bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Field Effects on the Behavior of Radicals in Protein and DNA Environments
Authors: Mohtat N. , Cozens F. L. , Hancock‐Chen T. , Scaiano J. C. , McLean J. , Kim J.
Published: January 2008

We have examined the behavior of radical pairs derived by hydrogen abstraction of triplet benzophenone and some of its derivatives from bovine serum albumin, human serum albumin and calf thymus DNA. They have been investigated by means of nanosecond laser flash photolysis techniques. The dynamics of radical pair behavior are shown to be sensitive to external magnetic fields; these effects are interpreted using the established model for the influence of magnetic fields on radical pairs in micellar aggregates, in which intersystem crossing of the radical pair is slowed by the external magnetic field. Our results indicate that proteins and DNA can confine the radicals for a sufficiently long period of time for spin evolution to be affected by external fields. In proteins the radical pair retains its geminate character (i.e. remains confined) for about 0.5–1 μs. Interestingly, the magnetic field effects observed in proteins and in DNA seem to occur in distinct timescales; for example, for 2,3,4,5,6‐pentafluorobenzophenone bound to DNA, the magnetic field alters the radical reactivity only over times ≤50 ns, suggesting poor confinement. The timescale for these effects can be increased by promoting Coulombic attraction between DNA and the radical precursor. Electron transfer interactions play a role in the case of DNA.
UV‐Induced Nucleic Acid–Protein Cross‐Linking: Manual on Planning of Irradiation Experiments and Calculation of Absorbed Dose and Quantum Yield
Authors: Dobrov Eugene N. , Nikogosyan David N.
Published: January 2008

We have developed methods of photochemical quantitation of photobiological studies on UV‐induced nucleic acid–protein cross‐linking. Cases relating to incoherent low‐intensity UV sources, laser UV sources and high‐intensity laser UV sources are considered. In the case of low‐intensity UV radiation the most important point is the correct determination of absorbed dose. The laser UV pulse energy is easily measured and the short‐pulse irradiation also has the advantage of "freezing" the conformation of complexes under study. However, the use of high‐intensity laser UV irradiation leads to realizations of two‐quantum processes both in nucleic acid chromophores–bases and in solvent–water, which complicates singificantly the processing of results. In this paper methods for calculating the absorbed dose and the quantum yield of cross‐linking for all above‐mentioned cases are given as well as practical advice.
Lethal Consequences of Simulated Solar Radiation on the Nematode Caenorhabditis elegans in the Presence and Absence of Photosensitizers
Authors: Mills DeEtta K. , Hartman Philip S.
Published: January 2008

Abstract— The partial destruction of the earth's protective ozone layer has raised concerns about the impact of increased UV radiation on the earth's biological systems. In this study, polychromatic light sources were employed to observe the biological responses of the soil nematode Caenorhabditis elegans to simulated solar UV. Using various filter combinations, action spectra were constructed that approximated those generated previously with monochromatic radiation. In both cases, a mutant strain (rad‐3) progressively lost its hypersensitivity as shorter wavelengths were filtered out. In addition, both wild type and radiation‐sensitive (rad) mutants were irradiated with several combinations of filtered light sources in the presence and absence of two exogenous photosensitizers (ethidium bromide and bromodeoxyuridine). Treatment with either of the introduced photosensitizers increased photosensitivity to solar UV. Solar UV also induced a fluence‐dependent reduction in fertility in wild‐type animals. These experiments extend previous data and substantially expand our understanding of the biological responses of C. elegans to solar radiation.
The Effects of Photodynamic Therapy on Human Neutrophil Migration Using Bacteriochlorin a
Authors: Schuitmaker J. J. , de Koster B. M. , Elferink J. G. R.
Published: January 2008

Abstract— Bacteriochlorin a photodynamic therapy (BCA‐PDT) caused inhibition of interleukin (IL)‐8‐activated neutrophil migration, at concentrations that did not induce membrane damage. Random migration and migration induced by other chemoattractants were also inhibited, indicating that the effect of BCA‐PDT was not at the level of chemoattractant‐receptor interaction but down stream. The BCA‐PDT completely blocked superoxide production of phorbol ester‐stimulated neutrophils, indicating that superoxide production by neutrophils present in the tumor before and during BCA‐PDT is not the cause of inactivation of tumor cells. Both type I and type II quenchers prevented inhibition by BCA‐PDT but only in electroporated cells. Confocal laser scanning microscopy showed that the fluorescence of BCA was located inside the cell. These results show that the effects of BCA‐PDT are intracellular and of a mixed type I/type II character and that the neutrophils present in the tumor during illumination probably do not contribute to tumor eradication by releasing reactive oxygen species.
Light Induces lnositol Trisphosphate Elevation in Blepharisma japonicum
Authors: Fabczak Hanna , Walerczyk Mirostawa , Groszynska Boiena , Fabcza Stanistaw
Published: January 2008

