bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of forest harvesting on the occurrence of landslides and debris flows in steep terrain of central Japan
Authors: Imaizumi Fumitoshi , Sidle Roy C. , Kamei Rieko 
Published: August 2007

AbstractLandslides and debris flows associated with forest harvesting can cause much destruction and the influence of the timing of harvesting on these mass wasting processes therefore needs to be assessed in order to protect aquatic ecosystems and develop improved strategies for disaster prevention. We examined the effects of forest harvesting on the frequency of landslides and debris flows in the Sanko catchment (central Japan) using nine aerial photo periods covering 1964 to 2003. These photographs showed a mosaic of different forest ages attributable to the rotational management in this area since 1912. Geology and slope gradient are rather uniformly distributed in the Sanko catchment, facilitating assessment of forest harvesting effects on mass wasting without complication of other factors. Trends of new landslides and debris flows correspond to changes in slope stability explained by root strength decay and recovery; the direct impact of clearcutting on landslide occurrence was greatest in forest stands that were clearcut 1 to 10 yr earlier with progressively lesser impacts continuing up to 25 yr after harvesting. Sediment supply rate from landslides in forests clearcut 1 to 10 yr earlier was about 10‐fold higher than in control sites. Total landslide volume in forest stands clearcut 0 to 25 yr earlier was 5·8 × 103 m3 km−2 compared with 1·3 × 103 m3 km−2 in clearcuts >25 yr, indicating a fourfold increase compared with control sites during the period when harvesting affected slope stability. Because landslide scars continue to produce sediment after initial failure, sediment supply from landslides continues for 45 yr in the Sanko catchment. To estimate the effect of forest harvesting and subsequent regeneration on the occurrence of mass wasting in other regions, changes in root strength caused by decay and recovery of roots should be investigated for various species and environmental conditions. Copyright © 2007 John Wiley & Sons, Ltd.
ERK1/2 and p38 MAP kinases control prion protein fragment 90–231‐induced astrocyte proliferation and microglia activation
Authors: Thellung Stefano , Villa Valentina , Corsaro Alessandro , Pellistri Francesca , Venezia Valentina , Russo Claudio , Aceto Antonio , Robello Mauro , Florio Tullio 
Published: August 2007

AbstractAstrogliosis and microglial activation are a common feature during prion diseases, causing the release of chemoattractant and proinflammatory factors as well as reactive free radicals, involved in neuronal degeneration. The recombinant protease‐resistant domain of the prion protein (PrP90–231) displays in vitro neurotoxic properties when refolded in a β‐sheet‐rich conformer. Here, we report that PrP90–231 induces the secretion of several cytokines, chemokines, and nitric oxide (NO) release, in both type I astrocytes and microglial cells. PrP90–231 elicited in both cell types the activation of ERK1/2 MAP kinase that displays, in astrocytes, a rapid kinetics and a proliferative response. Conversely, in microglia, PrP90–231‐dependent MAP kinase activation was delayed and long lasting, inducing functional activation and growth arrest. In microglial cells, NO release, dependent on the expression of the inducible NO synthase (iNOS), and the secretion of the chemokine CCL5 were Ca2+ dependent and under the control of the MAP kinases ERK1/2 and p38: ERK1/2 inhibition, using PD98059, reduced iNOS expression, while p38 blockade by PD169316 inhibited CCL5 release. In summary, we demonstrate that glial cells are activated by extracellular misfolded PrP90–231 resulting in a proliferative/secretive response of astrocytes and functional activation of microglia, both dependent on MAP kinase activation. In particular, in microglia, PrP90–231 activated a complex signalling cascade involved in the regulation of NO and chemokine release. These data argue in favor of a causal role for misfolded prion protein in sustaining glial activation and, possibly, glia‐mediated neuronal death. © 2007 Wiley‐Liss, Inc.
Crb1 is a determinant of retinal apical Müller glia cell features
Authors: van de Pavert Serge A. , Sanz Alicia Sanz , Aartsen Wendy M. , Vos Rogier M. , Versteeg Inge , Beck Susanne C. , Klooster Jan , Seeliger Mathias W. , Wijnholds Jan 
Published: August 2007

