bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of Chlorophyll(ide) Fluorescence Yield Induced by a Short Light Pulse as a Probe to Monitor the Early Steps of Etioplast Phototransformation in Dark‐Grown Leaves
Authors: Eullaffroy Philippe , Popovic Radovan , Franck Fabrice
Published: January 2008

The fluorescence yield of chlorophyll(ide) (Chl[ide]) excited by weak modulated light was recorded at room temperature during a 2 h period after a short actinic light pulse that transformed all photoactive protochlorophyllide in dark‐grown barley leaves. A typical pattern of fluorescence yield variations was found whatever the age of the leaf but with age‐dependent changes in rates. Its successive phases were related to the Chl(ide) spectral shifts observed in low‐temperature emission spectra. The fluorescence yield started at a high level and strongly declined during the formation of Chlide695from Chlide668within a few seconds. It increased to a transient maximum during the Shibata shift (15–25 min) that resulted in Chl(ide)682. A final, slow decrease to a steady state occurred during the final red shift to Chl685. Pretreatments with δ‐aminolevulinic acid, chloramphenicol or 1, 10‐phenanthroline resulted in correlated modifications of Chl(ide) fluorescence yield transients and shifts of the low‐temperature Chl(ide) emission band. The complex response of the final decrease phase of the fluorescence yield to these compounds suggests that it results both from the assembly of photosynthetic Chl proteins and from the reorganization of the etioplast membrane system. From these results it is concluded that continuous recordings of Chl(ide) fluorescence yield after a short light pulse represent a useful tool to monitor the kinetics of pigment–protein organization and primary thylakoid assembly triggered by Pchlide photoreduction.
Tryptophan Photolysis Leads to a UVB‐lnduced 66 kDa Photoproduct of Ribulose‐1,5 Bisphosphate Carboxylase/Oxygenase (Rubisco) In Vitro and In Vivo
Authors: Gerhardt Karen E. , Wilson Michael I. , Greenberg Bruce M.
Published: January 2008

Abstract— Proteins are vulnerable to environmental UVB (290‐320 nm) because aromatic amino acids, particularly Trp, absorb in this spectral region. We have shown previously that UVB impacts on ribulose‐l,5‐bisphosphate carboxylase/oxygenase (Rubisco), resulting in the formation of a 66 kDa photoproduct in vivo (Wilson et al, Plant Physiol. 109,221–229, 1995). To determine if Trp photolysis is involved in the production of this specific protein photoproduct, the effects of UVB on a homogeneous preparation of Rubisco were examined. A UVB photoproduct of 66 kDa, identical to the in vivo product, was formed in vitro. The 66 kDa product was shown by immunological methods to be a cross‐link between a large subunit (53 kDa) and a small subunit (14 kDa). Time‐resolved Trp fluorescence was used to demonstrate that a Trp fluorescence signal is lost with kinetics that mirror the rate of formation of the 66 kDa photoproduct, indicating that a Trp photolysis step is involved in the mechanism of photoproduct formation. The relative rates of both Trp photolysis and 66 kDa photoproduct formation did not change with Rubisco concentration, consistent with a monomolecular reaction that would occur between sub‐units within a Rubisco holoenzyme complex. Finally, formation of the 66 kDa photoproduct was found to be pH dependent.
Electric‐Field Effects in 13‐Demethyl‐11,14‐Epoxyretinal‐Bacteriorhodopsin Films
Authors: Kolodner Paul , Lukashev Evgeniy P. , Ching Yuan‐chin , Rousso I. , Sheves M.
Published: January 2008

Abstract— We report the results of experiments on the application of electric fields across thin, dry Alms of a bacteriorho‐dopsin (BR) analog pigment in which the retinal chro‐mophore has been replaced with 13‐demethyl‐11,14‐epoxyretinal. As previously observed in other BR variants with low Schiff‐base pK values, this pigment exhibits protonation and deprotonation of the Schiff base under an applied electric field, depending on the initial Schiff‐base protonation state or effective pH. At low effective pH, a fast (<200 μs) deprotonation reaction dominates. At high pH, an apparently different mechanism leads to Schiff‐base protonation on the time scale of seconds. Comparison of our results with a simple model suggests that the external field causes a shift in the pK of the Schiff base by1–2 pH units.
Laser Flash Photolysis of Tolmetin: A Photoadiabatic Decarboxylation with a Triplet Carbanion as the Key Intermediate in the Photodecomposition
Authors: Sortino S. , Scaiano J. C.
Published: January 2008

Abstract— The transient photochemistry of tolmetin (TM), 5‐(p‐toluoyl)‐1‐methyl‐2‐pyrrolyacetic acid, a drug belonging to the nonsteroidal anti‐inflammatory class, has been studied in aqueous solution by using nanosecond laser flash photolysis techniques. The photoreactivity of TM is characterized by an adiabatic pathway involving a triplet carbanion as the key intermediate in the photodecarboxylation. A short‐lived triplet is proposed as the precursor of this transient species. A minor channel for laser photodecomposition involving photoionization has also been identified. This latter photoprocess occurs predominantly through a biphotonic mechanism.
Control by Ring Substitution of the Conformation Change Dynamics in Photochromic Polypeptides
Authors: Cooper Thomas M. , Natarajan Lalgudi V. , Miller Cory G.
Published: January 2008

