bluuebunny/crossref_metadata_2025 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

Aim  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

The 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

Although 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

Percutaneous 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

Background 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

Large‐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.
Development of the nervous system in the acorn worm Balanoglossus simodensis: insights into nervous system evolution
Authors: Miyamoto Norio , Nakajima Yoko , Wada Hiroshi , Saito Yasunori
Published: July 2010

SUMMARY
To examine the evolutionary origin of the chordate nervous system, an outgroup comparison with hemichordates is needed. When the nervous systems of chordates and hemichordates are compared, two possibilities have been proposed, one of which is that the chordate nervous system has evolved from the nervous system of hemichordate‐like larva and the other that it is comparable to the adult nervous system of hemichordates. To address this issue, we investigated the entire developmental process of the nervous system in the acorn worm Balanoglossus simodensis. In tornaria larvae, the nervous system developed along the longitudinal ciliary band and the telotroch, but no neurons were observed in the ventral band or the perianal ciliary ring throughout the developmental stages. The adult nervous system began to develop at the dorsal midline at the Krohn stage, considerably earlier than metamorphosis. During metamorphosis, the larval nervous system was not incorporated into the adult nervous system. These observations strongly suggest that the hemichordate larval nervous system contributes little to the newly formed adult nervous system.
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

We 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

The 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

Antagonists 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

We 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

Neurotrophic 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

Strategies 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.
Dynamic changes of CB1‐receptor expression in hippocampi of epileptic mice and humans
Authors: Maglóczky Zsófia , Tóth Kinga , Karlócai Rita , Nagy Sára , Erőss Loránd , Czirják Sándor , Vajda János , Rásonyi György , Kelemen Anna , Juhos Vera , Halász Péter , Mackie Ken , Freund Tamás F.
Published: July 2010

The endocannabinoid system plays a central role in retrograde synaptic communication, and controls both glutamatergic and γ‐aminobutyric acid (GABA)ergic transmission via type 1 cannabinoid (CB1) receptor. Both in sclerotic human hippocampi and in the chronic phase of pilocarpine‐induced epilepsy in mice with sclerosis, CB1‐receptor–positive interneuron somata were preserved both in the dentate gyrus and in the CA1 area, and the density of CB1‐immunostained fibers increased considerably in the dentate molecular layer. This suggests that, although CB1 receptors are known to be reduced in density on glutamatergic axons, the CB1‐receptor–expressing GABAergic axons sprout, or there is an increase of CB1‐receptor levels on these fibers. The changes of CB1 immunostaining in association with the GABAergic inhibitory system appear to correlate with the severity of pyramidal cell loss in the CA1 subfield. These results confirm the involvement of the endocannabinoid system associated with GABAergic transmission in human temporal lobe epilepsy (TLE), as well as in the chronic phase of the pilocarpine model in mice. Pharmacotherapy aimed at the modulation of endocannabinoid‐mediated retrograde synaptic signaling should take into account the opposite change in CB1‐receptor expression observed on glutamatergic versus GABAergic axon terminals.
New therapeutic approaches for epilepsies, focusing on reorganization of the GABAA receptor subunits by neurosteroids
Authors: Murashima Yoshiya L. , Yoshii Mitsunobu
Published: July 2010

Neurosteroids such as allopregnanolone (THP) act as positive allosteric modulators of γ‐aminobutyric acid (GABA)A receptors and have exerted anticonvulsant properties. However, their role in the regulation of epileptogenesis is unclear. It has been shown that circulating levels of THP fluctuate during development and seizure episodes. Furthermore, both chronic administration of THP and its withdrawal transiently increase expression of the alpha4 subunit of the GABAA receptor in the brain. The steroidogenic enzymes, 5‐alpha‐reductase (5aR) and 3‐alpha‐hydroxysteroid dehydrogenase (3aHSD) have been identified as well, indicating that various cell types are involved in the biosynthesis of neuroactive steroids in the brain. The purpose of the present study is to examine how GABAA receptor–modulating neurosteroids contribute to the epileptogenesis by using the epileptic mutant EL mouse.

Male EL mice and control animals, DDY mice, were used. EL mice show secondary generalized seizures, which initiate primarily at the parietal cortex and generalize through the hippocampus. In the interictal period during development, changes of THP, 5aR, 3aSDH, and GABAA receptor alpha4, gamma2, and delta subunits were investigated by western blotting in the hippocampus.

In EL mice, levels of the neurosteroid THP and the steroidogenic enzymes 5aR and 3aSDH significantly increased at 3 weeks of age, and rapidly decreased thereafter (5–10 weeks). The sharp withdrawal was observed before mice experienced frequent seizures. In contrast, GABAA alpha4, gamma2, and delta expressions were upregulated (3–8 weeks).

