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PubMed1998

A new view of specific and nonspecific thalamocortical connections.

Past theories about the circuitry that promotes integration of the whole cerebral cortex and thalamus during forebrain activities that underlie different states of consciousness have relied on the intralaminar nuclei as the sources of diffuse thalamocortical projections that could facilitate spread of activity across many cortical areas. Evidence is presented to show the presence of a matrix of superficially projecting cells extending throughout the whole thalamus that could form a substrate for diffusion of activity across the cortex. The superficially projecting cells in monkeys are distinguished by immunoreactivity for the calcium-binding protein calbindin. They are found in all thalamic nuclei and are increased in some nuclei. They not only project to superficial layers of the cortex but do so over wide areas, unconstrained by boundaries between areas. They are innervated by subcortical inputs that lack the topographic order and physiological precision of the principal sensory pathways. Superimposed on the matrix, but only in certain nuclei, is a core of cells characterized by immunoreactivity for another calcium-binding protein, parvalbumin. These project to middle layers of the cortex in an area-specific and topographically ordered manner. They are innervated by subcortical inputs that are typically precise in having a high degree of topographic order and readily identifiable physiological properties. The parvalbumin cells provide the sensory and other inputs to the cortex that are to be used as a basis for perception. The diffusely projecting calbindin cells can form a basis for the engagement of multiple cortical areas and thalamic nuclei, especially when recruited by corticothalamic connections. Diffusion of activity across multiple areas and thalamic nuclei is essential for the binding of all aspects of sensory experience into a single framework of consciousness.

Animals↗
PubMed2001

Mechanisms for facilitated target location and the optimal number of molecules in the diffusion search process.

We investigate the number N of molecules needed to perform independent diffusion in order to achieve bonding of a single molecule to a specific site in time t(0). For a certain range of values of t(0), an increase from N to kN molecules (k>1) results in the decrease of search time from t(0) to t(0)/k. In this regime, increasing the number of molecules is an effective way of speeding up the search process. However when N> or =N0 (optimal number of N) the reduction of time from t(0) to t(0)/k can be achieved only by an exponentially large increase in the number of molecules [from N to N exp(ck) for some c>0].

Binding Sites↗
PubMed2002

Intermolecular biological electron transfer: an electrochemical approach.

We investigated the electron transfer (ET) rates between a well-defined gold electrode and cytochrome c immobilized at the carboxylic acid terminus of alkanethiol self-assembled monolayers (SAMs) by using the potential modulated electroreflectance technique. A logarithmic plot of ET rates against the chain length of the alkanethiol is linear with long chain alkanethiols. The ET rates become independent of the chain length with short alkanethiols. It is proposed that the rate-limiting ET step through short alkyl chains results from a configurational rearrangement process preceding the ET event. This "gating" process arises from a rearrangement of the cytochrome c from a thermodynamically stable binding form on the carboxylic acid terminus to a configuration, which facilitates the most efficient ET pathways (surface diffusion process). We propose that the lysine-13 of mammalian cytochrome c facilitates the most efficient ET pathway to the carboxylate terminus and this proposal is supported by the ET reaction rate of a rat cytochrome c mutant (RC9-K13A) [Elektrokhimiya (2001) in press], in which lysine-13 is replaced by alanine. The ET rate of K13A is more than six orders of magnitude smaller than that of the native protein.

Animals↗
PubMed2006

Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus.

Group A streptococcus (GAS) depends on a hyaluronic acid (HA) capsule to evade phagocytosis and to interact with epithelial cells. Paradoxically, GAS also produces hyaluronidase (Hyl), an enzyme that cleaves HA. A common assumption is that Hyl digests structurally identical HA in human tissue to promote bacterial spread. We inactivated the gene encoding extracellular hyaluronidase, hylA, in a clinical Hyl(+) isolate. Hyl(+) and an isogenic Hyl(-) mutant were injected subcutaneously into mice with or without high-molecular-weight dextran blue. The Hyl(-) strain produced small lesions with dye concentrated in close proximity. The Hyl(+) strain produced identical lesions, but the dye diffused subcutaneously. However, Hyl(+) bacteria were not isolated from unaffected skin stained by dye diffusion. Thus, Hyl digests tissue HA and facilitates spread of large molecules but is not sufficient to cause subcutaneous diffusion of bacteria or to affect lesion size. GAS capsule expression was assayed periodically during broth culture and was reduced in Hyl(+) strains relative to Hyl(-) strains at the onset and the end of active capsule synthesis but not during peak synthesis in mid-exponential phase. Thus, Hyl is not sufficiently active to remove capsule during peak synthesis. To demonstrate a possible nutritional role for Hyl, GAS was shown to grow with N-acetylglucosamine but not d-glucuronic acid (both components of HA) as a sole carbon source. However, only Hyl(+) strains could grow utilizing HA as a sole carbon source, suggesting that Hyl may permit the organism to utilize host HA or its own capsule as an energy source.

