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  • 1
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    SMA observations towards the compact, short-lived bipolar water maser outflow in the LkH{alpha}234 region (2016)
    Oxford University Press
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    Publication Date: 2016-08-03
    Description: We present Submillimeter Array (SMA) 1.35 mm subarcsecond angular resolution observations towards the LkHα234 intermediate-mass star-forming region. The dust emission arises from a filamentary structure of ~5 arcsec (~4500 au) enclosing VLA 1-3 and MM 1, perpendicular to the different outflows detected in the region. The most evolved objects are located at the southeastern edge of the dust filamentary structure and the youngest ones at the northeastern edge. The circumstellar structures around VLA 1, VLA 3, and MM 1 have radii between ~200 and ~375 au and masses in the ~0.08–0.3 M range. The 1.35 mm emission of VLA 2 arises from an unresolved ( r 135 au) circumstellar disc with a mass of ~0.02 M . This source is powering a compact (~4000 au), low radial velocity (~7 km s –1 ) SiO bipolar outflow, close to the plane of the sky. We conclude that this outflow is the ‘large-scale’ counterpart of the short-lived, episodic, bipolar outflow observed through H 2 O masers at much smaller scales (~180 au), and that has been created by the accumulation of the ejection of several episodic collimated events of material. The circumstellar gas around VLA 2 and VLA 3 is hot (~130 K) and exhibits velocity gradients that could trace rotation. There is a bridge of warm and dense molecular gas connecting VLA 2 and VLA 3. We discuss the possibility that this bridge could trace a stream of gas between VLA 3 and VLA 2, increasing the accretion rate on to VLA 2 to explain why this source has an important outflow activity.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 2
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    Opsin Repertoire and Expression Patterns in Horseshoe Crabs: Evidence from the Genome of Limulus polyphemus (Arthropoda: Chelicerata) (2016)
    Oxford University Press
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    Publication Date: 2016-06-05
    Description: Horseshoe crabs are xiphosuran chelicerates, the sister group to arachnids. As such, they are important for understanding the most recent common ancestor of Euchelicerata and the evolution and diversification of Arthropoda. Limulus polyphemus is the most investigated of the four extant species of horseshoe crabs, and the structure and function of its visual system have long been a major focus of studies critical for understanding the evolution of visual systems in arthropods. Likewise, studies of genes encoding Limulus opsins, the protein component of the visual pigments, are critical for understanding opsin evolution and diversification among chelicerates, where knowledge of opsins is limited, and more broadly among arthropods. In the present study, we sequenced and assembled a high quality nuclear genomic sequence of L. polyphemus and used these data to annotate the full repertoire of Limulus opsins. We conducted a detailed phylogenetic analysis of Limulus opsins, including using gene structure and synteny information to identify relationships among different opsin classes. We used our phylogeny to identify significant genomic events that shaped opsin evolution and therefore the visual system of Limulus . We also describe the tissue expression patterns of the 18 opsins identified and show that transcripts encoding a number, including a peropsin, are present throughout the central nervous system. In addition to significantly extending our understanding of photosensitivity in Limulus and providing critical insight into the genomic evolution of horseshoe crab opsins, this work provides a valuable genomic resource for addressing myriad questions related to xiphosuran physiology and arthropod evolution.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    A spider-like outflow in Barnard 5 - IRS 1: the transition from a collimated jet to a wide-angle outflow? (2014)
    Oxford University Press
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    Publication Date: 2014-06-05
    Description: We present line and continuum observations made with the Submillimeter Array of the young stellar object Barnard 5 - IRS1 located in the Perseus molecular cloud. Our 12 CO(2–1) line observations resolve the high-velocity bipolar north-east–south-west outflow associated with this source. We find that the outflowing gas shows different structures at three different velocity regimes, in both lobes, resulting in a spider-like morphology. In addition to the low-velocity, cone-like (wide-angle) lobes that have previously been observed, we report the presence of intermediate-velocity parabolic shells emerging very close to the Class I protostar, as well as high-velocity molecular bullets that appear to be associated with the optical/IR jet emanating from this source. These compact high-velocity features reach radial velocities of about 50 km s –1 away from the cloud velocity. We interpret that the peculiar spider-like morphology is a result of the molecular material being entrained by a wind with both a collimated jet-like component and a wide-angle component. We suggest that the outflow is in a transitional evolutionary phase between a mostly jet-driven flow and an outflow in which the entrainment is dominated by the wide-angle wind component. We also detect 1300 μm continuum emission at the position of the protostar, which likely arises from the dusty envelope and disc surrounding the protostar. Finally, we report the detection of 13 CO(2–1) and SO(6 5 –5 4 ) emission arising from the outflow and the location of the young stellar object.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    ZBTB42 mutation defines a novel lethal congenital contracture syndrome (LCCS6) (2014)
    Oxford University Press