Abstract— In order to develop new systems that couple photochromism with molecular conformation change, a series of spiropyrans having different ring substituents were attached to poly(L‐glutamic acid). The polypeptides were dissolved in hexafluoroisopropanol and dark adapted so that the dye was in the merocyanine form. Following adaptation by white light and dye photoconversion from the merocyanine to spiropyran forms, polypeptide dark‐adaptation kinetics were monitored by circular dichroism (CD) and dye dark adaptation was monitored by UV/ visible. Light adaptation caused a light‐induced coil‐to‐helix transition, with dark adaptation resulting in relaxation back to the coil. The dark‐adaptation rate constant measured by UV/visible was equal to that measured by CD, demonstrating close coupling between dye state and polypeptide conformation. By varying the substituents on the spiropyran ring, dark‐adaptation half lives were varied from less than a minute to 2 h, representing nearly three orders of magnitude.
Photohemolysis Sensitized by the Furocoumarin Imperatorin and Its Oxyfunctionatized Derivatives
Authors: Potapenko Alexander Ya. , Kyagova Alla A. , Andina Elena S. , Zhuravel Natalia N. , Lysenko Eugene P. , Möller Marianne , Stopper Helga , Adam Waldemar , Saha‐Möller Chantu R.
Published: January 2008

Abstract— The dark and photosensitized (366 nm) hemolytic effects of imperatorin and its photooxidation products, the hydroperoxides I and II as well as the corresponding alcohol of the hydroperoxide I (imperatorin alcohol), were studied on human erythrocytes. Imperatorin was shown to photosensitize hemolysis, its fluence (D) dependence of the rate of photohemolysis (V) followed the equation V = V0+ aD2+ bD1/2 in which V0 is the dark hemolysis rate and a and b are constants. At fluences below 200 kJ/m2 the main hemolytic contribution derives from the bD1/2 component, which is due to the in situ formation of the imperatorin hydroperoxides, while at fluences higher than 200 kJ/m2 the main contribution corresponds to the aD2 component due to the two‐photon damage of cell membranes. Hydroperoxides I and II induce oxyhemoglobin cross‐linking, as well as its conversion to methemoglobin and hemichrome. These reactions involve hydroxyl and alkoxy radicals, as the hemolysis and oxyhemoglobin conversion could be inhibited by t‐butanol and butylated hydrotoluene. For comparison, the dark hemolytic effect of the imperatorin alcohol was approximately 10‐fold less than of the hydroperoxides.
Spectral UV Irradiance on Vertical Surfaces: A Case Study
Authors: Webb Ann R. , Weihs P. , Blumthaler M.
Published: January 2008

Abstract— The UV spectral irradiance on horizontal and vertically oriented surfaces was measured throughout a cloudless day (18 July 1995) at Izana station, Tenerife, using a Bentham DTM300 spectroradiometer scanning from 290 to 500 nm in steps of 5 nm. Results show that irradiance measured on a horizontal surface is not proportional to irradiance on a vertical surface. The relation between the two depends upon orientation of the vertical surface, zenith angle and wavelength. At short UVB wavelengths surfaces directed toward the solar azimuth received their maximum irradiances much closer to solar noon than the maxima for longer wavelengths. Some vertical surfaces also received significantly more irradiance than the horizontal surface at long wavelengths during all but the central hours of the day, while at short wavelengths all vertical irradiances were less than the horizontal except for the measurements at the extreme ends of the day. Erythemally effective radiation followed the diurnal pattern of irradiations for short UVB wavelengths.
The Fluorescent Probe Prodan Characterizes the Warfarin Binding Site on Human Serum Albumin
Authors: Moreno F. , Cortijo M. , González‐Jiménez J.
Published: January 2008

Abstract— The fluorescent probe Prodan (6‐propionyl‐2‐dimethyl‐aminonaphthalene) binds with high affinity to human serum albumin (HSA). The spectral characteristics of the Prodan bound to the protein are very different from the free Prodan in solution. These differences allowed the spectra to be deconvoluted into log‐normal bands in order to quantify the bound and unbound ligand and to calculate the binding constant at different temperatures. From such temperature dependence, we found the binding to be exothermic with a van't Hoff enthalpy of ‐22.8 kJ mol‐1. Thermodynamic analysis suggests that the in teraction may be mainly caused by hydrophobic forces and electrostatic interactions. The above analysis of the spectra and the measures of the fluorescence polarization during the successive presence of six specific drugs suggest that the Prodan binding site corresponds with the warfarin binding site on HSA, whereas under the present experimental conditions the other characteristic binding sites of HSA were not affected. Thus, this fluorescent probe provides a rapid and simple means for the characterization of a specific binding site on HSA and also for detecting potential or nonspecific drug‐protein interactions.
Light Activates Reduction of Methotrexate by NADPH in the Ternary Complex with Escherichia coli Dihydrofolate Reductase
Authors: Chen Yong Qing , Gulotta Miriam , Cheung H. T. Andrew , Callender Robert
Published: January 2008

Abstract— Methotrexate (MTX), a strong inhibitor of dihydrofolate reductase (DHFR), has been widely used for chemotherapy for many types of cancer as well as for juvenile rheumatoid arthritis. It mimics folate substrates and binds tightly to the active site of DHFR, perhaps in a conformation close to the transition state of the folate catalyzed reaction. Absorption, fluorescence and ultrasensitive Raman difference spectroscopies show that light‐activated MTX reacts with NADPH in the enzyme active site, producing 5,8‐dihydromethotrexate (5,8‐dihydro‐MTX) and NADP+. The reaction, which proceeds with a hydride transfer between C4 (pro‐R side) of the nicotinamide ring and N5 of the pteridine ring, is similar to that between folate and NADPH except that the hydride is transferred to C6 in this case. Hence, MTX is catalytically competent in its excited state. Most experiments were performed on the Escherichia coli enzyme, but preliminary studies show that the reaction also occurs with human DHFR.
Ruby Laser Irradiation (694 nm) of Human Skin Biopsies: Assessment by Electron Spin Resonance Spectroscopy of Free Radical Production and Oxidative Stress during Laser Depilation
Authors: Haywood Rachel M. , Wardman Peter , Gault David T. , Linge Claire
Published: January 2008

