bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast cancer instructs dendritic cells to prime interleukin 13–secreting CD4+ T cells that facilitate tumor development
Authors: Aspord Caroline , Pedroza-Gonzalez Alexander , Gallegos Mike , Tindle Sasha , Burton Elizabeth C. , Su Dan , Marches Florentina , Banchereau Jacques , Palucka A. Karolina
Published: April 2007

We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417–1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon γ) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid β2 microglobulin–deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development.
Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers
Authors: Sood Rashmi , Zogg Mark , Westrick Randal J. , Guo Yi-he , Kerschen Edward J. , Girardi Guillermina , Salmon Jane E. , Coughlin Shaun R. , Weiler Hartmut
Published: April 2007

We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which fetal loss is triggered when the maternal prothrombotic state coincides with fetal gene defects that reduce activation of the protein C anticoagulant pathway within the placenta. Fetal loss is caused by disruption of placental morphogenesis at the stage of labyrinth layer formation and occurs in the absence of overt placental thrombosis, infarction, or perfusion defects. Platelet depletion or elimination of protease-activated receptor 4 (Par4) from the mother allows normal placentation and prevents fetal loss. These findings establish a cause–effect relationship for the observed epidemiologic association between maternal FvL status and fetal loss and identify fetal gene defects as risk modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is mediated by Par4-dependent activation of maternal platelets at the fetomaternal interface and likely involves a pathogenic pathway independent of occlusive thrombosis. Our results further demonstrate that the interaction of two given thrombosis risk factors produces markedly disparate consequences on disease manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed in which this interaction occurs.
A subset of dendritic cells induces CD4+ T cells to produce IFN-γ by an IL-12–independent but CD70-dependent mechanism in vivo
Authors: Soares Helena , Waechter HaeNa , Glaichenhaus Nicholas , Mougneau Evelyne , Yagita Hideo , Mizenina Olga , Dudziak Diana , Nussenzweig Michel C. , Steinman Ralph M.
Published: April 2007

Interferon (IFN)-γ, a cytokine critical for resistance to infection and tumors, is produced by CD4+ helper T lymphocytes after stimulation by cultured dendritic cells (DCs) that secrete a cofactor, interleukin (IL)-12. We have identified a major IL-12–independent pathway whereby DCs induce IFN-γ–secreting T helper (Th)1 CD4+ T cells in vivo. This pathway requires the membrane-associated tumor necrosis family member CD70 and was identified by targeting the LACK antigen from Leishmania major within an antibody to CD205 (DEC-205), an uptake receptor on a subset of DCs. Another major DC subset, targeted with 33D1 anti-DCIR2 antibody, also induced IFN-γ in vivo but required IL-12, not CD70. Isolated CD205+ DCs expressed cell surface CD70 when presenting antigen to T cell receptor transgenic T cells, and this distinction was independent of maturation stimuli. CD70 was also essential for CD205+ DC function in vivo. Detection of the IL-12–independent IFN-γ pathway was obscured with nontargeted LACK, which was presented by both DC subsets. This in situ analysis points to CD70 as a decision maker for Th1 differentiation by CD205+ DCs, even in Th2-prone BALB/c animals and potentially in vaccine design. The results indicate that two DC subsets have innate propensities to differentially affect the Th1/Th2 balance in vivo and by distinct mechanisms.
Elementary Mechanisms Producing Facilitation of Cav2.1 (P/Q-type) Channels
Authors: Chaudhuri Dipayan , Issa John B. , Yue David T.
Published: April 2007

The regulation of CaV2.1 (P/Q-type) channels by calmodulin (CaM) showcases the powerful Ca2+ decoding capabilities of CaM in complex with the family of CaV1-2 Ca2+ channels. Throughout this family, CaM does not simply exert a binary on/off regulatory effect; rather, Ca2+ binding to either the C- or N-terminal lobe of CaM alone can selectively trigger a distinct form of channel modulation. Additionally, Ca2+ binding to the C-terminal lobe triggers regulation that appears preferentially responsive to local Ca2+ influx through the channel to which CaM is attached (local Ca2+ preference), whereas Ca2+ binding to the N-terminal lobe triggers modulation that favors activation via Ca2+ entry through channels at a distance (global Ca2+ preference). CaV2.1 channels fully exemplify these features; Ca2+ binding to the C-terminal lobe induces Ca2+-dependent facilitation of opening (CDF), whereas the N-terminal lobe yields Ca2+-dependent inactivation of opening (CDI). In mitigation of these interesting indications, support for this local/global Ca2+ selectivity has been based upon indirect inferences from macroscopic recordings of numerous channels. Nagging uncertainty has also remained as to whether CDF represents a relief of basal inhibition of channel open probability (Po) in the presence of external Ca2+, or an actual enhancement of Po over a normal baseline seen with Ba2+ as the charge carrier. To address these issues, we undertake the first extensive single-channel analysis of CaV2.1 channels with Ca2+ as charge carrier. A key outcome is that CDF persists at this level, while CDI is entirely lacking. This result directly upholds the local/global Ca2+ preference of the lobes of CaM, because only a local (but not global) Ca2+ signal is here present. Furthermore, direct single-channel determinations of Po and kinetic simulations demonstrate that CDF represents a genuine enhancement of open probability, without appreciable change of activation kinetics. This enhanced-opening mechanism suggests that the CDF evoked during action-potential trains would produce not only larger, but longer-lasting Ca2+ responses, an outcome with potential ramifications for short-term synaptic plasticity.
Probing the Cavity of the Slow Inactivated Conformation of Shaker Potassium Channels
Authors: Panyi Gyorgy , Deutsch Carol
Published: April 2007

