bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll‐like receptor (TLR) 2 and TLR4 deficiencies exert differential in vivo effects against Schistosoma japonicum
Authors: ZHANG M. , GAO Y. , DU X. , ZHANG D. , JI M. , WU G.
Published: October 2010

Little is known about the functions of Toll‐like receptor 2 (TLR2) and TLR4 in innate/acquired responses to Schistosoma japonicum. Through in vivo study, the contributions of TLR2 and TLR4 to host immune responses during S. japonicum infection were investigated. Early infection experiments showed higher protein and mRNA levels of IL‐12, IFN‐γ and IL‐4 in dermal tissues and retroauricular draining lymph nodes respectively in TLR2−/− mice on day four post‐infection and opposite changes in TLR4−/− mice. In the acute infection with S. japonicum for 6 weeks, TLR2−/− mice manifested lower egg burden as well as the enhancement of T cell activation and upregulated expression of some cytotoxic genes, as assayed by Th1/Th2 cytokine secretion and DNA microarray analysis. Also, the opposite parasitological and immunological effects were observed in TLR4−/− mice. These results demonstrate that during S. japonicum infection, TLR2 and TLR4 might direct distinct adaptive immune responses since the early stage, which may lead to different infection outcomes.
Costs of HIV/AIDS outpatient services delivered through Zambian public health facilities
Authors: Bratt John H. , Torpey Kwasi , Kabaso Mushota , Gondwe Yebo
Published: October 2010

Objective  To present evidence on unit and total costs of outpatient HIV/AIDS services in ZPCT‐supported facilities in Zambia; specifically, to measure unit costs of selected outpatient HIV/AIDS services, and to estimate total annual costs of antiretroviral therapy (ART) and prevention of mother‐to‐child transmission (PMTCT) in Zambia.

Methods  Cost data from 2008 were collected in 12 ZPCT‐supported facilities (hospitals and health centres) in four provinces. Costs of all resources used to produce ART, PMTCT and CT visits were included, using the perspective of the provider. All shared costs were distributed to clinic visits using appropriate allocation variables. Estimates of annual costs of HIV/AIDS services were made using ZPCT and Ministry of Health data on numbers of persons receiving services in 2009.

Results  Unit costs of visits were driven by costs of drugs, laboratory tests and clinical labour, while variability in visit costs across facilities was explained mainly by differences in utilization. First‐year costs of ART per client ranged from US$278 to US$523 depending on drug regimen and facility type; costs of a complete course of antenatal care (ANC) including PMTCT were approximately US$114. Annual costs of ART provided in ZPCT‐supported facilities were estimated at US$14.7–$40.1 million depending on regimen, and annual costs of antenatal care including PMTCT were estimated at US$16 million. In Zambia as a whole, the respective estimates were US$41.0–114.2 million for ART and US$57.7 million for ANC including PMTCT.

Conclusions  Consistent with the literature, total costs of services were dominated by drugs, laboratory tests and clinical labour. For each visit type, variability across facilities in total costs and cost components suggests that some potential exists to reduce costs through greater harmonization of care protocols and more intensive use of fixed resources. Improving facility‐level information on the costs of resources used to produce services should be emphasized as an element of health systems strengthening.
Refugee settlement workers’ perspectives on home safety issues for people from refugee backgrounds
Authors: Campbell Emma Jean , Turpin Merrill June
Published: October 2010

Background/aim:  Refugees experience higher levels of emotional, psychological and physical distress than the general migrant population during settlement in a new country. Safety in the home can be a major concern and is an issue of which occupational therapists should be aware. Occupational therapists working with refugees in many contexts feel unprepared and overwhelmed. As refugee settlement workers attend to home safety of refugees during the settlement process, this study aimed to develop an in‐depth understanding of their perceptions of this issue. Such information can contribute to occupational therapists’ knowledge and practice when working with refugees.

Methods:  An exploratory qualitative case study approach used 16 semi‐structured interviews and observation of a settlement worker assisting newly arrived refugees. Participants were settlement service staff (an occupational therapist, case coordinators and cultural support workers).

Results:  Three themes are reported: considerations for safety in the homes of refugees; factors influencing home safety for refugees; and sensitivity to culture. Participants described tailoring home safety‐related services to each individual based on factors that influence home safety and sensitivity to culture.

Conclusion:  Awareness of home safety issues can increase cultural competence and inform practice and policy.
Understanding crossmatch testing in organ transplantation: A case‐based guide for the general nephrologist
Authors: MULLEY WILLIAM R , KANELLIS JOHN
Published: October 2010

Crossmatching of potential renal donors against potential renal transplant recipients has been performed for over 40 years and is a mandatory component of the transplant work‐up process. However, gone are the days when all that was available was the T‐cell complement‐dependent cytotoxicity crossmatch. There are now many more options available for determining the likelihood of donor‐specific antibody‐mediated responses including flow crossmatching and the ‘virtual’ crossmatch. In addition, assays to determine the extent of sensitization of cell‐mediated responses are being examined. This article builds an understanding of modern day crossmatch interpretation using a case‐based approach in order to provide a framework for the general nephrologist to determine the likely immune consequences of a particular donor–recipient pairing.
Outcome of different post‐orchiectomy management for stage I seminoma: Japanese multi‐institutional study including 425 patients
Authors: Kamba Tomomi , Kamoto Toshiyuki , Okubo Kazutoshi , Teramukai Satoshi , Kakehi Yoshiyuki , Matsuda Tadashi , Ogawa Osamu
Published: October 2010

Objectives:  To clarify the contemporary clinical outcome of stage I seminoma and to provide information on treatment options to patients.