Abstract Human skin biopsies (hair‐bearing scalp skin and non‐hair‐bearing breast skin) were treated with t‐butylhydro‐peroxide, irradiated with UV light (UVR) or irradiated with 694 nm ruby laser red light. Free‐radical production and oxidative stress were assessed with electron spin resonance spectroscopy (ESR) using the ascorbate radical as a marker. In comparison with both UVR and t‐butyl‐hydroperoxide (which readily induce the ascorbate radical in hair‐bearing and hairless skin), 694 nm red light does not result in the formation of the ascorbate radical in detectable concentrations. Spin‐trapping experiments with the spin trap 5,5‐dimethyl‐l‐pyrroline N‐oxide (DMPO) showed that while free radicals could be detected after treatment of skin with t‐butylhydroperoxide, radicals could not be trapped after laser treatment. Treatment of lasered skin (containing DMPO) with t‐bu‐tylhydroperoxide produced radical adducts as well as the ascorbate radical, demonstrating that the laser neither depletes endogenous ascorbate nor the preadministered spin trap. It is concluded that 694 nm red light does not induce oxidative stress in human skin in levels comparable either to t‐butyl hydroperoxide or UV light.
Laser Photolysis of Chromium(lll) Porphyrins in Toluene Solutions. Effects of Oxygen on the Photodissociation Yields of the Axial Ligands
Authors: Inamo Masahiko , Hoshino Mikio
Published: January 2008

The effects of oxygen on the photochemical reactions of chromium(III) porphyrins with axial nitrogenous bases in toluene are studied by nanosecond laser flash photolysis. The photodissociation of the axial bases is confirmed to occur via both the excited states 4S1 and 6T1 (and/or 4T1) on the basis of the effect of oxygen on the quantum yield of photoreaction.
13‐Acetoxy‐13‐desmethylretinal‐14‐3H: Synthesis and Interaction with Bacterioopsin
Authors: Seltzer Stanley
Published: January 2008

The title compound (4) was synthesized in three steps from 1,1‐dimethoxy‐7‐methyl‐9‐(2′,6′,6′‐trimethyl‐1‐cy‐clohexen‐1‐yl)‐4E,6E,8E‐nonatrien‐3‐one (1). Interaction of 4 with bacterioopsin produced a pigment absorbing at 573 nm, which, on long standing in the dark, moves to 406 nm, mirroring the behavior of nonradioactive 4 with bacterioopsin (S. Seltzer, J. Org. Chem. 60, 1189–1194, 1993). Compound 4 was designed to test for the involvement of a nucleophilic side chain, presumably asp‐212, in catalyzing the dark cis‐trans isomerization of bound retinal, through its attack at C‐13. Such a mechanism is anticipated to lead to a cross‐linked product where the nucleophile replaces the 13‐acetoxy group when 4 is substituted for the natural chromophore. The protein, reconstituted with 4, after extensive washing, solubilization in dimethylsulfoxide and extensive dialysis retains its radioactivity suggesting the establishment of a cross‐link. Solution in 6 M urea, however, results in substantial loss of radioactivity, suggesting that the unfolded labeled protein suffers hydrolysis of the very labile 13‐enolester group followed by proton exchange.
Fluorescence Studies of Lens Epithelial Cells and Their Constituents
Authors: Atherton Stephen J. , Lambert Chris , Schultz Joanne , Williams Natalie , Zigman Seymour
Published: January 2008

Steady‐state and time‐resolved fluorescence measurements have been made of human and rabbit lens epithelial cells and their total soluble protein. Excitation at 350 nm results in broad fluorescence spectra peaking at 450 nm and stretching into the visible past 650 nm. The fluorescence excitation spectra peak around 350 nm. We assign the species responsible for this absorption and fluorescence as NADPH. Because the absorption of near‐UV light (300–400 nm) is responsible for cell damage and death, we postulate that excited states of NADPH are implicated in the mechanisms of cell damage. Preirradia‐tion with 355 nm light leads to a loss of NADPH fluorescence but with no change in decay kinetics. Possible mechanisms for cell damage are explored.
(2+4)‐Cycloaddition with Singlet Oxygen.17O‐lnvestigation of the Reactivity of Furfuryl Alcohol Endoperoxide¶
Authors: Braun André M. , Dahn Hans , Gassmann Ernst , Gerothanassis Ioannis , Jakob Laurent , Kateva Jordanka , Martinez Claudia G. , Oliveros Esther
Published: January 2008

In earlier work, the use of furfuryl alcohol as a specific singlet oxygen acceptor was proposed because of the high ratio between the rate constants of chemical reaction and physical quenching. In contrast to furfuryl aldehyde, a number of products are formed by this type II photo‐oxidation of furfuryl alcohol. These products may be derived from the endoperoxide of furfuryl alcohol as a common intermediate. The present work focuses on the reactivity of this endoperoxide that was marked specifically by the use of17O2as a source for singlet oxygen. The analyses of the stable products, their yields and their labeling distribution reveal a strong solvent effect on the primary reaction pathways, and nucleophilic substitution reactions leading to hydroperoxide intermediates are dominant.
Preparation, Phototoxicity and Biodistribution Studies of Anti‐Carcinoembryonic Antigen Monoclonal Antibody‐Phthalocyanine Conjugates
Authors: Carcenac Magali , Larroque Christian , Langlois Rejean , van Lier Johan E. , Artus Jean‐Claude , Pelegrin Andre
Published: January 2008

