Differential Single-stranded DNA Binding Properties of the Paralogous SsbA and SsbB Proteins from Streptococcus pneumoniae

The naturally transformable Gram-positive bacterium Streptococcus pneumoniae has two single-stranded DNA-binding (SSB) proteins, designated SsbA and SsbB. The SsbA protein is similar in size to the well characterized SSB protein from Escherichia coli (SsbEc). The SsbB protein, in contrast, is a smaller protein that is specifically induced during natural transformation and has no counterpart in E. coli. In this report, the single-stranded DNA (ssDNA) binding properties of the SsbA and SsbB proteins were examined and compared with those of the SsbEc protein. The ssDNA binding characteristics of the SsbA protein were similar to those of the SsbEc protein in every ssDNA binding assay used in this study. The SsbB protein differed from the SsbA and SsbEc proteins, however, both in its binding to short homopolymeric dT(n) oligomers (as judged by polyacrylamide gel-shift assays) and in its binding to the longer naturally occurring X and M13 ssDNAs (as judged by agarose gel-shift assays and electron microscopic analysis). The results indicate that an individual SsbB protein binds to ssDNA with an affinity that is similar or higher than that of the SsbA and SsbEc proteins. However, the manner in which multiple SsbB proteins assemble onto a ssDNA molecule differs from that observed with the SsbA and SsbEc proteins. These results represent the first analysis of paralogous SSB proteins from any bacterial species and provide a foundation for further investigations into the biological roles of these proteins

The Influence of Setting on Care Coordination for Childhood Asthma

Asthma affects 7.1 million children in the United States, disproportionately burdening African American and Latino children. Barriers to asthma control include insufficient patient education and fragmented care. Care coordination represents a compelling approach to improve quality of care and address disparities in asthma. The sites of The Merck Childhood Asthma Network Care Coordination Programs implemented different models of care coordination to suit specific settings—school district, clinic or health care system, and community—and organizational structures. A variety of qualitative data sources were analyzed to determine the role setting played in the manifestation of care coordination at each site. There were inherent strengths and challenges of implementing care coordination in each of the settings, and each site used unique strategies to deliver their programs. The relationship between the lead implementing unit and entities that provided (1) access to the priority population and (2) clinical services to program participants played a critical role in the structure of the programs. The level of support and infrastructure provided by these entities to the lead implementing unit influenced how participants were identified and how asthma care coordinators were integrated into the clinical care team.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/1/MCAN_Settings_Manuscript_20150708.docxhttp://deepblue.lib.umich.edu/bitstream/2027.42/113262/3/MCAN_Settings_Manuscript_20150708.pdfDescription of MCAN_Settings_Manuscript_20150708.docx : Main ArticleDescription of MCAN_Settings_Manuscript_20150708.pdf : Main Article with Title Page and Abstrac

Flight Demonstration of Integrated Airport Surface Technologies for Increased Capacity and Safety

A flight demonstration was conducted to address airport surface movement area capacity and safety issues by providing pilots with enhanced situational awareness information. The demonstration presented an integration of several technologies to government and industry representatives. These technologies consisted of an electronic moving map display in the cockpit, a Differential Global Positioning system (DGPS) receiver, a high speed very high frequency (VHF) data link, an Airport Surface Detection Equipment (ASDE-3) radar, and the Airport Movement Area Safety System (AMASS). Aircraft identification was presented to an air traffic controller on an AMASS display. The onboard electronic map included the display of taxi routes, hold instructions, and clearances, which were sent to the aircraft via data link by the controller. The map also displayed the positions of other traffic and warning information, which were sent to the aircraft automatically from the ASDE-3/AMASS system. This paper describes the flight demonstration in detail, along with test results

Motor crosslinking augments elasticity in active nematics

In active materials, uncoordinated internal stresses lead to emergent long-range flows. An understanding of how the behavior of active materials depends on mesoscopic (hydrodynamic) parameters is developing, but there remains a gap in knowledge concerning how hydrodynamic parameters depend on the properties of microscopic elements. In this work, we combine experiments and multiscale modeling to relate the structure and dynamics of active nematics composed of biopolymer filaments and molecular motors to their microscopic properties, in particular motor processivity, speed, and valency. We show that crosslinking of filaments by both motors and passive crosslinkers not only augments the contributions to nematic elasticity from excluded volume effects but dominates them. By altering motor kinetics we show that a competition between motor speed and crosslinking results in a nonmonotonic dependence of nematic flow on motor speed. By modulating passive filament crosslinking we show that energy transfer into nematic flow is in large part dictated by crosslinking. Thus motor proteins both generate activity and contribute to nematic elasticity. Our results provide new insights for rationally engineering active materials

