bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetraamine‐modified octreotide and octreotate: labeling with 99mTc and preclinical comparison in AR4‐2J cells and AR4‐2J tumor‐bearing mice
Authors: Nikolopoulou Anastasia , Maina Theodosia , Sotiriou Petros , Cordopatis Paul , Nock Berthold A.
Published: August 2005

Two somatostatin analogues, [99mTc]Demotide and [99mTc]Demotate 4, were compared with [99mTc]Demotate 1, a previously reported somatostatin receptor subtype 2 (sst2) targeting tracer. Conjugates were prepared by coupling an open‐chain tetraamine chelator to D‐Phe1 of [Tyr3]‐octreotide or [Tyr3]‐octreotate, respectively, via a p‐benzylaminodiglycolic acid spacer adopting solid‐phase peptide synthesis techniques. Peptide conjugates were collected in a highly pure form after chromatographic purification. Eventually, [99mTc]Demotide and [99mTc]Demotate 4 were obtained in ∼1 Ci/µmol specific activity and >96% purity after labeling under alkaline conditions. Demotide and Demotate 4 exhibited similar high binding affinities for the sst2 expressed in AR4‐2J cells with IC50 values 0.16 and 0.10 nM, respectively. The (radio)metallated analogues [99mTc]Demotide and [99mTc]Demotate 4 showed equally high affinities to the sst2 during saturation binding assays in AR4‐2J cell membranes (Kds 0.08 and 0.07 nM, respectively). During incubation at 37 °C with AR4‐2J cells, the radiopeptides internalized effectively via a receptor‐mediated process, with [99mTc]Demotate 4 exhibiting a faster internalization rate than [99mTc]Demotide. After injection in athymic mice bearing sst2‐expressing AR4‐2J tumors, the radiotracers showed high and specific uptake in the tumor (>25%ID/g at 1 h) and in the sst2–positive organs. However, both [99mTc]Demotide and [99mTc]Demotate 4 showed unfavorably higher background activity, especially in the abdomen, in comparison to [99mTc]Demotate 1 and are, therefore, less suited than [99mTc]Demotate 1 for sst2‐targeted tumor imaging in man. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.
Ubiquity of ‘Power’ and the Advantage of Terminological Pluralism: Japan's Foreign Policy Discourse
Authors: HAGSTRÖM LINUS
Published: August 2005

This article demonstrates that ubiquitous references to ‘power’ in English-language foreign policy discourse can be understood in the light of the inclination in international relations theory to place power on a par with capability. It makes two claims: that such a concept of power is ill-fitted for foreign policy analysis; and that much clarity would be gained by following the Japanese example of terminological pluralism and thus abandoning ‘power’ as a catch-all term. Foreign policy analysis would benefit from adopting a concept that takes power to reside in specific relationships. Its adoption would moreover dissolve a power paradox associated with the analysis of Japan's post-Cold War foreign policy.
ENTHUSIASM AND ENLIGHTENMENT: FAITH AND PHILOSOPHY IN THE THOUGHT OF CHRISTIAN THOMASIUS
Authors: AHNERT THOMAS
Published: August 2005

“Enthusiasm” has been described as the intellectual opposite of the Enlightenment, its “anti-self”. It stood for a religion of the “heart” rather than the “head”, and was associated with the extreme, millenarian sects on the fringes of established Protestantism. The relationship between religious enthusiasm and enlightened philosophy, however, could be closer than is often thought. Here I focus on the example of the jurist and philosopher Christian Thomasius (1655–1728), who is considered to be one of the first and most influential representatives of the early Enlightenment in Protestant Germany. Usually, Thomasius is described as a sort of classical enlightened thinker who separated the question of religious truth from the pursuit of secular philosophy, and it is implied that the interpretation of Thomasius's religious beliefs contributes little, if anything, to the understanding of his philosophical views. His religious views, however, not only were regarded by contemporaries as an example of religious “enthusiasm”. These “enthusiastic” religious beliefs were also more important to his philosophy than is often argued. They were part of a programme for religious and intellectual renewal and reform which, Thomasius believed, would prepare the reform of Lutheran philosophy from the obsolete, “scholastic” intellectual traditions it had inherited from the papal church. This essay examines the often complex development of Thomasius's religious views in their historical context and their significance for his wider “enlightened” intellectual interests.
WILLIAM JAMES: “PESSIMISM OF THE INTELLECT, OPTIMISM OF THE WILL”
Authors: STROUT CUSHING
Published: August 2005

William James, The Varieties of Religious Experience: A Study in Human Nature, centenary edition, foreword Micky James, intro. Eugene Taylor and Jeremy Carrette (Routledge, 2002)

Charles Taylor, Varieties of Religion Today: William James Revisited (Harvard University Press, 2002)

William James and a Science of Religions, ed. Wayne Proudfoot (Columbia University Press, 2004)

William James has a secure reputation as a pioneer psychologist and as a founding father of the philosophy of pragmatism. In his own time, however, he was best known and most popular among the laity for “The Will to Believe” (1895) and for The Varieties of Religious Experience: A Study in Human Nature (1902), which were defenses erected on behalf of religion in an increasingly secular world. Religious liberals treated the Bible as one human document among others and Christian faith as one tradition among many, but they “sought to salvage what they could of traditional belief, piety, and ethic.” James was part of this movement that took science, empiricism, and modern philosophy as a point of departure, but his contribution to it was distinctive, original, and (in his own idiom) unusually “tough-minded.”
INTELLECTUALS AND POWER, OR, WHAT'S LOVE GOT TO DO WITH IT?
Authors: JAY MARTIN
Published: August 2005