In the brain of EL mice, positive neurosteroids such as THP were withdrawn before mice experienced repetitive seizures, which may likely be a trigger for ictogenesis and epileptogenesis. Furthermore, reorganization of the GABAA receptor subunits may lead to a hypersensitivity of the receptor to neurosteroids. Therefore, GABAA receptor–regulating neurosteroids may be a promising target for the development of novel antiepileptic agents.
Females, their estrogens, and seizures
Authors: Velíšková Jana , De Jesus Glendis , Kaur Ramanjot , Velíšek Libor
Published: July 2010

Estrogens are essential for normal brain functions. The effects of estrogens on seizures are contradictory. More studies are necessary to determine under which conditions the estrogens have proconvulsant effects and when the estrogens may have beneficial action in patients with epilepsy.
Magnetoencephalographic correlates of different types of aura in temporal lobe epilepsy
Authors: Fukao Kenjiro , Inoue Yushi , Yagi Kazuichi
Published: July 2010

Purpose:  To estimate magnetoencephalography (MEG) correlates of different types of aura in temporal lobe epilepsy (TLE).

Methods:  MEG study was performed on 57 patients (26 male and 31 female) with TLE, whose ages ranged from 14–46 years (mean 27 years). Interictal magnetoencephalograms showing discharges were analyzed, and spike‐dipole clusters were categorized into left and right inferotemporal‐horizontal (IH) and superotemporal‐vertical (SV) types. Auras were classified into autonomic, auditory, and psychic seizures. The correlation between the four types of interictal spike‐dipole and three types of aura was analyzed using Fisher’s exact probability test.

Results:  IH type correlated with autonomic seizures (p = 0.0004), whereas SV type correlated with both auditory (p = 0.0002) and psychic seizures (p = 0.042). When subdivided into left and right, left IH type correlated with autonomic seizures (p = 0.046), but right IH type did not. Right SV type correlated with both auditory (p = 0.014) and psychic seizures (p = 0.002), but left SV did not correlate with either. Both types did not correlate with “no aura.”

Conclusions:  Using our proposed classification of spike‐dipoles, MEG distinguishes auras of mesial temporal origin from those of lateral temporal region. Furthermore, by adopting our classification, laterality of spike‐dipoles is clearly demonstrated in auditory and psychic seizures.
Validity and Reliability of the Arabic Adapted Version of the DN4 Questionnaire (Douleur Neuropathique 4 Questions) for Differential Diagnosis of Pain Syndromes with a Neuropathic or Somatic Component
Authors: Harifi Ghita , Ouilki Imane , El Bouchti Imane , Ait Ouazar Mariam , Belkhou Ahlam , Younsi Rachid , Amine Mohamed , Tazi Imane , Abouqal Redouane , Niamane Redouane , El Hassani Selma
Published: July 2010

Background:  Verbal descriptors of pain can provide a basis for distinguishing neuropathic pain (NP) from pain of non‐neuropathic origin. Much research has been undertaken to develop screening tools for this purpose. The DN4 questionnaire (NP in four questions), is one of theses tools, which was developed and validated in French in 2005. The purpose of this work is to provide an Arabic, culturally appropriate, reliable, and valid version of the DN4 interview questionnaire for the diagnosis of NP.

Methods:  A study was conducted consisting of two phases. In the first phase, translation and cultural adaptation of the questionnaire into dialectal Arabic according to international guidelines was accomplished. The final version was reviewed by an expert panel, then tested on a group of 30 patients. The second phase was the validation of the translated version. The analysis of psychometric properties included reliability (internal consistency, inter‐rater agreement) and validity (receiver operating characteristics curve analysis and determination of sensitivity, specificity, and positive and negative predictive values).

Results:  A sample of 170 subjects (129 women, 75%; age: 49.5 ± 12.4 years), 94 (55.3%) with NP and 76 with non‐neuropathic pain was enrolled. The questionnaire was reliable (Cronbach's alpha coefficient: 0.63, inter‐rater agreement coefficient: 0.96 [0.94–0.97]) and valid for a cut‐off value ≥ 3 points, which was the best value to discriminate between NP and NNP subjects.

