Network Thermodynamics And Morphogenesis

Network thermodynamics is a method of representing thermodynamic systems as equivalent electrical circuits which allows the application of well-developed techniques of network analysis to thermodynamic problems (Oster, G. F., Perelson, A. S. and Katchalsky, A. 1973, Network Thermodynamics: Dynamical Modelling of Biophysical Systems. Q. Rev. Biophys., 6, 1-134). This dissertation covers four aspects. First, the relevant graph theory, circuit theory including normal tree analysis, and systems theory are summarized to provide a context and working vocabulary for the subsequent sections. Next, a systematic approach is presented for representing thermodynamic systems as equivalent circuits based on dynamical, dimensional, topological and mathematical similarities. Its use is demonstrated by designing an equivalent circuit to represent a primitive autocatalytic reaction-diffusion system (based on the Brusselator) capable of evolving stable asymmetries in the distribution of reactants. This is an example of a morphogenetic system, that is a dynamical chemical system capable of evolving stable changes in structure over time. The resulting equivalent circuit is analyzed using a general circuit simulation language Spice (Dowell, R., Newton, A. R. and Pederson, D. O. 1976. Spice VAX Version 2X.x User\u27s Guide. Department of Electrical Engineering and Computer Sciences, University of California, Berkeley). Using several different sets of boundary conditions, initial system states and system topologies as examples, the versatility of the equivalent circuit method is demonstrated. When the most asymmetrical topology and open boundary conditions are used, and a non-linear positive feedback loop is used to represent the autocatalytic step, the circuit response shows stable potential differences between distributed subcircuit regions. The final section is a note outlining a method for the sequential synthesis and analysis of a morphogenetic automaton based on network thermodynamics

Glutamate efflux mediated by Corynebacterium glutamicum MscCG, Escherichia coli MscS, and their derivatives

AbstractCorynebacterium glutamicum is used in microbial biotechnology for the production of amino acids, in particular glutamate. The mechanism of glutamate excretion, however, is not yet fully understood. Recently, evidence was provided that the NCgl1221 gene product from C. glutamicum ATCC 13869, a MscS-type mechanosensitive efflux channel, is responsible for glutamate efflux [1]. The major difference of NCgl1221 and the homologous protein MscCG of C. glutamicum ATCC 13032 from Escherichia coli MscS and most other MscS-type proteins is the presence of an additional, 247 amino acid long C-terminal domain. By topology analysis, we show that this domain in MscCG carries a transmembrane segment. We have generated selected C-terminal truncations of MscCG, gain-of-function and loss-of-function constructs of both E. coli MscS and C. glutamicum MscCG, as well as fusion constructs of the two proteins. These mutant proteins were investigated for mechanosensitive efflux, MS channel activity, glutamate excretion and their impact on membrane potential. We provide evidence that the channel domain of MscCG mediates glutamate efflux in response to penicillin treatment, and that the E. coli MscS channel is to some extent able to function in a similar manner. We further show that the C-terminal domain of MscCG has a significant impact for function and/or regulation of MscCG. Significantly, a positive effect on glutamate efflux of the C-terminal extension of MscCG from C. glutamicum was also observed when fused to the E. coli MscS channel

cAMP activates adenylate and guanylate cyclase of Dictyostelium discoideum cells by binding to different classes of cell-surface receptors. A study with extracellular Ca2+