Animals↗
PubMed2005

Uncertainty in white matter fiber tractography.

In this work we address the uncertainty associated with fiber paths obtained in white matter fiber tractography. This uncertainty, which arises for example from noise and partial volume effects, is quantified using a Bayesian modeling framework. The theory for estimating the probability of a connection between two areas in the brain is presented, and a new model of the local water diffusion profile is introduced. We also provide a theorem that facilitates the estimation of the parameters in this diffusion model, making the presented method simple to implement.

Algorithms↗
PubMed2003

Facilitated transport of sodium or potassium chloride across vesicle membranes using a ditopic salt-binding macrobicycle.

A synthetic receptor, with an ability to bind sodium or potassium chloride as a contact ion-pair, is shown to effectively transport either salt across vesicle membranes. Significant transport is observed even when the transporter: phospholipid ratio is as low as 1:2500. Chloride efflux from unilamellar vesicles is monitored using a chloride selective electrode. Mechanistic studies indicate that the facilitated efflux is due to the uncomplexed transporter diffusing into the vesicle and the transporter-salt complex diffusing out. Vesicle influx experiments are also reported, where the facilitated influx of chloride and sodium ions into vesicles is observed directly by 35Cl and 23Na NMR, respectively.

Biological Transport↗
PubMed1980

The diffusion of the computed tomography (CT) scanner in the United States.

The rising cost of medical care in the United States is a problem generally familiar to all interested in health care policy. In recent years the contribution of technology to this rising cost has been debated. The computed tomography (CT) scanner has come to exemplify the problem of "technology run wild." The scanner was introduced into the United States in 1973 and has diffused rapidly into virtually every area of the country. However, despite the large number of scanners, they are mal-distributed by institutional setting and geographic location. A number of Federal policies have been developed to deal with medical technology. The case of the CT scanner illustrates the failure of these policies. The CT scanner was not well evaluated before it diffused into practice, and it appears that Federal reimbursement policy facilitated its spread. Federal policies designed to slow diffusion or to assure optimal placement or wise use of scanners have not had demonstrable effects. The case of the CT scanner suggests the need to alter Federal policies toward medical technologies.

Government↗
PubMed1985

Facilitated carbon dioxide transport in bovine albumin solutions.

Steady-state CO2 diffusion in the presence of a CO2 gradient was measured in thin layers of bovine albumin solutions containing different amounts of buffer base, added as NaHCO3, and/or of NaCl. In the same solutions, electrical potentials due to the CO2 diffusion across the layers were measured. Addition of carbonic anhydrase induced a chemical reaction equilibrium to exist for the CO2 reaction system, and led to equilibrium values for facilitated CO2 transport due to a bicarbonate flux and to maximum values for the diffusion potential. The diffusion potentials are generated due to the large differences in the ionic mobilities of albumin and other ionic species such as bicarbonate. The diffusion potential markedly reduces the facilitated CO2 flux. The presence of sodium chloride had no significant effect on the CO2 transport rate. The total mass transfer rates of CO2 in albumin solutions were considerably lower than those found by Stroeve and Ziegler (23) in hemoglobin solutions at identical concentrations of buffer base.

Albumins↗
PubMed2006

Improving the linearity of infrared diffuse reflection spectroscopy data for quantitative analysis: an application in quantifying organophosphorus contamination in soil.

Diffuse reflection data are presented for ethyl methylphosphonate in a fine Utah dirt sample as a model system for organophosphate-contaminated soil. The data revealed a chemometric artifact when the spectra were represented in Kubelka-Munk units that manifests as a linear dependence of spectral peak height on variations in the observed baseline position (i.e., the position of the observed transmission intensity where no absorption features occur in the sample spectrum). We believe that this artifact is the result of the mathematical process by which the raw data are converted into Kubelka-Munk units, and we developed a numerical strategy for compensating for the observed effect and restoring chemometric precision to the diffuse reflection data for quantitative analysis while retaining the benefits of linear calibration afforded by the Kubelka-Munk approach. We validated our Kubelka-Munk correction strategy by repeating the experiment using a simpler system--pure caffeine in potassium bromide. The numerical preprocessing includes conventional multiplicative scatter correction coupled with a baseline offset correction that facilitates the use of quantitative diffuse reflection data in the Kubelka-Munk formalism for the quantitation of contaminants in a complex soil matrix, but is also applicable to more fundamental diffuse reflection quantitative analysis experiments.

Linear Models↗
PubMed1988

One-dimensional diffusion of Escherichia coli DNA-dependent RNA polymerase: a mechanism to facilitate promoter location.

