Background:Little is known about how global signaling network properties influence cardiac myocyte hypertrophy. Results: New 106 species computational model exhibited enriched cross-talk motifs and modular organization, predicting Ras as the most influential hub. Conclusion: Multiple levels of network organization modulate hypertrophic outcomes. Significance: Rather than acting through isolated pathways, cardiac hypertrophy signaling is a highly integrated network.

T.'ipure 3 is a t>-pical plot of the fluidity and agglutinating behavior of a \\-esrerll Pennsylvania high volatile A coal. In obtaining the data for this particular curve, a mixture of 1 part of coal and nine parts of inert (loo-temperature char) was used. Size consistency of both coal and char was 35 X 200 mesh.All points of spccific interest are evident in Figure 3. These include: the iniri:il fusion tempei,:iture, -4; the point of maximum fluidity, B; ant1 the maximum r tance point, C. In addition, the fluidity range ia readilj-a;iparent.Another example illustrating the applicability of the unit for research stlitlie.* is phoivn in Figure -1. .Is is well known, the addition of alkaline d t s t o a caking coal materially alters its behnvioi~ during c:tihonization. This is well illustrated in Figure 4, n-hich slion-s the cffect of adding incrensing amounts of soclinm carl,oriate t o :t bed of caking coal and diluent char. Only the uice point is plotted, this point being of primarjinterwt in so far as fluid bed operability is concerned. DISCUSSION The above are only two examples of studies for Tvhich the unitIt has been applied with siiccess to metallurgical has been used. 971 coking problems, using techniques similar to those described by BreR-er and Xtkinson ( 1 ) .The dilution technlque presents no problem because a few standard coal-diluent ratios suffice to cover a broad range of caking strengths. The incl eased flexibility of the apparatus more than offsets the occacional need for 3, rerun on a borderline sample. Usually a general knowledge of the sample source permits one to choo-e the proper dilution ratio immediately. ACK%OWLEDGRIESTThe author gratefully acknowledges the assistance of 8. .\.Jones for his many helpful suggestions in the design and construction of the described apparatus.

The effects of the local environment on surface-enhanced Raman scattering (SERS) spectra utilizing gold, silver, and gold/silver striped nanorod array substrates was investigated. The arrays were fabricated using an electrochemical metal deposition into an anodic aluminum oxide template. The analyte chosen for this study was p-nitroso-N,N-dimethylaniline (p-NDMA), which has an electronic structure that is highly sensitive to its surrounding environment. Changes in the peak positions and peak ratios were used to probe the influence of water and the striping pattern on the SERS signal of p-NDMA. We present the results of the fabrication and characterization of the nanorod array substrates, as well as SERS spectra of p-NDMA in both polar and nonpolar environments and SERS spectra on a variety of striped nanorod arrays. The Raman data suggests that the p-NDMA molecule exists in a more polarized state when bound to the gold as compared to the silver rods. We have attempted to use these differences to determine whether the SERS signal predominantly arises from the tips of the rods or from the interior of the array.

No abstract

Protein-protein interactions networks (PPINs) are known to share a highly conserved structure across all organisms. What is poorly understood, however, is the structure of the child interface interaction networks (IINs), which map the binding sites proteins use for each interaction. In this study we analyze four independently constructed IINs from yeast and humans and find a conserved structure of these networks with a unique topology distinct from the parent PPIN. Using an IIN sampling algorithm and a fitness function trained on the manually curated PPINs, we show that IIN topology can be mostly explained as a balance between limits on interface diversity and a need for physico-chemical binding complementarity. This complementarity must be optimized both for functional interactions and against mis-interactions, and this selectivity is encoded in the IIN motifs. To test whether the parent PPIN shapes IINs, we compared optimal IINs in biological PPINs versus random PPINs. We found that the hubs in biological networks allow for selective binding with minimal interfaces, suggesting that binding specificity is an additional pressure for a scale-free-like PPIN. We confirm through phylogenetic analysis that hub interfaces are strongly conserved and rewiring of interactions between proteins involved in endocytosis preserves interface binding selectivity.

Stoichiometric balance, or dosage balance, implies that proteins that are subunits of obligate complexes (e.g. the ribosome) should have copy numbers expressed to match their stoichiometry in that complex. Establishing balance (or imbalance) is an important tool for inferring subunit function and assembly bottlenecks. We show here that these correlations in protein copy numbers can extend beyond complex subunits to larger protein-protein interactions networks (PPIN) involving a range of reversible binding interactions. We develop a simple method for quantifying balance in any interface-resolved PPINs based on network structure and experimentally observed protein copy numbers. By analyzing such a network for the clathrin-mediated endocytosis (CME) system in yeast, we found that the real protein copy numbers were significantly more balanced in relation to their binding partners compared to randomly sampled sets of yeast copy numbers. The observed balance is not perfect, highlighting both under and overexpressed proteins. We evaluate the potential cost and benefits of imbalance using two criteria. First, a potential cost to imbalance is that ‘leftover’ proteins without remaining functional partners are free to misinteract. We systematically quantify how this misinteraction cost is most dangerous for strong-binding protein interactions and for network topologies observed in biological PPINs. Second, a more direct consequence of imbalance is that the formation of specific functional complexes depends on relative copy numbers. We therefore construct simple kinetic models of two sub-networks in the CME network to assess multi-protein assembly of the ARP2/3 complex and a minimal, nine-protein clathrin-coated vesicle forming module. We find that the observed, imperfectly balanced copy numbers are less effective than balanced copy numbers in producing fast and complete multi-protein assemblies. However, we speculate that strategic imbalance in the vesicle forming module allows cells to tune where endocytosis occurs, providing sensitive control over cargo uptake via clathrin-coated vesicles.

No abstract

No abstract