McGraw-Hill Book Research Articles

Characterization of a Disease-associated Mutation Affecting a Putative Splicing Regulatory Element in Intron 6b of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene

Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR mutations are classified as "splicing mutations," but for almost 40% of these, their role in affecting the pre-mRNA splicing of the gene is not yet defined. In this work, we describe a new splicing mutation detected in three unrelated Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002-1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA level, this mutation creates an aberrant inclusion of a sequence of 101 nucleotides between exons 6b and 7. This sequence corresponds to a portion of intron 6b and resembles a cryptic exon because it is characterized by an upstream ag and a downstream gt sequence, which are most probably recognized as 5'- and 3'-splice sites by the spliceosome. Through functional analysis of this splicing defect, we show that this mutation abolishes the interaction of the splicing regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic splicing regulatory element and creates a new recognition motif for the SRp75 splicing factor, causing activation of the cryptic exon. Our results show that the c.1002-1110_1113delTAAG mutation creates a new intronic splicing regulatory element in intron 6b of the CFTR gene exclusively recognized by SRp75.

A Neural Circuit Mechanism Integrating Motivational State with Memory Expression in Drosophila

Behavioral expression of food-associated memory in fruit flies is constrained by satiety and promoted by hunger, suggesting an influence of motivational state. Here, we identify a neural mechanism that integrates the internal state of hunger and appetitive memory. We show that stimulation of neurons that express neuropeptide F (dNPF), an ortholog of mammalian NPY, mimics food deprivation and promotes memory performance in satiated flies. Robust appetitive memory performance requires the dNPF receptor in six dopaminergic neurons that innervate a distinct region of the mushroom bodies. Blocking these dopaminergic neurons releases memory performance in satiated flies, whereas stimulation suppresses memory performance in hungry flies. Therefore, dNPF and dopamine provide a motivational switch in the mushroom body that controls the output of appetitive memory.

Myosin Loop 2 Is Involved in the Formation of a Trimeric Complex of Twitchin, Actin, and Myosin

Molluscan smooth muscles exhibit a low energy cost contraction called catch. Catch is regulated by twitchin phosphorylation and dephosphorylation. Recently, we found that the D2 fragment of twitchin containing the D2 site (Ser-4316) and flanking immunoglobulin motifs (TWD2-S) formed a heterotrimeric complex with myosin and with actin in the region that interacts with myosin loop 2 (Funabara, D., Hamamoto, C., Yamamoto, K., Inoue, A., Ueda, M., Osawa, R., Kanoh, S., Hartshorne, D. J., Suzuki, S., and Watabe, S. (2007) J. Exp. Biol. 210, 4399-4410). Here, we show that TWD2-S interacts directly with myosin loop 2 in a phosphorylation-sensitive manner. A synthesized peptide, CAQNKEAETTGTHKKRKSSA, based on the myosin loop 2 sequence (loop 2 peptide), competitively inhibited the formation of the trimeric complex. Isothermal titration calorimetry showed that TWD2-S binds to the loop 2 peptide with a K(a) of (2.44 +/- 0.09) x 10(5) m(-1) with two binding sites. The twitchin-binding peptide of actin, AGFAGDDAP, which also inhibited formation of the trimeric complex, bound to TWD2-S with a K(a) of (5.83 +/- 0.05) x 10(4) m(-1) with two binding sites. The affinity of TWD2-S to actin and myosin was slightly decreased with an increase of pH, but this effect could not account for the marked pH dependence of catch in permeabilized fibers. The complex formation also showed a moderate Ca(2+) sensitivity in that in the presence of Ca(2+) complex formation was reduced.

Tangier Disease in Severely Progressive Coronary and Peripheral Artery Disease

A 37-year-old man was first referred to our lipid clinic in December 2007 for plasma lipid alteration. He presented with large, orange tonsils (Figure 1) and hepatosplenomegaly. There was no evidence of corneal opacities nor of other ocular abnormalities, and there were no nervous system abnormalities as assessed by sensitive and motor electromyography. Figure 1. Orange large tonsils. Hematologic abnormalities included thrombocytopenia and erythrocytes with altered morphology (stomatocytes; Figure 2) and function (decreased osmotic resistance). Serum levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were 58, 184, and 4 mg/dL, respectively; plasma apolipoprotein A-I concentrations were very low (3.9 mg/dL); and apolipoprotein A-II plasma levels were 1.7 mg/dL. Figure 2. Peripheral blood erythrocytes with numerous stomatocytes. The patient’s father (58 years of age) had serum levels of total cholesterol, HDL cholesterol, and apolipoprotein A-I of 127, 25, and 99.5 mg/dL, respectively. Moreover, he had a …

