Searching for O2_2 in the SMC:Constraints on Oxygen Chemistry at Low Metallicities

We present a 39 h integration with the Odin satellite on the ground-state 118.75 GHz line of O2 towards the region of strongest molecular emission in the Small Magellanic Cloud. Our 3sigma upper limit to the O2 integrated intensity of <0.049 K km/s in a 9'(160 pc) diameter beam corresponds to an upper limit on the O2/H2 abundance ratio of <1.3E-6. Although a factor of 20 above the best limit on the O2 abundance obtained for a Galactic source, our result has interesting implications for understanding oxygen chemistry at sub-solar metal abundances. We compare our abundance limit to a variety of astrochemical models and find that, at low metallicities, the low O2 abundance is most likely produced by the effects of photo-dissociation on molecular cloud structure. Freeze-out of molecules onto dust grains may also be consistent with the observed abundance limit, although such models have not yet been run at sub-solar initial metallicities.Comment: 4 pages, accepted to A&A Letter

Tracing the sites of obscured star formation in the Antennae galaxies with Herschel-PACS

FIR imaging of interacting galaxies allows locating even hidden sites of star formation and measuring of the relative strength of nuclear and extra-nuclear star formation. We want to resolve the star-forming sites in the nearby system of the Antennae. Thanks to the unprecedented sharpness and depth of the PACS camera onboard ESA's Herschel Space Observatory, it is possible for the first time to achieve a complete assessment of individual star-forming knots in the FIR with scan maps at 70, 100, and 160 um. We used clump extraction photometry and SED diagnostics to derive the properties related to star-forming activity. The PACS 70, 100, and 160 um maps trace the knotty structure of the most recent star formation along an arc between the two nuclei in the overlap area. The resolution of the starburst knots and additional multi-wavelength data allow their individual star formation history and state to be analysed. In particular, the brightest knot in the mid-infrared (K1), east of the southern nucleus, exhibits the highest activity by far in terms of dust heating and star formation rate, efficiency, and density. With only 2 kpc in diameter, this area has a 10-1000 um luminosity, which is as high as that of our Milky Way. It shows the highest deficiency in radio emission in the radio-to-FIR luminosity ratio and a lack of X-ray emission, classifying it as a very young complex. The brightest 100 and 160 um emission region (K2), which is close to the collision front and consists of 3 knots, also shows a high star formation density and efficiency and lack of X-ray emission in its most obscured part, but an excess in the radio-to-FIR luminosity ratio. This suggests a young stage, too, but different conditions in its interstellar medium. Our results provide important checkpoints for numerical simulations of interacting galaxies when modelling the star formation and stellar feedback.Comment: 4 pages, 4 figures, 2 tables (A&A Herschel special issue

Weak localization in disordered systems at the ballistic limit

The weak localization (WL) contribution to the two-level correlation function is calculated for two-dimensional disordered conductors. Our analysis extends to the nondiffusive (ballistic) regime, where the elastic mean path is of order of the size of the system. In this regime the structure factor (the Fourier transform of the two-point correlator) exhibits a singular behavior consisting of dips superimposed on a smooth positive background. The strongest dips appear at periods of the periodic orbits of the underlying clean system. Somewhat weaker singularities appear at times which are sums of periods of two such orbits. The results elucidate various aspects of the weak localization physics of ballistic chaotic systems.Comment: 13 pages, 13 figure

The Role of Dwarf Galaxy Interactions in Shaping the Magellanic System and Implications for Magellanic Irregulars

We present a novel pair of numerical models of the interaction history between the Large and Small Magellanic Clouds (LMC and SMC, respectively) and our Milky Way (MW) in light of recent high precision proper motions (Kallivayalil et al. 2006a,b). Given the new velocities, cosmological simulations of structure formation favor a scenario where the Magellanic Clouds (MCs) are currently on their first infall towards our Galaxy (Boylan-Kolchin et al. 2011, Busha et al. 2011). We illustrate here that the observed irregular morphology and internal kinematics of the MCs (in gas and stars) are naturally explained by interactions between the LMC and SMC, rather than gravitational interactions with the MW. This picture further supports a first infall scenario (Besla et a. 2007). In particular, we demonstrate that the Magellanic Stream, a band of HI gas trailing behind the MCs 150 degrees across the sky, can be accounted for by the action of LMC tides on the SMC before the system was accreted by the MW. We further demonstrate that the off-center, warped stellar bar of the LMC and its one-armed spiral, can be naturally explained by a recent direct collision with the SMC. Such structures are key morphological characteristics of a class of galaxies referred to as Magellanic Irregulars (de Vaucouleurs & Freeman 1972), the majority of which are not associated with massive spiral galaxies. We infer that dwarf-dwarf galaxy interactions are important drivers for the morphological evolution of Magellanic Irregulars and can dramatically affect the efficiency of baryon removal from dwarf galaxies via the formation of extended tidal bridges and tails. Such interactions are important not only for the evolution of dwarf galaxies but also have direct consequences for the buildup of baryons in our own MW, as LMC-mass systems are believed to be the dominant building blocks of MW-type halos.Comment: 33 pages, 21 figures, Accepted for publication in MNRAS, Dec 23 201

The RAST Server: Rapid Annotations using Subsystems Technology

<p>Abstract</p> <p>Background</p> <p>The number of prokaryotic genome sequences becoming available is growing steadily and is growing faster than our ability to accurately annotate them.</p> <p>Description</p> <p>We describe a fully automated service for annotating bacterial and archaeal genomes. The service identifies protein-encoding, rRNA and tRNA genes, assigns functions to the genes, predicts which subsystems are represented in the genome, uses this information to reconstruct the metabolic network and makes the output easily downloadable for the user. In addition, the annotated genome can be browsed in an environment that supports comparative analysis with the annotated genomes maintained in the SEED environment.</p> <p>The service normally makes the annotated genome available within 12–24 hours of submission, but ultimately the quality of such a service will be judged in terms of accuracy, consistency, and completeness of the produced annotations. We summarize our attempts to address these issues and discuss plans for incrementally enhancing the service.</p> <p>Conclusion</p> <p>By providing accurate, rapid annotation freely to the community we have created an important community resource. The service has now been utilized by over 120 external users annotating over 350 distinct genomes.</p

SYT1-associated neurodevelopmental disorder: a case series.

Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1I368T and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals' phenotypes, suggesting that the efficiency of SYT1-mediated neurotransmitter release is critical to cognitive development. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1

Comparative Genomics Study of Multi-Drug-Resistance Mechanisms in the Antibiotic-Resistant Streptococcus suis R61 Strain

BACKGROUND: Streptococcus suis infections are a serious problem for both humans and pigs worldwide. The emergence and increasing prevalence of antibiotic-resistant S. suis strains pose significant clinical and societal challenges. RESULTS: In our study, we sequenced one multi-drug-resistant S. suis strain, R61, and one S. suis strain, A7, which is fully sensitive to all tested antibiotics. Comparative genomic analysis revealed that the R61 strain is phylogenetically distinct from other S. suis strains, and the genome of R61 exhibits extreme levels of evolutionary plasticity with high levels of gene gain and loss. Our results indicate that the multi-drug-resistant strain R61 has evolved three main categories of resistance. CONCLUSIONS: Comparative genomic analysis of S. suis strains with diverse drug-resistant phenotypes provided evidence that horizontal gene transfer is an important evolutionary force in shaping the genome of multi-drug-resistant strain R61. In this study, we discovered novel and previously unexamined mutations that are strong candidates for conferring drug resistance. We believe that these mutations will provide crucial clues for designing new drugs against this pathogen. In addition, our work provides a clear demonstration that the use of drugs has driven the emergence of the multi-drug-resistant strain R61

A qualitative study exploring midlife women’s stages of change from domestic violence towards freedom

Gold OABackground Domestic Violence (DV) remains a significant global health problem for women in contemporary society. Existing literature on midlife women’s experiences of domestic violence is limited and focuses on health implications. Leaving a violent relationship is a dynamic process that often requires multiple attempts and separations prior to final termination. The aim of this study was to explore the process of leaving a violent relationship for midlife women. Methods This qualitative study involved fifteen women aged between 40–55 who had accessed residential and non-residential community support services for domestic violence within the UK. Community-based support agencies provided these women with access to letters of invitation and participant information sheet explaining the study. The women notified agency staff who contacted the research team to arrange a mutually convenient time to meet within a safe place for both the women and researchers. It was stressed to all potential participants that no identifiable information would be shared with the agency staff. Women were considered survivors of DV if they defined themselves as such. Data were gathered through semi structured interviews, transcribed verbatim and thematically analysed. Results Midlife women appear to differ from younger women by transitioning quickly though the stages of change, moving rapidly through the breaking free onto the maintenance stage. This rapid transition is the resultant effect of living with long-term violence causing a shift in the women’s perception towards the violent partner, with an associated reclamation of power from within the violent relationship. A realisation that rapid departure from the violence may be critical in terms of personal safety, and the realisation that there was something ‘wrong’ within the relationship, a ‘day of dawning’ that had not been apparent previously appears to positively affect the trajectory of leaving. Conclusions Midlife women appeared to navigate through the stages of change in a rapid linear process, forging ahead and exiting the relationship with certainty and without considering options. Whilst these findings appear to differ from younger women’s process of leaving, further research is needed to explore and understand the optimum time for intervention and support to maximise midlife women’s opportunities to escape an abusive partner, before being reflected appropriately in policy and practice.This study received funding from The Research and Knowledge Transfer Office, The University of Chester, and from the Western Australian Health Promotion Foundation – ‘Healthway

Molecular Dynamics Simulation of the Complex PBP-2x with Drug Cefuroxime to Explore the Drug Resistance Mechanism of Streptococcus suis R61

Drug resistance of Streptococcus suis strains is a worldwide problem for both humans and pigs. Previous studies have noted that penicillin-binding protein (PBPs) mutation is one important cause of β-lactam antibiotic resistance. In this study, we used the molecular dynamics (MD) method to study the interaction differences between cefuroxime (CES) and PBP2x within two newly sequenced Streptococcus suis: drug-sensitive strain A7, and drug-resistant strain R61. The MM-PBSA results proved that the drug bound much more tightly to PBP2x in A7 (PBP2x-A7) than to PBP2x in R61 (PBP2x-R61). This is consistent with the evidently different resistances of the two strains to cefuroxime. Hydrogen bond analysis indicated that PBP2x-A7 preferred to bind to cefuroxime rather than to PBP2x-R61. Three stable hydrogen bonds were formed by the drug and PBP2x-A7, while only one unstable bond existed between the drug and PBP2x-R61. Further, we found that the Gln569, Tyr594, and Gly596 residues were the key mutant residues contributing directly to the different binding by pair wise energy decomposition comparison. By investigating the binding mode of the drug, we found that mutant residues Ala320, Gln553, and Thr595 indirectly affected the final phenomenon by topological conformation alteration. Above all, our results revealed some details about the specific interaction between the two PBP2x proteins and the drug cefuroxime. To some degree, this explained the drug resistance mechanism of Streptococcus suis and as a result could be helpful for further drug design or improvement