bluuebunny/crossref_metadata_2025 huggingface dataset:
Wikipedia(s) on the language map of the world
Authors: Dalby Andrew
Published: June 2007

This article will not try to describe the whole Wikimedia galaxy. It will stick to Wikipedia in English, and that's ambitious enough. The English-language Wikipedia, by far the biggest of them, now (28th November 2006) contains 1,506,659 articles. The German Wikipedia reached 500,000 articles on 23rd November (note in passing: the English Wikipedia has added that many articles to its total in just six months), while the French Wikipedia reached the 400,000 milestone on 27th November. The newest and smallest Wikipedia, number 250, is in the Lak language of Dagestan, in the Caucasus, with one article and 20 users.

One more statistical measure will show how much Wikipedia matters. People who Google already know that for a great many Google searches one or more Wikipedia entries will turn up high on the first page of the results. They don't all know that Wikipedia now comes eleventh in alexa.com's traffic ranking of world websites. For a strictly non-commercial site with relatively academic content, that is astonishing success; what's more, the trend is steadily upwards, though it will be hard to overtake the top four: yahoo.com, msn.com, google.com, and the highly popular Chinese search engine, baidu.com.
The Critical Dictionary and the Wiki World
Authors: Adams Michael
Published: June 2007

A new utopian lexicography – online? Today, dictionary users are Web users: they imagine that a static paper text is necessarily less richly informative than a hyperlinked megatext. They expect to move among texts as interest and curiosity direct, not to be constrained by linear, editorially directed matter of the old-fashioned kind. The nodes of an infinite hyperlinked search may map a universe of small, classically organized texts, but those who travel the Web for information and ideas expect to click around on impulse. Further, they often expect to participate in the public construction of know-ledge, contributing and editing Web content whenever they feel competent to do so. They are hyper-Romantics who have conflated their imaginations and the scapes of human know-ledge into a hypertextual hyperuniverse. Future dictionaries of English should acknowledge these new user inclinations to the extent compatible with the highest lexicographical standards. These ideas are discussed further.
Using Fuzzy Tree Fragments to explore English grammar
Authors: Aarts Bas , Nelson Gerald , Wallis Sean
Published: June 2007

Readers of ET may recall two papers, the first by the late Sidney Greenbaum (‘ICE: the International Corpus of English,’ ET7, 1991, 3–7), the second and by Akiva Quinn & Nick Porter (‘Investigating English Usage with ICECUP’, ET10, 1994, pp. 21–24) which introduced the International Corpus of English (ICE) and its search facility ICECUP (the ICE Corpus Utility Programme). The present paper has a two-fold aim: to (re-)acquaint readers with ICE and discuss the latest developments in ICECUP – including its recent release on CD-ROM. The International Corpus of English was initiated by Sidney Greenbaum, whose aim was to set up a number of identically constructed corpora (for the purpose of grammar research) in the world's various English-speaking countries.
China EFL: Teaching with movies
Authors: Qiang Niu , Hai Teng , Wolff Martin
Published: June 2007

Some observations on using motion pictures to teach Business English. THE USE of motion pictures or other captioned films as part of teaching English as a foreign language has markedly increased in recent years in China. Because of this, we undertook a four-year experiment to determine how effective the use of English-language movies has been in the teaching of business. From this experiment it became clear that a cavalier use of movies in effect misused them. The appropriate and effective use of motion pictures requires a range of elements: (1) movies that are at one and the same time educational, informative, and entertaining; (2) a workbook linked to such movies that enables students to get ready beforehand; (3) most importantly, a range of classroom activities to induce and elicit timely and optimal output from the students, so as to make talking and writing about communication easier and more effective. Activities such as dubbing, story retelling, acting, discussing, debating, and role playing are only a few of the effective techniques a teacher can employ to engage the students.
Cercarial dermatitis and lake eutrophication in south-central Chile
Authors: VALDOVINOS C. , BALBOA C.
Published: June 2007

