bluuebunny/crossref_metadata_2025 huggingface dataset:
Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic
Authors: Kurz CM , Baranowska U , Łupiński S , Göthert M , Malinowska B , Schlicker E
Published: July 2009

Background and purpose: We examined whether cannabinoid CB1and histamine H3receptors resemble α2‐adrenoceptors in that their presynaptically mediated cardiovascular effects are less marked in urethane‐ than in pentobarbitone‐anaesthetized pithed rats.

Experimental approach: Effects of the cannabinoid agonist CP‐55,940 and the H3receptor agonist imetit on electrically induced tachycardic and vasopressor responses, respectively, was compared in pithed rats anaesthetized with urethane or pentobarbitone. The affinity of urethane for the three receptors was measured by radioligand binding studies in rat brain cortex membranes and its potency assessed in superfused mouse tissues preincubated with3H‐noradrenaline.

Key results: The neurogenic tachycardic response was less markedly inhibited by CP‐55,940 in urethane‐ than in pentobarbitone‐anaesthetized pithed rats. Imetit inhibited the neurogenic vasopressor response after pentobarbitone but not after urethane. The catecholamine‐induced tachycardic and vasopressor response did not differ between rats anaesthetized with either compound. Urethane 10 mM (plasma concentration reached under anaesthesia) did not affect binding to CB1or H3receptors and α2adrenoceptors, nor did it alter the inhibitory effect of agonists at the three receptors on electrically evoked3H‐noradrenaline release.

Conclusions and implications: Urethane, but not pentobarbitone, abolished the H3receptor‐mediated vascular response in pithed rats and attenuated the CB1receptor‐mediated cardiac response much more than pentobarbitone. The weaker effects of CB1, H3and α2receptor agonists cannot be explained by antagonism by urethane at the three receptorsin vitro. Pentobarbitone, but not urethane, is suitable as an anaesthetic for investigations of inhibitory presynaptic receptor function in pithed and anaesthetized rats.
Bioavailability of diazepam after intramuscular injection of its water‐soluble prodrug alone or with atropine–pralidoxime in healthy volunteers
Authors: Abbara C , Rousseau JM , Turcant A , Lallement G , Comets E , Bardot I , Clair P , Diquet B
Published: July 2009

Background and purpose:  The aim of this study was to assess the relative bioavailability of diazepam after administration of diazepam itself or as a water‐soluble prodrug, avizafone, in humans.

Experimental approach:  The study was conducted in an open, randomized, single‐dose, three‐way, cross‐over design. Each subject received intramuscular injections of avizafone (20 mg), diazepam (11.3 mg) or avizafone (20 mg) combined with atropine (2 mg) and pralidoxime (350 mg) using a bi‐compartmental auto‐injector (AIBC). Plasma concentrations of diazepam were quantified using a validated LC/MS–MS assay, and were analysed by both a non‐compartmental approach and by compartmental modelling.

Key results:  The maximum concentration (Cmax) of diazepam after avizafone injection was higher than that obtained after injection of diazepam itself (231 vs. 148 ng·mL−1), while area under the curve (AUC) values were equal. Diazepam concentrations reached their maximal value faster after injection of avizafone. Injection of avizafone with atropine–pralidoxime (AIBC) had no effect on diazepam Cmax and AUC, but the time to Cmax was increased, relative to avizafone injected alone. According to the Akaike criterion, the pharmacokinetics of diazepam after injection as a prodrug was best described as a two‐compartment with zero‐order absorption model. When atropine and pralidoxime were injected with avizafone, the best pharmacokinetic model was a two‐compartment with a first‐order absorption model.

Conclusion and implications:  Diazepam had a faster entry to the general circulation and achieved higher Cmax after injection of prodrug than after the parent drug. Administration of avizafone in combination with atropine and pralidoxime by AIBC had no significant effect on diazepam AUC and Cmax.
The K+ channels KCa3.1 and Kv1.3 as novel targets for asthma therapy
Authors: Bradding Peter , Wulff Heike
Published: July 2009

Asthma affects 10% of the UK population and is an important cause of morbidity and mortality at all ages. Current treatments are either ineffective or carry unacceptable side effects for a number of patients; in consequence, development of new approaches to therapy are important. Ion channels are emerging as attractive therapeutic targets in a variety of non‐excitable cells. Ion channels conducting K+ modulate the activity of several structural and inflammatory cells which play important roles in the pathophysiology of asthma. Two channels of particular interest are the voltage‐gated K+ channel Kv1.3 and the intermediate conductance Ca2+‐activated K+ channel KCa3.1 (also known as IKCa1 or SK4). Kv1.3 is expressed in IFNγ‐producing T cells while KCa3.1 is expressed in T cells, mast cells, macrophages, airway smooth muscle cells, fibroblasts and epithelial cells. Both channels play important roles in cell activation, migration, and proliferation through the regulation of membrane potential and calcium signalling. We hypothesize that KCa3.1‐ and/or Kv1.3‐dependent cell processes are one of the common denominators in asthma pathophysiology. If true, these channels might serve as novel targets for the treatment of asthma. Emerging evidence lends support to this hypothesis. Further validation through the study of the role that these channels play in normal and asthmatic airway cell (patho)physiology and in vivo models will provide further justification for the assessment of small molecule blockers of Kv1.3 and KCa3.1 in the treatment of asthma.
Conservation Value of Sites of Hybridization in Peripheral Populations of Rare Plant Species
Authors: THOMPSON JOHN D. , GAUDEUL MYRIAM , DEBUSSCHE MAX
Published: July 2009