Publishing in Hard Times

The former head of Pearson Education, McGraw-Hill Book Publishing, and Harcourt Brace Jovanovich presents an assessment of the state of publishing during this recession. The paper analyses actions taken by publishers in previous downturns, recommends approaches to dealing with recessions that maintain long-term health of the business. Recessions can mask more profound problems, such as happened in the newspaper industry and as is occurring in trade publishing. The paper also analyzes outlook for college and school publishing.

Subordination to periodic processes and synchronization

We study the subordination to a process that is periodic in the natural time scale, and equivalent to a clock with N states. The rationale for this investigation is given by a set of many interacting clocks with N states. The natural time scale representation corresponds to the dynamics of an individual clock with no interaction with the other clocks of this set. We argue that the cooperation among the clocks of this set has the effect of generating a global clock, whose times of sojourn in each of its N states are described by a distribution density with an inverse power law form and power index μ < 2 . This is equivalent to extending the widely used subordination method from fluctuation–dissipation processes to periodic processes, thereby raising the question of whether special conditions exist of perfect synchronization, signaled by regular oscillations, and especially by oscillations with no damping. We study first the case of a Poisson subordination function. We show that in spite of the random nature of the subordination method the procedure has the effect of creating damped oscillations, whose damping vanishes in the limiting case of N ≫ 1 , thereby suggesting a condition of perfect synchronization in this limit. The Bateman’s mathematical arguments [H. Bateman, Higher Transcendental Functions, vol. III, Robert K Krieger, Publishing Company, Inc. Krim.Fr. Drive Malabar, FL; Copyright 1953 by McGraw-Hill Book Company Inc.] indicate that the condition of perfect synchronization is possible also in the non-Poisson case, with μ < 2 , although it may lie beyond the range of computer simulation. To make the theoretical predictions accessible to numerical simulation, we use a subordination function whose survival probability is a Mittag–Leffler exponential function. This method prevents us from directly establishing the macroscopic coherence emerging from μ = 2 , which generates a perfect form of 1 / f noise. However, it affords indirect evidence that perfect synchronization signaled by undamped regular oscillations may be produced in this case. Furthermore, we explore a condition characterized by an excellent agreement between theory and numerical simulation, where the long-time region relaxation, with a perfect inverse power law decay, emerging from the subordination to ordinary fluctuation–dissipation processes, is replaced by exponentially damped regular oscillations.

High temperature strength and failure of the Ni-base superalloy PM 3030

The strength, fatigue life and fracture behavior of the oxide dispersion strengthened (ODS) nickel-base superalloy PM 3030 are investigated. The high Al content in PM 3030 leads to the formation of coherent γ′ particles and, thus, to additional precipitation strengthening. A coarse and elongated grain structure (R34) and two isotropic batches with mean grain sizes of 1 μm (R90) and 17 μm (R901315) are considered. Compressive constant strain rate tests and high cycle fatigue (HCF) tests are performed. Optical, scanning and transmission electron microscopy (OM, SEM and TEM) are carried out. The properties are compared with those of the solely oxide dispersion strengthened Ni-base alloy PM 1000 [Estrin, Y., Heilmaier, M., Drew, G., 1999. Creep properties of an oxide dispersion strengthened nickel-base alloy: the effect of grain orientation and grain aspect ratio. Mater. Sci. Eng. A 272(1), 163–173]. It is found that additional γ′ hardening provides an increase in quasi-static strength by about a factor 2 and in HCF life by about a factor 10 2–10 3 at temperatures up to 850 °C. When fatigue life is compared at a fixed ratio of stress amplitude-to-yield or ultimate compressive strength, R34 shows a fatigue life similar to that of PM 1000 at lower temperature (e.g. 600 °C) indicating that the quasi-static strength advantage is proportionally translated into improved fatigue performance; for higher temperatures (850 °C) however, R34 shows a shorter fatigue life as compared to PM 1000. Grain size reduction, as exemplified with the fine grain R90 batch, also provides an increase in strength up to the equicohesion temperature ( T E) [Dieter, G.E., 1986. Mechanical Metallurgy. SI Metric ed. McGraw-Hill Book Company, London]. Above T E, faster diffusion and grain boundary sliding [Raj, R., Ashby, M.F., 1971. On the grain boundary sliding and diffusional creep. Metall. Trans. 2, 1113–1127; Spingarn, J.R., Nix, W.D., 1978. Diffusional creep and diffusionally accommodated grain rearrangement. Acta Metall. 26, 1389–1398] lead to a drastic drop in strength for the R90 material. In contrast, the batch with intermediate grain size (R901315) shows strength comparable to that of R34 up to 850 °C. Furthermore, R901315 shows improved crack tolerance compared to its coarse grain counterpart R34. Due to premature crack initiating coarse oxide particles however, R901315 does not show any improvement in elongation to failure during tensile tests. Eliminating those coarse particles is expected to improve the ductility and toughness of this isotropic batch.