Cercarial dermatitis is caused by exposure to the cercariae of schistosome species which have birds or mammals as their definitive hosts. A public alarm was raised in the summer of 2004 when this parasitic disease was observed for the first time in south-central Chile at Laguna Chica de San Pedro (36° 51″ S, 73° 05″ W). Swimmers at this eutrophic lake were surveyed in order to estimate the amount of cercarial dermatitis in the area; participants were observed during the summers of 2004 and 2005 for clinical signs of cercarial dermatitis and 25Chilina dombeyanasnails were collected monthly from Laguna Chica de San Pedro during one year and then examined for animal schistosome cercariae. We found that 3% of the swimmers had pruritic maculopapular rashes on their legs, arms, necks, or other body parts and that between 9·1% (May 2006) and 52·4% (November 2004) of the snails examined were infected with the bird schistosome cercariaeTrichobilharziasp.
Attention Training in the Reduction and Reappraisal of Intrusive Thoughts
Authors: Watson Chris , Purdon Christine
Published: June 2007

Attention Training (ATT) is an auditory attention-focusing technique that attempts to reduce the perseverative self-focused processing characteristic of anxiety and mood disorders. The present study investigated the effects of one session of ATT in the reduction and reappraisal of intrusive thoughts in a university sample reporting high levels of obsessive-compulsive symptoms. One-hundred and eight participants identified their most distressing intrusive thought and spent 7 minutes monitoring their stream of consciousness while recording occurrences of the identified thought. They then rated the unpleasantness of the intrusive thought, their attempts to dismiss the thought from consciousness, and their perceived success in reducing the frequency of the thought. Participants were then randomly assigned to receive one session of ATT, thought replacement instructions (TR), distraction instructions (DI), or no intervention (CONT). Participants then repeated the thought monitoring interval and ratings. ATT was expected to be the most effective in decreasing the frequency and unpleasantness of intrusive thoughts. However, contrary to hypotheses, all groups reported similar decreases across intervals. Implications of these findings are discussed.
‘I Hated Everything About School’: An Examination of the Relationship between Dislike of School, Teenage Pregnancy and Educational Disengagement
Authors: Hosie Alison C.S.
Published: June 2007

This article explores the educational experiences of 93 young women who experienced pregnancy at school in England, in order to examine the relationship between dislike of school, teenage pregnancy and educational disengagement. The article argues that a strong dislike of school, pre-pregnancy, is often at the root of disengagement before pregnancy, a situation often exacerbated when the news of pregnancy is met with prevailing negative attitudes within school. However, once pregnant, educational alternatives to school frequently provide a route back into, and a changed perception of education. Tackling pre-pregnancy dislike of school may have important implications for both the support and prevention aspects of the Government's teenage pregnancy strategy.
Introduction: Themed Section on the Costs of Long-Term Care for Older People
Authors: Bowes Alison
Published: June 2007

Cost has long been a preoccupation in policy documents concerned with the care and support of older people (Means and Smith, 1998; Royal Commission, 1999). A history of moral panic about the ageing population coupled with a stereotype of older people as a dependent and ‘unproductive’ sector of society have combined to produce negatively focused debate, lacking in evidential support. Most recently, Wanless (2006) has highlighted the limitations of the evidence base and the narrowness of debate concerning the provision of social care services, arguing both for more informed debate and for consideration of the impact of developments in services and alternative funding models.
Care by Spouses, Care by Children: Projections of Informal Care for Older People in England to 2031
Authors: Pickard Linda , Wittenberg Raphael , Comas-Herrera Adelina , King Derek , Malley Juliette
Published: June 2007

The future market costs of long-term care for older people will be affected by the extent of informal care. This paper reports on projections of receipt of informal care by disabled older people from their spouses and (adult) children to 2031 in England. The paper shows that, over the next 30 years, care by spouses is likely to increase substantially. However, if current patterns of care remain the same, care by children will also need to increase by nearly 60 per cent by 2031. It is not clear that the supply of care by children will rise to meet this demand.
Improving Equity and Sustainability in UK Funding for Long-Term Care: Lessons from Germany
Authors: Glendinning Caroline
Published: June 2007

