bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIODIVERSITY RESEARCH: Diversity and distribution of macroinvertebrates in lentic habitats in massively altered landscapes in south‐eastern Australia
Authors: Sam Lake P. , Thomson James R. , Lada Hania , Nally Ralph Mac , Reid David , Stanaway Jarom , Taylor Andrea C. 
Published: July 2010

AbstractAim  We investigated whether faunas of lentic macroinvertebrates differed among two landscape types: (1) those that are largely covered in forests (presumed to be in a more pre‐human‐impact condition) and (2) those that are completely cleared for agricultural exploitation (massively altered).Location  Five pairs of landscapes (each pair referred to as a region) – one of each landscape type – across a 30,000 km2 region of north‐central Victoria, Australia.Methods  Each individual waterbody was surveyed three times (austral spring 2006, autumn 2007, and spring 2007) for invertebrates. Waterbodies were characterized by measurements of static (e.g. abutting vegetation cover) and labile (e.g. pH) variables. Data were analysed using hierarchical Bayesian models of species richness, α‐ and β‐diversities and functional feeding groups. Assemblage composition was related to landscape and in‐waterbody characteristics.Results  Neither measured, nor asymptotic estimates of, species richness differed among landscape types, notwithstanding consistent differences in in‐waterbody habitat characteristics among waterbodies in the two landscape types. There were no discernible differences in patterns of α‐ and β‐diversities at landscape scales relating to landscape type. Habitat diversity of waterbodies at the landscape scale did not affect β‐diversity, although distinct waterbodies within landscapes tended to have more distinct faunas.Main conclusions  The lentic macroinvertebrate faunas are relatively homogeneous over the entire region, with little differentiation between wooded and cleared landscapes. The regional fauna may be a homogenized subset of native species, possibly arising from the huge numerical predominance of lentic habitats in agricultural landscapes producing ‘spill‐over’ effects into forested landscapes. Of taxa more frequently found in one or other landscape type, trophic group diversity was greater in forested landscapes.
BIODIVERSITY LETTER: The North American Pleistocene overkill hypothesis and the re‐wilding debate
Authors: Wolverton Steve 
Published: July 2010

AbstractThe conservation agenda to re‐wild North America may or may not be realistic in terms of political ecology. However, it represents a real conservation recommendation to re‐wild North America with the extant megafauna most closely related to those that became extinct at the end of the Pleistocene. The recommendation is based on the presumption that society bears an ethical responsibility to re‐wild because humans caused the extinctions. However, the extent to which Pleistocene megafaunal extinctions were the result of overkill is hotly debated. As a result, the ethical imperative for North American re‐wilding should be questioned. It will not be questioned unless members of the conservation community read the extensive archaeological and geological literature concerning the North American Pleistocene extinctions. Overlooking the assumptions underlying this particular recommendation is costly to conservation science and to archaeology because it represents an over‐simplified, unwieldy and troubling fusion of the two.
PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti‐tumour activity
Authors: Leal JFM , Martínez‐Díez M , García‐Hernández V , Moneo V , Domingo A , Bueren‐Calabuig JA , Negri A , Gago F , Guillén‐Navarro MJ , Avilés P , Cuevas C , García‐Fernández LF , Galmarini CM 
Published: July 2010

BACKGROUND AND PURPOSE PM01183 is a new synthetic tetrahydroisoquinoline alkaloid that is currently in phase I clinical development for the treatment of solid tumours. In this study we have characterized the interactions of PM01183 with selected DNA molecules of defined sequence and its in vitro and in vivo cytotoxicity.EXPERIMENTAL APPROACH DNA binding characteristics of PM01183 were studied using electrophoretic mobility shift assays, fluorescence‐based melting kinetic experiments and computational modelling methods. Its mechanism of action was investigated using flow cytometry, Western blot analysis and fluorescent microscopy. In vitro anti‐tumour activity was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and the in vivo activity utilized several human cancer models.KEY RESULTS Electrophoretic mobility shift assays demonstrated that PM01183 bound to DNA. Fluorescence‐based thermal denaturation experiments showed that the most favourable DNA triplets providing a central guanine for covalent adduct formation are AGC, CGG, AGG and TGG. These binding preferences could be rationalized using molecular modelling. PM01183−DNA adducts in living cells give rise to double‐strand breaks, triggering S‐phase accumulation and apoptosis. The potent cytotoxic activity of PM01183 was ascertained in a 23‐cell line panel with a mean GI50 value of 2.7 nM. In four murine xenograft models of human cancer, PM01183 inhibited tumour growth significantly with no weight loss of treated animals.CONCLUSIONS AND IMPLICATIONS PM01183 is shown to bind to selected DNA sequences and promoted apoptosis by inducing double‐strand breaks at nanomolar concentrations. The potent anti‐tumour activity of PM01183 in several murine models of human cancer supports its development as a novel anti‐neoplastic agent.
Participation of CYP2C8 and CYP3A4 in the N‐demethylation of imatinib in human hepatic microsomes
Authors: Nebot Noelia , Crettol Severine , D'Esposito Fabrizio , Tattam Bruce , Hibbs David E , Murray Michael 
Published: July 2010