Slow inactivation involves a local rearrangement of the outer mouth of voltage-gated potassium channels, but nothing is known regarding rearrangements in the cavity between the activation gate and the selectivity filter. We now report that the cavity undergoes a conformational change in the slow-inactivated state. This change is manifest as altered accessibility of residues facing the aqueous cavity and as a marked decrease in the affinity of tetraethylammonium for its internal binding site. These findings have implications for global alterations of the channel during slow inactivation and putative coupling between activation and slow-inactivation gates.
Unusual Delayed Presentation of a Nail Gun Injury Through the Skull Base
Authors: Lee Alice D. , Oh Young S.
Published: April 2007

Published reports of nail gun injuries to the face are uncommon. We describe an unusual delayed presentation with injury through the infratemporal fossa and a literature review. A 55‐year‐old patient presented 2 weeks after an unrecognized injury with complaints of a headache. Imaging revealed a nail traversing the infratemporal fossa with intracranial extension. The nail was removed through a preauricular approach without sequelae. Nail gun missiles to the face are uncommon, dramatic, but often nonfatal because of their relative low velocity. Patients are usually diagnosed at the time of injury, evaluated with computed tomography and angiography, and treated with surgery.
Radioimmunotherapy With Astatine‐211 Using Chimeric Monoclonal Antibody U36 in Head and Neck Squamous Cell Carcinoma
Authors: Cheng Junping , Ekberg Tomas , Engström Mats , Nestor Marika , Jensen Holger J. , Tolmachev Vladimir , Anniko Matti
Published: April 2007

Objectives: In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine‐211‐labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT‐SCC7 in vivo.

Study Design: Xenograft tumors were inoculated subcutaneously in nude mice. Astatine‐211‐labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36.

Methods: In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only.

Results: The biodistribution experiments demonstrated that astatine‐211‐labeled U36 could target UT‐SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05).

Conclusion: The study illustrates the specific binding of astatine‐211‐labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.
Important Clinical Symptoms in Patients Undergoing Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis
Authors: Ling Francis T. K. , Kountakis Stilianos E.
Published: April 2007

Objective: To evaluate the prevalence and severity of individual Rhinosinusitis Task Force (RSTF) symptoms in patients with chronic rhinosinusitis (CRS) undergoing functional endoscopic sinus surgery (FESS).

Methods: Retrospective analysis of prospectively collected data in 201 patients treated with FESS. The prevalence and severity of individual RSTF major and minor symptom scores graded on a visual analogue scale (VAS) were compared. Correlation between absolute improvement in individual symptom scores at 1‐year postoperative was performed.

Results: One‐hundred fifty‐eight of 201 patients met inclusion criteria giving a response rate of 78%. The average age was 49.4 (range 18–80) with a male‐to‐female ratio of 1.1:1. The preoperative leading mean symptom scores were postnasal drip (5.8 ± 0.3), nasal obstruction (5.7 ± 0.3), and facial congestion (5.1 ± 0.3). These symptoms were also the most prevalent with 82%, 84%, and 79% of patients reporting these symptoms, respectively. Postoperative symptom improvements were significant (P < .0001) across all RSTF domains except fever. The highest percentage improvement was seen with facial congestion (93%), nasal obstruction (92%), and postnasal drip (85%). Multivariate analysis revealed significant (P < .0001) high correlation between improvements of facial pain/pressure with facial congestion (R = 0.72), facial congestion with nasal obstruction (R = 0.65), and facial pain/pressure with headache (R = 0.72).

Conclusion: The top three RSTF symptoms were postnasal drip, nasal obstruction, and facial congestion in terms of prevalence and severity. Symptom scores improved after FESS. Of these symptoms, the degree of improvement of facial pain/pressure, facial congestion, nasal obstruction, and headache are highly correlated.
Tacrolimus: A New Option in Therapy‐Resistant Chronic External Otitis
Authors: Caffier Philipp P. , Harth Wolfgang , Mayelzadeh Babak , Haupt Heidemarie , Sedlmaier Benedikt
Published: April 2007

Objective: To evaluate the efficacy of the novel topical immune modulator tacrolimus in chronic uninfectious otherwise therapy‐resistant external otitis (EO).

Study Design: Prospective clinical study.

Patients and Methods: There were 53 patients aged 5 to 83 years. An ear wick containing 0.1% tacrolimus ointment (Protopic) was inserted into the external auditory canal every 2nd to 3rd day. Altogether, the wick was changed three times. The pre‐, intra‐ and posttherapeutic state of the clinical parameters otalgia, edema, otorrhea, erythema, pruritus, and desquamation was rated by means of a 6‐point score system. Treatment efficiency was evaluated on the basis of follow‐up investigations at 3‐month intervals, a standardized findings sheet, and photograph documentation.

