bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival and reproduction of enchytraeid worms, Oligochaeta, in different soil types amended with energetic cyclic nitramines
Authors: Dodard Sabine G. , Sunahara Geoffrey I. , Kuperman Roman G. , Sarrazin Manon , Gong Ping , Ampleman Guy , Thiboutot Sonia , Hawari Jalal
Published: October 2005

Hexanitrohexaazaisowurtzitane (CL-20), a new polycyclic polynitramine, has the same functional nitramine groups (N-NO2) as the widely used energetic chemicals hexahydro-1,3,5-trinitro-1,3,5-triazacyclohexane (royal demolition explosive [RDX]) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (high-melting explosive [HMX]). Potential impacts of CL-20 as an emerging contaminant must be assessed before its use. The effects of CL-20, RDX, or HMX on adult survival and juvenile production by potworms Enchytraeus albidus and Enchytraeus crypticus were studied in three soil types, including Sassafras sandy loam (1.2% organic matter [OM], 11% clay, pH 5.5), an agricultural soil (42% OM, 1% clay, pH 8.2), and a composite agricultural-forest soil (23% OM, 2% clay, pH 7.9) by using ISO method 16387 (International Standard Organization, Geneva, Switzerland). Results showed that CL-20 was toxic to E. crypticus with median lethal concentration values for adult survival ranging from 0.1 to 0.7 mg/kg dry mass (DM) when using the three tested soils. In addition, CL-20 adversely affected juvenile production by both species in all soils tested, with median effective concentration (EC50) values ranging from 0.08 to 0.62 mg/kg DM. Enchytraeus crypticus and E. albidus were similarly sensitive to CL-20 exposure in the composite agricultural-forest soil, which supported reproduction by both species and enabled comparisons. Correlation analysis showed weak or no relationship overall among the soil properties and reproduction toxicity endpoints. Neither RDX nor HMX affected (p > 0.05) adult survival of either species below 658 and 918 mg/kg DM, respectively, indicating that CL-20 is more toxic to enchytraeids than RDX or HMX. Examination of data shows that CL-20 should be considered as a potential reproductive toxicant to soil invertebrates, and that safeguards should be considered to minimize the potential for release of CL-20 into the environment.
Confocal Fluorescence Microscopy for High-Throughput Screening of G-Protein Coupled Receptors
Authors: Heilker Ralf , Zemanova Lenka , Valler Martin J. , Nienhaus G. U.
Published: October 2005

In the pharmaceutical industry, G-protein coupled receptors (GPCRs) are the most successful group of therapeutic targets. Finding compounds that interfere with the ligand-GPCR interaction in a specific and selective way is a major focus of pharmaceutical research today. As compound libraries of large pharmaceutical companies have increased to hundreds of thousands of test compounds, there is a growing need for miniaturization of drug discovery assays to save bioreagents and to reduce the consumption of test compounds. Due to its high sensitivity combined with a femtoliter-sized measurement volume, confocal fluorescence microscopy enables designs for GPCR binding assays with tiny sample volumes. The GPCRs are prepared in the form of plasma membrane fragments from GPCR-overexpressing cells or may be integrated into virus-like particles (VLiPs). One technique to extract binding data from confocal fluorescence experiments is the socalled fluorescence intensity distribution analysis (FIDA). In this review article, we describe the applicability of FIDA to GPCR-focussed high-throughput screening (HTS) and compare FIDA to two other GPCR-adaptable drug discovery techniques for ligand binding studies, the scintillation proximity assay (SPA) and macroscopic fluorescence polarization (FP) measurements. FIDA measures the absolute concentrations of both GPCR-bound and unbound ligand, thereby providing an internal control to the drug screening data. FIDA is amenable to work with relatively low amounts of GPCRs so that the assay may be carried out with biomembranes of a low GPCR density. Moreover, the fluorescence intensity readout of the FIDA technique may be combined with other confocal fluorescence readouts such as fluorescence anisotropy or lifetime. The combination of a low sample volume with an information-rich measurement means that confocal fluorescence spectroscopy can bring substantial benefits as a bioassay platform to pharmaceutical GPCRdirected research.
Medicinal Plants with Inhibitory Properties Against Snake Venoms
Authors: Soares Andreimar M. , Ticli Fabio K. , Marcussi Silvana , Lourenco Miriam V. , Januario Ana H. , Sampaio Suely V. , Giglio Jose R. , Lomonte Bruno , Pereira Paulo S.
Published: October 2005