Immunophototherapy of cancer combines the specificity of a monoclonal antibody (MAb) to an overexpressed tumor marker with the phototoxic properties of a conjugated dye. Aluminum tetrasulfophthalocyanine (AlPcS4) was covalently coupled to a 35A7 MAb directed against carcinoembryonic antigen (CEA) via a five‐carbon spacer chain (A1) to yield conjugates with a molar ratio ranging from 5 to 16 mol of AlPcS4 per mol of 35A7 MAb. Conjugates were labeled with radioiodine for characterization. The immunoreactivity of the conjugates, determined in a direct binding assay on CEA coupled to sepharose, was not modified by the coupled AlPcS4A1 molecules. In vivo, these conjugates were evaluated in nude mice bearing human colon carcinoma xenografts (T380). 35A7 MAb‐(AlPcS4A1)s, 35A7 MAb‐(AlPcS4A1,)12 and 35A7 MAb‐(AIPcS4A,)16 conjugates displayed a tumor uptake of 35 ± 5.0%, 40 ± 5.7% and 32 ± 3.3% of the injected dose per gram of tumor tissue, respectively, corresponding to an uptake of 97%, 104% and 91% as compared to that of the unconjugated 35A7 MAb. In each experimental group, the tumor‐to‐normal tissue ratios obtained with the conjugates were almost identical to those obtained with unconjugated 35A7 MAb. Average values of 1.8, 7 and about 30 were obtained for blood, liver and muscle, respectively. Phototoxic efficacy of the 35A7 MAb‐(AlPcS4A,)12 conjugate was demonstrated in vitro on the LoYo cell line giving a 91 % growth inhibition for a 2.50 μ/mL AlPcS4A1 concentration. We conclude that these conjugates demonstrate clear in vivo tumor‐seeking capacity and in vitro photocytotoxic properties. Such conjugates could thus be promising candidate drugs for clinical photodynamic therapy of cancers expressing CEA.
The ALCAM Shedding by the Metalloprotease ADAM17/TACE Is Involved in Motility of Ovarian Carcinoma Cells
Authors: Rosso Ombretta , Piazza Tiziana , Bongarzone Italia , Rossello Armando , Mezzanzanica Delia , Canevari Silvana , Orengo Anna Maria , Puppo Andrea , Ferrini Silvano , Fabbi Marina
Published: January 2008

Previous findings indicated that the activated leukocyte cell adhesion molecule (ALCAM) is expressed by tumors and plays a role in tumor biology. In this study, we show that ALCAM is shed from epithelial ovarian cancer (EOC) cells in vitro, leading to the generation of a soluble ALCAM (sALCAM), consisting of most of the extracellular domain. A similar sALCAM molecule was also found in the ascitic fluids and sera from EOC patients, suggesting that this process also occurs in vivo. sALCAM is constitutively produced by EOC cells, and this process can be enhanced by cell treatment with pervanadate, phorbol 12-myristate 13-acetate (PMA), or epidermal growth factor (EGF), a known growth factor for EOC. Pharmacologic inhibitors of matrix metalloproteinases (MMP) and of a disintegrin and metalloproteases (ADAM), and the tissue inhibitor of metalloproteinase-3, significantly inhibited sALCAM release by EOC cells. The ADAM17/TACE molecule was expressed in EOC cell lines and ADAM17/TACE silencing by specific small interfering RNA–reduced ALCAM shedding. In addition, inhibitors of ADAM function blocked EOC cell motility in a wound-healing assay. Conversely, a recombinant antibody blocking ALCAM adhesive functions and inducing ALCAM internalization enhanced EOC cell motility. Altogether, our data suggest that the disruption of ALCAM-mediated adhesion is a relevant step in EOC motility, and ADAM17/TACE takes part in this process, which may be relevant to EOC invasive potential. (Mol Cancer Res 2007;5(12):1246–53)
Inhibition of Intestinal Polyposis with Reduced Angiogenesis in ApcMin/+ Mice Due to Decreases in c-Myc Expression
Authors: Yekkala Krishna , Baudino Troy A.
Published: January 2008

The c-myc oncogene plays an important role in tumorigenesis and is frequently deregulated in many human cancers, including gastrointestinal cancers. In humans, mutations of the adenomatous polyposis coli (Apc) tumor suppressor gene occur in most colorectal cancers. Mutation of Apc leads to stabilization of β-catenin and increases in β-catenin target gene expression (c-myc and cyclin D1), whose precise functional significance has not been examined using genetic approaches. ApcMin/+ mice are a model of familial adenomatous polyposis and are heterozygous for an Apc truncation mutation. We have developed a model for examining the role of c-Myc in Apc-mediated tumorigenesis. We crossed c-myc+/− mice to ApcMin/+ to generate ApcMin/+ c-myc+/− animals. The compound ApcMin/+ c-myc+/− mice were used to evaluate the effect of c-myc haploinsufficiency on the ApcMin/+ phenotype. We observed a significant reduction in tumor numbers in the small intestine of ApcMin/+ c-myc+/− mice compared with control ApcMin/+ c-myc+/+ mice. In addition, we observed one to three polyps per colon in ApcMin/+ c-myc+/+ mice, whereas only two lesions were observed in the colons of ApcMin/+ mice that were haploinsufficient for c-myc. Moreover, reduction in c-myc levels resulted in a significant increase in the survival of these animals. Finally, we observed marked decreases in vascular endothelial growth factor, EphA2, and ephrin-B2 expression as well as marked decreases in angiogenesis in intestinal polyps in ApcMin/+ c-myc+/− mice. This study shows that c-Myc is critical for Apc-dependent intestinal tumorigenesis in mice and provides a potential therapeutic target in the treatment of colorectal cancer. (Mol Cancer Res 2007;5(12):1296–303)
Defective in Mitotic Arrest 1/Ring Finger 8 Is a Checkpoint Protein That Antagonizes the Human Mitotic Exit Network
Authors: Tuttle Robyn L. , Bothos John , Summers Matthew K. , Luca Francis C. , Halazonetis Thanos D.
Published: January 2008