Abstract:  Populations at the periphery of a species’ range are of interest to conservation biologists because they can show marked genetic differentiation from populations at the center of a range and because of potential hybridization among rare and common species. We examined two closely related Cyclamen species. One is a narrow endemic, and the other is more geographically widespread (both protected by law in continental southern France). We used floral traits and genetic variability to test for hybridization among the species in peripheral populations of the rare species. The species co‐occurred on Corsica in a disjunct, peripheral part of the distribution of the endemic species and in an ecologically marginal area for the widespread species. The two species have hybridized and the endemic species showed high levels of introgression with its widespread congener. Genetic and floral variability in sites with both species was markedly higher than in sites with a single species. Our results highlight the need for a conservation strategy that integrates hybrid populations because they represent a source of novel diversity that may have adaptive potential.
Obscuring Ecosystem Function with Application of the Ecosystem Services Concept
Authors: PETERSON MARKUS J. , HALL DAMON M. , FELDPAUSCH‐PARKER ANDREA M. , PETERSON TARLA RAI
Published: July 2009

Abstract:  Conservationists commonly have framed ecological concerns in economic terms to garner political support for conservation and to increase public interest in preserving global biodiversity. Beginning in the early 1980s, conservation biologists adapted neoliberal economics to reframe ecosystem functions and related biodiversity as ecosystem services to humanity. Despite the economic success of programs such as the Catskill/Delaware watershed management plan in the United States and the creation of global carbon exchanges, today's marketplace often fails to adequately protect biodiversity. We used a Marxist critique to explain one reason for this failure and to suggest a possible, if partial, response. Reframing ecosystem functions as economic services does not address the political problem of commodification. Just as it obscures the labor of human workers, commodification obscures the importance of the biota (ecosystem workers) and related abiotic factors that contribute to ecosystem functions. This erasure of work done by ecosystems impedes public understanding of biodiversity. Odum and Odum's radical suggestion to use the language of ecosystems (i.e., emergy or energy memory) to describe economies, rather than using the language of economics (i.e., services) to describe ecosystems, reverses this erasure of the ecosystem worker. Considering the current dominance of economic forces, however, implementing such solutions would require social changes similar in magnitude to those that occurred during the 1960s. Niklas Luhmann argues that such substantive, yet rapid, social change requires synergy among multiple societal function systems (i.e., economy, education, law, politics, religion, science), rather than reliance on a single social sphere, such as the economy. Explicitly presenting ecosystem services as discreet and incomplete aspects of ecosystem functions not only allows potential economic and environmental benefits associated with ecosystem services, but also enables the social and political changes required to ensure valuation of ecosystem functions and related biodiversity in ways beyond their measurement on an economic scale.
Atypical rolandic epilepsy
Authors: Fejerman Natalio
Published: July 2009

Typical benign rolandic epilepsy (BRE) is a frequent and well‐delineated epileptic syndrome in childhood. Mild cognitive and behavioral difficulties are increasingly recognized in the course of BRE and should not be considered as atypical features. Atypical features are recognized on electroclinical grounds. These features, particularly early age at onset and frequent spikes or spike‐wave discharges, seem to be risk factors for neuropsychological deficits but also for an atypical evolution of BRE. Atypical evolutions of BRE are defined by the appearance of severe neuropsychological impairments and continuous spike‐and‐waves during slow sleep (CSWSS). The clinical expressions of these situations correspond to the syndromes known as atypical benign focal epilepsy of childhood (ABFEC), status of BRE, Landau‐Kleffner syndrome (LKS), and CSWSS syndrome, which may be part of a continuum related to BRE.
CSWS‐related autistic regression versus autistic regression without CSWS
Authors: Tuchman Roberto
Published: July 2009

Continuous spike‐waves during slow‐wave sleep (CSWS) and Landau‐Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.
From rolandic epilepsy to continuous spike‐and‐waves during sleep and Landau‐Kleffner syndromes: Insights into possible genetic factors
Authors: Rudolf Gabrielle , Valenti Maria P. , Hirsch Edouard , Szepetowski Pierre
Published: July 2009

Epilepsy is a frequent neurologic disease in childhood, characterized by recurrent seizures and sometimes with major effects on social, behavioral, and cognitive development. Childhood focal epilepsies particularly are age‐related diseases mainly occurring during developmental critical periods. A complex interplay between brain development and maturation processes and susceptibility genes may contribute to the development of various childhood epileptic syndromes associated with language and cognitive deficits. Indeed, the Landau‐Kleffner syndrome (LKS), the continuous spike‐and‐waves during sleep syndrome (CSWS), and the benign childhood epilepsy with centrotemporal spikes (BCECTS) or benign rolandic epilepsy, are different entities that are considered as part of a single continuous spectrum of disorders. Genetic predisposition with simple to complex modes of inheritance has long been suspected for this wide group of childhood focal epilepsies. Recent reports on the involvement of the SRPX2 and ELP4 genes with possible roles in cell motility, migration, and adhesion have provided first insights into the complex molecular bases of childhood focal epilepsies.
Acquired cognitive dysfunction with focal sleep spiking activity
Authors: Paquier Philippe F. , Verheulpen Denis , De Tiège Xavier , Van Bogaert Patrick
Published: July 2009

