26,936 research outputs found
Electron transport chain complex II sustains high mitochondrial membrane potential in hematopoietic stem and progenitor cells
The role of mitochondria in the fate determination of hematopoietic stem and progenitor cells (HSPCs) is not solely limited to the switch from glycolysis to oxidative phosphorylation, but also involves alterations in mitochondrial features and properties, including mitochondrial membrane potential (ΔΨmt). HSPCs have a high ΔΨmt even when the rates of respiration and phosphorylation are low, and we have previously shown that the minimum proton flow through ATP synthesis (or complex V) enables high ΔΨmt in HSPCs. Here we show that HSPCs sustain a unique equilibrium between electron transport chain (ETC) complexes and ATP production. HSPCs exhibit high expression of ETC complex II, which sustains complex III in proton pumping, although the expression levels of complex I or V are relatively low. Complex II inhibition by TTFA caused a substantial decrease of ΔΨmt, particularly in HSPCs, while the inhibition of complex I by Rotenone mainly affected mature populations. Functionally, pharmacological inhibition of complex II reduced in vitro colony-replating capacity but this was not observed when complex I was inhibited, which supports the distinct roles of complex I and II in HSPCs. Taken together, these data highlight complex II as a key regulator of ΔΨmt in HSPCs and open new and interesting questions regarding the precise mechanisms that regulate mitochondrial control to maintain hematopoietic stem cell self-renewal
The NJL-jet model for quark fragmentation functions
A description of fragmentation functions which satisfy the momentum and
isospin sum rules is presented in an effective quark theory. Concentrating on
the pion fragmentation function, we first explain why the elementary (lowest
order) fragmentation process q --> q \pi is completely inadequate to describe
the empirical data, although the "crossed" process \pi --> q \bar{q} describes
the quark distribution functions in the pion reasonably well. Taking into
account cascade-like processes in a generalized jet-model approach, we then
show that the momentum and isospin sum rules can be satisfied naturally,
without the introduction of ad hoc parameters. We present results for the
Nambu--Jona-Lasinio (NJL) model in the invariant mass regularization scheme and
compare them with the empirical parametrizations. We argue that the NJL-jet
model, developed herein, provides a useful framework with which to calculate
the fragmentation functions in an effective chiral quark theory.Comment: 21 pages, 7 figure
Instanton Calculus in R-R 3-form Background and Deformed N=2 Super Yang-Mills Theory
We study the ADHM construction of instantons in N=2 supersymmetric Yang-Mills
theory deformed in constant Ramond-Ramond (R-R) 3-form field strength
background in type IIB superstrings. We compare the deformed instanton
effective action with the effective action of fractional D3/D(-1) branes at the
orbifold singularity of C^2/Z_2 in the same R-R background. We find discrepancy
between them at the second order in deformation parameters, which comes from
the coupling of the translational zero modes of the D(-1)-branes to the R-R
background. We improve the deformed action by adding a term with space-time
dependent gauge coupling. Although the space-time action differs from the
action in the omega-background, both actions lead to the same instanton
equations of motion at the lowest order in gauge coupling.Comment: 27 pages, version to appear in JHE
Spontaneous structure formation in a network of chaotic units with variable connection strengths
As a model of temporally evolving networks, we consider a globally coupled
logistic map with variable connection weights. The model exhibits
self-organization of network structure, reflected by the collective behavior of
units. Structural order emerges even without any inter-unit synchronization of
dynamics. Within this structure, units spontaneously separate into two groups
whose distinguishing feature is that the first group possesses many
outwardly-directed connections to the second group, while the second group
possesses only few outwardly-directed connections to the first. The relevance
of the results to structure formation in neural networks is briefly discussed.Comment: 4 pages, 3 figures, REVTe
BPS Monopole Equation in Omega-background
We study deformed supersymmetries in N=2 super Yang-Mills theory in the
Omega-backgrounds characterized by two complex parameters . When one of the -parameters vanishes, the theory has
extended supersymmetries. We compute the central charge of the algebra and
obtain the deformed BPS monopole equation. We examine supersymmetries preserved
by the equation.Comment: 14 pages, typos corrected, published version in JHE
Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells
Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases
The chemotherapeutic agent DMXAA as a unique IRF3-dependent type-2 vaccine adjuvant
5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent type I interferon (IFN) inducer, was evaluated as a chemotherapeutic agent in mouse cancer models and proved to be well tolerated in human cancer clinical trials. Despite its multiple biological functions, DMXAA has not been fully characterized for the potential application as a vaccine adjuvant. In this report, we show that DMXAA does act as an adjuvant due to its unique property as a soluble innate immune activator. Using OVA as a model antigen, DMXAA was demonstrated to improve on the antigen specific immune responses and induce a preferential Th2 (Type-2) response. The adjuvant effect was directly dependent on the IRF3-mediated production of type-I-interferon, but not IL-33. DMXAA could also enhance the immunogenicity of influenza split vaccine which led to significant increase in protective responses against live influenza virus challenge in mice compared to split vaccine alone. We propose that DMXAA can be used as an adjuvant that targets a specific innate immune signaling pathway via IRF3 for potential applications including vaccines against influenza which requires a high safety profile
A Note on the Picard-Fuchs Equations for N=2 Seiberg-Witten Theories
A concise presentation of the PF equations for N=2 Seiberg-Witten theories
for the classical groups of rank r with N_f massless hypermultiplets in the
fundamental representation is provided. For N_f=0, all r PF equations can be
given in a generic form. For certain cases with N_f\neq zero, not all equations
are generic. However, in all cases there are at least r-2 generic PF equations.
For these cases the classical part of the equations is generic, while the
quantum part can be formulated using a method described in a previous paper by
the authors, which is well suited to symbolic computer calculations.Comment: 25 pages, Latex; some new references adde
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