Orientia tsutsugamushi ankyrin repeat-containing protein family members are Type 1 secretion system substrates that traffic to the host cell endoplasmic reticulum

Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and to where they localize in the host cell are not known. We determined that O. tsutsugamushi transcriptionally expresses 20 unique ank genes as well as genes for both T1SS and T4SS during infection of mammalian host cells. Examination of the Anks’ C-termini revealed that the majority of them resemble T1SS substrates. Escherichia coli expressing a functional T1SS was able to secrete chimeric hemolysin proteins bearing the C-termini of 19 of 20 O. tsutsugamushi Anks in an HlyBD-dependent manner. Thus, O. tsutsugamushi Anks C-termini are T1SS-compatible. Conversely, Coxiella burnetii could not secrete heterologously expressed Anks in a T4SS-dependent manner. Analysis of the subcellular distribution patterns of 20 ectopically expressed Anks revealed that, while 6 remained cytosolic or trafficked to the nucleus, 14 localized to, and in some cases, altered the morphology of the endoplasmic reticulum. This study identifies O. tsutsugamushi Anks as T1SS substrates and indicates that many display a tropism for the host cell secretory pathway

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

Theory of Star Formation

We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde

Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction

High temperature superconductivity (Tc onset at 34K) in the high pressure orthorhombic phase of FeSe

We have studied the structural and superconducting properties of tetragonal FeSe under pressures up to 26GPa using synchrotron radiation and diamond anvil cells. The bulk modulus of the tetragonal phase is 28.5(3)GPa, much smaller than the rest of Fe based superconductors. At 12GPa we observe a phase transition from the tetragonal to an orthorhombic symmetry. The high pressure orthorhombic phase has a higher Tc reaching 34K at 22GPa.Comment: 15 pages, 4 figure

Using the signal-to-noise ratio of GPS records to detect motion of structures

Although major breakthroughs have been achieved during the last decades in the use of Global Positioning System (GPS) technology on structural health monitoring, the mitigation of the biases and errors impeding its positioning accuracy remains a challenge. This paper tests an alternative approach that can increase the reliability of the GPS system in structural monitoring by using the spectral content of the signal-to-noise ratio (SNR) of GPS signals to detect frequencies of antenna vibrations. This approach suggests the potential of using SNR data analysis as a supplement to low-quality positioning solution or as a near real-time alert of excessive vibration proceeding the position solution calculation. Experiments, involving a GPS antenna subjected to vertical vibrations of 0.4- to 4.5-cm amplitude at a range of frequencies between 0.007 and 1 Hz, examine the dynamic multipath-induced SNR response corresponding to the antenna motion. Synchronised fluctuations in the SNR time series were observed to reflect the antenna motion and their spectral content to include the frequencies of motion. SNR records from the GPS monitoring of the Wilford suspension bridge were used to validate the SNR sensitivity to controlled vibrations of the bridge deck. The natural frequency of 1.64 Hz was extracted from SNR measurements using spectral analysis on a 6-mm amplitude vibration, and the frequency of the semistatic displacement (∼0.02 Hz) was revealed in the SNR records permitting, after appropriate filtering, the estimation of a few millimetre semistatic displacement from the GPS time series without the need for any other sensor

Nurse titrated analgesia and sedation in intensive care increases the frequency of comfort assessment and reduces midazolam use in paediatric patients following cardiac surgery

BACKGROUND Pain and sedation protocols are suggested to improve the outcomes of patients within paediatric intensive care. However, it is not clear how protocols will influence practice within individual units. OBJECTIVES Evaluate a nurse led pain and sedation protocols impact on pain scoring and analgesic and sedative administration for post-operative cardiac patients within a paediatric intensive care unit. METHODS A retrospective chart review was performed on 100 patients admitted to a tertiary paediatric intensive care unit pre and post introduction of an analgesic and sedative protocol. Stata12 was used to perform Chi-squared or Student's t-test to compare data between the groups. RESULTS Post protocol introduction documentation of pain assessments increased (pre protocol 3/24h vs post protocol 5/24h, p=0.006). Along with a reduction in administration of midazolam (57.6mcg/kg/min pre protocol vs 24.5mcg/kg/min post protocol, p=0.0001). Children's pain scores remained unchanged despite this change, with a trend towards more scores in the optimal range in the post protocol group (5 pre protocol vs 12 post protocol, p=0.06). CONCLUSIONS Introducing a pain and sedation protocol changed bedside nurse practice in pain and sedation management. The protocol has enabled nurses to provide pain and sedation management in a consistent and timely manner and reduced the dose of midazolam required to maintain comfort according to the patients COMFORT B scores. Individual evaluation of practice change is recommended to units who implement nurse led analgesic and sedative protocols to monitor changes in practice

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Long-period surface motion of the multi-patch Mw9.0 Tohoku-Oki earthquake

We show that it is possible to capture the oscillatory ground motion induced by the Tohoku-Oki event for periods ranging from 3 to 100s using Precise Point Positioning (PPP). We find that the ground motions of the sedimentary basins of Japan were large (respectively > 0.15m/s and >0.15m/s2 for velocity and acceleration) even for periods larger than 3s. We compare geodetic observables with a Ground Motion Prediction Equation (GMPE) designed for Japan seismicity and find that the Spectral Acceleration (SA) is well estimated for periods larger than 3s and distances ranging from 100 to 500km. At last, through the analysis of the displacement attenuation plots, we show that the 2011 Tohoku-Oki event is likely composed of multiple rupture patches as suggested before by time-reversal inversions of seismic data