The syndrome of continuous spike‐waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non‐REM sleep, and takes the form of continuous bilateral and diffuse slow spike‐waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F‐fluorodeoxyglucose (PET‐FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike‐waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET‐FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.
Neurophysiology of CSWS‐associated cognitive dysfunction
Authors: Seri Stefano , Thai Jade Ndoc , Brazzo Daniela , Pisani Francesco , Cerquiglini Antonella
Published: July 2009

The phenomenon of continuous spikes and waves during slow‐wave sleep (CSWS) is associated with a number of epileptic syndromes, which share a behavioral phenotype characterized by deterioration of cognitive, behavioral, or sensorimotor functions. Available evidence seems to suggest that spike‐wave activity is a result of a complex interaction between cortical and subcortical inhibitory networks and can “per se” produce a transient loss of underlying cortical functions. Syndromes like Landau‐Kleffner syndrome, CSWS, and phenomena such as negative myoclonus could share in common—at least at the neurophysiological level—some similarities. Differences in behavioral phenotypes could be explained in term of maturational and genetic differences, as well as by the functional specificity of the involved areas.
Some facts about sleep relevant for Landau‐Kleffner syndrome
Authors: Mascetti Laura , Foret Ariane , Bonjean Maxime , Matarazzo Luca , Dang‐Vu Thanh , Maquet Pierre
Published: July 2009

Our understanding of the neural mechanisms of non–rapid eye movement sleep (NREM) is steadily increasing. Given the intriguing activation of paroxysmal activity during NREM sleep in patients with Landau‐Kleffner syndrome (LKS), a thorough characterization of commonalities and differences between the neural correlates of LKS paroxysms and normal sleep oscillations might provide useful information on the neural underpinning of this disorder. Especially, given the suspected role of sleep in brain plasticity, this type of information is needed to assess the link between cognitive deterioration and electroencephalography (EEG) paroxysms during sleep.
The surgical treatment of Landau‐Kleffner syndrome
Authors: Cross J. Helen , Neville Brian G. R.
Published: July 2009

The medical management of Landau‐Kleffner syndrome is usually effective for seizure control and eventual seizure remission. However, the response for language and behavior is often poor. Surgery, in the form of multiple subpial transections (MSTs) to include Wernicke’s area has been suggested as a way forward if electrophysiologic lateralization can be demonstrated. Surgical series in the literature are few and outcome from surgery variable
Sign language in Landau‐Kleffner syndrome
Authors: Deonna Thierry , Prelaz‐Girod Anne‐Claude , Mayor‐Dubois Claire , Roulet‐Perez Eliane
Published: July 2009

This article reviews the history of sign language (SL) and the rationale for its use in children with profound auditory agnosia due to Landau‐Kleffner syndrome (LKS), illustrated by studies of children and adults followed for many years and rare cases from the literature. The reasons that SL was successful and brought some children out of isolation while it could not be implemented in others are discussed. The nowadays earlier recognition and treatment of LKS and better awareness of the crucial need to maintain communication have certainly improved the outcome of affected children. Alternatives to oral language, even for less severe cases, are increasingly accepted. SL can be learned at different ages with a clear benefit, but the ambivalence of the patients and their families with the world and culture of the deaf may sometimes explain its refusal or limited acceptance. There are no data to support the fear that SL learning may delay or prevent oral language recovery in children with LKS. On the contrary, SL may even facilitate this recovery by stimulating functionally connected core language networks and by helping speech therapy and auditory training.
TRANSPLANTATION AND CELLULAR ENGINEERING: Long‐term storage does not alter functionality of in vitro generated human erythroblasts: implications for ex vivo generated erythroid transfusion products
Authors: Migliaccio Giovanni , Sanchez Massimo , Leblanc Amanda , Masiello Francesca , Tirelli Valentina , Migliaccio Anna Rita , Najfeld Vesna , Whitsett Carolyn
Published: July 2009

BACKGROUND: Cultured human erythroid cells derived in vitro may represent alternative transfusion products. It is unknown, however, if these ex vivo expanded erythroid cells remain functional or develop genetic abnormalities after storage.

STUDY DESIGN AND METHODS: Using mononuclear cells from four adult blood donors, erythroblasts were generated ex vivo in expansion cultures supplemented with stem cell factor, interleukin‐3, erythropoietin (EPO), dexamethasone, and estradiol. The viability and in vitro function of freshly expanded or short (1‐2 months)‐ and long (8 years)‐term‐stored erythroblasts cryopreserved in dimethyl sulfoxide were compared. Erythroblast function was defined as ability to proliferate in expansion media and mature in response to EPO. Cell number was determined manually and expressed as fold increase. Viability was assessed by trypan blue and propidium iodide exclusion. Maturation was evaluated by morphologic analyses and CD36/CD235a expression profiling. Cytogenetic evaluation included karyotype and multicolor fluorescence in situ hybridization analyses.