cAMP induces a transient increase of cAMP and cGMP levels in Dictyostelium discoideum cells. Fast binding experiments reveal three types of cAMP-binding site (S, H and L), which have different off-rates (t0.5, 0.7-15 s) and different affinities (Kd, 15-450 nM). A time- and cAMP-concentration-dependent transition of H- to L-sites occurs during the binding reaction. Extracellular Ca2+ had multiple effects on cAMP-binding sites. (i) The number of H + L-sites increased 2.5-fold, while the number of S-sites was not strongly affected. (ii) The Kd of the S-sites was reduced from 16 nM to 5 nM (iii) The conversion of H-sites to L-sites was inhibited up to 80%. The kinetics of the cAMP-induced cAMP accumulation was not strongly altered by Ca2+, but the amount of cAMP produced was inhibited up to 80%. The kinetics of the cAMP-induced cGMP accumulation was strongly altered; maximal levels were obtained sooner, and the Ka was reduced from 15 to 3.5 nM cAMP. Ca2+, Mg2+ and Mn2+ increased the number of binding sites, all with EC50 = 0.5 mM. The S-sites and the cGMP response were modified by equal Ca2+ concentrations and by higher concentrations of Mg2+ and Mn2+ (EC50 are respectively 0.4 mM, 2.5 mM and about 25 mM). The conversion of H- to L-sites and the cAMP response were specifically inhibited by Ca2+ with EC50 = 20 µM. It is concluded that cAMP activates guanylate cyclase through the S-sites; adenylate cyclase is activated by the H + L-sites, in which the appearance of the L-sites during the binding reaction represents the coupling of occupied surface cAMP receptors to adenylate cyclase.

Bear Steans Warren Spector e-mail message to Mary Kay Scucci

These are internal communications of employees of Bear Stearns Companies, Inc. during the Global Financial Crisis

Apathy dimensions in Parkinson's disease

OBJECTIVE: Apathy is a prominent and disabling symptom in Parkinson's disease (PD) and is a multidimensional behaviour, but which dimensions are specifically affected is unclear. Therefore, the aim of this preliminary study was to determine the psychometric properties of the Dimensional Apathy Scale (DAS) and explore the multidimensional profile of apathy in PD patients.  METHODS: Thirty-four PD patients, with 30 of their informants/carers, and 34 healthy controls, with 30 of their informants, completed the DAS, Apathy Evaluation Scale and the Geriatric Depression Scale Short Form. Motor staging and independent living status were recorded.  RESULTS: Comparative group analyses revealed that PD patients were significantly more apathetic on self-rated executive (p = 0.01) and initiation (p = 0.03) dimensions than controls, where only executive apathy was significantly higher in ratings of patients' informants/carers compared with controls' informants (p = 0.02). A third of patients were impaired on at least one apathy dimension. Additionally, patients with apathy tended to have more impaired activities of daily living, while none of the apathy dimensions related to motor disability.  CONCLUSION: Our findings show the DAS is a valid and reliable multidimensional apathy tool for use in PD. PD is characterised by an executive apathy profile as determined by informants/carers, although patients described both executive and initiation apathy. This indicates a lack of motivation for planning, organisation and attention and lack of initiation of thoughts or behaviours. Further research is needed to determine the cognitive underpinnings of this emerging apathy profile and the clinical impact in PD. Copyright © 2017 John Wiley & Sons, Ltd

Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis

Follmann M, Ochrombel I, Kraemer R, et al. Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis. BMC Genomics. 2009;10(1):621.Background: The maintenance of internal pH in bacterial cells is challenged by natural stress conditions, during host infection or in biotechnological production processes. Comprehensive transcriptomic and proteomic analyses has been conducted in several bacterial model systems, yet questions remain as to the mechanisms of pH homeostasis. Results: Here we present the comprehensive analysis of pH homeostasis in C. glutamicum, a bacterium of industrial importance. At pH values between 6 and 9 effective maintenance of the internal pH at 7.5 +/- 0.5 pH units was found. By DNA microarray analyses differential mRNA patterns were identified. The expression profiles were validated and extended by 1D-LC-ESI-MS/MS based quantification of soluble and membrane proteins. Regulators involved were identified and thereby participation of numerous signaling modules in pH response was found. The functional analysis revealed for the first time the occurrence of oxidative stress in C. glutamicum cells at neutral and low pH conditions accompanied by activation of the iron starvation response. Intracellular metabolite pool analysis unraveled inhibition of the TCA and other pathways at low pH. Methionine and cysteine synthesis were found to be activated via the McbR regulator, cysteine accumulation was observed and addition of cysteine was shown to be toxic under acidic conditions. Conclusions: Novel limitations for C. glutamicum at non-optimal pH values were identified by a comprehensive analysis on the level of the transcriptome, proteome, and metabolome indicating a functional link between pH acclimatization, oxidative stress, iron homeostasis, and metabolic alterations. The results offer new insights into bacterial stress physiology and new starting points for bacterial strain design or pathogen defense

