Trafficking and processing of bacterial proteins by mammalian cells: Insights from chondroitinase ABC.

Background: There is very little reported in the literature about the relationship between modifications of bacterial proteins and their secretion by mammalian cells that synthesize them. We previously reported that the secretion of the bacterial enzyme Chondroitinase ABC by mammalian cells requires the strategic removal of at least three N-glycosylation sites. The aim of this study was to determine if it is possible to enhance the efficacy of the enzyme as a treatment for spinal cord injury by increasing the quantity of enzyme secreted or by altering its cellular location. Methodology/principal findings: To determine if the efficiency of enzyme secretion could be further increased, cells were transfected with constructs encoding the gene for chondroitinase ABC modified for expression by mammalian cells; these contained additional modifications of strategic N-glycosylation sites or alternative signal sequences to direct secretion of the enzyme from the cells. We show that while removal of certain specific N-glycosylation sites enhances enzyme secretion, N-glycosylation of at least two other sites, N-856 and N-773, is essential for both production and secretion of active enzyme. Furthermore, we find that the signal sequence directing secretion also influences the quantity of enzyme secreted, and that this varies widely amongst the cell types tested. Last, we find that replacing the 3’UTR on the cDNA encoding Chondroitinase ABC with that of β-actin is sufficient to target the enzyme to the neuronal growth cone when transfected into neurons. This also enhances neurite outgrowth on an inhibitory substrate. Conclusion/significance: Some intracellular trafficking pathways are adversely affected by cryptic signals present in the bacterial gene sequence, whilst unexpectedly others are required for efficient secretion of the enzyme. Furthermore, targeting chondroitinase to the neuronal growth cone promotes its ability to increase neurite outgrowth on an inhibitory substrate. These findings are timely in view of the renewed prospects for gene therapy, and of direct relevance to strategies aimed at expressing foreign proteins in mammalian cells, in particular bacterial proteins

Structurally dynamic spin market networks

The agent-based model of stock price dynamics on a directed evolving complex network is suggested and studied by direct simulation. The stationary regime is maintained as a result of the balance between the extremal dynamics, adaptivity of strategic variables and reconnection rules. The inherent structure of node agent "brain" is modeled by a recursive neural network with local and global inputs and feedback connections. For specific parametric combination the complex network displays small-world phenomenon combined with scale-free behavior. The identification of a local leader (network hub, agent whose strategies are frequently adapted by its neighbors) is carried out by repeated random walk process through network. The simulations show empirically relevant dynamics of price returns and volatility clustering. The additional emerging aspects of stylized market statistics are Zipfian distributions of fitness.Comment: 13 pages, 5 figures, accepted in IJMPC, references added, minor changes in model, new results and modified figure

Risk, Uncertainty, and the Perceived Threat of Terrorist Attacks: Evidence of Flight-to-Quality

© 2013 World Scientific Publishing Company and Midwest Finance Association. Information provided by the US Department of Homeland Security regarding potential terrorist attacks significantly affects US Treasury securities markets. When the government announces heightened terror alert levels, investors\u27 perceptions of risk increase and investors purchase 1-month and 1-year Treasury bills and 3-year, 5-year, 7-year, and 10-year US Treasuries in a flight-to-quality episode. Partial anticipation of increased threat level announcements is stronger than the anticipation of announcements regarding the federal funds rate during the 10 days prior to an announcement

A cell lineage analysis of segmentation in the chick embryo

We have studied the lineage history of the progenitors of the somite mesoderm and of the neural tube in the chick embryo by injecting single cells with the fluorescent tracer, rhodamine-lysine-dextran. We find that, although single cells within the segmental plate give rise to discrete clones in the somites to which they contribute, neither the somites nor their component parts (sclerotome, dermatome, myotome or their rostral and caudal halves) are `compartments' in the sense defined in insects. Cells in the rostral two thirds or so of the segmental plate contribute only to somite tissue and divide about every 10 h, while those in the caudal portions of this structure contribute both to the somites and to intermediate and lateral plate mesoderm derivatives. In the neural tube, the descendants of individual prospective ventral horn cells remain together within the horn, with a cycle time of 10 h. We have also investigated the role of the cell division cycle in the formation and subsequent development of somites. A single treatment of 2-day chick embryos with heat shock or a variety of drugs that affect the cell cycle all produce repeated anomalies in the pattern of somites and vertebrae that develop subsequent to the treatment. The interval between anomalies is 6-7 somites (or a multiple of this distance), which corresponds to 10 h. This interval is identical to that measured for the cell division cycle. Given that cell division synchrony is seen in the presomitic mesoderm, we suggest that the cell division cycle plays a role in somite formation. Finally, we consider the mechanisms responsible for regionalization of derivatives of the somite, and conclude that it is likely that both cell interactions and cell lineage history are important in the determination of cell fates

