Unconventional cosmology on the (thick) brane

We consider the cosmology of a thick codimension 1 brane. We obtain the matching conditions leading to the cosmological evolution equations and show that when one includes matter with a pressure component along the extra dimension in the brane energy-momentum tensor, the cosmology is of non-standard type. In particular one can get acceleration when a dust of non-relativistic matter particles is the only source for the (modified) Friedman equation. Our equations would seem to violate the conservation of energy-momentum from a 4D perspective, but in 5D the energy-momentum is conserved. One could write down an effective conserved 4D energy-momentum tensor attaching a ``dark energy'' component to the energy-momentum tensor of matter that has pressure along the extra dimension. This extra component could, on a cosmological scale, be interpreted as matter-coupled quintessence. We comment on the effective 4D description of this effect in terms of the time evolution of a scalar field (the 5D radion) coupled to this kind of matter.Comment: 9 pages, v2. eq.(17) corrected, comments on effective theory change

Self-Dual Supersymmetric Dirac-Born-Infeld Action

We present a self-dual N=1 supersymmetric Dirac-Born-Infeld action in three dimensions. This action is based on the supersymmetric generalized self-duality in odd dimensions developed originally by Townsend, Pilch and van Nieuwenhuizen. Even though such a self-duality had been supposed to be very difficult to generalize to a supersymmetrically interacting system, we show that Dirac-Born-Infeld action is actually compatible with supersymmetry and self-duality in three-dimensions. The interactions can be further generalized to arbitrary (non)polynomial interactions. As a by-product, we also show that a third-rank field strength leads to a more natural formulation of self-duality in 3D. We also show an interesting role played by the third-rank field strength leading to a supersymmetry breaking, in addition to accommodating a Chern-Simons form.Comment: 12 pages, no figure

Nonlinear electrodynamics and CMB polarization

Recently WMAP and BOOMERanG experiments have set stringent constraints on the polarization angle of photons propagating in an expanding universe: $\Delta \alpha = (-2.4 \pm 1.9)^\circ$. The polarization of the Cosmic Microwave Background radiation (CMB) is reviewed in the context of nonlinear electrodynamics (NLED). We compute the polarization angle of photons propagating in a cosmological background with planar symmetry. For this purpose, we use the Pagels-Tomboulis (PT) Lagrangian density describing NLED, which has the form $L\sim (X/\Lambda^4)^{\delta - 1}\; X$, where $X=1/4 F_{\alpha\beta} F^{\alpha \beta}$, and $\delta$ the parameter featuring the non-Maxwellian character of the PT nonlinear description of the electromagnetic interaction. After looking at the polarization components in the plane orthogonal to the ($x$)-direction of propagation of the CMB photons, the polarization angle is defined in terms of the eccentricity of the universe, a geometrical property whose evolution on cosmic time (from the last scattering surface to the present) is constrained by the strength of magnetic fields over extragalactic distances.Comment: 17 pages, 2 figures, minor changes, references adde

CRISPR transcriptional repression devices and layered circuits in mammalian cells

A key obstacle to creating sophisticated genetic circuits has been the lack of scalable device libraries. Here we present a modular transcriptional repression architecture based on clustered regularly interspaced palindromic repeats (CRISPR) system and examine approaches for regulated expression of guide RNAs in human cells. Subsequently we demonstrate that CRISPR regulatory devices can be layered to create functional cascaded circuits, which provide a valuable toolbox for engineering purposes.National Institutes of Health (U.S.) (Grant 5R01CA155320-04)National Institutes of Health (U.S.) (Grant P50 GM098792)Korea (South). Ministry of Science, Information and Communication Technolgy. Intelligent Synthetic Biology Center of Global Frontier Project (2013M3A6A8073557

Enzyme sequestration as a tuning point in controlling response dynamics of signalling networks

Signalling networks result from combinatorial interactions among many enzymes and scaffolding proteins. These complex systems generate response dynamics that are often essential for correct decision-making in cells. Uncovering biochemical design principles that underpin such response dynamics is a prerequisite to understand evolved signalling networks and to design synthetic ones. Here, we use in silico evolution to explore the possible biochemical design space for signalling networks displaying ultrasensitive and adaptive response dynamics. By running evolutionary simulations mimicking different biochemical scenarios, we find that enzyme sequestration emerges as a key mechanism for enabling such dynamics. Inspired by these findings, and to test the role of sequestration, we design a generic, minimalist model of a signalling cycle, featuring two enzymes and a single scaffolding protein. We show that this simple system is capable of displaying both ultrasensitive and adaptive response dynamics. Furthermore, we find that tuning the concentration or kinetics of the sequestering protein can shift system dynamics between these two response types. These empirical results suggest that enzyme sequestration through scaffolding proteins is exploited by evolution to generate diverse response dynamics in signalling networks and could provide an engineering point in synthetic biology applications