Results: The short‐term results showed a clear improvement in 85% of the patients and significant reductions of the severity levels for all clinical parameters investigated (P < .001). Concerning the long‐term results, a one‐time treatment cycle led to complete healing in 46% of the patients throughout a follow‐up of 10 to 22 months. Of the patients, 54% had recurrent EO events with significantly extended mean symptom‐free intervals. Reapplied tacrolimus treatment patterns attenuated the relapsing course of disease and significantly reduced the number of EO episodes. Within the observation period, no relevant side effects were observed, except for a local feeling of heat, occasional skin burning, and itching.

Conclusions: The topical application of 0.1% tacrolimus ointment in the outer ear canal appears to be an effective and well‐tolerated new option in corticosteroid‐free treatment of chronic therapy‐resistant EO.
Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway
Authors: Longman Dasa , Plasterk Ronald H.A. , Johnstone Iain L. , Cáceres Javier F.
Published: April 2007

The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1–7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these genes have been found in several species. Whereas in humans NMD is linked to splicing, PTC definition occurs independently of exon boundaries in Drosophila. Here, we have conducted an analysis of the cis-acting sequences and trans-acting factors that are required for NMD in C. elegans. We show that a PTC codon is defined independently of introns in C. elegans and, consequently, components of the exon junction complex (EJC) are dispensable for NMD. We also show a distance-dependent effect, whereby PTCs that are closer to the 3′ end of the mRNA are less sensitive to NMD. We also provide evidence for the existence of previously unidentified components of the NMD pathway that, unlike known smg genes, are essential for viability in C. elegans. A genome-wide RNA interference (RNAi) screen resulted in the identification of two such novel NMD genes, which are essential for proper embryonic development, and as such represent a new class of essential NMD genes in C. elegans that we have termed smgl (for smg lethal). We show that the encoded proteins are conserved throughout evolution and are required for NMD in C. elegans and also in human cells.
Multiscale image analysis of microcellular solids: application to hybrid silica xerogels
Authors: GOMMES CÉDRIC J. , PIRARD JEAN‐PAUL , BLACHER SILVIA
Published: April 2007

A general methodology is proposed to characterize microcellular solids, the structure of which consists of a three‐dimensional network of filamentary structures. The analysis is based on transmission electron microscopy observation of the filaments individually and of their spatial arrangement. The micrographs are analyzed with grey‐tone digital image analysis techniques, such as opening granulometry and correlation analysis. The methodology is applied to hybrid organic–inorganic low‐density silica solids synthesized by the sol–gel method with an organically modified co‐reactant. The quantitative impact of the co‐reactant on each structural level of the structure is assessed quantitatively.
Method for determination of the displacement field in patterned nanostructures by TEM/CBED analysis of split high‐order Laue zone line profiles
Authors: SPESSOT A. , FRABBONI S. , BALBONI R. , ARMIGLIATO A.
Published: April 2007

A method to extract accurate information on the displacement field distribution from split high‐order Laue zones lines in a convergent‐beam electron diffraction pattern of nanostructures has been developed. Starting from two‐dimensional many beam dynamical simulation of HOLZ patterns, we assembled a recursive procedure to reconstruct the displacement field in the investigated regions of the sample, based on the best fit of a parametrized model. This recursive procedure minimizes the differences between simulated and experimental patterns, taken in strained regions, by comparing the corresponding rocking curves of a number of high‐order Laue zone reflections. Due to its sensitivity to small displacement variations along the electron beam direction, this method is able to discriminate between different models, and can be also used to map a strain field component in the specimen. We tested this method in a series of experimental convergent‐beam electron diffraction patterns, taken in a shallow trench isolation structure. The method presented here is of general validity and, in principle, it can be applied to any sample where not negligible strain gradients along the beam direction are present.
High‐resolution compact X‐ray microscopy
Authors: TAKMAN P. A. C. , STOLLBERG H. , JOHANSSON G. A. , HOLMBERG A. , LINDBLOM M. , HERTZ H. M.
Published: April 2007

We demonstrate compact full‐field soft X‐ray transmission microscopy with sub 60‐nm resolution operating at λ= 2.48 nm. The microscope is based on a 100‐Hz regenerative liquid‐nitrogen‐jet laser‐plasma source in combination with a condenser zone plate and a micro‐zone plate objective for high‐resolution imaging onto a 2048 × 2048 pixel CCD detector. The sample holder is mounted in a helium atmosphere and allows imaging of both dry and wet specimens. The microscope design enables fast sample switching and the sample can be pre‐aligned using a visible‐light microscope. High‐quality images can be acquired with exposure times of less than 5 min. We demonstrate the performance of the microscope using both dry and wet samples.
Scanning probe microscopies applied to the study of the domain wall in a ferroelectric crystal
Authors: CANET‐FERRER J. , MARTÍN‐CARRÓN L. , MARTÍNEZ‐PASTOR J. , VALDÉS J. L. , PEÑA A. , CARVAJAL J. J. , DIAZ F.
Published: April 2007

