240 research outputs found
Telomeres and the natural lifespan limit in humans
An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
Orphan CpG Islands Identify Numerous Conserved Promoters in the Mammalian Genome
CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are “orphans” that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development
The 2010 very high energy gamma-ray flare & 10 years of multi-wavelength observations of M 87
Abridged: The giant radio galaxy M 87 with its proximity, famous jet, and
very massive black hole provides a unique opportunity to investigate the origin
of very high energy (VHE; E>100 GeV) gamma-ray emission generated in
relativistic outflows and the surroundings of super-massive black holes. M 87
has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray
emission displays strong variability on timescales as short as a day. In this
paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and
VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE
was detected triggering further observations at VHE (H.E.S.S.), X-rays
(Chandra), and radio (43 GHz VLBA). The excellent sampling of the VHE gamma-ray
light curve enables one to derive a precise temporal characterization of the
flare: the single, isolated flare is well described by a two-sided exponential
function with significantly different flux rise and decay times. While the
overall variability pattern of the 2010 flare appears somewhat different from
that of previous VHE flares in 2005 and 2008, they share very similar
timescales (~day), peak fluxes (Phi(>0.35 TeV) ~= (1-3) x 10^-11 ph cm^-2
s^-1), and VHE spectra. 43 GHz VLBA radio observations of the inner jet regions
indicate no enhanced flux in 2010 in contrast to observations in 2008, where an
increase of the radio flux of the innermost core regions coincided with a VHE
flare. On the other hand, Chandra X-ray observations taken ~3 days after the
peak of the VHE gamma-ray emission reveal an enhanced flux from the core. The
long-term (2001-2010) multi-wavelength light curve of M 87, spanning from radio
to VHE and including data from HST, LT, VLA and EVN, is used to further
investigate the origin of the VHE gamma-ray emission. No unique, common MWL
signature of the three VHE flares has been identified.Comment: 19 pages, 5 figures; Corresponding authors: M. Raue, L. Stawarz, D.
Mazin, P. Colin, C. M. Hui, M. Beilicke; Fig. 1 lightcurve data available
online: http://www.desy.de/~mraue/m87
Simultaneous observations of PKS 2155-304 with H.E.S.S., Fermi, RXTE and ATOM: spectral energy distributions and variability in a low state
We report on the first simultaneous observations that cover the optical,
X-ray, and high energy gamma-ray bands of the BL Lac object PKS 2155-304. The
gamma-ray bands were observed for 11 days, between 25 August and 6 September
2008, jointly with the Fermi Gamma-ray Space Telescope and the H.E.S.S.
atmospheric Cherenkov array, providing the first simultaneous MeV-TeV spectral
energy distribution with the new generation of gamma-ray telescopes. The ATOM
telescope and the RXTE and Swift observatories provided optical and X-ray
coverage of the low-energy component over the same time period. The object was
close to the lowest archival X-ray and Very High Energy state, whereas the
optical flux was much higher. The light curves show relatively little (~30%$)
variability overall when compared to past flaring episodes, but we find a clear
optical/VHE correlation and evidence for a correlation of the X-rays with the
high energy spectral index. Contrary to previous observations in the flaring
state, we do not find any correlation between the X-ray and VHE components.
Although synchrotron self-Compton models are often invoked to explain the SEDs
of BL Lac objects, the most common versions of these models are at odds with
the correlated variability we find in the various bands for PKS 2155-304.Comment: Accepted for publication in the Astrophysical Journa
Constraints on axionlike particles with H.E.S.S. from the irregularity of the PKS 2155-304 energy spectrum
Axionlike particles (ALPs) are hypothetical light (sub-eV) bosons predicted in some extensions of the Standard Model of particle physics. In astrophysical environments comprising high-energy gamma rays and turbulent magnetic fields, the existence of ALPs can modify the energy spectrum of the gamma rays for a sufficiently large coupling between ALPs and photons. This modification would take the form of an irregular behavior of the energy spectrum in a limited energy range. Data from the H.E.S.S. observations of the distant BL Lac object PKS 2155-304 (z=0.116) are used to derive upper limits at the 95% C.L. on the strength of the ALP coupling to photons, ggammaa<2.1×10-11GeV-1 for an ALP mass between 15 and 60 neV. The results depend on assumptions on the magnetic field around the source, which are chosen conservatively. The derived constraints apply to both light pseudoscalar and scalar bosons that couple to the electromagnetic fieldFil: Medina, Maria Clementina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto Argentino de Radioastronomia (i); ArgentinaFil: H.E.S. S. collaboration
Gene family expansions and contractions are associated with host range in plant pathogens of the genus Colletotrichum
Background:
Many species belonging to the genus Colletotrichum cause anthracnose disease on a wide range of plant species. In addition to their economic impact, the genus Colletotrichum is a useful model for the study of the evolution of host specificity, speciation and reproductive behaviors. Genome projects of Colletotrichum species have already opened a new era for studying the evolution of pathogenesis in fungi.
Results:
We sequenced and annotated the genomes of four strains in the Colletotrichum acutatum species complex (CAsc), a clade of broad host range pathogens within the genus. The four CAsc proteomes and secretomes along with those representing an additional 13 species (six Colletotrichum spp. and seven other Sordariomycetes) were classified into protein families using a variety of tools. Hierarchical clustering of gene family and functional domain assignments, and phylogenetic analyses revealed lineage specific losses of carbohydrate-active enzymes (CAZymes) and proteases encoding genes in Colletotrichum species that have narrow host range as well as duplications of these families in the CAsc. We also found a lineage specific expansion of necrosis and ethylene-inducing peptide 1 (Nep1)-like protein (NLPs) families within the CAsc.
Conclusions:
This study illustrates the plasticity of Colletotrichum genomes, and shows that major changes in host range are associated with relatively recent changes in gene content
Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer’s disease
Multi-messenger observations of a binary neutron star merger
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
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