Abstract— Photoinduced formation of inositol 1,4,5‐trisphosphate (Ins[1,4,5]P3) was examined using a specific radioimmu‐noassay to investigate the molecular mechanisms of light signal transduction mediating photophobic responses in the ciliate Blepharisma japonicum. Application of light stimuli of moderate intensity to dark‐adapted cells induced a rapid and significant increase in the basal level of Ins (1,4,5)P3, with a peak at about 20 s. Thereafter, the level of Ins (1,4,5)P3 declined to the resting value within the subsequent 100 s. Light stimuli of higher intensity raised the cell Ins (1,4,5)P3 content to still higher levels within about 20 s, but the decaying time course was considerably prolonged. In ciliates incubated under dark conditions with agents interfering with the inositol signalling pathway, like neomycin and Li+ the basal levels of Ins (1,4,5)P3 were lower than in control cells. A photoinduced rise of Ins (1,4,5)P3, content in ciliates treated with neomycin or Li+ was significantly inhibited in a dose‐dependent manner. Depolarizing ionic stimuli in dark‐adapted ciliates induced no significant alterations of the resting Ins (1,4,5)P3 level, indicating a lack of a contribution of this kind of stimulation to the inositol turnover. These studies are the first in vivo demonstration of a possible role for inositol trisphosphate as a second messenger in the light signal transduction process in the ciliate B. japonicum.
Ground‐and Excited‐State Characterization of an Electrostatic Complex between Tetrakis‐(4‐Sulfonatophenyl)porphyrin and 16‐Pyrimidinium Crown‐4
Authors: Larsen Randy W. , Helms Michael K. , Everett W. Russell , Jameson David M.
Published: January 2008

Abstract— We report the formation of an electrostatic complex between (16‐pyrimidinium crown‐4)tetranitrate (16PC4) and tetrakis‐(4‐sulfonatophenyl)porphyrin (4SP) in aqueous solution. Ground‐state complex formation results in a red shift of the 4SP visible absorption bands and a decrease in absorbance of the Soret band. The equilibrium constant for complex formation (determined from optical titrations) is found to be (2.0 ± 0.2) × 105M−1. In addition, the data fit to an expression describing a 1:1 stoichiometry. Excitation of the complex results in quenching of both the excited singlet and triplet states of the associated porphyrin. The singlet‐state lifetime decreases from 10 ns for the free porphyrin to 1.5 ns in the presence of 16PC4 at low solution ionic strengths. In addition, evidence is presented for triplet‐state quenching within the complex with kq= (1.1 ± 0.1) × 104 s−1. The mechanism of quenching is tentatively assigned to electron transfer from either the excited singlet or excited triplet state of the porphyrin to the ground state of the 16PC4.
A Probability‐based Multivariate Statistical Algorithm for Autofluorescence Spectroscopic Identification of Oral Carcinogenesis
Authors: Wang Chih‐Yu , Chen Chin‐Tin , Chiang Chun‐Pin , Young Shueng‐Tsong , Chow Song‐Nan , Chiang Huihua Kenny
Published: January 2008

Abstract— A probability‐based multivariate statistical algorithm combining partial least‐squares (PLS) and logistic regression was developed to identify the development stages of oral cancer through analysis of autofluorescence spectra of oral tissues. Tissues were taken from a 7, 12‐dimethyl‐benz[a]anthracene‐induced hamster buecal pouch carcinogenesis model. Analyses were conducted at various excitation wavelengths, ranging from 280 nm to 400 nm in 20 nm increments, to assess classification performance at different excitations. For each excitation the PLS analysis and logistic regression were combined, on the basis of cross validation, to calculate the posterior probabilities of samples belonging to four stages of cancer development: normal tissues, hyperplasia, dysplasia and early cancers and frankly invasive cancers. Results showed that the 320 nm excitation wavelength optimally classified the cancer development stages: the accuracy rates for identifying samples at that excitation were 91.7%, 83.3%, 66.7% and 83.3% for the four respective stages. The average accuracy rate was 81.3%. These results suggest that the algorithm described in this study might be useful for the detection of human oral cancers.
Excited‐state Acidity of Bifunctional Compounds. 7. Long Distance, Solvent‐assisted Excited‐state Proton Transfer in Olivacine
Authors: Cabo Jaqueline L. do , Faria Herbert B. , Portugal Samira G. M. , Silva Marco A. A. , Brinn Ira M.
Published: January 2008

Abstract— By use of fluorescence spectroscopy and time‐correlated single photon counting, solvent‐assisted excited‐state proton transfer (ESPT) has been observed for olivacine in two organic solvents, 1,4‐dioxane and methanol. Because of spectral overlap, factor analysis was used to determine the emission spectrum of the proton‐transferred (PT) species. The ESPT is not observed in the nonpolar solvent n‐hexane. For the first time in a system of this type, the individual excited‐state rate constants have been calculated exactly from time‐resolved single photon counting results. Because the PT process involves a path of more than 6 Å, its individual rate constant is extremely low, approximately 107 s−1.
Diel Cycles of DNA Damage and Repair in Eggs and Larvae of Northern Anchovy, Engraulis mordax, Exposed to Solar Ultraviolet Radiation
Authors: Vetter Russell D. , Kurtzman Aaron , Mori Toshio
Published: January 2008

Abstract— Damage from UVB radiation (280–320 nm) in the form of cyclobutane pyrimidine dimers (CPD) in DNA and the capacity for their repair were measured in newly spawned eggs and yolk‐sac larvae of northern anchovy, Engraulis mordax, exposed to natural diel cycles of sunlight. The CPD were measured by a newly developed chemiluminescent immunoblot assay capable of measuring CPD in samples as small as 50 ng DNA. Eggs and yolk‐sac larvae exposed to full irradiance levels died. At lower dose rates, equivalent to deeper more natural locations in the water column, there was a diel cycle of dimer concentration that tracked solar intensity. This diel cycle was due to the interaction of damage and repair processes. Repair of CPD in anchovy eggs and larvae could be attributed to true photodependent repair that could be stopped by moving samples into the dark. The CPD present at sunset remained until the following morning. The diel cycles of damage and repair were maintained over at least 4 days without a long‐term upward or downward trend in dimer concentration. This indicates that at the UVB doses used for these experiments, there was no long‐term accumulation of CPD nor an induction of increased repair capacity. Unhatched embryos spawned in the dark also exhibited a strong photorepair response, suggesting that photolyase expression was innate and not dependent on previous light exposure. The diel cycle observed here indicates that, at least for northern anchovy, the CPD concentration at the time of sampling is a good indicator of dose rate but a poor indicator of cumulative dose (i.e. late afternoon samples have the highest cumulative dose but relatively low CPD concentrations). The CPD immunoassay described here has the required sensitivity for measuring DNA damage in wild populations of ichthyoplankton exposed to natural sunlight. These results will guide the collection and interpretation of field data on natural levels of CPD in wild larvae collected at different depths and times of the day.
Toxic and Phototoxic Properties of the Protozoan Pigments Blepharismin and Oxyblepharismin*
Authors: Terazima Masayo Noda , Iio Hideo , Harumoto Terue
Published: January 2008