Methods:  A retrospective analysis of 425 patients who underwent orchiectomy for stage I seminoma between 1985 and 2006 at 25 hospitals in Japan. Relapse‐free survival rates were calculated using the Kaplan–Meier method and clinicopathological factors associated with relapse were examined by univariate and multivariate analyses using the Cox proportional hazards model.

Results:  A total of 30 out of 425 patients had relapsed. Relapse‐free survival rates at 10 years were 79, 94 and 94% in the surveillance, chemotherapy and radiotherapy groups, respectively. Post‐orchiectomy management and rete testis invasion were identified as independent predictive factors associated with relapse. Rete testis invasion remained to be an independent predictive factor, even if the cases with relapses in the contralateral testis were censored. Only one patient, who relapsed after adjuvant radiotherapy, died of the disease. Overall survival at 10 years was 100, 100 and 99% in the surveillance, chemotherapy and radiotherapy groups, respectively. More than half of the patients were lost to follow up within 5 years.

Conclusions:  The outcome of Japanese patients with stage I seminoma is similar to previously published Western reports. Surveillance policy is becoming a popular option in Japan, although the relapse rate in patients opting for surveillance policy is higher than those opting for adjuvant chemotherapy or radiotherapy. Rete testis invasion is an independent predictive factor associated with relapse regardless of the post‐orchiectomy management. Long‐term follow up is mandatory for detection of late relapse.
Dopamine attenuates evoked inhibitory synaptic currents in central amygdala neurons
Authors: Naylor Jennifer C. , Li Qiang , Kang‐Park Maeng‐hee , Wilson Wilkie A. , Kuhn Cynthia , Moore Scott D.
Published: October 2010

The central nucleus of the amygdala (CeA) plays a critical role in regulating the behavioral, autonomic and endocrine response to stress. Dopamine (DA) participates in mediating the stress response and DA release is enhanced in the CeA during stressful events. However, the electrophysiological effects of DA on CeA neurons have not yet been characterized. Therefore, the purpose of this study was to identify and characterize the effect of DA application on electrophysiological responses of CeA neurons in coronal brain sections of male Sprague–Dawley rats. We used whole‐cell patch‐clamp electrophysiological techniques to record evoked synaptic responses and to determine basic membrane properties of CeA neurons both before and after DA superfusion. DA (20–250 μm) did not significantly alter membrane conductance over the voltage range tested. However, DA significantly reduced the peak amplitude of evoked inhibitory synaptic currents in CeA neurons. Pretreatment with the D2receptor antagonist eticlopride failed to significantly block the inhibitory effects of DA. In contrast, pretreatment with the D1receptor antagonist SCH‐23390 significantly reduced the effects of DA on evoked inhibitory neurotransmission in these neurons. Moreover, bath superfusion of the specific D1receptor agonist SKF‐39393, but not the D2receptor agonist quinpirole, significantly reduced peak amplitude of evoked inhibitory synaptic events. DA reduced the frequency of miniature IPSCs without altering the amplitude, while having no effect on the amplitude of IPSCs elicited by pressure application of GABA. These results suggest that DA may modulate inhibitory synaptic transmission in CeA through D1receptor activation primarily by a presynaptic mechanism.
Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons
Authors: Michaelsen K. , Zagrebelsky M. , Berndt‐Huch J. , Polack M. , Buschler A. , Sendtner M. , Korte M.
Published: October 2010

Tropomyosin‐related kinase (Trk) receptors modulate neuronal structure and function both during development and in the mature nervous system. Interestingly, TrkB and TrkC are expressed as full‐length and as truncated splice variants. The cellular function of the kinase‐lacking isoforms remains so far unclear. We investigated the role of the truncated receptor TrkB.T1 in the hippocampus of transgenic mice overexpressing this splice variant by analyzing both neuronal structure and function. We observed an impairment in activity‐dependent synaptic plasticity as indicated by deficits in long‐term potentiation and long‐term depression in acute hippocampal slices of transgenic TrkB.T1 mice. In addition, dendritic complexity and spine density were significantly altered in TrkB.T1‐overexpressing CA1 neurons. We found that the effect of TrkB.T1 overexpression differs between subgroups of CA1 neurons. Remarkably, overexpression of p75NTR and its activation by chemical induction of long‐term depression in slice cultures rescued the TrkB.T1‐dependent morphological alterations specifically in one of the two subgroups observed. These findings suggest that the TrkB.T1 and p75NTR receptor signaling systems might be cross‐linked. Our findings demonstrate that TrkB.T1 regulates the function and the structure of mature pyramidal neurons. In addition, we showed that the ratio of expression levels of p75NTR and TrkB.T1 plays an important role in modulating dendritic architecture and synaptic plasticity in the adult rodent hippocampus, and, indeed, that the endogenous expression patterns of both receptors change reciprocally over time. We therefore propose a new function of TrkB.T1 as being dominant‐negative to p75NTR.
The musculature of Squatinella rostrum (Milne, 1886) (Rotifera: Lepadellidae) as revealed by confocal laser scanning microscopy with additional new data on its trophi and overall morphology
Authors: Wilts Eike F. , Wulfken Diana , Ahlrichs Wilko H. , Martínez Arbizu Pedro
Published: October 2010

Wilts, E.F., Wulfken, D., Ahlrichs, W.H. and Martínez Arbizu, P. 2012. The musculature of Squatinella rostrum (Milne, 1886) (Rotifera: Lepadellidae) as revealed by confocal laser scanning microscopy with additional new data on its trophi and overall morphology.—Acta Zoologica (Stockholm) 93: 14–27.