Mark Lilla, The Reckless Mind: Intellectuals in Politics (New York: New York Review of Books, 2001)

Eric Hobsbawm, Interesting Times: A Twentieth-Century Life (New York: Pantheon, 2002)

“Great writers are either husbands or lovers,” Susan Sontag explained in a 1963 essay on Camus. “Some writers supply the solid virtues of a husband: reliability, intelligibility, generosity, decency. There are other writers in whom one prizes the gifts of a lover, gifts of temperament rather than of moral goodness. Notoriously, women tolerate qualities in a lover—moodiness, selfishness, unreliability, brutality—that they never countenance in a husband, in return for excitement, an infusion of intense feeling. In the same way, readers put up with unintelligibility, obsessiveness, painful truths, lies, bad grammar—if, in compensation, the writer allows them to savor rare emotions, and dangerous sensations.” Camus was “the ideal husband of contemporary letters,” she opined, but “as in life, so in art both are necessary, husband and lovers. It's a great pity when one is forced to choose between them.”
Variational grand-canonical electronic structure method for open systems
Authors: Jacobi Shlomit , Baer Roi
Published: August 2005

An ab initio method is developed for variational grand-canonical molecular electronic structure of open systems based on the Gibbs–Peierls–Boguliobov inequality. We describe the theory and a practical method for performing the calculations within standard quantum chemistry codes using Gaussian basis sets. The computational effort scales similarly to the ground-state Hartree–Fock method. The quality of the approximation is studied on a hydrogen molecule by comparing to the exact Gibbs free energy, computed using full configuration-interaction calculations. We find the approximation quite accurate, with errors similar to those of the Hartree–Fock method for ground-state (zero-temperature) calculations. A further demonstration is given of the temperature effects on the bending potential curve for water. Some future directions and applications of the method are discussed. Several appendices give the mathematical and algorithmic details of the method.
Water liquid-vapor equilibria predicted by refined ab initio derived potentials
Authors: Hernández-Cobos Jorge , Saint-Martin Humberto , Mackie A. D. , Vega L. F. , Ortega-Blake Iván
Published: August 2005

Coexistence properties for water near the critical point using several ab initio models were calculated using grand canonical Monte Carlo simulations with multiple histogram reweighting techniques. These models, that have proved to yield a good reproduction of the water properties at ambient conditions, perform rather well, improving the performance of a previous ab initio model. It is also shown that bulk geometry and dipole values, predicted by the simulation, can be used and a good approximation obtained with a polarizable rigid water model but not when polarization is excluded.
Multielectron wave-packet propagation: General theory and application
Authors: Kuleff Alexander I. , Breidbach Jörg , Cederbaum Lorenz S.
Published: August 2005

An ab initio method for multielectron wave-packet propagation in relatively large systems is presented. It allows the description of ultrafast electron dynamics processes before the coupling with the nuclear motion becomes important. The method is applied to the amino acid glycine for the investigation of the migration of hole charge following the ionization of the system. Two different mechanisms of ultrafast charge migration are identified and discussed. It is shown that the electron correlation can be the driving force for the charge-transfer dynamics in glycine.
Pronounced non-Condon effects in the ultrafast infrared spectroscopy of water
Authors: Schmidt J. R. , Corcelli S. A. , Skinner J. L.
Published: August 2005

In the context of vibrational spectroscopy in liquids, non-Condon effects refer to the dependence of the vibrational transition dipole moment of a particular molecule on the rotational and translational coordinates of all the molecules in the liquid. For strongly hydrogen-bonded systems, such as liquid water, non-Condon effects are large. That is, the bond dipole derivative of an OH stretch depends strongly on its hydrogen-bonding environment. Previous calculations of nonlinear vibrational spectroscopy in liquids have not included these non-Condon effects. We find that for water, inclusion of these effects is important for an accurate calculation of, for example, homodyned and heterodyned three-pulse echoes. Such echo experiments have been “inverted” to obtain the OH stretch frequency time-correlation function, but by necessity the Condon and other approximations are made in this inversion procedure. Our conclusion is that for water, primarily because of strong non-Condon effects, this inversion may not lead to the correct frequency time-correlation function. Nevertheless, one can still make comparison between theory and experiment by calculating the experimental echo observables themselves.
Comment on “Theoretical study of the photoinduced transfer among the ground state and two metastable states in [Fe(CN)5NO]2−” [J. Chem. Phys. 122, 074314 (2005)]
Authors: Schaniel D. , Woike Th. , Delley B. , Schefer J. , Imlau M.
Published: August 2005