RESULTS: Equivalent numbers (>80%) of erythroblasts were viable after short‐ and long‐term storage. Freshly expanded and short‐ and long‐term‐stored erythroblasts equally doubled in number (fold increase, 2.4) retaining an immature phenotype (23% of the cells were CD36highCD235aneg) when cultured for 4 days under expansion conditions. The numbers of freshly expanded and short‐term‐stored erythroblasts that matured when exposed for 4 days to EPO were also similar (approx. 22% of the cells became CD36negCD235ahigh). In spite of the massive amplification, ex vivo generated erythroblasts demonstrated a normal (46,XY) karyotype with no obvious genomic rearrangements.

CONCLUSION: Ex vivo expanded erythroblasts remain functional and genetically normal after long‐term storage.
IMMUNOHEMATOLOGY: Rapid screening of granulocyte antibodies with a novel assay: flow cytometric granulocyte immunofluorescence test
Authors: Nguyen Xuan Duc , Flesch Brigitte , Sachs Ulrich J. , Kroll Hartmut , Klüter Harald , Müller‐Steinhardt Michael
Published: July 2009

BACKGROUND: White blood cell (WBC)‐associated antibodies can lead to severe pulmonary transfusion reactions (transfusion‐related acute lung injury [TRALI]). Investigation of a large number of blood donor samples using the standard granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) proved to be difficult to perform due to the time‐consuming process and the large quantity of test cells required. This study describes the novel flow cytometric GIFT (Flow‐GIFT) method for a rapid detection of granulocyte antibodies by flow cytometric analysis.

STUDY DESIGN AND METHODS: A total of 141 sera were analyzed for the presence of granulocyte antibodies that were previously associated with suspected TRALI. As test cells whole blood samples from human neutrophil antigen (HNA)‐typed donors were isolated using cell sedimentation in a ficoll density gradient. WBCs were incubated with the respective serum and binding of antibodies to the test cells was detected using fluorescein isothiocyanate–conjugated anti‐human antibody. Standard GIFT and GAT were performed as reference methods.

RESULTS: Seven sera containing anti‐HNA‐3a, CD16, and HLA Class I were negative in the standard GIFT and eight sera containing anti‐HNA‐2a, anti‐CD16, and anti‐HLA Class I were not detected in the GAT. The novel Flow‐GIFT was able to detect all granulocyte antibodies, which were only detectable in a combination of standard GIFT and GAT. In serial dilution tests, the Flow‐GIFT detected the antibodies at higher dilutions than the reference methods GIFT and GAT.

CONCLUSION: The Flow‐GIFT method permits rapid detection of granulocyte antibodies requiring fewer donor test cells. This method is ideal for automation and will potentially open the way for screening of granulocyte antibodies in a large donor population.
Genetic Exchange Within and Between Assemblages of Giardia duodenalis
Authors: LASEK‐NESSELQUIST ERICA , WELCH DAVID MARK , THOMPSON RICHARD CHRISTOPHER ANDREW , STEUART ROBERT F. , SOGIN MITCHELL L.
Published: July 2009

ABSTRACT. Meiotic sex evolved early in the history of eukaryotes. Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis), a parasitic protist belonging to an early diverging lineage of eukaryotes, shows no cytological or physiological evidence of meiotic or sexual processes. Recent molecular analyses challenge the idea that G. duodenalis is a strictly clonal organism by providing evidence of recombination between homologous chromosomes within one subgroup (Assemblage A) of this species as well as genetic transfer from one subgroup to another (Assemblage A–B). Because recombination is not well documented and because it is not known whether the observed inter‐assemblage transfer represents true reciprocal genetic exchange or a non‐sexual process, we analyzed genic sequences from all major subgroups (Assemblages A–G) of this species. For all assemblages, we detected molecular signatures consistent with meiotic sex or genetic exchange, including low levels of heterozygosity, as indicated by allelic sequence divergence within isolates, and intra‐ and inter‐assemblage recombination. The identification of recombination between assemblages suggests a shared gene pool and calls into question whether it is appropriate to divide the genetically distinct assemblages of G. duodenalis into a species complex.
Influence of carrion smell and rebaiting time on the efficiency of pitfall traps to dung beetle sampling
Authors: Flechtmann Carlos Alberto Hector , Tabet Vinicius Gomes , Quintero Ingrid
Published: July 2009

Dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) are very useful insects, as they improve the chemo‐physical properties of soil, clean pastures from dung pads, and help control symbovine flies associated with bovine cattle. Their importance makes it fundamental to sample and survey them adequately. The objectives of the present study were to determine the influence of decaying insects trapped in pitfalls on the attractiveness of Moura pigSus scrofaL. (Suidae) and collared peccaryTayassu tajacu(L.) (Tayassuidae) dung used as baits to lure dung beetles, and to establish how long these baits remain attractive to dung beetles when used in these traps. Some dung beetle species seemed to be able to discriminate against foul smell from decaying insects within the first 24 h, hence decreasing trap efficiency. This was more evident in peccary dung‐baited traps, which proved to be the least attractive bait. Attractiveness lasted only 24 h for peccary dung, after which it became unattractive, whereas the pig dung bait was highly attractive for 48 h, after which its attractiveness diminished but was not completely lost.
Hidradenitis suppurativa (acne inversa): early inflammatory events at terminal follicles and at interfollicular epidermis*
Authors: Laffert Maximilian von , Helmbold Peter , Wohlrab Johannes , Fiedler Eckhard , Stadie Volker , Marsch Wolfgang Christian
Published: July 2009

Please cite this paper as: Hidradenitis suppurativa (acne inversa): early inflammatory events at terminal follicles and at interfollicular epidermis. Experimental Dermatology 2010; 19: 533–537.

Abstract:  Hidradenitis suppurativa (acne inversa) is a chronic suppurative and scarring inflammatory disease with predilection in the apocrine gland‐bearing areas. Histological investigations in the 1990s showed keratotic occlusion of the terminal follicle structure to be the initial cause. Our investigations describe and reproduce the morphology and try to figure out very early lesions of HS. A total of 262 operative specimens from 60 patients were investigated by routine histology and 11 operative specimens by immunohistochemistry: HS is dominated by a heterogeneous histological image. 82% of the surgical specimens showed mild or pronounced follicular hyperkeratosis, whereas an isotopic hyperplasia of follicular epithelium was evident in 77%. Pronounced perifolliculitis was seen in 68% and rupture of the follicle structure in 28%. Features which had not so far been described in detail were: epidermal psoriasiform hyperplasia (43%) and subepidermal interfollicular inflammatory infiltrate (78%). In all 11 specimens, immunohistochemical investigations showed a perifollicular and subepidermal inflammation of CD‐3‐, CD‐4‐, CD‐68‐, CD‐79‐ and CD‐8‐cells, the latter with a striking selective epitheliotropism. To conclude, we could show follicular hyperkeratosis and lymphocytic perifollicular inflammation as early patterns in pathogenesis, whereas rupture of the follicle structure takes place later. Finally, it seems that there are two hot spots of inflammatory events (perifollicular and subepidermal) composed of a comparable inflammatory cell mixture. The CD‐8 cell epitheliotropism (follicular and epidermal) described here and its influence in follicular hyperkeratosis, in hyperplasia of follicular epithelium and in epidermal psoriasiform hyperplasia will be of further interest, for instance, concerning early pharmacological intervention.
Autophagy 16‐like 1 rs2241880 G allele is associated with Crohn’s disease in German children
Authors: Lacher Martin , Schroepf Sebastian , Ballauff Antje , Lohse Peter , Von Schweinitz Dietrich , Kappler Roland , Koletzko Sibylle
Published: July 2009

Aim:  Genome‐wide association studies have described an association of the ATG16L1 (autophagy 16‐like 1) gene rs2241880 variant with Crohn’s disease (CD). Therefore, we evaluated this polymorphism in early‐onset CD in 152 children and 253 controls and for the first time determined ATG16L1 colonic expression in German CD children.

Methods:  Investigation of rs2241880 allele frequencies using a predesigned single nucleotide polymorphism genotyping assay. Analysis of digenic epistasis between rs2241880 and the three common nucleotide‐binding oligomerization domain containing two (NOD2/CARD15) mutations. Determination of ATG16L1 gene expression in large‐bowel biopsies of selected patients and controls using real‐time polymerase chain reaction.

Results:  The rs2241880G risk allele frequency was higher in CD compared with controls (63.0% vs. 47.4%; p = 0.0002). No epistasis between NOD2/CARD15 mutations and rs2241880 was observed; however, carriers of both variants had significantly increased disease risk. Transcriptional analysis did not reveal over‐ or underexpression of ATG16L1 in CD patients compared with controls.

Conclusion:  We confirmed the association of CD with ATG16L1 rs2241880 variant in early‐onset CD. As no epistatic interaction with three common NOD2/CARD15 mutations was observed, the p.Thr300Ala substitution is an independent risk factor for paediatric CD and supports the role for autophagy in disease pathogenesis.
Exclusion of NEU1 and PPGB from candidate genes for a lysosomal storage disease in Japanese Black cattle
Authors: MASOUDI Ali Akbar , YAMATO Osamu , YONEDA Kazuhiro , TSUJI Takehito , MIKAMI Osamu , KUNIEDA Tetsuo
Published: July 2009

