Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia

Statewide geographic variation in outcomes for adults with acute myeloid leukemia in North Carolina

BACKGROUND: Population-based studies have demonstrated survival disparities related to socioeconomic factors for patients with acute myeloid leukemia (AML). The objective of the current study was to determine whether the local health care infrastructure, represented by Area Health Education Centers (AHEC) region, or treating center experience, represented by National Cancer Institute Comprehensive Cancer Center (NCICCC) designation, were associated with outcomes among patients with AML in North Carolina. METHODS: Patients who were diagnosed with AML from 2003 to 2009 were identified using the University of North Carolina Lineberger Integrated Cancer Information and Surveillance System, a database linking insurance claims to the North Carolina Cancer Registry. A Cox proportional-hazards model was used to explore survival based on AHEC region. A subset of patients who received inpatient chemotherapy was examined to evaluate the impact of treatment at an NCICCC. RESULTS: Nine hundred patients were identified in the study period, 553 of whom received inpatient chemotherapy therapy within 30 days of diagnosis. Almost one-half of these patients (n5294) received chemotherapy at a non-NCICCC. Among the patients who received intensive inpatient therapy, residence in 3 of 9 AHEC regions was associated with a higher risk of mortality (hazard ratio: range, 1.97-4.03; P<.01) at 1 year in multivariate analysis. Treatment at a non-NCICCC was not associated with an increased risk of mortality at 1 year (hazard ratio, 1.25; 95% confidence interval, 0.95-1.65). CONCLUSIONS: Survival among patients with AML in North Carolina varies according to geographic region. Further examination of local practice and referral patterns may inform strategies to improve AML outcomes across the state

Influence of treating facility, provider volume, and patient-sharing on survival of patients with multiple myeloma

Background: Population-based studies suggest that patients with multiple myeloma (MM) have better outcomes when treated at high-volume facilities, but the relative contribution of provider expertise and hospital resources to improved outcomes is unknown. This study explored how treating facility, individual provider volume, and patient-sharing between MM specialists and community providers influenced outcomes for patients with MM. Patients and Methods: A state cancer registry linked to public and private insurance claims was used to identify a cohort of patients diagnosed with MM in 2006 through 2012. Three multivariable Cox models were used to examine how the following factors impacted overall survival: (1) evaluation at an NCI-designated Comprehensive Cancer Center (NCICCC), (2) the primary oncologist's volume of patients with MM, and (3) patient-sharing between MM specialists and community oncologists. Results: A total of 1,029 patients diagnosed with MM in 2006 through 2012 were identified. Patients who were not evaluated at an NCICCC had an increased risk of mortality compared with those evaluated at an NCICCC (hazard ratio [HR], 1.50; 95% CI, 1.21-1.86; P,.001). Compared with patients treated by NCICCC MM specialists, those treated by both low-volume community providers (HR, 1.47; 95% CI, 1.14-1.90; P,.01) and high-volume community providers (HR, 1.29; 95% CI, 1.04-1.61; P,.05) had a higher risk of mortality. No difference in mortality was seen between patients treated by NCICCC MM specialists and those treated by the highest-volume community oncologists in the ninth and tenth deciles (HR, 1.08; 95% CI, 0.84-1.37; P 5.5591). Patients treated by community oncologists had a higher risk of mortality regardless of patient-sharing compared with patients treated by MM specialists (eg, community oncologist with a history of sharing vs NCICCC MM specialist: HR, 1.49; 95% CI, 1.10-2.02; P,.05). Conclusions: Findings of this study add to the accumulating evidence showing that patients with MM benefit from care at high-volume facilities, and suggest that similar outcomes can be achieved by the highest-volume providers in the community