The mechanism of promoter location by DNA-dependent RNA polymerase of Escherichia coli was investigated. The occupancies of DNA fragments carrying the A1 promoter of bacteriophage T7 were analyzed as a function of the length of flanking sequences adjacent to the promoter. Competition between the promoters on different fragments showed qualitatively that DNA sequences downstream of the promoter enhanced promoter occupancy, whereas upstream flanking sequences had little or no influence on occupancy. This was studied quantitatively by using a set of DNA fragments with four identical A1 promoters (I-IV) equidistant from each other, but with different lengths of flanking sequences upstream from promoter I and downstream from promoter IV. The relative occupancies of these promoters showed that downstream DNA sequences of up to 250 base pairs increased the occupancy of the adjacent promoter, whereas upstream sequences longer than 70 base pairs had little or no effect on occupancy. Promoter occupancies measured as a function of the length of the downstream flanking DNA sequences were fit by a published theory that takes into account an enhancement of signal-sequence location by linear diffusion.

Bacterial Proteins↗
PubMed2000

Surface diffusion coefficients for room acoustics: free-field measures.

A surface diffusion coefficient is needed in room acoustics to enable the quality of diffusing surfaces to be evaluated. It may also facilitate more accurate geometric room acoustic models. This paper concentrates on diffusion coefficients derived from free-field polar responses. An extensive set of two- and three-dimensional measurements and predictions was used to test the worth of different diffusion coefficient definitions. The merits and problems associated with these types of coefficients are discussed, and past parameters reviewed. Two new coefficients are described. The new measure based on the autocorrelation function is forwarded as the best free-field coefficient. The strengths and weaknesses of the coefficient are defined.

Acoustics↗
PubMed1998

Serum from diabetic BB/W rats enhances calcium currents in primary sensory neurons.

We examined the hypothesis that exposure of nondiabetic rat dorsal root ganglion (DRG) neurons to sera from diabetic BB/W rats would produce an increase in calcium currents associated with impaired regulation of the inhibitory G protein-calcium channel complex. Acutely dissociated rat DRGs were incubated for 18-24 h in medium supplemented with sera (10% vol/vol) from either diabetic rats with neuropathy or age-matched, nondiabetic controls. Exposure of DRG neurons to sera from diabetic BB/W rats resulted in a surface membrane immunofluorescence pattern when treated with an anti-rat light-chain antibody that was not observed in neurons exposed to control sera. Calcium current density (IDCa) was assessed with the use of the whole cell variation of the patch-clamp technique. IDCa in neurons exposed to diabetic sera was significantly increased compared with neurons exposed to control sera. Guanine nucleotide-binding (G) protein regulation of calcium channel function was examined with the use of a two-pulse "facilitation" or IDCa enhancement protocol in the presence of activators [guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)] or antagonists [guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and pertussis toxin (PTX)] of G protein function. Facilitation was significantly decreased in neurons exposed to diabetic sera. Intracellular diffusion of neurons with GDP beta s blocked facilitation, whereas dialysis with GTP gamma s increased facilitation to a similar magnitude in neurons exposed to either diabetic or control sera. Treatment with PTX resulted in a significant increase in IDCa and approximately 50% decrease in facilitation in neurons treated with control sera but no significant changes in neurons exposed to diabetic sera. We conclude that serum from diabetic BB/W rats with neuropathy contains an autoimmune immunoglobulin that impairs regulation of the inhibitory G protein-calcium channel complex, resulting in enhanced calcium influx. Regulation of the inhibitory G protein-calcium channel complex involves PTX-sensitive and -insensitive G proteins.

Animals↗
PubMed1999

Water transport across yeast vacuolar and plasma membrane-targeted secretory vesicles occurs by passive diffusion.

To determine whether solute transport across yeast membranes was facilitated, we measured the water and solute permeations of vacuole-derived and late secretory vesicles in Saccharomyces cerevisiae; all permeations were consistent with passive diffusive flow. We also overexpressed Fps1p, the putative glycerol facilitator in S. cerevisiae, in secretory vesicles but observed no effect on water, glycerol, formamide, or urea permeations. However, spheroplasts prepared from the strain overexpressing Fps1p showed enhanced glycerol uptake, suggesting that Fps1p becomes active only upon insertion in the plasma membrane.

Aquaporins↗
PubMed2006

Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy.

