Showing papers by "University of Erlangen-Nuremberg published in 1996"

Nucleus-Independent Chemical Shifts: A Simple and Efficient Aromaticity Probe

Abstract: The ability to sustain a diatropic ring current is the defining characteristic of aromatic species.1-7 Cyclic electron delocalization results in enhanced stability, bond length equalization, and special magnetic as well as chemical and physical properties.1 In contrast, antiaromatic compounds sustain paratropic ring currents3 despite their localized, destabilized structures.1-7 We have demonstrated the direct, quantitative relationships among energetic, geometrical, and magnetic criteria of aromaticity in a wide-ranging set of aromatic/antiaromatic fivemembered rings.5a While the diamagnetic susceptibility exaltation (Λ) is uniquely associated with aromaticity, it is highly dependent on the ring size (area2) and requires suitable calibration standards.6 Aromatic stabilization energies (ASEs) of strained and more complicated systems are difficult to evaluate. CC bond length variations in polybenzenoid hydrocarbons can be just as large as those in linear conjugated polyenes.2 The abnormal proton chemical shifts of aromatic molecules are the most commonly employed indicators of ring current effects.1 However, the ca. 2-4 ppm displacements of external protons to lower magnetic fields are relatively modest (e.g., δH ) 7.3 for benzene vs 5.6 for dC-H in cyclohexene). In contrast, the upfield chemical shifts of protons located inside aromatic rings are more unusual. The six inner hydrogens of [18]annulene, for example, resonate at -3.0 ppm vs δ ) 9.28 for the outer protons. This relationship is inverted dramatically in the antiaromatic [18]annulene dianion, C18H18, where δ ) 20.8 and 29.5 (in) vs. -1.1 (out).8 Similar demonstrations of paratropic ring currents in antiaromatic compounds are well documented.3,8,9 Chemical shifts of encapsulated 3He atoms are now employed as experimental and computed measures of aromaticity in fullerenes and fullerene derivatives.10 While the rings of most aromatic systems are too small to accommodate atoms internally, the chemical shifts of hydrogens in bridging positions have long been used as aromaticity and antiaromaticity probes.9 δLi+ can be employed similarly, with the advantage that Li+ complexes with individual rings in polycyclic systems can be computed.4,11 We now propose the use of absolute magnetic shieldings, computed at ring centers (nonweighted mean of the heavy atom coordinates) with available quantum mechanics programs,12 as a new aromaticity/antiaromaticity criterion. To correspond to the familiar NMR chemical shift convention, the signs of the computed values are reversed: Negative “nucleus-independent chemical shifts” (NICSs) denote aromaticity; positive NICSs, antiaromaticity (see Table 1 for selected results). Figure 1, a plot of NICSs vs the ASEs for our set of five-membered ring heterocycles,5a provides calibration. The equally good correlations with magnetic susceptibility exaltations and with structural variations establish NICS as an effective aromaticity criterion. Unlike Λ,6 NICS values for [n]annulenes (Table 1) show only a modest dependence on ring size. The 10 π electron systems give significantly higher values than those with 6 π electrons. The antiaromatic 4n π electron compounds, cyclobutadiene (27.6), pentalene (18.1), heptalene (22.7), and planar D4h cyclooctatetraene (30.1), all show highly positive NICSs. Like the Li+-complex probe,4 the NICS evaluates the aromaticity and antiaromaticity