A two-dimensional, transient, compressible isothermal and two-phase model for the air-side electrode of PEM fuel cells

A two-dimensional, transient, compressible, isothermal and two-phase flow of reactant–product mixture in the air-side electrode of proton exchange membrane fuel cells (PEMFC) are numerically studied in the present paper. The mixture is composed of four species: oxygen, nitrogen, liquid water and water vapor. The governing PDE’s are conservation of the water vapor and oxygen species, momentum equation of the mixture ( gas + liquid ), mass conservation of the liquid phase, and mass conservation of the mixture. In this study, a separate PDE for the mass conservation of the liquid water is solved to calculate the saturation levels. The capillary pressure was used to determine the slip velocity between the phases. A full compressible form of the momentum equation was used, with the ∇ ⋅ V preserved in the equation. The Maxwell–Stefan equation was used to model the diffusive fluxes of the multi-component gas mixture. The strongly coupled equations are solved based on a recently developed finite volume SIMPLER scheme of S.V. Patankar, Numerical Heat Transfer and Fluid Flow, Hemisphere Publishing Corp., McGraw-Hill Book Company, 1984. The computational domain consists of two regions; an open area (gas delivery channel) linked to a porous gas diffusion layer (GDL). A single (unified) set of the PDE’s are used for the whole domain with the corresponding properties of each sub-domain. A polarization curve for the whole spectrum of the dry and wet regions were obtained. The results were compared with the experiments of E.A. Ticianelli, C.R. Derouin, A. Redondo, S. Srinivasan, J. Electrochem. Soc. 135 (1988) 2209, and good agreements were achieved.

Predicting Naming Latencies with an Analogical Model

Skousen's (1989, Analogical modeling of language, Kluwer Academic Publishers, Dordrecht) Analogical Model (AM) predicts behavior such as spelling pronunciation by comparing the characteristics of a test item (a given input word) to those of individual exemplars in a data set of previously encountered items. While AM and other exemplar-based models enjoy continuing success in their ability to predict what a participant's response to a given task will be, it does not yet include a widely tested mechanism for extending its predictions to other measures of interest in psycholinguistics such as response time (RT). This article reports the results of applying a formula derived in Estes (1959, in: Koch, Psychology: A study of a science, McGraw-Hill Book Co., Inc.) for approximating "mean predicted latency" in decision tasks to the alternative responses and their associated probabilities predicted by AM. The model is tested against six sets of data from previously published naming studies.