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    Publication Date: 2014-11-21
    Description: Lethal congenital contracture syndrome (LCCS) is a lethal autosomal recessive form of arthrogryposis multiplex congenita (AMC). LCCS is genetically heterogeneous with mutations in five genes identified to date, all with a role in the innervation or contractile apparatus of skeletal muscles. In a consanguineous Saudi family with multiple stillbirths presenting with LCCS, we excluded linkage to all known LCCS loci and combined autozygome analysis and whole-exome sequencing to identify a novel homozygous variant in ZBTB42 , which had been shown to be enriched in skeletal muscles, especially at the neuromuscular junction. Knockdown experiments of zbtb42 in zebrafish consistently resulted in grossly abnormal skeletal muscle development and myofibrillar disorganization at the microscopic level. This severe muscular phenotype is successfully rescued with overexpression of the human wild-type ZBTB42 gene, but not with the mutant form of ZBTB42 that models the human missense change. Our data assign a novel muscular developmental phenotype to ZBTB42 in vertebrates and establish a new LCCS6 type caused by ZBTB42 mutation.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 5
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    A very young, compact bipolar H2O maser outflow in the intermediate-mass star-forming LkH{alpha} 234 region (2014)
    Oxford University Press
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    Publication Date: 2014-06-06
    Description: We report multi-epoch Very Long Baseline Interferometry (VLBI) H 2 O maser observations towards the compact cluster of young stellar objects (YSOs) close to the Herbig Be star LkHα 234. This cluster includes LkHα 234 and at least nine more YSOs that are formed within projected distances of ~10 arcsec (~9000 au). We detect H 2 O maser emission towards four of these YSOs. In particular, our VLBI observations (including proper motion measurements) reveal a remarkable very compact (~0.2 arcsec = ~180 au), bipolar H 2 O maser outflow emerging from the embedded YSO Very Large Array (VLA) 2. We estimate a kinematic age of ~40 yr for this bipolar outflow, with expanding velocities of ~20 km s –1 and momentum rate M w V w ~= 10 –4 –10 –3 M  yr –1 km s –1  (/4), powered by a YSO of a few solar masses. We propose that the outflow is produced by recurrent episodic jet ejections associated with the formation of this YSO. Short-lived episodic ejection events have previously been found towards high-mass YSOs. We show now that this behaviour is also present in intermediate-mass YSOs. These short-lived episodic ejections are probably related to episodic increases in the accretion rate, as observed in low-mass YSOs. We predict the presence of an accretion disc associated with VLA 2. If detected, this would represent one of the few known examples of intermediate-mass stars with a disc–YSO–jet system at scales of a few hundred astronomical units.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    Flap endonucleases pass 5'-flaps through a flexible arch using a disorder-thread-order mechanism to confer specificity for free 5'-ends (2012)
    Oxford University Press
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    Publication Date: 2012-05-23
    Description: Flap endonucleases (FENs), essential for DNA replication and repair, recognize and remove RNA or DNA 5'-flaps. Related to FEN specificity for substrates with free 5'-ends, but controversial, is the role of the helical arch observed in varying conformations in substrate-free FEN structures. Conflicting models suggest either 5'-flaps thread through the arch, which when structured can only accommodate single-stranded (ss) DNA, or the arch acts as a clamp. Here we show that free 5'-termini are selected using a disorder-thread-order mechanism. Adding short duplexes to 5'-flaps or 3'-streptavidin does not markedly impair the FEN reaction. In contrast, reactions of 5'-streptavidin substrates are drastically slowed. However, when added to premixed FEN and 5'-biotinylated substrate, streptavidin is not inhibitory and complexes persist after challenge with unlabelled competitor substrate, regardless of flap length or the presence of a short duplex. Cross-linked flap duplexes that cannot thread through the structured arch react at modestly reduced rate, ruling out mechanisms involving resolution of secondary structure. Combined results explain how FEN avoids cutting template DNA between Okazaki fragments and link local FEN folding to catalysis and specificity: the arch is disordered when flaps are threaded to confer specificity for free 5'-ends, with subsequent ordering of the arch to catalyze hydrolysis.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    De-repression of FOXO3a death axis by microRNA-132 and -212 causes neuronal apoptosis in Alzheimer's disease (2013)
    Oxford University Press
    Details
    Publication Date: 2013-07-03
    Description: Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder for which the mechanisms leading to profound neuronal loss are incompletely recognized. MicroRNAs (miRNAs) are recently discovered small regulatory RNA molecules that repress gene expression and are increasingly acknowledged as prime regulators involved in human brain pathologies. Here we identified two homologous miRNAs, miR-132 and miR-212, downregulated in temporal cortical areas and CA1 hippocampal neurons of human AD brains. Sequence-specific inhibition of miR-132 and miR-212 induces apoptosis in cultured primary neurons, whereas their overexpression is neuroprotective against oxidative stress. Using primary neurons and PC12 cells, we demonstrate that miR-132/212 controls cell survival by direct regulation of PTEN, FOXO3a and P300, which are all key elements of AKT signaling pathway. Silencing of these three target genes by RNAi abrogates apoptosis caused by the miR-132/212 inhibition. We further demonstrate that mRNA and protein levels of PTEN, FOXO3a, P300 and most of the direct pro-apoptotic transcriptional targets of FOXO3a are significantly elevated in human AD brains. These results indicate that the miR-132/miR-212/PTEN/FOXO3a signaling pathway contributes to AD neurodegeneration.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Observation of unpaired substrate DNA in the flap endonuclease-1 active site (2013)
