407 research outputs found
Genome mapping and characterization of the Anopheles gambiae heterochromatin
<p>Abstract</p> <p>Background</p> <p>Heterochromatin plays an important role in chromosome function and gene regulation. Despite the availability of polytene chromosomes and genome sequence, the heterochromatin of the major malaria vector <it>Anopheles gambiae </it>has not been mapped and characterized.</p> <p>Results</p> <p>To determine the extent of heterochromatin within the <it>An. gambiae </it>genome, genes were physically mapped to the euchromatin-heterochromatin transition zone of polytene chromosomes. The study found that a minimum of 232 genes reside in 16.6 Mb of mapped heterochromatin. Gene ontology analysis revealed that heterochromatin is enriched in genes with DNA-binding and regulatory activities. Immunostaining of the <it>An. gambiae </it>chromosomes with antibodies against <it>Drosophila melanogaster </it>heterochromatin protein 1 (HP1) and the nuclear envelope protein lamin Dm<sub>0 </sub>identified the major invariable sites of the proteins' localization in all regions of pericentric heterochromatin, diffuse intercalary heterochromatin, and euchromatic region 9C of the 2R arm, but not in the compact intercalary heterochromatin. To better understand the molecular differences among chromatin types, novel Bayesian statistical models were developed to analyze genome features. The study found that heterochromatin and euchromatin differ in gene density and the coverage of retroelements and segmental duplications. The pericentric heterochromatin had the highest coverage of retroelements and tandem repeats, while intercalary heterochromatin was enriched with segmental duplications. We also provide evidence that the diffuse intercalary heterochromatin has a higher coverage of DNA transposable elements, minisatellites, and satellites than does the compact intercalary heterochromatin. The investigation of 42-Mb assembly of unmapped genomic scaffolds showed that it has molecular characteristics similar to cytologically mapped heterochromatin.</p> <p>Conclusions</p> <p>Our results demonstrate that <it>Anopheles </it>polytene chromosomes and whole-genome shotgun assembly render the mapping and characterization of a significant part of heterochromatic scaffolds a possibility. These results reveal the strong association between characteristics of the genome features and morphological types of chromatin. Initial analysis of the <it>An. gambiae </it>heterochromatin provides a framework for its functional characterization and comparative genomic analyses with other organisms.</p
An Inhibitory Role of the G-Protein Regulator AGS3 in mTOR-Dependent Macroautophagy
Macroautophagy is a cellular process whereby the cell sequesters and recycles cytosolic constituents in a lysosome-dependent manner. It has also been implicated in a number of disorders, including cancer and neurodegeneration. Although a previous report that AGS3 over-expression promotes macroautophagy suggests a stimulatory role of AGS3 in this process, we have found that knock-down of AGS3, unexpectedly, also induces macroautophagy, indicating an inhibitory function of endogenous AGS3 in macroautophagy. Interestingly, AGS3 phosphorylation is decreased upon induction of mammalian target of rapamycin (mTOR)-dependent macroautophagy. Moreover, unlike wild-type AGS3, over-expression of an AGS3 mutant lacking this modification fails to enhance macroautophagic activity. These observations imply that AGS3 phosphorylation may participate in the modulation of macroautophagy
Trkalian fields: ray transforms and mini-twistors
We study X-ray and Divergent beam transforms of Trkalian fields and their
relation with Radon transform. We make use of four basic mathematical methods
of tomography due to Grangeat, Smith, Tuy and Gelfand-Goncharov for an integral
geometric view on them. We also make use of direct approaches which provide a
faster but restricted view of the geometry of these transforms. These reduce to
well known geometric integral transforms on a sphere of the Radon or the
spherical Curl transform in Moses eigenbasis, which are members of an analytic
family of integral operators. We also discuss their inversion. The X-ray (also
Divergent beam) transform of a Trkalian field is Trkalian. Also the Trkalian
subclass of X-ray transforms yields Trkalian fields in the physical space. The
Riesz potential of a Trkalian field is proportional to the field. Hence, the
spherical mean of the X-ray (also Divergent beam) transform of a Trkalian field
over all lines passing through a point yields the field at this point. The
pivotal point is the simplification of an intricate quantity: Hilbert transform
of the derivative of Radon transform for a Trkalian field in the Moses basis.