Double Exponential Instability of Triangular Arbitrage Systems

If financial markets displayed the informational efficiency postulated in the efficient markets hypothesis (EMH), arbitrage operations would be self-extinguishing. The present paper considers arbitrage sequences in foreign exchange (FX) markets, in which trading platforms and information are fragmented. In Kozyakin et al. (2010) and Cross et al. (2012) it was shown that sequences of triangular arbitrage operations in FX markets containing 4 currencies and trader-arbitrageurs tend to display periodicity or grow exponentially rather than being self-extinguishing. This paper extends the analysis to 5 or higher-order currency worlds. The key findings are that in a 5-currency world arbitrage sequences may also follow an exponential law as well as display periodicity, but that in higher-order currency worlds a double exponential law may additionally apply. There is an "inheritance of instability" in the higher-order currency worlds. Profitable arbitrage operations are thus endemic rather that displaying the self-extinguishing properties implied by the EMH.Comment: 22 pages, 22 bibliography references, expanded Introduction and Conclusion, added bibliohraphy reference

Quantum cat maps with spin 1/2

We derive a semiclassical trace formula for quantized chaotic transformations of the torus coupled to a two-spinor precessing in a magnetic field. The trace formula is applied to semiclassical correlation densities of the quantum map, which, according to the conjecture of Bohigas, Giannoni and Schmit, are expected to converge to those of the circular symplectic ensemble (CSE) of random matrices. In particular, we show that the diagonal approximation of the spectral form factor for small arguments agrees with the CSE prediction. The results are confirmed by numerical investigations.Comment: 26 pages, 3 figure

Capacitance fluctuations causing channel noise reduction in stochastic Hodgkin-Huxley systems

Voltage-dependent ion channels determine the electric properties of axonal cell membranes. They not only allow the passage of ions through the cell membrane but also contribute to an additional charging of the cell membrane resulting in the so-called capacitance loading. The switching of the channel gates between an open and a closed configuration is intrinsically related to the movement of gating charge within the cell membrane. At the beginning of an action potential the transient gating current is opposite to the direction of the current of sodium ions through the membrane. Therefore, the excitability is expected to become reduced due to the influence of a gating current. Our stochastic Hodgkin-Huxley like modeling takes into account both the channel noise -- i.e. the fluctuations of the number of open ion channels -- and the capacitance fluctuations that result from the dynamics of the gating charge. We investigate the spiking dynamics of membrane patches of variable size and analyze the statistics of the spontaneous spiking. As a main result, we find that the gating currents yield a drastic reduction of the spontaneous spiking rate for sufficiently large ion channel clusters. Consequently, this demonstrates a prominent mechanism for channel noise reduction.Comment: 18 page

Halothane hepatitis with renal failure treated with hemodialysis and exchange transfusion

A 38-year-old white female, hepatitis B antigen negative, developed fluminating hepatic failure associated with oliguria and severe azotemia after two halothane anesthesia and without exposure to other hepatotoxic drugs or blood transfusions. She was treated with multiple hemodialysis and exchange blood transfusion. The combined treatment corrected the uremic abnormalities and improved her level of consciousness. The liver and kidney function gradually improved, and she made a complete recovery, the first recorded with hepatic and renal failure under these post-anesthetic conditions. Further evaluation of this combined treatment used for this patient is warranted. © 1974 The Japan Surgical Society

Drivers and outcomes of work alienation: reviving a concept

This article sheds new light on an understudied construct in mainstream management theory, namely, work alienation. This is an important area of study because previous research indicates that work alienation is associated with important individual and organizational outcomes. We tested four antecedents of work alienation: decision-making autonomy, task variety, task identity, and social support. Moreover, we examined two outcomes of alienation: deviance and performance, the former measured 1 year after the independent variables were measured, and the latter as rated by supervisors. We present evidence from a sample of 283 employees employed at a construction and consultancy organization in the United Kingdom. The results supported the majority of our hypotheses, indicating that alienation is a worthy concept of exploration in the management sciences

On the Computational Complexity of Measuring Global Stability of Banking Networks

Threats on the stability of a financial system may severely affect the functioning of the entire economy, and thus considerable emphasis is placed on the analyzing the cause and effect of such threats. The financial crisis in the current and past decade has shown that one important cause of instability in global markets is the so-called financial contagion, namely the spreading of instabilities or failures of individual components of the network to other, perhaps healthier, components. This leads to a natural question of whether the regulatory authorities could have predicted and perhaps mitigated the current economic crisis by effective computations of some stability measure of the banking networks. Motivated by such observations, we consider the problem of defining and evaluating stabilities of both homogeneous and heterogeneous banking networks against propagation of synchronous idiosyncratic shocks given to a subset of banks. We formalize the homogeneous banking network model of Nier et al. and its corresponding heterogeneous version, formalize the synchronous shock propagation procedures, define two appropriate stability measures and investigate the computational complexities of evaluating these measures for various network topologies and parameters of interest. Our results and proofs also shed some light on the properties of topologies and parameters of the network that may lead to higher or lower stabilities.Comment: to appear in Algorithmic