The monogonont rotifer Squatinella rostrum was investigated with light, scanning electron and confocal laser scanning microscopy to reveal new morphological data on its inner and outer anatomy. In total, the visualized somatic musculature displays five paired longitudinal muscles (musculi longitudinales I–V) and nine circular muscles (musculi circulares I–IX). Compared to other species, S. rostrum is characterized by the absence of several longitudinal and circular muscles (e.g. musculus longitudinalis capitis, corona sphincter and pars coronalis). A reconstruction of the mastax musculature revealed a total number of seven paired and two unpaired mastax muscles. Possibly homologous somatic and mastax muscles in other, thus far investigated rotifers are discussed. Moreover, we provide a phylogenetic evaluation of the revealed morphological characters and suggest possible autapomorphic characters supporting Squatinella and Lepadellidae. Finally, we refer to some striking similarities in the morphology, ecology and way of movement of Squatinella and Bryceella that may indicate a closer relationship of both taxa.
Central and peripheral neuronal pathways revealed by backfilling with neurobiotin in the optic, tentacular and small labial nerves ofLymnaea stagnalis
Authors: Tuchina Oksana P. , Zhukov Valery V. , Meyer‐Rochow V. Benno
Published: October 2010

Tuchina, O.P., Zhukov, V.V. and Meyer‐Rochow, V.B. 2012. Central and peripheral neuronal pathways revealed by backfilling with neurobiotin in the optic, tentacular and small labial nerves ofLymnaea stagnalis. —Acta Zoologica(Stockholm)93: 28–47.

The TOLm complex inLymnaea stagnaliscontains nervesn. tentacularis, n. opticusandn. labialis minor. Ligatures close to where the complex enters the central nervous system (CNS) did not prevent penetration of retrograde‐transported neurobiotin into fibres of an adjacent nerve. Axonal bifurcation within the common nerve trunk or tight junctions may be involved, providing a basis for peripheral axon reflexes. Peripheral terminations ofn. tentacularis,n. labialis minorandn. opticusrevealed numerous cell bodies in the tentacular epithelium, some in the tentacle and lip region, and some in the retina. These cell bodies’ central projections were mapped by neurobiotin and verified by dissections of the cerebro‐cerebral commissure and cerebro‐pleural connective. Afferent fibres of the nerves form dense sensory neuropils in the ipsilateral cerebral ganglia. Direct connections betweenn. tentacularisand some visceral as well as parietal nerves were demonstrated by backfillings throughn. pallialis dexter internus et externus,n. pallialis sinisterandn. intestinalis. Labelling ofn. tentacularisrevealed neuronal bodies in every ganglion and stained fibres in most of the peripheral nerves. Fewer neurons were identified throughn. labialis minorandn. opticus. We discuss our results in relation to different behavioural forms like defence and feeding reactions inL. stagnalis.
VOLATILITY AND COVARIATION ESTIMATION WHEN MICROSTRUCTURE NOISE AND TRADING TIMES ARE ENDOGENOUS
Authors: Robert Christian Yann , Rosenbaum Mathieu
Published: October 2010

This paper considers practically appealing procedures for estimating intraday volatility measures of financial assets. The underlying microstructure model accommodates the inherent properties of ultra high‐frequency data with the assumption of continuous efficient price processes. In this model, microstructure noise and trading times are endogenous but do not only depend on the prices. Using the (observed) last traded prices of the assets, we develop a new approach that enables to approximate the values of the efficient prices at some random times. Based on these approximated values, we build an estimator of the integrated volatility and give its asymptotic theory. We also give a consistent estimator of the integrated covariation when two assets (asynchronous by construction of the model) are observed.
Barriers to adaptive reasoning in community ecology
Authors: McLachlan Athol J. , Ladle Richard J.
Published: October 2010

Recent high‐profile calls for a more trait‐focused approach to community ecology have the potential to open up novel research areas, generate new insights and to transform community ecology into a more predictive science. However, a renewed emphasis on function and phenotype also requires a fundamental shift in approach and research philosophy within community ecology to more fully embrace evolutionary reasoning. Such a subject‐wise transformation will be difficult due to at least four factors: (1) the historical development of the academic discipline of ecology and its roots as a descriptive science; (2) the dominating role of the ecosystem concept in the driving of contemporary ecological thought; (3) the practical difficulties associated with defining and identifying (phenotypic) adaptations, and; (4) scaling effects in ecology; the difficulty of teasing apart the overlapping and shifting hierarchical processes that generate the observed environment‐trait correlations in nature. We argue that the ability to predict future ecological conditions through a sufficient understanding of ecological processes will not be achieved without the placement of the concept of adaptation at the centre of ecology, with influence radiating outwards through all the related (and rapidly specializing) sub‐disciplines.
Hubs and bottlenecks in plant molecular signalling networks
Authors: Dietz Karl‐Josef , Jacquot Jean‐Pierre , Harris Gary
Published: October 2010

Conditional control of plant cell function and development relies on appropriate signal perception, signal integration and processing. The development of high throughput technologies such as proteomics and interactomics has enabled the identification of protein interaction networks that mediate signal processing from inputs to appropriate outputs. Such networks can be depicted in graphical representations using nodes and edges allowing for the immediate visualization and analysis of the network’s topology. Hubs are network elements characterized by many edges (often degree grade k ≥ 5) which confer a degree of topological importance to them. The review introduces the concept of networks, hubs and bottlenecks and describes four examples from plant science in more detail, namely hubs in the redox regulatory network of the chloroplast with ferredoxin, thioredoxin and peroxiredoxin, in mitogen activated protein (MAP) kinase signal processing, in photomorphogenesis with the COP9 signalosome, COP1 and CDD, and monomeric GTPase function. Some guidance is provided to appropriate internet resources, web repositories, databases and their use. Plant networks can be generated from existing public databases and this type of analysis is valuable in support of existing hypotheses, or to allow for the generation of new concepts or ideas. However, intensive manual curating of in silico networks is still always necessary.

