Nonlinear saturation of electrostatic waves: mobile ions modify trapping scaling

The amplitude equation for an unstable electrostatic wave in a multi-species Vlasov plasma has been derived. The dynamics of the mode amplitude $\rho(t)$ is studied using an expansion in $\rho$; in particular, in the limit $\gamma\rightarrow0^+$, the singularities in the expansion coefficients are analyzed to predict the asymptotic dependence of the electric field on the linear growth rate $\gamma$. Generically $|E_k|\sim \gamma^{5/2}$, as $\gamma\rightarrow0^+$, but in the limit of infinite ion mass or for instabilities in reflection-symmetric systems due to real eigenvalues the more familiar trapping scaling $|E_k|\sim \gamma^{2}$ is predicted.Comment: 13 pages (Latex/RevTex), 4 postscript encapsulated figures which are included using the utility "uufiles". They should be automatically included with the text when it is downloaded. Figures also available in hard copy from the authors ([email protected]

Universal trapping scaling on the unstable manifold for a collisionless electrostatic mode

An amplitude equation for an unstable mode in a collisionless plasma is derived from the dynamics on the two-dimensional unstable manifold of the equilibrium. The mode amplitude $\rho(t)$ decouples from the phase due to the spatial homogeneity of the equilibrium, and the resulting one-dimensional dynamics is analyzed using an expansion in $\rho$. As the linear growth rate $\gamma$ vanishes, the expansion coefficients diverge; a rescaling $\rho(t)\equiv\gamma^2\,r(\gamma t)$ of the mode amplitude absorbs these singularities and reveals that the mode electric field exhibits trapping scaling $|E_1|\sim\gamma^2$ as $\gamma\rightarrow0$. The dynamics for $r(\tau)$ depends only on the phase $e^{i\xi}$ where $d\epsilon_{{k}} /dz=|{\epsilon_{{k}}}|e^{-i\xi/2}$ is the derivative of the dielectric as $\gamma\rightarrow0$.Comment: 11 pages (Latex/RevTex), 2 figures available in hard copy from the Author ([email protected]); paper accepted by Physical Review Letter

Functional astrocyte-neuron lactate shuttle in a human stem cell-derived neuronal network

The NT2.D1 cell line is one of the most well-documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of the neuronal cells, and more recently we have investigated the functional properties of their associated astrocytes. We now show for the first time that human stem cell-derived astrocytes produce glycogen and that co-cultures of these cells demonstrate a functional astrocyte-neuron lactate shuttle (ANLS). The ANLS hypothesis proposes that during neuronal activity, glutamate released into the synaptic cleft is taken up by astrocytes and triggers glucose uptake, which is converted into lactate and released via monocarboxylate transporters for neuronal use. Using mixed cultures of NT2-derived neurons and astrocytes, we have shown that these cells modulate their glucose uptake in response to glutamate. Additionally, we demonstrate that in response to increased neuronal activity and under hypoglycaemic conditions, co-cultures modulate glycogen turnover and increase lactate production. Similar results were also shown after treatment with glutamate, potassium, isoproterenol, and dbcAMP. Together, these results demonstrate for the first time a functional ANLS in a human stem cell-derived co-culture. © 2013 ISCBFM

Best practices in intercultural health: five case studies in Latin America

The practice of integrating western and traditional indigenous medicine is fast becoming an accepted and more widely used approach in health care systems throughout the world. However, debates about intercultural health approaches have raised significant concerns. This paper reports findings of five case studies on intercultural health in Chile, Colombia, Ecuador, Guatemala, and Suriname. It presents summary information on each case study, comparatively analyzes the initiatives following four main analytical themes, and examines the case studies against a series of the best practice criteria

Epstein-Barr virus-encoded EBNA1 inhibits the canonical NF-κB pathway in carcinoma cells by inhibiting IKK phosphorylation

Background The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all EBV-associated tumours, including undifferentiated nasopharyngeal carcinoma (NPC), where it is indispensable for viral replication, genome maintenance and viral gene expression. EBNA1's transcription factor-like functions also extend to influencing the expression of cellular genes involved in pathways commonly dysregulated during oncogenesis, including elevation of AP-1 activity in NPC cell lines resulting in enhancement of angiogenesis in vitro. In this study we sought to extend these observations by examining the role of EBNA1 upon another pathway commonly deregulated during carcinogenesis; namely NF-κB. Results In this report we demonstrate that EBNA1 inhibits the canonical NF-κB pathway in carcinoma lines by inhibiting the phosphorylation of IKKα/β. In agreement with this observation we find a reduction in the phosphorylation of IκBα and reduced phosphorylation and nuclear translocation of p65, resulting in a reduction in the amount of p65 in nuclear NF-κB complexes. Similar effects were also found in carcinoma lines infected with recombinant EBV and in the EBV-positive NPC-derived cell line C666-1. Inhibition of NF-κB was dependent upon regions of EBNA1 essential for gene transactivation whilst the interaction with the deubiquitinating enzyme, USP7, was entirely dispensable. Furthermore, in agreement with EBNA1 inhibiting p65 NF-κB we demonstrate that p65 was exclusively cytoplasmic in 11 out of 11 NPC tumours studied. Conclusions Inhibition of p65 NF-κB in murine and human epidermis results in tissue hyperplasia and the development of squamous cell carcinoma. In line with this, p65 knockout fibroblasts have a transformed phenotype. Inhibition of p65 NF-κB by EBNA1 may therefore contribute to the development of NPC by inducing tissue hyperplasia. Furthermore, inhibition of NF-κB is employed by viruses as an immune evasion strategy which is also closely linked to oncogenesis during persistent viral infection. Our findings therefore further implicate EBNA1 in playing an important role in the pathogenesis of NPC