BACKGROUND AND PURPOSEImatinib is a clinically important inhibitor of tyrosine kinases that are dysregulated in chronic myelogenous leukaemia and gastrointestinal stromal tumours. Inter‐individual variation in imatinib pharmacokinetics is extensive, and influences drug safety and efficacy. Hepatic cytochrome P450 (CYP) 3A4 has been implicated in imatinib N‐demethylation, but the clearance of imatinib decreases during prolonged therapy. CYP3A phenotype correlates with imatinib clearance at the commencement of therapy, but not at steady state. The present study evaluated the possibility that multiple CYPs may contribute to imatinib oxidation in liver.EXPERIMENTAL APPROACHImatinib biotransformation in human liver microsomes (n= 20) and by cDNA‐expressed CYPs was determined by LC–MS. Relationships between imatinib N‐demethylation and other drug metabolizing CYPs were assessed.KEY RESULTSN‐desmethylimatinib formation was correlated with microsomal oxidation of the CYP3A4 substrates testosterone (ρ= 0.60;P< 0.01) and midazolam (ρ= 0.46;P< 0.05), and the CYP2C8 substrate paclitaxel (ρ= 0.58;P< 0.01). cDNA‐derived CYPs 2C8, 3A4, 3A5 and 3A7 supported imatinib N‐demethylation, but 10 other CYPs were inactive; in kinetic studies, CYP2C8 was a high‐affinity enzyme with a catalytic efficiency ∼15‐fold greater than those of CYPs 3A4 and 3A5. The CYP3A inhibitors ketoconazole and troleandomycin, and the CYP2C8 inhibitors quercetin and paclitaxel decreased imatinib oxidation. From molecular modelling, the imatinib structure could be superimposed on a pharmacophore for CYP2C8 substrates.CONCLUSIONS AND IMPLICATIONSCYP2C8 and CYPs 3A contribute to imatinib N‐demethylation in human liver. The involvement of CYP2C8 may account in part for the wide inter‐patient variation in imatinib pharmacokinetics observed in clinical practice.
The Changing Face of the Templars: Current Trends in Historiography
Authors: Nicholson Helen J. 
Published: July 2010

AbstractAlthough French, German and British scholars of the nineteenth and early twentieth centuries did much to lay the foundations of scholarly study of the Knights Templars, until the 1970s there were few good general histories of the Templars. Over the last three decades, there has been enormous growth in scholarly research and publication on the history of the Templars, although the mushrooming myths about the order make it difficult for non‐experts to distinguish between good and bad history. The Templars were a religious order, protected by the pope. They were also a military order, which fought against Islam in defence of Christian pilgrims and Christian territory and played a key role in the crusades. Their leading members were knights, but most of their members were not warriors, and included priests and women, who served God through prayer rather than by fighting. As well as castles and estates in the Middle East, they had property throughout Europe; they served kings and popes as diplomats and advisors. Far from being secretive – as the mythmakers claim – they opened their churches to local people and lodged travellers in their houses. They were pious men who shared the same faith as the Christians they protected. Historians disagree over where the initiative for the order came from – was it the idea of the first Templars themselves, or did Churchmen suggest it to them? The significance of the Templars’ operations in the ‘crusader kingdoms’ in Palestine and Syria has been much discussed. Historians also disagree over the causes of the trial of the Templars (1307–1312), and how far the Templars were innocent victims of a struggle for supremacy between the papacy and the monarchy of France.
Percutaneous liver biopsy in clinical practice
Authors: Al Knawy Bandar , Shiffman Mitchell 
Published: July 2010