Contents

Summary
919

I.
Introduction
920

II.
The emergence of the concept of the hub and bottleneck
921

III.
General properties of protein–protein interaction hubs and bottlenecks
922

IV.
Date vs party hubs in networks
923

V.
Structural basis for multiple interactions of hub proteins
923

VI.
Bottlenecks in networks
923

VII.
Global network analysis of protein–protein interactions in plants
924

VIII.
Protein hubs in the cellular redox signalling network
928

IX.
Mitogen‐activated protein (MAP) kinases as signalling hubs
929

X.
Hubs in photomorphogenesis
930

XI.
Monomeric GTPases
932

XII.
Towards quantitative characterization of signalling hubs
933

XIII.
Outlook
933

Acknowledgements
934

References
934
Psychophysiological and behavioral measures for detecting concealed information: The role of memory for crime details
Authors: Nahari Galit , Ben‐Shakhar Gershon
Published: October 2010

This study examined the role of memory for crime details in detecting concealed information using the electrodermal measure, Symptom Validity Test, and Number Guessing Test. Participants were randomly assigned to three groups: guilty, who committed a mock theft; informed‐innocents, who were exposed to crime‐relevant items; and uninformed‐innocents, who had no crime‐relevant information. Participants were tested immediately or 1 week later. Results showed (a) all tests detected the guilty in the immediate condition, and combining the tests improved detection efficiency; (b) tests' efficiency declined in the delayed condition, mainly for peripheral details; (c) no distinction between guilty and informed innocents was possible in the immediate, yet some distinction emerged in the delayed condition. These findings suggest that, while time delay may somewhat reduce the ability to detect the guilty, it also diminishes the danger of accusing informed‐innocents.
Interactions with Great SkuasStercorarius skuaas a factor in the long‐term decline of an Arctic SkuaStercorarius parasiticuspopulation
Authors: DAWSON NEIL M. , MACLEOD COLIN D. , SMITH MALCOLM , RATCLIFFE NORMAN
Published: October 2010

Many of the UK’s seabird species have displayed high variation in breeding success since the 1980s, largely due to changes in the availability of Lesser SandeelsAmmodytes marinus, their main prey. During this time, Arctic SkuasStercorarius parasiticusexperienced a rapid decline in the UK and the species has subsequently been placed on the Red List of birds of conservation concern. Although shortage of Lesser Sandeels is likely to be an influential factor, the Arctic Skua’s breeding range overlaps with that of the Great SkuaStercorarius skua, a larger bird with a more varied diet, and interspecific interactions for nesting habitat may exert an additional pressure on Arctic Skua breeding populations. Results from four censuses, spanning 21 years, were used to model habitat use and analyse distributional change in nesting Arctic Skuas at a major colony located on Fetlar, Shetland, Scotland. The decline in Arctic Skuas was not uniform across the island and competition with Great Skuas for nest‐sites appears to have influenced localized breeding distribution. By 2006, Arctic Skuas had been almost entirely excluded from shrub heath, blanket bog and coastal heath habitats, which were identified as preferred habitat in 1986. In 2006, Arctic Skua breeding territories were mainly restricted to one core area of preferred habitat where over 90% nested in high density as this habitat became increasingly occupied by Great Skuas. The more generalist foraging habit of the Great Skua allowed the population to grow rapidly as numbers of the more specialist Arctic Skua decreased during times of low sandeel availability. Our model suggests that both interspecific competition for territories with Great Skuas and food limitation have played important roles in the decline of Arctic Skuas on Fetlar.
Anti‐inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGFβ1 regulation
Authors: Stienen Martin N , Haghikia Aiden , Dambach Hannes , Thöne Jan , Wiemann Martin , Gold Ralf , Chan Andrew , Dermietzel Rolf , Faustmann Pedro M. , Hinkerohe Daniel , Prochnow Nora
Published: October 2010

BACKGROUND AND PURPOSE The involvement of astrocytes as immune‐competent players in inflammation and the pathogenesis of epilepsy and seizure‐induced brain damage has recently been recognized. In clinical trials and practice, levetiracetam (LEV) has proven to be an effective antiepileptic drug (AED) in various forms of epileptic seizures, when applied as mono‐ or added therapy. Little is known about the mechanism(s) of action of LEV. Evidence so far suggests a mode of action different from that of classical AEDs. We have shown that LEV restored functional gap junction coupling and basic membrane properties in an astrocytic inflammatory model in vitro.

EXPERIMENTAL APPROACH Here, we used neonatal rat astrocytes co‐cultured with high proportions (30%) of activated microglia or treated with the pro‐inflammatory cytokine interleukin‐1β to provoke inflammatory responses. Effects of LEV (50 µg·mL−1) on electrophysiological properties of astrocytes (by whole cell patch clamp) and on secretion of TGFβ1 (by elisa) were studied in these co‐cultures.

KEY RESULTS LEV restored impaired astrocyte membrane resting potentials via modification of inward and outward rectifier currents, and promoted TGFβ1 expression in inflammatory and control co‐cultures. Furthermore, LEV and TGFβ1 exhibited similar facilitating effects on the generation of astrocyte voltage‐gated currents in inflammatory co‐cultures and the effects of LEV were prevented by antibody to TGFβ1.