Theoretical study of incoherent phi photoproduction on a deuteron target

We study the photoproduction of phi mesons in deuteron, paying attention to the modification of the cross section from bound protons to the free ones with the aim of comparing with recent results at LEPS. For this purpose we take into account Fermi motion in single scattering and rescattering of the phi to account for phi absorption on a second nucleon as well as the rescattering of the proton. We find that the contribution of the double scattering is much smaller than the typical cross section of gamma p to phi p in free space, which implies a very small screening of the phi production in deuteron. The contribution from the proton rescattering, on the other hand, is found to be not negligible compared to the cross section of gamma p to phi p in free space, and leads to a moderate reduction of the phi photoproduction cross section on a deuteron at forward angles if LEPS set up is taken into account. The Fermi motion allows contribution of the single scattering in regions forbidden by phase space in the free case. In particular, we find that for momentum transferred squared close to the maximum value, the Fermi motion changes drastically the shape of d sigma / dt, to the point that the ratio of this cross section to the free one becomes very sensitive to the precise value of t chosen, or the size of the bin used in an experimental analysis. Hence, this particular region of t does not seem the most indicated to find effects of a possible phi absorption in the deuteron. This reaction is studied theoretically as a function of t and the effect of the experimental angular cuts at LEPS is also discussed, providing guidelines for future experimental analyses of the reaction.Comment: 17 pages, 16 figure

Genome-wide transcriptional profiling and structural magnetic resonance imaging in the maternal immune activation model of neurodevelopmental disorders

Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation. Genome-wide transcriptional profiling revealed that prenatal immune activation caused a differential expression of 116 and 251 genes in the medial prefrontal cortex and nucleus accumbens, respectively. A large part of genes that were commonly affected in both brain areas were related to myelin functionality and stability. Subsequent epigenetic analyses indicated that altered DNA methylation of promoter regions might contribute to the differential expression of myelin-related genes. Quantitative relaxometry comparing T1, T2, and myelin water fraction revealed sparse increases in T1 relaxation times and consistent reductions in T2 relaxation times. Together, our multi-system approach demonstrates that prenatal viral-like immune activation causes myelin-related transcriptional and epigenetic changes in corticostriatal areas. Even though these abnormalities do not seem to be associated with overt white matter reduction, they may provide a molecular mechanism whereby prenatal infection can impair myelin functionality and stability

Cell shape analysis of random tessellations based on Minkowski tensors

To which degree are shape indices of individual cells of a tessellation characteristic for the stochastic process that generates them? Within the context of stochastic geometry and the physics of disordered materials, this corresponds to the question of relationships between different stochastic models. In the context of image analysis of synthetic and biological materials, this question is central to the problem of inferring information about formation processes from spatial measurements of resulting random structures. We address this question by a theory-based simulation study of shape indices derived from Minkowski tensors for a variety of tessellation models. We focus on the relationship between two indices: an isoperimetric ratio of the empirical averages of cell volume and area and the cell elongation quantified by eigenvalue ratios of interfacial Minkowski tensors. Simulation data for these quantities, as well as for distributions thereof and for correlations of cell shape and volume, are presented for Voronoi mosaics of the Poisson point process, determinantal and permanental point processes, and Gibbs hard-core and random sequential absorption processes as well as for Laguerre tessellations of polydisperse spheres and STIT- and Poisson hyperplane tessellations. These data are complemented by mechanically stable crystalline sphere and disordered ellipsoid packings and area-minimising foam models. We find that shape indices of individual cells are not sufficient to unambiguously identify the generating process even amongst this limited set of processes. However, we identify significant differences of the shape indices between many of these tessellation models. Given a realization of a tessellation, these shape indices can narrow the choice of possible generating processes, providing a powerful tool which can be further strengthened by density-resolved volume-shape correlations.Comment: Chapter of the forthcoming book "Tensor Valuations and their Applications in Stochastic Geometry and Imaging" in Lecture Notes in Mathematics edited by Markus Kiderlen and Eva B. Vedel Jense