Solving the Beck and Wieland model with optimal experimentation in DualPC

Currently, there is a renewed interest in the use of optimal experimentation (adaptive control) in economics. Example are found in [Amman, H. M. & Kendrick, D. A. (1999). Should macroeconomic policy makers consider parameter covariances. Computational Economics 14, 263–267; Amman, H. M. & Kendrick, D. A. (2003). Mitigation of the Lucas critique with stochastic control methods. Journal of Economic Dynamics and Control 27, 2035–2057; Cosimano, T. F. Optimal experimentation and the perturbation method in the neighborhood of the augmented linear regulator problem. Journal of Economics, Dynamics and Control (in press); Cosimano, T. F., & Gapen, M. T. (2005b). Recursive methods of dynamic linear economics and optimal experimentation using the perturbation method, Working paper. Notre Dame, Indiana, USA: Department of Finance, University of Notre Dame; Cosimano, T. F., & Gapen, M. T. (2005a). Program notes for optimal experimentation and the perturbation method in the neighborhood of the augmented linear regulator problem, Working paper. Notre Dame, Indiana, USA: Department of Finance, University of Notre Dame; Cosimano, T. F., & Gapen, M. T. (2006). An algorithm for approximating optimal experimentation problems using the perturbation method, Working paper. Notre Dame, Indiana, USA: Department of Finance, University of Notre Dame; Tesfaselassie, M. F., Schaling, E., & Eijffinger, S. (2007). Learning about the term structure and optimal rules for inflation targeting, Working paper. Tilburg, The Netherlands: Tilburg University; Tucci, M. P. (1997). Adaptive control in the presence of time-varying parameters. Journal of Economic Dynamics and Control, 22, 39–47; Wieland, V. (2000a). Learning by doing and the value of optimal experimentation. Journal of Economic Dynamics and Control, 24, 501–543; Wieland, V., (2000b). Monetary policy, parameter uncertainty and optimal learning. Journal of Monetary Economics, 46, 199–228] . In this paper we present the Beck & Wieland model [Beck, G., & Wieland, V. (2002). Learning and control in a changing economic environment. Journal of Economic Dynamics and Control, 26, 1359–1378] and the methodology to solve this model with time-varying parameters using the various control methods described in [Kendrick, D. A. (1981). Stochastic control for economic models (1st ed.), New York, NY, USA: McGraw-Hill Book Company; Kendrick, D. A. (2002). Stochastic control for economic models (2nd ed.) Available at url: http://www.eco.utexas.edu/faculty/Kendrick] . Furthermore, we also provide numerical results using the DualPC software [Amman, H. M., & Kendrick, D. A. (1999). The DualI/DualPC software for optimal control models: User’s guide. Working paper, Austin, TX 78712, USA: Center for Applied Research in Economics, University of Texas] and show first evidence that optimal experimentation or Dual Control may produce better results than Expected Optimal Feedback.

Mathematical properties and parameter estimation for transit compartment pharmacodynamic models

One feature of recent research in pharmacodynamic modelling has been the move towards more mechanistically based model structures. However, in all of these models there are common sub-systems, such as feedback loops and time-delays, whose properties and contribution to the model behaviour merit some mathematical analysis. In this paper a common pharmacodynamic model sub-structure is considered: the linear transit compartment. These models have a number of interesting properties as the length of the cascade chain is increased. In the limiting case a pure time-delay is achieved [Milsum, J.H., 1966. Biological Control Systems Analysis. McGraw-Hill Book Company, New York] and the initial behaviour becoming increasingly sensitive to parameter value perturbation. It is also shown that the modelled drug effect is attenuated, though the duration of action is longer. Through this analysis the range of behaviours that such models are capable of reproducing are characterised. The properties of these models and the experimental requirements are discussed in order to highlight how mathematical analysis prior to experimentation can enhance the utility of mathematical modelling.

Hydromagnetic stagnation point flow by a perturbation technique

An analysis is performed to study the momentum, heat and mass transfer characteristics of MHD natural convection flow and heat generating/absorbing fluid at the stagnation point of an isothermal two-dimensional porous body immersed in a fluid saturated porous medium. The results are obtained by solving the coupled non-linear partial differential equations describing the conservation of mass, momentum and energy by a perturbation technique [A. Aziz, T.Y. Na, Perturbation Methods in Heat Transfer, Springer-Verlag, Berlin, 1984 (pp. 1–184), R. Kenneth Cramer, Shih-I Pai, Magnetofluid Dynamics for Engineers and Applied Physicists, McGraw-Hill Book Company, New York, 1973 (pp. 164–171).]. These results are presented to illustrate the influence of the Hartmann number, Prandtl number, and dimensionless heat generation/absorption coefficient and suction injection parameter. Numerical results for the dimensionless velocity profiles, the temperature profiles, the local friction coefficient and the local Nusselt number are presented for various parameters. These effects of the different parameters on the velocity and temperature as well as the skin friction and wall heat transfer are presented graphically.