CONCLUSIONS AND IMPLICATIONS Our data suggest that LEV is likely to reduce the harmful spread of excitation elicited by seizure events within the astro‐glial functional syncytium, with stabilizing consequences for neuronal–glial interactions.
Comparative bioactivation of the novel anti‐tuberculosis agent PA‐824 inMycobacteriaand a subcellular fraction of human liver
Authors: Dogra M , Palmer BD , Bashiri G , Tingle MD , Shinde SS , Anderson RF , O'Toole R , Baker EN , Denny WA , Helsby NA
Published: October 2010

BACKGROUND AND PURPOSEPA‐824 is a 2‐nitroimidazooxazine prodrug currently in Phase II clinical trial for tuberculosis therapy. It is bioactivated by a deazaflavin (F420)‐dependent nitroreductase (Ddn) isolated fromMycobacterium tuberculosisto form a des‐nitro metabolite. This releases toxic reactive nitrogen species which may be responsible for its anti‐mycobacterial activity. There are no published reports of mammalian enzymes bioactivating this prodrug. We have investigated the metabolism of PA‐824 following incubation with a subcellular fraction of human liver, in comparison with purified Ddn,M. tuberculosisandMycobacterium smegmatis.

EXPERIMENTAL APPROACHPA‐824 (250 µM) was incubated with the 9000×gsupernatant (S9) of human liver homogenates, purified Ddn,M. tuberculosisandM. smegmatisfor metabolite identification by liquid chromatography mass spectrometry analysis.

KEY RESULTSPA‐824 was metabolized to seven products by Ddn andM. tuberculosis,with the major metabolite being the des‐nitro product. Six of these products, but not the des‐nitro metabolite, were also detected inM. smegmatis. In contrast, only four of these metabolites were observed in human liver S9; M3, a reduction product previously proposed as an intermediate in the Ddn‐catalyzed des‐nitrification and radiolytic reduction of PA‐824; two unidentified metabolites, M1 and M4, which were products of M3; and a haem‐catalyzed product of imidazole ring hydration (M2).

CONCLUSIONS AND IMPLICATIONSPA‐824 was metabolized by des‐nitrification in Ddn andM. tuberculosis,but this does not occur in human liver S9 andM. smegmatis. Thus, PA‐824 was selectively bioactivated inM. tuberculosisand there was no evidence for ‘cross‐activation’ by human enzymes.
Critical role of the JNK‐p53‐GADD45α apoptotic cascade in mediating oxidative cytotoxicity in hippocampal neurons
Authors: Choi Hye Joung , Kang Ki Sung , Fukui Masayuki , Zhu Bao Ting
Published: October 2010

BACKGROUND AND PURPOSEGlutamate‐induced oxidative stress plays a critical role in the induction of neuronal cell death in a number of disease states. We sought to determine the role of the c‐Jun NH2‐terminal kinase (JNK)‐p53‐growth arrest and DNA damage‐inducible gene (GADD) 45α apoptotic cascade in mediating glutamate‐induced oxidative cytotoxicity in hippocampal neuronal cells.

EXPERIMENTAL APPROACHHT22 cells, a mouse hippocampal neuronal cell line, were treated with glutamate to induce oxidative stressin vitro. Kainic acid‐induced oxidative damage to the hippocampus in rats was used as anin vivomodel. The signalling molecules along the JNK‐p53‐GADD45α cascade were probed with various means to determine their contributions to oxidative neurotoxicity.

KEY RESULTSTreatment of HT22 cells with glutamate increased the mRNA and protein levels of GADD45α, and these increases were suppressed by p53 knock‐down. Knock‐down of either p53 or GADD45α also prevented glutamate‐induced cell death. Glutamate‐induced p53 activation was preceded by accumulation of reactive oxygen species, and co‐treatment withN‐acetyl‐cysteine prevented glutamate‐induced p53 activation and GADD45α expression. Knock‐down of MKK4 or JNK, or the presence of SP600125 (a JNK inhibitor), each inhibited glutamate‐induced p53 activation and GADD45α expression. In addition, we also confirmed the involvement of GADD45α in mediating kainic acid‐induced hippocampal oxidative neurotoxicityin vivo.

CONCLUSIONS AND IMPLICATIONSActivation of the JNK‐p53‐GADD45α cascade played a critical role in mediating oxidative cytotoxicity in hippocampal neurons. Pharmacological inhibition of this signalling cascade may provide an effective strategy for neuroprotection.
Down‐regulation of some miRNAs by degrading their precursors contributes to anti‐cancer effect of mistletoe lectin‐I
Authors: Li Lin‐Na , Zhang Hua‐Dong , Zhi Run , Yuan Shou‐Jun
Published: October 2010

BACKGROUND AND PURPOSE Mistletoe lectin‐I (ML‐I), the main anti‐cancer component of mistletoe extracts, was originally thought to act exclusively on 28S rRNA. Here, we investigate the down‐regulating effect and mechanism of CM‐1, an ML‐I isolated from Chinese mistletoe, on some miRNAs.

EXPERIMENTAL APPROACH The anti‐cancer effects of CM‐1 were assessed in vitro and in vivo in colorectal cancer cells. The miRNAs down‐regulated by CM‐1 were identified by miRNA microarray assay and validated by qRT‐PCR analysis. The suppression of host gene transcription or by degradation of precursors was determined by qRT‐PCR and enzyme activity assays respectively. The qRT‐PCR, Western blot and immunohistochemistry were used to examine the expression of their target gene and related downstream effector. Cell proliferation was assayed in stably transfected HEK‐293 cells with different levels of these miRNAs.