A systematic review of physical activity promotion strategies

This article was first published in:British Journal of Sports Medicine:1996:30:84-89We have reviewed randomised controlled trials of physical activity promotion to provide recent and reliable information on the effectiveness of physical activity promotion. Computerised databases and references of references were searched. Experts were contacted and asked for information about existing work. Studies assessed were randomised controlled trials of healthy, free living, adult subjects, where exercise behaviour was the dependent variable. Eleven trials were identified. No United Kingdom based studies were found. Interventions that encourage walking and do not require attendance at a facility are most likely to lead to sustainable increases in overall physical activity. Brisk walking has the greatest potential for increasing overall activity levels of a sedentary population and meeting current public health recommendations. The small number of trials limits the strength of any conclusions and highlights the need for more research

The correlation between the health-related fitness of healthy participants measured at home as opposed to fitness measured by sport scientists in a laboratory

BACKGROUND : Fitness is defined in the health context as a state of good health or physical condition, primarily as a result of exercise and proper nutrition. Conventional methods of measuring fitness are expensive, time consuming and require specialised methods. There is a need for noninvasive, fast methods of assessing health-related fitness and activity in athlete and non-athlete populations. The aim of this study was to establish any correlation between participants’ self-assessed health-related fitness (HRF) index and the HRF index determined by sports scientists, as well as the laboratory-assessed HRF index and maximum oxygen uptake (VO2max) determined by sports scientists via direct methods in a laboratory, and finally, to determine any potential correlation between an activity-recall questionnaire (Kasari) and VO2max. METHOD : The participants consisted of 169 male and female volunteers between the ages of 18 and 55 years, taking neither supplements nor medication. The University of Pretoria’s HRF index protocol was first carried out by participants on their own at home, and then in the laboratory under the supervision of sport scientists. The complete datasets of 150 participants were statistically analysed to establish correlations. RESULTS : The results indicated highly significant and substantial correlations (ρ = 0.696, p < 0.001) between the participants’ self-assessed HRF index and measurements by the sports scientists. There were moderate correlations between the laboratoryassessed HRF index and the direct VO2max (ρ = 0 512, p < 0.005), as well as the indirect VO2max (ρ = 0.588; p < 0.001). A significant correlation was found between the self-assessed HRF index and the indirect VO2max (ρ = 0.454; p < 0.001). The Kasari questionnaire correlated only weakly with the indirect VO2max (ρ = 0.278, p < 0.002) and not at all with the direct VO2max (ρ = 0.072, p = 0.731). CONCLUSION : Indications are that this test protocol may be conducted at home by individuals, without supervision, to determine exercise ability or fitness, or to monitor changes in physical fitness, thereby limiting expenses and costs.Momentum Interactivehttp://www.safpj.co.za/index.php/safpjhb201

Temporal variability in gas emissions at Bagana volcano revealed by aerial, ground, and satellite observations

Bagana is a remote, highly active volcano, located on Bougainville Island in southeastern Papua New Guinea. The volcano has exhibited sustained and prodigious sulfur dioxide gas emissions in recent decades, accompanied by frequent episodes of lava extrusion. The remote location of Bagana and its persistent activity have made it a valuable case study for satellite observations of active volcanism. This remoteness has also left many features of Bagana relatively unexplored. Here, we present the first measurements of volcanic gas composition, achieved by unoccupied aerial system (UAS) flights through the volcano's summit plume, and a payload comprising a miniaturized MultiGAS. We combine our measurements of the molar CO2/SO2 ratio in the plume with coincident remote sensing measurements (ground- and satellite-based) of SO2 emission rate to compute the first estimate of CO2 flux at Bagana. We report low SO2 and CO2 fluxes at Bagana from our fieldwork in September 2019, ∼320 ± 76 td−1 and ∼320 ± 84 td−1, respectively, which we attribute to the volcano's low level of activity at the time of our visit. We use satellite observations to demonstrate that Bagana's activity and emissions behavior are highly variable and advance the argument that such variability is likely an inherent feature of many volcanoes worldwide and yet is inadequately captured by our extant volcanic gas inventories, which are often biased to sporadic measurements. We argue that there is great value in the use of UAS combined with MultiGAS-type instruments for remote monitoring of gas emissions from other inaccessible volcanoes