IFEMS, an Interactive Finite Element Modeling System Using a CAD/CAM System

A method of coupling a CAD/CAM system with a general purpose finite element mesh generator is described. The three computer programs which make up the interactive finite element graphics system are discussed

Frequency-Dependent Gating of Synaptic Transmission and Plasticity by Dopamine

The neurotransmitter dopamine (DA) plays an important role in learning by enhancing the saliency of behaviorally relevant stimuli. How this stimulus selection is achieved on the cellular level, however, is not known. Here, in recordings from hippocampal slices, we show that DA acts specifically at the direct cortical input to hippocampal area CA1 (the temporoammonic (TA) pathway) to filter the excitatory drive onto pyramidal neurons based on the input frequency. During low-frequency patterns of stimulation, DA depressed excitatory TA inputs to both CA1 pyramidal neurons and local inhibitory GABAergic interneurons via presynaptic inhibition. In contrast, during high-frequency patterns of stimulation, DA potently facilitated the TA excitatory drive onto CA1 pyramidal neurons, owing to diminished feedforward inhibition. Analysis of DA's effects over a broad range of stimulus frequencies indicates that it acts as a high-pass filter, augmenting the response to high-frequency inputs while diminishing the impact of low-frequency inputs. These modulatory effects of DA exert a profound influence on activity-dependent forms of synaptic plasticity at both TA-CA1 and Schaffer-collateral (SC)-CA1 synapses. Taken together, our data demonstrate that DA acts as a gate on the direct cortical input to the hippocampus, modulating information flow and synaptic plasticity in a frequency-dependent manner

Distance-Dependent Homeostatic Synaptic Scaling Mediated by A-Type Potassium Channels

Many lines of evidence suggest that the efficacy of synapses on CA1 pyramidal neuron dendrites increases as a function of distance from the cell body. The strength of an individual synapse is also dynamically modulated by activity-dependent synaptic plasticity, which raises the question as to how a neuron can reconcile individual synaptic changes with the maintenance of the proximal-to-distal gradient of synaptic strength along the dendrites. As the density of A-type potassium channels exhibits a similar gradient from proximal (low)-to-distal (high) dendrites, the A-current may play a role in coordinating local synaptic changes with the global synaptic strength gradient. Here we describe a form of homeostatic plasticity elicited by conventional activity blockade (with tetrodotoxin) coupled with a block of the A-type potassium channel. Following A-type potassium channel inhibition for 12 h, recordings from CA1 somata revealed a significantly higher miniature excitatory postsynaptic current (mEPSC) frequency, whereas in dendritic recordings, there was no change in mEPSC frequency. Consistent with mEPSC recordings, we observed a significant increase in AMPA receptor density in stratum pyramidale but not stratum radiatum. Based on these data, we propose that the differential distribution of A-type potassium channels along the apical dendrites may create a proximal-to-distal membrane potential gradient. This gradient may regulate AMPA receptor distribution along the same axis. Taken together, our results indicate that A-type potassium channels play an important role in controlling synaptic strength along the dendrites, which may help to maintain the computational capacity of the neuron

Frequency-Dependent Signal Transmission and Modulation by Neuromodulators

The brain uses a strategy of labor division, which may allow it to accomplish more elaborate and complicated tasks, but in turn, imposes a requirement for central control to integrate information among different brain areas. Anatomically, the divergence of long-range neuromodulator projections appears well-suited to coordinate communication between brain areas. Oscillatory brain activity is a prominent feature of neural transmission. Thus, the ability of neuromodulators to modulate signal transmission in a frequency-dependent manner adds an additional level of regulation. Here, we review the significance of frequency-dependent signal modulation in brain function and how a neuronal network can possess such properties. We also describe how a neuromodulator, dopamine, changes frequency-dependent signal transmission, controlling information flow from the entorhinal cortex to the hippocampus

Super-resolution imaging and estimation of protein copy numbers at single synapses with DNA-PAINT

In the brain, the strength of each individual synapse is defined by the complement of proteins present or the "local proteome." Activity-dependent changes in synaptic strength are the result of changes in this local proteome and posttranslational protein modifications. Although most synaptic proteins have been identified, we still know little about protein copy numbers in individual synapses and variations between synapses. We use DNA-point accumulation for imaging in nanoscale topography as a single-molecule super-resolution imaging technique to visualize and quantify protein copy numbers in single synapses. The imaging technique provides near-molecular spatial resolution, is unaffected by photobleaching, enables imaging of large field of views, and provides quantitative molecular information. We demonstrate these benefits by accessing copy numbers of surface AMPA-type receptors at single synapses of rat hippocampal neurons along dendritic segments

Clinical Notes: Bacteremia Associated with Colonoscopy

Twenty-eight patients had a total of 168 blood cultures before and at regular intervals during colonoscopy. No bacteremia was found. Based on our results and other reports, we recommend antibiotic prophylaxis during colonoscopy only for those patients with prosthetic heart valves and for those with valvular heart disease who also have advanced liver disease

Mutant methionyl-tRNA synthetase from bacteria enables site-selective N-terminal labeling of proteins expressed in mammalian cells