AbstractPercutaneous liver biopsy (PLB) is the standard procedure for obtaining hepatic tissue for histopathological examination, and remains an essential tool in the diagnosis and management of parenchymal liver diseases. The use of liver biopsy (LB) is increasing with the advent of liver transplantation and the progress being made in antiviral therapeutic agents. While blind percutaneous needle biopsy is the traditional technique, the use of ultrasound (US) guidance has increased considerably. Literatures were reviewed to assess the existing clinical practice of PLB with an emphasis on the technique, the operator, types of biopsy needles, quality of LB specimens and the risk of complications. The best available evidence indicates that the use of ultrasound‐guided biopsy (UGB) is superior to blind needle biopsy (BNB). The odds ratios of the controlled studies showed that BNB carried a higher risk for major complications, postbiopsy pain and biopsy failure. Therefore, percutaneous LB under US control is superior to BNB and it is recommended that UGB be considered the standard of care for this important and widely used invasive procedure in the field of clinical hepatology.
Prevalence and genotype distribution of hepatitis C virus among apparently healthy individuals in Mongolia: a population‐based nationwide study
Authors: Baatarkhuu Oidov , Kim Do Young , Ahn Sang Hoon , Nymadawa Pagvajav , Dahgwahdorj Yagaanbuyant , Shagdarsuren Manaljav , Park Jun Yong , Choi Jong Won , Oyunbileg Janchiv , Oyunsuren Tsendsuren , Han Kwang Hyub 
Published: July 2010

AbstractBackground and Aims: Hepatitis C virus (HCV) is one of the major causes of liver cirrhosis and hepatocellular carcinoma (HCC) in Mongolia. However, there are no data concerning nationwide prevalence of HCV infection in Mongolia. We intended to investigate the population‐based prevalence of HCV infection and genotype distribution among 1512 apparently healthy individuals in this country.Methods: Between April 2003 and December 2005, sera from 1512 residents of Ulaanbaatar and 12 provinces were collected by two‐stage cluster random sampling, and anti‐HCV was tested. Anti‐HCV‐positive samples were tested for HCV RNA by reverse transcription polymerase chain reaction, and HCV genotype was determined.Results: The mean age of the subjects was 46.2±17.8 years, and 812 (53.7%) were male. Overall, the prevalence of anti‐HCV was 15.6% (236/1512) and HCV RNA was detected in 167 subjects (11.0%), with the most common genotype being 1b (165/167, 98.8%). When the HCV RNA‐positive subjects were categorized by decade of age, the prevalence in each age group was as follows: 2.5% in subjects ≤10 years of age, 4.5% in teens, 10.1% in 20's, 12.5% in 30's, 24.2% in 40's, 29.0% in 50's and 32.6% in subjects ≥61 years of age. The seroprevalence of anti‐HCV in a risk group, nurses, was not significantly different from the general population in each decade of age (P>0.05).Conclusions: Approximately 11.0% of apparently healthy population had detectable HCV RNA in Mongolia, and the predominant genotype of HCV was 1b. Preventive and therapeutic strategies for chronic hepatitis C are urgently warranted in this HCV‐endemic area.
Amniotic membrane induces epithelialization in massive posttraumatic wounds
Authors: Insausti Carmen L. , Alcaraz Antonia , García‐Vizcaíno Eva M. , Mrowiec Anna , López‐Martínez María C. , Blanquer Miguel , Piñero Antonio , Majado María J. , Moraleda José M. , Castellanos Gregorio , Nicolás Francisco J. 
Published: July 2010