Envenomations due to snake bites are commonly treated by parenteral administration of horse or sheep-derived polyclonal antivenoms aimed at the neutralization of toxins. However, despite the widespread success of this therapy, it is still important to search for different venom inhibitors, either synthetic or natural, that could complement or substitute for the action of antivenoms. Several plants have been utilized in folk medicine as antiophidian. However, only a few species have been scientifically investigated and still less had their active components isolated and characterized both structurally and functionally. This article presents a review of plants showing neutralizing properties against snake venoms which were assayed in research laboratories, correlating them with ethnopharmacological studies, as (i) the part of the plant used as antidote, (ii) its respective genus and family and (iii) inhibition of the main pharmacological, toxic and enzymatic activities of snake venoms and isolated toxins. Protective activity of many of these plants against the lethal action of snake venoms has been confirmed by biological assays. Compounds in all of them belong to chemical classes capable of interacting with macromolecular targets (enzymes or receptors). Popular culture can often help to guide scientific studies. In addition, biotechnological application of these inhibitors, as helpful alternative or supplemental treatments to serum therapy, and also as important models for synthesis of new drugs of medical interest, needs to be better oriented and scientifically explored.
Xanthones as Antimalarial Agents: Discovery, Mode of Action, and Optimization
Authors: Riscoe M. , Kelly J. X. , Winter R.
Published: October 2005

It is believed that at no time in the history of the human race malaria has been absent. This disease, which is caused by protozoa of the genus Plasmodium, in all likelihood has been responsible for the death of about half of all people who ever lived. Even today, after attempts at intervention on a worldwide scale, malaria remains the most significant parasitic disease in the tropics and sub-tropics, where it causes at least 500 million clinical episodes and claims 1.5 million lives each year, mostly young children and pregnant women. Widespread resistance to the best and least expensive antimalarials, chloroquine and S/P (i.e., a combination of sulfadoxine and pyrimethamine), combined with an increasing tolerance to insecticides in the mosquito vector, threaten a global malaria tragedy unless new countermeasures are developed. For malaria therapy, the great panacea would be the development of a long-lasting vaccine, but until this becomes a reality, people living in and traveling to endemic regions must rely on a dwindling cache of more expensive drugs; many beyond the economic reach of impoverished people living in malarious regions of the world. Our course to recognition of xanthones as potential antimalarial agents took a rather circuitous route, involving both serendipity and empiricism, and is described together with mechanistic details of drug action. From a chance encounter with a sea urchin collected near the city of Cannon Beach on the Oregon coast to naturally occurring and functionalized xanthones, it is revealed how these compounds target the Plasmodium parasites most vulnerable feature - the digestive vacuole.
Synthesis of Xanthones: An Overview
Authors: Sousa M. E. , Pinto M. M.M.
Published: October 2005

Among the known synthetic routes to obtain xanthones, the Grover, Shah, and Shah reaction, the cyclodehydration of 2, 2-dihydroxybenzophenones and electrophilic cycloacylation of 2-aryloxybenzoic acids are the most popular methods. Due to important biological applications of xanthones, some synthetic strategies leading to more complex derivatives have been widely explored in the past years. Thus, the purpose of this review is to report some recent improvements of the classical synthetic methods as well as of some nonclassical methods to obtain simple oxygenated xanthones. The strategies for introduction of substituents into the xanthonic nucleus are also summarized. Furthermore, different approaches used to synthesize complex structures, with an emphasis on the total synthesis of bioactive natural products, accomplished in the last twenty years, are also discussed. Besides the synthesis of xanthones, the reactivity of the xanthonic nucleus and its role as a key intermediate for the synthesis of other important classes of compounds are also highlighted.
The vengeance puzzle—retributive justice or hostile aggression?
Authors: Schmid Jeannette
Published: October 2005

Vengeance is understood as a blend of instrumental and hostile aggression. Taking the Berkowitz neoassociationistic aggression model as a basis, 84 students received a priming manipulation (anger, fear, or control condition). Afterwards, they judged one of four vengeance scenarios that differed in victim‐perpetrator relationship (coworker vs. stranger) and in the attributed motive of the perpetrator. Priming had an influence on judgments of injustice and on anticipated fury, but no effect whatsoever on aggression (measured as the decrease in well‐being wished for the perpetrator). The type of relationship had an effect only on anticipated disappointment. The main effects of motive were found on aggression and on the anticipated feeling of the perpetrator after the act. Aggression could be predicted from the motive of the perpetrator and well‐being of the victim after the transgression. Neither anticipated fury, importance of deterrence, nor judgment of injustice predicted aggression. Aggr. Behav. 00:1–12, 2005. © 2005 Wiley‐Liss, Inc.
Evaluation of the effectiveness of an anti‐bullying programme in primary schools
Authors: O'Moore Astrid Mona , Minton Stephen James
Published: October 2005