This paper argues for a transformation of arrangements for accessing and allocating public resources for long-term care in the UK. Currently these arrangements are fragmented, inequitable and not always well targeted. While not necessarily advocating a social insurance approach, the experience of Germany nevertheless shows how simplicity, transparency and equity of access can be combined with strong cost control levers and political sustainability. An opportunity to transform ways of accessing and distributing public resources for long-term care arises with the piloting of ‘individual budgets’ in 13 English local authorities from 2006. The paper argues that the principles underpinning individual budgets should be extended, with the UK government taking a strong national lead.
Future costs of long-term care for older people – some useful sources
Authors: Dawson Alison
Published: June 2007

The websites listed here provide electronic resources relevant to different aspects of the costs of long-term care. Many include links to additional reports, research papers, reviews and other sources of information. They should be regarded as a representative sample rather than an exhaustive list of relevant information currently available on the Internet. Only English language sites have been included. All website addresses were available on 30 March 2007.
Sollen morbid Adipöse restriktiv oder malabsorptiv operiert werden?
Authors: Langer
Published: June 2007

Die morbide Adipositas stellt ein erhebliches medizinisches und gesellschaftliches Problem dar. Die chirurgische Behandlung ist heutzutage die einzige effiziente Therapieform zur dauerhaften, nachhaltigen Gewichtsreduktion bei Patienten mit einem Body Mass Index über 40 kg/m². Die bariatrischen Operationen werden unterschieden in restriktive, malabsorptive oder Kombinationsverfahren. Alle gängigen Operationsverfahren haben sich grundsätzlich als effizient erwiesen mit einer Reduktion des Übergewichtes zwischen 50–80%. Komorbiditäten und Lebensqualität werden signifikant verbessert. Die Operations-Mortalität ist gering (0–1%). Der minimal-invasive Zugang mittels Laparoskopie stellt den Standard dar. Verfahren mit einer vornehmlich restriktiven Komponente zeigen insgesamt weniger Komplikationen sowohl im Kurz- als auch Langzeitverlauf. Unter den restriktiven Verfahren hat sich die Magenbypass-Operation als Standardmethode weltweit etabliert. Die bariatrische Chirurgie stellt letzten Endes nur ein Modul einer multimodalen und interdisziplinären Therapie dar. Dazu gehören auch Änderungen des Lebensstils, psychologische Betreuung, Ernährungsberatung und metabolische Kontrolle.
Seeding of equatorial plasma bubbles with electric fields from an Es‐layer instability
Authors: Tsunoda Roland T.
Published: June 2007

Evidence is presented that supports the suggestion by Tsunoda (2006) that a polarization electric field, if generated by a sporadic‐E (Es) layer instability (Cosgrove and Tsunoda, 2002), should map to the base of the F layer and seed equatorial plasma bubbles. Seeding, which leads to bubble development, seems to be a four‐step process operating in the bottomside F layer: (1) amplification of seed perturbations in a region of westward‐drifting plasma, which is found below the velocity‐shear node; (2) upward transference of this modulation through a rotational velocity shear to eastward‐drifting plasma; (3) further seed amplification, when the F layer begins to descend; and (4) bubble growth from the seed via the Rayleigh‐Taylor instability. The time available for interaction between F‐region plasma and elongated channels of enhanced polarization electric field (the latter formed by the mentioned instability) appears to be crucial for seed amplification. The need for a descending F layer to increase interaction time with the eastward‐drifting plasma is appealing because plasma bubbles display a propensity to appear after, and not during, the postsunset rise of the F layer. Although plausible, the need for Es presence, perhaps low solar activity, and a multistep process suggest that this mechanism may be a more occasional contributor than the collisional‐shear instability (Hysell and Kudeki, 2004).
Earth reflectance and polarization intercomparison between SCIAMACHY onboard Envisat and POLDER onboard ADEOS‐2
Authors: Tilstra L. G. , Stammes P.
Published: June 2007