We discuss the computational results of the “Theoretical study of the photoinduced transfer among the ground state and two metastable states in [Fe(CN)5NO]2−” [J. Chem. Phys. 122, 074314 (2005)] with respect to our previously reported polarized absorption study on the metastable states SI and SII in Na2[Fe(CN)5NO]∙2H2O [D. Schaniel, J. Schefer, B. Delley, M. Imlau, and Th. Woike, Phys. Rev. B 66, 085103 (2002)].
Response to “Comment on ‘Theoretical study of the photoinduced transfer among the ground state and two metastable states in [Fe(CN)5NO]2−” [J. Chem. Phys. 122, 074314 (2005)]
Authors: Ishikawa Takeshi , Tanaka Kiyoshi
Published: August 2005

The response to the Comment on “Theoretical study of the photoinduced transfer among the ground state and two metastable states in [Fe(CN)5NO]2−” is given. Since the character of a few higher excited states (higher than the seventh state) was not presented in our paper and discussed in the comment, the character of these states is given using our unpublished results for comparison. A significant mixing of several configurations is found in the wave functions of these states.
A low-resistance, thermally stable Ohmic contact to n-GaSb
Authors: Robinson J. A. , Mohney S. E.
Published: August 2005

Ohmic contacts to gallium antimonide have been studied in recent years in an attempt to develop a low-resistance, thermally stable metallization. We present a study of Pd3In7∕X∕Au (X=Pt, W, WSi2, or WSiN) contacts that utilize Pd and In to obtain a low contact resistance, and a diffusion barrier (X) to ensure thermal stability of the contact beneath the gold cap. Contacts utilizing WSiN as the diffusion barrier exhibit specific contact resistance values comparable to the best previously reported, but with greatly improved thermal stability and shallow reaction morphology. The Pd3In7∕WSiN∕Au contact provides a specific contact resistance of 1.8×10−6Ωcm2 after annealing at 325°C for 1min or 350°C for 30s (n≅2×1018cm−3). Field emission is identified as the mechanism for current transport in these contacts. The reaction depth of the contact remains less than 30nm after at least 400h at 250°C in an evacuated ampoule, along with an increase in specific contact resistance to 7×10−6Ωcm2.
Nonaxisymmetric effects of stratified spin-up in an axisymmetric annular channel
Authors: Smirnov S. A. , Boyer D. L. , Baines P. G.
Published: August 2005

Laboratory experiments were conducted on spin-up of a linearly stratified fluid in a rotating axisymmetric annular channel formed by two cylindrical coaxial walls and a flat bottom. Secular as well as instantaneous variation in rotation speeds was investigated for a range of Rossby numbers ε=ΔΩ∕Ω⩽1, where ΔΩ is the change in the rotation rate and Ω is the final rotation rate of the annulus. The experimental studies reported by Smirnov et al. [S. A. Smirnov, P. G. Baines, D. L. Boyer, S. I. Voropayev, and A. N. Srdic-Mitrovic, “Long-time evolution of linearly stratified spin-up flows in axisymmetric geometries,” Phys. Fluids 17, 016601 (2005)] were extended to (i) explore the density structure of the corner regions formed adjacent to the inner and outer sidewalls of the annular channel during spin-up, and to (ii) investigate the role of the boundary conditions at the vertical sidewalls in the development of nonaxisymmetric disturbances and formation of large columnar eddies at late spin-up times. The latter was achieved by introducing roughness elements in the form of vertical prisms at the inner sidewall. Observations demonstrated that isopycnals (surfaces of constant density) experience large vertical displacements near the lateral boundaries during spin-up. The density gradient reduces to near zero in the corner regions, where the fluid is stirred, and increases above/below them near the outer/inner sidewalls, respectively. The relative height of the corner regions h∕H (H is the depth of the fluid layer) was found to be determined only by the relative values of the Rossby (ε) and Burger (Bu) numbers and follows the experimental dependence h∕H=0.54ε1∕2∕Bu. A flow stability regime diagram is presented as a function of the Rossby and Burger numbers. Introduction of roughness elements at the inner sidewall did not alter significantly the process and time scales of stratified spin-up, large eddy formation, and subsequent relaxation to the initial state obtained with smooth sidewalls. This finding confirms that the growth of instability in the sidewall shear layers studied by Smirnov et al. does not depend on viscosity.
Improved photoluminescence of 1.26μm InGaAs∕GaAs quantum wells assisted by Sb surfactant and indium-graded intermediate layers
Authors: Chang Yi-An , Kuo Hao-Chung , Chang Ya-Hsien , Wang Shing-Chung
Published: August 2005

We have grown high-quality InGaAs∕GaAs quantum wells (QWs) with emission wavelength range of 1.2–1.26μm by metalorganic chemical vapor depositions. By incorporating Sb surfactant and the indium-graded intermediate layers into InGaAs∕GaAs QWs, the photoluminescence (PL) intensity of the 1.26-μm In0.45Ga0.55As∕GaAs QW is enhanced by a factor of 20 and the full width at half maximum value is reduced from 60.4meVto35.9meV. The good crystalline quality is proved by temperature-dependent PL, which shows that the activation energies of In0.45Ga0.55As and Sb-assisted indium-graded In0.45Ga0.55As QWs are 20.87meV and 27.09meV.
Template-free synthesis of helical hexagonal microtubes of indium nitride
Authors: Luo Shudong , Zhou Weiya , Wang Wenxin , Zhang Zengxing , Liu Lifeng , Dou Xinyuan , Wang Jianxiong , Zhao Xiaowei , Liu Dongfang , Gao Yan , Song Li , Xiang Yanjuan , Zhou Jianjun , Xie Sishen
Published: August 2005