ABSTRACTLarge‐surface or deep wounds often become senescent in the inflammatory or proliferation stages and cannot progress to reepithelialization. This failure makes intervention necessary to provide the final sealing epithelial layer. The best current treatment is autologous skin graft, although there are other choices such as allogenic or autologous skin substitutes and synthetic dressings. Amniotic membrane (AM) is a tissue of interest as a biological dressing due to its biological properties and immunologic characteristics. It has low immunogenicity and beneficial reepithelialization effects, with antiinflammatory, antifibrotic, antimicrobial, and nontumorigenic properties. These properties are related to its capacity to synthesize and release cytokines and growth factors. We report the use of AM as a wound dressing in two patients with large and deep traumatic wounds. Negative pressure wound therapy followed by AM application was capable of restoring skin integrity avoiding the need for skin graft reconstruction. AM induced the formation of a well‐structured epidermis. To understand this effect, we designed some assays on human keratinocyte‐derived HaCaT cells. AM treatment of HaCaT induced ERK1/2 and SAP/JNK kinases phosphorylation and c‐jun expression, a gene critical for keratinocytes migration; however, it did not affect cell cycle distribution. These data suggest that AM substantially modifies the behavior of keratinocytes in chronic wounds, thereby allowing effective reepithelialization.
Use of In Vivo Insert Molding to Form a Jellyfish Valve Leaflet
Authors: Kishi Ayumi , Isoyama Takashi , Saito Itsuro , Miura Hidekazu , Nakagawa Hidemoto , Kouno Akimasa , Ono Toshiya , Inoue Yusuke , Yamaguchi Sachiko , Shi Wei , Abe Yusuke , Imachi Kou , Noshiro Makoto 
Published: July 2010

AbstractWe developed an in vivo insert molding technique to form tissue‐derived biomaterials into the desired shape, and with sufficient strength and durability, for use in artificial organs. Molds of acrylic resin with inserted velour cloth were implanted under the skin of goats to form a circular leaflet for a jellyfish valve. The valve leaflets were successfully produced in the molds after 17–60 days. Dense connective tissue covered the velour cloth, and loose connective tissue was formed within it. Tissue was radially formed from the hole in the mold. The tissue was simultaneously formed and shrunk. It is necessary to increase the connected portion between the tissue inside and outside the mold so that the tissue can completely cover the inserted materials without shrinkage.
Nitric Oxide–Independent Stimulation of Soluble Guanylate Cyclase with BAY 41‐2272 in Cardiovascular Disease
Authors: Boerrigter Guido , Burnett John C. 
Published: July 2010

ABSTRACTThe nitric oxide (NO)–soluble guanylate cyclase (sGC)‐cyclic 3′,5′‐guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular regulation by promoting vasodilation and inhibiting vascular smooth muscle cell growth, platelet aggregation, and leukocyte adhesion. In pathophysiological states with endothelial dysfunction this signaling pathway is impaired. Activation of sGC has traditionally been achieved with nitrovasodilators; however, these drugs are associated with the development of tolerance and potentially deleterious cGMP‐independent actions. In this review the actions of BAY 41‐2272, the prototype of a new class of NO‐independent sGC stimulators, in cardiovascular disease models is discussed. BAY 41‐2272 binds to a regulatory site on the α‐subunit of sGC and stimulates the enzyme synergistically with NO. BAY 41‐2272 had antihypertensive actions and attenuated remodeling in models of systemic arterial hypertension. It also unloaded the heart in experimental congestive heart failure. BAY 41‐2272 reduced pulmonary vascular resistance in acute and chronic experimental pulmonary arterial hypertension. Furthermore, BAY 41‐2272 inhibited platelet aggregationin vitroand leukocyte adhesionin vivo.These findings make direct sGC stimulation with BAY 41‐2272 a promising new therapeutic strategy for cardiovascular diseases and warrant further studies. Finally, the significance of the novel NO‐ and heme‐independent sGC activator BAY 58‐2667, which activates two forms of NO‐insensitive sGC, is briefly discussed.
Metabotropic glutamate receptors as a target for anticonvulsant and anxiolytic action in immature rats
Authors: Mareš Pavel , Mikulecká Anna , Tichá Kateřina , Lojková‐Janečková Denisa , Kubová Hana 
Published: July 2010