Newly synthesized cellular proteins can be tagged with a variety of metabolic labels that distinguish them from preexisting proteins and allow them to be identified and tracked. Many such labels are incorporated into proteins via the endogenous cellular machinery and can be used in numerous cell types and organisms. Though broad applicability has advantages, we aimed to develop a strategy to restrict protein labeling to specified mammalian cells that express a transgene. Here we report that heterologous expression of a mutant methionyl-tRNA synthetase from Escherichia coli permits incorporation of azidonorleucine (Anl) into proteins made in mammalian (HEK293) cells. Anl is incorporated site-selectively at N-terminal positions (in competition with initiator methionines) and is not found at internal sites. Site selectivity is enabled by the fact that the bacterial synthetase aminoacylates mammalian initiator tRNA, but not elongator tRNA. N-terminally labeled proteins can be selectively conjugated to a variety of useful probes; here we demonstrate use of this system in enrichment and visualization of proteins made during various stages of the cell cycle. N-terminal incorporation of Anl may also be used to engineer modified proteins for therapeutic and other applications

Transport And Plugging Performance Evaluation Of A Novel Re-Crosslinkable Microgel Used For Conformance Control In Mature Oilfields With Super-Permeable Channels

Preformed particle gels (PPG) have been widely applied in oilfields to control excessive water production. However, PPG has limited success in treating opening features because the particles can be flushed readily during post-water flooding. We have developed a novel micro-sized Re-crosslinkable PPG (micro-RPPG) to solve the problem. The microgel can re-crosslink to form a bulk gel, avoiding being washed out easily. This paper evaluates the novel microgels\u27 transport and plugging performance through super-permeable channels. Micro-RPPG was synthesized and evaluated for this study. Its storage moduli after fully swelling are approximately 82 Pa. The microgel characterization, self-healing process, transportation behavior, and plugging performance were investigated. A sandpack model with multi-pressure taps was utilized to assess the microgel dispersions\u27 transport behavior and plugging efficiency. In addition, micro-optical visualization of the gel particles was deployed to study the particle size changes before and after the swelling process. Tube tests showed that micro-RPPG could be dispersed and remain as separate particles in water with a concentration below 8,000 ppm, which is a favorable concentration for gel treatment. However, during the flooding test, the amount of microgel can be entrapped in the sandpack, resulting in a higher microgel concentration (higher than 8,000 ppm), endowing the gel particles with re-crosslinking ability even with excessive water. The microgel could propagate through the sandpack model, and the required pressure gradient mainly depends on the average particle/pore ratio and gel concentration. The gel dispersion significantly reduced channel permeability, providing sufficient resistance to post-water flooding (more than 99.97 % permeability reduction). In addition, the evaluation of micro-RPPG retention revealed that it is primarily affected by both gel concentration particle/pore ratios. We have demonstrated that the novel recrosslinkable microgel can transport through large channels, but it can provide effective plugging due to its unique re-crosslinking property. However, by this property, the new microgel exhibits enhanced stability and demonstrates resistance to being flushed out in such high-permeability environments. Furthermore, with the help of novel technology, it is possible to overcome the inherited problems commonly associated with in-situ gel treatments, including chromatographic issues, low-quality control, and shearing degradation

An unbiased approach elucidates variation in (S)-(+)-linalool, a context-specific mediator of a tri-trophic interaction in wild tobacco

Plant volatile organic compounds (VOCs) mediate many interactions, and the function of common VOCs is especially likely to depend on ecological context. We used a genetic mapping population of wild tobacco, Nicotiana attenuata, originating from a cross of 2 natural accessions from Arizona and Utah, separated by the Grand Canyon, to dissect genetic variation controlling VOCs. Herbivory-induced leaf terpenoid emissions varied substantially, while green leaf volatile emissions were similar. In a field experiment, only emissions of linalool, a common VOC, correlated significantly with predation of the herbivore Manduca sexta by native predators. Using quantitative trait locus mapping and genome mining,we identified an (S)-(+)-linalool synthase (NaLIS). Genome resequencing, gene cloning, and activity assays revealed that the presence/absence of a 766-bp sequence in NaLIS underlies the variation of linalool emissions in 26 natural accessions. We manipulated linalool emissions and composition by ectopically expressing linalool synthases for both enantiomers, (S)-(+)- and (R)-(−)-linalool, reported to oppositely affect M. sexta oviposition, in the Arizona and Utah accessions.We used these lines to test ovipositingmoths in increasingly complex environments. The enantiomers had opposite effects on oviposition preference, but themagnitude of the effect depended strongly both on plant genetic background, and complexity of the bioassay environment. Our study reveals that the emission of linalool, a common VOC, differs by orders-of-magnitude among geographically interspersed conspecific plants due to allelic variation in a linalool synthase, and that the response of a specialist herbivore to linalool depends on enantiomer, plant genotype, and environmental complexity

Natural variation in linalool metabolites: One genetic locus, many functions?

The ubiquitous volatile linalool is metabolized in plants to nonvolatile derivatives. We studied Nicotiana attenuata plants which naturally vary in (S)‐(+)‐linalool contents, and lines engineered to produce either (R)‐(‐)‐ or (S)‐(+)‐linalool. Only (S)‐(+)‐linalool production was associated with slower growth of a generalist herbivore, and a large fraction was present as nonvolatile derivatives. We found that variation in volatile linalool and its nonvolatile glycosides mapped to the same genetic locus which harbored the biosynthetic gene, NaLIS, but that free linalool varied more in environmental responses. This study reveals how (S)‐(+)‐linalool and conjugates differ in their regulation and possible functions in resistance