Scanning near‐field optical microscopy is capable of measuring the topography and optical signals at the same time. This fact makes this technique a valuable tool in the study of materials at nanometric scale and, in particular, of ferroelectric materials, as it permits the study of their domains structure without the need of chemical etching and, therefore, not damaging the surface (as will be demonstrated later). We have measured the scanning near‐field optical microscopy transmission, as well as the topography, of an RbTiOPO4 single crystalline slab, which exhibits two different of macroscopic ferroelectric domains. A chemical selective etching has been performed to distinguish between them, obtaining areas with a noticeable roughness (C− domain) in comparison with the original flat aspect of the other ones (C+ domain). The effects of the selective chemical etching have been quantified in topographic images obtained by means of our fibre tip probe, and have been compared to topographic images obtained by Atomic Force Microscopy, with a better resolution. The near‐field optical transmission images recorded have been obtained under different excitation wavelengths. These images are modulated by the light scattering due to the grains at the rough surface, which depends on the excitation wavelength used. In addition, they show a significant optical contrast due to the variations of the dielectric constant on the proximity of the ferroelectric domain wall.
Phylogeny of western Mediterranean Leptodirini, with an emphasis on genital characters (Coleoptera: Leiodidae: Cholevinae)
Authors: FRESNEDA JAVIER , SALGADO JOSÉ‐MARÍA , RIBERA IGNACIO
Published: April 2007

Abstract The tribe Leptodirini (Leiodidae: Cholevinae) is one of the largest radiations of Coleoptera in the subterranean environment. Although subjected to systematic and evolutionary studies, the phylogeny remains poorly understood. We assessed the phylogeny of the western Mediterranean lineages (Iberian Peninsula, Pyrenees and Sardinia) based on a cladistic analysis of fourteen characters of external morphology and twenty characters of the male and female genitalia, studied in 182 species belonging to thirty‐nine genera. We tested the monophyly of the traditional two main divisions of the group (infraflagellates and supraflagellates), as well as that of some ‘phyletic series’. The final matrix contained fifty‐eight terminal taxa, twenty‐four of which had different character state combinations. The strict consensus of the sixty most parsimonious trees recovered a monophyletic Leptodirini, but not their separation into infraflagellates and supraflagellates. The supraflagellates formed a paraphyletic group with respect to the infraflagellates (corresponding to our sampled ‘Speonomus’ series), with Notidocharis sister to all other included Leptodirini, and Speonomidius sister to Leptodirini excluding Notidocharis. The series ‘Spelaeochlamys’, including the Sardinian genera but excluding Pseudochlamys, was recovered as monophyletic with weak support. The ‘Quaestus’ series formed a polytomy with Pseudochlamys plus the ‘Speonomus’ series (including Bathysciola), which was recovered as monophyletic with strong support. Speonomus, Bathysciola, Quaestus and Troglophyes were para‐ or polyphyletic. Our results suggested the respective monophyletic origin of the Leptodirini from the Pyrenees (Pseudochlamys plus the ‘Speonomus’ series) and the Mediterranean coast plus Sardinia (series ‘Spelaeochlamys’). On the contrary, the Leptodirini of the Atlantic north coast of the Iberian Peninsula (series ‘Quaestus’ and ‘Speonomidius’) were not monophyletic.
Systematics of Sitonini (Coleoptera: Curculionidae: Entiminae), with a hypothesis on the evolution of feeding habits
Authors: VELÁZQUEZ DE CASTRO ANTONIO J. , ALONSO‐ZARAZAGA MIGUEL ÁNGEL , OUTERELO RAIMUNDO
Published: April 2007

AbstractA new classification of Sitonini Gistel into ten genera is proposed, derived from a phylogenetic analysis based on morphology. Two subgenera ofSitona,CharagmusandCoelositona, are promoted to genus level.Sitonais restricted to the former nominotypical subgenus and redefined using apomorphies, and several species previously included in it are transferred to the genusCoelositonaGonzález. The species composition of the genusCharagmusSchönherr is unchanged.Andriongen.n.is described (type species:Curculio regensteinensisHerbst, 1794).CatachaenusSchönherr, 1840 is synonymized withEugnathusSchönherr, 1834 (syn.n.).Homalorhinus lutosusHochhuth, 1847 is removed from Sitonini. The relationships represented by the new classification correspond with the evolution of Fabaceae (Leguminosae), mostly with the group of ‘temperate herbaceous tribes’ or Hologalegina. This group is divided into the sister clades, Loteae s.l. and IRLC (inverted repeat‐lacking clade) – a clade well defined by the loss of a structural mutation in the genome of the chloroplast.Andriondoes not feed on Hologalegina.CharagmusandCoelositonafeed on species of Loteae s.l., whereas members of the genusSitonafeed on species in IRLC. This ability to feed on IRLC plants seems to have been a key trait that enabled the radiation ofSitonainto more than 100 species. A key to the genera of Sitonini and illustrations of important morphological features are provided. A new structure is described from the internal sac, the ‘hamuli’. The variability of hamuli between the species of Sitonini is an important new tool in the taxonomy of this tribe. New combinations:Eugnathus circulus(Eydoux & Souleyet, 1839),E. mangarinicus(Voss, 1925),E. scintillans(Pascoe, 1874),E. sulcifrons(Heller, 1934),Charagmus gressorius(Fabricius, 1792),Ch. intermediusKüster, 1847,Ch. griseus(Fabricius, 1775),Ch. cachectusGyllenhal, 1834,Ch. stierliniReitter, 1903,Ch. variegatus(Fåhraeus, 1840),Coelositona ribesi(González, 1971),C. cambricus(Stephens, 1831),C. cinerascens(Fåhraeus, 1840),C. limosus(Rossi, 1792),C. ocellatus(Küster, 1849),C. latipennis(Gyllenhal, 1834),C. puberulus(Reitter, 1903),C. villosus(Allard, 1869),Andrion regensteinense(Herbst, 1794) andAnemeroides lutosus(Hochhuth, 1847).
Phylogenetic utility of dynamin and triose phosphate isomerase
Authors: HARDY NATE B.
Published: April 2007