Single crystalline indium nitride (InN) helical microtubes with a hexagonal hollow cross section have been synthesized in bulk quantities by nitriding indium oxide powder in ammonia flux. As-prepared InN microtubes grow along the [0001] direction with typical outer diameters of 1–3μm, wall thickness of 50–80nm and lengths up to hundreds of microns. The InN microtubes exhibit both right-handed and left-handed helicities with helical angles ranging from zero to about 30°. Variation of helicity can be observed in a single tube. A number of observations demonstrate that the growth of the tubular structure occurs by the spiraling of the warped InN nanobelts. Photoluminescence spectrum of the microtubes presents a strong emission peak centered at 700nm at room temperature.
HIV binding, penetration, and primary infection in human cervicovaginal tissue
Authors: Maher Diane , Wu Xiaoyun , Schacker Timothy , Horbul Julie , Southern Peter
Published: August 2005

We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3–4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against β1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract.
Three globin lineages belonging to two structural classes in genomes from the three kingdoms of life
Authors: Vinogradov Serge N. , Hoogewijs David , Bailly Xavier , Arredondo-Peter Raúl , Guertin Michel , Gough Julian , Dewilde Sylvia , Moens Luc , Vanfleteren Jacques R.
Published: August 2005

Although most globins, including the N-terminal domains within chimeric proteins such as flavohemoglobins and globin-coupled sensors, exhibit a 3/3 helical sandwich structure, many bacterial, plant, and ciliate globins have a 2/2 helical sandwich structure. We carried out a comprehensive survey of globins in the genomes from the three kingdoms of life. Bayesian phylogenetic trees based on manually aligned sequences indicate the possibility of past horizontal globin gene transfers from bacteria to eukaryotes.
blastp
searches revealed the presence of 3/3 single-domain globins related to the globin domains of the bacterial and fungal flavohemoglobins in many bacteria, a red alga, and a diatom. Iterated
psi-blast
searches based on groups of globin sequences found that only the single-domain globins and flavohemoglobins recognize the eukaryote 3/3 globins, including vertebrate neuroglobins, α- and β-globins, and cytoglobins. The 2/2 globins recognize the flavohemoglobins, as do the globin coupled sensors and the closely related single-domain protoglobins. However, the 2/2 globins and the globin-coupled sensors do not recognize each other. Thus, all globins appear to be distributed among three lineages: (
i
) the 3/3 plant and metazoan globins, single-domain globins, and flavohemoglobins; (
ii
) the bacterial 3/3 globin-coupled sensors and protoglobins; and (
iii
) the bacterial, plant, and ciliate 2/2 globins. The three lineages may have evolved from an ancestral 3/3 or 2/2 globin. Furthermore, it appears likely that the predominant functions of globins are enzymatic and that oxygen transport is a specialized development that accompanied the evolution of metazoans.
Polymorphism of DNA–anionic liposome complexes reveals hierarchy of ion-mediated interactions
Authors: Liang Hongjun , Harries Daniel , Wong Gerard C. L.
Published: August 2005

Self-assembled DNA delivery systems based on anionic lipids (ALs) complexed with DNA mediated by divalent cations have been recently introduced as an alternative to cationic lipid–DNA complexes because of their low cytotoxicity. We investigate AL–DNA complexes induced by different cations by using synchrotron small angle x-ray scattering and confocal microscopy to show how different ion-mediated interactions are expressed in the self-assembled structures and phase behavior of AL–DNA complexes. The governing interactions in AL–DNA systems are complex: divalent ions can mediate strong attractions between different combinations of the components (such as DNA–DNA and membrane–membrane). Moreover, divalent cations can coordinate nonelectrostatically with lipids and modify the resultant membrane structure. We find that at low membrane charge densities AL–DNA complexes organize into a lamellar structure of alternating DNA and membrane layers crosslinked by ions. At high membrane charge densities, a new phase with no analog in cationic lipid–DNA systems is observed: DNA is expelled from the complex, and a lamellar stack of membranes and intercalated ions is formed. For a subset of the ionic species, high ion concentrations generate an inverted hexagonal phase comprised of DNA strands wrapped by ion-coated lipid tubes. A simple theoretical model that takes into account the electrostatic and membrane elastic contributions to the free energy shows that this transition is consistent with an ion-induced change in the membrane spontaneous curvature,
c
0
. Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical
c
0
that agrees well with experimental values.
Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600
Authors: Huh Kyung-Won , DeMasi Joseph , Ogawa Hidesato , Nakatani Yoshihiro , Howley Peter M. , Münger Karl
Published: August 2005

The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130. However, there is ample evidence that E7 has additional cellular targets that contribute to its transforming potential. We isolated HPV-16 E7 associated cellular protein complexes by tandem affinity purification and mass spectrometry and identified the 600-kDa retinoblastoma protein associated factor, p600, as a cellular target of E7. Association of E7 with p600 is independent of the pocket proteins and is mediated through the N terminal E7 domain, which is related to conserved region 1 of the adenovirus E1A protein and importantly contributes to cellular transformation independent of pRB binding. Depletion of p600 protein levels by RNA interference substantially decreased anchorage-independent growth in HPV-positive and -negative human cancer cells. Therefore, p600 is a cellular target of E7 that regulates cellular pathways that contribute to anchorage-independent growth and cellular transformation.
Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain
Authors: Stuart Lynda M. , Deng Jiusheng , Silver Jessica M. , Takahashi Kazue , Tseng Anita A. , Hennessy Elizabeth J. , Ezekowitz R. Alan B. , Moore Kathryn J.
Published: August 2005

Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfection assays, the mammalian Croquemort paralogue CD36 confers binding and internalization of Gram-positive and, to a lesser extent, Gram-negative bacteria. By mutational analysis, we show that internalization of S. aureus and its component lipoteichoic acid requires the COOH-terminal cytoplasmic portion of CD36, specifically Y463 and C464, which activates Toll-like receptor (TLR) 2/6 signaling. Macrophages lacking CD36 demonstrate reduced internalization of S. aureus and its component lipoteichoic acid, accompanied by a marked defect in tumor necrosis factor-α and IL-12 production. As a result, Cd36−/− mice fail to efficiently clear S. aureus in vivo resulting in profound bacteraemia. Thus, response to S. aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain, which initiates TLR2/6 signaling.
An extraordinary retrotransposon family encoding dual endonucleases
Authors: Kojima Kenji K. , Fujiwara Haruhiko
Published: August 2005

Retrotransposons commonly encode a reverse transcriptase (RT), but other functional domains are variable. The acquisition of new domains is the dominant evolutionary force that brings structural variety to retrotransposons. Non-long-terminal-repeat (non-LTR) retrotransposons are classified into two groups by their structure. Early branched non-LTR retrotransposons encode a restriction-like endonuclease (RLE), and recently branched non-LTR retrotransposons encode an apurinic/apyrimidinic endonuclease-like endonuclease (APE). In this study, we report a novel non-LTR retrotransposon family Dualen, identified from the Chlamydomonas reinhardtii genome. Dualen encodes two endonucleases, RLE and APE, with RT, ribonuclease H, and cysteine protease. Phylogenetic analyses of the RT domains revealed that Dualen is positioned at the midpoint between the early-branched and the recently branched groups. In the APE tree, Dualen was branched earlier than the I group and the Jockey group. The ribonuclease H domains among the Dualen family and other non-LTR retrotransposons are monophyletic. Phylogenies of three domains revealed the monophyly of the Dualen family members. The domain structure and the phylogeny of each domain imply that Dualen is a retrotransposon conserving the domain structure just after the acquisition of APE. From these observations, we discuss the evolution of domain structure of non-LTR retrotransposons.
Mass spectrometry of the M. smegmatis proteome: Protein expression levels correlate with function, operons, and codon bias
Authors: Wang Rong , Prince John T. , Marcotte Edward M.
Published: August 2005

The fast-growing bacterium Mycobacterium smegmatis is a model mycobacterial system, a nonpathogenic soil bacterium that nonetheless shares many features with the pathogenic Mycobacterium tuberculosis, the causative agent of tuberculosis. The study of M. smegmatis is expected to shed light on mechanisms of mycobacterial growth and complex lipid metabolism, and provides a tractable system for antimycobacterial drug development. Although the M. smegmatis genome sequence is not yet completed, we used multidimensional chromatography and tandem mass spectrometry, in combination with the partially completed genome sequence, to detect and identify a total of 901 distinct proteins from M. smegmatis over the course of 25 growth conditions, providing experimental annotation for many predicted genes with an ∼5% false-positive identification rate. We observed numerous proteins involved in energy production (9.8% of expressed proteins), protein translation (8.7%), and lipid biosynthesis (5.4%); 33% of the 901 proteins are of unknown function. Protein expression levels were estimated from the number of observations of each protein, allowing measurement of differential expression of complete operons, and the comparison of the stationary and exponential phase proteomes. Expression levels are correlated with proteins' codon biases and mRNA expression levels, as measured by comparison with codon adaptation indices, principle component analysis of codon frequencies, and DNA microarray data. This observation is consistent with notions that either (1) prokaryotic protein expression levels are largely preset by codon choice, or (2) codon choice is optimized for consistency with average expression levels regardless of the mechanism of regulating expression.
Social recognition memory requires two stages of protein synthesis in mice
Authors: Richter Karin , Wolf Gerald , Engelmann Mario
Published: August 2005

Olfactory recognition memory was tested in adult male mice using a social
discrimination task. The testing was conducted to begin to characterize the
role of protein synthesis and the specific brain regions associated with
activity in this task. Long-term olfactory recognition memory was blocked when
the protein synthesis inhibitor anisomycin was injected 20 min before,
immediately after, or 6 h after sampling. No effect was observed when
anisomycin was administered 3 h or 18 h after sampling. Immunohistochemical
analysis of Fos expression revealed that sampling-like exposure to a juvenile
increased the activity of a subset of cells in the accessory olfactory bulb
and the brain areas that are associated with it. Additionally, increased Fos
expression was measured in the main olfactory bulb and the piriform cortex,
whereas no signs of activation were seen in the cortical nucleus of the
amygdala, all components of the main olfactory system. No increases in Fos
immunoreactivity were observed after 4 h. Our data suggest that long-lasting
olfactory recognition memory requires two stages of protein synthesis. The
first stage takes place within 1–2 h and the second stage between
6–7 h after sampling. The first but not the second stage is paralleled
by an increase in the number of Fos-immunoreactive cells in brain areas
associated with both the main and accessory olfactory systems. It therefore
appears that the role of the second stage of protein synthesis in recognition
memory depends on the integrity of the first stage of protein synthesis.
Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification
Authors: Nakagawa Koji , Kuzumaki Noboru
Published: August 2005