A nationwide programme to prevent and manage bullying in Irish schools, based on that implemented in Norway in 1996, is currently being developed, and pilot work with a sample of primary schools within a single county of Ireland has been conducted and evaluated (the staff and pupils of 42 primary schools having been involved). A network of professionals (11 teachers) were trained to co‐ordinate the anti‐bullying programme in the schools, subsequent activities involving their training teachers (a total of 197) and parents in three to five schools each. In evaluation, pupils from 22 of the schools completed modified versions of the Olweus Bully/Victim Questionnaire [Olweus, 1989; Whitney and Smith, 1993]. Teachers completed a questionnaire (concerning their knowledge and feelings about bullying [Rigby, 1997]) both before and after the implementation of the anti‐bullying training programme. Significant reductions were found in pupils' reports of having been victimised after the implementation of the programme. Overall, 19.6 per cent fewer children were victimised. There was a reduction of 50.0 per cent amongst those frequently victimised within the last school term, and of 43.0 per cent in reports of having been bullied within the last five school days. A reduction of 17.3 per cent in pupils' reports of having taken part in bullying others was also observed after the implementation of the programme. There were, in particular, significant reductions (69.2 per cent) in reports of frequently bullying others within the last school term, and of 51.8 per cent in reports of having taken part in bullying others within the last five school days. Whilst the programme was shown to reduce the incidence of pupils' involvement in bullying behaviour, the perennial challenge of attempting to increase the levels of pupils' reporting of bullying to teachers and parents remains a challenge for the authors to attend to in the further development of the nationwide anti‐bullying programme. Aggr. Behav. 00:1–14, 2005. © 2005 Wiley‐Liss, Inc.
Psychological correlates of peer victimisation in preschool: social cognitive skills, executive function and attachment profiles
Authors: Monks Claire P. , Smith Peter K. , Swettenham John
Published: October 2005

Most research into peer victimisation has focussed on children aged 8 years and above and has included a study of the correlates of victimisation, including cognitive and social skills, and attachment profiles. Recent research has started to investigate aggression and victimisation in younger groups and has found that the nature of aggression differs from that in older children in terms of the types of victimisation involved and the stability of the roles. This study investigated some of the correlates of roles taken in victimisation in 104 children aged 4–6 years, using a cartoon methodology to elicit peer nominations for aggressor, victim, and defender. It examined the social cognitive abilities, executive function skills, and attachment profiles of aggressors, victims, and defenders. Victims did not exhibit poor performance on the social cognitive tasks or have insecure attachment qualities as has been found with victims during middle childhood. Aggressors did not perform highly on the social cognitive tasks in contrast to older aggressors and bullies. Defenders were found to perform above average (although not significantly different from other groups) on the social cognitive tasks. These findings are related to the nature of aggression and victimisation at this age, and a developmental change hypothesis is proposed to accommodate them. Aggr. Behav. 00:1–18, 2005. © 2005 Wiley‐Liss, Inc.
Comparative anatomy of the facial motor nucleus in mammals, with an analysis of neuron numbers in primates
Authors: Sherwood Chet C.
Published: October 2005

The facial motor nucleus (VII) contains motoneurons that innervate the facial muscles of expression. In this review, the comparative anatomy of this brainstem nucleus is examined. Several aspects of the anatomical organization of the VII appear to be common across mammals, such as the distribution of neuron types, general topography of muscle representation, and afferent connections from the midbrain and brainstem. Phylogenetic specializations are apparent in the proportion of neurons allocated to the representation of subsets of muscles and the degree of differentiation among subnuclei. These interspecific differences may be related to the elaboration of certain facial muscles in the context of socioecological adaptations such as whisking behavior, sound localization, vocalization, and facial expression. Furthermore, current evidence indicates that direct descending corticomotoneuron projections in the VII are present only in catarrhine primates, suggesting that this connectivity is an important substrate for the evolution of enhanced mobility and flexibility in facial expression. Data are also presented from a stereologic analysis of VII neuron numbers in 18 primate species and a scandentian. Using phylogenetic comparative statistics, it is shown that there is not a correlation between group size and VII neuron number (adjusted for medulla volume) among primates. Great apes and humans, however, display moderately more VII neurons that expected for their medulla size. © 2005 Wiley‐Liss, Inc.
Nature's experiments in brain diversity
Authors: Marino Lori , Hof Patrick R.
Published: October 2005

This special issue of The Anatomical Record originates from a symposium on the evolution of neurobiological specializations in mammals held at the American Association of Anatomists annual meeting in San Diego in April 2005. The symposium, co‐organized by Patrick R. Hof and Lori Marino, provided the impetus for extending the discussion to a greater range of species. This special issue is the product of that goal and is fueled by the philosophy that it is largely against a backdrop of brain diversity that we can extract the higher‐order commonalities across brains that may lead us to uncovering general higher‐order principles of brain and behavioral evolution. Several major themes emerge from this issue. These are that there are no simple brains, that brains reflect ecology, and that brain evolution is a detective story. The 12 articles in this issue are outstanding reflections of these themes. © 2005 Wiley‐Liss, Inc.
Diversity of mammalian photoreceptor properties: Adaptations to habitat and lifestyle?
Authors: Peichl Leo
Published: October 2005