contributions of individual rings in polycyclic systems. Scheme 1 (HF/6-31+G*, data from Table 1) shows NICSs for selected examples. The benzenoid aromatic NICSs provide evidence both for localized and “perimeter” models. The naphthalene (1) NICS (-9.9) resembles that of benzene (-9.7), as do the NICSs for the outer rings of phenanthrene (2) (-10.2) and triphenylene (3); the aromaticity of the central rings of the latter two are reduced. The NICS of the central ring of anthracene (4) (-13.3) exceeds the benzene value in contrast to the outer ring NICS (-8.2). Remarkably, the NICS (-7.0) for the seven-membered ring of azulene (5) is very close to that of the tropylium ion (-7.6 ppm), whereas the azulene five-membered ring NICS (-19.7) is even larger in magnitude than that of the cyclopentadienyl anion (-14.3). The four-membered rings in benzocyclobutadiene (6) (NICS ) 22.5) and in biphenylene (7) (19.0) are antiaromatic, but less so than cyclobutadiene itself (27.6). The six-membered rings in these polycycles are still aromatic, but their NICSs (-2.5 (1) (a) Minkin, V. I.; Glukhovtsev, M. N.; Simkin, B. Y. Aromaticity and Antiaromaticity; Wiley: New York, 1994. (b) Garratt, P. J. Aromaticity; Wiley: New York, 1986. (c) Eluidge, J. A.; Jackman, L. M. J. Chem. Soc. 1961, 859. (2) Schleyer, P. v. R.; Jiao, H. Pure Appl. Chem. 1996, 28, 209. (3) Pople, J. A.; Untch, K. G. J. Am. Chem. Soc. 1966, 88, 4811. (4) Jiao, H; Schleyer, P. v. R. AIP Conference Proceedings 330, E.C.C.C.1, Computational Chemistry; Bernardi, F., Rivail, J.-L., Eds.; American Institute of Physics: Woodbury, New York, 1995; p 107. (5) (a) Schleyer, P. v. R.; Freeman, P.; Jiao, H.; Goldfuss, B. Angew. Chem., Int. Ed. Engl. 1995, 34, 337. (b) Jiao, H.; Schleyer, P. v. R. Unpublished IGLO results. (c) Kutzelnigg, W.; Fleischer, U.; Schindler, M. In NMR: Basic Princ. Prog.; Springer: Berlin, 1990; Vol. 23, p 165. (6) Dauben, H. J., Jr.; Wilson, J. D.; Laity, J. L. In Non-Benzenoid Aromatics; Synder, J., Ed.; Academic Press, 1971; Vol. 2, and references cited. The partitioning of ring current or ring current susceptabilitites among various rings in polycyclic syestems were considered earlier, e.g., by Aihara (Aihara, J. J. Am. Chem. Soc. 1985, 207, 298 and refs cited) and by Mallion (Haigh, C. W.; Mallion, J. Chem. Phys. 1982, 76, 1982). (7) Fleischer, U.; Kutzelnigg, W.; Lazzeretti, P.; Mühlenkamp, V. J. Am. Chem. Soc. 1994, 116, 5298. (8) Sondheimer, F. Acc. Chem. Res. 1972, 5, 81. (9) (a) Hunandi, R. J. J. Am. Chem. Soc. 1983, 105, 6889. (b) Pascal, R. A., Jr.; Winans, C. G.; Van Engen, D. J. Am. Chem. Soc. 1989, 111, 3007. (10) (a) Bühl, M.; Thiel, W.; Jiao, H.; Schleyer, P. v. R.; Saunders, M.; Anet, F. A. L. J. Am. Chem. Soc. 1994, 116, 7429 and references cited. (b) Bühl, M.; van Wüllen, C. Chem. Phys. Lett. 1995, 247, 63. The authors have shown that the negative absolute shielding in the center of C60 is nearly the same as δ3He, computed at the same level. (11) Paquette, L. A.; Bauer, W.; Sivik, M. R.; Bühl, M.; Feigel, M.; Schleyer, P. v. R. J. Am. Chem. Soc. 1990, 112, 8776. (12) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T. A.; Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Stewart, J. P.; Head-Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian 94, ReVision B.2; Gaussian Inc., Pittsburgh, PA, 1995. Figure 1. Plot of NICSs (ppm) vs the aromatic stabilization energies (ASEs, kcal/mol)5a for a set of five-membered ring heterocycles, C4H4X (X ) as shown) (cc ) 0.966). 6317 J. Am. Chem. Soc. 1996, 118, 6317