Commentary: Aspirin and cancer prevention

1 Kune GA, Kune S. The Melbourne Colorectal Cancer Study. A Description of the Investigation. Melbourne, Australia: University of Melbourne, Department of Surgery Publication, 1986. pp. 1–31. 2 Kune S. An epidemiological study of colorectal cancer. PhD dissertation. University of Melbourne, 1985; pp. 1–378. No. 8608980, pp. 1–407, Ann Arbor, MI: University Microfilms International, 1986 (copyright). 3 Kune S, Kune GA, Watson L. The Melbourne colorectal cancer study: incidence data on age, sex, site, migrants and religion. Int J. Epidemiol 1986;15:483–93. 4 SPSS-x User’s Guide. New York: McGraw-Hill Book Co., 1983. 5 Baker RJ, Nelder JA. The GLIM System. Release 3. Oxford, England: Numerical Algorithm Group, 1978. 6 Adena MA, Wilson SR. Generalized Linear Models in Epidemiological Research: Case Control Studies. Sydney, Australia: INTSTAT Foundation, 1982. 7 Kune S, Kune GA, Watson LF. Case-control study of dietary etiological factors: the Melbourne colorectal cancer study. Nutr Cancer 1987;9:21–42. 8 Garabrant DH, Peters JM, Mack TM, Bernstein L. Job activity and colon cancer risk. Am J Epidemiol 1984;119:1005–14. 9 Wu AH, Paganini-Hill A, Ross RK, Henderson SBE. Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study. Br J Cancer 1987;55:687–94. 10 Burkitt DP. Non-infective disease of the large bowel. Br Med Bull 1984;40:387–89. 11 Correa P, Haenszel W. The epidemiology of large bowel cancer. Adv Cancer Res 1978;26:1–141. 12 Kune GA, Bremond A, Bahnson CB. Personality and psychosocial factors in breast cancer patients. In: Dennerstein L, Fraser I (eds). Hormones and Behaviour. Amsterdam: Elsevier/North-Holland Biomedical Press, 1986. pp. 585–89. 13 Cooper CL, Cooper RFD, Faragher EB. A prospective study of the relationship between breast cancer and life events, type A behaviour, social support and coping skills. Stress Med 1986;2:271–77. 14 Potter JD, McMichael AJ. Large bowel cancer in women in relation to reproductive and hormonal factors: a case control study. J Natl Cancer Inst 1983;71:703–9. 15 Weiss NS, Daling JR, Chow WH. Incidence of cancer of the large bowel in women in relation to reproductive and hormonal factors. J Natl Cancer Inst 1981;76:57–60. 16 Kune GA, Kune S, Watson LF. History of colorectal polypectomy and risk of subsequent colorectal cancer. Br J Surg 1987;75:1064–65. 17 Friedman GD, Goldhaber MK, Quesenberry CP Jr. Cholecystectomy and large bowel cancer. Lancet 1987;1:906–8. 18 Kune GA, Kune S, Watson LF. Large bowel cancer after cholecystectomy. Am J Surg 1988. (in press).

Stereospecific Proton Transfer by a Mobile Catalyst in Mammalian Fructose-1,6-bisphosphate Aldolase

Class I fructose-1,6-bisphosphate aldolases catalyze the interconversion between the enamine and iminium covalent enzymatic intermediates by stereospecific exchange of the pro(S) proton of the dihydroxyacetone-phosphate C3 carbon, an obligatory reaction step during substrate cleavage. To investigate the mechanism of stereospecific proton exchange, high resolution crystal structures of native and a mutant Lys(146) --> Met aldolase were solved in complex with dihydroxyacetone phosphate. The structural analysis revealed trapping of the enamine intermediate at Lys(229) in native aldolase. Mutation of conserved active site residue Lys(146) to Met drastically decreased activity and enabled trapping of the putative iminium intermediate in the crystal structure showing active site attachment by C-terminal residues 360-363. Attachment positions the conserved C-terminal Tyr(363) hydroxyl within 2.9A of the C3 carbon in the iminium in an orientation consistent with incipient re face proton transfer. We propose a catalytic mechanism by which the mobile C-terminal Tyr(363) is activated by the iminium phosphate via a structurally conserved water molecule to yield a transient phenate, whose developing negative charge is stabilized by a Lys(146) positive charge, and which abstracts the C3 pro(S) proton forming the enamine. An identical C-terminal binding mode observed in the presence of phosphate in the native structure corroborates Tyr(363) interaction with Lys(146) and is consistent with transient C terminus binding in the enamine. The absence of charge stabilization and of a mobile C-terminal catalyst explains the extraordinary stability of enamine intermediates in transaldolases.