All mammalian retinae contain rod photoreceptors for low‐light vision and cone photoreceptors for daylight and color vision. Most nonprimate mammals have dichromatic color vision based on two cone types with spectrally different visual pigments: a short‐wavelength‐sensitive (S‐)cone and a long‐wavelength‐sensitive (L‐)cone. Superimposed on this basic similarity, there are remarkable differences between species. This article reviews some striking examples. The density ratio of cones to rods ranges from 1:200 in the most nocturnal to 20:1 in a few diurnal species. In some species, the proportion of the spectral cone types and their distribution across the retina deviate from the pattern found in most mammals, including a complete absence of S‐cones. Depending on species, the spectral sensitivity of the L‐cone pigment may peak in the green, yellow, or orange, and that of the S‐cone pigment in the blue, violet, or near‐ultraviolet. While exclusive expression of one pigment per cone is the rule, some species feature coexpression of the L‐ and S‐pigment in a significant proportion of their cones. It is widely assumed that all these variations represent adaptations to specific visual needs associated with particular habitats and lifestyles. However, in many cases we have not yet identified the adaptive value of a given photoreceptor arrangement. Comparative anatomy is a fruitful approach to explore the range of possible arrangements within the blueprint of the mammalian retina and to identify species with particularly interesting or puzzling patterns that deserve further scrutiny with physiological and behavioral assays. © 2005 Wiley‐Liss, Inc.
Study on immunocapture–chemiluminescence assay of lipase activity in a biological sample
Authors: Ichibangase Tomoko , Hamabe Chie , Ohba Yoshihito , Kishikawa Naoya , Nakashima Kenichiro , Kayamori Yuzo , Kang Dongchon , Hamasaki Naotaka , Kuroda Naotaka
Published: October 2005

A new approach for the determination of lipase (triacylglycerol lipase, EC.3.1.1.3) activity in a biological sample was investigated by combining an immunocapture technique with a chemiluminescence (CL) assay method in order to eliminate interference with CL detection. The proposed method consists of an immunocapture step to trap lipase and a subsequent step for CL detection of the activity of the captured lipase. The CL detection is based on the luminol–hydrogen peroxide (H2O2)–horseradish peroxidase (HRP) reaction and utilizes a proenhancer substrate [a lauric acid ester of 2‐(4‐hydroxyphenyl)‐4,5‐diphenylimidazole (HDI)] which liberates an active enhancer, HDI, by enzymatic hydrolysis. A polyclonal antibody prepared with porcine pancreas lipase was used for the immunocapture. The proposed immunocapture–CL method effectively eliminated the interference with the CL reaction from biological components and enabled the determination of spiked porcine pancreas lipase activity in serum samples in the range 0.41–1.1 UHDI (1 UHDI corresponds to the amount which liberates 1 pmol HDI/min at 37°C from the substrate). The method was further applied to the assay of the activity for human pancreas lipase in serum and the results showed good correlation (r = 0.871) with those by the conventional colorimetric method. Copyright © 2005 John Wiley & Sons, Ltd.
Revision of collagen molecular structure
Authors: Okuyama Kenji , Xu Xiaozhen , Iguchi Makoto , Noguchi Keiichi
Published: October 2005

Based on the fiber diffraction data from native collagen, Rich and Crick proposed the 10/3‐helical model with a 28.6 Å axial repeat in 1955 (Rich A.; Crick, F. H. C. Nature (Lond) 1955, 176, 915–916). We obtained the 7/2‐helical structure with a 20 Å axial repeat from the single crystal analysis of (Pro–Pro–Gly)10. Since the latter structure could explain fiber diffraction patterns from native collagen, we proposed this structure as a new model for collagen in 1977 (Okuyama et al., Polym J 1977, 9, 341–343). These two structural models were refined against observed continuous intensity data from native collagen using a linked‐atom least‐squares method. It was found that the diffraction data from native collagen could be explained by the 7/2‐helical model better than, or at least the same as, the prevailing 10/3‐helical model. Together with the evidence that recent single crystal analyses of many model peptides have supported the 7/2‐helical model and there was no such active support for the 10/3‐helical model, it was concluded that the average molecular structure of native collagen seems to be closer to the 7/2‐helical symmetry than the other one. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 181–191, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Identification of triterpenoid compounds of Centella asiatica by thin‐layer chromatography and mass spectrometry
Authors: Bonfill Mercè , Mangas Susana , Cusidó Rosa M , Osuna Lidia , Piñol M. Teresa , Palazón Javier
Published: October 2005

The identification of the four principal triterpenoid components of Centella asiatica has been achieved by TLC on silica gel plates and mass spectrometry, as a modification of the method described in the European Pharmacopoeia (5th edn). A combination of ethyl acetate and methanol as the mobile phase was found to be successful in separating these compounds from the rest of the main components of the extract. The spots were detected with anisaldehyde solution. The separated compounds were confirmed by MALDI ‐TOF mass spectrometry. Copyright © 2005 John Wiley & Sons, Ltd.
Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B1 can disrupt protein targeting
Authors: Singh Jasbir , Dani Harinder M. , Sharma R. , Steinberg Pablo
Published: October 2005

Cell culture and western blotting studies revealed that aflatoxin B1 (AFB1) inhibits the biosynthesis of two of the constituent polypeptides of signal recognition particle (SRP) (SRP54 and 72). SRP escorts polyribosomes carrying signal peptides from free form in the cytosol to the bound form on endoplasmic reticulum (ER) membrane during protein targeting. These effects of AFB1 on SRP biosynthesis may inhibit the formation of functional SRP. Our experiments have further shown that AFB1 also inhibits the biosynthesis/translocation of a secretory protein, preprolactin, which fails to appear in the lumen of ER consequent to the treatment with this hepatocarcinogen. The results of the experiments presented in this article therefore enable us to infer for the first time that aflatoxin B1 may inhibit the functioning of SRP as an escort and deplete the ER of polyribosomes for secretory protein synthesis. As these secretory proteins are important components of the plasma membrane, gap junctions and intercellular matrix, their absence from these locations could disturb cell to cell communication leading to tumorigenesis. Copyright © 2005 John Wiley & Sons, Ltd.
A microscopic study of kidney tissue in familial mediterranean fever patients
Authors: Sarı Kılıçaslan Seda M. , Ayvalı Cevat , Taştan Hakkı
Published: October 2005

