may indicate incomplete or poor-quality genomes. However, further novel variants may remain to be documented. Combining outputs with multilocus sequence typing (Institut Pasteur scheme) revealed multiple KL and OCL types in collections of a single sequence type (ST) representing each of the two predominant globally distributed clones, ST1 of GC1 and ST2 of GC2, and in collections of other clones comprising >20 isolates each (ST10, ST25, and ST140), indicating extensive within-clone replacement of these loci. The databases are available at https://github.com/katholt/Kaptive and will be updated as further locus types become available

    Why do some young cool stars show spot modulation while others do not?

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    We present far-red, intermediate resolution spectroscopy of 572 photometrically selected, low-mass stars (0.2<M/M_sun<0.7) in the young open cluster NGC 2516, using the FLAMES spectrograph at the Very Large Telescope. Precise radial velocities confirm membership for 210 stars that have published rotation periods from spot-modulated light curves and for another 144 stars in which periodic modulation could not be found. The two sub-samples are compared and no significant differences are found between their positions in colour-magnitude diagrams, the distribution of their projected equatorial velocities or their levels of chromospheric activity. We rule out differing observational sensitivity as an explanation and conclude that otherwise similar objects, with equally high levels of chromospheric activity, do not exhibit spot-induced light curve modulation because their significant spot coverage is highly axisymmetric. We propose that the spot coverage consists of large numbers of small, dark spots with diameters of about 2 degrees. This explains why about half of cluster members do not exhibit rotationally modulated light curves and why the light curve amplitudes of those that do have mean values of only 0.01-0.02 mag.Comment: Accepted for publication in MNRAS, 11 pages. Electronic tables available from the author

    Clinical faculty associates serving as hybrid teacher educators: Personal and professional impacts

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    BackgroundUniversity supervisors in teacher education assume a complex and demanding role, which is essential to the development of prospective teachers, but is often underappreciated or ignored.AimThis descriptive study was designed to explore former clinical faculty associates’ (CFAs’) perceptions of the challenges and opportunities inherent in their work as CFAs, and the influence of this experience on their future professional work.Materials and methodsUsing survey research methodology, followed by selected individual interviews, this paper focuses on the experiences of CFAs, highly respected PK-6 teachers employed by the university for 2–3 years to serve as university supervisors.Results and conclusionAlthough participants reported facing several professional and personal challenges as CFAs, they also described opportunities to participate in a wide variety of professional experiences that positively impacted their future work. Furthermore, most reported feeling the CFA experience was professionally renewing and brought opportunities to build strong personal and professional relationships that cross institutional boundaries

    K19 capsular polysaccharide of acinetobacter baumannii is produced via a Wzy polymerase encoded in a small genomic island rather than the KL19 capsule gene cluster

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    © 2016 The Authors.Polymerization of the oligosaccharides (K units) of complex capsular polysaccharides (CPSs) requires a Wzy polymerase, which is usually encoded in the gene cluster that directs K unit synthesis. Here, a gene cluster at the Acinetobacter K locus (KL) that lacks a wzy gene, KL19, was found in Acinetobacter baumannii ST111 isolates 28 and RBH2 recovered from hospitals in the Russian Federation and Australia, respectively. However, these isolates produced long-chain capsule, and a wzy gene was found in a 6.1 kb genomic island (GI) located adjacent to the cpn60 gene. The GI also includes an acetyltransferase gene, atr25, which is interrupted by an insertion sequence (IS) in RBH2. The capsule structure from both strains was→3)-α-D-GalpNAc-(1→4)-α-D-GalpNAcA-(1→3)-β-D-QuipNAc4NAc-(1→, determined using NMR spectroscopy. Biosynthesis of the K unit was inferred to be initiated with QuiNAc4NAc, and hence the Wzy forms the β-(1→3) linkage between QuipNAc4NAc and GalpNAc. The GalpNAc residue is 6-O-acetylated in isolate 28 only, showing that atr25 is responsible for this acetylation. The same GI with or without an IS in atr25 was found in draft genomes of other KL19 isolates, as well as ones carrying a closely related CPS gene cluster, KL39, which differs from KL19 only in a gene for an acyltransferase in the QuiNAc4NR synthesis pathway. Isolates carrying a KL1 variant with the wzy and atr genes each interrupted by an ISAba125 also have this GI. To our knowledge, this study is the first report of genes involved in capsule biosynthesis normally found at the KL located elsewhere in A. baumannii genomes
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