The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>While many molecules involved in axon guidance have been identified, the cellular and molecular mechanisms by which these molecules regulate growth cone morphology during axon outgrowth remain to be elucidated. The actin cytoskeleton of the growth cone underlies the formation of lamellipodia and filopodia that control growth cone outgrowth and guidance. The role of the Arp2/3 complex in growth cone filopodia formation has been controversial, and other mechanisms of growth cone filopodia formation remain to be described.</p> <p>Results</p> <p>Here we show that mutations in genes encoding the Arp2/3 complex (<it>arx </it>genes) caused defects in axon guidance. Analysis of developing growth cones <it>in vivo </it>showed that <it>arx </it>mutants displayed defects in filopodia and reduced growth cone size. Time-lapse analysis of growth cones in living animals indicated that <it>arx </it>mutants affected the rate of growth cone filopodia formation but not filopodia stability or length. Two other actin modulatory proteins, UNC-115/abLIM and UNC-34/Enabled, that had been shown previously to affect axon guidance had overlapping roles with Arp2/3 in axon guidance and also affected the rate of filopodia initiation but not stability or length.</p> <p>Conclusion</p> <p>Our results indicate that the Arp2/3 complex is required cell-autonomously for axon guidance and growth cone filopodia initiation. Furthermore, they show that two other actin-binding proteins, UNC-115/abLIM and UNC-34/Enabled, also control growth cone filopodia formation, possibly in parallel to Arp2/3. These studies indicate that, <it>in vivo</it>, multiple actin modulatory pathways including the Arp2/3 complex contribute to growth cone filopodia formation during growth cone outgrowth.</p

Psychometric Properties of the Altarum Consumer Engagement (ACE) Measure of Activation in Patients with Prediabetes.

BackgroundPatient activation is associated with better outcomes in chronic conditions.ObjectiveWe evaluated the psychometric properties of the 12-item Altarum Consumer Engagement™ Measure (ACE-12) in patients with prediabetes.ParticipantsACE-12 was administered to patients in the Prediabetes Informed Decisions and Education Study.Main measuresWe conducted an exploratory factor analysis followed by confirmatory factor analytic models. We evaluated item response categories using item characteristic curves. Construct validity was assessed by examining correlations of the ACE-12 scales with education, depressive symptoms, self-rated health, hemoglobin A1c, body mass index, and weight loss.Key resultsParticipants (n = 515) had a median age of 58; 56% were female; 17% Hispanic; 54% were non-White. The scree plot and Tucker and Lewis reliability coefficient (0.95) suggested three factors similar to the original scales. One item loaded on the navigation rather than the informed choice scale. Ordinal alpha coefficients for the original scales were commitment (0.75); informed choice (0.71); and navigation (0.54). ICCs indicated that one or more of the response categories for 5 of the 12 items were never most likely to be selected. Patients with lower education were less activated on the commitment (r = - 0.124, p = 0.004), choice (r = - 0.085, p = 0.009), and overall score (r = - 0.042, p = 0.011). Patients with depressive symptoms had lower commitment (r = - 0.313, p ≤ 0.001) and overall scores (r = - 0.172, p = 0.012). Patients with poorer health scored lower on the Commitment (r = - 0.308, p ≤ 0.001), Navigation (r = - 0.137, p ≤ 0.001), and overall score (r = - 0.279, p ≤ 0.001).ConclusionThe analyses provide some support for the psychometric properties of the ACE-12 in prediabetic patients. Future research evaluating this tool among patients with other chronic conditions are needed to determine whether Q1 (I spend a lot of time learning about health) should remain in the informed choice or be included in the navigation scale. Additional items may be needed to yield acceptable reliability for the navigation scale

Southern Massive Stars at High Angular Resolution: Observational Campaign and Companion Detection

Multiplicity is one of the most fundamental observable properties of massive O-type stars and offers a promising way to discriminate between massive star formation theories. Nevertheless, companions at separations between 1 and 100 mas remain mostly unknown due to intrinsic observational limitations. [...] The Southern MAssive Stars at High angular resolution survey (SMASH+) was designed to fill this gap by providing the first systematic interferometric survey of Galactic massive stars. We observed 117 O-type stars with VLTI/PIONIER and 162 O-type stars with NACO/SAM, respectively probing the separation ranges 1-45 and 30-250mas and brightness contrasts of Delta H < 4 and Delta H < 5. Taking advantage of NACO's field-of-view, we further uniformly searched for visual companions in an 8''-radius down to Delta H = 8. This paper describes the observations and data analysis, reports the discovery of almost 200 new companions in the separation range from 1mas to 8'' and presents the catalog of detections, including the first resolved measurements of over a dozen known long-period spectroscopic binaries. Excluding known runaway stars for which no companions are detected, 96 objects in our main sample (DEC < 0 deg; H<7.5) were observed both with PIONIER and NACO/SAM. The fraction of these stars with at least one resolved companion within 200mas is 0.53. Accounting for known but unresolved spectroscopic or eclipsing companions, the multiplicity fraction at separation < 8'' increases to f_m = 0.91 +/- 0.03. The fraction of luminosity class V stars that have a bound companion reaches 100% at 30mas while their average number of physically connected companions within 8'' is f_c = 2.2 +/- 0.3. This demonstrates that massive stars form nearly exclusively in multiple systems. Additionally, the nine non-thermal (NT) radio emitters observed by SMASH+ are all resolved [...]Comment: 57 pages, 20 figures, 7 tables; accepted for publication in ApJ