Familial Mediterranean Fever (FMF) is an autosomal recessive hereditary disease leading mostly to renal failure and nephrotic syndrome. The ultrastructure of kidney has not been fully investigated in FMF associated renal disease. The aim of this study is to provide further evidence on the ultrastructure of kidney in patients with FMF who suffer from renal disease. Renal biopsies obtained from two patients who were diagnosed with FMF renal disease complications were examined. Examination of renal tissue by light and electron microscopy identified degenerations both in tubules and the filtration barrier. Foot processes were partly effaced. Amorphous material was found in thickened glomerular basement membranes. Fibrous material deposits in thick Bowman's capsule wall were also seen. Finally, degeneration in the form of folding of plasma membrane and vacuolization as well as fusion in mitochondria cristae, was observed. Accumulation of tissue remnants in the lumen was also found in tubules. Copyright © 2005 John Wiley & Sons, Ltd.
A multi‐biomarker analysis of DNA damage in automobile painters
Authors: Testa A. , Festa F. , Ranaldi R. , Giachelia M. , Tirindelli D. , De Marco A. , Owczarek M. , Guidotti M. , Cozzi R.
Published: October 2005

The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint‐shops in Italy and in 37 control subjects. The controls were healthy blood donors (14 smokers, 23 non‐smokers) that were matched with the experimental population for gender and age. Air samples were analyzed regularly at the work places, and elevated concentrations of benzene and toluene were detected consistently. The exposed group had higher frequencies of CAs (both chromosome‐ and chromatid‐type), micronuclei, and SCE (P < 0.5 – P < 0.001). Furthermore, exposed and control subjects were also genotyped for GSTM1 and GSTT1 polymorphism. No significant associations were detected between the biomarker responses and either the GSTM1 or GSTT1 genotype of the subjects, but the small sample size does not allow definite conclusions on the relationship between the genetic polymorphism and the biomarkers. The results indicate that automobile painters have increased levels of clastogenic and possible aneugenic damage and that smoking may be a confounding factor for the responses. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Towards a methodology for the characterization of fire resistive materials with respect to thermal performance models
Authors: Bentz Dale P. , Prasad Kuldeep R. , Yang Jiann C.
Published: October 2005

A methodology is proposed for the characterization of fire resistive materials with respect to thermal performance models. Typically in these models, materials are characterized by their densities, heat capacities, thermal conductivities, and any enthalpies (of reaction or phase changes). For true performance modelling, these thermophysical properties need to be determined as a function of temperature for a wide temperature range from room temperature to over 1000°C. Here, a combined experimental/theoretical/modelling approach is proposed for providing these critical input parameters. Particularly, the relationship between the three‐dimensional microstructure of the fire resistive materials and their thermal conductivities is highlighted. Published in 2005 by John Wiley & Sons, Ltd.
TRAIL‐induced death of human adult oligodendrocytes is mediated by JNK pathway
Authors: Jurewicz Anna , Matysiak Mariola , Andrzejak Stanisław , Selmaj Krzysztof
Published: October 2005

Tumor necrosis‐related apoptosis‐inducing ligand (TRAIL) induces apoptosis of oligodendrocytes, target cells of immune attack in multiple sclerosis (MS). TRAIL‐induced human oligodendrocyte (hOL) death depends on TRAIL ligation with its receptor 1 (TRAIL‐R1). However, the intracellular signaling initiated with ligation of TRAIL‐R1 in hOLs is unknown. We defined that intracellular transduction signaling involved in TRAIL‐induced death of hOLs is associated with strong activation of c‐jun NH2‐terminal kinase (JNK) and a dominant negative mutant of MKK4/SEK1, MAP kinase upstream of JNK, inhibited TRAIL‐induced apoptosis of hOLs. The immunoprecipitation experiments showed that JNK3 isoform was predominantly activated upon hOLs exposure to TRAIL and JNK‐3 activation occurred before mitochondrial membrane dysfunction. The other mitogen‐activated protein kinase p38 and ERK, as well as calpains and serine proteases, were not activated during TRAIL‐induced hOL death. Accordingly, the calpain inhibitor, ZLLY.FMK, p38 kinase inhibitor, SB 203580, and serine proteases inhibitor, TPCK, did not protect hOLs from TRAIL‐induced apoptosis. These results demonstrate that JNK pathway is critically involved in hOL death induced by TRAIL and might have significant importance in designing new molecules to protect immune‐mediated hOLs demise. © 2005 Wiley‐Liss, Inc.
Cell cycle inhibitors p21 and p16 are required for the regulation of Schwann cell proliferation
Authors: Atanasoski Suzana , Boller Danielle , De Ventura Lukas , Koegel Heidi , Boentert Matthias , Young Peter , Werner Sabine , Suter Ueli
Published: October 2005