Abstract Dynamin and triose phosphate isomerase (Tpi), two markers suggested as potentially useful for insect phylogenetics, have been sequenced for 12 scale insect taxa (Hemiptera: Coccoidea). Protocols are given for their amplification using conventional polymerase chain reaction, and their phylogenetic utility has been evaluated using several qualitative criteria and a modified version of the partition addition bootstrap alteration approach. Dynamin and Tpi fragments are easy to amplify and are evolving at a rate comparable with widely used nuclear ribosomal markers. The dynamin fragment has a single short intron. The Tpi fragment has three introns. One possible drawback to the use of the dynamin fragment as a phylogenetic marker is that its short length limits accurate modelling of complex substitution processes.
Natural disasters, climate change and mental health considerations for rural Australia
Authors: Morrissey Shirley A. , Reser Joseph P.
Published: April 2007

This paper addresses a very salient feature of rural life and landscapes in Australia, natural disasters, and offers a psychological perspective on individual and community perceptions, responses, preparedness and planning. The convergent perspective offered reflects research and practice findings and insights from social and environmental psychology, as well as clinical, health and community psychology. The objective is to briefly characterise how these psychological approaches frame the psychological and social reality of these threats and events, and to canvas what insights and evidence‐based best practice psychology have to offer allied professionals and paraprofessionals, and rural communities, as they experience and come to terms with the vagaries and extremes of the Australian environment.
SHORT WAVES‐INDUCED ENHANCEMENT OF PROLIFERATION OF HUMAN CHONDROCYTES: INVOLVEMENT OF EXTRACELLULAR SIGNAL‐REGULATED MAP‐KINASE (ERK)
Authors: Wang Jue‐Long , Chan Rai‐Chi , Cheng He‐Hsiung , Huang Chun‐Jen , Lu Yih‐Chau , Chen I‐Shu , Liu Shiuh‐Inn , Hsu Shu‐Shong , Chang Hong‐Tai , Huang Jong‐Khing , Chen Jin‐Shyr , Ho Chin‐Man , Jan Chung‐Ren
Published: April 2007

Short‐wave diathermy (SWD) is a form of radiofrequency radiation that is used therapeutically by physiotherapists. The cellular mechanisms of SWD are unclear. The present study was performed to explore the effect of different conditions of short‐wave exposure on the proliferation of cultured human chondrocytes.

Cells exposed to short waves once per day for seven consecutive days exhibited a significant increase in proliferation by 42% compared with the control cells. In cells that were treated with short waves twice per day for seven consecutive days, or only once on Day 1 and then examined for proliferation on Day 7, cell proliferation was greater than the control cells by 40% and 30%, respectively.

Given the importance of mitogen‐activated protein kinases (MAPK) in the proliferation of different cell types, efforts were extended to explore the role of three major types of MAPK; that is, extracellular signal‐regulated kinase (ERK), c‐Jun NH2‐terminal protein kinase (JNK) and p38.

4. It was found that the level of phosphorylated ERK (phospho‐ERK 1 and ERK 2) increased significantly within 5–120 min following consecutive exposure to short waves for 7 days. Exposure to short waves failed to alter the intensity of phosphorylated JNK and p38 within 0–240 min.

Cells were exposed to short waves once for seven consecutive days in the presence of 0, 10 µmol/L, 20 µmol/L or 50 µmol/L PD98059 (an ERK inhibitor). PD98059 totally inhibited short waves‐induced enhancement of proliferation without altering normal control viability. In the presence of short waves and PD98059, the cell viability was lower than the normal control. Together, the data suggest that short waves could increase proliferation in human chondrocytes through activation of the ERK pathway, which is also involved in maintaining normal cell proliferation under physiological conditions.
HIGH‐DOSE TAURINE SUPPLEMENTATION INCREASES SERUM PARAOXONASE AND ARYLESTERASE ACTIVITIES IN EXPERIMENTAL HYPOTHYROIDISM
Authors: Dirican Melahat , Taş Sibel , Sarandöl Emre
Published: April 2007

Hypothyroidism is accompanied by hyperlipidaemia and oxidative stress and is associated with several complications, such as atherosclerosis. Paraoxonase activity has been reported to decrease in several situations associated with atherosclerosis and oxidative stress. In the present study, the effects of different doses of taurine on serum paraoxonase and arylesterase activities, as well as on the serum lipid profile, were investigated in hypothyroid rats.

Forty male Sprague‐Dawley rats were randomly divided into five groups as follows: Group 1, rats received normal rat chow and tap water; Group 2, rats received standard rat chow + 0.05% propylthiouracil (PTU) in the drinking water; and Groups 3–5, taurine‐supplemented PTU groups (standard rat chow + 0.5, 2 or 3% taurine in the drinking water, respectively, in addition to PTU). Paraoxon or phenylacetate were used as substrates to measure paraoxonase and arylesterase activity, respectively. Plasma and tissue malondialdehyde (MDA) levels, indicators of lipid peroxidation, were determined using the thiobarbituric‐acid reactive substances method. Serum triglyceride, total cholesterol and high‐density lipoprotein–cholesterol (following precipitation with dextran sulphate–magnesium chloride) were determined using enzymatic methods.