A molecular pathway homologous to the S. cerevisiae mitotic exit network (MEN) and S. pombe septation initiation network has recently been described in higher eukaryotes and involves the tumor suppressor kinase LATS1 and its subunit MOB1A. The yeast MEN/septation initiation network pathways are regulated by the ubiquitin ligase defective in mitotic arrest 1 (Dma1p), a checkpoint protein that helps maintain prometaphase arrest when cells are exposed to microtubule poisons. We identified here the RING domain protein ring finger 8 (RNF8) as the human orthologue of the yeast protein Dma1p. Like its yeast counterparts, human DMA1/RNF8 localized at the midbody and its depletion by siRNA compromised mitotic arrest of nocodazole-treated cells in a manner dependent on the MEN. Depletion of MAD2, a spindle checkpoint protein, also compromised mitotic arrest, but in a MEN-independent manner. Thus, two distinct checkpoint pathways maintain mitotic arrest in cells exposed to microtubule poisons. (Mol Cancer Res 2007;5(12):1304–11)
Constructing Gene Networks Using Variational Bayesian Variable Selection
Authors: Tienda-Luna Isabel M. , Yin Yufang , Huang Yufei , Ruiz Padillo Diego P. , Carrion Perez Maria C. , Wang Yufeng
Published: January 2008

We propose a Bayesian approach for constructing gene networks based on microarray data. Especially, we focus on Bayesian methods that can provide soft (probabilistic) information. This soft information is attractive not only for its ability to measure the level of confidence of the solution, but also because it can be used to realize Bayesian data integration, an extremely important task in gene network research. We propose a variable selection formulation of gene regulation and develop an inference solution based on a variational Bayesian expectation maximization (VBEM) learning rule. This solution has better performance and lower complexity than the popular Monte Carlo sampling techniques. In addition, we develop a method to incorporate the often needed constraints into the VBEM algorithm, making it much more suitable for common cases of small data size. To further illustrate the advantage of the VBEM algorithm, we demonstrate a Bayesian data integration scheme using the soft information obtained from the VBEM algorithm. The efficacy of the proposed VBEM algorithm and the corresponding Bayesian data integration scheme is evaluated on both simulated data and the yeast cell cycle microarray data sets.
Analog-Based Free Testosterone Test Results Linked to Total Testosterone Concentrations, Not Free Testosterone Concentrations
Authors: Fritz Kristofer S , McKean Alastair J S , Nelson Jerald C , Wilcox R Bruce
Published: January 2008

Background: Analog-based free testosterone test results, sex hormone binding globulin (SHBG) concentrations, and total testosterone concentrations are somehow related. This study used new experiments to clarify these relationships.

Methods: An analog-based free testosterone immunoassay and a total testosterone immunoassay were applied to well-defined fractions of serum testosterone. First, they were applied to the 2 fractions (retentate and dialysate) of normal male serum obtained by equilibrium dialysis. Second, they were applied to covaried concentrations of SHBG and total testosterone. Third, they were applied to decreasing concentrations of SHBG and protein-bound testosterone, offset by increasing concentrations of protein-free testosterone, while total testosterone was held constant.

Results: The analog-based free testosterone assay and the total testosterone assay detected and reported serum testosterone test results from serum retentate, whereas neither assay detected the free testosterone in serum dialysate. Test results reported by the analog-based free testosterone assay followed varied concentrations of SHBG and total testosterone. When total testosterone was held constant, however, analog-based free testosterone test results did not follow varied concentrations of serum proteins or of free testosterone.

Conclusion: An analog-based free testosterone immunoassay reported free testosterone test results that were related to total testosterone concentrations under varied experimental conditions. This alleged free testosterone assay did not detect serum free testosterone (the test results it reported were nonspecific) and should not be used for this purpose.
Do JPEG Encoders Differ Significantly in Quality?
Authors: Cunningham Jeffrey
Published: January 2008

The claim is often made that JPEG encoders vary a great deal in their abilities to produce small, acceptable quality JPEG files. It has often been asserted that PhotoShop produces poor quality, “bloated” JPEGs when compared with PaintShop Pro, ImageOptimizer, or even PhotoShop's poor web-cousin ImageReady. For web use, where excessive download times may mean the difference between someone spending serious time browsing a site or hitting their back button in exasperation, this is an important issue. And having spent many hours building up a website that has been perhaps generously referred to as a “graphics-pig”, I myself had an interest in finding out if these aims were true. So I did some research, wrote an analysis code and performed a number of experiments from which emerged some useful results.
Digital Imaging for Photographic Collections: Foundations for Technical Standard
Authors: Dale Robin
Published: January 2008

The goal of this project report, sponsored by The National Endowment for the Humanities, Division of Preservation and Access, is “to offer some guidance to libraries, archives, and museums in their efforts to convert photographic collections to digital form.” To date, there are no standards for measuring the quality of digital images created from photographs. Therefore, this report is primarily concerned with developing tools to measure image quality. Other technical and managerial issues related to digital imaging projects in general are also addressed.
Digital Culture: Maximising the Nation's Investment, a Synthesis of JISC/NPO Studies on the Preservation of Electronic Records
Authors: Meyer Lars
Published: January 2008

This publication serves a guide to the issues and challenges associated with the preservation of electronic records, regardless of the kind media on which they are stored. The intended audience is anyone involved in the creation, delivery, or preservation of electronic records. The report focuses on administrative and managerial issues rather than specific technical solutions.
Phosphorylation of SNAP-25 at Ser187 Mediates Enhancement of Exocytosis by a Phorbol Ester in INS-1 Cells
Authors: Shu Yilong , Liu Xin , Yang Yan , Takahashi Masami , Gillis Kevin D.
Published: January 2008