Regulated cell proliferation is a crucial prerequisite for Schwann cells to achieve myelination in development and regeneration. In the present study, we have investigated the function of the cell cycle inhibitors p21 and p16 as potential regulators of Schwann cell proliferation, using p21‐ or p16‐deficient mice. We report that both inhibitors are required for proper withdrawal of Schwann cells from the cell cycle during development and following injury. Postnatal Schwann cells express p21 exclusively in the cytoplasm, first detectable at postnatal day 7. This cytoplasmic p21 expression is necessary for proper Schwann cell proliferation control in the late development of peripheral nerves. After axonal damage, p21 is found in Schwann cell nuclei during the initiation of the proliferation period. This stage is critically regulated by p21, since loss of p21 leads to a strong increase in Schwann cell proliferation. Unexpectedly, p21 levels are upregulated in this phase suggesting that the role of p21 may be more complex than purely inhibitory for the Schwann cell cycle. However, inhibition of Schwann cell proliferation is the overriding crucial function of p21 and p16 in peripheral nerves as revealed by the consequences of loss‐of‐function in development and after injury. Different mechanisms appear to underlie the inhibitory function, depending on whether p21 is cytoplasmic or nuclear. © 2005 Wiley‐Liss, Inc.
Systemic injections of lipopolysaccharide accelerates myelin phagocytosis during Wallerian degeneration in the injured mouse spinal cord
Authors: Vallières Nicolas , Berard Jennifer L. , David Samuel , Lacroix Steve
Published: October 2005

The phagocytic cell response within the injured spinal cord is inefficient, allowing myelin debris to remain for prolonged periods of time within white matter tracts distal to the injury. Several proteins associated with this degenerating myelin are inhibitory to axon growth and therefore prevent severed axons from regenerating. Inflammatory agents such as lipopolysaccharide (LPS) can stimulate both the migration and phagocytic activity of macrophages. Using in situ hybridization, we found that the expression of the LPS membrane receptor, CD14, was enhanced in the mouse dorsal column following a dorsal hemisection. Double labeling studies showed that microglia and macrophages are the two major cell types expressing CD14 mRNA following spinal cord injury (SCI). We therefore tested whether systemic injections of LPS would increase the number and phagocytic activity of macrophages/microglia in the ascending sensory tract (AST) of the mouse dorsal column following a dorsal hemisection. Mice were treated daily via intraperitoneal injections of either LPS or phosphate‐buffered saline (PBS). At 7 days post‐SCI, greater numbers of activated mononuclear phagocytes were present in the AST undergoing Wallerian degeneration (WD) in LPS‐treated animals compared with controls. Animals treated with LPS also exhibited greater Oil Red O staining, which is specific for degenerating myelin and macrophages phagocytosing myelin debris. Myelin clearance was confirmed at 7 days using Luxol Fast Blue staining and on toluidine blue‐stained semi‐thin sections. These results indicate that it is possible to manipulate the innate immune response to accelerate myelin clearance during WD in the injured mouse spinal cord. © 2005 Wiley‐Liss, Inc.
Differential oxidative stress in oligodendrocytes and neurons after excitotoxic insults and protection by natural polyphenols
Authors: Ibarretxe Gaskon , Sánchez‐Gómez María Victoria , Campos‐Esparza María Rosario , Alberdi Elena , Matute Carlos
Published: October 2005

Oligodendrocytes are vulnerable to overactivation of both their AMPA receptors and their high‐ and low‐affinity kainate receptors. Depending on the intensity of the insult and the type of receptor activated, excitotoxic oligodendrocyte death mediated by these receptors has different characteristics. One important consequence at a cellular level is the ensuing oxidative stress, related to Ca2+‐dependent alterations in mitochondrial functioning. We observed that oxidative stress associated with selective AMPA receptor activation is much higher than that associated with the selective activation of high‐ and low‐affinity kainate receptors. Moreover, excitotoxic insults generate more intense oxidative stress in oligodendrocytes than in cortical neurons, though similar alterations in [Ca2+]i and mitochondrial potential were observed in both cell types. Nanomolar concentrations of mangiferin and morin, two natural polyphenols with antioxidant properties, partially protect oligodendrocytes as well as cortical neurons from mild, but not intense, insults mediated by AMPA receptors. In addition to presenting oxygen radical scavenging activity, mangiferin and morin attenuate the intracellular Ca2+ overload subsequent to the activation of AMPA receptors, a mechanism that may contribute to their protective properties. The inclusion of these antioxidant agents in therapeutic strategies for the treatment of diseases in which oligodendrocyte as well as neuron loss occurs may prove to be beneficial. © 2005 Wiley‐Liss, Inc.
Simvastatin affects cell motility and actin cytoskeleton distribution of microglia
Authors: Kuipers Hedwich F. , Rappert Angelika A.C. , Mommaas A. Mieke , Van Haastert Elise S. , Van Der Valk Paul , Boddeke Hendrikus W.G.M. , Biber Knut P.H. , Van Den Elsen Peter J.
Published: October 2005