Human Y Chromosome Azoospermia Factors (AZF) Mapped to Different Subregions in Yq11

Abstract: In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia wereanalysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involvingseveral DNA loci, while an additional patient had an inherited deletion. They were mapped to three differentsubregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second andthird subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletionsobserved were not overlapping but the extension of the deleted Y DNA in each subregion was similar in eachpatient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phasewhen the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletionoccurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesisloci in Yq11 and that each locus is active during a different phase of male germ cell development. As the mostsevere phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc.Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed. INTRODUCTIONGenes for male germ cell development are present on the Ychromosome in different species groups (1–3). In men, theposition of a spermatogenesis locus was mapped in theeuchromatic part of the long Y arm (Yq11). It was called‘azoospermia factor’ (AZF), as the first six men observed withterminal deletions in Yq were azoospermic (4). Mature spermcells were not detectable in their seminal fluid. In all cases, the Ydeletions included the large heterochromatin block of the long Yarm (Yq12) and an undefined amount of the adjacent euchromatin(Yq11). Subsequently, the presence of AZF in Yq11 wasconfirmed by numerous studies at both cytogenetic (5) andmolecular level (6–8). However, the genetic complexity of AZFcould not be revealed by these analyses.This first became possible by the detection of sterile patientswith small interstitial deletions (i.e. microdeletions) in Yq11. Ina study with 13 sterile men suffering from idiopathic azoospermiatwo different microdeletions in Yq11 were observed (9). Theywere mapped to two non overlapping positions in Yq11 interval6 (10). However, further studies of Yq11 microdeletionsassociated to the phenotype of male sterility, only confirmed theposition of an AZF locus in distal Yq11 (11,12). The mostextensive study was performed by Reijo et al. (13) on 89 sterile

Benchmark Computations of Laminar Flow Around a Cylinder

Abstract: An overview of benchmark computations for 2D and 3D laminar flows around a cylinder is given, which have been defined for a comparison of different solution approaches for the incompressible Navier-Stokes equations developed within the Priority Research Programme. The exact definitions of the benchmarks are recapitulated and the numerical schemes and computers employed by the various participating groups are summarized. A detailed evaluation of the results provided is given, also including a comparison with a reference experiment. The principal purpose of the benchmarks is discussed and some general conclusions which can be drawn from the results are formulated.

Frequency of primary tumors of the heart

Abstract: Primary tumors of the heart are rare. Based upon the data of 22 large autopsy series, the frequency of primary cardiac tumors is approximately 0.02%--corresponding to 200 tumors in 1 million autopsies (Table I).

"Sniffin' sticks": screening of olfactory performance.

Abstract: "Sniffin' Sticks" is a new test of nasal chemosensory performance based on pen-like odour-dispensing devices. This portable test is suited for repetitive, inexpensive screening of odour identification. The test includes a forced odour-identification task for seven odours performed by means of a list of four items (multiple-choice). In 146 subjects the basic screening test was compared to a down-scaled version of the UPSIT (CC-SIT). Sniffin' Sticks exhibited a relatively higher coefficient of correlation with the subjects' age; they also demonstrated the women's superior olfactory sensitivity more pronounced when compared to men. In addition, the coefficient of correlation between age and olfactory performance was slightly higher when the sticks were used. Preliminary investigations in nine patients with impaired olfactory function (i.e., anosmic or hyposmic patients) revealed significantly lower scores in patients compared to healthy controls matched for age and sex (p < 0.001). It is concluded that Sniffin' Sticks may be useful in the routine clinical assessment of olfactory performance where both time and costs matter.