Abstract— The toxic and phototoxic properties of blepharismin and oxyblepharismin that were purified from the pigments of a ciliated protozoan, Blepharisma japonicum, by thin‐layer chromatography, were investigated in detail. The toxicity was tested against the ciliated protozoan Dileptus margaritifer, which is relatively sensitive to blepharismin. Although oxyblepharismin has been believed to be neither toxic nor phototoxic, it was found that oxyblepharismin is toxic in the dark and is also phototoxic. This shows that oxyblepharismin can act as a photosensitizer. The toxicity and phototoxicity of these pigments were compared with those of hypericin, which is known to be a typical, strong photosensitizer from plants. It was concluded that blepharismin and oxyblepharismin have strong intrinsic toxicities in the dark compared with hypericin, but their phototoxicities are slightly weaker than that of hypericin. This strong intrinsic toxicity supports our proposal that blepharismin acts as a defensive device against predators in the dark as well as in the light. The decrease in the defensive ability and the increase in the resistance to photokilling of Blepharisma concomitant with its color change from red to blue‐purple in response to weak illumination can be explained by the decrease in toxicity and phototoxicity of the pigment itself and by the decrease in amount of the pigment.
Structure and Conformation of Photosynthetic Pigments and Related Compounds. 12. A Crystallographic Analysis of Porphyrin‐quinones and Their Precursors
Authors: Senge Mathias O. , Speck Marcus , Wiehe Arno , Dieks Henrik , Aguirre Santiago , Kurreck Harry
Published: January 2008

Abstract. A comprehensive crystallographic analysis of 10 porphyrin quinone precursors (dimethoxybenzene derivatives), and six porphyrin quinones has been performed. The free bases and zinc(II) complexes of the porphyrin quinones are of the 5,10,15‐triaryl/alkyl‐20‐quinone‐porphyrin type and carry various bridging and quinone units. The structural and conformational parameters were determined for all compounds; the donor‐acceptor separation distances range from 6.3 to 10.9 Å. Knowledge of these data is a prerequisite for a detailed interpretation of theoretical and spectroscopic studies on such systems. Despite the obvious influence of the type and geometry of the bridging unit and quinone on the spatial arrangement of the donor and acceptor components, a large variety of different packing arrangements in the crystal were observed. These include π stacking, aggregate formation and axial ligation in the zinc(II) porphyrins. The latter often utilized the quinone (or dimethoxy) oxygen atoms for coordination to zinc(II) centers leading to porphyrin quinone dimers and even polymers.
Stereocontrolled Photooxygenations–A Valuable Synthetic Tool§
Authors: Adam Waldemar , Saha‐Möller Chantu R. , Schambony Simon B. , Schmid Katharina S. , Wirth Thomas
Published: January 2008

The stereochemical course of the singlet‐oxygen ene reaction with acyclic olefins may be controlled if in the substrate conformational fixation (1,3‐allylic strain) an allyl‐ic substituent for interaction with the attacking oxygen enophile aligns. Various substrates were chosen to elucidate the features of the olefin that are necessary to control the sense (threo versus erythro) and the extent of the ii‐facial preference of the singlet‐oxygen attack. Depending on the electronic properties of the double bond and the nature of the allylic substituent, threo or erythro selectivity may be imposed through hydrogen bonding, electrostatic and steric effects and stereoelectronic alignment. Such directing properties, especially that of the hydroxy group, were also confirmed in the other reaction modes of singlet oxygen, namely the [4+2] cycloaddition to chiral naphthylenic alcohols and the [2+2] cycloaddition to an adamantylidene‐substituted allylic alcohol. The syntheses of the natural products Merucathin and Iso‐dihydromahubanolide B are two examples in which such stereocontrolled photooxygenations have been used as key steps to build up the required chirality diastereose‐lectively.
Role of Nuclear Factor‐KB in Colon Cancer Cell Apoptosis Mediated by Aminopyropheophorbide Photosensitization
Authors: Matroule Jean‐Yves , Hellin Anne‐Cecile , Morliere Patrice , Fabiano A.‐S. , Santus Rend , Merville Marie‐Paule , Piette Jacques
Published: January 2008