Discussion:  This study represents the second validation DN4 in a language different from the original after the Spanish adaptation. These results support the high discriminatory value of the DN4 questionnaire for identification of NP.
RHCE*ceCF encodes partial c and partial e but not CELO, an antigen antithetical to Crawford
Authors: Hipsky Christine Halter , Lomas‐Francis Christine , Fuchisawa Akiko , Reid Marion E. , Moulds Marilyn , Christensen JoAnn , Nickle Pam , Vege Sunitha , Westhoff Connie
Published: July 2010

BACKGROUND: RH43 (Crawford) is encoded by RHCE*ce with nucleotide changes 48G>C, 697C>G, and 733C>G (RHCE*ceCF). We investigated the Rh antigen expression and antibody specificities in four patients with this allele.

STUDY DESIGN AND METHODS: Hemagglutination tests, DNA extraction, polymerase chain reaction (PCR)‐restriction fragment length polymorphism, allele‐specific PCR, reticulocyte RNA isolation, reverse transcription‐PCR cDNA analyses, cloning, and sequencing were performed by standard procedures.

RESULTS: Red blood cells (RBCs) from two patients typed D+C−E−c+e+/−, hrS−/+W, hrB− and their serum was reactive (3+) with all RBC samples of common Rh phenotype tested, but nonreactive with Rhnull or D−– RBCs (apparent alloanti‐Rh17). At the RHCE locus, Patient 1 was homozygous for RHCE*ceCF, and Patient 2 inherited RHCE*ceCF in trans to a silenced RHCE*cE. Cross‐testing of serum and RBCs from these two samples showed mutual compatibility, indicating that both antibodies define the same novel high‐prevalence antigen on Rhce. Two additional patients, one whose serum contained alloanti‐c but the RBCs typed C+c+ and one whose serum contained anti‐e but the RBCs typed E+e+, also had RHCE*ceCF. RHCE*Ce was present in trans in the former and RHCE*cE in the latter patient.

CONCLUSION: We report that amino acid changes on RhceCF (Trp16Cys, Gln233Glu, and Leu245Val) alter the protein to the extent that c and e antigens are partial, and a high‐prevalence antigen, we have named CELO (provisional ISBT Number 004058; RH58) is not expressed. CELO is antithetical to RH43 (Crawford).
A Wavelet‐Based Extension of Generalized Linear Models to Remove the Effect of Spatial Autocorrelation. 基于小波扩展广义线性模型消除空间自相关的影响
Authors: Carl Gudrun , Kühn Ingolf
Published: July 2010

Biogeographical studies are often based on a statistical analysis of data sampled in a spatial context. However, in many cases standard analyses such as regression models violate the assumption of independently and identically distributed errors. In this article, we show that the theory of wavelets provides a method to remove autocorrelation in generalized linear models (GLMs). Autocorrelation can be described by smooth wavelet coefficients at small scales. Therefore, data can be decomposed into uncorrelated and correlated parts. Using an appropriate linear transformation, we are able to extend GLMs to autocorrelated data. We illustrate our new method, called the wavelet‐revised model (WRM), by applying it to multiple regression with response variables conforming to various distributions. Results are presented for simulated data and real biogeographical data (species counts of the plant genus Utricularia [bladderworts] in grid cells throughout Germany). The results of our WRM are compared with those of GLMs and models based on generalized estimating equations. We recommend WRMs, especially as a method that allows for spatial nonstationarity. The technique developed for lattice data is applicable without any prior knowledge of the real autocorrelation structure.
The Legitimacy of Social Entrepreneurship: Reflexive Isomorphism in a Pre–Paradigmatic Field
Authors: Nicholls Alex
Published: July 2010

Following Kuhn, this article conceptualizes social entrepreneurship as a field of action in a pre–paradigmatic state that currently lacks an established epistemology. Using approaches from neo–institutional theory, this research focuses on the microstructures of legitimation that characterize the development of social entrepreneurship in terms of its key actors, discourses, and emerging narrative logics. This analysis suggests that the dominant discourses of social entrepreneurship represent legitimating material for resource–rich actors in a process of reflexive isomorphism. Returning to Kuhn, the article concludes by delineating a critical role for scholarly research on social entrepreneurship in terms of resolving conflicting discourses within its future paradigmatic development.
Growth of ZnO Nanobrushes Using a Two‐Step Aqueous Solution Method
Authors: Park Jae Young , Choi Sun‐Woo , Asokan Kandasami , Kim Sang Sub
Published: July 2010

