Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments

International audienceFunctions of septin cytoskeletal polymers in tumorigenesis are still poorly defined. Their role in the regulation of cytokinesis and cell migration were proposed to contribute to cancer associated aneuploidy and metastasis. Overexpression of Septin 9 (Sept9) promotes migration of cancer cell lines. SEPT9 mRNA and protein expression is increased in breast tumors compared to normal and peritumoral tissues and amplification of SEPT9 gene was positively correlated with breast tumor progression. However, the existence of multiple isoforms of Sept9 is a confounding factor in the analysis of Sept9 functions. In the present study, we analyze the protein expression of Sept9_i2, an uncharacterized isoform, in breast cancer cell lines and tumors and describe its specific impact on cancer cell migration and Sept9 cytoskeletal distribution. Collectively, our results showed that, contrary to Sept9_i1, Sept9_ i2 did not support cancer cell migration, and induced a loss of subnuclear actin filaments. These effects were dependent on Sept9_i2 specific N-terminal sequence. Sept9_i2 was strongly down-regulated in breast tumors compared to normal mammary tissues. Thus our data indicate that Sept9_i2 is a negative regulator of breast tumorigenesis. We propose that Sept9 tumorigenic properties depend on the balance between Sept9_i1 and Sept9_i2 expression levels

What Does It Take? California County Funding Requests for Recovery-Oriented Full Service Partnerships Under the Mental Health Services Act

The need to move mental health systems toward more recovery-oriented treatment modes is well established. Progress has been made to define needed changes but evidence is lacking about the resources required to implement them. The Mental Health Services Act (MHSA) in California was designed to implement more recovery-oriented treatment modes. We use data from county funding requests and annual updates to examine how counties budgeted for recovery-oriented programs targeted to different age groups under MHSA. Findings indicate that initial per-client budgeting for Full Services Partnerships under MHSA was maintained in future cycles and counties budgeted less per client for children. With this analysis, we begin to benchmark resource allocation for programs that are intended to be recovery-oriented, which should be evaluated against appropriate outcome measures in the future to determine the degree of recovery-orientation

Associations between long-term adherence to healthy diet and recurrent depressive symptoms in Whitehall II Study

PURPOSE: We examined whether long-term adherence to three diet quality scores-the Alternative Healthy Eating Index-2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH) and  transformed-Mediterranean Diet Score (tMDS), Alternative Healthy Eating Index-2010 (AHEI-2010) and Dietary Approach to Stop Hypertension (DASH) is associated with the risk of recurrent depressive symptoms. METHODS: Analyses were conducted on a sample of 4949 men and women from the Whitehall II study. Diet scores were calculated using data collected from food frequency questionnaires repeated over 11 years of exposure (1991/1993-2002/2004). Recurrence of depressive symptoms was defined when participants reported at least two episodes of depressive symptoms (assessed by Center for Epidemiologic Studies Depression Scale and use of antidepressants) over the four phases of follow-up (2002/04-2015/16). RESULTS: After adjustment for potential cofounders, higher scores on AHEI-2010, DASH and tMDS at the end of the exposure period were associated with lower risk of recurrent depressive symptoms over the 13-year follow-up. Repeat measures of dietary history showed that participants who maintained a high AHEI-2010 score over the 11-year exposure period had a 19% (OR 0.81, 95% CI 0.65-1.00) lower odds of recurrent depressive symptoms compared to those who maintained a low AHEI score. Participants whose AHEI-2010 score decreased over time had a 1.34-fold increased odds (95% CI 1.02-1.75) of developing recurrent depressive symptoms compared to those maintaining a high AHEI-2010. No robust associations were observed for long-term tMDS and DASH. CONCLUSION: Our findings suggest that long-term adherence to healthy diet defined by Alternative Healthy Eating Index-2010 confers protection against recurrent depressive symptoms

Stability Considerations for Final Focus Systems of Future Linear Colliders

The final focus systems for the future linear colliders need to focus beams to nm-range spot sizes at the collision point. The design spot size varies from several nm for 500 GeV to the one nm range for 3 TeV. In order to keep the beams in collision and to maintain the luminosity stringent stability optimization must be applied. We discuss different sources of beam perturbations and estimate the expected beamline stability based on previous experimental observations. Possible measures for beam stabilization are discussed and plans of further collaborative efforts are outlined

System Size, Energy and Centrality Dependence of Pseudorapidity Distributions of Charged Particles in Relativistic Heavy Ion Collisions

