The FANCD2-FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2

The Fanconi Anemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2-FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here we report the first structural insight into the human FANCD2-FANCI complex by obtaining the cryo- EM structure. The complex contains an inner cavity, large enough to accommodate a double stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain is observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2-FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain

Azumaya Objects in Triangulated Bicategories

We introduce the notion of Azumaya object in general homotopy-theoretic settings. We give a self-contained account of Azumaya objects and Brauer groups in bicategorical contexts, generalizing the Brauer group of a commutative ring. We go on to describe triangulated bicategories and prove a characterization theorem for Azumaya objects therein. This theory applies to give a homotopical Brauer group for derived categories of rings and ring spectra. We show that the homotopical Brauer group of an Eilenberg-Mac Lane spectrum is isomorphic to the homotopical Brauer group of its underlying commutative ring. We also discuss tilting theory as an application of invertibility in triangulated bicategories.Comment: 23 pages; final version; to appear in Journal of Homotopy and Related Structure

Pulmonary contusion in a collegiate diver: a case report

Abstract Introduction Pulmonary contusions typically occur after high-energy trauma and have rarely been reported as occurring during participation in sports. This is the first reported case of a pulmonary contusion occurring in a sport other than football. Case Presentation A 19-year-old Caucasian man impacted the water awkwardly after diving off a one-meter springboard. He complained of chest discomfort and produced immediate hemoptysis. Computed tomography confirmed the diagnosis of pulmonary contusion. The athlete recovered without complications and returned to activity one week after injury. Conclusion Immediate hemoptysis following blunt chest trauma during sports activity may indicate an underlying pulmonary contusion. No specific guidelines exist for return to athletic competition following pulmonary contusion, but a progressive return to activities once symptoms resolve appears to be a reasonable approach.</p

Census politics in deeply divided societies

Population censuses in societies that are deeply divided along ethnic, religious or linguistic lines can be sensitive affairs – particularly where political settlements seek to maintain peace through the proportional sharing of power between groups. This brief sets out some key findings from a research project investigating the relationship between census politics and the design of political institutions in Bosnia and Herzegovina, Kenya, Lebanon and Northern Ireland

Ultrahigh Thermoelectric Performance in Mosaic Crystals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111928/1/adma201501030-sup-0001-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/111928/2/adma201501030.pd

Effects of galaxy-halo alignment and adiabatic contraction on gravitational lens statistics

We study the strong gravitational lens statistics of triaxial cold dark matter (CDM) halos occupied by central early-type galaxies. We calculate the image separation distribution for double, cusp and quad configurations. The ratios of image multiplicities at large separations are consistent with the triaxial NFW model, and at small separations are consistent with the singular isothermal ellipsoid (SIE) model. At all separations, the total lensing probability is enhanced by adiabatic contraction. If no adiabatic contraction is assumed, naked cusp configurations become dominant at approximately 2.5'', which is inconsistent with the data. We also show that at small-to-moderate separations, the image multiplicities depend sensitively on the alignment of the shapes of the luminous and dark matter projected density profiles. In constrast to other properties that affect these ratios, the degree of alignment does not have a significant effect on the total lensing probability. These correlations may therefore be constrained by comparing the theoretical image separation distribution to a sufficiently large lens sample from future wide and deep sky surveys such as Pan-Starrs, LSST and JDEM. Understanding the correlations in the shapes of galaxies and their dark matter halo is important for future weak lensing surveys.Comment: 10 pages, 7 figure

Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1/UAF1 Complex

The human deubiquitinase USP1 plays important roles in cancer-related processes, such as the DNA damage response, and the maintenance of the undifferentiated state of osteosarcoma cells. USP1 deubiquitinase activity is critically regulated by its interaction with the WD40 repeat-containing protein UAF1. Inhibiting the function of the USP1/UAF1 complex sensitizes cancer cells to chemotherapy, suggesting that this complex is a relevant anticancer target. Intriguingly, whereas UAF1 has been reported to locate in the cytoplasm, USP1 is a nuclear protein, although the sequence motifs that mediate its nuclear import have not been functionally characterized. Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1/UAF1 complex. Using a cellular relocation assay based on these results, we map the UAF1-binding site to a highly conserved 100 amino acid motif in USP1. Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs. Importantly, our findings have practical implications for the development of USP1-directed therapies. First, the UAF1-interacting region of USP1 identified here might be targeted to disrupt the USP1/UAF1 interaction with therapeutic purposes. On the other hand, we describe a cellular relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1/UAF1 complex

Golden gravitational lensing systems from the Sloan Lens ACS Survey. II. SDSS J1430+4105: A precise inner total mass profile from lensing alone

We study the SLACS strong lensing system SDSSJ1430+4105 at z=0.285. The lensed source (z=0.575) of this system has a complex morphology with several subcomponents. Its subcomponents span a radial range from 4 to 10kpc in the lens plane. Therefore we can constrain the slope of the total projected mass profile around the Einstein radius (R_E) from lensing alone. We measure a density profile that is slightly but not significantly shallower than isothermal at R_E. We decompose the mass of the lensing galaxy into a de Vaucouleurs (deV) component to trace the stars and an additional dark component. The spread of multiple image components over a large radial range also allows us to determine the amplitude of the deV and dark matter components separately. We get a mass to light ratio of M_deV/L_B~5.5\pm1.5M/L_sun,B and a dark matter fraction within R_E of ~20 to 40%. Modelling the star formation history assuming composite stellar populations at solar metallicity to the galaxy's photometry yields a mass to light ratio of M_star,salp/L_B~4.0_{-1.3}^{+0.6}M/L_sun,B and M_star,chab/L_B~2.3_{-0.8}^{+0.3}M/L_sun,B for Salpeter and Chabrier IMFs, respectively. Hence, the mass to light ratio derived from lensing is more Salpeter-like, in agreement with results for massive Coma galaxies and other nearby massive early type galaxies. We examine the consequences of the galaxy group in which the lensing galaxy is embedded, showing that it has little influence on the mass to light ratio obtained for the deV component of the lensing galaxy. Finally, we decompose the projected, azimuthally averaged 2D density distribution of the deV and dark matter component of the lensing signal into spherically averaged 3D density profiles. We can show that the 3D dark and luminous matter density within R_E~0.6R_eff of this SLACS galaxy is similar to the values of Coma galaxies with the same velocity dispersions.Comment: 24 pages, 21 figures, 11 tables, accepted for publication by MNRA

Blood Pressure and Job Domains Among Hotel Housekeepers

Hotel housekeepers have challenging working conditions, putting them at risk for poor health such as hypertension. Despite their risks, few studies have measured their blood pressure (BP). The purpose of this study was to explore hotel housekeepers’ blood pressure and the associations between work and BP. Methods: A community engagement approach was used to recruit study participants. Data sources included questionnaires, and BP measurement. Results: Over 25% of the 39 hotel housekeepers reported hypertension diagnosis and/or antihypertensive medication used. Across the job domains, job satisfaction was correlated with diastolic BP, and workload was correlated with systolic BP. There were difference in blood pressure reading, diagnosis and job domains between workers affiliated with union and those with no union affiliation. Discussion: Hypertension is a major concern among this worker group and warrants further investigation. Studies targeting union and non-union workers are needed, given their differences. Researchers will likely benefit from a community engagement approach with hotel housekeepers