A case of lysosomal storage disease has been reported in a calf of Japanese Black cattle. Lysosomal storage diseases are hereditary diseases caused by deficiency of lysosomal hydrolases. The clinical and pathological features and accumulated substrates of the affected animal indicated a possibility of sialidosis or galactosialidosis caused by deficiency of neuraminidase (NEU1) or protective protein for β‐galactosidase (PPGB). In the present study, we investigated nucleotide sequences of the genes encoding these two proteins to evaluate whether mutation of these genes is involved in this disease. We determined cattle genomic sequences of these two genes by using bovine EST sequences and the nucleotide sequences of all exons of these genes were compared between affected and normal animals. The results showed several nucleotide substitutions, but none of them was a functional mutation or specific to the affected animal. Furthermore, genotyping of the microsatellite markers in the vicinity of these two genes revealed no homozygosity of the chromosomal regions including these genes in the affected animal. These findings indicated that neither NEU1 nor PPGB gene is responsible for the lysosomal storage disease of Japanese Black cattle and therefore the disease is neither sialidosis nor galactosialidosis.
MHC microsatellites in a Southern Brazilian population
Authors: Sens‐Abuázar C. , Santos P. S. C. , Bicalho M. G. , Petzl‐Erler M. L. , Sperandio‐Roxo V.
Published: July 2009

Microsatellites are short tandem repeats of 1–6 bp DNA fragments, which are found throughout the genome. Due to their high levels of polymorphism, many of them are used as markers for population studies. Here we report an investigation on four microsatellites (D6S273, D6S2792, STR_MICA and D6S2810) located within the major histocompatibility complex in a sample of 281 Southern Brazilians of European ancestry. Allelic and haplotypic frequencies are described, as well as linkage disequilibrium (LD) between alleles of these microsatellites and alleles of three HLA genes: HLA‐B, HLA‐DRB1 and HLA‐DQB1. The most polymorphic microsatellite was D6S2810, located close to the HLA‐B locus. Strong LD was observed between alleles of microsatellites and HLA genes. The strongest associations occurred among STR_MICA*A5.1–HLA‐B*13, STR_MICA*A6–HLA‐B*49, STR_MICA*A9–HLA‐B*39, STR_MICA*A9–HLAB*57, D6S2810*334–HLA‐B*14, D6S2810*334–HLA‐B*38, STR_MICA*A5.1–HLA‐DRB1*1501–HLA‐DQB1*0602 and D6S2810*344–HLA‐DRB1*0411–HLA‐DQB1*0302. This study contributes with important information on HLA haplotypes, and is potentially useful in resolving cases of low resolution HLA genotyping ambiguities.
Furthering the Understanding of Parent–Child Relationships: A Nursing Scholarship Review Series. Part 1: Introduction
Authors: Lutz Kristin F. , Anderson Lori S. , Pridham Karen A. , Riesch Susan K. , Becker Patricia T.
Published: July 2009

PURPOSE.  Understanding the parent–child relationship is fundamental to nursing of children and families. The purpose of this integrative review is to explore nursing scholarship published from 1980–2008 concerning parent–child relationships. Study approaches are examined, critiqued, and future directions for research identified.

CONCLUSIONS.  A historical review of nursing research is presented and methods described as an introduction to a review series of the parent–child relationship.

IMPLICATIONS.  Definition and explication of the parent–child relationship is a first‐step in understanding factors amenable to nursing intervention. A clear definition of the concept of parent–child relationship will support further study using appropriate theoretical frameworks, and enable development and testing of supportive nursing interventions.
Electrophoretic Codeposition of La0.6Sr0.4Co0.8Fe0.2O3−δ and Carbon Nanotubes for Developing Composite Cathodes for Intermediate Temperature Solid Oxide Fuel Cells
Authors: Santillán Maria J. , Caneiro Alberto , Lovey Francisco C. , Quaranta Nancy , Boccaccini Aldo R.
Published: July 2009

Carbon nanotubes (CNTs)/La0.6Sr0.4Co0.8Fe0.2O3−δ (LSCF) composite films have been fabricated by electrophoretic codeposition on Ce0.9Gd0.1O1.95 (CGO) substrates. CNTs are used as a sacrificial phase to produce ordered porous LSCF cathodes for intermediate temperature solid oxide fuel cells. The synthesis of LSCF powder by a modified sol–gel route is presented. The possible mechanism of formation of CNT/LSCF composite nanoparticles in suspension is discussed. Moreover the optimal suspension composition and the conditions for achieving successful electrophoretic deposition (EPD) of CNTs/LSCF composite nanoparticles were evaluated. Experimental results showed that the CNTs were homogeneously distributed and mixed with LSCF nanoparticles forming a mesh‐like structure, which resulted in a highly porous LSCF film when the CNTs were burned out during heat treatment in air at 800°C for 2 h. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X‐ray diffraction (XRD) techniques were employed to characterize the microstructure of the precursors and of the composite films.
Development of an In Situ Surface Deformation and Temperature Measurement Technique for a Solid Oxide Fuel Cell Button Cell
Authors: Guo Huang , Iqbal Gulfam , Kang Bruce S.
Published: July 2009

