Quark and Nucleon Self-Energy in Dense Matter

In a recent work we introduced a nonlocal version of the Nambu--Jona-Lasinio(NJL) model that was designed to generate a quark self-energy in Euclidean space that was similar to that obtained in lattice simulations of QCD. In the present work we carry out related calculations in Minkowski space, so that we can study the effects of the significant vector and axial-vector interactions that appear in extended NJL models and which play an important role in the study of the $\rho$, $\omega$ and $a_1$ mesons. We study the modification of the quark self-energy in the presence of matter and find that our model reproduces the behavior of the quark condensate predicted by the model-independent relation $_{\rho} = <\bar qq>_0(1-\sigma_N\rho_N/f_{\pi}^2m_{\pi}^2 +...)$, where $\sigma_N$ is the pion-nucleon sigma term and $\rho_N$ is the density of nuclear matter. (Since we do not include a model of confinement, our study is restricted to the analysis of quark matter. We provide some discussion of the modification of the above formula for quark matter.) The inclusion of a quark current mass leads to a second-order phase transition for the restoration of chiral symmetry. That restoration is about 80% at twice nuclear matter density for the model considered in this work. We also find that the part of the quark self-energy that is explicitly dependent upon density has a strong negative Lorentz-scalar term and a strong positive Lorentz-vector term, which is analogous to the self-energy found for the nucleon in nuclear matter when one makes use of the Dirac equation for the nucleon. In this work we calculate the nucleon self -energy in nuclear matter using our model of the quark self-energy and obtain satisfactory results.Comment: 19 pages, 8 figures, 2 tables, revte

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Epigenetic reader BRD4 (Bromodomain-Containing Protein 4) governs nucleus-encoded mitochondrial transcriptome to regulate cardiac function

BACKGROUND: BET (Bromodomain and Extra-Terminal) epigenetic reader proteins, in particular BRD4, have emerged as potential therapeutic targets in a number of pathological conditions, including cancer and cardiovascular disease. Small molecule BET protein inhibitors, such as JQ1, have demonstrated efficacy in reversing cardiac hypertrophy and heart failure in preclinical models. Yet, genetic studies elucidating the biology of BET proteins in the heart have not been conducted to validate pharmacological findings and unveil potential pharmacological side effects. METHODS: By engineering a cardiomyocyte-specific BRD4 (bromodomain-containing protein 4) knockout mouse, we investigated the role of BRD4 in cardiac pathophysiology. We performed functional, transcriptomic, and mitochondrial analysis to evaluate BRD4 function in developing and mature hearts. RESULTS: Unlike pharmacological inhibition, loss of BRD4 protein triggered progressive declines in myocardial function, culminating in dilated cardiomyopathy. Transcriptome analysis of BRD4 knockout mouse heart tissue identified early and specific disruption of genes essential to mitochondrial energy production and homeostasis. Functional analysis of isolated mitochondria from these hearts confirmed that BRD4 ablation triggered significant changes in mitochondrial electron transport chain protein expression and activity. Computational analysis identified candidate transcription factors participating in the BRD4-regulated transcriptome. In particular, ESRRα (estrogen-related receptor alpha), a key nuclear receptor in metabolic gene regulation, was enriched in promoters of BRD4-regulated mitochondrial genes. CONCLUSIONS: In aggregate, we describe a previously unrecognized role for BRD4 in regulating cardiomyocyte mitochondrial homeostasis, observing that its function is indispensable to the maintenance of normal cardiac function

Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function

Background: BET (bromodomain and extraterminal) epigenetic reader proteins, in particular BRD4 (bromodomain-containing protein 4), have emerged as potential therapeutic targets in a number of pathological conditions, including cancer and cardiovascular disease. Small-molecule BET protein inhibitors such as JQ1 have demonstrated efficacy in reversing cardiac hypertrophy and heart failure in preclinical models. Yet, genetic studies elucidating the biology of BET proteins in the heart have not been conducted to validate pharmacological findings and to unveil potential pharmacological side effects. Methods: By engineering a cardiomyocyte-specific BRD4 knockout mouse, we investigated the role of BRD4 in cardiac pathophysiology. We performed functional, transcriptomic, and mitochondrial analyses to evaluate BRD4 function in developing and mature hearts. Results: Unlike pharmacological inhibition, loss of BRD4 protein triggered progressive declines in myocardial function, culminating in dilated cardiomyopathy. Transcriptome analysis of BRD4 knockout mouse heart tissue identified early and specific disruption of genes essential to mitochondrial energy production and homeostasis. Functional analysis of isolated mitochondria from these hearts confirmed that BRD4 ablation triggered significant changes in mitochondrial electron transport chain protein expression and activity. Computational analysis identified candidate transcription factors participating in the BRD4-regulated transcriptome. In particular, estrogen-related receptor α, a key nuclear receptor in metabolic gene regulation, was enriched in promoters of BRD4-regulated mitochondrial genes. Conclusions: In aggregate, we describe a previously unrecognized role for BRD4 in regulating cardiomyocyte mitochondrial homeostasis, observing that its function is indispensable to the maintenance of normal cardiac function