Megakaryoblastic leukemia 1 (MKL1) was originally identified as a gene translocated in megakaryoblastic leukemia. It has been shown that MKL1 functions as a RhoA‐regulated transcriptional coactivator of serum response factor (SRF). In order to identify a protein that regulates the function of MKL1, we performed yeast two‐hybrid screening and isolated cDNA that encodes UBC9, an E2 enzyme of small ubiquitin‐related modifier‐1 (SUMO‐1), as an MKL1‐binding protein. UBC9 was found to physically interact with MKL1 by GST pull‐down assay, and MKL1 was covalently modified with SUMO‐1 in 293T cells and in vitro reconstitution system. MKL1 sumoylation is enhanced by either serum stimulation or co‐expression of constitutively active form of RhoA. Mutational analysis showed that lysine residues at 499, 576, and 624 are the major acceptor sites for SUMO‐1. In addition, reporter gene analysis revealed that mutation of the three sumoylation sites strongly enhances the transcriptional activity of MKL1. The covalent attachment of SUMO‐1 to MKL1 by gene fusion represses MKL1‐dependent transcription in a complementary manner. Finally, mutation of the sumoylation sites of MKL1 also enhances SRF‐dependent transcription without affecting MKL1‐SRF interaction. The combined results demonstrated that MKL1 is sumoylated and this modification represses transcriptional activity of MKL1.
SEI family of nuclear factors regulates p53‐dependent transcriptional activation
Authors: Watanabe‐Fukunaga Rie , Iida Satoshi , Shimizu Yusuke , Nagata Shigekazu , Fukunaga Rikiro
Published: August 2005

SEI family proteins, p34SEI‐1 and SEI‐2(TRIP‐Br2), are nuclear factors that are implicated in cell cycle regulation through interaction with CDK4/CyclinD and E2F‐1/DP‐1 complexes. Here we report that the SEI family proteins regulate transcriptional activity of p53 tumor suppressor protein. Expression of SEI‐1, SEI‐2 or SEI‐3 strongly stimulates p53‐dependent gene activation in HeLa and U2OS cells but not in p53‐deficient Saos2 or p53‐knockdown HeLa cells. SEI proteins possess an intrinsic transactivation activity, interact with the coactivator CREB‐binding protein, and cooperate synergistically with the ING family of chromatin‐associated proteins to stimulate the transactivation function of p53. Doxycycline‐induced expression of SEI proteins results in activation of the p21 gene and inhibition of cell growth, but the growth arrest was not suppressed by the siRNA‐mediated knockdown of the endogenous p53 protein. These results indicate that the SEI family of nuclear proteins regulates p53 transcriptional activity and a p53‐independent signaling pathway leading to growth inhibition.
The influence of ambient and elevated ozone concentrations on photosynthesis in Populus nigra
Authors: REICHENAUER T. , BOLHÀR‐NORDENKAMPF H. R. , EHRLICH U. , SOJA G. , POSTL W. F. , HALBWACHS F.
Published: August 2005

Light‐saturated net leaf photosynthesis (Asat), CO2 response curves (A/Ci), current photochemical capacity (Fv/Fm) and pigment contents were measured in leaves of Populus nigra (Clone T107) which had been exposed to ozone stress in open‐top chambers for the entire growth period. Surprisingly, not only elevated (ao+, i.e. ambient air + 50 mm3 m−3 ozone) but also ambient (aa) ozone concentrations led to a reduction in Asat, in comparison with leaves exposed to air containing almost no ozone (cf−, i.e. charcoal filtered ambient air). The very small change in leaf conductance (g1) indicated that the decrease in Asat was not due to stomatal limitation. This finding was supported by the fact that, a decrease in carboxylation efficiency (CE) correlated with a loss in Asat. In comparison to cf− leaves, aa leaves showed no change in current photochemical capacity (Fv/Fm) throughout the whole experiment. However, a marked decline in Fv/Fm in ao+ leaves was observed at a time when Asat and CE were already decreased by about 45% and 60% respectively.

As the chlorophyll b content of leaves is known to correlate with the amount of LHC and PSII centres, it was used to normalize fluorescence parameters in relation to PSII centres present. The normalized values for Fm and F0 increased with the dosage of ozone in ao+ leaves but not in aa leaves, indicating a change of the pigment content of PSII in the former, but not in the latter.

These data led to the conclusion that ozone interacts primarily with components of the Calvin cycle, which results in a decrease in Asat, with subsequent feedback on the current photochemical capacity of PSII centres.
Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children
Authors: Waser M. , Von Mutius E. , Riedler J. , Nowak D. , Maisch S. , Carr D. , Eder W. , Tebow G. , Schierl R. , Schreuer M. , Braun‐Fahrländer C. ,   The ALEX Study team
Published: August 2005

Background:  An increasing number of studies report pet exposure to be associated with lower risk of asthma and allergies. This ‘protective pet effect’ has been suggested to result from a modified T‐helper (Th)2‐cell response, or because of increased microbial load in homes where pets are kept. We examined the associations between pet contact and the occurrence of asthma and allergies in children of the rural Allergy and Endotoxin (ALEX) population, taking farm animal contact, endotoxin and cat allergen levels in mattress dust into account.

