bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of okadaic acid‐induced neuronal death and the effect of estrogens
Authors: Yi Kun Don , Covey Douglas F. , Simpkins James W. 
Published: November 2008

AbstractSerine/threonine protein phosphatases are important mediators of general cellular function as well as neurodegenerative processes. We have previously shown inhibition of protein phosphatases to be as neurotoxic as glutamate‐induced neuronal death but resistant to neuroprotection by estrogens. In this study, the mechanism by which phosphatase inhibition via okadaic acid (OA) induced neurotoxicity is explored. Neurons were exposed to OA or glutamate in the presence or absence of various protein kinases inhibitors, and/or one of four estrogens. Both OA and glutamate induced cell death via increased reactive oxygen species, protein carbonylation, lipid peroxidation, caspase‐3 activity, and mitochondrial dysfunction. All estrogens attenuated glutamate‐mediated responses, but not OA‐induced responses. In addition, inhibition of protein kinase C and mitogen‐activated protein kinase pathway was neuroprotective against glutamate but not OA toxicity. Interestingly, inhibition of mitogen‐activated protein kinase pathway with PD98096 or U0126 caused a decrease in reactive oxygen species production suggesting that activation of ERK1/2 could further exacerbate the oxidative stress caused by glutamate‐induced toxicity; however, these inhibitors had no effect on OA‐induced toxicity. Collectively, these results indicate that both glutamate and OA neurotoxicities are mediated by persistent activation of ERK1/2 and/or protein kinase C and a resulting oxidative stress, and that protein phosphatase activity is an important and necessary aspect of estrogen‐mediated neuroprotection.
Gating deficits in isolation‐reared rats are correlated with alterations in protein expression in nucleus accumbens
Authors: Roncada Paola , Bortolato Marco , Frau Roberto , Saba Pierluigi , Flore Giovanna , Soggiu Alessio , Pisanu Salvatore , Amoresano Angela , Carpentieri Andrea , Devoto Paola 
Published: November 2008

AbstractThe isolation‐rearing (IR) paradigm, consisting of the social deprivation for 6–9 weeks after weaning, induces a spectrum of aberrant behaviors in adult rats. Some of these alterations such as sensorimotor gating deficits are reminiscent of the dysfunctions observed in schizophrenia patients. Although gating impairments in IR rats have been linked to impairments in the cortico‐mesolimbic system, the specific molecular mechanisms underlying this relation are unclear. To elucidate the neurochemical modifications underlying the gating disturbances exhibited by IR rats, we compared their pre‐pulse inhibition (PPI) of the acoustic startle reflex with that of socially reared (SR) controls, and correlated this index to the results of proteomic analyses in prefrontal cortex and nucleus accumbens from both groups. As expected, IR rats exhibited significantly lower startle amplitude and PPI than their SR counterparts. Following behavioral testing, IR and SR rats were killed and protein expression profiles of their brain regions were examined using two‐dimensional electrophoresis based proteomics. Image analysis in the Coomassie blue‐stained gel revealed that three protein spots were differentially expressed in the nucleus accumbens of IR and SR rats. Mass spectrometry (matrix‐assisted laser desorption ionization‐time of flight and MS/MS) identified these spots as heat shock protein 60 (HSP60), α‐synuclein (α‐syn), and 14‐3‐3 protein ζ/δ. While accumbal levels of HSP60 was decreased in IR rats, α‐syn and 14‐3‐3 proteins were significantly increased in IR in comparison with SR controls. Notably, these two last alterations were significantly correlated with different loudness intensity‐specific PPI deficits in IR rats. In view of the role of these proteins in synaptic trafficking and dopaminergic regulation, these findings might provide a neurochemical foundation for the gating alterations and psychotic‐like behaviors in IR rats.
Na+/K+‐ATPase‐mediated signal transduction and Na+/K+‐ATPase regulation
Authors: Zhang Linan , Zhang Zhe , Guo Huicai , Wang Yongli 
Published: November 2008

