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Collective diffusion and a random energy landscape

Starting from a master equation in a quantum Hamiltonian form and a coupling to a heat bath, we derive an evolution equation for a collective hopping process under the influence of a stochastic energy landscape. Different equations result for an arbitrary occupation number per lattice site or in a system under exclusion. Based on scaling arguments it will be demonstrated that both systems belong below the critical dimension d(c) to the same universality class, leading to anomalous diffusion in the long time limit. The dynamical exponent z can be calculated by an epsilon=d(c)-d expansion. Above the critical dimension we discuss the differences in the diffusion constant for sufficient high temperatures. For a random potential we find a higher mobility for systems with exclusion.

Journal Article↗

Spin filtering in a hybrid ferromagnetic-semiconductor microstructure.

We fabricated a hybrid structure in which cobalt and permalloy micromagnets produce a local in-plane spin-dependent potential barrier for high-mobility electrons at the GaAs/AlGaAs interface. Spin effects are observed in ballistic transport in the range of tens of mT of the external field and are attributed to switching between Zeeman and Stern-Gerlach modes--the former dominating at low electron densities.

Journal Article↗

Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine.

Pharmacological effects of amantadine on dopaminergic transmission are proposed to result from an uncompetitive antagonism at glutamate N-methyl-D-aspartate (NMDA) receptors. However, our previous studies examining amantadine-mediated dopamine receptor regulation in the rat striatum revealed a discrepancy from a direct interference with glutamate transmission. Preliminary in vitro binding data from the literature suggested the interaction of amantadine with the sigma1 receptor. Therefore, we have now further characterized the pharmacological properties of amantadine and memantine at this receptor and investigated its involvement in the modulation of striatal dopaminergic transmission. Our binding studies using [3H]-(+)SKF-10,047 indicated that amantadine and memantine behave as ligands of the sigma(1) receptor in rat forebrain homogenates (Ki values of 7.44 +/- 0.82 and 2.60 +/- 0.62 microm, respectively). In NG108-15 neuroblastoma cells, both drugs (amantadine (100 microm) and memantine (10 microm)) potentiated the bradykinin-induced mobilization of intracellular Ca2+, mimicking the effect of the sigma1 receptor agonist PRE-084 (1 microm). Finally, we previously showed that in striatal membranes from amantadine-treated rats, the functional coupling of dopamine receptors with G-proteins was enhanced. Similarly, PRE-084 dose-dependently increased the [35S]GTPgammaS binding induced by dopamine (Emax 28 and 26% of basal, 0.3 and 1 mg/kg PRE-084, respectively). By contrast, BD1047, which is without effect on its own, antagonized the effects of amantadine and PRE-084. Together, these data demonstrate that aminoadamantanes behave as sigma1 receptor agonists, and confirm an involvement of this receptor in modulating dopamine receptors exerted by therapeutically relevant concentrations of amantadine.

Amantadine↗

Determinants of tenure in allied health and nursing education.

AIM: This paper presents a prospective cross-sectional study that investigated the tenure rate and the primary criterion use in granting tenure in nursing and allied health education in the United States of America. BACKGROUND: Given the recent trend by highly skilled professionals to seek employment in other countries, a clear understanding of the conditions of service in higher education is important to educators contemplating the relocating to another country. The preponderance of the published literature on academic tenure is from the United States of America, where educators continue to debate the value of the tenure system and the criteria to be used in tenure decisions. METHOD: We surveyed the deans of National League for Nursing accredited programmes (n = 187) and deans of allied health programmes belonging to the association of schools of allied health professions (n = 75) in the United States of America. The questionnaire sought demographic and institution-related information, tenure rate and weightings attached to teaching, scholarship and service in tenure decision. The data were collected in 2002. FINDINGS: Allied health and nursing educators had 47% and 35% tenure rates, respectively. The overwhelming majority of the deans in our study, 77%, ranked teaching as the primary criterion used in tenure decisions in their institutions. On the other hand, fewer than 25% rated scholarship and fewer than 5% rated service as the most important criterion used for tenure in their institution. The responses of the deans were modulated by the type and ownership of the institution in which they were employed and the characteristics of the educators. CONCLUSION: The implications for preparing future educators in the United States of America for long-term careers in allied health and nursing professions are that: (1) teaching is less highly valued in research-oriented universities; and (2) heavy teaching workloads may be detrimental to the chances of obtaining tenure. Replication of the study in other countries would have the potential to facilitate the employment mobility and educator exchange.

Allied Health Occupations↗

Stimulation of non-selective cation channels providing Ca2+ influx into platelets by platelet-activating factor and other aggregation inducers.