Preeclampsia — A State of Sympathetic Overactivity

Abstract: Background Preeclampsia is characterized by a marked increase in peripheral vascular resistance leading to an increase in blood pressure, but the triggering mechanisms are unclear. Methods To determine whether augmented sympathetic vasoconstrictor activity may be an important mechanism in mediating the increase in vasomotor tone, we measured postganglionic sympathetic-nerve activity in the blood vessels of skeletal muscle by means of intraneural microelectrodes in nine women with preeclampsia, eight normotensive pregnant women, six normotensive nonpregnant women, and seven nonpregnant women with hypertension, both at rest and during noninvasive cardiovascular-reflex testing (with the Valsalva maneuver and the cold pressor test). Results The mean (±SE) rate of sympathetic-nerve activity in the normotensive pregnant women (10±1 bursts per minute) was not significantly different from that in normotensive nonpregnant women (12±2 bursts per minute) or hypertensive nonpregnant women (15±3 bursts per minute). In...

Tetracyclines: antibiotic action, uptake, and resistance mechanisms.

Abstract: Tetracyclines probably penetrate bacterial cells by passive diffusion and inhibit bacterial growth by interfering with protein synthesis or by destroying the membrane. A growing number of various bacterial species acquire resistance to the bacteriostatic activity of tetracycline. The two widespread mechanisms of bacterial resistance do not destroy tetracycline: one is mediated by efflux pumps, the other involves an EF-G-like protein that confers ribosome protection. Oxidative destruction of tetracycline has been found in a few species. Several efflux transporters, including multidrug-resistance pumps and tetracycline-specific exporters, confer bacterial resistance against tetracycline. Single amino acids of these carrier proteins important for tetracycline transport and substrate specificity have been identified, allowing the mechanism of tetracycline transport to begin to emerge.

High dimensional integration of smooth functions over cubes

Abstract: We construct a new algorithm for the numerical integration of functions that are defined on a \(d\)-dimensional cube. It is based on the Clenshaw-Curtis rule for \(d=1\) and on Smolyak's construction. This way we make the best use of the smoothness properties of any (nonperiodic) function. We prove error bounds showing that our algorithm is almost optimal (up to logarithmic factors) for different classes of functions with bounded mixed derivative. Numerical results show that the new method is very competitive, in particular for smooth integrands and \(d \ge 8\).

Estimation of gas solubilities in salt solutions at temperatures from 273 K to 363 K

Abstract: The objective of this article is to extend the model of Schumpe (1993) to a wider temperature range. To this end, solubility data reported in the literature for temperatures from 273.15 to 363.15 K were analyzed to obtain a set of 892 Sechenov constants for different gas/salt/temperature combinations. Gas solubility was expressed in the form of the Bunsen coefficient (volume of gas, reduced to 273.15 K and 101.3 kPa, absorbed per unit volume of solvent at 101.3 kPa partial pressure). Only the relative solubility is considered and any out of various proportional measures (Schumpe et al., 1982) could be used.

Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma.

Abstract: The mechanism that may cause degenerative fibrotic skin lesions was studied in situ using skin biopsies from patients with systemic sclerosis (SSc), localized scleroderma, or keloids, and at the initial disease stage in the University of California at Davis (UCD) lines 200/206 chickens, which develop a hereditary systemic connective tissue disease resembling human SSc and permit study of disease stages not accessible in humans. Frozen skin sections were analyzed simultaneously for apoptosis by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labeling and indirect immunofluorescence staining of cell markers with tetramethylrhodamine isothiocyanate conjugates. The results showed that endothelial cells are clearly the first cells to undergo apoptosis in the skin of UCD-200/206 chickens, a process that seems to be induced by anti-endothelial cell antibodies. In human fibrotic skin diseases, apoptotic endothelial cells could only be detected in early inflammatory disease stages of SSc and localized scleroderma.