The AIMSS Project - I. Bridging the star cluster-galaxy divide

We describe the structural and kinematic properties of the first compact stellar systems discovered by the Archive of Intermediate Mass Stellar Systems project. These spectroscopically confirmed objects have sizes (∼6 < Re [pc] < 500) and masses (∼2 × 106 < M∗/M� < 6 × 109) spanning the range of massive globular clusters, ultracompact dwarfs (UCDs) and compact elliptical galaxies (cEs), completely filling the gap between star clusters and galaxies. Several objects are close analogues to the prototypical cE, M32. These objects, which are more massive than previously discovered UCDs of the same size, further call into question the existence of a tight mass–size trend for compact stellar systems, while simultaneously strengthening the case for a universal ‘zone of avoidance’ for dynamically hot stellar systems in the mass–size plane. Overall, we argue that there are two classes of compact stellar systems (1) massive star clusters and (2) a population closely related to galaxies. Our data provide indications for a further division of the galaxy-type UCD/cE population into two groups, one population that we associate with objects formed by the stripping of nucleated dwarf galaxies, and a second population that formed through the stripping of bulged galaxies or are lower mass analogues of classical ellipticals. We find compact stellar systems around galaxies in low- to high-density environments, demonstrating that the physical processes responsible for forming them do not only operate in the densest clusters

Radio Galaxy Zoo: The Distortion of Radio Galaxies by Galaxy Clusters

We study the impact of cluster environment on the morphology of a sample of 4304 extended radio galaxies from Radio Galaxy Zoo. A total of 87% of the sample lies within a projected 15 Mpc of an optically identified cluster. Brightest cluster galaxies (BCGs) are more likely than other cluster members to be radio sources, and are also moderately bent. The surface density as a function of separation from cluster center of non-BCG radio galaxies follows a power law with index $-1.10\pm 0.03$ out to $10~r_{500}$ ($\sim 7~$Mpc), which is steeper than the corresponding distribution for optically selected galaxies. Non-BCG radio galaxies are statistically more bent the closer they are to the cluster center. Within the inner $1.5~r_{500}$ ($\sim 1~$Mpc) of a cluster, non-BCG radio galaxies are statistically more bent in high-mass clusters than in low-mass clusters. Together, we find that non-BCG sources are statistically more bent in environments that exert greater ram pressure. We use the orientation of bent radio galaxies as an indicator of galaxy orbits and find that they are preferentially in radial orbits. Away from clusters, there is a large population of bent radio galaxies, limiting their use as cluster locators; however, they are still located within statistically overdense regions. We investigate the asymmetry in the tail length of sources that have their tails aligned along the radius vector from the cluster center, and find that the length of the inward-pointing tail is weakly suppressed for sources close to the center of the cluster.Comment: 23 pages, 17 figures, 2 tables. Supplemental data files available in The Astronomical Journal or contact autho

Genome-Wide Association Study Identifies Loci for Liver Enzyme Concentrations in Mexican Americans: The GUARDIAN Consortium.

ObjectivePopulations of Mexican American ancestry are at an increased risk for nonalcoholic fatty liver disease. The objective of this study was to determine whether loci in known and novel genes were associated with variation in aspartate aminotransferase (AST) (n = 3,644), alanine aminotransferase (ALT) (n = 3,595), and gamma-glutamyl transferase (GGT) (n = 1,577) levels by conducting the first genome-wide association study (GWAS) of liver enzymes, which commonly measure liver function, in individuals of Mexican American ancestry.MethodsLevels of AST, ALT, and GGT were determined by enzymatic colorimetric assays. A multi-cohort GWAS of individuals of Mexican American ancestry was performed. Single-nucleotide polymorphisms (SNP) were tested for association with liver outcomes by multivariable linear regression using an additive genetic model. Association analyses were conducted separately in each cohort, followed by a nonparametric meta-analysis.ResultsIn the PNPLA3 gene, rs4823173 (P = 3.44 × 10-10 ), rs2896019 (P = 7.29 × 10-9 ), and rs2281135 (P = 8.73 × 10-9 ) were significantly associated with AST levels. Although not genome-wide significant, these same SNPs were the top hits for ALT (P = 7.12 × 10-8 , P = 1.98 × 10-7 , and P = 1.81 × 10-7 , respectively). The strong correlation (r2  = 1.0) for these SNPs indicated a single hit in the PNPLA3 gene. No genome-wide significant associations were found for GGT.ConclusionsPNPLA3, a locus previously identified with ALT, AST, and nonalcoholic fatty liver disease in European and Japanese GWAS, is also associated with liver enzymes in populations of Mexican American ancestry

Shape and structure of N=Z 64Ge; Electromagnetic transition rates from the application of the Recoil Distance Method to knock-out reaction

Transition rate measurements are reported for the first and the second 2+ states in N=Z 64Ge. The experimental results are in excellent agreement with large-scale Shell Model calculations applying the recently developed GXPF1A interactions. Theoretical analysis suggests that 64Ge is a collective gamma-soft anharmonic vibrator. The measurement was done using the Recoil Distance Method (RDM) and a unique combination of state-of-the-art instruments at the National Superconducting Cyclotron Laboratory (NSCL). States of interest were populated via an intermediate-energy single-neutron knock-out reaction. RDM studies of knock-out and fragmentation reaction products hold the promise of reaching far from stability and providing lifetime information for excited states in a wide range of nuclei