Paradoxical signaling regulates structural plasticity in dendritic spines

Transient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics

Protein Structure Prediction Using Basin-Hopping

Associative memory Hamiltonian structure prediction potentials are not overly rugged, thereby suggesting their landscapes are like those of actual proteins. In the present contribution we show how basin-hopping global optimization can identify low-lying minima for the corresponding mildly frustrated energy landscapes. For small systems the basin-hopping algorithm succeeds in locating both lower minima and conformations closer to the experimental structure than does molecular dynamics with simulated annealing. For large systems the efficiency of basin-hopping decreases for our initial implementation, where the steps consist of random perturbations to the Cartesian coordinates. We implemented umbrella sampling using basin-hopping to further confirm when the global minima are reached. We have also improved the energy surface by employing bioinformatic techniques for reducing the roughness or variance of the energy surface. Finally, the basin-hopping calculations have guided improvements in the excluded volume of the Hamiltonian, producing better structures. These results suggest a novel and transferable optimization scheme for future energy function development

Absorbtion Kinetics of Some Purines, Pyrimidines, and Nucleosides in Taenia Crassiceps Larvae

Paper by Gary L. Uglem and Michael G. Lev

Pathogenic fungus in feral populations of the invasive North American bullfrog in Argentina

Nearly a third (32.4%) of the world?s amphibian species are either threatened with extinction or already extinct (1). The chytrid fungus Batrachochytrium dendrobatidis (Bd) (Chytridiomycetes: Ryzophydiales) (2) has been recognized as responsible for mass mortalities or population extinctions of numerous anuran species in different continents (e.g., 3,4,5 and citations therein). There is evidence that legal and illegal trade in amphibians as pets, food and for bio-control is one of the reasons for the spread of Bd (6,7,8,9).The North American bullfrog, Lithobates catesbeianus (Shaw, 1802) (Anura: Ranidae), has been introduced accidentally or intentionally for aquaculture into numerous countries (10). L. catesbeianus is a highly invasive species that disperses rapidly within an ecosystem (11). The oldest report of specimens of L. catesbeianus parasitized by Bd dates from 1928, and corresponds to individuals from the State of California, USA (12). Bullfrogs can be asymptomatically infected with Bd (13), and infected specimens can readily spread the disease into new geographic regions (14).Initial unsuccessful attempts to introduce bullfrogs into Argentina for farming date from 1935. A subsequent successful introduction occurred during the 1980s (10,15). Escaped individuals became established and the species spread rapidly (16). Nevertheless assessments of the presence of Bd in feral bullfrogs from Argentina are lacking (17,18).Fil: Ghirardi, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Lopez, Javier Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Sanabria, Eduardo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Juan. Facultad de Filosofía, Humanidades y Artes. Instituto de Ciencias Básicas; ArgentinaFil: Quiroga, Lorena Beatriz. Universidad Nacional de San Juan. Facultad de Filosofía, Humanidades y Artes. Instituto de Ciencias Básicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Levy, Michael G.. University of North Carolina; Estados Unido

Adiabatic connection at negative coupling strengths

The adiabatic connection of density functional theory (DFT) for electronic systems is generalized here to negative values of the coupling strength $\alpha$ (with {\em attractive} electrons). In the extreme limit $\alpha\to-\infty$ a simple physical solution is presented and its implications for DFT (as well as its limitations) are discussed. For two-electron systems (a case in which the present solution can be calculated exactly), we find that an interpolation between the limit $\alpha\to-\infty$ and the opposite limit of infinitely strong repulsion ($\alpha\to+\infty$) yields a rather accurate estimate of the second-order correlation energy E\cor\glt[\rho] for several different densities $\rho$, without using virtual orbitals. The same procedure is also applied to the Be isoelectronic series, analyzing the effects of near-degeneracy.Comment: 9 pages, submitted to PR

Conservation status of the Georgia Blind Salamander (Eurycea wallacei) from the Floridan Aquifer of Florida and Georgia

The Georgia Blind Salamander (Eurycea wallacei) is a poorly understood stygobitic plethodontid salamander found in the Floridan Aquifer of Florida and Georgia, USA. Its distribution is poorly delimited and little information is available on the ecology and life history of the species. We summarize existing information on the Georgia Blind Salamander and report new findings with regard to distribution, conservation status, and aspects of its ecology and life history from recent surveys in Florida and Georgia, including anecdotal observations made by local cave divers. We also  present data on the prevalence of Batrachochytrium dendrobatidis and discuss potential measures and challenges involved in conservation. Georgia Blind Salamanders are known from at least 35 localities within five United States Geological Survey (USGS) HUC8 watersheds in Florida and Georgia, all within the groundwater of the Upper Floridan Aquifer. Some populations may be large, as cave divers have observed >100 salamanders in a single dive at three localities and reported densities up to 10 salamanders per square meter. We confirm through direct observation that the Dougherty Plain Cave Crayfish (Cambarus cryptodytes) is a predator of E. wallacei. Although we found no evidence that any populations of the Georgia Blind Salamander have been infected by amphibian chytrid fungus, clear threats remain and include: (1) An “at risk” ranking by USGS of the Floridian Aquifer for contamination; (2) overharvesting of groundwater; (3) the presence of an emergent infectious amphibian disease in surface amphibians in the region (e.g., amphibian chytrid fun- gus); and (4) a lack of data on the basic biology and ecology of the species. We recommend the following conservation actions: (1) Better regulations and improved methods for retaining pesticide and fertilizer contaminants on the surface; (2) regulatory review of agricultural crops grown in the region and the establishment of systems and crops that do not require center pivot irrigation; (3) regular monitoring for disease across the range of the species; and (4) establishment of multiple assurance colonies such that captive specimens genetically represent at least half of the known populations

ATRX promotes gene expression by facilitating transcriptional elongation through guanine-rich coding regions

ATRX is a chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. It also influences the expression level of specific genes; however, deposition of H3.3 at transcribed genes is currently thought to occur independently of ATRX. We focused on a set of genes, including the autism susceptibility gene Neuroligin 4 (Nlgn4), that exhibit decreased expression in ATRX-null cells to investigate the mechanisms used by ATRX to promote gene transcription. Overall TERRA levels, as well as DNA methylation and histone modifications at ATRX target genes are not altered and thus cannot explain transcriptional dysregulation.We found thatATRX does not associate with the promoter of these genes, but rather binds within regions of the gene body corresponding to high H3.3 occupancy. These intragenic regions consist of guanine-rich DNA sequences predicted to form non-B DNA structures called G-quadruplexes during transcriptional elongation.We demonstrate thatATRX deficiency corresponds to reduced H3.3 incorporation and stalling ofRNApolymerase II at these G-rich intragenic sites. These findings suggest that ATRX promotes the incorporation of histone H3.3 at particular transcribed genes and facilitates transcriptional elongation through G-rich sequences. The inability to transcribe genes such as Nlgn4 could cause deficits in neuronal connectivity and cognition associated with ATRX mutations in humans

Dealing with Complexity in Agent-Oriented Software Engineering: The Importance of Interactions

Comisión Interministerial de Ciencia y Tecnología (CICYT) SETI (TIN2009-07366)Junta de Andalucía P07-TIC-2533 (Isabel)Junta de Andalucía TIC-590

Design of an airborne launch vehicle and an air launched space booster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77293/1/AIAA-1993-3955-297.pd