Nuclear transport requires freely diffusing nuclear transport proteins to facilitate movement of cargo molecules through the nuclear pore. We analyzed dynamic properties of importin alpha, importin beta, Ran and NTF2 in nucleus, cytoplasm and at the nuclear pore of neuroblastoma cells using fluorescence correlation spectroscopy. Mobile components were quantified by global fitting of autocorrelation data from multiple cells. Immobile components were quantified by analysis of photobleaching kinetics. Wild-type Ran was compared to various mutant Ran proteins to identify components representing GTP or GDP forms of Ran. Untreated cells were compared to cells treated with nocodazole or latrunculin to identify components associated with cytoskeletal elements. The results indicate that freely diffusing importin alpha, importin beta, Ran and NTF2 are in dynamic equilibrium with larger pools associated with immobile binding partners such as microtubules in the cytoplasm. These findings suggest that formation of freely diffusing nuclear transport intermediates is in competition with binding to immobile partners. Variation in concentrations of freely diffusing nuclear transport intermediates among cells indicates that the nuclear transport system is sufficiently robust to function over a wide range of conditions.

Active Transport, Cell Nucleus↗
PubMed1983

Studies in the mechanism of phenylethylamine uptake by rabbit erythrocytes.

The mechanism of phenylethylamine (PEA) uptake by in vitro rabbit erythrocyte preparations involve both a larger component of passive diffusion and an Na+-dependent facilitated transport system. This is reflected by the fast rate and lack of saturation of PEA erythrocyte uptake, and by the decrease in PEA tissue/medium ratio when the amine was incubated in an Na+-free medium or in the presence of ouabain. Results obtained after the addition of iodoacetamide or by the use of glucose-free medium suggest the Na+-K+ gradient as the driving force responsible for operation of the carrier mechanism. Preliminary results indicate that amphetamine PEA share a similar mechanism for their uptake by rabbit erythrocytes. At the levels normally present in rabbit blood (c. 1 X 10(-8)M), about one-third of the PEA is found in the serum and only a very small portion of it (less than 1%) is present as the "biologically active" non-ionized amine. Most of the remaining phenylethylamine is bound to plasma protein or inside the erythrocytes.

Animals↗
PubMed2005

Diffusion tensor tractography of the limbic system.

BACKGROUND AND PURPOSE: The limbic system, relevant to memory and emotion, is an interesting subject of study in healthy and diseased individuals. It consists of a network of gray matter structures interconnected by white matter fibers. Although gray matter components of this system have been studied by using MR imaging, the connecting fibers have not been analyzed to the same degree. Cerebrospinal fluid (CSF) signal intensity contamination of the fornix and cingulum, the 2 major white matter tracts of the limbic system, can alter diffusion-tensor imaging (DTI) measurements and affect tractography. We investigated the effect of CSF signal intensity suppression on fiber tracking of the limbic connections and characterized the diffusion properties of these structures in healthy volunteers. METHODS: Nine healthy individuals were scanned with standard and CSF-suppressed DTI. Tractography of the fornix and cingulum was performed for both acquisition methods. We report mean diffusivity and fractional anisotropy measurements of the crus, body, and columns of the fornix, and descending, superior, and anterior portions of the cingulum. RESULTS: Diffusion measurements were improved and tractography was facilitated by using CSF-suppressed DTI. In particular, tract volume increased, whereas decreases of the mean diffusivity and increases of diffusion anisotropy more accurately represented the underlying tissue by minimizing deleterious partial volume averaging from CSF. This was particularly true for the fornix because it is in closest contact to CSF. Diffusion measurements throughout the limbic connections were consistent in healthy volunteers. CONCLUSION: We recommend the use of CSF suppression when performing diffusion-tensor tractography of the limbic system.

Adult↗
PubMedDate not supplied

Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for MR imaging of acute hepatitis in a rat model.

This work was conducted to test the hypothesis that contrast-enhanced MRI with hepatocyte-specific contrast agents facilitates quantitation and mapping of diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine (Gd-BOPTA/Dimeg, Bracco SpA, Millano, Italy) is a new paramagnetic hepatocyte-specific contrast agent currently undergoing clinical trials. We have assessed the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver diseases in a rat model of chemically induced hepatitis. The study was based on the measurements of in vivo liver relaxation times as well as on the acquisition of standard SE images. Acute hepatitis considerably reduced the degree of T1 shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images was inferior, in terms of both strength and duration, to that recorded in control rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our results show that gadobenate dimeglumine-enhanced MR imaging has the potential for visualization of hepatitis and for assessment of liver function. Our conclusions differ from those previously published on this subject by other authors. The reasons that led to differing conclusions are discussed.

Acute Disease↗
PubMed1990

Diffusional and electrokinetic redistribution at the synapse: a physicochemical basis of synaptic competition.

Coinnervating nerve terminals may compete for "stabilizing factors" confined within the postsynaptic cell. The competition could be achieved through a diffusion-mediated trapping the factor, facilitated by an activity-dependent electrokinetic migration of the factor toward the synaptic site. We have examined the evidence for diffusional and electrokinetic motions of cell surface and cytoplasmic components, the profile and magnitude of the electric field produced by the synaptic current, and the plausibility that these motions underlie the process of synaptic competition.

Animals↗