Serum paraoxonase and arylesterase activities were increased and plasma and tissue MDA levels and serum triglyceride levels were reduced in a dose‐dependent manner in taurine‐treated hypothyroid rats. Taurine concentrations were positively correlated with enzyme activities and negatively correlated with MDA and triglyceride levels.

Further studies are needed to investigate the role of taurine supplementation in hypothyroidism in human subjects.
NARIRUTIN INHIBITS AIRWAY INFLAMMATION IN AN ALLERGIC MOUSE MODEL
Authors: Funaguchi Norihiko , Ohno Yasushi , La Bu Lin Bai , Asai Toshihiro , Yuhgetsu Hideyuki , Sawada Masahiro , Takemura Genzou , Minatoguchi Shinya , Fujiwara Takako , Fujiwara Hisayoshi
Published: April 2007

Flavonoids are naturally occurring compounds that possess anti‐allergic, anti‐inflammatory, antiproliferative and anti‐oxidant properties. In the present study, we investigated whether the flavonoid narirutin could reduce airway inflammation in ovalbumin (OVA)‐sensitized/challenged NC/Nga mice, a model of allergic eosinophilic airway inflammation.

Mice were initially immunized intraperitoneally with OVA on Days 0 and 7 and then challenged with inhaled OVA on Days 14, 15 and 16. In addition, some mice received narirutin orally at doses of 0.1, 1 or 10 mg/kg bodyweight daily on Days 7–16.

At 10 mg/kg, but not 0.1 or 1 mg/kg, narirutin significantly diminished OVA‐induced airway inflammation caused by infiltration of lung tissue with inflammatory and mucus‐producing cells, as well as reduced eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid (BALF), interleukin (IL)‐4 levels in BALF and IgE levels in serum.

The mechanism of the anti‐inflammatory effect of narirutin are likely to be associated with a reduction in the OVA‐induced increases of IL‐4 and IgE in a murine model of allergic eosinophilic airway inflammation. These findings suggest that narirutin may be an effective new tool in the treatment of bronchial asthma.
ARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION
Authors: Durante William , Johnson Fruzsina K , Johnson Robert A
Published: April 2007

Arginase is the focal enzyme of the urea cycle hydrolysing l‐arginine to urea and l‐ornithine. Emerging studies have identified arginase in the vasculature and have implicated this enzyme in the regulation of nitric oxide (NO) synthesis and the development of vascular disease.

Arginase inhibits the production of NO via several potential mechanisms, including competition with NO synthase (NOS) for the substrate l‐arginine, uncoupling of NOS resulting in the generation of the NO scavenger, superoxide and peroxynitrite, repression of the translation and stability of inducible NOS protein, inhibition of inducible NOS activity via the generation of urea and by sensitization of NOS to its endogenous inhibitor asymmetric dimethyl‐l‐arginine.

Upregulation of arginase inhibits endothelial NOS‐mediated NO synthesis and may contribute to endothelial dysfunction in hypertension, ageing, ischaemia–reperfusion and diabetes.

Arginase also redirects the metabolism of l‐arginine to l‐ornithine and the formation of polyamines and l‐proline, which are essential for smooth muscle cell growth and collagen synthesis. Therefore, the induction of arginase may also promote aberrant vessel wall remodelling and neointima formation.

Arginase represents a promising novel therapeutic target that may reverse endothelial and smooth muscle cell dysfunction and prevent vascular disease.
SICKLE CELL DISEASE: ROLE OF REACTIVE OXYGEN AND NITROGEN METABOLITES
Authors: Wood Katherine C , Granger D Neil
Published: April 2007

Sickle cell disease (SCD) is an inherited disorder of haemoglobin synthesis that is associated with significant morbidity and mortality due to sequelae of episodic vaso‐occlusive events: pain crises and multiorgan damage. The microvascular responses to the initiation, progression and resolution of vaso‐occlusive events are consistent with an inflammatory phenotype as suggested by activation of multiple cell types, an oxidatively stressed environment and endothelial cell dysfunction.

Decreased anti‐oxidant defences in SCD patients and mice are accompanied by activation of enzymatic (NADPH oxidase, xanthine oxidase) and non‐enzymatic (sickle haemoglobin auto‐oxidation) sources of reactive oxygen species. The resultant oxidative stress leads to dysfunction/activation of arteriolar and venular endothelial cells, resulting in impaired vasomotor function and blood cell–endothelial cell adhesion.

Changes in substrate and cofactor availability for endothelial cell nitric oxide synthase may underlie reactive oxygen‐ and nitrogen‐induced events that contribute to SCD‐induced vasculopathy.

The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease.
IDENTIFICATION OF ANTIMICROBIAL ACTIVITY FROM GOAT CERVICAL EPITHELIUM
Authors: Rana Manish , Mittal Deepak , Pereira Ben MJ
Published: April 2007

In mammals, antimicrobial peptides are present in epithelial cells of the respiratory, gastrointestinal and urinogenital tracts. In the present study, we report the identification and partial characterization of an antimicrobial peptide in extracts prepared from goat cervical epithelial tissue.