AbstractA number of studies suggest that Na+/K+‐ATPase in caveolae interacts with neighboring membrane proteins and organizes cytosolic cascades of signaling proteins to send messages to intracellular organelles in different tissues, mostly in cardiac myocytes. Low concentration of ouabain binding to Na+/K+‐ATPase activates Src/epidermal growth factor receptor complex to initiate multiple signal pathways, which include PLC/IP3/CICR, PI3K, reactive oxygen species (ROS), PLC/DG/PKC/Raf/MEK/ERK1/2, and Ras/Raf/MEK/ERK1/2 pathways. In cardiac myocytes, the resulting downstream events include the induction of some early response proto‐oncogenes, activation of transcription factors, activator protein‐1, and nuclear factor‐κB, the regulation of a number of cardiac growth‐related genes, and the stimulation of protein synthesis and myocyte hypertrophy and apoptosis. Conversely, several factors acting through signal pathways, such as protein kinases, Ca2+, ROS, etc., can modulate the activity of the Na+/K+‐ATPase.
Solanum indicum ssp. distichum extract is effective against l‐NAME‐induced hypertension in rats
Authors: Bahgat Ashraf , Abdel‐Aziz Heba , Raafat Mohamed , Mahdy Amina , El‐Khatib Aiman S. , Ismail Ahmed , Khayyal Mohamed T. 
Published: November 2008

Abstract Solanum indicum ssp. distichum is used as a vegetable in some parts of Africa and claimed in folk medicine to guard against cardiovascular disorders. It was of interest to study the potential blood pressure lowering effects of a standardized extract of the fruit. An ethanolic extract of the fruit, standardized to contain > 0.15% chlorogenic acids, was tested orally in both normotensive rats and in those rendered hypertensive by twice daily intraperitoneal injection of NW‐nitro‐l‐arginine methylester (l‐NAME) for 1 week. The extract was either given at the same time as l‐NAME or after the establishment of hypertension. The systolic blood pressure (SBP) was measured non‐invasively using a tail cuff computer‐aided monitoring device. Treatment of normotensive rats with the extract (30–300 mg/kg) for 4 weeks showed no hypotensive effect. Giving the extract (100 and 300 mg/kg) orally once daily during the 1 week hypertension induction period with l‐NAME prevented the development of hypertension. Administration of the extract orally for 1 week after the establishment of hypertension tended to normalize the blood pressure. Pharmacological evidence for the antihypertensive activity of S. distichum is hereby reported for the first time. The extract showed good prophylactic as well as curative effect against l‐NAME‐induced hypertension, whereby its content of chlorogenic acids may play a minor role. Other constituents may be responsible for the antihypertensive action. The findings support further development of the extract as a potential therapeutically useful antihypertensive agent.
Population approaches in paediatrics
Authors: Chatelut Etienne 
Published: November 2008

AbstractPopulation pharmacokinetic (PK) approach is now often used to evaluate PK characteristics of a new compound during its clinical development. Recently, new legislation governing the development and authorization of medicines for use in children aged 0–17 years was introduced in the European Union. Among the strategies proposed in relation to clinical aspects, use of population PKs is stated. In this manuscript, comparison between standard PK and population PK methods will be briefly addressed to understand why the second is particularly adapted to perform PK studies in paediatrics. Then, specific patients’ characteristics (covariates) in paediatrics will be presented. Examples of PK and PK–pharmacodynamic (PK–PD) studies will be finally given. The number of population PK studies published still exceeds largely those of PK–PD.
Minutes from the round table held at Paris on July 6, 2007†
Authors: Laveille Christian , Vis Peter 
Published: November 2008

AbstractA symposium called “Contribution of modelling in the paediatric drug development” was organized at Paris on July 5‐6, 2007 under the auspices of INSERM. The following issues were highlighted and discussed by the participants at the end of the meeting during a round table:• What is the place of modelling at a preclinical stage in the paediatric development?• What is the place of modelling at a clinical stage in the paediatric development?• What are the requirements for an evaluation based on modelling?• What are the recommendations and guidelines need to be established to facilitate the use of modelling techniques in paediatrics?This paper summarizes the discussion around these four questions.
Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else?
Authors: Ralf Paus Lübeck , Schallreuter K. U. , Bahadoran P. , Picardo M. , Slominski A. , Elassiuty Y. E. , Kemp E. H. , Giachino C. , Liu J. B. , Luiten R. M. , Lambe T. , Le Poole I. C. , Dammak I. , Onay H. , Zmijewski M. A. , Dell’Anna M. L. , Zeegers M. P. , Cornall R. J. , Paus R. , Ortonne J. P. , Westerhof W. 
Published: November 2008