Modular Composition of Gene Transcription Networks

Predicting the dynamic behavior of a large network from that of the composing modules is a central problem in systems and synthetic biology. Yet, this predictive ability is still largely missing because modules display context-dependent behavior. One cause of context-dependence is retroactivity, a phenomenon similar to loading that influences in non-trivial ways the dynamic performance of a module upon connection to other modules. Here, we establish an analysis framework for gene transcription networks that explicitly accounts for retroactivity. Specifically, a module's key properties are encoded by three retroactivity matrices: internal, scaling, and mixing retroactivity. All of them have a physical interpretation and can be computed from macroscopic parameters (dissociation constants and promoter concentrations) and from the modules' topology. The internal retroactivity quantifies the effect of intramodular connections on an isolated module's dynamics. The scaling and mixing retroactivity establish how intermodular connections change the dynamics of connected modules. Based on these matrices and on the dynamics of modules in isolation, we can accurately predict how loading will affect the behavior of an arbitrary interconnection of modules. We illustrate implications of internal, scaling, and mixing retroactivity on the performance of recurrent network motifs, including negative autoregulation, combinatorial regulation, two-gene clocks, the toggle switch, and the single-input motif. We further provide a quantitative metric that determines how robust the dynamic behavior of a module is to interconnection with other modules. This metric can be employed both to evaluate the extent of modularity of natural networks and to establish concrete design guidelines to minimize retroactivity between modules in synthetic systems.United States. Air Force Office of Scientific Research (FA9550-12-1-0129

Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L.

Cholinesterase inhibition is one of the most treatment strategies against Alzheimer's disease (AD) where metal accumulation is also strongly associated with pathology of the disease. In the current study, we assessed inhibitory effect against acetyl- (AChE) and butyrylcholinesterase (BChE) and metal-chelating capacity of twelve diterpenes: arucadiol, miltirone, tanshinone IIa, 1-oxomiltirone, cryptotanshinone, 1,2-didehydromiltirone, 1,2-didehydrotanshinone IIa, 1b-hydroxycryptotanshinone, 15,16- dihydrotanshinone, tanshinone I, isotanshinone II, 1(S)-hydroxytanshinone IIa, and rosmarinic acid, isolated from Perovskia atriplicifolia and Salvia glutinosa. The compounds were tested at 10 µg/mL using ELISA microtiter assays against AChE and BChE. QSAR and molecular docking studies have been also performed on the active compounds. All of the compounds showed higher [e.g., IC50 = 1.12 ± 0.07 µg/mL for 1,2-didehydromiltirone, IC50 = 1.15 ± 0.07 µg/mL for cryptotanshinone, IC50 = 1.20 ± 0.03 µg/mL for arucadiol, etc.)] or closer [1,2-didehydrotanshinone IIa (IC50 = 5.98 ± 0.49 µg/mL) and 1(S)-hydroxytanshinone IIa (IC50 = 5.71 ± 0.27 µg/mL)] inhibition against BChE as compared to that of galanthamine (IC50 = 12.56 ± 0.37 µg/mL), whereas only 15,16-dihydrotanshinone moderately inhibited AChE (65.17 ± 1.39%). 1,2-Didehydrotanshinone IIa (48.94 ± 0.26%) and 1(S)-hydroxytanshinone IIa (47.18 ± 5.10%) possessed the highest metal-chelation capacity. The present study affords an evidence for the fact that selective BChE inhibitors should be further investigated as promising candidate molecules for AD therapy.Ciencias AmbientalesCiencias de la AlimentaciónFarmaciaIngeniería, Industria y ConstrucciónMedicin

Comparative Analysis of Acid Sphingomyelinase Distribution in the CNS of Rats and Mice Following Intracerebroventricular Delivery

Niemann-Pick A (NPA) disease is a lysosomal storage disorder (LSD) caused by a deficiency in acid sphingomyelinase (ASM) activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO) mice could be partially alleviated by intracerebroventricular (ICV) infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat

Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an