KEY RESULTS CM‐1 showed prominent anti‐neoplastic activity towards CLY and HT‐29 cells both in vitro and in vivo. The miR‐135a&b were the miRNAs most down‐regulated by CM‐1. Their host gene transcription was largely up‐regulated, while their precursors were degraded directly by CM‐1. The expression of their target gene adenomatous polyposis coli and the phosphorylation of related effector β‐catenin were both significantly up‐regulated. The IC50 values of CM‐1 on derivative HEK‐293 cells with high miR‐135a&b levels were 2–4 times lower than that of control cells.

CONCLUSIONS AND IMPLICATIONS CM‐1 down‐regulated some miRNAs by degrading their precursors, which contributes to its prominent anti‐cancer activity.

LINKED ARTICLE This article is commented on by Rushworth, pp. 346–348 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01075.x
Myocardial oxidative stress contributes to transgenic β2‐adrenoceptor activation‐induced cardiomyopathy and heart failure
Authors: Xu Q , Dalic A , Fang L , Kiriazis H , Ritchie RH , Sim K , Gao X‐M , Drummond G , Sarwar M , Zhang Y‐Y , Dart AM , Du X‐J
Published: October 2010

BACKGROUND AND PURPOSE While maintaining cardiac performance, chronic β‐adrenoceptor activation eventually exacerbates the progression of cardiac remodelling and failure. We examined the adverse signalling pathways mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) after chronic β2‐adrenoceptor activation.

EXPERIMENTAL APPROACH Mice with transgenic β2‐adrenoceptor overexpression (β2‐TG) and non‐transgenic littermates were either untreated or treated with an antioxidant (N‐acetylcysteine, NAC) or NADPH oxidase inhibitors (apocynin, diphenyliodonium). Levels of ROS, phosphorylated p38 mitogen‐activated protein kinase (MAPK), pro‐inflammatory cytokines and collagen content in the left ventricle (LV) and LV function were measured and compared.

KEY RESULTS β2‐TG mice showed increased ROS production, phosphorylation of p38 MAPK and heat shock protein 27 (HSP27), expression of pro‐inflammatory cytokines and collagen, and progressive ventricular dysfunction. β2‐adrenoceptor stimulation similarly increased ROS production and phosphorylation of p38 MAPK and HSP27 in cultured cardiomyocytes. Treatment with apocynin, diphenyliodonium or NAC reduced phosphorylation of p38 MAPK and HSP27 in both cultured cardiomyocytes and the LV of β2‐TG mice. NAC treatment (500 mg·kg−1·day−1) for 2 weeks eliminated the up‐regulated expression of pro‐inflammatory cytokines and collagen in the LV of β2‐TG mice. Chronic NAC treatment to β2‐TG mice from 7 to 10 months of age largely prevented progression of ventricular dilatation, preserved contractile function (fractional shortening 37 ± 5% vs. 25 ± 3%, ejection fraction 52 ± 5% vs. 32 ± 4%, both P < 0.05), reduced cardiac fibrosis and suppressed matrix metalloproteinase activity.

CONCLUSION AND IMPLICATIONS β2‐adrenoceptor stimulation provoked NADPH oxidase‐derived ROS production in the heart. Elevated ROS activated p38 MAPK and contributed significantly to cardiac inflammation, remodelling and failure.

LINKED ARTICLE This article is commented on by Di Lisa et al., pp. 1009–1011 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.01130.x
Human Vocal Cord Infection with the Microsporidium Anncaliia algerae
Authors: CALI ANN , NEAFIE RONALD , WEISS LOUIS M. , GHOSH KAYA , VERGARA REBECCA B. , GUPTA RACHNA , TAKVORIAN PETER M.
Published: October 2010

ABSTRACT. We describe a biopsy proven case of microsporidial infection of the false vocal cords in a 69‐yr‐old male with a history of chronic lymphocytic leukemia. The patient had hoarseness for several weeks before his admission to the hospital for shortness of breath. He had received chemotherapy with fludarabine 6 wk before this hospital admission. A biopsy of vocal cord nodules demonstrated an organism that was identified as Anncaliia algerae by electron microscopy. Molecular analysis of the small subunit RNA gene amplified by polymerase chain reaction further confirmed the identification of this organism as A. algerae. This case illustrates the ability of this insect pathogen to cause disease in immune‐compromised mammalian hosts.
Amniotic Fluid Embolism—Apropos Two Consecutive Cases*
Authors: Ječmenica Dragan , Baralić Ivanka , Alempijević Djordje , Pavlekić Snežana , Kiurski Milosav , Terzić Milan
Published: October 2010

Abstract:  Amniotic fluid embolism (AFE) is a sporadic, unpredictable, and usual fatal obstetric complication. The paper deals with two cases of maternal deaths because of AFE verified by medicolegal autopsy. In both the cases, several known risk factors associated with AFE, such as increased maternal age (41 and 35 years), diabetes, augmented labor, and cesarean delivery, were identified. Clinical features were typical, including sudden onset of cardiovascular and respiratory symptoms. In the patient who survived longer, both clinical and autopsy signs of disseminated intravascular coagulopathy were present, while they were absent in the case where death occurred rapidly. This paper describes briefly the particular features to look for at autopsy and stresses the importance of histology examination and staining techniques.
Simultaneous Identification and δ13C Classification of Drugs Using GC with Concurrent Single Quadrupole and Isotope Ratio Mass Spectrometers*
Authors: Muccio Zeland , Jackson Glen P.
Published: October 2010