Abstract:  The pathobiology of vitiligo has been hotly disputed for as long as one remembers, and has been a magnet for endless speculation. Evidently, the different schools of thought – ranging, e.g. from the concept that vitiligo essentially is a free‐radical disorder to that of vitiligo being a primary autoimmune disease – imply very different consequences for the best therapeutic strategies that one should adopt. As a more effective therapy for this common, often disfiguring pigmentary disorder is direly needed, we must strive harder to settle the pathogenesis debate definitively – on the basis of sound experimental evidence, rather than by a war of dogmatic theories.Recognizing, however, that it is theories which tend to guide our experimental designs and choice of study parameters, the various pathogenesis theories on the market deserve to be critically, yet unemotionally re‐evaluated. This Controversies feature invites you to do so, and to ask yourself: Is there something important or worthwhile exploring in other pathogenesis scenarios than those already favoured by you that may help you improve your own study design, next time you have a fresh look at vitiligo?Vitiligo provides a superb model for the study of many fundamental problems in skin biology and pathology. Therefore, even if it later turns out that, as far as your own vitiligo pathogenesis concept is concerned, you have barked‐up the wrong tree most of the time, chances are that you shall anyway have generated priceless new insights into skin function along the way.
Transcatheter closure of an atrial septal defect in a newborn with aortic stenosis
Authors: Beitzke Albrecht , Zobel Gerfried , Nagel Bert , Koestenberger Martin 
Published: November 2008

AbstractAim: A newborn with valvular aortic stenosis and a 5 mm atrial septal defect (ASD) underwent emergency aortic valvotomy. The small left ventricle of the newborn with signs of fibroelastosis showed good function but a reduced compliance and caused a large left to right shunt at atrial level.Methods and Results: As the patient became respirator‐dependant the ASD was interventionally closed with an 18 mm Amplatzer® PFO occluder. The patient could be weaned from the ventilator within two days and had an uneventful recovery.Conclusion: Interventional closure of an ASD is possible even in the newborn period and should be considered as an alternative to surgery.
Late gas accretion on to primordial minihaloes: a model for Leo T, dark galaxies and extragalactic high-velocity clouds
Authors: Ricotti Massimo 
Published: November 2008

Abstract
In this Letter, we revisit the idea of reionization feedback on dwarf galaxy formation. We show that primordial minihaloes with vcir &lt; 20 km s−1 stop accreting gas after reionization, as it is usually assumed, but in virtue of their increasing concentration and the decreasing temperature of the intergalactic medium as redshift decreases below z= 3, they have a late phase of gas accretion and possibly star formation. We expect that pre-reionization fossils that evolved on the outskirts of the Milky Way or in isolation show a bimodal star formation history with 12- and &lt;10-Gyr old population of stars. Leo T fits with this scenario. Another prediction of the model is the possible existence of a population of gas-rich minihaloes that never formed stars. More work is needed to understand whether a subset of compact high-velocity clouds can be identified as such objects or whether an undiscovered population of dark galaxies exists in the voids between galaxies.
The Design and Development of a Closed Chamber for the in‐situ Quantification of Dryland Soil Carbon Dioxide Fluxes
Authors: HOON STEPHEN R. , THOMAS ANDREW D. , LINTON PATRICIA E 
Published: November 2008