Localization and Equipartition of Energy in the beta-FPU Chain : Chaotic Breathers

The evolution towards equipartition in the $\beta$-FPU chain is studied considering as initial condition the highest frequency mode. Above an analytically derived energy threshold, this zone-boundary mode is shown to be modulationally unstable and to give rise to a striking localization process. The spontaneously created excitations have strong similarity with moving exact breathers solutions. But they have a finite lifetime and their dynamics is chaotic. These chaotic breathers are able to collect very efficiently the energy in the chain. Therefore their size grows in time and they can transport a very large quantity of energy. These features can be explained analyzing the dynamics of perturbed exact breathers of the FPU chain. In particular, a close connection between the Lyapunov spectrum of the chaotic breathers and the Floquet spectrum of the exact ones has been found. The emergence of chaotic breathers is convincingly explained by the absorption of high frequency phonons whereas a breather's metastability is for the first time identified. The lifetime of the chaotic breather is related to the time necessary for the system to reach equipartition. The equipartition time turns out to be dependent on the system energy density $\epsilon$ only. Moreover, such time diverges as $\epsilon^{-2}$ in the limit $\epsilon \to 0$ and vanishes as $\epsilon^{-1/4}$ for $\epsilon \to \infty$.Comment: 20 pages, Revtex - Submitted to Physica

Chassis organism from Corynebacterium glutamicum – a top-down approach to identify and delete irrelevant gene clusters

Unthan S, Baumgart M, Radek A, et al. Chassis organism from Corynebacterium glutamicum – a top-down approach to identify and delete irrelevant gene clusters. Biotechnology Journal. 2015;10(2):290-301

Dynamically controlled deposition of colloidal nanoparticles suspension in evaporating drops using laser radiation

Dynamic control of the distribution of polystyrene suspended nanoparticles in evaporating droplets is investigated using a 2.9 μm high power laser. Under laser radiation a droplet is locally heated and fluid flows are induced that overcome the capillary flow, and thus a reversal of the coffee-stain effect is observed. Suspension particles are accumulated in a localised area, one order of magnitude smaller than the original droplet size. By scanning the laser beam over the droplet, particles can be deposited in an arbitrary pattern. This finding raises the possibility for direct laser writing of suspended particles through a liquid layer. Furthermore, a highly uniform coating is possible by manipulating the laser beam diameter and exposure time. The effect is expected to be universally applicable to aqueous solutions independent of solutes (either particles or molecules) and deposited substrates

Apathy is associated with executive functioning in first episode psychosis

<p>Abstract</p> <p>Background</p> <p>The underlying nature of negative symptoms in psychosis is poorly understood. Investigation of the relationship between the different negative subsymptoms and neurocognition is one approach to understand more of the underlying nature. Apathy, one of the subsymptoms, is also a common symptom in other brain disorders. Its association with neurocognition, in particular executive functioning, is well documented in other brain disorders, but only studied in one former study of chronic patients with schizophrenia. This study investigates the association between apathy and neurocognitive functioning in patients with first episode psychosis (FEP), with the hypothesis that apathy is more associated with tests representing executive function than tests representing other neurocognitive domains.</p> <p>Methods</p> <p>Seventy-one FEP patients were assessed with an extensive neuropsychological test battery. Level of apathy was assessed with the abridged Apathy Evaluation Scale (AES-C-Apathy).</p> <p>Results</p> <p>AES-C-Apathy was only significantly associated with tests from the executive domain [Semantic fluency (r = .37, p < .01), Phonetic fluency (r = .25, p < .05)] and working memory [Letter Number Span (r = .26; p =< .05)]; the first two representing the initiation part of executive function. Confounding variables such as co-occuring depression, positive symptoms or use of antipsychotic medication did not significantly influence the results.</p> <p>Conclusion</p> <p>We replicated in FEP patients the relationship between apathy and executive functioning reported in another study for chronic patients with schizophrenia. We also found apathy in FEP to have the same relationship to executive functioning, as assessed with the Verbal fluency tests, as that reported in patients with other brain disorders, pointing to a common underlying nature of this symptom across disorders.</p