Abstract:  In this study, δ13C values of six cocaine samples were identified and classified using a single quadrupole mass spectrometer and an isotope ratio mass spectrometry (IRMS) as simultaneous gas chromatography detectors. Our instrument modification is simple to use and is useful (i) when the sample is of limited size or can only be injected once, (ii) to help identify peaks in a complicated IRMS chromatogram, and (iii) to help differentiate very simple systems when impurity profiling is not possible. The EI‐MS confirmed the identity of cocaine in each sample. The IRMS data distinguished 12 of the 15 possible pair‐wise comparisons at the 95% CL. Three samples could not be differentiated by their δ13C ratios for cocaine. ANOVA demonstrated that the measurement variance was consistently larger than the sample variance. As the δ13C values clearly show, this technique enables the exclusion of a potential common source even when two samples have otherwise identical chemical and physical properties.
Sex pheromone of the red clover casebearer moth, Coleophora deauratella, an invasive pest of clover in Canada
Authors: Evenden M. L. , Mori B. A. , Gries R. , Otani J.
Published: October 2010

The red clover casebearer, Coleophora deauratella Lienig & Zeller (Lepidoptera: Coleophoridae), is an invasive pest of Trifolium species (Fabaceae) in Canada. We identified candidate sex pheromone components from female pheromone gland extracts using coupled gas chromatographic–electroantennographic analysis detection. Three compounds elicited an electrophysiological response from antennae and were identified as: (Z)‐7‐dodecenyl acetate, (Z)‐5‐dodecenyl acetate, and (Z)‐7‐dodecen‐1‐ol. Field tests of the candidate pheromone components revealed that males were attracted to a binary mixture of (Z)‐7‐dodecenyl acetate and (Z)‐5‐dodecenyl acetate. Male moth trap capture was greatest in traps baited with lures containing 100:10 or 100:20 ratios of these pheromone components, respectively. Trap capture was reduced when (Z)‐5‐dodecenyl acetate was present below 10 or above 20% of (Z)‐7‐dodecenyl acetate. Equal numbers of male moths were captured in traps baited with 10, 100, and 1 000 μg of the attractive binary mixture. These findings allow for the development of a pheromone‐based monitoring system for this invasive pest of clover in Canada.
CROSSING BORDERS WITHIN: STANLEY CAVELL AND THE POLITICS OF INTERPRETATION
Authors: Saito Naoko , Standish Paul
Published: October 2010

The matter of crossing borders in the creation of democratic communities arises in ways that are pressing, both within the nation‐state and on a global scale. Tensions between tendencies toward nationalism and the cosmopolitan call for global understanding touch the heart of ideas of democracy as beginning at home—at political, psychological, and existential levels. Yet in both orientations there is a certain consolidation of what John Dewey called the “we.” In this essay Naoko Saito and Paul Standish address questions concerning the “I's” relation to the “we.” It is through an exploration of the apparently apolitical approach of Stanley Cavell, through what he calls the “politics of interpretation,” that Saito and Standish try to give substance to the critical destabilization of these terms and tensions that they believe to be necessary. Cavell's Wittgensteinian approach to skepticism and his account of the Emersonian sense of the tragic help to demonstrate the need to meet the political crisis of democracy with language of a more subtly critical kind. The antifoundationalism Cavell derives from these sources, with its concomitant notion of philosophy as translation, provides us with a language that answers to the problems of the “we.” This is, the authors conclude, a better formulation of, and a more hopeful response to, the challenge of crossing borders within. It touches despair but realizes within it the prophetic power of language. And it shows the political crisis in which democracy finds itself to be something that is not peculiar to our times but internal to the very nature of our (political) lives.
“DARING TO SAY”: STANLEY CAVELL AND DESIGNS ON LITERACY
Authors: Fulford Amanda
Published: October 2010

In this essay Amanda Fulford examines the subject of inter‐cultural understanding from two perspectives: first, through considering Naoko Saito's exploration of translation and inter‐/intra‐cultural understanding, and second, through a discussion of work from the field of literacy studies, in particular the New London Group's “pedagogy of multiliteracies.” In her consideration of the different approaches taken to the challenge of multicultural and globalized societies, and the experiences of encounters with language, Fulford pursues four principal themes: learning from difference, active design of meaning, a relation with language, and transformation of the individual. She shows how Saito's use of American philosophy, in particular Henry David Thoreau's Walden and Stanley Cavell's readings of Thoreau, can play a crucial role in any reconsideration of teaching and learning in adult literacy education. Fulford further demonstrates how Thoreau's notion of the “father tongue” is central to the idea of learning from difference and to our use of language. She concludes by proposing that literacy education and research within the field of literacy studies could benefit from the kind of philosophical conversation, across the borders of subject and epistemology, that an exposure to, and consideration of, the ideas of Thoreau and Cavell on what it means to read and write can offer.
In VitroApproaches to Evaluate Placental Drug Transport by Using Differentiating JEG‐3 Human Choriocarcinoma Cells
Authors: Ikeda Kenji , Utoguchi Naoki , Tsutsui Hidenobu , Yamaue Satoko , Homemoto Manami , Nakao Erina , Hukunaga Yumi , Yamasaki Kyohei , Myotoku Michiaki , Hirotani Yoshihiko
Published: October 2010