Molecular Determinants for G Protein βγ Modulation of Ionotropic Glycine Receptors

The ligand-gated ion channel superfamily plays a critical role in neuronal excitability. The functions of glycine receptor (GlyR) and nicotinic acetylcholine receptor are modulated by G protein betagamma subunits. The molecular determinants for this functional modulation, however, are still unknown. Studying mutant receptors, we identified two basic amino acid motifs within the large intracellular loop of the GlyR alpha(1) subunit that are critical for binding and functional modulation by Gbetagamma. Mutations within these sequences demonstrated that all of the residues detected are important for Gbetagamma modulation, although both motifs are necessary for full binding. Molecular modeling predicts that these sites are alpha-helixes near transmembrane domains 3 and 4, near to the lipid bilayer and highly electropositive. Our results demonstrate for the first time the sites for G protein betagamma subunit modulation on GlyRs and provide a new framework regarding the ligand-gated ion channel superfamily regulation by intracellular signaling.

Purification, Characterization, and Cloning of a Spodoptera frugiperda Sf9 β-N-Acetylhexosaminidase That Hydrolyzes Terminal N-Acetylglucosamine on the N-Glycan Core

Paucimannosidic glycans are often predominant in N-glycans produced by insect cells. However, a beta-N-acetylhexosaminidase responsible for the generation of paucimannosidic glycans in lepidopteran insect cells has not been identified. We report the purification of a beta-N-acetylhexosaminidase from the culture medium of Spodoptera frugiperda Sf9 cells (Sfhex). The purified Sfhex protein showed 10 times higher activity for a terminal N-acetylglucosamine on the N-glycan core compared with tri-N-acetylchitotriose. Sfhex was found to be a homodimer of 110 kDa in solution, with a pH optimum of 5.5. With a biantennary N-glycan substrate, it exhibited a 5-fold preference for removal of the beta(1,2)-linked N-acetylglucosamine from the Man alpha(1,3) branch compared with the Man alpha(1,6) branch. We isolated two corresponding cDNA clones for Sfhex that encode proteins with >99% amino acid identity. A phylogenetic analysis suggested that Sfhex is an ortholog of mammalian lysosomal beta-N-acetylhexosaminidases. Recombinant Sfhex expressed in Sf9 cells exhibited the same substrate specificity and pH optimum as the purified enzyme. Although a larger amount of newly synthesized Sfhex was secreted into the culture medium by Sf9 cells, a significant amount of Sfhex was also found to be intracellular. Under a confocal microscope, cellular Sfhex exhibited punctate staining throughout the cytoplasm, but did not colocalize with a Golgi marker. Because secretory glycoproteins and Sfhex are cotransported through the same secretory pathway and because Sfhex is active at the pH of the secretory compartments, this study suggests that Sfhex may play a role as a processing beta-N-acetylhexosaminidase acting on N-glycans from Sf9 cells.

On the Hydrolysis of the Tetravalent Uranium Ion U4+

The formation of the hydrolytic complexes of U(IV) has been investigated at 25.00°C by measuring the Emf of a cell containing inert metal sponge and glass electrodes, in 3 mol·dm−3 aqueous NaClO4 solutions containing both U(VI) and U(IV) at acidities ranging between 10−0.5 and 10−1.8 mol·dm−3. The lower limit of acidity is imposed by the precipitation of the sparingly soluble oxides of U(IV) whereas the upper limit has been chosen in order to avoid large corrections for the liquid junction potential. The experimental data have been treated using classical graphical methods (Rossotti, F.J.C., Rossotti, H.: The Determination of Stability Constants. McGraw Hill Book Company, Inc. New York (1961)) and by the computerized least-squares program LETAGROP-ETITR (Sillen, L.G., Warnqvist, B.: Arkiv for Kemi. 31, 315–39 (1969)). The results can be explained by assuming the formation of two mononuclear complexes, U(OH)3+ and \(\mathop {{\rm U(OH)}}\nolimits_4^0\). The obtained formation constants in the 3 mol·dm−3 NaClO4 ionic medium are: \({\rm log}_{10}^\ast\beta_{1}=-1.62\pm 0.02\) and \({\rm log}_{10}^\ast\beta_{4} = -7.70 \pm 0.04\). The formal standard potential * E 6,4 for the couple UO2 2 +/U4 + at the same conditions is 335.7± 0.5 mV.