The occurrence of atopic dermatitis in north Europe: an international questionnaire study

Abstract: Background: Atopic dermatitis is a common multifactorial disease that seems to be increasing in frequency. Objective: Our purpose was to determine the increased prevalence of atopic dermatitis in North Europe. Methods: Approximately 3000 7-year-old school children in Denmark, Germany, and Sweden were enrolled in a cross-sectional questionnaire study that was conducted in the autumn of 1992 with common protocols and standardized procedures. Results: The response rate was 90%. The frequency of atopic dermatitis was calculated to be 15.6% (95% confidence interval 14.2% to 17%) with some regional differences. Girls more often had flexural eczema and outnumbered boys in a ratio of 1.3:1.0. Boys more often had a personal history of asthma, whereas girls more often had a family history of asthma. Conclusion: The increasing prevalence of atopic dermatitis has been confirmed. This simple questionnaire model works well, is cost effective, and is sufficiently sensitive and specific to conduct large-scale epidemiologic investigations in school children.

Combustion in a Porous Medium-Advances and Applications

Abstract: In this paper research and development work of the authors is described, which led to the design of a new combustor-heat exchanger system based on the combustion in porous media. Combustion in inert porous media is possible if the Peclet-number is high enough ( > 65), so that quenching of the flame inside the pores is prohibited. The heat transfer from the combustion zone, to the porous medium itself is very effective because of the very large surface between them. The combustion temperature can be controlled through the porous medium temperature. Prompt and thermal NOx formation, which is temperature dependent, can be controlled by appropriate cooling of the combustion zone. The heat transfer mechanisms in the combustor are discussed and new designs of porous materials are proposed, which allow a high power density and a better control of the temperature level in the combustion zone. The possible application field and the expected benefits of this combustion technique are discussed.

Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase.

Abstract: Nitric oxide (NO) synthase (iNOS) is required for the resolution of acute cutaneous leishmaniasis in resistant C57BL/6 mice. As is the case in several other infections, the clinically cured host organism still harbors small amounts of live Leishmania major parasites. Here, we demonstrate lifelong expression of iNOS at the site of the original skin lesion and in the draining lymph node of long-term-infected C57BL/6 mice. iNOS activity in the lymph node was dependent on CD4+, but not on the CD8+ T cells. By double labeling techniques, iNOS and L. major were each found in macrophages (F4/80+, BM-8+, and/or MOMA-2+) and dendritic cells (NLDC-145+), but not in granulocytes or endothelial cells. In situ triple labeling of lymph node sections revealed that approximately 30-40% of the L. major foci were associated with iNOS-positive macrophages or dendritic cells. The majority of the L. major foci (60-70%), however, was located in areas that were negative for both iNOS and the macrophage and dendritic cell markers. In L. major-infected C57BL/6 mice, which had cured their cutaneous lesions, administration of L-N6-iminoethyl-lysine (L-NIL), a potent inhibitor of iNOS, led to a 10(4)-10(5)-fold increase of the parasite burden in the cutaneous and lymphoid tissue and caused clinical recrudescence of the disease. Persistent expression of iNOS and resumption of parasite replication after application of L-NIL was also observed in resistant C3H/HeN and CBA/J mice. We conclude that iNOS activity is crucial for the control of Leishmania persisting in immunocompetent hosts after resolution of the primary infection. Failure to maintain iNOS activity might be the mechanism underlying endogenous reactivation of latent infections with NO-sensitive microbes during phases of immunosuppression.

The Coding of the Three-Dimensional Structure of Molecules by Molecular Transforms and Its Application to Structure-Spectra Correlations and Studies of Biological Activity

Abstract: A molecular transform, derived from an equation used in electron diffraction studies, is developed that allows the representation of the three-dimensional structure of a molecule by a fixed number of values. Various atomic properties can be taken into account giving high flexibility to this representation of a molecule. This 3D-MoRSE (Molecule Representation of Structures based on Electron diffraction) code retains important structural features such as the mass (see ref 35) and the amount of branching as evidenced by an investigation of monosubstituted benzene derivatives. Furthermore, this molecular representation was able to distinguish between benzene, cyclohexane, and naphthalene derivatives in a dataset of great structural variety. This molecular representation was used in counterpropagation neural networks to distinguish between dopamine D1 and D2 agonists and to group 31 steroids binding to the corticosteroid binding globulin receptor into compounds of high, medium, and low activity. Great promise ...