To elucidate the mechanism of the receptor-stimulated Ca2+ entry into human platelets, the influence of Ca(2+)-mobilizing agonists on plasma membrane potential (Em) has been studied. Em changes were registered using potentiometric probe 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide. The agonist effect on Em varied from hyperpolarization to slight and slow rise. On the contrary, after loading of platelets with intracellular Ca2+ indicator quin2, platelet-activating factor (PAF), thrombin, vasopressin, ADP and thromboxane-A2-mimetic U46619 cause substantial transient membrane depolarization. Similar effects were observed after platelet loading with other Ca2+ chelators fura-2 and indo-1. Agonist-induced depolarization considerably reduced if quin2-loaded platelets were suspended in isoosmotic choline-containing medium. Using Ba2+ as a substitute of Ca2+, we have demonstrated that in choline-containing medium PAF-induced Ba2+ entry into platelets results in membrane depolarization. Dependence on Ba2+ concentration and depolarization kinetics correlates with the dose dependence and kinetics of Ba2+ entry detected by quin2 fluorescence. The agonists also stimulate considerable Na+, Li+ and Cs+ inward currents into platelets. Na(+)-dependent depolarization is 2-5-fold suppressed by extracellular Ca2+ [median inhibitory concentration (IC50) approximately 0.3 mM]. Ni2+ and Cd2+ at similar concentrations block Ca2+ entry and agonist-induced Na2+ current (IC50 for both cations approximately 50 microM). Agonist-induced depolarization is blocked by the adenylate cyclase stimulator prostaglandin E1 and the protein kinase C stimulator phorbol ester. It is concluded that agonists stimulate Ca2+ entry into human platelets via receptor-operated channels which are not strictly selective toward divalent cations and are permeable to Na+, Li+ and Cs+.

Aminoquinolines↗

Effects of intracellular Ca2+ chelating on noradrenaline release in normoxic and anoxic hearts.

1. Ischaemia and anoxia induce excessive noradrenaline (NA) release in the heart by a mechanism independent of both nerve activity and extracellular Ca2+. The present study was designed to examine the potential role of intracellular Ca2+ mobilization in anoxic NA release in the heart by chelating intracellular free Ca2+. 2. In normoxic hearts, preloading with an intracellular free Ca2+ chelator (BAPTA) reduced neuronal NA release by 65%, confirming the effectiveness of the loading protocol. Release of NA independent of nerve activity occurred in hearts subjected to a 40 min period of anoxic, substrate-free and nominal Ca(2+)-free perfusion. Loading hearts with BAPTA prior to anoxia failed to reduce NA overflow (1561 +/- 147 vs 1496 +/- 206 pmol/g over 40 min). Infusion with BAPTA (20 mumol/L) during the first 25 min of the anoxic period reduced the quantity of anoxic NA release by approximately 25% from 2013 +/- 124 to 1476 +/- 207 pmol/g (P < 0.05). 3. Our results confirm that anoxic NA release is predominantly a Ca(2+)-independent process with Ca2+ mobilization from endogenous storage playing only a minor contributing role.

Animals↗

The presence of the parasite Demodex folliculorum on the skin surface of the eyelid.

It is well established that Demodectic mites can infest the meibomian glands, eyelash and hair follicles of the eyelid. In this study, scanning electron microscopy revealed Demodex folliculorum occurring freely on the skin surface of the eyelid. This indicates some mobility and implies further vector potential. Exoskeletons from these parasites also occur on the eyelid.

Animals↗

Impact of imported malaria on the burden of disease in northeastern Venezuela.

BACKGROUND: Many countries throughout the world are reporting an increasing number of imported malaria cases. It is now well documented that population movements play an important role in the spread and introduction of malaria infection in nonendemic areas. METHODS: We evaluated the contribution of imported malaria to the overall malaria burden of disease in an already endemic malaria region in Venezuela, where malaria is exclusively caused by Plasmodium vivax. To estimate the magnitude of this contribution, we retrospectively analyzed cases of imported malaria in Sucre, Venezuela, during a 10-year period (1987-1998). RESULTS: During this period, 1,755 (3.8% of the total) cases of imported malaria were identified. Most of these cases were imported from the Meridian states into Sucre. In Latin America, a major factor in the reemergence and spread of malaria is human migration. Surveillance of imported cases of malaria in Venezuela would allow us to continue evaluating population migration dynamics and its epidemiologic impact on malaria transmission. CONCLUSION: Enhanced surveillance, such as the one shown in this study, would help the early identification of nonindigenous Plasmodium species and also of resistant Plasmodium strains with a potential to spread locally. Population mobility and imported malaria cases may add to the magnitude of malaria burden in some regions of Latin America. Furthermore, malaria treatment guidelines at local and national levels need to incorporate imported malaria cases in their treatment algorithms and into chemoprophylactic recommendations for travelers.