In this paper, we compare reflectance and polarization measurements from two different satellite instruments, namely, the imager Polarization and Directionality of the Earth's Reflectances (POLDER) and the spectrometer Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY). Both instruments are able to measure not only the Earth reflectance but also the state of linear polarization of the detected light. The aim of this paper is to validate the SCIAMACHY reflectance and polarization data using the fact that POLDER is well calibrated. This validation requires a careful search for suitable, collocated data having identical solar and viewing angles. For the reflectance, there is a disagreement between POLDER and SCIAMACHY of up to 20% in the wavelength interval 400–1000 nm, which we attribute to SCIAMACHY. As for the linear polarization, we present for the first time clear evidence for the existence of discrepancies in the SCIAMACHY polarization retrieval for polarization measurement devices 2, 3, and 4.
Differential evolution based prediction of rain attenuation over a LOS terrestrial link situated in the southern United Kingdom
Authors: Develi Ibrahim
Published: June 2007

The principal objective of a rain attenuation prediction method is to achieve acceptable estimates of the attenuation incurred on the signal due to rain. In this paper, a differential evolution (DE) based model for predicting rain attenuation in a terrestrial point‐to‐point line of sight (LOS) link at 97 GHz is proposed using previously available experimental data obtained in the southern United Kingdom. Rainfall rate and percentage of time are used as input data in the proposed prediction model. Excellent agreement between the experimental data and the model output indicates that the presented DE based method may efficiently be used for accurate prediction of the rain attenuation levels.
On the relative importance of mineral phase transitions and viscosity stratification in controlling the sinking rates of detached slab remnants
Authors: Shahnas M. Hosein , Jarvis Gary T.
Published: June 2007

We employ a two‐dimensional control‐volume model of convection in a cylindrical shell to study sinking rates of cold parcels of material in the Earth's mantle. Our model uses periodic boundary conditions, at 0 and 360 degrees, to eliminate side‐wall effects and includes mineral phase transitions at 410 km and 660 km depths and a depth‐dependent viscosity. We compare the rates of sinking of cold material with and without phase boundaries and with and without viscosity increases with depth. When the viscosity increase is sufficiently large we find the sinking rate is relatively insensitive to the presence or absence of phase boundaries; the effects of viscosity dominate. If recent estimates of large viscosity increases in the lower mantle are correct, our model could account for mid‐mantle slab remnants of Jurassic age independent of the existence of phase transition boundaries in the mantle.
Banana‐polarized solitons in anisotropic plasmas related to Ulysses observations
Authors: Sauer K. , Mjølhus E. , Dubinin E. , Baumgärtel K.
Published: June 2007

Localized magnetic compressions associated with a rotation in the magnetic field direction have recently been reported after surveying Ulysses high‐resolution data. Although the observed structures have similarities to usual Hall‐MHD solitons, the banana‐type polarization of the described rare events is a decisive signature which counts against such an interpretation. The present paper considers stationary wave forms in an anisotropic plasma with different temperatures parallel (T∥) and transverse (T⊥) to the ambient magnetic field in the phase velocity gap between the slow and the intermediate mode. It is shown that for slow solar wind conditions (A = T∥/T⊥ >1 and β⊥ ≈ 1) bright solitons with banana‐type polarization (“bright bananas”) exist which in many respects resemble the observed Ulysses magnetic events. The necessary condition for the appearance of “bright bananas” is that the slow mode becomes faster than the intermediate mode which is achieved for sufficiently strong temperature anisotropy A.
Connection between bow shock and cusp energetic ions
Authors: Lin Y. , Wang X. Y. , Chang S.‐W.
Published: June 2007