Activation of diacylglycerol (DAG) signaling pathways with phorbol esters dramatically enhances Ca2+-triggered exocytosis from both endocrine cells and neurons, however the relevant targets of DAG are controversial. A possible effector mechanism for this signaling pathway is phosphorylation of SNAP-25 (25 kDa synaptosome-associated protein) at Ser187 by PKC. Here, we investigated the role of Ser187 in the enhancement of exocytosis by the phorbol ester PMA (phorbol 12-myristate 13-acetate). We used patch-clamp measurements of membrane capacitance together with photorelease of caged-Ca2+and membrane depolarization to study exocytosis. Expression of the nonphosphorylatable S187C SNAP-25 mutant did not attenuate the enhancement of exocytosis by PMA in either bovine chromaffin cells or the INS-1 insulin-secreting cell line. To test the effects of Ser187 mutations under conditions in which the endogenous SNAP-25 is disabled, we expressed botulinum toxin serotype E to cleave SNAP-25 in INS-1 cells. Coexpression of a toxin-resistant mutant (TR), but not wild-type SNAP-25, was able to rescue PMA-modulated exocytosis. Coexpression of the toxin with the TR-S187C SNAP-25 mutant was able to completely block the enhancement of exocytosis by PMA in response to photoelevation of [Ca2+]ito low μmlevels or to a depolarizing train. The phospho-mimetic S187E mutation enhanced the small, fast burst of exocytosis evoked by photelevation of Ca2+, but, like PMA, had smaller effects on exocytosis evoked by a depolarizing train. This work supports the hypothesis that phosphorylation of Ser187 of SNAP-25 by PKC is a key step in the enhancement of exocytosis by DAG.
THE EUROPEAN ASSOCIATION FOR CHILDREN IN HOSPITAL (EACH) CHARTER
Authors: Brandazzi Giuliana Filippazzi
Published: January 2008

The European Association for Children in Hospital (EACH) Charter, adopted in 1988 in Leiden, Netherlands, is a list of the rights of all children before, during, and after a hospital stay. The rights mentioned in the charter apply to all sick children regardless of their illness, age, or disability, their origin or social or cultural background, or any possible reason for treatment, whether as inpatients or outpatients.

All rights mentioned in the charter and all measures derived from it must, in the first place, be in the best interests of children and enhance their well-being.

The rights/needs of children in hospital include accommodation for parents, support for parents and children, informed participation in the decision-making process, and care in pediatric units by staff who are adequately trained.

The EACH Charter is in line with corresponding and binding rights stipulated at the United Nations Convention on the Rights of the Child and refers to children as being aged 0 to 18 years.

Some of the goals of the EACH Charter are still unachieved, such as: the right of children to have their parents with them in the hospital;painless medical treatment;to receive information they can understand;the possibility for children to have their own say in the care plan;opportunities for play and education in the ward;to have contact with peers; anda healing environment.
Early beaten-copper pattern: its long-term effect on intelligence quotients in 95 children with craniosynostosis
Authors: van der Meulen Jacques , van der Vlugt Joris , Okkerse Jolanda , Hofman Bert
Published: January 2008

Object

The aim of this study was to analyze the presence of beaten-copper patterns (BCPs) in children with craniosynostosis before 18 months of age and its association with their IQ at a later age.

Methods

The authors conducted a retrospective analysis of 538 cephalograms (obtained at a mean patient age of 1.16 years) from 95 patients. The BCP location and percentage of brain surface area covered were related to patient IQ scores obtained by the same psychologist using the Snijders–Oomen Nonverbal Intelligence Test–Revised, 51/2–17, and the Wechsler Preschool and Primary Scale of Intelligence–Revised.

Results

As much as 71.6% of patients presented with a BCP before 18 months of age (mean surface area of BCP 20.3%, 93% of patients presented with bilateral BCPs). The mean IQ was 95 ± 21.3 (range 50–136) at a mean patient age of 8.4 ± 2.59 years. There was a significant increase in the surface area covered by BCPs in the first 3 years of life (p < 0.001) and a significant difference in IQs between syndromic (30 cases, mean IQ 88.9) and nonsyndromic craniosynostosis cases (54 cases, mean IQ 98.9, p = 0.03). No significant correlation was found between IQ and the appearance of BCPs on presurgery radiographs (Pearson correlation coefficient = 0.143, p = 0.19) or their location (Spearman rank correlation coefficient = 0.091, p = 0.45). The BCPs appeared predominantly in the occipital region (41.1%).

Conclusions

Although the radiographic appearance of a BCP before the age of 18 months is an uncommon finding in healthy children, a craniosynostosis study group showed a preoperative BCP incidence of 71.6% and an increased incidence during the period of rapid brain expansion in the first 3 years of life. Note, however, that the presence of such a pattern had no significant long-term effect on patient intelligence levels.
Genetic alterations in a papillary glioneuronal tumor
Authors: Faria Claudia , Miguéns José , Antunes João Lobo , Barroso Cândida , Pimentel José , Martins Maria Do Carmo , Moura-Nunes Vasco , Roque Lúcia
Published: January 2008