Sexually Transmitted Infections and Prostatic Inflammation/Cell Damage as Measured by Serum Prostate Specific Antigen Concentration

Although inflammation and cell damage due to STIs are hypothesized to contribute to the later development of prostate disease, few clinical studies have been done to investigate the extent to which sexually transmitted agents infect and induce an inflammatory immune response in the prostate. We indirectly investigated this question by measuring serum PSA, a possible marker of prostatic inflammation and cell damage, in men with documented STIs. Archived serum specimens from young men with laboratory confirmed exudative STIs, including gonorrhea, chlamydia and trichomonosis, and young men with no STI diagnoses were identified in 2 prospective studies of patients at Baltimore City STI clinics, that is 84 in the STI Transmission and Acquisition Study, and 61 in the Mucosal Immunity Study. Serum specimens from visits before, during and after STI diagnoses in men with at least 1 exudative STI diagnosis and from all visits in men with no STI diagnoses were tested for total PSA concentration. After combining the studies patients with STIs were more likely to have a 40% or greater increase in PSA than patients with no STI diagnoses (32% vs 2%, p <0.01). These findings suggest that STIs may contribute to prostatic inflammation and cell damage in a subset of infected men. Further studies are warranted to replicate study findings and determine host and infection characteristics associated with large PSA increases.

Rho Family Guanine Nucleotide Exchange Factor Brx Couples Extracellular Signals to the Glucocorticoid Signaling System

Glucocorticoids regulate many crucial biologic functions through their cytoplasmic/nuclear glucocorticoid receptors (GR). Excess, deficiency, or alteration in tissue sensitivity to glucocorticoids has been associated with major causes of human morbidity and mortality. Brx, a cytoplasmic Rho family guanine nucleotide exchange factor, binds to and influences the activity of several nuclear hormone receptors. We examined the functional and molecular interactions between GR and Brx. The glucocorticoid sensitivity of lymphocytes obtained from mice haplo-insufficient for Brx was significantly decreased. Conversely, GR-mediated transcriptional activity of a glucocorticoid response element (GRE)-mediated glucocorticoid-responsive promoter was enhanced by Brx in a guanine nucleotide exchange factor domain-dependent fashion. Brx interacted with GR, forming a ternary complex with RhoA. In a chromatin immunoprecipitation assay, Brx and RhoA were co-precipitated with GREs only in the presence of ligand-activated GR. Extracellularly administered lysophosphatidic acid, which activates its signaling cascade through a specific membrane GTP-binding protein (G-protein)-coupled receptor in a G-protein alpha(13)-, Brx-, and RhoA-dependent fashion, enhanced GR transcriptional activity, whereas depletion of endogenous Brx attenuated this effect. These findings suggest that glucocorticoid signaling and, hence, the tissue sensitivity to glucocorticoids, may be coupled to extracellular signals via Brx and small G-proteins. Nuclear Brx might act as a local GRE-GR-transcriptosome activator by mediating the effect of small G-proteins on glucocorticoid-regulated genes.

Medical world annual 1967. Compiled by the Editors of Medical World News. 9¼ × 6 in. Pp. 245 + xiv. Illustrated. 1967. London: McGraw-Hill Book Company. 81s

Journal Article Medical world annual 1967. Compiled by the Editors of Medical World News. 9¼ × 6 in. Pp. 245 + xiv. Illustrated. 1967. London: McGraw-Hill Book Company. 81s Get access Medical World Annual 1967. Compiled by the Editors of Medical World News. 9¼ × 6 in. Pp. 245 + xiv. Illustrated. 1967. London: McGraw-Hill Book Company. 81s. British Journal of Surgery, Volume 54, Issue 12, December 1967, Page 1039, https://doi.org/10.1002/bjs.1800541221 Published: 08 December 2005