Translational perspectives on perfusion-diffusion mismatch in ischemic stroke

Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion–diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice

The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken

The replacement histone H2A.Z is variously reported as being linked to gene expression and preventing the spread of heterochromatin in yeast, or concentrated at heterochromatin in mammals. To resolve this apparent dichotomy, affinity-purified antibodies against the N-terminal region of H2A.Z, in both a triacetylatedandnon- acetylatedstate, areusedin native chromatin immmuno-precipitation experiments with mononucleosomes from three chicken cell types. The hyperacetylated species concentrates at the 50 end of active genes, both tissue specific and housekeeping but is absent from inactive genes, while the unacetylated form is absent from both active and inactive genes. A concentration of H2A.Z is also found at insulators under circumstances implying a link to barrier activity but not to enhancer blocking. Although acetylated H2A.Z is widespread throughout the interphase genome, at mitosis its acetylation is erased, the unmodified form remaining. Thus, although H2A.Z may operate as an epigenetic marker for active genes, its N-terminal acetylation does not

The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken

The replacement histone H2A.Z is variously reported as being linked to gene expression and preventing the spread of heterochromatin in yeast, or concentrated at heterochromatin in mammals. To resolve this apparent dichotomy, affinity-purified antibodies against the N-terminal region of H2A.Z, in both a triacetylatedandnon- acetylatedstate, areusedin native chromatin immmuno-precipitation experiments with mononucleosomes from three chicken cell types. The hyperacetylated species concentrates at the 50 end of active genes, both tissue specific and housekeeping but is absent from inactive genes, while the unacetylated form is absent from both active and inactive genes. A concentration of H2A.Z is also found at insulators under circumstances implying a link to barrier activity but not to enhancer blocking. Although acetylated H2A.Z is widespread throughout the interphase genome, at mitosis its acetylation is erased, the unmodified form remaining. Thus, although H2A.Z may operate as an epigenetic marker for active genes, its N-terminal acetylation does not

Supersymmetry, quark confinement and the harmonic oscillator

We study some quantum systems described by noncanonical commutation relations formally expressed as [q,p]=ihbar(I + chi H), where H is the associated (harmonic oscillator-like) Hamiltonian of the system, and chi is a Hermitian (constant) operator, i.e. [H,chi]=0 . In passing, we also consider a simple (chi=0 canonical) model, in the framework of a relativistic Klein-Gordon-like wave equation.Comment: To be published in Journal of Physics A: Mathematical and Theoretical (2007

Novel modeling formalisms and simulation tools in computational biosystems

Living organisms are complex systems that emerge from the fundamental building blocks of life. Systems Biology is a recent field of science that studies these complex phenomena at the cellular level (Kitano 2002). Understanding the mechanisms of the cell is essential for research and development in several areas such as drug discovery and biotechnological production. In the latter, metabolic engineering is used for building mutant microbial strains with increased productivity of compounds with industrial interest, such as biofuels (Stephanopoulos 1998). Using computational models of cellular metabolism, it is possible to systematically test and predict the optimal manipulations, such as gene knockouts, that produce the ideal phenotype for a specific application. These models are typically built in an iterative cycle of experiment and refinement, by multidisciplinary research teams that include biologists, engineers and computer scientists. The interconnection between different cellular processes, such as metabolism and genetic regulation, reflects the importance of the holistic approach claimed by the Systems Biology paradigm in replacement of traditional reductionist methods. Although most cellular components have been studied individually, the behavior of the cell emerges from the network-level interaction and requires an integrative analysis. Recent high–throughput methods have generated the so- called omics data (e.g.: genomics, transcriptomics, proteomics, metabolomics, fluxomics) that have allowed the reconstruction of biological networks (Palsson 2006). However, despite the great advances in the area, we are still far from a whole-cell computational model that is able to simulate all the components of a living cell. Due to the enormous size and complexity of intracellular biological networks, computational cell models tend to be partial and focused on the application of interest. Also, due to the multidisciplinarity of the field, these models are based on several different kinds of formalisms. Therefore, it is important to develop a framework with common modeling formalisms, analysis and simulation methods, that is able to accommodate different kinds biological networks, with different types of entities and their interactions, into genome-scale integrated models. Cells are composed by thousands of components that interact in myriad ways. Despite this intricate interconnection it is usual to divide and classify these networks according to biological function. The main types of networks are signaling, gene regulatory and metabolic. Signal transduction is a process for cellular communication where the cell receives and responds to external stimuli through signaling cascades (Gomperts et al. 2009; Albert and Wang 2009). These cascades affect gene regulation, which is the method for controlling gene expression, and consequently several cellular functions (Schlittand and Brazma 2007; Karlebach and Sgamir 2008). Many genes encode enzymes which are responsible for catalyzing biochemical reactions. The complex network of these reactions forms the cellular metabolism that sustains the cell’s growth and energy requirements (Steuer and Junker 2009; Palsson 2006). The objectives of this work, in the context of a PhD thesis, consist in re-search and selection of an appropriate modeling formalism to develop a framework for integration of different biological networks, with focus on regulatory and metabolic networks, and the implementation of suitable analysis, simulation and optimization methods. To achieve these goals, it is necessary to resolve many modeling issues, such as the integration of discrete and continuous events, representation of network topology, support for different levels of abstraction, lack of parameters and model complexity. This framework will be used for the implementation of an integrated model of E. coli, a widely used organism for industrial application

Goldstone-Mode Phonon Dynamics in the Pyrochlore Cd2Re2O7

We have measured the polarized Raman scattering spectra of Cd2Re2O7, the first superconducting pyrochlore, as a function of temperature. For temperatures below the cubic-to-tetragonal structural phase transition (SPT) at 200K, a peak with B1 symmetry develops at zero frequency with divergent intensity. We identify this peak as the first observation of the Goldstone phonon in a crystalline solid. The Goldstone phonon is a collective excitation that exists due to the breaking of the continuous symmetry with the SPT. Its emergence coincides with that of a Raman-active soft mode. The order parameter for both features derives from an unstable doubly-degenerate vibration (with Eu symmetry) of the O1 atoms which drives the SPT.Comment: 4+ pages, 4 figures. Updated figures and text. Accepted to PR