Aminopyropheophorbide (APP) is a second generation of photosensitizer for photodynamic therapy (PDT). We demonstrated that APP strongly absorbed red light and, after being taken up by colon cancer cells (HCT‐116 cells), was localized in cytoplasmic and internal membranes but not in mitochondria. The APP‐mediated photosensitization was cytotoxic for HCT‐116 cells through an induction of apoptosis. Indeed, DNA fragmentation (DNA laddering and terminal deoxyuridine nick‐end labeling) and chromatin condensation (4′,6‐diamidine‐2′‐phenylindole staining) could be visualized soon after photosensitization. Because nuclear factor (NF)‐KB is involved in the response to many photosensitizers, we also demonstrated its nuclear translocation in two waves: a rapid and transient one, followed by a slow and sustained phase. The NF‐KB turned out to be involved in an antia‐poptotic response to APP‐mediated photosensitization because the HCT‐116 cell line expressing the dominant negative mutant of inhibitor‐KBα was more sensitive to apoptosis as measured by DNA fragmentation and caspase activation. These data unambiguously show that a membrane‐located photosensitizer can lead to effective apoptosis, reinforcing the idea that PDT can be an effective means to eradicate colon cancer cells.
Formation of Tryptophan Radicals in Irradiated Aqueous Solutions of Hexachloroplatinate(IV): A Flash Photolysis Study
Authors: Zang Ling , Rodgers Michael A. J.
Published: January 2008

The oxidation of tryptophan photosensitized by PtCl62‐has been investigated in aqueous solutions at different pH using nanosecond laser flash photolysis. Cationic and neutral radicals of tryptophan were detected at pH 2.8 and 8.5, respectively. The generation of the radical was attributed to oxidation by Cl2‐that was formed from the homolytic bond cleavage in the excited state of PtCl62‐The bimolecular rate constant derived from the kinetics analysis, 2.8 × 0.2 times; 109M‐1s‐1, is in good agreement with the value obtained in earlier pulse radiolysis studies. Both the cationic and neutral radicals decayed by second‐order kinetics, consistent with the dimerization process.
pH‐Dependent Chalcogenopyrylium Dyes as Potential Sensitizers for Photodynamic Therapy: Selective Retention in Tumors by Exploiting pH Differences between Tumor and Normal Tissue
Authors: Bellnier David A. , Young David N. , Detty Michael R. , Camacho Susan H. , Oseroff Allan R.
Published: January 2008

Ideal photosensitizers have long‐wavelength absorption and strong tumor selectivity with rapid clearance from normal tissues. The telluroselenopyrylium dye 1 that absorbs light at 795 nm (ε= 285000 M1cm‐1) has a novel property that enhances the tumor specificity and normal tissue clearance. After intralesional injection to both tumors and surrounding skin, it disappeared from the normal skin of BALB/c mice faster than it did from subcu‐taneously implanted Colon 26 tumors, which resulted in therapeutic selectivity. In vivo reflectance spectroscopy showed that the half‐life in tumor was about 50 min while in skin it was around 12 min. This phenomenon appears to be related to the pH differences in normal skin versus tumor, because the rates of drug hydrolysis in solution were shown to be sensitive to changes in pH. Inhibition of tumor regrowth following intratumoral photosensitiz‐er administration depended on both light dose and drug dose, as well as the time interval between dye injection and irradiation; selectivity depended on the time interval. Although treatment parameters were not optimized efficacy was superior to systemic Photofrin® under our standard conditions. We discuss how new, more optimal, photosensitizers can be designed that use rates of hydrolysis to exploit the differences in pH between normal tissue and tumor.
Qβ Bacteriophage Photoinactivated by Methylene Blue Plus Light Involves Inactivation of Its Genomic RNA
Authors: Schneider J. Edward , Pye Quentin , Floyd Robert A.
Published: January 2008

Methylene blue (MB) is being used as a sensitizer for the photodynamic inactivation of viral contaminants, including the human immunodeficiency virus, in blood and blood components used in medical treatment. We recently showed that oxygen‐dependent photodynamic inactivation of the RNA bacteriophage QP with MB plus light (MB+L) is associated with the formation of 8‐oxo‐7,8‐dihydroguanine, protein carbonyls, RNA‐protein crosslinkages and minor amounts of RNA strand breaks. We report herein, with the use of infectious RNA assays, that the lethal lesions in Qβ phage following MB+L exposure can be accounted for, and thereby most likely reside in, the RNA component of the phage but that the protein component of the virion contributes to the inactivation. The formation of RNA‐protein crosslinkages as the primary inactivating type of lesion is put forth as the most probable model of the inactivation mechanism due to the sensitivity with which RNA‐protein crosslinks are formed in response to MB+L exposure and the expectation of the powerful inactivating power of this type of lesion.
A New Photoisomerization of Bilirubin
Authors: Cheng Lingjiang , Lightner David A.
Published: January 2008

Photoirradiation of solutions of natural (4Z,15Z)‐biliru‐bin‐IXα in chloroform with ˜366 nm UV light leads rapidly to a new photoisomer that has been characterized by NMR spectroscopy and by its (ground‐state reaction) adducts with methanol and other protic nucleophiles. Unlike the previously described Z →E geometric isomeri‐zation important in phototherapy of neonatal jaundice, the new photoisomerization involves regiospecific pho‐toautomerization to afford 2‐ethenyl‐18‐ethylidene‐l,10,19,22,24‐pentahydro‐2,7,13,17‐tetramethyl‐l,19‐dioxo‐21H‐biline‐8,12‐dipropanoic acid.
Studies on Pyry I retinal Analogues of Bacteriorhodopsin
Authors: Das Joydip , Crouch Rosalie K. , Govindjee Rajni , Balashov Sergei , Ebrey Thomas
Published: January 2008