AbstractMutations in the human Crumbs homologue‐1 (CRB1) gene cause retinal blinding diseases, such as Leber congenital amaurosis and retinitis pigmentosa. In the previous studies we have shown that Crb1 resides in retinal Müller glia cells and that loss of Crb1 results in retinal degeneration (particularly in the inferior temporal quadrant of the mouse eye). Degeneration is increased by exposure to white light. Here, we studied the role of light and aging to gain a better understanding of the factors involved in the progress of retinal disease. Our data reveal that light is neither sufficient nor required to induce retinal disorganization and degeneration in young Crb1−/− mutant mice, suggesting that it rather modulates the retinal phenotype. Gene expression profiling showed that expression of five genes is altered in light‐exposed Crb1−/− mutant retinas. Three of the five genes are involved in chromosome stabilization (Pituitary tumor transforming gene 1 or Pttg1, Establishment of cohesion 1 homolog 1 or Esco1, and a gene similar to histone H2B). In aged retinas, degeneration of photoreceptors, inner retinal neurons, and retinal pigment epithelium was practically limited to the inferior temporal quadrant. Loss of Crb1 in Müller glia cells resulted in an irregular number and size of their apical villi. We propose that Crb1 is required to regulate number and size of these Müller glia cell villi. The subsequent loss of retinal integrity resulted in neovascularization, in which blood vessels of the choroid protruded into the neural retina. © 2007 Wiley‐Liss, Inc.
Are numbers special? Comparing the generation of verbal materials from ordered categories (months) to numbers and other categories (animals) in an fMRI study
Authors: Ischebeck Anja , Heim Stefan , Siedentopf Christian , Zamarian Laura , Schocke Michael , Kremser Christian , Egger Karl , Strenge Hans , Scheperjans Filip , Delazer Margarete 
Published: August 2007

AbstractMonths, days of the week, and numbers differ from other verbal concepts because they are ordered in a sequence, whereas no order is imposed on members of other categories, such as animals or tools. Recent studies suggest that numbers activate a representation of their quantity within the intraparietal sulcus (IPS) automatically, that is, in tasks that do not require the processing of quantity. It is unclear, however, whether ordered verbal materials in general and not only numbers activate the IPS in such tasks. In the present functional magnetic resonance imaging study word generation of months, numbers, and animals were compared. Word generation of numbers and nonnumerical materials from an ordered category (months) activated the IPS more strongly than generating items from a not‐ordered category such as animals or the verbal control conditions. An ROI analysis of three subregions within the anterior IPS revealed that the most anterior and lateral of these regions, human intraparietal area hIP2, shows a greater sensitivity to ordered materials than the other two areas, hIP1 and hIP3. Interestingly, no difference in activation was observed within the IPS between numbers and months suggesting that the activation of the IPS might not be modulated by the additional quantity information carried by numbers. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Increased hepatotoxicity of tumor necrosis factor–related apoptosis-inducing ligand in diseased human liver
Authors: Volkmann Xandra , Fischer Ute , Bahr Matthias J. , Ott Michael , Lehner Frank , MacFarlane Marion , Cohen Gerald M. , Manns Michael P. , Schulze-Osthoff Klaus , Bantel Heike 
Published: August 2007

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not in most normal cells and has therefore been proposed as a promising antitumor agent. Recent experiments suggested that isolated primary human hepatocytes but not monkey liver cells are susceptible to certain TRAIL agonists, raising concerns about the use of TRAIL in cancer treatment. Whether TRAIL indeed exerts hepatotoxicityin vivoand how this is influenced by chemotherapeutic drugs or liver disease are completely unknown. Employing different forms of recombinant TRAIL, we found that the cytokine can induce proapoptotic caspase activity in isolated human hepatocytes. However in marked contrast, these different TRAIL preparations induced little or no cytotoxicity when incubated with tissue explants of fresh healthy liver, an experimental model that may more faithfully mimic thein vivosituation. In healthy liver, TRAIL induced apoptosis only when combined with histone deacetylase inhibitors. Strikingly, however, TRAIL alone triggered massive apoptosis accompanied by caspase activation in tissue explants from patients with liver steatosis or hepatitis C viral infection. This enhanced sensitivity of diseased liver was associated with an increased expression of TRAIL receptors and up-regulation of proapoptotic Bcl-2 proteins.Conclusion:These results suggest that clinical trials should be performed with great caution when TRAIL is combined with chemotherapy or administered to patients with inflammatory liver diseases.
Determinants of skin sensitisation potential
Authors: Roberts David W. , Aptula Aynur O. 
Published: August 2007