Nitric oxide-induced apoptosis: p53-dependent and p53-independent signalling pathways.

Abstract: Nitric oxide (NO) generation initiates apoptotic cell death in different experimental systems. In RAW 264.7 macrophages the appearance of typical apoptotic markers is linked to inducible NO synthase induction. Mechanistically, accumulation of tumour suppressor p53 precedes apoptotic DNA fragmentation. With the use of S-nitroglutathione (GSNO) we correlated a dose-dependent p53 up-regulation to DNA fragmentation measured after 4 h and 8 h, respectively. Our studies revealed a linear correlation between the potency of five different NO donors with respect to apoptosis induction and p53 accumulation. Furthermore, we probed for NO-induced apoptosis after stable transfection of RAW 264.7 macrophages with plasmids encoding p53 antisense RNA. Clones with down-regulated p53 levels in response to GSNO exhibited a marked reduction in DNA fragmentation. Expression of the inducible NO synthase in response to lipopolysaccharide and interferon-gamma caused apoptosis in RAW 264.7 macrophages and neomycin-vector controls within 24 h. In contrast, p53 antisense RNA-expressing clones appeared highly resistant towards endogenous NO, although inducible NO synthase induction with concomitant nitrite production remained unchanged. For RAW 264.7 macrophages our results established a functional role of the tumour suppressor p53 during NO-induced apoptotic cell death. However, p53 antisense experiments and the use of the p53-negative cell line U937 substantiated p53-independent signalling pathways operative during NO-mediated apoptosis.

Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product

Abstract: Recognition of virus-infected cells by CD8+ cytotoxic T lymphocytes requires that the viral proteins be processed into peptides, the derived peptides transported into the endoplasmic reticulum and inserted into the binding groove of a major histocompatibility complex class I molecule, and the antigenic complex exported to the cell surface. However, viral pathogens can disrupt this process and interfere with immune recognition. These mechanisms may be vital to large viruses such as human cytomegalovirus (CMV), which causes persistent infection despite producing over 200 potentially antigenic proteins during the sequential immediate-early, early and late phases of viral gene expression. Products of CMV early-phase gene expression can globally block class I presentation and prevent recognition of infected cells by cytotoxic T lymphocytes, but an essential viral transcription factor, the 72K principal immediate-early protein, is abundantly expressed before this blockade. However, only a few host CD8+ cytotoxic T lymphocytes specific for immediate-early protein are present in seropositive individuals, and these lyse CMV-infected cells poorly. Here we demonstrate selective abrogation of immediate-early peptide presentation by a CMV matrix protein with associated kinase activity and suggest that modification of a viral protein can result in limiting access to the processing machinery and evasion of cytotoxic-T-cell recognition.

The Arabidopsis thaliana AtSUC2 Gene is Specifically Expressed in Companion Cells

Abstract: : Polyclonal antisera against a fusion protein of β-galactosidase and the 20 C-terminal amino acids of the Arabidopsis thaliana sucrose carrier AtSUC2 were used to determine the cellular localization of the AtSUC2 protein. Using fluorescence-labelling on sections from different organs of Arabidopsis the AtSUC2 protein was immunolocalized exclusively in companion cells. The presented data indicate that phloem loading in Arabidopsis may be catalyzed by the AtSUC2 sucrose carrier which transports sucrose into the companion cells. No evidence for a participation of the second Arabidopsis sucrose transporter AtSUC1 has been obtained.