AbstractThis paper describes the design features and capabilities of a portable automated in‐situ closed chamber (ISCC) for the quantification of CO2 fluxes in dryland soils where both photosynthetic and respiratory components may be associated with a cyanobacterial crust. The processes of CO2 flux in dryland soils are briefly described in order to clarify the conditions that make quantification of these fluxes problematic. The instrumentation currently available for in‐situ soil CO2 flux measurements is then reviewed demonstrating their inadequacies for the dryland environment. The ISCC described here is a member of the closed or enrichment class of soil respiration chambers. The ISCC, however, features an optical window possessing high (>90%) transmission in the photosynthetic active region (PAR) of the solar irradiance spectrum, permitting observations of photosynthesis. The ISCC possesses automatic venting and purging so that gaseous concentrations inside the chamber do not change from ambient sufficiently to significantly affect diffusion. The ISCC features both active and passive cooling employing internal solid‐state Peltier coolers and external aluminised Mylar respectively. This avoids severe disturbance of the microclimate within the chamber due to admission of high fluxes of PAR and permits in‐situ operation under a wide range of ambient field temperatures (~ −5 to 40°C). Sensors internal to the chamber monitor temperature, relative humidity, irradiance and pressure. In this implementation the ISCC is coupled to a portable gas chromatograph (Agilent GC‐3000) to sample the chamber atmosphere. Indicative data for Kalahari Sand soils of Botswana are presented as an illustration of the general performance characteristics.
Human Adaptive Responses to Catastrophic Landscape Disruptions During the Holocene at Numundo, PNG
Authors: PARR J.F. , BOYD W.E. , HARRIOTT V. , TORRENCE R. 
Published: November 2008

AbstractPrehistoric land use and social activity in West New Britain, PNG, are well documented, although the landscapes – largely shaped by catastrophic volcanic eruptions – in which these took place, and the relationships people had with these landscapes, are poorly understood. We define the evolving landscape at Numundo, from prior to the Witori‐Kimbe 2 eruption (W‐K2, ca. 3600 BP) to after the Witori‐Kimbe 4 eruption (W‐K4, ca. 1400 BP), using fossil phytolith and coral evidence at eight archaeological sites to provide environmental evidence of the human responses to periodic catastrophic events. From ca. 5900 to 3600 BP, all the sites were coastal and disturbed. Early disturbance reflected natural forest recovery after W‐K1 (ca. 5900 BP), whereas the later landscape was largely shaped by human activity. In contrast, forest regrowth was limited after W‐K2 and open environments typical of human activity with a mosaic of regenerating, disturbed and managed vegetation, persisted until W‐K3. Environmental recovery from W‐K3 and W‐K4 (ca. 1700 BP and ca. 1400 BP) differed completely, reflecting severity of the volcanism and the short time between eruptions. The landscape after W‐K3 was largely a naturally recovering landscape, in contrast to effective vegetation recovery and significant human exploitation of the landscape – again a mosaic of regenerating, disturbed and managed vegetation – after W‐K4. The social history is one in which people evolved increasingly flexible land‐use practices, enabling them to re‐settle this periodically disrupted landscape, and to take advantage of an increasingly broad range of habitats suitable for cultivation. The human response to this highly dynamic landscape represents a close relationship between social and natural processes, as people became increasingly better at re‐settling an unpredictably disrupted landscape; both the social and environmental processes within this landscape become equally influential and instrumental in shaping the effects of the other.
MODIS‐derived NDVI Characterisation of Drought‐Induced Evergreen Dieoff in Western North America
Authors: YUHAS ANDREW N. , SCUDERI LOUIS A. 
Published: November 2008

AbstractVegetation stress or mortality can be the result of many factors including drought‐induced water deficit, insect infestations and failures of, or fluctuations in, precipitation sources typical to an area. Reduction of cover and reduced health are identifiable in remotely‐sensed multispectral satellite images. A suite of images from NASA's MODIS sensor was used to calculate the Normalised Difference Vegetation Index (NDVI) during the 2000–2006 North American growing seasons. Fluctuations in NDVI over this period show a significant decline in vegetative health in the region with specific areas showing changes linked to moisture sources, prevailing wind patterns, slope aspect and solar radiation receipt. Ground‐truthing of these areas has confirmed the extent and magnitude of the dieoff signal. Historically, dieoff has been reversed through regeneration as climate conditions return to a normal regime. However, quantification of recent vegetative change in western North America suggests that the degree of change may be too severe for regrowth to occur and may have far‐reaching impacts on a scale unseen in modern times. The loss of vegetative habitat and native species in semi‐arid regions and lack of regeneration in these marginal ecosystems due to prolonged drought are growing global problems. Similar drought stress impacts on marginal ecotypes have also been observed in semi‐arid regions of Australia, South America, Asia and Africa. Observations of the spatial pattern of temperate forest vegetation globally can be used to develop a precise picture of vegetative health in these regions and how they are reacting to global climate change.
A metapopulation model for the introgression from genetically modified plants into their wild relatives
Authors: Meirmans Patrick G. , Bousquet Jean , Isabel Nathalie 
Published: November 2008