A low‐temperature template‐free two‐step aqueous solution route has been successfully developed to prepare ZnO nanobrushes. First, hexagonal ZnO microrods were grown from the precursor solutions containing zinc nitrate hexahydrate and hexamethylenetetramine. In the second step, well‐aligned vertical ZnO nanorods were grown particularly on the facet planes of hexagonal ZnO microrods from the precursor solutions of zinc nitrate hexahydrate and NH4OH. This two‐step aqueous process consequently produces ZnO nanostructures with a nanobrush shape. Structure and morphology of the synthesized ZnO nanobrushes were investigated by using X‐ray diffraction, field‐emission scanning electron microscopy, and photoluminescence.
Patterns of aggregation behaviour in six species of cockroach: comparing two experimental approaches
Authors: Varadínová Zuzana , Stejskal Václav , Frynta Daniel
Published: July 2010

Cockroaches (Blattaria) are considered universally gregarious insects. In this study, we tested the hypothesis that even related species and/or males and females of the same species may exhibit different aggregation patterns. We compared aggregation behaviour in six cockroach species belonging to three groups: Eublaberus, Blaberus, and Gromphadorhina‐Princisia (all Blaberidae). For comparison, binary choice and free aggregation arena tests were used. The results revealed that blaberid clades clearly differed in their aggregation patterns. Females of Eublaberus species aggregated, whereas only a low aggregation tendency was recorded in conspecific males. Both sexes of Blaberus species aggregated, especially when tested in the arena. The Madagascar hissing cockroaches of the Gromphadorhina‐Princisia clade are not gregarious – the aggregation tendency was entirely absent in males of the two species studied and in females of Princisia vanwaerebeki van Herrewege, and was only weakly demonstrated in females of Gromphadorhina portentosa (Schaum). The observed patterns of aggregation are compared with previous reports concerning social behaviour of blaberid species.
Predicting Competitive‐Unethical Negotiating Behavior and Its Consequences
Authors: Volkema Roger , Fleck Denise , Hofmeister Agnes
Published: July 2010

This study examines the relationships between negotiators' attitudes toward competitive and unethical tactics, their actual use of those tactics, and their subsequent perceptions of performance and reputation in two‐party, e‐mail‐based negotiations. The results indicate several predictors of competitive‐unethical behavior, including a negotiator's attitude toward competitive‐unethical tactics, early use of competitive‐unethical tactics, and the behavior of a negotiating counterpart. Furthermore, it was the perceived honesty of one's counterpart rather than the actual use of competitive‐unethical behaviors that was associated with a negotiator's perceptions of the collective or joint outcome. The implications of these findings are discussed, along with suggestions for future research.
Transformative Women, Problem‐Solving Men? Not Quite: Gender and Mediators' Perceptions of Mediation
Authors: Nelson Noa , Zarankin Adi , Ben‐Ari Rachel
Published: July 2010

A large field study examined female and male mediators' perceptions of their jobs, looking in particular at their attitudes toward mediation styles lying on the continuum between instrumental and transformative. Based on scholarship on gender and negotiation literature that has portrayed women as more interpersonal and somewhat less task oriented than men, we expected female mediators to be more transformative and less instrumental in their practice than their male peers.

Our study was both qualitative and quantitative: we formulated the content of twenty in‐depth interviews into an extensive questionnaire, answered by a representative sample of 189 Israeli mediators. Compared with their male counterparts, we found female mediators to be more transformative, but no less instrumental, in their view of mediation's goals and orientation. They were also somewhat more facilitative in preferred style, while male mediators were somewhat more directive. We also found additional intriguing gender differences, including that women mediators reported higher job satisfaction than did male mediators, but they also displayed a greater readiness to perceive failure in mediation.
Consensus Arbitration: A Negotiation‐Based Decision‐Making Process for Arbitrators
Authors: Witkin Nathan
Published: July 2010

In reaching their decisions, arbitrators are currently expected to act like judges by listening fully to both sides and then withdrawing to write the final and complete decision. But because of some key differences between their roles, I argue, arbitrators and judges should exercise completely different styles of decision making. Unlike judges, who make decisive rulings in order to enforce the law, arbitrators are empowered and chosen by the parties themselves to handle specific disputes or govern continuing relationships. Instead of shifting a negotiated process into an authoritative one, arbitrators have the capacity to solicit input from parties as they craft the award. Under a new model of arbitration that I call “consensus arbitration,” arbitrators would facilitate negotiation between the parties but retain the power to break impasses with partial, incomplete decisions, behaving more like facilitators than judges.
Microparticles – messengers of biological information
Authors: Hoyer Friedrich Felix , Nickenig Georg , Werner Nikos
Published: July 2010