AbstractSkin sensitisation is an important toxicological endpoint. The possibility that chemicals used in the workplace and in consumer products might cause skin sensitisation is a major concern for individuals, for employers and for marketing. In European REACH (Registration, Evaluation, and Authorisation of Chemicals) legislation, the sensitising potential should therefore be assessed for chemicals below the 10 ton threshold. Development of methods for prediction of skin sensitisation potential without animal testing has been an active research area for some time, but has received further impetus with the advent of REACH and the EU Cosmetics Directive (EU 2003). This paper addresses the issue of non‐animal based prediction of sensitisation by a mechanistic approach. It is known that the sequence of molecular, biomolecular and cellular events between exposure to a skin sensitiser and development of the sensitised state involves several stages, in particular penetration through the stratum corneum, covalent binding to carrier protein, migration of Langerhans cells, presentation of the antigen to naïve T‐cells. In this paper each of these stages is considered with respect to the extent to which it is dependent on the chemical properties of the sensitiser. The evidence suggests that, although penetration of the stratum corneum, stimulation of migration and maturation of Langerhans cells, and antigen recognition are important events in the induction of sensitisation, except in certain specific circumstances they can be taken for granted. They are not important factors in determining whether a compound will be a sensitiser or not, nor are they important factors in determining how potent one sensitiser will be relative to another. The ability to bind covalently to carrier protein is the major structure‐dependent determinant of skin sensitisation potential. A chemistry‐based prediction strategy is proposed involving reaction mechanistic domain assignment, reactivity and hydrophobicity determination, and application of quantitative mechanistic modelling (QMM) or read‐across. Copyright © 2007 John Wiley & Sons, Ltd.
Chemical reactivity indices and mechanism‐based read‐across for non‐animal based assessment of skin sensitisation potential
Authors: Roberts David W. , Aptula Aynur O. , Patlewicz Grace , Pease Camilla 
Published: August 2007

AbstractThe skin sensitisation potential of chemicals is currently assessed using in vivo methods where the murine local lymph node assay (LLNA) is typically the method of first choice. Current regulatory initiatives are driving the impetus for the use of in vitro/in silico alternative approaches to provide the relevant information needed for the effective assessment of skin sensitisation, for both hazard characterisation and risk assessment purposes. A chemical must undergo a number of steps for it to induce skin sensitisation but the main determining step is formation of a stable covalent association with carrier protein. The ability of a chemical to react covalently with carrier protein nucleophiles relates to both its electrophilic reactivity and its hydrophobicity.This paper focuses on quantitative indices of electrophilic reactivity with nucleophiles, in a chemical mechanism‐of‐action context, and compares and contrasts the experimental approaches available to generate reactivity data that are suitable for mathematical modelling and making predictions of skin sensitisation potential, using new chemistry data correlated against existing in vivo bioassay data. As such, the paper goes on to describe an illustrative example of how quantitative kinetic measures of reactivity can be usefully and simply applied to perform mechanism‐based read‐across that enables hazard characterisation of skin sensitisation potential. An illustration of the types of quantitative mechanistic models that could be built using databases of kinetic measures of reactivity, hydrophobicity and existing in vivo bioassay data is also given. Copyright © 2007 John Wiley & Sons, Ltd.
Computational chemistry approach for the early detection of drug‐induced idiosyncratic liver toxicity
Authors: Cruz‐Monteagudo Maykel , Cordeiro M. Natália D. S. , Borges Fernanda 
Published: August 2007

AbstractIdiosyncratic drug toxicity (IDT), considered as a toxic host‐dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clinical trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually <1/5000), IDT is often life threatening and is one of the major reasons new drugs never reach the market or are withdrawn post marketing. Computational methodologies, like the computer‐based approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant analysis (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D molecular structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over‐fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross‐validation statistics and predictivity on an external subset of chemicals. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, respectively in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA‐based desirability analysis was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacologically related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, respectively. The computational approach proposed here can be considered as a useful tool in early IDT prognosis. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Primitive versus derived traits in the developmental program of the vertebrate head: views from cyclostome developmental studies
Authors: Kuratani Shigeru , Ota Kinya G. 
Published: August 2007

AbstractEvolution can be viewed as a series of changes in the developmental program along the phylogenetic tree. To better understand the early evolution of the vertebrate skull, we can use the embryos of the cyclostome species as models. By comparing the cyclostome developmental patterns with those of gnathostomes, it becomes possible to distinguish the primitive and derived parts of the developmental program as taxon‐specific traits. These traits are often recognizable as developmental constraints that define taxa by biasing the developmental trajectories within a certain limited range, resulting in morphological homologies in adults. These developmental constraints are distributed on the phylogenetic tree like the morphological character states of adult animals and are associated with specific regions of the tree. From this perspective, we emphasize the importance of considering gene expression and embryonic anatomy as the mechanistic bases that can result in homologous or nonhomologous morphological patterns at later developmental stages. Taking the acquisition of the jaw and trabecula cranii as examples, we demonstrate that a set of embryonic features can be coupled or decoupled during evolution and development. When they are coupled, they exert an ancestral developmental constraint that results in homologous morphological patterns, and when they are decoupled, the ancestral constraints tend to be abandoned, generating a new body plan. The heterotopy behind the specification of the oral domain is an example of decoupling, based on shifted tissue interactions. We also stress the importance of “developmental burden” in determining the sequential order of changes through evolution.J. Exp. Zool. (Mol. Dev. Evol.) 310B:294–314, 2008. © 2007 Wiley‐Liss, Inc.
Management of blood pressure after acute ischemic stroke: An evidence‐based guide for the hospitalist
Authors: Cumbler Ethan , Glasheen Jeffrey 
Published: August 2007