Cost of Illness↗

Pharmaceutical suspensions: micro electrophoretic properties.

The microelectrophoretic properties of the drugs griseofulvin, betamethasone, nalidixic acid and thiabendazole in aqueous dispersion have been examined and the zeta potentials calculated from the measured mobilities. Variation in magnitude of particle charge with pH of dispersion is reported and related to the chemical structure and the surface characteristics. The effect of adding anionic (sodium dodecyl sulphate) cationic (dodecyl trimethyl bromide) and non-ionic (polyoxyethylene glycol monoethers of hexadecanol) surface-active agents, and mixtures of these ionic and non-ionic species, on the electrophoretic properties of the drug dispersions has been measured. The results reported agree with those found previously for a model polystyrene latex suspension system under the same conditions.

Betamethasone↗

Comparative Responses of Invasive and Native Plant Species to Combined Cd and Microplastic Pollution.

The co-occurrence of heavy metal contamination and biodegradable microplastic (polylactic acid, PLA) pollution poses increasing risks to terrestrial plant communities and soil functioning, yet species-specific responses to combined stress remain poorly understood. Cd and microplastics frequently co-occur in agricultural soils, where microplastics can alter cadmium mobility, bioavailability, and transport pathways, potentially modifying metal toxicity and plant stress responses compared with single-pollutant exposure. We investigated the responses of the invasive Bidens pilosa and the native Solanum nigrum grown in monoculture and mixed culture under combined cadmium (Cd) and biodegradable microplastic (PLA) stress by integrating plant growth, photosynthetic performance, oxidative physiology, and rhizosphere biochemical processes. Combined Cd-MP exposure markedly reduced plant growth, chlorophyll content (SPAD), photosystem II efficiency (Fv/Fm), nitrogen accumulation, biomass production, and rhizosphere enzyme activities associated with carbon, nitrogen, and phosphorus cycling. However, B. pilosa maintained greater physiological stability under stress, characterized by higher antioxidant enzyme activities (SOD, CAT, POD), lower reactive oxygen species (H2O2, O2&#x2d9;-) accumulation, and reduced lipid peroxidation (MDA), whereas S. nigrum exhibited stronger oxidative damage and functional impairment. Multivariate analyses further revealed that root antioxidant capacity was closely associated with rhizosphere microbial enzyme activity, suggesting a root-centered regulatory mechanism linking plant stress tolerance to soil functioning. Overall, the invasive species showed greater tolerance to combined contamination and maintained relatively higher rhizosphere functional activity than the native species, indicating that multi-pollutant stress may alter competitive interactions between invasive and native plants in contaminated environments.

Cadmium↗

Nerve growth factor regulates adrenergic expression.

The mechanism by which nerve growth factor (NGF) regulates adrenergic expression was examined in PC-12 cells transfected with a rat phenylethanolamine N-methyl-transferase (PNMT) promoter-luciferase reporter gene construct pGL3RP893. NGF treatment increased PNMT promoter-driven luciferase activity in a dose- and time-dependent manner. Induction was attenuated by inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) pathway ( approximately 60%) but not by inhibition of the protein kinase A (PKA), protein kinase C, phosphoinositol kinase, or p38 MAPK pathways. Deletion PNMT promoter-luciferase reporter gene constructs showed that the NGF-responsive sequences lay within the proximal -392 base pairs (bp) of PNMT promoter, wherein binding elements for Egr-1 (-165 bp) and Sp1 (-48 bp) reside. Western analysis further showed that NGF increased nuclear levels of Egr-1, but not Sp1 or the catalytic subunit of PKA. Gel mobility shift assays showed increased potential for Egr-1, but not Sp1, protein-DNA binding complex formation. Mutation of either the Egr-1 or Sp1 binding sites in the PNMT promoter attenuated NGF activation. NGF, combined with pituitary adenylyl cyclase-activating protein (PACAP), another PNMT transcriptional activator, cooperatively stimulated PNMT promoter driven-luciferase activity beyond levels observed with either neurotrophin alone. Finally, post-transcriptional control seems to be another important mechanism by which neurotrophins regulate the adrenergic phenotype. NGF, PACAP, and a combination of the two stimulated both intron-retaining and intronless PNMT mRNA and PNMT protein, but to different extents.