Introduction

Microparticles

Methodological aspects

Understanding microparticles – from biomarker to messenger

Understanding microparticles – intercellular communication pathways

Conclusions and perspectives

Conflict of interest

Endothelial cell apoptosis is a pivotal step in the development of atherosclerotic disease. Regeneration of the damaged endothelium is an attractive therapy option in the prevention and treatment of atherosclerotic disease. Apoptosis is associated with the release of microparticles (MP). Besides their role as marker of cell damage, recent reports have underlined their role as signalling elements in cell–cell communication. In this review, we focus on the emerging role of circulating MP as transmitters of biological information in cardiovascular disease.
Use of Cervista HPV HR assay for detection of human papillomavirus in samples with hybrid capture borderline negative results
Authors: Galan‐Sanchez Fatima , Rodriguez‐Iglesias Manuel A.
Published: July 2010

Galan‐Sanchez F, Rodriguez‐Iglesias MA. Use of Cervista HPV HR assay for detection of human papillomavirus in samples with hybrid capture borderline negative results. APMIS 2010; 118: 681–4.

We have evaluated Cervista HPV HR for papillomavirus detection in 65 samples previously borderline negative by the hybrid capture method (Digene), using InnoLipa and sequencing as confirmatory techniques. Nine samples were found to be positive by Cervista HPV HR, of which five (7.6%) were confirmed by InnoLipa. Four samples (6.1%) were false positive, of which three samples were reactive for A9 probes. The Cervista HPV HR assay can detect HPV‐positive samples from those with hybrid capture borderline results but can produce false‐positive results when tested for reactivity with A9 probes.
C‐reactive protein in gingival crevicular fluid may be indicative of systemic inflammation
Authors: Megson Emma , Fitzsimmons Tracy , Dharmapatni Kencana , Mark Bartold P.
Published: July 2010

Megson E, Fitzsimmons T, Dharmapatni K, Bartold PM. C‐reactive protein in gingival crevicular fluid may be indicative of systemic inflammation. J Clin Periodontol 2010; 37: 797–804. doi: 10.1111/j.1600‐051X.2010.01603.x.

Background and Aim: Periodontitis is associated with elevated C‐reactive protein (CRP) in both serum and gingival crevicular fluid (GCF). Although the liver is the primary source of CRP, extra‐hepatic production of CRP has been reported. This study aimed to determine whether CRP in GCF is produced locally in the gingivae.

Materials and Methods: Gingivae and GCF were collected from non‐periodontitis and periodontitis sites. Presence of CRP in gingivae was assessed by immunohistochemistry. CRP in GCF was measured using ELISA. Gene expression for CRP in gingivae was determined using real‐time polymerase chain reaction.

Results: CRP was found in both the gingivae and GCF. No gingivae had detectable amounts of CRP mRNA. Not all patients with periodontitis had detectable levels of CRP in the GCF. Some non‐periodontitis patients had detectable levels of CRP in the GCF.

Conclusion: CRP in the GCF appears to be of systemic origin, and therefore may be indicative of systemic inflammation from either a periodontal infection or inflammatory disease elsewhere. The correlation between levels of CRP in GCF and serum requires validation in future studies.
Primate‐specific regulation of natural killer cells
Authors: Parham Peter , Abi‐Rached Laurent , Matevosyan Lilit , Moesta Achim K. , Norman Paul J. , Older Aguilar Anastazia M. , Guethlein Lisbeth A.
Published: July 2010

Natural killer (NK) cells are circulating lymphocytes that function in innate immunity and placental reproduction. Regulating both development and function of NK cells is an array of variable and conserved receptors that interact with major histocompatibility complex (MHC) class I molecules. Families of lectin‐like and immunoglobulin‐like receptors are determined by genes in the natural killer complex (NKC) and leukocyte receptor complex (LRC), respectively. As a consequence of the strong, varying pressures on the immune and reproductive systems, NK cell receptors and their MHC class I ligands evolve rapidly, are highly diverse and exhibit dramatic species‐specific differences. The variable, polymorphic family of killer cell immunoglobulin‐like receptors (KIR) that regulate human NK cell development and function arose recently, from a single‐copy gene during the evolution of simian primates. Our studies of KIR and MHC class I genes in representative species show how these two unlinked but functionally intertwined genetic complexes have co‐evolved. In humans, combinations of KIR and HLA class I factors are associated with infectious diseases, including HIV/AIDS, autoimmunity, reproductive success and the outcome of therapeutic transplantation. The extraordinary, and unanticipated, divergence of human NK cell receptors and MHC class I ligands from their mouse counterparts can in part explain the difficulties experienced in finding informative mouse models for human diseases. Non‐human primate models have far greater potential, but to realize their promise will first require more complete definition of the genetics and function of KIR and MHC variation in non‐human primate species, at a level comparable to that achieved for the human species.