Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae

Extracytoplasmic solute receptors (ESRs) are important components of solute uptake systems in bacteria, having been studied extensively as parts of ATP binding cassette transporters. Herein we report the first crystal structure of an ESR protein from a functionally characterized electrochemical ion gradient-dependent secondary transporter. This protein, SiaP, forms part of a tripartite ATP-independent periplasmic transporter specific for sialic acid in Haemophilus influenzae. Surprisingly, the structure reveals an overall topology similar to ATP binding cassette ESR proteins, which is not apparent from the sequence, demonstrating that primary and secondary transporters can share a common structural component. The structure of SiaP in the presence of the sialic acid analogue 2,3-didehydro-2-deoxyN-acetylneuraminic acid reveals the ligand bound in a deep cavity with its carboxylate group forming a salt bridge with a highly conserved Arg residue. Sialic acid binding, which obeys simple bimolecular association kinetics as determined by stopped-flow fluorescence spectroscopy, is accompanied by domain closure about a hinge region and the kinking of an alpha-helix hinge component. The structure provides insight into the evolution, mechanism, and substrate specificity of ESR-dependent secondary transporters that are widespread in prokaryotes

European follow-up of incorrect biomarker results for colorectal cancer demonstrates the importance of quality improvement projects

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Charge-Coupled Device Panoramic Radiography: Area Image Distortion Factors as Selected Image Layer Contours

Svrha: Svrha ove studije bila je odrediti svojstva čimbenika izobličenja kontura razlučivanja odabranog sloja slike ortopantomografa OP 100®Instrumentarium Imaging, Tuusula, Finland) kombiniranog sa senzorom vrste CCD (charge-coupled device) tipa (Trophy Radiologie, Vincennes, France). Materijal i metode: Upotrebom mreže kojom se određuje razlučivanje postavljene u razmacima uzduž iskustveno ustanovljenih putanja projekcijskog snopa, konture sloja slike proizvodene ortopantomografom OP 100® modificiranim s osjetilom DigiPan® prethodno su određene za granice razlučivanja od 4,0, 3,0 i 1,5 lp m m 1. Za određivanje čimbenika povećanja uz odabrane granice razlučivanja i vodoravne angulacije snopa bila je upotrebljena jedna šestokutna ispitna naprava, uz uporabu mjernog algoritma koji pripada vlastitom softwareu (programskoj podršci) osjetila DigiPan®. Zatim su upotrebljena vodoravna i okomita povećanja kako be se odredili čimbenici izobličenja za svaku konturu razlučivanja uzduž odabrane angulacije snopa. Rezultati: Uz konture razlučivanja sloja slike od 4 lp m m 1 svi čimbenici izobličenja površine bili su približno jedinica. U području omeđenom tim konturama razlučivanja mjerni je algoritam kompenzirao učinke izobličenja svojstvene povećanju, uzrokovanom geometrijom snopa X-zraka. Uz 1,5 lp m m 1 čimbenici izobličenja površine kretali su se od 1,16 do 1,19 facijalno i 1,14 do 1,22 lingvalno u odnosu prema konturi sloja slike najvećeg razlučivanja. Kontura sloja slike s najvećim prostornim razlučivanjem bila je postavljena lingvalno u odnosu spram geometrijskome središtu žarišta. Zaključak: Upotrebom osjetila DigiPan® i uređaja OP 100® ustanovljene vrijednosti izobličenja odgovaraju vrijednostima već ustanovljenim s pomoću konvencionalnih receptora vrste film/zaslon. U području najvećeg razlučivanja mjerni algoritam programa djelotvorno je kompenzirao izobličenje povećanja projekcionog snopa.Objectives: The aim of this study was to determine the distortion factor characteristics for selected image layer resolution contours of the Orthopantomograph OP 100® (Instrumentarium Imaging, Tuusula, Finland), combined with the DigiPan® (Trophy Radiologie, Vincennes, France) charge-coupled device receptor. Material and Methods: Using a resolution grid positioned at intervals along empirically determined beam projection paths, the image layer contours produced with the DigiPan® modification o f the Orthopantomograph OP 100® had previously been determined for resolution limits o f 4.0, 3.0 and 1.5 Ip m m 1. An hexagonal test device was used to determine the magnification factors at the selected resolution limits and horizontal beam angulations using the resident measurement algorithm o f the DigiPan® proprietary software. The horizontal and vertical magnifications were then used to determine the distortion factors at each resolution contour along selected beam angulations. Results: At the image layer resolution contours of 4 Ip m m 1 all area distortion factors approached unity. Furthermore, in the region bounded by these resolution contours the measurement algorithm compensated for the inherent magnification distortion artefact caused by the X-ray beam geometry. At 1.5 Ip m m 1, the area distortion factors ranged from 1.16 to 1.19 facially and 1.14 to 1.22 lingually to image layer contour of maximum resolution. The image layer contour of maximum spatial resolution was positioned lingually to the geometric center o f the focal trough. Conclusion: Using the DigiPan®, and the op 100® the distortion values conform o f those previously found using conventional film/screen receptors. In the region o f maximum resolution, the software measurement algotirhm effectively compensated for beam- projection magnification distortion