A near-IR study of the host galaxies of 2Jy radio sources at 0.03 < z < 0.5: I - the data

We present the results of a program of K- and Ks-band imaging of a sample of 2Jy radio galaxies with redshifts 0.03 < z < 0.5, for which the host galaxy morphologies and structural parameters (effective radius, Sersic index and unresolved nuclear point source contribution) have been determined using GALFIT. Two-thirds of our sample are best modelled as being hosted by massive elliptical galaxies with Sersic indices of n=4-6, with the remainder being better suited either by a mixture of morphological components (usually a bulge plus a small, less luminous, disk component) or by more disky galaxy models with n=1-2. Our measured galaxy sizes are generally in very good agreement with other imaging programs, both space- and ground-based. We also determine a slightly higher average nuclear point source contribution than similar HST-based programs. This is due to our inability to separate the AGN emission from compact circum-nuclear stellar emission, but does not bias our modelling of the remainder of the host galaxies and our results remain robust. We also observe that roughly half of the objects in our sample are either undergoing major or minor merger activity or are clearly morphologically disturbed.Comment: Accepted for publication in MNRAS. 31 pages, 9 figures, 6 tables. Landscape table 4 added as extra included figur

Fundamental Neutron Physics: a White Paper on Progress and Prospects in the US

Fundamental neutron physics, combining precision measurements and theory, probes particle physics at short range with reach well beyond the highest energies probed by the LHC. Significant US efforts are underway that will probe BSM CP violation with orders of magnitude more sensitivity, provide new data on the Cabibbo anomaly, more precisely measure the neutron lifetime and decay, and explore hadronic parity violation. World-leading results from the US Fundamental Neutron Physics community since the last Long Range Plan, include the world's most precise measurement of the neutron lifetime from UCN$\tau$, the final results on the beta-asymmetry from UCNA and new results on hadronic parity violation from the NPDGamma and n-${^3}$He runs at the FNPB (Fundamental Neutron Physics Beamline), precision measurement of the radiative neutron decay mode and n-${}^4$He at NIST. US leadership and discovery potential are ensured by the development of new high-impact experiments including BL3, Nab, LANL nEDM and nEDM@SNS. On the theory side, the last few years have seen results for the neutron EDM from the QCD $\theta$ term, a factor of two reduction in the uncertainty for inner radiative corrections in beta-decay which impacts CKM unitarity, and progress on {\it ab initio} calculations of nuclear structure for medium-mass and heavy nuclei which can eventually improve the connection between nuclear and nucleon EDMs. In order to maintain this exciting program and capitalize on past investments while also pursuing new ideas and building US leadership in new areas, the Fundamental Neutron Physics community has identified a number of priorities and opportunities for our sub-field covering the time-frame of the last Long Range Plan (LRP) under development. This white paper elaborates on these priorities.Comment: arXiv admin note: text overlap with arXiv:2304.0345

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

DNA binding compatibility of the Streptococcus pneumoniae SsbA and SsbB proteins.

BACKGROUND: Streptococcus pneumoniae has two paralogous, homotetrameric, single-stranded DNA binding (SSB) proteins, designated SsbA and SsbB. Previous studies demonstrated that SsbA and SsbB have different solution-dependent binding mode preferences with variable DNA binding capacities. The impact of these different binding properties on the assembly of multiple SsbAs and SsbBs onto single-stranded DNA was investigated. METHODOLOGY/PRINCIPAL FINDINGS: The complexes that were formed by the SsbA and SsbB proteins on dT(n) oligomers of defined lengths were examined by polyacrylamide gel electrophoresis. Complexes containing either two SsbAs or two SsbBs, or mixed complexes containing one SsbA and one SsbB, could be formed readily, provided the dT(n) oligomer was long enough to satisfy the full binding mode capacities of each of the bound proteins under the particular solution conditions. Complexes containing two SsbAs or two SsbBs could also be formed on shorter dT(n) oligomers via a "shared-strand binding" mechanism in which one or both proteins were bound using only a portion of their potential binding capacity. Mixed complexes were not formed on these shorter oligomers, however, indicating that SsbA and SsbB were incompatible for shared-strand binding. Additional experiments suggested that this shared-strand binding incompatibility may be due in part to differences in the structure of a loop region on the outer surface of the subunits of the SsbA and SsbB proteins. CONCLUSION/SIGNIFICANCE: These results indicate that the SsbA and SsbB proteins may co-assemble on longer DNA segments where independent binding is possible, but not on shorter DNA segments where coordinated interactions between adjacent SSBs are required. The apparent compatibility requirement for shared-strand binding could conceivably serve as a self-recognition mechanism that regulates the manner in which SsbA and SsbB interact in S. pneumoniae