A novel experimental technique is developed to measure the in situ surface deformation and temperature of a solid oxide fuel cell (SOFC) anode surface along with the cell electrochemical performance. The experimental setup consists of a NexTech Probostat™ SOFC button cell test apparatus integrated with a Sagnac interferometric optical method and an infrared sensor for in situ surface deformation and temperature measurements, respectively. The button cell is fed with hydrogen or simulated coal syngas under SOFC operating conditions. The surface deformation is measured over time to estimate the anode structural degradation. The cell surface transient temperature is also monitored with different applied current densities under hydrogen and simulated coal syngas. The experimental results are useful to validate and develop SOFC structural durability and electrochemical models.
Antibody‐Directed Enzyme Prodrug Therapy: A Promising Approach for a Selective Treatment of Cancer Based on Prodrugs and Monoclonal Antibodies
Authors: Tietze Lutz F. , Krewer Birgit
Published: July 2009

The antibody‐directed enzyme prodrug therapy allows a selective liberation of cytotoxic agents from non‐toxic prodrugs in cancerous tissue by targeted antibody–enzyme conjugates. We have developed a series of novel glycosidic prodrugs based on the natural antibiotic CC‐1065 and the duocarmycins, which are up to 4800 times less toxic than the drugs liberated from these prodrugs in the presence of the activating enzyme (e.g., β‐d‐galactosidase). Furthermore, the drugs show very high cytotoxicities with IC50 values of as low as 4.5 pm. In this report, we summarize our recent results on the development and biological evaluation of these novel third‐generation prodrugs with higher water solubility, higher difference in cytotoxicity between the prodrugs and the corresponding drugs and improved cytotoxicity of the drugs as compared with previous compounds.
Legal Accountability in the Service‐Based Welfare State: Lessons from Child Welfare Reform
Authors: Noonan Kathleen G. , Sabel Charles F. , Simon William H.
Published: July 2009

Current trends intensify the longstanding problem of how the rule of law should be institutionalized in the welfare state. Welfare programs are being redesigned to increase their capacities to adapt to rapidly changing conditions and to tailor their responses to diverse clienteles. These developments challenge the understanding of legal accountability developed in the Warren Court era. This article reports on an emerging model of accountable administration that strives to reconcile programmatic flexibility with rule‐of‐law values. The model has been developed in the reform of state child protective services systems, but it has potentially broad application to public law. It also has novel implications for such basic rule‐of‐law issues as the choice between rules and standards, the relation of bureaucratic and judicial control, the proper scope of judicial intervention into dysfunctional public agencies, and the justiciability of “positive” (or social and economic) rights.
Maybe He's Depressed: Mental Illness as a Mitigating Factor for Drug Offender Accountability
Authors: Paik Leslie
Published: July 2009

Given the often perplexing relationship between mental illness and substance abuse among offenders, this article looks at how a juvenile drug court staff's presumptions of a youth's mental illness affect its decision‐making process. Based on thirteen months of ethnographic fieldwork at a Southern California juvenile drug court, this article uses Manzo and Travers's “law in action” approach to analyze how the staff readjusts its application of normal remedies (a concept developed by Robert Emerson) designed to respond to a youth's noncompliance when it suspects mental illness may be influencing the youth's actions. In doing so, it highlights how court staff's considerations of youth mental disorders arise out of its everyday work practices. Furthermore, the article discusses how staff negotiations around a youth's mental illness create tensions for the juvenile drug court's accountability‐based model of therapeutic jurisprudence, because assessments of mental illness tend to mitigate responsibility for a youth's behavior.
Science and the Death Penalty: DNA, Innocence, and the Debate over Capital Punishment in the United States
Authors: Aronson Jay D. , Cole Simon A.
Published: July 2009

The death penalty debate in the United States has recently undergone a fundamental shift. The possibility of executing the innocent has emerged as some abolitionists' most salient argument, displacing debates over such issues as fairness, deterrence, and cost. Innocence has managed to move to the fore of the debate in part because of the success of death penalty opponents in attaching epistemological certainty to one particular category of postconviction exonerations, those vouched for by the authority of DNA evidence. We suggest that such moves are primarily rhetorical because, while DNA evidence may be more accurate and reliable than other forensic science, it still fundamentally probabilistic in nature and is prone to uncertainties at all stages of its production. Yet, because of the certainty attached to DNA evidence in public discourse, it can be used as a lever with which to challenge law's claims to truth‐making authority, and to undermine public trust in the death penalty. A few abolitionists and other scholars have expressed misgivings about the abolitionist embrace of the innocence argument. We push this concern further, suggesting that both abolitionists and death penalty reformers, who seek to promote a “scientific” death penalty centered on DNA evidence, draw upon a mythologized notion of “science” as a producer of epistemic certainty.
Gated Communities in Law's Gaze: Material Forms and the Production of a Social Body in Legal Adjudication
Authors: Levi Ron
Published: July 2009

This article focuses on the legal geography of gated communities. Sociolegal research has paid comparatively little attention to how specific material forms fare within legal contexts. Drawing on work in legal geography and in science and technology studies, this article isolates judicial decisions that deal with the borders of gated communities from other cases involving private homeowner associations. By focusing on these boundary disputes in which outsiders are excluded from the area, this article finds that courts are resisting the localism presented by gated communities and are instead articulating a social imaginary in which the landscape flows uninterrupted by the exclusionary presence of gates. In contrast to the privatopia literature, this article finds that courts are not complicit in promoting neoliberal visions of community. The social imaginary being developed by courts resists the spatial differentiation of gated communities, producing in its place a thoroughly modern polity in which legal, economic, and political relations flow easily between those inside and outside the gate.
Perfluorooctane sulphonate in raw and drinking water sources in the United Kingdom
Authors: McLaughlin Clare L. , Blake Simon , Hall Tom , Harman Mark , Kanda Rakesh , Foster Jim , Rumsby Paul C.
Published: July 2009