Robust neural networks with on-line learning for blind identification and blind separation of sources

Abstract: Two unsupervised, self-normalizing, adaptive learning algorithms are developed for robust blind identification and/or blind separation of independent source signals from a linear mixture of them. One of these algorithms is developed for on-line learning of a single-layer feed-forward neural network model and a second one for a feedback (fully recurrent) neural network model. The proposed algorithms are robust, efficient, fast and suitable for real-time implementations. Moreover, they ensure the separation of extremely weak or badly scaled stationary signals, as well as a successful separation even if the mixture matrix is very ill-conditioned (near singular). The performance of the proposed algorithms is illustrated by computer simulation experiments.

Tissue acidosis in nociception and pain.

Abstract: Publisher Summary This chapter focuses on the tissue acidosis in nociception and pain Local imbalance of perfusion and metabolism may be suggested to be the common mechanism generating tissue acidosis Even in inflammation, the metabolic turn-over may be more enhanced, for example, by accumulation of inflammatory cells, than the local blood flow that should lead to lactic acid accumulation Leukocytes, as well as myocytes, can actively transport lactic acid into the interstitial space The delayed hyperalgesia observed with experimental tissue acidosis in humans seems to be reflected in a concomitantly delayed decrease of mechanical thresholds of cutaneous nociceptors, in vitro, which occurs upon repeated or prolonged exposure to low pH A striking feature of pH-induced pain and nociceptor excitation is the synergism with mediators of inflammation encountered with tissue acidosis in inflamed areas Preventing tissue acidosis may neither be possible nor even desirable; however, blocking pH-induced nociceptor excitation may be of great help to controlling pain of various origins

The sink-specific and stress-regulated Arabidopsis STP4 gene: enhanced expression of a gene encoding a monosaccharide transporter by wounding, elicitors, and pathogen challenge.

Abstract: A cDNA for the Arabidopsis STP4 gene (for sugar transport protein 4) was isolated, and the properties of the encoded protein were studied in Schizosaccharomyces pombe. The STP4 monosaccharide H+ symporter is composed of 514 amino acids and has a calculated molecular mass of 57.1 kD. RNA gel blot analyses revealed that STP4 is expressed primarily in roots and flowers of Arabidopsis. This was shown in more detail with STP4 promoter-beta-glucuronidase (GUS) plants yielding strong STP4-driven GUS activity in root tips and anthers. Wounding of plants transformed with STP4-GUS constructs resulted in a rapid increase in GUS activity in cells directly adjacent to the lesion. This was confirmed by RNase protection analyses in Arabidopsis wild-type plants showing a strong, wound-induced increase in STP4 mRNA levels. STP4 expression was induced rapidly in suspension-cultured Arabidopsis cells that were treated with the Pseudomonas syringae elicitor or with chitin or in Arabidopsis plants that were exposed to fungal attacks. Our data suggest that the role of STP4 is to catalyze monosaccharide import into classic sinks, such as root tips and anthers, and, most importantly, to meet the increased carbohydrate demand of cells responding to environmental stress.

High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeficiency virus type 1 infection.

Abstract: A large number of nef alleles were obtained from peripheral blood mononuclear cells (PBMC) of four long-term nonprogressing survivors of human immunodeficiency virus type 1 (HIV-1) infection and from five individuals with progressive HIV-1 infection. These primary nef alleles were characterized by DNA sequence analysis and for their ability to downregulate CD4 surface expression. Intact nef open reading frames that directed the expression of Nef protein were recovered from all of the individuals. Most of the Nef proteins derived from three of four individuals with nonprogressive infection and from all five individuals with progressive infection were functional as judged by their ability to induce a decrease in surface CD4 expression. In contrast, one individual with nonprogressive HIV-1 infection yielded an unusually high frequency of disrupted nef open reading frames and Nef proteins defective for CD4 downregulation. Approximately 70% of the nef clones obtained from the PBMC of this individual at eight time points over a 12-year period were disrupted or defective for CD4 downregulation. While functional Nef proteins were demonstrated early in the course of infection (1983), functional nef alleles have surprisingly not come to predominate over time in PBMC DNA in this individual.