Adrenal Glands↗

A Hydrogen-Oxidizing, Fe(III)-Reducing Microorganism from the Great Bay Estuary, New Hampshire.

A dissimilatory Fe(III)- and Mn(IV)-reducing bacterium was isolated from bottom sediments of the Great Bay estuary, New Hampshire. The isolate was a facultatively anaerobic gram-negative rod which did not appear to fit into any previously described genus. It was temporarily designated strain BrY. BrY grew anaerobically in a defined medium with hydrogen or lactate as the electron donor and Fe(III) as the electron acceptor. BrY required citrate, fumarate, or malate as a carbon source for growth on H(2) and Fe(III). With Fe(III) as the sole electron acceptor, BrY metabolized hydrogen to a minimum threshold at least 60-fold lower than the threshold reported for pure cultures of sulfate reducers. This finding supports the hypothesis that when Fe(III) is available, Fe(III) reducers can outcompete sulfate reducers for electron donors. Lactate was incompletely oxidized to acetate and carbon dioxide with Fe(III) as the electron acceptor. Lactate oxidation was also coupled to the reduction of Mn(IV), U(VI), fumarate, thiosulfate, or trimethylamine n-oxide under anaerobic conditions. BrY provides a model for how enzymatic metal reduction by respiratory metal-reducing microorganisms has the potential to contribute to the mobilization of iron and trace metals and to the immobilization of uranium in sediments of Great Bay Estuary.

Journal Article↗

Naturally occurring lactococcal plasmid pAH90 links bacteriophage resistance and mobility functions to a food-grade selectable marker.

The bacteriophage resistance plasmid pAH90 (26,490 bp) is a natural cointegrate plasmid formed via homologous recombination between the type I restriction-modification specificity determinants (hsdS) of two smaller lactococcal plasmids, pAH33 (6,159 bp) and pAH82 (20,331 bp), giving rise to a bacteriophage-insensitive mutant following phage challenge (D. O'Sullivan, D. P. Twomey, A. Coffey, C. Hill, G. F. Fitzgerald, and R. P. Ross, Mol. Microbiol. 36:866-876; 2000). In this communication we provide evidence that the recombination event is favored by phage infection. The entire nucleotide sequence of plasmid pAH90 was determined and found to contain 24 open reading frames (ORFs) responsible for phenotypes which include restriction-modification, phage adsorption inhibition, plasmid replication, cadmium resistance, cobalt transport, and conjugative mobilization. The cadmium resistance property, encoded by the cadA gene, which has an associated regulatory gene (cadC), is of particular interest, as it facilitated the selection of pAH90 in other phage-sensitive lactococci after electroporation. In addition, we report the identification of a group II self-splicing intron bounded by two exons which have the capacity to encode a relaxase implicated in conjugation in gram-positive bacteria. The functionality of this intron was evident by demonstrating splicing in vivo. Given that pAH90 encodes potent phage defense systems which act at different stages in the phage lytic cycle, the linkage of these with a food-grade selectable marker on a replicon that can be mobilized among lactococci has significant potential for natural strain improvement for industrial dairy fermentations which are susceptible to phage inhibition.

Bacterial Proteins↗

Regulation of ornithine utilization in Pseudomonas aeruginosa (PAO1) is mediated by a transcriptional regulator, OruR.

We have used transpositional mutagenesis of a proline auxotroph (PAO951) to isolate an ornithine utilization (oru) mutant of Pseudomonas aeruginosa (PAO951-4) that was unable to use ornithine efficiently as the sole carbon and nitrogen source. DNA sequence analysis of the inactivated locus confirmed that the transposon had inserted into a locus whose product demonstrated significant primary sequence homology to members of the AraC family of transcriptional activators. DNA mobility shift assays affirmed this potential regulatory function and indicated that the inactivated gene encodes a transcriptional regulator, which has been designated OruR. In trying to define the ornithine utilization phenotype further, a similar inactivation was engineered in the wild-type strain, PAO1. The resulting isolate (PAO1R4) was totally unable to use ornithine as the sole carbon source. Despite the intensified phenotype, this isolate failed to demonstrate significant changes in any of the catabolic or anabolic enzymes that are known to be subject to regulation by the presence of either ornithine or arginine. It did, however, show modified levels of an enzyme, ornithine acetyltransferase (OAcT), that was previously thought to have merely an anaplerotic activity. Definition of this oruR locus and its effects upon OAcT activity provide evidence that control of ornithine levels in P. aeruginosa may have a significant impact upon how the cell is able to monitor and regulate the use of arginine and glutamate as sources of either carbon or nitrogen.