Statin treatment is proposed to be a new potential therapy for multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. The effects of statin treatment on brain cells, however, are hardly understood. We therefore evaluated the effects of simvastatin treatment on the migratory capacity of brain microglial cells, key elements in the pathogenesis of MS. It is shown that exposure of human and murine microglial cells to simvastatin reduced cell surface expression of the chemokine receptors CCR5 and CXCR3. In addition, simvastatin treatment specifically abolished chemokine‐induced microglial cell motility, altered actin cytoskeleton distribution, and led to changes in intracellular vesicles. These data clearly show that simvastatin inhibits several immunological properties of microglia, which may provide a rationale for statin treatment in MS. © 2005 Wiley‐Liss, Inc.
Grindability of cast Ti–Hf alloys
Authors: Kikuchi Masafumi , Takahashi Masatoshi , Sato Hideki , Okuno Osamu , Nunn Martha E. , Okabe Toru
Published: October 2005

As part of our systematic studies characterizing the properties of titanium alloys, we investigated the grindability of a series of cast Ti–Hf alloys. Alloy buttons with hafnium concentrations up to 40 mass% were made using an argon‐arc melting furnace. Each button was cast into a magnesia‐based mold using a dental titanium casting machine; three specimens were made for each metal. Prior to testing, the hardened surface layer was removed. The specimens were ground at five different speeds for 1 min at 0.98 N using a carborundum wheel on an electric dental handpiece. Grindability was evaluated as the volume of metal removed per minute (grinding rate) and the volume ratio of metal removed compared to the wheel material lost (grinding ratio). The data were analyzed using ANOVA. A trend of increasing grindability was found with increasing amounts of hafnium, although there was no statistical difference in the grindability with increasing hafnium contents. We also found that hafnium may be used to harden or strengthen titanium without deteriorating the grindability. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Development of a sustained‐release system for perivascular delivery of dipyridamole
Authors: Zhu Weiwei , Masaki Takahisa , Bae You Han , Rathi Ramesh , Cheung Alfred K. , Kern Steven E.
Published: October 2005

Vascular access grafts implanted in dialysis patients are prone to failure in the long‐term because of stenosis and occlusion caused by neointimal hyperplasia. Local delivery of antiproliferative drugs may be effective to prevent this consequence while minimizing the systemic side effects they cause. We developed a combination of poly(lactide‐co‐glycolide) (PLGA) microspheres with ReGel®, an injectable copolymer, as a sustained‐release system for perivascular delivery of an antiproliferative drug, dipyridamole. Dipyridamole‐incorporated PLGA microspheres with various molecular weights (MWs) of PLGA were prepared by oil‐in‐water emulsion method. Encapsulation efficiency and surface morphology of microspheres were characterized. In vitro release kinetics of dipyridamole from ReGel or from microspheres/ReGel was experimentally determined. Without microspheres, 40% of the dipyridamole was released from ReGel as an initial burst in the first 3 days followed by continuous release in the subsequent 2 weeks. The use of PLGA microspheres decreased the initial burst and extended dipyridamole release from 23 to 35 days with increasing MW of PLGA. The highest MW PLGA showed a lag time of 17 days before consistent drug release occurred. Mixing microspheres and ReGel with two different MW PLGA achieved a continuous release for 35 days with little initial burst. In vivo release of dipyridamole from microspheres/ReGel exhibited a comparable release pattern to that seen in vitro. This injectable platform is a promising technique for sustained perivascular delivery of antiproliferative drugs. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Improved proton affinity measurements for proline and modified prolines using triple quadrupole and ion trap mass spectrometers
Authors: Mezzache S. , Bruneleau N. , Vekey K. , Afonso C. , Karoyan P. , Fournier F. , Tabet J.‐C.
Published: October 2005

Proton affinity (PA) of compounds such as proline, cis‐3‐methylproline, cis‐3‐ethylproline, cis‐3‐isopropylproline and cis‐3‐isopentanylproline was determined by kinetic method with amines as the reference bases. The effective temperatures determined using ion trap and triple quadrupole mass spectrometers were found to be significantly different. In the case of the triple quadrupole instruments, the effective temperature depends significantly on the collision energy. The influence of the apparent basicity (GBapp) on the effective temperature may be used to estimate the difference in protonation entropy (ΔΔS°) between the sample and reference compounds. In case of the ion trap mass spectrometer, the variation of the effective temperature as a function of the excitation amplitude is small, so it is difficult to account for the contribution of the entropy effects to the proton affinity value. A better estimation of the PA and ΔΔS° values for the investigated molecules is obtained by combining the GBapp and Teff data pairs that are obtained from both the mass spectrometers. Copyright © 2005 John Wiley & Sons, Ltd.
A novel approach to perform metabolite screening during the quantitative LC–MS/MS analyses of in vitro metabolic stability samples using a hybrid triple‐quadrupole linear ion trap mass spectrometer
Authors: Shou Wilson Z. , Magis Lisa , Li Austin C. , Naidong Weng , Bryant Matthew S.
Published: October 2005