The retinal analogues 3‐methyl‐5‐(l‐pyryl)‐2E,4E‐penta‐dienal (1) and 3,7‐dimethyl‐9‐(l‐pyryl)‐2E,4E,6E,8E‐non‐atetraenal (2), which contain the tetra aromatic pyryl system, have been synthesized and characterized in order to examine the effect of the extended ring system on the binding capabilities and the function of bacteriorhodopsin (bR). The two bR mutants, E194Q and E204Q, known to have distinct proton‐pumping patterns, were also examined so that the effect of the bulky ring system on the proton‐pumping mechanism could be studied. Both retin‐als formed pigments with all three bacterioopsins, and these pigments were found to have absorption maxima in the range 498–516 nm. All the analogue pigments showed activity as proton pumps. The pigment formed from wild‐type apoprotein bR with 1 (with the shortened polyene side chain) showed an M intermediate at 400 nm and exhibited fast proton release followed by proton uptake. Extending the polyene side chain to the length identical with retinal, analogue 2 with wild‐type apoprotein gave a pigment that shows M and O intermediates at 435 nm and 650 nm, respectively. This pigment shows both fast and slow proton release at pH 7, suggesting that the pKa of the proton release group (in the M‐state) is higher in this pigment compared to native bR. Hydrogen azide ions were found to accelerate the rise and decay of the O intermediate at neutral pH in pyryl 2 pigment. The pigments formed between 2 and E194Q and E204Q showed proton‐pumping behavior similar to pigments formed with the native retinal, suggesting that the size of the chromophore ring does not alter the protein conformation at these sites.
OPTIMAL VORONOI DIAGRAM CONSTRUCTION WITH n CONVEX SITES IN THREE DIMENSIONS
Authors: HARRINGTON PAUL , DÚNLAING COLM Ó. , YAP CHEE K.
Published: January 2008

This paper presents a worst-case optimal algorithm for constructing the Voronoi diagram for n disjoint convex and rounded semi-algebraic sites in 3 dimensions.

Rather than extending optimal 2-dimensional methods,32,16,20,2 we base our method on a suboptimal 2-dimensional algorithm, outlined by Lee and Drysdale and modified by Sharir25,30 for computing the diagram of circular sites.

For complexity considerations, we assume the sites have bounded complexity, i.e., the algebraic degree is bounded as is the number of algebraic patches making up the site. For the sake of simplicity we assume that the sites are what we call rounded. This assumption simplifies the analysis, though it is probably unnecessary.

Our algorithm runs in time O(C(n)) where C(n) is the worst-case complexity of an n-site diagram. For spherical sites C(n) is θ(n2), but sharp estimates do not seem to be available for other classes of site.
Complete Suppression of Tumor Formation by High Levels of Basement Membrane Collagen
Authors: Harris Ann , Harris Henry , Hollingsworth Michael A.
Published: January 2008

Suppression of tumorigenicity was first shown in hybrids produced by the fusion of a range of different highly malignant tumor cells with diploid fibroblasts. Cytogenetic analysis of these hybrids revealed that suppression involved a genetic region located in one specific chromosome donated to the hybrid cell by the fibroblast parent. The identity of the gene responsible for this dramatic effect has remained obscure. We now present strong evidence that the primary determinant is the gene specifying collagen XV, a proteoglycan closely associated with the basement membrane. We transfected a line of highly tumorigenic human cervical carcinoma cells with an expression vector carrying the full-length cDNA of the human collagen XV gene. We selected clones making various amounts of collagen XV, examined their growth in vitro, and tested their tumorigenicity in nude mice. High levels of collagen XV altered the growth properties of the cells in three-dimensional cultures. Moreover, we found that, in a dose-dependent manner, the production of collagen XV completely suppressed tumorigenicity in clones that synthesized this molecule at high levels. Immunohistologic studies suggest that suppression is associated with extracellular deposition of the proteoglycan at the cell periphery. (Mol Cancer Res 2007;5(12):1241–5)
Mutation I136V Alters Electrophysiological Properties of the NaV1.7 Channel in a Family with Onset of Erythromelalgia in the Second Decade
Authors: Cheng Xiaoyang , Dib-Hajj Sulayman D , Tyrrell Lynda , Waxman Stephen G
Published: January 2008

Background:

Primary erythromelalgia is an autosomal dominant pain disorder characterized by burning pain and skin redness in the extremities, with onset of symptoms during the first decade in the families whose mutations have been physiologically studied to date. Several mutations of voltage-gated Na+ channel NaV1.7 have been linked with primary erythromelalgia. Recently, a new substitution NaV1.7/I136V has been reported in a Taiwanese family, in which pain appeared at later ages (9–22 years, with onset at 17 years of age or later in 5 of 7 family members), with relatively slow progression (8–10 years) to involvement of the hands. The proband reported onset of symptoms first in his feet at the age of 11, which then progressed to his hands at the age of 19. The new mutation is located in transmembrane segment 1 (S1) of domain I (DI) in contrast to all NaV1.7 mutations reported to date, which have been localized in the voltage sensor S4, the linker joining segments S4 and S5 or pore-lining segments S5 and S6 in DI, II and III.

Results:

In this study, we characterized the gating and kinetic properties of I136V mutant channels in HEK293 cells using whole-cell patch clamp. I136V shifts the voltage-dependence of activation by −5.7 mV, a smaller shift in activation than the other erythromelalgia mutations that have been characterized. I136V also decreases the deactivation rate, and generates larger ramp currents.