Epstein-Barr virus-encoded EBNA1 enhances RNA polymerase III-dependent EBER expression through induction of EBER-associated cellular transcription factors

Background Epstein-Barr Virus (EBV)-encoded RNAs (EBERs) are non-polyadenylated RNA molecules transcribed from the EBV genome by RNA polymerase III (pol III). EBERs are the most abundant viral latent gene products, although the precise mechanisms by which EBV is able to achieve such high levels of EBER expression are not fully understood. Previously EBV has been demonstrated to induce transcription factors associated with EBER expression, including pol III transcription factors and ATF-2. We have recently demonstrated that EBV-encoded nuclear antigen-1 (EBNA1) induces cellular transcription factors, and given these findings, we investigated the role of EBNA1 in induction of EBER-associated transcription factors. Results Our data confirm that in epithelial cells EBNA1 can enhance cellular pol III transcription. Transient expression of EBNA1 in Ad/AH cells stably expressing the EBERs led to induction of both EBER1 and EBER2 and conversely, expression of a dominant negative EBNA1 led to reduced EBER expression in EBV-infected Ad/AH cells. EBNA1 can induce transcription factors used by EBER genes, including TFIIIC, ATF-2 and c-Myc. A variant chromatin precipitation procedure showed that EBNA1 is associated with the promoters of these genes but not with the promoters of pol III-transcribed genes, including the EBERs themselves. Using shRNA knock-down, we confirm the significance of both ATF-2 and c-Myc in EBER expression. Further, functional induction of a c-Myc fusion protein led to increased EBER expression, providing c-Myc binding sites upstream of EBER1 were intact. In vivo studies confirm elevated levels of the 102 kD subunit of TFIIIC in the tumour cells of EBV-positive nasopharyngeal carcinoma biopsies. Conclusions Our findings reveal that EBNA1 is able to enhance EBER expression through induction of cellular transcription factors and add to the repertoire of EBNA1's transcription-regulatory properties

Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro yet has overwhelmingly anti-inflammatory consequences in vivo

The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequencespecific manner to the 3= untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by the overexpression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent antiinflammatory cytokine interleukin 10 (IL-10). Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of proinflammatory factors via direct or indirect mechanisms. We recently described a knock-in mouse strain in which the substitution of 2 amino acids of the endogenous TTP protein renders it constitutively active as an mRNA-destabilizing factor. Here we investigate the impact on the IL-10-mediated anti-inflammatory response. It is shown that the gain-of-function mutation of TTP impairs IL-10-mediated negative feedback control of macrophage function in vitro. However, the in vivo effects of TTP mutation are uniformly anti-inflammatory despite the decreased expression of IL-10

Observational Constraints on the Molecular Gas Content in Nearby Starburst Dwarf Galaxies

Using star formation histories derived from optically resolved stellar populations in nineteen nearby starburst dwarf galaxies observed with the Hubble Space Telescope, we measure the stellar mass surface densities of stars newly formed in the bursts. By assuming a star formation efficiency (SFE), we then calculate the inferred gas surface densities present at the onset of the starbursts. Assuming a SFE of 1%, as is often assumed in normal star-forming galaxies, and assuming that the gas was purely atomic, translates to very high HI surface densities (~10^2-10^3 Msun pc^-2), which are much higher than have been observed in dwarf galaxies. This implies either higher values of SFE in these dwarf starburst galaxies or the presence of significant amounts of H_2 in dwarfs (or both). Raising the assumed SFEs to 10% or greater (in line with observations of more massive starbursts associated with merging galaxies), still results in HI surface densities higher than observed in 10 galaxies. Thus, these observations appear to require that a significant fraction of the gas in these dwarf starbursts galaxies was in the molecular form at the onset of the bursts. Our results imply molecular gas column densities in the range 10^19-10^21 cm^-2 for the sample. In those galaxies where CO observations have been made, these densities correspond to values of the CO-H_2 conversion factor (X_CO) in the range >3-80x10^20 cm^-2 (K km s^-1)^-1, or up to 40x greater than Galactic X_CO values.Comment: 8 pages, 4 figures, 2 table