Abstract: Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low‐molecular‐weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG‐3 choriocarcinoma cells under different culture conditions and establishing the appropriate model ofin vitrosyncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG‐3 cell layers. The mRNA expression levels of non‐expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E‐cadherin (ECAD) and cadherin‐11 (CDH11), which are adherens junction–associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG‐3 cells cultured in the Dulbecco’s modified Eagle’s medium (DMEM)/Ham’s F‐12 (1:1) mixed medium (CS‐C®; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG‐3 cell‐differentiation patterns. The differentiation pattern of JEG‐3 cultured in CS‐C resembled the syncytiotrophoblast‐like differentiation signal characterizationsin vivo. In conclusion, the syncytiotrophoblast‐like models of differentiating JEG‐3 cells cultured in CS‐C might be appropriate for evaluating drug transport across the placental trophoblast.
Clinical relevance of FLT3 receptor protein expression in Indian patients with acute leukemia
Authors: VORA Hemangini H , SHUKLA Shilin N , BRAHAMBHATT Birwa V , MEHTA Shalvi H , PATEL Nupur A , PARIKH Sonia K , SHAH Kruti N , SHAH Pankaj M
Published: October 2010

Aim:  FLT3 is a receptor tyrosine kinase that plays an important role in the pathogenesis of leukemia. The present study aimed to evaluate the role of FLT3 protein in patients with acute leukemia.

Method:  FLT3 protein was quantified by flow cytometry on leukemic blasts using CD135 antibody in 160 patients with acute leukemia.

Results:  We demonstrated FLT3 protein expression (>20%) in 82% of acute myeloid leukemia (AML), 60% of B‐lineage acute lymphoblastic leukemia (B‐ALL), 23% of T‐lineage acute lymphoblastic leukemia (T‐ALL) and 80% of biphenotypic leukemia. Further, FLT3 expression was seen to be significantly higher in AMLM2, M4, and M5 than in AMLM3. In B‐ALL, FLT3 was found to be higher in pro‐B‐ALL and lower in early B‐ALL. A CD34 expression >20% was associated with FLT3 positive B‐ALL. When correlated with disease status, all patients in the relapsed AML group had FLT3 > 20% at diagnosis. Unlike AML, the relapsed group of B‐ALL showed a lower incidence of FLT3 than the remission group.

Conclusion:  In summary, our data imply that there is frequent overexpression of the FLT3 protein in AML and B‐ALL patients of Indian origin. In future, the FLT3 protein level may be used to select patients for whom FLT3 inhibitor therapy may be indicated.
Mitomycin‐C, 5‐fluorouracil, and leucovorin as a salvage therapy in patients with metastatic colorectal adenocarcinoma
Authors: KANG Eun Joo , CHOI Yoon Ji , KIM Jung Seon , KIM Seung Tae , PARK Kyong Hwa , CHOI In Keun , OH Sang Chul , SEO Jae Hong , SHIN Sang Won , KIM Jun Suk , KIM Yeul Hong
Published: October 2010

Aim: There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin‐C, 5‐fluorouracil (5‐FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5‐FU/leucovorin and irinotecan/5‐FU/leucovorin.

Methods: We retrospectively analyzed 46 patients who had received mitomycin‐C/5FU/leucovorin between March 2008 and December 2009. All patients had failed prior first‐line and second‐line therapy containing oxaliplatin, irinotecan, and 5‐FU.

Results: The median age of the patients was 57.0 years (range, 34.0–76.0) and their median Eastern Cooperative Oncology Group performance status was 1 (0–2). A complete or partial response was not observed in any patient and stable disease was observed in 19 patients (41.3%). The median duration of follow up was 29 weeks (range 8–87 weeks). Median progression‐free survival was 10 weeks (95%CI8–12) and median overall survival was 38 weeks (95%CI32–44). Grade 3 and 4 hematological toxicities included neutropenia in five patients (10.8%) and thrombocytopenia in four patients (8.8%). Grade 3 or 4 non‐hematologic toxicities included nausea and vomiting in two patients. There were no treatment‐related deaths.

Conclusion: The combination regimen of mitomycin‐C/5‐FU/leucovorin showed marginal activity and tolerable toxicity profiles in heavily pretreated metastatic colorectal cancer patients.
AX J1749.1−2733 and AX J1749.2−2725 – the close pair of X-ray pulsars behind the Galactic Centre: an optical identification
Authors: Karasev D. I. , Lutovinov A. A. , Burenin R. A.
Published: October 2010

Two faint X-ray pulsars, AX J1749.2−2725 and AX J1749.1−2733, located in the direction of the Galactic Centre, were studied in detail using data from the INTEGRAL, XMM–Newton and Chandra observatories in X-rays, the SOFI/NTT instrument in the infrared and the RTT150 telescope in the optical. X-ray positions of both sources were determined with an uncertainty better than ∼1 arcsec, which allowed us to identify their infrared counterparts. From the subsequent analysis of infrared and optical data, we conclude that the counterparts of both pulsars are likely to be massive stars of B0–B3 class located behind the Galactic Centre at distances of 12–20 kpc, depending on the type, probably in the further parts of the Galactic spiral arms. In addition, we investigated the extinction law towards the Galactic bulge and found that it is significantly different from the standard one.
A prescription for the turbulent heating of astrophysical plasmas
Authors: Howes G. G.
Published: October 2010

The ion-to-electron heating ratio due to the dissipation of Alfvénic turbulence in astrophysical plasmas is calculated based on a cascade model for turbulence in weakly collisional plasmas. Conditions for validity of this model are discussed, a prescription for the turbulent heating is presented and it is applied to predict turbulent heating in accretion discs and the interstellar medium.