Conclusion:

The I136V substitution in NaV1.7 alters channel gating and kinetic properties. Each of these changes may contribute to increased excitability of nociceptive dorsal root ganglion neurons, which underlies pain in erythromelalgia. The smaller shift in voltage-dependence of activation of NaV1.7, compared to the other reported cases of inherited erythromelalgia, may contribute to the later age of onset and slower progression of the symptoms reported in association with this mutation.
Developing A Regional Imaging Education Initiative
Authors: Clareson Tom
Published: January 2008

Amigos Library Services, a not-for-profit membership organization providing support and services to libraries and cultural institutions throughout the southwestern United States, has been working since 1994 to answer member needs for education and information on digital imaging. Aided by an initial grant from the National Endowment for the Humanities in 1998-99, and continuing support until 2001, the Amigos Imaging Service is developing a continuing education model for imaging, focusing on hands-on, practical information.
Stage One Digitization Project Report: Part I
Authors: Ewbank Lynn
Published: January 2008

When Dr. John L. Ferguson, director of the Arkansas History Commission, met with the archivists in late February, 1999, to ask if we had any ideas for an Arkansas Natural and Cultural Resources Council (ANCRC) grant project, hope sprang anew in my heart. The previous September the Arkansas State Library had sponsored my attendance at “Planning for Digitization.” Held at the Denver Public Library by the Western Council of Libraries, this workshop showcased digital possibilities through examining digital technology, existing digital projects and funding sources. Most impressive were the tours of the Denver Public Library's (DPL) Western History Project. Sitting at a computer workstation, I was able to search for photographs, then view high resolution digital images captured from original prints and negatives by the library's digital lab (also included as part of the tour). Best of all, I could view corresponding MARC records created by researchers headed by a photograph cataloging specialist.
Mass-Deacidification: Where It Fits In with Reformatting
Authors: Strauss Robert J.
Published: January 2008

When I was asked to write an article about how mass-deacidification fits into a library's preservation program, to reflect particularly on the relationship of deacidification to reformatting decisions (which today I assume means using digital technology), I thought that this would either be a very short article or possibly a confusing one. I will leave it to the reader to make their final judgment, but I do want to state at the outset that I will not be arguing that a choice must be made to either deacidify or reformat collections. My assumption is that using the most appropriate preservation option does not preclude choosing to both deacidify and to reformat the same item.
Heterogeneity in Synaptic Vesicle Release at Neuromuscular Synapses of Mice Expressing SynaptopHluorin
Authors: Wyatt Ryan M. , Balice-Gordon Rita J.
Published: January 2008

Mammalian neuromuscular junctions are useful model synapses to study the relationship between synaptic structure and function, although these have rarely been studied together at the same synapses. To do this, we generated transgenic lines of mice in which thethy1.2promoter drives expression of synaptopHluorin (spH) as a means of optically measuring synaptic vesicle distribution and release. SpH is colocalized with other synaptic vesicle proteins in presynaptic terminals and does not alter normal synaptic function. Nerve stimulation leads to readily detectable and reproducible fluorescence changes in motor axon terminals that vary with stimulus frequency and, when compared with electrophysiological recordings, are reliable indicators of neurotransmitter release. Measurements of fluorescence intensity changes reveal a surprising amount of heterogeneity in synaptic vesicle release throughout individual presynaptic motor axon terminals. Some discrete terminal regions consistently displayed a greater rate and extent of release than others, regardless of stimulation frequency. The amount of release at a particular site is highly correlated to the relative abundance of synaptic vesicles there, indicating that a relatively constant fraction of the total vesicular pool, ∼30%, is released in response to activity. These studies reveal previously unknown relationships between synaptic structure and function at mammalian neuromuscular junctions and demonstrate the usefulness of spH expressing mice as a tool for studying neuromuscular synapses in adults, as well as during development and diseases that affect neuromuscular synaptic function.
SIESTA AND SLEEP HABITS OF ADOLESCENTS IN GREECE
Authors: Paraskakis Emmanouil , Hitas Michail , Ntouros Thomas , Ntokos Michail , Hatzimichail Athanasios , Kalmanti Maria
Published: January 2008

INTRODUCTION: The study of adolescents' sleep habits is of increasing scientific interest because of the variability of sleep patterns and the frequency of sleep disorders in those of this age group.

OBJECTIVE: The aim of our study was to investigate the sleep habits of adolescents living in Greece.

METHODS: We analyzed responses given to preconstructed questionnaires on sleep habits and disturbances from 1331 high school students (mean age: 15 years [range: 14–18 years]). The students were attending high schools of rural, semiurban, and urban areas of Thrace, Ipirus, and Crete (all in Greece).

RESULTS: The median nocturnal and total sleep duration was 7.75 hours (range: 2.5–12.3 hours) and 8.5 hours (range: 2.5–14.0 hours), respectively, and the average bedtime was 11:30 pm. Male students, older adolescents, and residents of towns were going to bed later than female students, younger adolescents, and residents of villages (P = .039, .0003, and .056, respectively). Siesta on a regular basis was reported by 43% and on an occasional basis by 46% of the students. Siesta median duration was 2 hours (range: 0.5–4.5 hours). Daytime sleepiness, difficulties in morning awakening, difficulties in falling asleep, and night awakenings were reported by 15.6%, 14%, 17.2%, and 8.11%, respectively. Students who practiced siesta reported less daytime sleepiness (P < .0001). Significant differences were observed between boys and girls regarding sleep disturbances.

CONCLUSIONS: Adolescents in provincial Greece present quite a different sleep pattern compared with their northern European peers, characterized by a late bedtime and midday siesta. Similar to their peers in other countries, considerable rates of sleep disturbances were reported.
EVALUATION OF LEARNING DIFFICULTIES IN EPILEPTIC CHILDREN WITH IDIOPATHIC GENERALIZED EPILEPSY AND WELL-CONTROLLED SEIZURES
Authors: Prassouli Alexia , Antoniadou Ioanna , Attilakos Achilleas , Sarafidou J. , Mastroyianni Sotiria , Voudris Konstantinos , Scardoutsou Angelliki , Katsarou Eustathia , Konstantopoulos Andreas
Published: January 2008

INTRODUCTION: Children with symptomatic epilepsy have more learning difficulties (LDs) than those with idiopathic or cryptogenic epilepsies. However, there is little information on the prevalence of LDs in well-defined pediatric epileptic populations.