Characterization of Metal-Doped Methylated Microporous Silica for Molecular Separations

Novel silica xerogels are prepared and developed by sol-gel method in the present study. The preparation involves cobalt-doping within the organic templated silica matrices, where methyltriethoxysilane (MTES), which contains methyl groups as a covalently bonded organic template is used. The synthesis and surface properties of cobalt-doped methylated microporous silica xerogels with different MTES and cobalt content are revealed by surface and microstructural techniques, such as TGA, FTIR, X-ray and N2 adsorption measurements. The doping process enhances the thermal stability of the silica xerogels up to ~ 560 °C in oxidizing atmosphere. Besides, this process has no significant effect on the incorporation of the organic template within the silica matrix. As result of the promoted densification of the xerogels either by increasing MTES content and heat treatment, there is structural change of the silica xerogels such as decreasing the micropore volume and broadening of the pore size distribution. Heat treatment and increasing the cobalt oxide content from 5 to 10% weight ratio resulted in samples with approximately the same structural parameters. This suggests that the cobalt particles are homogeneously dispersed in the silica matrix. The novel silica xerogels exhibit trend toward micropores formation suggesting that these doped silica xerogels can be precursor materials for molecular sieve silica membranes applications. Two silica membranes, hydrophobic and cobalt-doped hydrophobic, are prepared and their performance is examined by the study of transport of He, H2 and N2. Preliminary results show that the microporous structure obtained in the unsupported cobalt-doped hydrophobic material are preserved after coating inside the tubular support

Characterization of Metal-Doped Methylated Microporous Silica for Molecular Separations

Novel silica xerogels are prepared and developed by sol-gel method in the present study. The preparation involves cobalt-doping within the organic templated silica matrices, where methyltriethoxysilane (MTES), which contains methyl groups as a covalently bonded organic template is used. The synthesis and surface properties of cobalt-doped methylated microporous silica xerogels with different MTES and cobalt content are revealed by surface and microstructural techniques, such as TGA, FTIR, X-ray and N2 adsorption measurements. The doping process enhances the thermal stability of the silica xerogels up to ~ 560 °C in oxidizing atmosphere. Besides, this process has no significant effect on the incorporation of the organic template within the silica matrix. As result of the promoted densification of the xerogels either by increasing MTES content and heat treatment, there is structural change of the silica xerogels such as decreasing the micropore volume and broadening of the pore size distribution. Heat treatment and increasing the cobalt oxide content from 5 to 10% weight ratio resulted in samples with approximately the same structural parameters. This suggests that the cobalt particles are homogeneously dispersed in the silica matrix. The novel silica xerogels exhibit trend toward micropores formation suggesting that these doped silica xerogels can be precursor materials for molecular sieve silica membranes applications. Two silica membranes, hydrophobic and cobalt-doped hydrophobic, are prepared and their performance is examined by the study of transport of He, H2 and N2. Preliminary results show that the microporous structure obtained in the unsupported cobalt-doped hydrophobic material are preserved after coating inside the tubular support

Trans-generational transmission of the Glossina pallidipes hytrosavirus depends on the presence of a functional symbiome