Methods:  Information about contact with pets and farm animals, asthma and allergy were collected for 812 children by a standardized parents’ questionnaire and an interview. Mattress dust endotoxin and cat allergen levels as well as specific IgE and IgG4 antibodies to Fel d1 were determined.

Results:  Current contact with dogs was inversely associated with diagnosed hay fever (OR 0.26, 95% CI 0.11–0.57), diagnosed asthma (OR 0.29, 95% CI 0.12–0.71), sensitization to cat allergen (OR 0.48, 95% CI 0.23–0.99) and to grass pollen (OR 0.55, 95% CI 0.33–0.94), but not with increased IgG4 levels. Early and current contact with cats were associated with reduced risk of wheezing (OR 0.48, 95% CI 0.23–1.00, and OR 0.49, 95% CI 0.26–0.92, respectively) and grass pollen sensitization. Adjustment for farm animal contact but not for endotoxin and cat allergen exposure attenuated these associations and the effect of pet was stronger among farmers’ children.

Conclusion:  Although pet exposure was very frequent in this rural population, the inverse relation between current dog contact, asthma and allergy was mostly explained by simultaneously occurring exposure to stable animals or was restricted to farm children. In addition, a subtle form of pet avoidance may contribute to the protective effect of pet.
A genome‐wide screen on the genetics of atopy in a multiethnic European population reveals a major atopy locus on chromosome 3q21.3
Authors: Kurz T. , Altmueller J. , Strauch K. , Rüschendorf F. , Heinzmann A. , Moffatt M. F. , Cookson W. O. C. M. , Inacio F. , Nürnberg P. , Stassen H. H. , Deichmann K. A.
Published: August 2005

Background:  Dissecting complex diseases in underlying distinct traits and studying these for their genetic basis might enhance the power as well as the specificity, of detection of disease genes. These phenoypes are known as intermediate phenotypes.

Objective:  We were interested in the atopic basis of asthma, and used the sensitization to mite (Dermatophagoides pteronyssinus) allergens as a pathophysiologically important intermediate phenotype.

Methods:  This time we performed a genome‐wide scan based on the same already used multiethnic European population consisting of 82 nuclear families with at least two affected siblings. We carried out nonparametric as well as parametric MOD‐score analyses based on the genotypes of 603 microsatellite markers.

Results:  In comparison with our first genome‐wide candidate region search three novel regions additionally appeared to be significant. We obtained significant results for the region 2p12 with a MOD score of 3.35 and for the region 16q21 with a MOD score of 4.18. The most significant result was found for the region 3q21.3 with the same microsatellite marker, which showed significant linkage to atopic dermatitis (AD) in another study with a MOD score of 4.51 and an nonparametric linkage analysis (NPL) of 4.00.

Conclusion:  Our findings indicate that atopy, allergic asthma, allergic rhinitis and AD on the one hand are distinct traits on both the clinical and genetic basis, but on the other hand, our results also underline that these traits are closely related diseases concerning the atopic basis of the traits.
The autologous serum skin test in the follow‐up of patients with chronic urticaria
Authors: Fusari A. , Colangelo C. , Bonifazi F. , Antonicelli L.
Published: August 2005

Background:  The presence of anti‐FcεRI and anti‐IgE autoantibodies in a subset of patients with chronic urticaria suggests their aetiopathogenetic role. In clinical practice, the presence of these antibodies is usually considered when the autologous serum skin test (ASST) is positive.

Aims:  To evaluate if the positive ASST follows up the activity of chronic urticaria.

Methods:  Autologous serum skin test and thyroid autoantibody detection were performed in 82 patients with chronic urticaria and repeated 1 year later, when the vast majority of patients were symptom‐free. Twenty patients with Hashimoto thyroiditis (HT), who had never suffered from urticaria, represented the control group.

Results:  At the start of the study, the prevalence of positive ASST was 46.6%. The association of HT–urticaria was 29.3%. ASST was positive in 62 and 39% of patients with and without HT, respectively (P > 0.05 ns). One year later, 28 of 34 patients with a positive ASST were symptom‐free, but 50% of them were positive for ASST. The ASST was positive in 86.7 and 8% of patients with and without HT, respectively (P < 0.001). In the control group, ASST was always negative.

Conclusions:  The co‐existence of autoimmune thyroiditis with chronic urticaria seems to induce a significant difference in the persistence of a positive ASST. Consistent with previous reports, a positive ASST correlates with disease exacerbation in chronic urticaria patients without thyroiditis. In patients with thyroiditis and urticaria, positive ASST persists even after the urticaria has disappeared, thus questioning whether a positive ASST to be a surrogate marker of the functional role of anti‐FcεRI and anti‐IgE autoantibodies.
Prevalence of nasal polyposis in France: a cross‐sectional, case–control study
Authors: Klossek JM. , Neukirch F. , Pribil C. , Jankowski R. , Serrano E. , Chanal I. , El Hasnaoui A.
Published: August 2005

Background:  The prevalence of nasal polyposis (NP) has never been established in France due to the lack of diagnostic tools for population‐based studies.