We present the first measurements of the pseudorapidity distribution of primary charged particles in Cu+Cu collisions as a function of collision centrality and energy, \sqrtsnn = 22.4, 62.4 and 200 GeV, over a wide range of pseudorapidity, using the PHOBOS detector. Making a global comparison of Cu+Cu and Au+Au results, we find that the total number of produced charged particles and the rough shape (height and width) of the pseudorapidity distributions are determined by the number of nucleon participants. More detailed studies reveal that a more precise matching of the shape of the Cu+Cu and Au+Au pseudorapidity distributions over the full range of pseudorapidity occurs for the same Npart/2A value rather than the same Npart value. In other words, it is the collision geometry rather than just the number of nucleon participants that drives the detailed shape of the pseudorapidity distribution and its centrality dependence at RHIC energies.Comment: Submitted to Physical Review Letter

System size and centrality dependence of charged hadron transverse momentum spectra in Au+Au and Cu+Cu collisions at sqrt(s) = 62.4 and 200 GeV

We present transverse momentum distributions of charged hadrons produced in Cu+Cu collisions at sqrt(s) = 62.4 and 200 GeV. The spectra are measured for transverse momenta of 0.25 < p_T < 5.0 GeV/c at sqrt(s) = 62.4 GeV and 0.25 < p_T < 7.0 GeV/c at sqrt(s) = 200 GeV, in a pseudo-rapidity range of 0.2 < eta < 1.4. The nuclear modification factor R_AA is calculated relative to p+p data at both collision energies as a function of collision centrality. At a given collision energy and fractional cross-section, R_AA is observed to be systematically larger in Cu+Cu collisions compared to Au+Au. However, for the same number of participating nucleons, R_AA is essentially the same in both systems over the measured range of p_T, in spite of the significantly different geometries of the Cu+Cu and Au+Au systems.Comment: 4 pages, 5 figures, submitted to Phys. Rev. Let

The Importance of Correlations and Fluctuations on the Initial Source Eccentricity in High-Energy Nucleus-Nucleus Collisions

In this paper, we investigate various ways of defining the initial source eccentricity using the Monte Carlo Glauber (MCG) approach. In particular, we examine the participant eccentricity, which quantifies the eccentricity of the initial source shape by the major axes of the ellipse formed by the interaction points of the participating nucleons. We show that reasonable variation of the density parameters in the Glauber calculation, as well as variations in how matter production is modeled, do not significantly modify the already established behavior of the participant eccentricity as a function of collision centrality. Focusing on event-by-event fluctuations and correlations of the distributions of participating nucleons we demonstrate that, depending on the achieved event-plane resolution, fluctuations in the elliptic flow magnitude $v_2$ lead to most measurements being sensitive to the root-mean-square, rather than the mean of the $v_2$ distribution. Neglecting correlations among participants, we derive analytical expressions for the participant eccentricity cumulants as a function of the number of participating nucleons, \Npart,keeping non-negligible contributions up to \ordof{1/\Npart^3}. We find that the derived expressions yield the same results as obtained from mixed-event MCG calculations which remove the correlations stemming from the nuclear collision process. Most importantly, we conclude from the comparison with MCG calculations that the fourth order participant eccentricity cumulant does not approach the spatial anisotropy obtained assuming a smooth nuclear matter distribution. In particular, for the Cu+Cu system, these quantities deviate from each other by almost a factor of two over a wide range in centrality.Comment: 18 pages, 10 figures, submitted to PR

Identified charged antiparticle to particle ratios near midrapidity in Cu+Cu collisions at sqrt(s) = 62.4 and 200 GeV

Antiparticle to particle ratios for identified protons, kaons and pions at sqrt(s) = 62.4 and 200 GeV in Cu+Cu collisions are presented as a function of centrality for the midrapidity region of 0.2 < eta < 1.4. No strong dependence on centrality is observed. For the / ratio at ~ 0.51 GeV/c, we observe an average value of 0.50 +/- 0.003_(stat) +/- 0.04_(syst) and 0.77 +/- 0.008_(stat) +/- 0.05_(syst) for the 10% most central collisions of 62.4 and 200 GeV Cu+Cu, respectively. The values for all three particle species measured at sqrt(s) = 200 GeV are in agreement within systematic uncertainties with that seen in both heavier and lighter systems measured at the same RHIC energy. This indicates that system size does not appear to play a strong role in determining the midrapidity chemical freeze-out properties affecting the antiparticle to particle ratios of the three most abundant particle species produced in these collisions.Comment: 5 Pages, 4 figures Made changes to the figures to include the panel numbers. Slight changes to the text. Updated data points from other experiment

System Size, Energy, Pseudorapidity, and Centrality Dependence of Elliptic Flow

This paper presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system

Latest Results from PHOBOS

This manuscript contains a summary of the latest physics results from PHOBOS, as reported at Quark Matter 2006. Highlights include the first measurement from PHOBOS of dynamical elliptic flow fluctuations as well as an explanation of their possible origin, two-particle correlations, identified particle ratios, identified particle spectra and the latest results in global charged particle production.Comment: 9 pages, 7 figures, PHOBOS plenary proceedings for Quark Matter 200