Recent studies suggest that most cases of myelodysplastic syndrome (MDS) are clonally heterogeneous, with a founding clone and multiple subclones. It is not known whether specific gene mutations ...typically occur in founding clones or subclones. We screened a panel of 94 candidate genes in a cohort of 157 patients with MDS or secondary acute myeloid leukemia (sAML). This included 150 cases with samples obtained at MDS diagnosis and 15 cases with samples obtained at sAML transformation (8 were also analyzed at the MDS stage). We performed whole-genome sequencing (WGS) to define the clonal architecture in eight sAML genomes and identified the range of variant allele frequencies (VAFs) for founding clone mutations. At least one mutation or cytogenetic abnormality was detected in 83% of the 150 MDS patients and 17 genes were significantly mutated (false discovery rate ≤0.05). Individual genes and patient samples displayed a wide range of VAFs for recurrently mutated genes, indicating that no single gene is exclusively mutated in the founding clone. The VAFs of recurrently mutated genes did not fully recapitulate the clonal architecture defined by WGS, suggesting that comprehensive sequencing may be required to accurately assess the clonal status of recurrently mutated genes in MDS.
Promoting an open research culture Nosek, B. A.; Alter, G.; Banks, G. C. ...
Science,
06/2015, Letnik:
348, Številka:
6242
Journal Article
Recenzirano
Odprti dostop
Author guidelines for journals could help to promote transparency, openness, and reproducibility
Transparency, openness, and reproducibility are readily recognized as vital features of science (
1
,
...2
). When asked, most scientists embrace these features as disciplinary norms and values (
3
). Therefore, one might expect that these valued features would be routine in daily practice. Yet, a growing body of evidence suggests that this is not the case (
4
–
6
).
Cassini Observes the Active South Pole of Enceladus Porco, C. C; Helfenstein, P; Thomas, P. C ...
Science (American Association for the Advancement of Science),
03/2006, Letnik:
311, Številka:
5766
Journal Article
Recenzirano
Cassini has identified a geologically active province at the south pole of Saturn's moon Enceladus. In images acquired by the Imaging Science Subsystem (ISS), this region is circumscribed by a chain ...of folded ridges and troughs at approximately55°S latitude. The terrain southward of this boundary is distinguished by its albedo and color contrasts, elevated temperatures, extreme geologic youth, and narrow tectonic rifts that exhibit coarse-grained ice and coincide with the hottest temperatures measured in the region. Jets of fine icy particles that supply Saturn's E ring emanate from this province, carried aloft by water vapor probably venting from subsurface reservoirs of liquid water. The shape of Enceladus suggests a possible intense heating epoch in the past by capture into a 1:4 secondary spin/orbit resonance.
Protective immunity to parasitic infections has been difficult to elicit by vaccines. Among parasites that evade vaccine-induced immunity is Toxoplasma gondii, which causes lethal secondary ...infections in chronically infected mice. Here we report that unlike susceptible C57BL/6J mice, A/J mice were highly resistant to secondary infection. To identify correlates of immunity, we utilized forward genetics to identify Nfkbid, a nuclear regulator of NF-κB that is required for B cell activation and B-1 cell development. Nfkbid-null mice ("bumble") did not generate parasite-specific IgM and lacked robust parasite-specific IgG, which correlated with defects in B-2 cell maturation and class-switch recombination. Though high-affinity antibodies were B-2 derived, transfer of B-1 cells partially rescued the immunity defects observed in bumble mice and were required for 100% vaccine efficacy in bone marrow chimeric mice. Immunity in resistant mice correlated with robust isotype class-switching in both B cell lineages, which can be fine-tuned by Nfkbid gene expression. We propose a model whereby humoral immunity to T. gondii is regulated by Nfkbid and requires B-1 and B-2 cells for full protection.
We analyze star formation (SF) as a function of stellar mass (M sub(*)) and redshift z in the All-Wavelength Extended Groth Strip International Survey. For 2905 field galaxies, complete to 10 ...super(10)(10 super(10.8)) M sub((.)) at z < 0.7(1), with Keck spectroscopic redshifts out to z = 1.1, we compile SF rates (SFRs) from emission lines, GALEX, and Spitzer MIPS 24 km photometry, optical-NIR M sub(*) measurements, and HST morphologies. Galaxies with reliable signs of SF form a distinct "main sequence" (MS), with a limited range of SFRs at a given M sub(*) and z (1 s c0.3 dex), and log(SFR) approximately proportional to log M sub(*). The range of log (SFR) remains constant to z > 1, while the MS as a whole moves to higher SFR as z increases. The range of the SFR along the MS constrains the amplitude of episodic variations of SF and the effect of mergers on the SFR. Typical galaxies spend 667%(95%) of their lifetime since z = 1 within a factor of 2(4) of their average SFR at a given M sub(*) and z. The dominant mode of the evolution of SF since z 6 1 is apparently a gradual decline of the average SFR in most individual galaxies, not a decreasing frequency of starburst episodes, or a decreasing factor by which SFRs are enhanced in starbursts. LIRGs at z 6 1 seem to mostly reflect the high SFR typical for massive galaxies at that epoch. The smooth MS may reflect that the same set of few physical processes governs SF prior to additional quenching processes. A gradual process like gas exhaustion may play a dominant role.
ABSTRACT
Scaling laws of dust, H i gas, and metal mass with stellar mass, specific star formation rate, and metallicity are crucial to our understanding of the build-up of galaxies through their ...enrichment with metals and dust. In this work, we analyse how the dust and metal content varies with specific gas mass (MH i/M⋆) across a diverse sample of 423 nearby galaxies. The observed trends are interpreted with a set of Dust and Element evolUtion modelS (DEUS) – including stellar dust production, grain growth, and dust destruction – within a Bayesian framework to enable a rigorous search of the multidimensional parameter space. We find that these scaling laws for galaxies with −1.0 ≲ log MH i/M⋆ ≲ 0 can be reproduced using closed-box models with high fractions (37–89 ${{\ \rm per\ cent}}$) of supernova dust surviving a reverse shock, relatively low grain growth efficiencies (ϵ = 30–40), and long dust lifetimes (1–2 Gyr). The models have present-day dust masses with similar contributions from stellar sources (50–80 ${{\ \rm per\ cent}}$) and grain growth (20–50 ${{\ \rm per\ cent}}$). Over the entire lifetime of these galaxies, the contribution from stardust (>90 ${{\ \rm per\ cent}}$) outweighs the fraction of dust grown in the interstellar medium (<10 ${{\ \rm per\ cent}}$). Our results provide an alternative for the chemical evolution models that require extremely low supernova dust production efficiencies and short grain growth time-scales to reproduce local scaling laws, and could help solving the conundrum on whether or not grains can grow efficiently in the interstellar medium.
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