AbstractMost models on introgression from genetically modified (GM) plants have focused on small spatial scales, modelling gene flow from a field containing GM plants into a single adjacent population of a wild relative. Here, we present a model to study the effect of introgression from multiple plantations into the whole metapopulation of the wild relative. The most important result of the model is that even very low levels of introgression and selection can lead to a high probability that the transgene goes to fixation in the metapopulation. Furthermore, the overall frequency of the transgene in the metapopulation, after a certain number of generations of introgression, depends on the population dynamics. If there is a high rate of migration or a high rate of population turnover, the overall transgene frequency is much higher than with lower rates. However, under an island model of population structure, this increased frequency has only a very small effect on the probability of fixation of the transgene. Considering these results, studies on the potential ecological risks of introgression from GM plants should look not only at the rate of introgression and selection acting on the transgene, but also at the metapopulation dynamics of the wild relative.
Is exfoliation syndrome a sign of systemic vascular disease?
Authors: Tarkkanen Ahti 
Published: November 2008

Abstract.Exfoliation syndrome (ES) is an age‐related disorder in which greyish‐white flakes accumulate in different tissues in the anterior eye. Its pathogenesis is not completely known, but it results in electron‐dense microfibrils. The finding that these can be seen outside the eye in many visceral organs inspired the theory that ES might be a part of a generalized disorder. It was postulated that ES might contribute to increased morbidity, mainly of systemic vascular diseases. This review is a summary of the existing knowledge. The prevalence of arterial hypertension (AHT) in elderly populations is > 30%. No differences have been found in the frequency of AHT among patients with ES or exfoliative glaucoma (EG) compared with those with primary open‐angle glaucoma (POAG) or no ES. There are conflicting reports of frequencies of ischaemic heart disease (IHD). A recent registry‐based study that used uniform criteria for IHD found no difference in the rate of IHD between patients with EG and those with POAG. However, findings of elevated homocysteine levels in the plasma and aqueous humour of patients with ES or EG suggest an increased vascular risk. No studies have yet been conducted to assess possible links between ES and systemic vascular diseases. In a single‐blind study, ES was associated with abdominal aortic aneurysm, but this was not found in a large, cross‐sectional investigation. The frequency of ES in patients with diabetes mellitus (DM) is only about half of that when compared in patients with no ES or with POAG. This finding warrants further studies. Molecular genetics research has found no common denominator for ES and the vascular diseases. There is no evidence that ES or EG are related to increased mortality for cardiovascular diseases. Further large‐scale, randomized clinical studies are required. At present there are no known medical indications that infer an increased systemic vascular risk or imply a need for the complete internal medical examination of a symptom‐free patient with newly diagnosed ES in the eye.
Considerations on fundamental issues in establishing a universal coverage system for health in China
Authors: Lei Hai Chao 
Published: November 2008

AbstractThis study discusses basic health services in China. In this study common sense and international experience in establishing a high‐performing health system were introduced. Five components are identified: basic qualified human resources for health; basic infrastructure; essential medicines; essential technology and procedures; and basic service pathways. Recommendations were presented based upon the Chinese situation. They are: increase public financing and lower private out‐of‐pocket payment for services; revitalize the functions of public facilities; merge different health financing schemes; co‐ordinate public fiscal and pricing policies; prioritize public financing to preventive and primary healthcare; establish and strengthen the partnership between public and private facilities and insurance schemes; and re‐organize the administrative system in health‐based upon the rules of simplicity, unity, and efficiency.