We also define the X-ray transform of the Riesz potential (of order 2) and
Biot-Savart integrals. Then, we discuss a mini-twistor respresentation,
presenting a mini-twistor solution for the Trkalian fields equation. This is
based on a time-harmonic reduction of wave equation to Helmholtz equation. A
Trkalian field is given in terms of a null vector in C3 with an arbitrary
function and an exponential factor resulting from this reduction.Comment: 37 pages, http://dx.doi.org/10.1063/1.482610
PTF11eon/SN2011dh: Discovery of a Type IIb Supernova From a Compact Progenitor in the Nearby Galaxy M51
On May 31, 2011 UT a supernova (SN) exploded in the nearby galaxy M51 (the
Whirlpool Galaxy). We discovered this event using small telescopes equipped
with CCD cameras, as well as by the Palomar Transient Factory (PTF) survey, and
rapidly confirmed it to be a Type II supernova. Our early light curve and
spectroscopy indicates that PTF11eon resulted from the explosion of a
relatively compact progenitor star as evidenced by the rapid shock-breakout
cooling seen in the light curve, the relatively low temperature in early-time
spectra and the prompt appearance of low-ionization spectral features. The
spectra of PTF11eon are dominated by H lines out to day 10 after explosion, but
initial signs of He appear to be present. Assuming that He lines continue to
develop in the near future, this SN is likely a member of the cIIb (compact
IIb; Chevalier and Soderberg 2010) class, with progenitor radius larger than
that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor.
Our data imply that the object identified in pre-explosion Hubble Space
Telescope images at the SN location is possibly a companion to the progenitor
or a blended source, and not the progenitor star itself, as its radius (~10^13
cm) would be highly inconsistent with constraints from our post-explosion
photometric and spectroscopic data
No barrier to emergence of bathyal king crabs on the Antarctic shelf
Cold-water conditions have excluded durophagous (skeleton-breaking) predators from the Antarctic seafloor for millions of years. Rapidly warming seas off the western Antarctic Peninsula could now facilitate their return to the continental shelf, with profound consequences for the endemic fauna. Among the likely first arrivals are king crabs (Lithodidae), which were discovered recently on the adjacent continental slope. During the austral summer of 2010‒2011, we used underwater imagery to survey a slope-dwelling population of the lithodid Paralomis birsteini off Marguerite Bay, western Antarctic Peninsula for environmental or trophic impediments to shoreward expansion. The population density averaged ∼4.5 individuals × 1,000 m(−2) within a depth range of 1,100‒1,500 m (overall observed depth range 841–2,266 m). Images of juveniles, discarded molts, and precopulatory behavior, as well as gravid females in a trapping study, suggested a reproductively viable population on the slope. At the time of the survey, there was no thermal barrier to prevent the lithodids from expanding upward and emerging on the outer shelf (400- to 550-m depth); however, near-surface temperatures remained too cold for them to survive in inner-shelf and coastal environments (<200 m). Ambient salinity, composition of the substrate, and the depth distribution of potential predators likewise indicated no barriers to expansion of lithodids onto the outer shelf. Primary food resources for lithodids—echinoderms and mollusks—were abundant on the upper slope (550–800 m) and outer shelf. As sea temperatures continue to rise, lithodids will likely play an increasingly important role in the trophic structure of subtidal communities closer to shore
Marriage and the crisis of peasant society in Gujarat, India
This contribution takes marriage as the example of a crisis of production and reproduction in rural India. Through the juxtaposition of ethnography separated by six decades, we detail a shift away from land and agriculture as the primary markers of status among the Patidars of central Gujarat, western India, in favour of a hierarchical understanding of international migration. The paper discusses the disconnect between a cultural revolution in favour of migration, and the failure of many to live up to their own cultural standards. More broadly, we reflect on the forces that simultaneously strengthen and dissolve caste inequality in the context of India's uneven growth
Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes
SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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