    Oxford University Press
    Details
    Publication Date: 2013-11-21
    Description: The structure- and strand-specific phosphodiesterase flap endonuclease-1 (FEN1), the prototypical 5'-nuclease, catalyzes the essential removal of 5'-single-stranded flaps during replication and repair. FEN1 achieves this by selectively catalyzing hydrolysis one nucleotide into the duplex region of substrates, always targeting the 5'-strand. This specificity is proposed to arise by unpairing the 5'-end of duplex to permit the scissile phosphate diester to contact catalytic divalent metal ions. Providing the first direct evidence for this, we detected changes induced by human FEN1 (hFEN1) in the low-energy CD spectra and fluorescence lifetimes of 2-aminopurine in substrates and products that were indicative of unpairing. Divalent metal ions were essential for unpairing. However, although 5'-nuclease superfamily-conserved active-site residues K93 and R100 were required to produce unpaired product, they were not necessary to unpair substrates. Nevertheless, a unique arrangement of protein residues around the unpaired DNA was detected only with wild-type protein, suggesting a cooperative assembly of active-site residues that may be triggered by unpaired DNA. The general principles of FEN1 strand and reaction-site selection, which depend on the ability of juxtaposed divalent metal ions to unpair the end of duplex DNA, may also apply more widely to other structure- and strand-specific nucleases.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    The SNM1B/APOLLO DNA nuclease functions in resolution of replication stress and maintenance of common fragile site stability (2013)
    Oxford University Press
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    Publication Date: 2013-11-22
    Description: SNM1B/Apollo is a DNA nuclease that has important functions in telomere maintenance and repair of DNA interstrand crosslinks (ICLs) within the Fanconi anemia (FA) pathway. SNM1B is required for efficient localization of key repair proteins, such as the FA protein, FANCD2, to sites of ICL damage and functions epistatically to FANCD2 in cellular survival to ICLs and homology-directed repair. The FA pathway is also activated in response to replication fork stalling. Here, we sought to determine the importance of SNM1B in cellular responses to stalled forks in the absence of a blocking lesion, such as ICLs. We found that depletion of SNM1B results in hypersensitivity to aphidicolin, a DNA polymerase inhibitor that causes replication stress. We observed that the SNM1B nuclease is required for efficient localization of the DNA repair proteins, FANCD2 and BRCA1, to subnuclear foci upon aphidicolin treatment, thereby indicating SNM1B facilitates direct repair of stalled forks. Consistent with a role for SNM1B subsequent to recognition of the lesion, we found that SNM1B is dispensable for upstream events, including activation of ATR-dependent signaling and localization of RPA, H2AX and the MRE11/RAD50/NBS1 complex to aphidicolin-induced foci. We determined that a major consequence of SNM1B depletion is a marked increase in spontaneous and aphidicolin-induced chromosomal gaps and breaks, including breakage at common fragile sites. Thus, this study provides evidence that SNM1B functions in resolving replication stress and preventing accumulation of genomic damage.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Formation and evolution of the water maser outflow event in AFGL 2591 VLA 3-N (2013)
    Oxford University Press
    Details
    Publication Date: 2013-03-02
    Description: In this paper we analyse multi-epoch very long baseline interferometry water maser observations carried out with the Very Long Baseline Array towards the high-mass star-forming region AFGL 2591. We detected maser emission associated with the radio continuum sources VLA 2 and VLA 3. In addition, a water maser cluster, VLA 3-N, was detected ~0.5 arcsec north of VLA 3. We concentrate the discussion of this paper on the spatio-kinematical distribution of the water masers towards VLA 3-N. The water maser emission towards the region VLA 3-N shows two bow-shock-like structures, northern and southern, separated from each other by ~100 mas (~330 au). The spatial distribution and kinematics of the water masers in this cluster have persisted over a time span of 7 yr. The northern bow shock has a somewhat irregular morphology, while the southern one has a remarkably smooth morphology. We measured the proper motions of 33 water maser features, which have an average proper motion velocity of ~1.3 mas yr –1 (~20 km s –1 ). The morphology and the proper motions of this cluster of water masers show systematic expanding motions that could imply one or two different centres of star formation activity. We made a detailed model for the southern structure, proposing two different kinematic models to explain the three-dimensional spatio-kinematical distribution of the water masers: (1) a static central source driving the two bow-shock structures and (2) two independent driving sources, one of them exciting the northern bow-shock structure, and the other one, a young runaway star moving in the local molecular medium exciting and moulding the remarkably smoother southern bow-shock structure. Future observations will be necessary to discriminate between the two scenarios, in particular by identifying the still unseen driving source(s).
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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