OBJECTIVE: Our goal was to evaluate LDs in epileptic children.

METHODS: We evaluated LDs in 37 epileptic children (18 boys and 19 girls; mean age: 8.29 ± 1.00 years) who had idiopathic generalized epilepsy (IGE) and were being treated with sodium-valproate monotherapy (22 with generalized tonic-clonic seizures and 15 with absence epilepsy). The mean duration of epilepsy and treatment was 3.48 ± 1.88 and 2.96 ± 1.80 years, respectively. All children attended mainstream schools, and their seizures were well controlled (without seizures for at least 6 months). We used the Athina Test for the Diagnosis of Learning Difficulties, a test that is partly based on the Illinois Test of Psycholinguistic Abilities, standardized in healthy Greek children.

RESULTS: Children with IGE performed significantly poorer in all subtests except the auditory closure subtest (Table 1). No significant difference was found between the 2 subgroups. A negative correlation was found between disease duration and the score in auditory memory (r = −0.368; P = .025).

CONCLUSIONS: Our results suggest an increased risk of LDs in children with IGE and well-controlled seizures. Early detection of the cognitive impact of IGE and subsequent intervention are needed to prevent educational underachievement.

TABLE 1.Athina Test for the Diagnosis of LDsSubjects With Inadequate Performance, % P Children With IGEHealthy ChildrenAuditory memory64.99.0.000Visual memory43.29.0.000Grammatic closure43.29.0.000Auditory closure16.29.0.125Graphophonological awareness32.49.0.000Visual-motor coordination43.225.0.010
VISUAL SEARCH ATTENTION AND EXECUTIVE FUNCTION IN CHINESE CHILDREN WITH WILLIAMS SYNDROME
Authors: Zhao Zheng-Yan , Shao Jie , Xie Chun-hong , Wang Yan-xia , Qin Yu-feng , Cornish Kim , Karmiloff-Smith Annette
Published: January 2008

INTRODUCTION: Williams syndrome (WS) is a rare neurodevelopmental disorder that is caused by a hemizygous deletion on chromosome 7q11.23. The interest of WS to neurocognitive scientists stems from the uneven profiles of cognitive abilities, with spatial cognition seriously impaired and language and face processing relatively proficient. We know relatively little about the visual search attention and executive function in children with WS.

OBJECTIVE: The objective of this study was to examine the nature of visual search attention and executive function in children with WS, compared with children with Down syndrome (DS), healthy chronological age–matched control subjects (CA), and healthy mental age–matched control subjects (MA).

METHODS: A total of 142 children were tested: 21 with WS, 25 with DS, 45 CA, and 41 MA. MA were matched to the children with WS and DS using the Peabody Picture Vocabulary Test. All participants were assessed on a set of computerized visual search tasks and Wilding Monster Sorting Test using a touch-screen.

RESULTS: The results showed that selective attention, switch, and sustained attention of children with WS all are less developed. Children with WS produced a large number of shape errors, and they also confused shape distractors with targets more than the other groups. Children with WS exhibited poorer executive performance as compared with both groups of typical children. They produced more repetitive errors than did children with DS.

CONCLUSIONS: These findings reveal distinct visual search deficits and atypically developing executive function in children with WS.
SCREENING OF MUTATIONS IN THE NPHS2 GENE IN GREEK PATIENTS WITH AUTOSOMAL-RECESSIVE STEROID-RESISTANT NEPHROTIC SYNDROME
Authors: Megremis Spyridon , Mitsioni Artemis , Mitsioni Andromachi , Stefanidis Constantinos , Kitsiou-Tzelli Sofia , Kanavakis Emmanuel , Synodinos-Traeger Joanne
Published: January 2008

INTRODUCTION: Mutations in the NPHS2 gene, encoding podocin, are a major cause of autosomal-recessive steroid-resistant nephrotic syndrome (SRNS) in childhood and have been observed in 6.4% to 30% of sporadic and 20% to 40% of familial cases.

OBJECTIVE: We investigated mutations in the coding region of the NPHS2 gene in Greek patients with SRNS and identified a novel A295T mutation.

METHODS: The study included 16 child patients with SRNS (14 families); 11 cases were sporadic, and 5 (from 3 families) were familial. All 8 exons of NPHS2, including intron boundaries, were screened for sequence variations by using denaturing gradient gel electrophoresis followed by specific characterization using direct DNA sequencing.

RESULTS: The results revealed 2 pathogenic genotypes in 2 patients with sporadic SRNS (R138Q/R138Q and R229Q/A295T). In addition, 3 previously described NPHS2 intronic polymorphisms (IVS3–46C→T, IVS3–21C→T, and IVS7+7A→G), 1 thus-far-unreported intronic variant (IVS3–17C→T), and 4 known silent mutations (G34G, S96S, A318A, and L346L) were detected in sporadic and familial cases as well as in healthy controls.