The vertically transmitted endosymbionts (Sodalis glossinidius and Wigglesworthia glossinidia) of the tsetse fly (Diptera: Glossinidae) are known to supplement dietary deficiencies and modulate the reproductive fitness and the defense system of the fly. Some tsetse fly species are also infected with the bacterium, Wolbachia and with the Glossina hytrosavirus (GpSGHV). Laboratory-bred G. pallidipes exhibit chronic asymptomatic and acute symptomatic GpSGHV infection, with the former being the most common in these colonies. However, under as yet undefined conditions, the asymptomatic state can convert to the symptomatic state, leading to detectable salivary gland hypertrophy (SGH+) syndrome. In this study, we investigated the interplay between the bacterial symbiome and GpSGHV during development of G. pallidipes by knocking down the symbionts with antibiotic. Intrahaemocoelic injection of GpSGHV led to high virus titre (109 virus copies), but was not accompanied by either the onset of detectable SGH+, or release of detectable virus particles into the blood meals during feeding events. When the F1 generations of GpSGHV-challenged mothers were dissected within 24 h post-eclosion, SGH+ was observed to increase from 4.5% in the first larviposition cycle to >95% in the fourth cycle. Despite being sterile, these F1 SGH+ progeny mated readily. Removal of the tsetse symbiome, however, suppressed transgenerational transfer of the virus via milk secretions and blocked the ability of GpSGHV to infect salivary glands of the F1 progeny. Whereas GpSGHV infects and replicates in salivary glands of developing pupa, the virus is unable to induce SGH+ within fully differentiated adult salivary glands. The F1 SGH+ adults are responsible for the GpSGHV-induced colony collapse in tsetse factories. Our data suggest that GpSGHV has co-evolved with the tsetse symbiome and that the symbionts play key roles in the virus transmission from mother to progeny

Cosmological distance indicators

We review three distance measurement techniques beyond the local universe: (1) gravitational lens time delays, (2) baryon acoustic oscillation (BAO), and (3) HI intensity mapping. We describe the principles and theory behind each method, the ingredients needed for measuring such distances, the current observational results, and future prospects. Time delays from strongly lensed quasars currently provide constraints on $H_0$ with < 4% uncertainty, and with 1% within reach from ongoing surveys and efforts. Recent exciting discoveries of strongly lensed supernovae hold great promise for time-delay cosmography. BAO features have been detected in redshift surveys up to z <~ 0.8 with galaxies and z ~ 2 with Ly-$\alpha$ forest, providing precise distance measurements and $H_0$ with < 2% uncertainty in flat $\Lambda$CDM. Future BAO surveys will probe the distance scale with percent-level precision. HI intensity mapping has great potential to map BAO distances at z ~ 0.8 and beyond with precisions of a few percent. The next years ahead will be exciting as various cosmological probes reach 1% uncertainty in determining $H_0$, to assess the current tension in $H_0$ measurements that could indicate new physics.Comment: Review article accepted for publication in Space Science Reviews (Springer), 45 pages, 10 figures. Chapter of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Ag

Black Hole Spin via Continuum Fitting and the Role of Spin in Powering Transient Jets

The spins of ten stellar black holes have been measured using the continuum-fitting method. These black holes are located in two distinct classes of X-ray binary systems, one that is persistently X-ray bright and another that is transient. Both the persistent and transient black holes remain for long periods in a state where their spectra are dominated by a thermal accretion disk component. The spin of a black hole of known mass and distance can be measured by fitting this thermal continuum spectrum to the thin-disk model of Novikov and Thorne; the key fit parameter is the radius of the inner edge of the black hole's accretion disk. Strong observational and theoretical evidence links the inner-disk radius to the radius of the innermost stable circular orbit, which is trivially related to the dimensionless spin parameter a_* of the black hole (|a_*| < 1). The ten spins that have so far been measured by this continuum-fitting method range widely from a_* \approx 0 to a_* > 0.95. The robustness of the method is demonstrated by the dozens or hundreds of independent and consistent measurements of spin that have been obtained for several black holes, and through careful consideration of many sources of systematic error. Among the results discussed is a dichotomy between the transient and persistent black holes; the latter have higher spins and larger masses. Also discussed is recently discovered evidence in the transient sources for a correlation between the power of ballistic jets and black hole spin.Comment: 30 pages. Accepted for publication in Space Science Reviews. Also to appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher). Changes to Sections 5.2, 6.1 and 7.4. Section 7.4 responds to Russell et al. 2013 (MNRAS, 431, 405) who find no evidence for a correlation between the power of ballistic jets and black hole spi

Smaller classes promote equitable student participation in STEM

Under embargo until: 2020-07-24As science, technology, engineering, and mathematics (STEM) classrooms in higher education transition from lecturing to active learning, the frequency of student interactions in class increases. Previous research documents a gender bias in participation, with women participating less than would be expected on the basis of their numeric proportions. In the present study, we asked which attributes of the learning environment contribute to decreased female participation: the abundance of in-class interactions, the diversity of interactions, the proportion of women in class, the instructor's gender, the class size, and whether the course targeted lower division (first and second year) or upper division (third or fourth year) students. We calculated likelihood ratios of female participation from over 5300 student–instructor interactions observed across multiple institutions. We falsified several alternative hypotheses and demonstrate that increasing class size has the largest negative effect. We also found that when the instructors used a diverse range of teaching strategies, the women were more likely to participate after small-group discussions.acceptedVersio