581 research outputs found
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OMMA enables population-scale analysis of complex genomic features and phylogenomic relationships from nanochannel-based optical maps.
BackgroundOptical mapping is an emerging technology that complements sequencing-based methods in genome analysis. It is widely used in improving genome assemblies and detecting structural variations by providing information over much longer (up to 1 Mb) reads. Current standards in optical mapping analysis involve assembling optical maps into contigs and aligning them to a reference, which is limited to pairwise comparison and becomes bias-prone when analyzing multiple samples.FindingsWe present a new method, OMMA, that extends optical mapping to the study of complex genomic features by simultaneously interrogating optical maps across many samples in a reference-independent manner. OMMA captures and characterizes complex genomic features, e.g., multiple haplotypes, copy number variations, and subtelomeric structures when applied to 154 human samples across the 26 populations sequenced in the 1000 Genomes Project. For small genomes such as pathogenic bacteria, OMMA accurately reconstructs the phylogenomic relationships and identifies functional elements across 21 Acinetobacter baumannii strains.ConclusionsWith the increasing data throughput of optical mapping system, the use of this technology in comparative genome analysis across many samples will become feasible. OMMA is a timely solution that can address such computational need. The OMMA software is available at https://github.com/TF-Chan-Lab/OMTools
Spitzer 24 um Images of Planetary Nebulae
Spitzer MIPS 24 um images were obtained for 36 Galactic planetary nebulae
(PNe) whose central stars are hot white dwarfs (WDs) or pre-WDs with effective
temperatures of ~100,000 K or higher. Diffuse 24 um emission is detected in 28
of these PNe. The eight non-detections are angularly large PNe with very low
H-alpha surface brightnesses. We find three types of correspondence between the
24 um emission and H-alpha line emission of these PNe: six show 24 um emission
more extended than H-alpha emission, nine have a similar extent at 24 um and
H-alpha, and 13 show diffuse 24 um emission near the center of the H-alpha
shell. The sizes and surface brightnesses of these three groups of PNe and the
non-detections suggest an evolutionary sequence, with the youngest ones being
brightest and the most evolved ones undetected. The 24 um band emission from
these PNe is attributed to [O IV] 25.9 um and [Ne V] 24.3 um line emission and
dust continuum emission, but the relative contributions of these three
components depend on the temperature of the central star and the distribution
of gas and dust in the nebula.Comment: 24 pages, 8 figures, to appear in the Astronomical Journal, September
issue. Relace previous file; two references are added and typos are correcte
Genome maps across 26 human populations reveal population-specific patterns of structural variation.
Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome
Effective cerebral connectivity during silent speech reading revealed by functional magnetic resonance imaging
Polycation-Ï€ Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family
Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al
Circular Single-Stranded Synthetic DNA Delivery Vectors for MicroRNA
Single-stranded (ss) circular oligodeoxynucleotides were previously found to undergo rolling circle transcription (RCT) by phage and bacterial RNA polymerases (RNAPs) into tandemly repetitive RNA multimers. Here, we redesign them to encode minimal primary miRNA mimics, with the long term aim of intracellular transcription followed by RNA processing and maturation via endogenous pathways. We describe an improved method for circularizing ss synthetic DNA for RCT by using a recently described thermostable RNA ligase, which does not require a splint oligonucleotide to juxtapose the ligating ends. In vitro transcription of four templates demonstrates that the secondary structure inherent in miRNA-encoding vectors does not impair their RCT by RNAPs previously shown to carry out RCT. A typical primary-miRNA rolling circle transcript was accurately processed by a human Drosha immunoprecipitate, indicating that if human RNAPs prove to be capable of RCT, the resulting transcripts should enter the endogenous miRNA processing pathway in human cells. Circular oligonucleotides are therefore candidate vectors for small RNA delivery in human cells, which express RNAPs related to those tested here
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Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM
Spitzer 24 um Survey for Dust Disks around Hot White Dwarfs
Two types of dust disks around white dwarfs (WDs) have been reported: small
dust disks around cool metal-rich WDs consisting of tidally disrupted
asteroids, and a large dust disk around the hot central WD of the Helix
planetary nebula (PN) possibly produced by collisions among Kuiper Belt-like
objects. To search for more dust disks of the latter type, we have conducted a
Spitzer MIPS 24 um survey of 71 hot WDs or pre-WDs, among which 35 are central
stars of PNe (CSPNs). Nine of these evolved stars are detected and their 24 um
flux densities are at least two orders of magnitude higher than their expected
photospheric emission. Considering the bias against detection of distant
objects, the 24 um detection rate for the sample is >~15%. It is striking that
seven, or ~20%, of the WD and pre-WDs in known PNe exhibit 24 um excesses,
while two, or 5-6%, of the WDs not in PNe show 24 um excesses and they have the
lowest 24 um flux densities. We have obtained follow-up Spitzer IRS spectra for
five objects. Four show clear continuum emission at 24 um, and one is
overwhelmed by a bright neighboring star but still show a hint of continuum
emission. In the cases of WD 0950+139 and CSPN K1-22, a late-type companion is
present, making it difficult to determine whether the excess 24 um emission is
associated with the WD or its red companion. High-resolution images in the
mid-IR are needed to establish unambiguously the stars responsible for the 24
um excesses.Comment: 45 pages, 18 figures, 6 tables, accepted for publication in the
September 2011 edition of the Astronomical Journa
The Yuan-Tseh Lee Array for Microwave Background Anisotropy
The Yuan-Tseh Lee Array for Microwave Background Anisotropy (AMiBA) is the
first interferometer dedicated to studying the cosmic microwave background
(CMB) radiation at 3mm wavelength. The choice of 3mm was made to minimize the
contributions from foreground synchrotron radiation and Galactic dust emission.
The initial configuration of seven 0.6m telescopes mounted on a 6-m hexapod
platform was dedicated in October 2006 on Mauna Loa, Hawaii. Scientific
operations began with the detection of a number of clusters of galaxies via the
thermal Sunyaev-Zel'dovich effect. We compare our data with Subaru weak lensing
data in order to study the structure of dark matter. We also compare our data
with X-ray data in order to derive the Hubble constant.Comment: accepted for publication in ApJ (13 pages, 7 figures); a version with
high resolution figures available at
http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/pho_highreso.pd
A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma
Background: Hepatocellular carcinoma (HCC) is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced HCC leading to an urgent need to seek for novel therapeutic options. We aimed to investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the proliferation and metastasis of HCC. Methodology/Principal Findings: A series of in vitro experiments including MTT, colony-forming, wound-healing, invasion, apoptosis and cell cycle assays were performed to examine the anti-proliferative and anti-metastatic effects of SAC on a metastatic HCC cell line MHCC97L. The therapeutic values of SAC single and combined with cisplatin treatments were examined in an in vivo orthotopic xenograft liver tumor model. The result showed that the proliferation rate and colony-forming abilities of MHCC97L cells were suppressed by SAC together with significant suppression of the expressions of proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA). Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC significantly induced apoptosis and necrosis of MHCC97L cells through suppressing Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC could significantly induce the S phase arrest of MHCC97L cells together with down-regulation of cdc25c, cdc2 and cyclin B1. In vivo xenograft liver tumor model demonstrated that SAC single or combined with cisplatin treatment inhibited the progression and metastasis of HCC tumor. Conclusions/Significance: Our data demonstrate the anti-proliferative and anti-metastatic effects of SAC on HCC cells and suggest that SAC may be a potential therapeutic agent for the treatment of HCC patients. © 2012 Ng et al.published_or_final_versio
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