SummaryAntagonists of group I of metabotropic glutamate receptors (mGluRs) exhibit anticonvulsant as well as anxiolytic action in adult rodents. Therefore, we started to study these effects in developing rats. Motor seizures induced by pentylenetetrazol (PTZ) and cortical epileptic afterdischarges (CxADs) elicited by electrical stimulation were used in immature rats. High doses of antagonists were needed to demonstrate anticonvulsant effects. Antagonist of mGluR1 AIDA [(R,S)‐1‐aminoindan‐1,5‐dicarboxylic acid] suppressed the tonic phase of PTZ‐induced generalized tonic–clonic seizures in 7‐, 12‐, and 18‐day‐old rats, but not in 25‐day‐old rats. No significant effect of AIDA against CxADs was found. Antagonists of mGluR5–MPEP [2‐methyl‐6‐(phenylethynyl)‐pyridine] and MTEP [3‐((2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl)pyridine] exhibited the same effect against PTZ‐induced seizures as AIDA. In addition, they exhibited an anticonvulsant action against CxADs in 12‐ and 18‐day‐old rats. No drug compromised motor performance. Anxiolytic action of all three antagonists was demonstrated in light/dark box or in elevated plus maze tests. Homing reaction was used as an age‐appropriate test of learning. AIDA did not affect homing, whereas the highest dose of MPEP compromised this behavior in 12‐ and partially in 18‐day‐old rats. The three antagonists possess age‐dependent anticonvulsant as well as anxiolytic action, with minimal negative side effects.
Evaluation of development‐specific targets for antiepileptogenic therapy using rapid kindling
Authors: Sankar Raman , Auvin Stéphane , Kwon Young Se , Pineda Eduardo , Shin Don , Mazarati Andréy 
Published: July 2010

SummaryWe used the method of rapid hippocampal kindling to assess the potential antiepileptogenic efficacy of a number of anticonvulsant medications. This method afforded a higher throughput than methods based on traditional kindling or post–status epilepticus models of epileptogenesis. This “compressed epileptogenesis” model also permitted the study of age‐dependent pharmacologic targets, and distinguished among antiepileptic drugs (AEDs) on the basis of their age‐specific antiepileptogenic efficacy. We found retigabine to be the most effective anticonvulsant therapy during early development. Topiramate seemed most effective further along development, whereas some drugs did not demonstrate an age‐specific effect. The method also reproduced some of the paradoxical pharmacologic findings previously shown with lamotrigine. Although the utility of this model for screening the antiepileptogenic therapies requires further validation, it introduces the ability to undertake development‐specific testing and a more rapid throughput than conventional methods.
Are the neurotrophic factors a suitable therapeutic target for the prevention of epileptogenesis?
Authors: Simonato Michele , Zucchini Silvia 
Published: July 2010

SummaryNeurotrophic factors are involved in the survival of neurons as well as in the proliferation and differentiation of neuronal precursors. Therefore, modulating their levels in lesion areas may exert favorable effects on seizure‐induced damage. However, it is unclear if damage limitation or repair may prevent epileptogenesis; it is also uncertain which neurotrophic factor should be administered for limiting or repairing damage while avoiding possible proepileptic effects. We used viral vectors to locally supplement fibroblast growth factor‐2 (FGF‐2) and brain‐derived neurotrophic factor (BDNF), when an epileptogenic damage was already in place. These vectors were tested in the pilocarpine model of status epilepticus–induced neurodegeneration and epileptogenesis. FGF‐2/BDNF expressing vectors increased neuronogenesis, limited neuronal damage, and reduced the occurrence of spontaneous seizures. These findings are discussed with consideration of the hurdles that will have to be overcome before clinical application.
Favorable effects of physical activity for recovery in temporal lobe epilepsy
Authors: Arida Ricardo Mario , Scorza Fulvio Alexandre , Cavalheiro Esper Abrão 
Published: July 2010

SummaryStrategies that are efficacious for preventing or treating of epilepsy have been extensively used. This review discusses the positive effects of physical exercise program in experimental models of epilepsy, and considerations of the potential application of physical exercise strategy for preventing or treating temporal lobe epilepsy (TLE) are highlighted. Findings from animal studies indicate that exercise can modulate neuronal vulnerability to epileptic insults. Exercise treatment before a precipitating brain insult demonstrates a reduced brain susceptibility in the kindling or the pilocarpine model of epilepsy. In view of the beneficial effect of exercise during the epileptogenesis process, studies analyzed the influence of exercise after the development of chronic epilepsy. Behavioral analysis showed a reduced frequency of seizures during physical exercise program. Metabolic, electrophysiologic, and immunohistochemical studies have confirmed the positive influence of exercise on epilepsy. Taken into account that exercise can exert beneficial actions such as reduction of seizure susceptibility as observed in animal studies, and improvement of quality of life and reduction of anxiety and depression of individuals with epilepsy, physical exercise can be a potential candidate to be integrated with conventional therapy for epilepsy.