A linkage between energetic ions in the bow shock and the cusp is established using a three‐dimensional (3‐D) self‐consistent global hybrid simulation, for a case of the interplanetary magnetic field (IMF) condition favoring high‐latitude magnetic reconnection and inter‐connection between field lines in the quasi‐parallel bow shock and the cusp. A diffuse ion distribution is obtained in the quasi‐parallel shock and foreshock region, where large‐amplitude waves and turbulence are present. Its energy spectrum is well described by an exponential function as in the case for upstream diffuse ions previously observed. These bow shock accelerated ions, upon being transmitted into the cusp region, form the bulk of cusp energetic ions. By tracing particles from the solar wind to the cusp, it is found that the source of acceleration for the cusp energetic ions is predominantly in the quasi‐parallel shock and foreshock region, through a Fermi‐type acceleration mechanism. Contribution to the cusp energetic ions from magnetosheath/cusp waves and magnetic reconnection appears relatively minor. Owing to the limitation of the model used, the magnetospheric source for energetic particles in the cusp cannot be fully investigated.
A new spectral ratio method using narrow band coda envelopes: Evidence for non‐self‐similarity in the Hector Mine sequence
Authors: Mayeda Kevin , Malagnini Luca , Walter William R.
Published: June 2007

The use of local and regional S‐wave coda is shown to provide stable amplitude ratios that better constrains source differences between event pairs. We first compared amplitude ratio performance between local and near‐regional S and coda waves in the San Francisco Bay region for moderate‐sized events, then applied the coda spectral ratio method to the 1999 Hector Mine mainshock and its larger aftershocks. We find (1) average amplitude ratio standard deviations using coda are ∼0.05 to 0.12, roughly a factor of 3 smaller than direct S‐waves for 0.2 < f < 15.0 Hz; (2) coda spectral ratios for the Mw 7.0 Hector Mine earthquake and its aftershocks show a clear departure from self‐similarity, consistent with other studies using the same datasets; and (3) event‐pairs (Green's function and target events) can be separated by ∼25 km for coda amplitudes without any appreciable degradation, in sharp contrast to direct waves.
Generation of DNA cleavage specificities of type II restriction endonucleases by reassortment of target recognition domains
Authors: Jurėnaitė-Urbanavičienė Sonata , Šerkšnaitė Jurgita , Kriukienė Edita , Giedrienė Jolanta , Venclovas Česlovas , Lubys Arvydas
Published: June 2007

Type II restriction endonucleases (REases) cleave double-stranded DNA at specific sites within or close to their recognition sequences. Shortly after their discovery in 1970, REases have become one of the primary tools in molecular biology. However, the list of available specificities of type II REases is relatively short despite the extensive search for them in natural sources and multiple attempts to artificially change their specificity. In this study, we examined the possibility of generating cleavage specificities of REases by swapping putative target recognition domains (TRDs) between the type IIB enzymes AloI, PpiI, and TstI. Our results demonstrate that individual TRDs recognize distinct parts of the bipartite DNA targets of these enzymes and are interchangeable. Based on these properties, we engineered a functional type IIB REase having previously undescribed DNA specificity. Our study suggests that the TRD-swapping approach may be used as a general technique for the generation of type II enzymes with predetermined specificities.
Relative resource abundance explains butterfly biodiversity in island communities
Authors: Yamamoto Naoaki , Yokoyama Jun , Kawata Masakado
Published: June 2007

Ecologists have long been intrigued by the factors that control the pattern of biodiversity, i.e., the distribution and abundance of species. Previous studies have demonstrated that coexisting species partition their resources and/or that the compositional similarity between communities is determined by environmental factors, lending support to the niche-assembly model. However, no attempt has been made to test whether the relative amount of resources that reflects relative niche space controls relative species abundance in communities. Here, we demonstrate that the relative abundance of butterfly species in island communities is significantly related to the relative biomasses of their host plants but not to the geographic distance between communities. In the studied communities, the biomass of particular host plant species positively affected the abundance of the butterfly species that used them, and consequently, influenced the relative abundance of the butterfly communities. This indicated that the niche space of butterflies (i.e., the amount of resources) strongly influences butterfly biodiversity patterns. We present this field evidence of the niche-apportionment model that propose that the relative amount of niche space explains the pattern of the relative abundance of the species in communities.
E-Cadherin Adhesion Activates c-Src Signaling at Cell–Cell Contacts
Authors: McLachlan Robert W. , Kraemer Astrid , Helwani Falak M. , Kovacs Eva M. , Yap Alpha S.
Published: June 2007