In vitro metabolic stability experiments using microsomes or other liver preparations are important components in the discovery and lead‐optimization stages of compound selection in the pharmaceutical industry. Currently, liquid chromatography–tandem mass spectrometric (LC–MS/MS) support of in vitro metabolic stability studies primarily involves the monitoring of disappearance of parent compounds, using selected reaction monitoring (SRM) on triple‐quadrupole instruments. If moderate to high turnover is observed, separate metabolite identification experiments are then conducted to characterize the biotransformation products. In this paper, we present a novel method to simultaneously perform metabolite screening in addition to the quantitative stability measurements, both within the same chromatographic run. This is accomplished by combining SRM and SRM‐triggered, information‐dependent acquisition (IDA) of MS/MS spectra on a hybrid triple‐quadrupole linear ion trap (QqQLIT) mass spectrometer. Microsomal stability experiments using model compounds, bufuralol, propranolol, imipramine, midazolam, verapamil and diclofenac, were used to demonstrate the applicability of our approach. This SRM + SRM‐IDA approach generated metabolic stability results similar to those obtained by conventional SRM‐only approach. In addition, MS/MS spectra from potential metabolites were obtained with the enhanced product ion (EPI) scan function of LIT during the same injection. These spectra were correlated to the spectra of parent compounds to confirm the postulated structures. The time–concentration profiles of identified metabolites were also estimated from the acquired data. This approach has been successfully used to support discovery programs. Copyright © 2005 John Wiley & Sons, Ltd.
Modelling of air drying of Hacıhaliloglu‐type apricots
Authors: Menges Hakan Okyay , Ertekin Can
Published: October 2005

In this study a laboratory dryer was used for the thin layer drying of sulfured and non‐sulfured apricots. The moisture ratio values throughout the drying process were calculated by 14 different mathematical models, namely Newton, Page, modified Page, modified Page‐II, Henderson and Pabis, logarithmic, two‐term, two‐term exponential, Wang and Singh, Thompson, diffusion approximation, modified Henderson and Papis, Verma et al. and Midilli et al. models. Root mean square error, reduced chi‐square, mean bias error, adjusted R‐square and modelling efficiency were used as statistical parameters to determine the most suitable model among them. According to the results, the Page model was chosen to explain the thin layer drying behaviour of sulfured and non‐sulfured apricots. The effects of drying air temperature (T) and velocity (V) on the constants and coefficients of the best moisture ratio model were determined by multiple regression analysis. The moisture ratio (MR) could be predicted by the Page model equation MR = exp(−ktn) with constants and coefficients k = 0.470893 + 0.078775V and n = 0.017786 exp(0.051935T) for sulfured apricots and k = 4.578252 + 1.144643T and n = 0.888040 + 0.145559V for non‐sulfured apricots. It is possible to predict the moisture content of the product with the generalised Page model incorporating the effects of drying air temperature and velocity on the model constants and coefficients in the ranges T = 70–80 °C and V = 1–3 m s−1. This developed model showed acceptable agreement with the experimental results, explained the drying behaviour of the product and could also be used for engineering applications. Copyright © 2005 Society of Chemical Industry
Placement of deep brain stimulator electrodes using real‐time high‐field interventional magnetic resonance imaging
Authors: Martin Alastair J. , Larson Paul S. , Ostrem Jill L. , Keith Sootsman W. , Talke Pekka , Weber Oliver M. , Levesque Nadja , Myers Jeffrey , Starr Philip A.
Published: October 2005

A methodology is presented for placing deep brain stimulator electrodes under direct MR image guidance. The technique utilized a small, skull‐mounted trajectory guide that is optimized for accurate alignment under MR fluoroscopy. Iterative confirmation scans are used to monitor device alignment and brain penetration. The methodology was initially tested in a human skull phantom and proved capable of achieving submillimeter accuracy over a set of 16 separate targets that were accessed. The maximum error that was obtained in this preliminary test was 2 mm, motivating use of the technique in a clinical study. Subsequently, a total of eight deep brain stimulation electrodes were placed in five patients. Satisfactory placement was achieved on the first pass in seven of eight electrodes, while two passes were required with one electrode. Mean error from the intended target on the first pass was 1.0 ± 0.8 mm (range = 0.1–1.9 mm). All procedures were considered technical successes and there were no intraoperative complications; however, one patient did develop a postoperative infection. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.
PROPELLER EPI: An MRI technique suitable for diffusion tensor imaging at high field strength with reduced geometric distortions
Authors: Wang Fu‐Nien , Huang Teng‐Yi , Lin Fa‐Hsuan , Chuang Tzu‐Chao , Chen Nan‐Kuei , Chung Hsiao‐Wen , Chen Cheng‐Yu , Kwong Kenneth K.
Published: October 2005

A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k‐space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off‐resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single‐shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin‐echo (FSE) technique. For DTI, the self‐navigated phase‐correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal‐to‐noise ratio (SNR) compared to single‐shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.