Amino Acid Sequence↗

Regulation of adhE (encoding ethanol oxidoreductase) by the Fis protein in Escherichia coli.

The adhE gene of Escherichia coli encodes a multifunctional ethanol oxidoreductase whose expression is 10-fold higher under anaerobic than aerobic conditions. Transcription of the gene is under the negative control of the Cra (catabolite repressor-activator) protein, whereas translation of the adhE mRNA requires processing by RNase III. In this report, we show that the expression of adhE also depends on the Fis (factor for inversion stimulation) protein. A strain bearing a fis::kan null allele failed to grow anaerobically on glucose solely because of inadequate adhE transcription. However, fis expression itself is not under redox control. Sequence inspection of the adhE promoter revealed three potential Fis binding sites. Electrophoretic mobility shift analysis, using purified Fis protein and adhE promoter DNA, showed three different complexes.

Alcohol Dehydrogenase↗

Endothelium-derived microparticles impair endothelial function in vitro.

Endothelial cell dysfunction (ECD) is emerging as the common denominator for diverse and highly prevalent cardiovascular diseases. Recently, an increased number of procoagulant circulating endothelial microparticles (EMPs) has been identified in patients with acute myocardial ischemia, preeclampsia, and diabetes, which suggests that these particles represent a surrogate marker of ECD. Our previous studies showed procoagulant potential of endothelial microparticles and mobilization of microparticles by PAI-1. The aim of this study was to test the effects of isolated EMPs on the vascular endothelium. EMPs impaired ACh-induced vasorelaxation and nitric oxide production by aortic rings obtained from Sprague-Dawley rats in a concentration-dependent manner. This effect was accompanied by increased superoxide production by aortic rings and cultured endothelial cells that were coincubated with EMPs and was inhibited by a SOD mimetic and blunted by an endothelial nitric oxide synthase inhibitor. Superoxide was also produced by isolated EMP. In addition, p22(phox) subunit of NADPH-oxidase was detected in EMP. Our data strongly suggest that circulating EMPs directly affect the endothelium and thus not only act as a marker for ECD but also aggravate preexisting ECD.

Animals↗

Lack of antilipolytic effect of lactate in subcutaneous abdominal adipose tissue during exercise.

The purpose of our study was to evaluate the potential inhibition of adipose tissue mobilization by lactate. Eight male subjects (age, 26. 25 +/- 1.75 yr) in good physical condition (maximal oxygen uptake, 59.87 +/- 2.77 ml. kg-1. min-1; %body fat, 10.15 +/- 0.89%) participated in this study. For each subject, two microdialysis probes were inserted into abdominal subcutaneous tissue. Lactate (16 mM) was perfused via one of the probes while physiological saline only was perfused via the other, both at a flow rate of 2.5 microl/min. In both probes, ethanol was also perfused for adipose tissue blood flow estimation. Dialysates were collected every 10 min during rest (30 min), exercise at 50% maximal oxygen consumption (120 min), and recovery (30 min) for the measurement of glycerol concentration. During exercise, glycerol increased significantly in both probes. However, no differences in glycerol level and ethanol extraction were observed between the lactate and control probes. These findings suggest that lactate does not impair subcutaneous abdominal adipose tissue mobilization during exercise.

Abdomen↗

Dental benefits of limited exposure to fluoridated water in childhood.

The effect of limited exposure to fluoridated water in childhood is of potential importance in highly-mobile modern society, but the subject has not been well-studied. This longitudinal study assessed caries experience and S. mutans proportions from fissure plaque in school-children who lived for at least the three years of the study in a non-fluoridated community (0.2 mg/L). Residence histories permitted division of the cohort into those who had lived all their lives in non-fluoridated communities, and those who had lived for some time previously in a fluoridated community. The children were aged 6-7 years at the beginning of the three-year study. Children with previous residence in the fluoridated communities developed 26.8% less caries in their permanent teeth during the study than did the children who had lived in non-fluoridated communities all their lives (p = 0.04), and had 29.8% less caries after three years (p = 0.02). Differences between the groups in S. mutans proportions from fissure plaque, sampled at six-monthly intervals throughout the study, could not be demonstrated. The dental benefits observed could not be attributed to socio-economic differences between the groups. Despite evidence that the benefits of limited ingestion of fluoridated water are topical in nature, the fact that many of the affected teeth in this study were unerupted at the time of the fluoride exposure means that pre-eruptive benefits cannot be ruled out.

Child↗