Methods:  Using a recently validated questionnaire/algorithm (90% specificity and sensitivity) in a population‐based random sample, the present cross‐sectional, case–control study allowed to determine NP prevalence and describe the principal aspects of NP epidemiology. A total of 10 033 subjects (≥18 years) were screened. After identification of subjects with NP and those without, another questionnaire was submitted to NP patients only for further data collection. Controls were individuals without NP, matched by gender and age to NP patients.

Results:  Nasal polyposis prevalence was 2.11% (95% CI 1.83–2.39). NP patients (n = 212, 45% males) were aged 49.4 ± 17.6 years. No gender preponderance was observed, but NP tended to increase with age. Mean duration of nasal symptoms was 22.4 ± 15.7 years. Among the 145 patients having already seen a doctor for their symptoms, 77.2% have been referred to a specialist, and 18.6% had a diagnosis of NP. Rhinorrhoea was reported by 39.9% of NP patients, blocked nose by 30.8%, and anosmia by 28.9%. Only 6.9% reported facial discomfort while 24.6% complained about general discomfort. Most NP patients (61.3%) had a pharmacological treatment, a nasal spray for the major part (76.9%).

Conclusion:  The present study provides valuable and reliable information on NP epidemiology in France; the collected information are in accordance with most published international data.
Maximum circumferential stress criterion applied to orthotropic materials
Authors: CARLONI C. , NOBILE L.
Published: August 2005

The topic of the paper is the extension of the Maximum Circumferential Tensile Stress Criterion to orthotropic materials, to obtain the crack initiation angle and the fracture loci. It includes the effects of orthotropy, load biaxiality and non‐singular terms. It requires the solution of the elastostatic problem of an orthotropic plate having a central inclined crack and subjected at infinity to a uniform biaxial load. It is assumed that the crack line does not coincide with an axis of elastic symmetry of the body. The original problem has been transformed by rotation into a system of coordinates with one axis along the crack. The effects of the rotation of the reference system on the stress–strain equations as well as on the equilibrium equations have been considered. The stress field is represented in terms of two potential functions and the crack problem is solved by means of the superposition principle.
Antiepileptic Drug Therapy: General Treatment Principles and Application for Special Patient Populations
Authors: Schachter Steven C.
Published: August 2005

Summary: Over the past 10 years, the goal of treating epilepsy has evolved from attaining complete control of seizures, regardless of medication‐related side effects or psychosocial problems, to enabling the patient to lead a lifestyle consistent with his or her capabilities. The recent introduction of new medications has brought hope to patients who have previously been unable to function optimally because of refractory seizures or side effects. A rational approach to selecting antiepileptic drug (AED) therapy for a particular patient would require a detailed understanding of the underlying cause(s) of seizures in that patient. Unfortunately, this is often not possible. Furthermore, currently available AEDs have been tested on the basis of seizure type rather than etiology. Nevertheless, an individualized empirical approach based on an open dialog with the patient and perseverance is often successful. There have also been significant advances in the understanding of seizures at the cellular level, notably in the role of γ‐aminobutyric acid. Medical, social, and psychosocial issues relevant to particular patient populations (such as women of childbearing age and elderly patients) also must be considered when treatment plans are formulated. The recent addition of new AEDs, with unique mechanisms of action and favorable pharmacokinetic and tolerability profiles, has greatly widened the range of therapeutic options for patients.
Temporal Lobe Epilepsy Surgery with Limited Resources: Results and Economic Considerations
Authors: Campos M. G. , Godoy J. , Mesa M.T. , Torrealba G. , Gejman R. , Huete I.
Published: August 2005

Summary: This study evaluates the surgical outcome of patients with medically refractory temporal lobe epilepsy (TLE) who underwent anterior temporal lobe lobectomy (ATL) based on data derived from noninvasive studies and assesses the economic costs entailed at a newly created epilepsy program in Chile. Seventeen ATL candidates underwent a presurgical evaluation. This included outpatient brain MRI and neuropsychological testing and inpatient scalp/sphenoidal prolonged video‐EEG monitoring. There were 10 females and 7 males, with a mean age of 23.8 years and a mean duration of seizure disorder of 12 years. Patients with congruent data localizing the seizure focus to one anterotemporal region underwent ATL. Seven patients underwent a left‐side ATL and 10 patients a right‐side ATL. The histopathological findings showed a lowgrade tumor in six patients, hippocampal sclerosis in five, neuronal migration disorder in four, and cavernous angiomas in two patients. The mean follow‐up period was 29·1 months. Seizure outcome was assessed with Engel's classification: class I, no seizures or only auras; class II, rare seizures; class III, >90% seizure reduction; class IV, <90% seizure reduction. Fifteen patients are now in class I, one patient in class II, and one in class IV. The total cost, including evaluation and surgery, was equivalent to US$ 5,020. Thus, well‐selected TLE patients can derive maximal benefit from ATL after a noninvasive presurgical evaluation. This finding is of great significance for the creation of epilepsy surgery programs in developing countries.