The bioactivity, as determined by radial and disc diffusion assays, was identified in a peptide of molecular mass 4.5 kDa purified by cation exchange and gel filtration techniques. The purified peptide exhibited antibacterial activity againstEscherichia coli(Gram‐negative) as well asBacillus subtilis(Gram‐positive) bacteria.

The minimum inhibitory concentration of the peptide estimated by liquid broth assay forE. coliandB. subtilissuspensions was 31 and 50 µg/mL, respectively, a result implying that the peptide is more efficient in inhibiting Gram‐negative than Gram‐positive bacteria.

Because the peptide has no spermicidal activity, we propose that it is responsible for protecting the female genital tract against bacteria.

Whether the peptide has potentials for use in the cryopreservation, storage and transport of semen remains to be determined.
RENOPROTECTIVE EFFECT OF TROLOX AGAINST ISCHAEMIA–REPERFUSION INJURY IN RATS
Authors: Wongmekiat Orawan , Thamprasert Kamthorn , Lumlertgul Dusit
Published: April 2007

Although α‐tocopherol has been shown to improve renal function following ischaemia–reperfusion (I/R) injury, its clinical use is not common because α‐tocopherol requires several days of pretreatment to exhibit anti‐oxidative benefits. The advent of trolox, a water‐soluble analogue of α‐tocopherol, has raised the possibility that this compound may function more rapidly during acute oxidative stress than the conventional α‐tocopherol.

The present study was undertaken to determine the effects of the short‐term administration of trolox on renal excretory function following I/R in rats.

Male Wistar rats were subjected to 45 min unilateral renal artery occlusion followed by 120 min reperfusion. The control I/R group was subjected to I/R and received saline as an intravenous bolus (2 mL/kg) followed by a continuous infusion of 2 mL/kg per h starting 30 min before ischaemia, whereas the three trolox‐treated I/R groups were given an i.v. bolus of trolox (2.5 mg/kg) followed by a continuous infusion (12 mg/kg per h) starting at 30 min before ischaemia, 5 min before reperfusion and 5 min after reperfusion, respectively. Renal function, malondialdehyde, glutathione and histopathology were evaluated.

Ischaemia–reperfusion produced a significant deterioration of renal function, which was accompanied by an elevated malondialdehyde and depleted glutathione content. Kidneys from control I/R rats demonstrated tubular cell transformation, brush border loss, vacuolation, cast formation and tubular obstruction. These changes were attenuated by trolox treatment, with the best improvement achieved when trolox was delivered 5 min before reperfusion.

The results demonstrate the renoprotective effects of the short‐term administration of trolox on I/R injury. These findings indicate the ability of trolox to overcome a major drawback of using α‐tocopherol and suggest that trolox may offer a therapeutic advantage over α‐tocopherol in acute ischaemic renal failure settings.
EXTRACELLULAR SIGNAL‐REGULATED KINASE PATHWAYS MAY MEDIATE THE PROTECTIVE EFFECT OF ELECTRICAL STIMULATION OF THE PARAVENTRICULAR NUCLEUS AGAINST ISCHAEMIA–REPERFUSION INJURY OF THE GASTRIC MUCOSA
Authors: Zhang Yong‐Mei , Wei Er‐Qing , Li Li , Qiao Wei‐Li , Wang Lin , Zhang Jian‐Fu
Published: April 2007

The aim of the present study was to elucidate the role of the extracellular signal‐regulated kinase (ERK) pathway in mediating the effects of electrical stimulation of the paraventricular nucleus (PVN) on apoptosis and proliferation induced by gastric ischaemia–reperfusion injury (GI/RI).

To investigate the effects of electrical stimulation of the hypothalamic PVN on gastric mucosal apoptosis and proliferation in response to ischaemia–reperfusion (I/R), we used a GI/RI model by clamping the coeliac artery for 30 min and then reperfusing the artery for 30 min or 1, 3 or 6 h. We used immunohistochemistry and western blotting to investigate the expression, activation and distribution of ERKs and the dynamic changes in their downstream cellular factors Bcl‐2 and Bax at different times subsequent to electrical stimulation of the PVN in the I/R‐injured gastric mucosa.

Electrical stimulation of the PVN markedly attenuated GI/RI at 30 min and 1 and 3 h after reperfusion. Electrical stimulation decreased gastric mucosal apoptosis, increased gastric mucosal proliferation and promoted the expression and activation of phosphorylated (p)‐ERK1/2 30 min after reperfusion. Electrical stimulation increased the expression of Bcl‐2 and decreased the expression of Bax at 30 min and 1 and 3 h after reperfusion. In contrast, inhibition of ERK1/2 activity by the specific upstream mitogen‐activated protein kinase kinase inhibitor PD98059 produced similar effects at 1 h after reperfusion in rats subjected to I/R with or without electrical stimulation of the PVN. Administration of PD98059 aggravated gastric mucosal injury, increased apoptosis, decreased proliferation in gastric mucosal cells, decreased the expression and activity of p‐ERK1/2 and Bcl‐2 expression and increased Bax expression.