Cadherin-based cell–cell contacts are prominent sites for phosphotyrosine signaling, being enriched in tyrosine-phosphorylated proteins and tyrosine kinases and phosphatases. The functional interplay between cadherin adhesion and tyrosine kinase signaling, however, is complex and incompletely understood. In this report we tested the hypothesis that cadherin adhesion activates c-Src signaling and sought to assess its impact on cadherin function. We identified c-Src as part of a cadherin-activated cell signaling pathway that is stimulated by ligation of the adhesion receptor. However, c-Src has a biphasic impact on cadherin function, exerting a positive supportive role at lower signal strengths, but inhibiting function at high signal strengths. Inhibiting c-Src under circumstances when it is activated by cadherin adhesion decreased several measures of cadherin function. This suggests that the cadherin-activated c-Src signaling pathway serves positively to support cadherin function. Finally, our data implicate PI3-kinase signaling as a target for cadherin-activated c-Src signaling that contributes to its positive impact on cadherin function. We conclude that E-cadherin signaling is an important activator of c-Src at cell–cell contacts, providing a key input into a signaling pathway where quantitative changes in signal strength may result in qualitative differences in functional outcome.
Naked2 Acts as a Cargo Recognition and Targeting Protein to Ensure Proper Delivery and Fusion of TGF-α–containing Exocytic Vesicles at the Lower Lateral Membrane of Polarized MDCK Cells
Authors: Li Cunxi , Hao Mingming , Cao Zheng , Ding Wei , Graves-Deal Ramona , Hu Jianyong , Piston David W. , Coffey Robert J.
Published: June 2007

Transforming growth factor-α (TGF-α) is the major autocrine EGF receptor ligand in vivo. In polarized epithelial cells, proTGF-α is synthesized and then delivered to the basolateral cell surface. We previously reported that Naked2 interacts with basolateral sorting determinants in the cytoplasmic tail of a Golgi-processed form of TGF-α and that TGF-α is not detected at the basolateral surface of Madin-Darby canine kidney (MDCK) cells expressing myristoylation-deficient (G2A) Naked2. By high-resolution microscopy, we now show that wild-type, but not G2A, Naked2-associated vesicles fuse at the plasma membrane. We further demonstrate that Naked2-associated vesicles are delivered to the lower lateral membrane of polarized MDCK cells independent of μ1B adaptin. We identify a basolateral targeting segment within Naked2; residues 1-173 redirect NHERF-1 from the apical cytoplasm to the basolateral membrane, and internal deletion of residues 37-104 results in apical mislocalization of Naked2 and TGF-α. Short hairpin RNA knockdown of Naked2 leads to a dramatic reduction in the 16-kDa cell surface isoform of TGF-α and increased cytosolic TGF-α immunoreactivity. We propose that Naked2 acts as a cargo recognition and targeting (CaRT) protein to ensure proper delivery, tethering, and fusion of TGF-α–containing vesicles to a distinct region at the basolateral surface of polarized epithelial cells.
The Utility of Heart Sounds and Systolic Intervals Across the Care Continuum
Authors: Peacock W. Frank , Harrison Alex , Maisel Alan S.
Published: June 2007