✓Papillary glioneuronal tumors (PGNTs) are rare lesions of the central nervous system, and no information exists on the genetic alterations in these neoplasms. The authors report on such a case in a child. Genetic studies revealed that the tumor was characterized by gains and structural alterations involving only chromosome 7 with breakpoints at 7p22. By using comparative genomic hybridization, the authors observed a high-level amplification region at 7p14~q12. Fluorescence in situ hybridization with a probe for EGFR revealed that this gene was not amplified. Similar to other patients with PGNTs, the patient in the present case fared well. From a genetic point of view the data in the present case are in accordance with previous findings of EGFR amplifications as uncommon in low-grade gliomas and gangliogliomas. Recurrent rearrangements of chromosome 7 have been noted in other mixed glioneuronal tumors. The data in this case suggest that genes located at chromosome 7 can also be involved in the pathogenesis of PGNT. In clinical terms it will be especially important to corroborate, through the analysis of further cases, the involvement of the chromosome 7p22 locus, a region where glial and neuronal linked genes (RAC1 and NXPH1) are known to be located.
Secular changes in body height and weight of Portuguese boys over one century
Authors: Cardoso Hugo F. V.
Published: January 2008

This study examines secular changes in attained height and weight in student boys from a military boarding school (Colégio Militar) in Lisbon, Portugal. Data for 1899–1906, 1929–1936, 1961–1966, and 1999–2006 obtained from the archives and medical files of the Colégio Militar were used in this study. In a century Portuguese boys increased in height by 10.5 cm at age 10 to 19.1 cm at age 14, at a mean increase of 1.54 cm per decade. The gain in weight was between 8.7 and 18.9 kg for 10‐ and 14‐year‐old boys, respectively, at a mean increase of 1.54 kg per decade. In the same period, age at peak height and weight velocity advanced ∼2 years, showing an acceleration of developmental tempo. However, most of the real gain in height and weight and the decrease in pubertal age occurred after 1961–1966. This mirrors major improvements in social and economic conditions that initiated in Portugal in the 1960s, and then by political events in the 1970s that promoted further progress. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.
Investigation of the stereoselectivity of an anti‐amino acid antibody using molecular modeling and ligand docking
Authors: Ranieri Daniel I. , Corgliano Danielle M. , Franco Elliott J. , Hofstetter Heike , Hofstetter Oliver
Published: January 2008

The structure of the binding site of the stereoselective anti‐D‐amino acid antibody 67.36 was modeled utilizing web antibody modeling (WAM) and SWISS‐MODEL. Although docking experiments performed with an aromatic amino acid as model ligand were unsuccessful with the WAM structure, ligand binding was achieved with the SWISS‐MODEL structure. Incorporation of side‐chain flexibility within the binding site resulted in a protein structure that stereoselectively binds to the D‐enantiomer of the model ligand. In addition to four hydrogen bonds that are formed between amino acid residues in the binding site and the ligand, a number of hydrophobic interactions are involved in the formation of the antibody‐ligand complex. The aromatic side chain of the ligand interacts with a tryptophan and a tyrosine residue in the binding site through π–π stacking. Fluorescence spectroscopic investigations also suggest the presence of tryptophan residues in the binding site, as ligand binding causes an enhancement of the antibody's intrinsic fluorescence at an emission wavelength of 350 nm. Based on the modeled antibody structure, the L‐enantiomer of the model ligand cannot access the binding site due to steric hindrance. Additional docking experiments performed with D‐phenylalanine and D‐norvaline showed that these ligands are bound to the antibody in a way analogous to the D‐enantiomer of the model ligand. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Calculation of weakly polar interaction energies in polypeptides using density functional and local Møller‐Plesset perturbation theory
Authors: Csontos József , Palermo Nicholas Y. , Murphy Richard F. , Lovas Sándor
Published: January 2008

The interaction energies of ubiquitous weakly polar interactions in proteins are comparable with those of hydrogen bonds, consequently, they stabilize local, secondary, and tertiary structures. However, the most widely‐used density functionals fail to describe the weakly polar interactions. Thus, it is important to find and test functionals which adequately describe and quantify the energetics of such interactions. For this purpose, interaction energies in the hydrophobic core of rubredoxin (PDB id: 1rb9) and in the S22 subset of the JSCH‐2005 benchmark database were computed with the BHandHLYP and PWPW91 functionals and with the pseudospectral implementation of the local MP2 (PS‐LMP2) method. The cc‐pVDZ, cc‐pVTZ(‐f), cc‐pVTZ, cc‐pVQZ(‐g), aug‐cc‐pVDZ, aug‐cc‐VTZ(‐f), and aug‐cc‐pVTZ basis sets were used for the calculations. In the S22 subset the PS‐LMP2 results were extrapolated to the complete basis set limit. Furthermore, thea posterioricounterpoise method of Boys and Bernardi was used to correct the basis set superposition errors in the calculation of interaction energies. Calculations using the BHandHLYP functional, both for the various weakly polar interactions in rubredoxin and for the dispersion interactions in the S22 subset, were in good agreement with those using the coupled cluster (CCSD(T)) and the resolution of identity MP2 (RIMP2) methods and clearly outperformed both the PWPW91 functional and the PS‐LMP2 method. The results for the S22 hydrogen bonded subset, obtained with PWPW91 calculations, were closest to those of the reference high level calculations. For the “mixed” (hydrogen bonded and dispersive) interactions in the S22 subset, results obtained with the BHandHLYP and PS‐LMP2 calculations agreed well with the reference calculations. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Monitoring glucocorticoid response to rehabilitation and research procedures in California and Steller sea lions
Authors: Petrauskas Lisa , Atkinson Shannon , Gulland Frances , Mellish Jo‐Ann , Horning Markus
Published: January 2008