These results indicate that the PVN protects against GI/RI and that this protection is associated with the inhibition of cellular apoptosis and the promotion of proliferation in the gastric mucosa, probably by activating the ERK pathway.
Back in the mirrored room: the enduring relevance of discursive practice
Authors: Sinclair Stacey L.
Published: April 2007

This article seeks to re‐engage a conversation regarding the importance of acknowledging the discursive content of the therapeutic process. Hare‐Mustin's (1994) article argued that psychotherapy is involved in the generation of values and norms, and thus requires ethical sensibilities. Her analysis recognized how particular socio‐cultural forces go unnoticed and suggested that unless therapists recognize their participation in discursive practices, they may unwittingly collude with and reinforce harmful cultural practices. The goal of this article is to revisit the ‘mirrored room’ so that family therapists can more deliberately evaluate their participation in cultural practices that impact on their work with clients. This article begins with a review of contemporary efforts to grapple with the issues Hare‐Mustin presented, and maintains that even contemporary approaches that assert a commitment to postmodern understandings remain incomplete without an analysis of discourse. The article then outlines the conceptual tools within discursive practice that advance the initial motivation of these contemporary efforts.
Recollections of parental style and perceptions of current family functioning at age 50
Authors: Tiffin P. A. , Pearce M. S. , Kaplan C. , Fundudis T. , Parker L.
Published: April 2007

It is hypothesized that recollections of an individual's parental behaviour towards them is associated with their view of their current family functioning. This hypothesis was tested for using data provided by 213 men and 270 women drawn at age 50 from the Newcastle Thousand Families Study. Relationships between retrospective reports of parental behaviour during childhood and perceptions of current family functioning at age 50 were investigated using a univariate regression analysis in order to explore the relationship between scores on the Parental Bonding Instrument (PBI) and the McMaster Family Assessment Device (FAD). Where a significant association was observed the relationship between subscale scores was further examined using a multivariate regression analysis including gender and self‐reported psychological well‐being (as measured by the General Health Questionnaire‐ GHQ) as covariates. Several statistically significant associations between PBI and FAD subscale scores were observed. Four of these remained statistically significant once gender and self‐reported psychological well‐being were adjusted for. In this population sample, aspects of recalled parental behaviour were associated with the health of current family functioning in several domains as reported by the FAD. These associations appear to be partly mediated by current psychological well‐being.
Learning overhypotheses with hierarchical Bayesian models
Authors: Kemp Charles , Perfors Andrew , Tenenbaum Joshua B.
Published: April 2007

Inductive learning is impossible without overhypotheses, or constraints on the hypotheses considered by the learner. Some of these overhypotheses must be innate, but we suggest that hierarchical Bayesian models can help to explain how the rest are acquired. To illustrate this claim, we develop models that acquire two kinds of overhypotheses – overhypotheses about feature variability (e.g. the shape bias in word learning) and overhypotheses about the grouping of categories into ontological kinds like objects and substances.
Preschool children learn about causal structure from conditional interventions
Authors: Schulz Laura E. , Gopnik Alison , Glymour Clark
Published: April 2007

The conditional intervention principle is a formal principle that relates patterns of interventions and outcomes to causal structure. It is a central assumption of experimental design and the causal Bayes net formalism. Two studies suggest that preschoolers can use the conditional intervention principle to distinguish causal chains, common cause and interactive causal structures even in the absence of differential spatiotemporal cues and specific mechanism knowledge. Children were also able to use knowledge of causal structure to predict the patterns of evidence that would result from interventions. A third study suggests that children's spontaneous play can generate evidence that would support such accurate causal learning.
Sensitivity to sampling in Bayesian word learning
Authors: Xu Fei , Tenenbaum Joshua B.
Published: April 2007

We report a new study testing our proposal that word learning may be best explained as an approximate form of Bayesian inference (Xu & Tenenbaum, in press). Children are capable of learning word meanings across a wide range of communicative contexts. In different contexts, learners may encounter different sampling processes generating the examples of word–object pairings they observe. An ideal Bayesian word learner could take into account these differences in the sampling process and adjust his/her inferences about word meaning accordingly. We tested how children and adults learned words for novel object kinds in two sampling contexts, in which the objects to be labeled were sampled either by a knowledgeable teacher or by the learners themselves. Both adults and children generalized more conservatively in the former context; that is, they restricted the label to just those objects most similar to the labeled examples when the exemplars were chosen by a knowledgeable teacher, but not when chosen by the learners themselves. We discuss how this result follows naturally from a Bayesian analysis, but not from other statistical approaches such as associative word‐learning models.
Story contexts increase susceptibility to the DRM illusion in 5‐year‐olds
Authors: Dewhurst Stephen A. , Pursglove Rhian C. , Lewis Charlie
Published: April 2007

False recognition in children aged 5, 8, and 11 years was investigated using the standard version of the Deese‐Roediger‐McDermott (DRM) procedure and an alternative version in which the DRM stimuli were embedded in stories designed to emphasize their overall theme. Relative to the 8‐ and 11‐year‐olds, the 5‐year‐olds falsely recognized fewer critical lures when the DRM stimuli were presented in lists, but falsely recognized more critical lures when the stimuli were presented in stories. Levels of false recognition in the 8‐ and 11‐year‐olds were not affected by study format. We argue that the story context enhanced the ability of the 5‐year‐olds to make inferences based on the theme of the DRM stimuli. The 5‐year‐olds then showed higher levels of false recognition than the older children owing to their inability to reject lure words consistent with the stories.