Acoustic cardiography is an exciting, new, easy‐to‐use, modernized technology that incorporates already proven techniques of phonocardiography. Application of acoustic cardiography to clinical practice can improve diagnosis and management of heart failure patients. Its clinical use should help address some of the need for robust, inexpensive, and widely accessible technology for proactive heart failure diagnosis and management. Acoustic cardiographically recorded measurements have been correlated with both cardiac catheterization and echocardiographically determined hemodynamic parameters. Heart sounds captured by acoustic cardiograms have proven to assist clinicians in assessing dyspneic patients in the emergency department by utilizing the strong specificity of an S3 for detecting acute decompensated heart failure. Acoustic cardiography offers a cost‐efficient, easy‐to‐use method to optimize the devices used in cardiac resyncronization therapy. The rapidly and easily obtainable information gathered by acoustic cardiography should foster its more widespread use in diagnosis and treatment of heart failure, including cardiac resyncronization therapy device optimization.
Hemodynamic Correlates of the Third Heart Sound and Systolic Time Intervals
Authors: Shah Sanjiv J. , Michaels Andrew D.
Published: June 2007

Bedside diagnostic tools remain important in the care of patients with heart failure. Over the past two centuries, cardiac auscultation and phonocardiography have been essential in understanding cardiac pathophysiology and caring for patients with heart disease. Diastolic heart sounds (S3 and S4) and systolic time intervals have been particularly useful in this regard. Unfortunately, auscultation skills have declined considerably, and systolic time intervals have traditionally required carotid pulse tracings. Newer technology allows the automated detection of heart sounds and measurement of systolic time intervals in a simple, inexpensive, noninvasive system. Using the newer system, the authors present data on the hemodynamic correlates of the S3 and abnormal systolic time intervals. These data serve as the foundation for using the system to better understand the test characteristics and pathophysiology of the S3 and systolic time intervals, and help to define their use in improving the bedside diagnosis and management of patients with heart failure.
Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium‐sensing receptor gene
Authors: Tõke Judit , Czirják Gábor , Patócs Attila , Enyedi Balázs , Gergics Péter , Csákváry Violetta , Enyedi Péter , Tóth Miklós
Published: June 2007

Introduction  Neonatal severe hyperparathyroidism (NSHPT) is induced by inactivating mutations of human calcium‐sensing receptor (CaSR). Only three heterozygous de novo inactivating mutations of CaSR causing NSHPT have been described. We report the case of a now 11‐year‐old boy with NSHPT and we characterize a novel inactivating mutation along with the results of some functional analyses.

Patient and methods  As a neonate the patient presented the clinical syndrome of NSHPT. At 6 years of age persisting hypercalcaemia without clinical symptoms was documented, and the patient remained completely symptom free without parathyroid surgery until his present age of 11 years. The entire coding region of the CaSR gene of the patient and his family members was sequenced. Functional investigation was performed in HEK‐293 cells, transiently transfected with wild type and mutant CaSR plasmid constructs.

Results  Sequence analysis revealed a novel de novo heterozygous mutation at codon 551 (AGG→AAG), predicting a change of arginine to lysine (R551K) and a known heterozygous polymorphism (A986S) on the same allele, which was inherited from the father. We demonstrated that the novel R551K mutation significantly reduced the calcium sensitivity of CaSR (EC50: from 3·38 ± 0·62–6·10 ± 0·83 mmol/l), which was not alleviated by the simultaneous presence of A986S polymorphism.

Conclusions  We present the fourth NSHPT case induced by a novel de novo heterozygous inactivating mutation (R551K) of the CaSR gene. The disease gradually reverted to a symptomless, benign condition resembling familial hypocalciuric hypercalcaemia without any surgical intervention.
Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis
Authors: MacRae V. E. , Wong S. C. , Smith W. , Gracie A. , McInnes I. , Galea P. , Gardner‐Medwin J. , Farquharson C. , Ahmed S. F.
Published: June 2007

Objective  Growth retardation in children with chronic inflammatory disease may be partly due to direct effects of pro‐inflammatory cytokines on the growth plate and requires further investigation.

Design  This study assessed the cytokine concentrations in serum and synovial fluid (SF) in juvenile idiopathic arthritis (JIA), and determined the effect of the biological fluid on cultured murine metatarsal growth.

Patients  Serum and SF were obtained from four children attending for arthrocentesis (child A, systemic; children B, C and D, oligoarticular). In addition, serum samples were obtained from four more children (children E and F, polyarticular; child G, oligoarticular).