CONCLUSIONS: These findings indicate that NPHS2 mutations are not a frequent cause of familial SRNS in Greek patients. Among patients with sporadic SRNS, the genotypes R138Q/R138Q and R229Q/A295T account for an allelic frequency of 18.2%. The R138Q mutation is well characterized. The novel mutation, A295T (883G→A), is predicted in silico to cause a structural alteration in the cytoplasmic domain of podocin (see the PolyPhen database at http://genetics.bwh.harvard.edu/pph). This is the first report of NPHS2 mutations in the Greek population and the first description of the A295T amino acid substitution.
EXPERIMENTAL RESEARCH OF SIMVASTATIN IN REVERSING PULMONARY VASCULAR REMODELING IN VIVO AND IN VITRO
Authors: Liu Hanmin , Liu Bin , Hua Yimin , Wang Xiaoqin , Yu Li , Zhou Tongfu
Published: January 2008

INTRODUCTION: Simvastatin was predicted to be a potential inhibitor to pulmonary vascular remodeling. This novel reversion induced by simvastatin has remained an uncertain mechanism.

OBJECTIVE: Our goal was to explore the role of simvastatin as a potential inhibitor of pulmonary vascular remodeling.

METHODS: We established a neointimal pulmonary hypertensive rat model receiving monocrotaline after pneumonectomy. Simvastatin was administered after the operation. Hemodynamic and vascular remodeling corresponding indices were detected. GATA-6, a gene transcription factor, was evaluated in vivo. Proliferation and the cellular cycle were assessed in cultured vascular smooth muscle cells (VSMCs). α-SM-actin, F-actin, and paxillin were detected to evaluate the phenotype changes.

RESULTS: Neointimal changes developed in 88.5% of right lung intraacinar arteries after pneumonectomy and monocrotaline administration. Mean pulmonary artery pressure, the right ventricle/(left ventricle + S) ratio, and media wall thickness significantly increased in rats that had pneumonectomy and were treated with monocrotaline but decreased significantly in simvastatin-treated rats. The expression of GATA-6 markedly decreased in these rats and was significantly upregulated after receiving simvastatin. In vitro, the proliferation was significantly downregulated in VSMCs with simvastatin compared to that with platelet-derived growth factor. α-SM-actin increased significantly, and F-actin or paxillin was downregulated in simvastatin-treated rats.

CONCLUSIONS: Our data indicate that simvastatin is most likely a pulmonary vascular remodeling inhibitor, which may reverse the proliferation of VSMCs and phenotype changes. Simvastatin can also upregulate GATA-6 expression in lung tissue.
DIAGNOSIS OF TUBERCULOSIS LYMPHADENITIS IN CHILDREN
Authors: Puiu Ileana , Stancu Polixenia , Bulucea Dumitru , Niculescu Carmen , Nicolescu Veronica Elena , Stoian Felicia
Published: January 2008

INTRODUCTION: Tuberculosis represents a major health problem, and the most frequent cause of extrapulmonary tuberculosis is tuberculous lymphadenitis.

OBJECTIVE: The aim of this study was to determine the relative contribution of tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy.

METHODS: Our study included 87 children (aged 6 months to 18 years) suffering from tuberculous lymphadenitis who were admitted to our tuberculosis center during a period of 10 years.

RESULTS: Our 10-year study of 1112 children with lymphadenopathy showed that tuberculous adenitis was encountered in 87 children (7.8%). The disease was present at all ages but was found more frequently between the ages of 10 and 18 years (39.1%). The most common location was the anterior cervical space in 43 children (49.4%), followed by the axillary and supraclavicular areas. Systemic clinical signs (fever, weight loss, tiredness, night sweats) were encountered by 69 children (79.3%). Granulomatous infection was confirmed in 19 children (21.8%) who had abnormal chest radiograph findings. The diagnosis of tuberculous lymphadenitis was based on histological demonstration of caseating epithelioid cell granulomas in the specimen obtained by excision biopsy in 56 cases (64.3%). Tuberculin skin-test results were positive in 76 cases (87.3%). Positive family history of tuberculosis was discovered in 72 cases (82.7%).

CONCLUSIONS: In most cases, the diagnosis was established on the basis of the specific histopathological aspect, tuberculin skin-test result, positive family history of tuberculosis, and the abnormal chest radiograph findings.
MEASURING QUALITY OF LIFE IN GREEK CHILDREN: FIRST PSYCHOMETRIC RESULTS OF THE GREEK VERSION OF THE PEDIATRIC QUALITY OF LIFE INVENTORY (PEDSQL) 4.0 GENERIC CORE SCALES
Authors: Gkoltsiou Konstantina , Papaevangelou Vassiliki , Tountas Yannis , Constantopoulos Andreas
Published: January 2008

INTRODUCTION: Health-related quality of life concerning children is a growing field of research. The Pediatric Quality of Life Inventory (PedsQL) is a promising instrument that is available in age-appropriate versions and parallel forms for both children and their parents.

OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of the Greek translation of the PedsQL 4.0 generic core scales in a sample of healthy children.

METHODS: After a successful pilot test, the Greek PedsQL was used in a cross-sectional study of 645 healthy 8- to 12-year-old schoolchildren and 567 of their caregivers within the framework of the European project (KIDSCREEN). Reliability of the instrument was assessed by Cronbach's α. Construct validity was assessed by exploring the intercorrelations between the 4 PedsQL subscales and between self- and proxy-report subscales. Impact of gender, health status, and socioeconomic class was detected.

RESULTS: All PedsQL scales showed satisfactory reliability (>.70). Correlations among self-report subscales and between self- and proxy-report subscales were significant. Girls reported lower health-related quality of life than boys on the emotional-functioning subscale. There were significant differences in scores between low and high socioeconomic groups. Healthy children scored significantly higher on all self- and proxy-report scales.

CONCLUSIONS: The PedsQL Greek version for children 8 to 12 years old is a valid and reliable instrument, replicating some of the earlier findings of the original version. The Greek PedsQL 4.0 version will be a valuable tool that can be used effectively in quality-of-life measurement in Greek clinical trials and population-based exercises.