There has been increasing interest in the widely used perfluorinated chemicals such as perfluorooctane sulphonate (PFOS). PFOS has been shown to be toxic, persistent and bioaccumulative in the environment and is a focus for restriction within the European Union. Limited monitoring data, especially in the United Kingdom, are available for PFOS in environmental waters, and even less for its detection in drinking water. Data available in the United Kingdom indicate that PFOS contamination of environmental waters has only occurred following specific incidents. Monitoring of 20 raw and treated drinking water sites in England, covering four seasonal periods, showed that PFOS is not a widespread background contaminant of raw and treated drinking water in England. Low levels of PFOS (0.012–0.208 μg/L) were detected at four specific sites, which were at a higher risk for contamination. At three of these sites, where PFOS was detected in both raw and final drinking water, treatment processes [chlorination, ozonation and granular activated carbon (GAC)] did not appear to remove PFOS. The findings of this work are pertinent to risk assessments now required by the drinking water quality regulations.
Victims and the sentencing process: developing participatory rights?
Authors: Doak Jonathan , Henham Ralph , Mitchell Barry
Published: July 2009

Recent years have seen a number of developments pertaining to the notion that victims should be afforded a ‘voice’ in the criminal justice system. The theoretical and structural parameters of the adversarial system are not, however, conducive to exercising such a role. For many, conferring procedural rights on victims jeopardises the due process rights of the accused, as well as the public nature of the criminal justice system. In light of the recent decision to roll out the ‘Victims' Focus Scheme’ across England and Wales, this paper explores a number of issues of principle that arise – not least the deeper policy implications of an apparent re-alignment of the normative parameters of the criminal justice system to incorporate the private interests of third parties.
Neuroethology of Oviposition Behavior in the Moth Manduca sexta
Authors: Reisenman Carolina E. , Riffell Jeffrey A. , Hildebrand John G.
Published: July 2009

Olfactory cues play decisive roles in the lives of most insect species, providing information about biologically relevant resources, such as food, mates, and oviposition sites. The nocturnal moth Manduca sexta feeds on floral nectar from a variety of plants (and thus serves as a pollinator), but females oviposit almost exclusively on solanaceous plants, which they recognize on the basis of olfactory cues. Plants, however, respond to herbivory by releasing blends of volatiles that attract natural enemies of herbivores. Thus, oviposition behavior probably results from the sensory evaluation not only of attractive host plant volatiles but also of repellent volatiles that indicate the acceptability or inappropriateness, respectively, of host plants for the females’ offspring. Here we describe results from chemical–ecological, neurophysiological, and behavioral experiments aimed at understanding the neural mechanisms that control oviposition behavior in M. sexta.
Evolution of Moth Sex Pheromone Desaturases
Authors: Rooney Alejandro P.
Published: July 2009

Moth sex pheromone communication has evolved to use complex blends of relatively simple long‐chain fatty acid precursors. Species specificity is derived from the unique stereochemistry of double bonds introduced into exact locations along the hydrocarbon backbone of fatty acids, which are reduced and then undergo a variety of chain‐shortening and functionalization reactions to form the pheromone blend. Key enzymes that have evolved to function in this system are the acyl coenzyme A desaturases, which catalyze the introduction of the double bonds. This report gives an overview of the evolution of these enzymes, with an introduction to the newly arisen field of “semiochemical genetics.”
Uptake of Materials from the Nasal Cavity into the Blood and Brain
Authors: Genter Mary Beth , Kendig Eric L. , Knutson Mitchell D.
Published: July 2009

Substances that enter the nasal cavity can access the bloodstream or central nervous system by processes including receptor cell uptake, transneuronal transport, and paracellular transport. Until recently, the molecular mechanisms by which agents move from the nasal cavity have not been described. Although the full complement of transporter proteins found in the nasal cavity has certainly not yet been identified, several recent observations have advanced this field substantially. We summarize here a representative sample of transporter proteins found in olfactory mucosa and/or nasal respiratory mucosa and the substrates that they transport into the brain and/or bloodstream.
Dendrodendritic Synapses and Functional Compartmentalization in the Olfactory Bulb
Authors: Mori Kensaku , Matsumoto Hideyuki , Tsuno Yusuke , Igarashi Kei M.
Published: July 2009

Odorant receptor maps in the glomerular layer of the mammalian olfactory bulb are organized into zones and domains. This organization is functionally related to specific odor‐induced behavioral responses. Mitral and tufted cells associated with a glomerulus (an odorant receptor channel) extend long lateral dendrites that form dendrodendritic synapses with granule cells associated with other channels. The knowledge of spatial distribution of these long dendrites with regard to the zonal and domain organization will help us to understand the logic of integration of signals from distinct odorant receptor channels in the olfactory bulb.