We used serum and fecal corticosteroid analysis to study the physiological response to a range of invasive and non‐invasive procedures in sea lions. Four experimental groups of California sea lions (Zalophus californianus; Group A: restraint only [n=9], Group B: gas anesthesia without surgery [n=10], Group C: minimally invasive surgery [n=10], and Group D: invasive surgery [n=5]) were monitored for adrenal response. Feces were collected opportunistically from 72 hr before 72 hr post procedure for corticosterone analysis. All experimental groups showed substantial individual variation and no significant change in corticosterone levels after the procedures. Additional fecal and serum corticoid samples were collected from six free‐ranging Steller sea lions (Eumetopias jubatus) in temporary captivity undergoing abdominal implantation of long‐term telemetry devices. Only one sea lion exhibited a significant fecal corticosterone increase in response to the surgery. Capture and restraint appear to elicit a greater glucocorticoid response than invasive or non‐invasive procedures. J. Exp. Zool. 309A:73–82, 2008. © 2008 Wiley‐Liss, Inc.
Separate but equal? The gendered nature of social capital in rural Philippine communities
Authors: Godquin Marie , Quisumbing Agnes R.
Published: January 2008

This paper explores the gender dimensions of group membership and social networks using a unique longitudinal data set from the rural Philippines. We investigate two types of social capital: membership in groups, or ‘formal’ social capital, and size of trust‐based networks or ‘informal’ social capital. Because men and women may have different propensities to invest in social capital, we analyse the determinants of group membership for men and women separately. We also disaggregate the analysis by type of group. The paper also examines the determinants of the density of social capital, proxied by the number of groups and the number of network members. Finally, it explores whether groups contribute to increased sizes of social networks. We find that men and women do not differ significantly in their probability of participating in groups or the number of groups they join. However, there are clear gender differences in the types of groups to which men and women belong. We also find that group membership does not, in general, increase network density. The size of one's informal networks is influenced by the location and migration decisions of one's sons and daughters, suggesting that sons and daughters play different roles in providing support to their households of origin. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis and preliminary biological evaluation of a 99mTc‐labeled hypericin derivative as a necrosis avid imaging agent
Authors: Fonge Humphrey , Jin Lixin , Wang Huaijun , Bormans Guy , Ni Yicheng , Verbruggen Alfons
Published: January 2008

Mono‐[123I]iodohypericin and mono‐[123I]iodohypericin monocarboxylic acid are iodine‐123‐labeled hypericin derivatives which have shown great promise in preclinical studies as necrosis avid imaging agents in animal models of infarction. In view of the more attractive properties of a 99mTc‐labeled hypericin derivative, we have synthesized a conjugate of protohypericin monocarboxylic acid with S‐benzoylmercaptoacetyldiglycyl‐diaminopentane in an overall yield of 15%. The conjugate was labeled with technetium‐99m by exchange labeling at pH 10 in a labeling yield of 95% followed by photocyclization to yield 99mTc‐mercaptoacetyldiglycyl‐1,5‐diaminopentylene hypericincarboxamide (99mTc‐13). The negatively charged 99mTc‐13 complex was purified by reversed phase high‐pressure liquid chromatography and the log P7.4 was determined to be 2.36. In normal NMRI mice, the complex showed slow hepatobiliary clearance while plasma clearance was rapid. The tracer was evaluated in rats with reperfused hepatic infarction by ex vivo autoradiography, gamma counting and histochemical techniques. Unlike the radioiodinated hypericin derivatives, the new tracer agent did not show preferential uptake in necrotic tissue on autoradiography and gamma counting techniques. Conjugation of hypericin with a 99mTc‐chelate, resulting in a change in size, charge and lipophilicity, had a profound effect on the necrosis avidity of the tracer agent. The results show that 99mTc‐13 is not suitable for imaging necrosis. Copyright © 2008 John Wiley & Sons, Ltd.
Persistence of defaunation effects on digestion and methane production in ewes
Authors: Bird S. H. , Hegarty R. S. , Woodgate R.
Published: January 2008

The effect of defaunation on feed digestion and on methane production of ewes was determined 10 and 25 weeks after defaunation. When fed a lucerne diet (800 g/day), the absence of protozoa did not change the apparent digestibility of dry matter, excretion of macro-minerals, or methane production 10 or 25 weeks post-treatment. Defaunation did, however, increase microbial protein flow by 22% (estimated from allantoin excretion) and the molar proportions of acetate and butyrate in the rumen, while decreasing excretion of copper and manganese. The fermentation data contrasts with previous studies that found defaunation reduced methanogenesis and rumen acetate proportions, but supports the hypothesis that a reduction in rumen acetate percentage is required to achieve reduced methanogenesis through defaunation.
IκB kinase β–induced phosphorylation of CARMA1 contributes to CARMA1–Bcl10–MALT1 complex formation in B cells
Authors: Shinohara Hisaaki , Maeda Shiori , Watarai Hiroshi , Kurosaki Tomohiro
Published: January 2008

Protein kinase C (PKC) β has been reported (Shinohara, H., T. Yasuda, Y. Aiba, H. Sanjo, M. Hamadate, H. Watarai, H. Sakurai, and T. Kurosaki. 2005. J. Exp. Med. 202:1423–1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Immunity. 23:561–574) to play a crucial role in B cell receptor (BCR)–mediated IκB kinase (IKK) activation through phosphorylation of caspase recruitment domain 11, Bimp3 (CARMA1). However, it remains unclear whether this PKCβ-mediated phosphorylation accounts fully for the activation status of CARMA1, because involvement of other kinases, such as phosphoinositide 3-kinase–dependent kinase 1, has also been suggested. We show that PKCβ mediates phosphorylation of CARMA1 on Ser668, which in turn is essential for BCR-mediated CARMA1–Bcl10–mucosal-associated lymphoid tissue 1 (MALT1) association and subsequent IKK activation. Our analyses also demonstrate that the downstream kinase IKKβ contributes to facilitating formation of the complex CARMA1–Bcl10–MALT1 by mediating phosphorylation of CARMA1. Hence, our data suggest that PKCβ is crucial for initial activation of IKK. The activated IKKβ does not merely function as an effector enzyme but also modifies the upstream signaling complex through a feedback mechanism, thereby optimizing the strength and duration of the nuclear factor κB signal.