AbstractHospitalists are frequently called upon to manage blood pressure after acute ischemic stroke. A review of both post infarction cerebral perfusion physiology and the data from randomized trials of antihypertensive therapy is necessary to explain why consensus guidelines for blood pressure management after stroke differ from those of other hypertensive emergencies. The peri‐infarct penumbra is the central concept in understanding post ischemic cerebral perfusion. This area of impaired cerebral blood flow is dependent on mean arterial blood pressure and acute reduction of blood pressure may expand the area of infarction. Review of clinical trials fails to show benefit from reduction of blood pressure after ischemic stroke and current guidelines suggest antihypertensive therapy be employed if the systemic blood pressure is greater than 180/105 mmHg after tPA is employed, or 220/120 mmHg when tPA is not used. Induced hypertension remains a promising but unproven therapy in the acute setting, but the evidence for long term control of blood pressure to less than 140/80 mmHG for secondary prevention of stroke is strong. Adherence to guidelines is poor but it is recognized that current evidence is limited by a lack of trials in which blood pressure is titrated to a pre‐specified goal, as is common in clinical practice. Journal of Hospital Medicine 2007;2:261–267. © 2007 Society of Hospital Medicine.
Temperature‐dependent localization of GPI‐anchored intestinal alkaline phosphatase in model rafts
Authors: Giocondi Marie‐Cécile , Besson Françoise , Dosset Patrice , Milhiet Pierre‐Emmanuel , Le Grimellec Christian 
Published: August 2007

AbstractIn plasma membranes, most of glycosylphosphatidylinositol (GPI)‐anchored proteins would be associated with rafts, a category of ordered microdomains enriched in sphingolipids and cholesterol (Ch). They would be also concentrated in the detergent resistant membranes (DRMs), a plasma membrane fraction extracted at low temperature. Preferential localization of GPI‐anchored proteins in these membrane domains is essentially governed by their high lipid order, as compared to their environment. Changes in the temperature are expected to modify the membrane lipid order, suggesting that they could affect the distribution of GPI‐anchored proteins between membrane domains. Validity of this hypothesis was examined by investigating the temperature‐dependent localization of the GPI‐anchored bovine intestinal alkaline phophatase (BIAP) into model raft made of palmitoyloleoylphosphatidylcholine/sphingomyelin/cholesterol (POPC/SM/Chl) supported membranes. Atomic force microscopy (AFM) shows that the inserted BIAP is localized in the SM/Chl enriched ordered domains at low temperature. Above 30°C, BIAP redistributes and is present in both the ‘fluid’ POPC enriched and the ordered SM/Chl domains. These data strongly suggest that in cells the composition of plasma membrane domains at low temperature differs from that at physiological temperature. Copyright © 2007 John Wiley & Sons, Ltd.
Docking study and free energy simulation of the complex between p53 DNA‐binding domain and azurin
Authors: De Grandis Valentina , Bizzarri Anna Rita , Cannistraro Salvatore 
Published: August 2007

AbstractMolecular interaction between p53 tumor suppressor and the copper protein azurin (AZ) has been demonstrated to enhance p53 stability and hence antitumoral function, opening new perspectives in cancer treatment. While some experimental work has provided evidence for AZ binding to p53, no crystal structure for the p53–AZ complex was solved thus far. In this work the association between AZ and the p53 DNA‐binding domain (DBD) was investigated by computational methods. Using a combination of rigid‐body protein docking, experimental mutagenesis information, and cluster analysis 10 main p53 DBD–AZ binding modes were generated. The resulting structures were further characterized by molecular dynamics (MD) simulations and free energy calculations. We found that the highest scored docking conformation for the p53 DBD–AZ complex also yielded the most favorable free energy value. This best three‐dimensional model for the complex was validated by using a computational mutagenesis strategy. In this structure AZ binds to the flexible L1 and s7–s8 loops of the p53 DBD and stabilizes them through protein–protein tight packing interactions, resulting in high degree of both surface matching and electrostatic complementarity. Copyright © 2007 John Wiley & Sons, Ltd.