Measurements  Anthropometry, cytokine levels and longitudinal bone growth were assessed.

Results  Cytokines were elevated to a variable extent in the samples. Although all serum samples were associated with reduced metatarsal growth, only SF from child A and child B reduced metatarsal growth. Metatarsals treated with child A's SF showed reduced proliferation, reduced proliferative and mineralizing zone width, and increased hypertrophic zone width. Tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐6 concentrations were elevated in child A's SF. However, SF exposure with neutralizing antibodies to these cytokines or IGF‐1 did not improve metatarsal growth.

Conclusion  SF and serum JIA samples can impair bone growth at the growth plate. In synovial fluid, the effect is variable but resistant to treatment with IL‐1β, IL‐6 and TNF‐α specific antibodies and IGF‐1, suggesting that other factors in this biological fluid may also have an effect on longitudinal growth through IGF‐1‐independent mechanisms.
GH responsiveness in a large multinational cohort of SGA children with short stature (NESTEGG) is related to the exon 3 GHR polymorphism
Authors: Tauber M. , Ester W. , Auriol F. , Molinas C. , Fauvel J. , Caliebe J. , Nugent T. , Fryklund L. , Ranke M. B. , Savage M. O. , Clark A. J. L. , Johnston L. B. , Hokken‐Koelega A. C. S. ,   on behalf of the NESTEGG group
Published: June 2007

Objective  The polymorphic deletion of exon 3 of the GH receptor (d3‐GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA).

Design  The study included short prepubertal SGA children treated with rhGH for 1 or 2 years.

Population  Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6·6 ± 2·3 years with a height at –3·0 ± 0·7 SDS at start of rhGH treatment; 193 ethnically matched controls.

Methods  The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated.

Results  The change in GV was significantly greater in SGA children carrying one or two copies of the d3‐GHR allele (P = 0·038 for the first year and P = 0·041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0·034) and in those with the fl/d3 genotype (P = 0·016).

Conclusion  Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature.
Autism: tactile perception and emotion
Authors: Pernon E. , Pry R. , Baghdadli A.
Published: June 2007

Background  For many years, and especially since Waynbaum and Wallon, psychology and psychopathology have dealt with cognitive perception, but have had little to do with the affective qualities of perception. Our aim was to study the influence of the sensory environment on people with autism.

Method  Several experiments were carried out using different forms of tactile stimulation (passive and active subjects).

Results  Our data showed specific responses in children with autism and intellectual disability. These children displayed a strong (positive) valence to the stimulation provided.

Conclusion  They were very attracted to the stimulation and were excited by it.
The Sentence Completion and Three Wishes tasks: windows into the inner lives of people with intellectual disabilities
Authors: Dykens E. , Schwenk K. , Maxwell M. , Myatt B.
Published: June 2007

Background  Measuring the self‐perceptions, thoughts, hopes and inner lives of persons with intellectual disabilities (ID) has long been a research challenge. Unlike objective or projective tests, semi‐projective tasks may provide persons with ID with just enough structure or cues to convey their self‐perceptions in a spontaneous and unbiased manner.

Methods  Sentence Completion and Three Wishes tasks were individually administered to 128 persons with ID aged 5–50 years (mean = 18.75 years). Participants had Prader–Willi, Williams or Down syndromes. Content analyses resulted in 19 codes that were used to reliably score both tasks by independent raters who achieved excellent levels of inter‐rater agreement. Participants also received IQ testing, and their parents or care providers completed the Child Behavior Checklist (CBCL).

Results  Frequent themes across both tasks included activities, positive affect, desired objects, and relationships with family and pets. No gender or IQ effects were found, and just a few codes showed modest age effects. Several responses, including dating, friends, food, and positive or negative self‐appraisals, were significantly related to either syndrome status or CBCL maladaptive behaviour.

Conclusions  Although not widely used, the Sentence Completion and Three Wishes tasks are useful semi‐projective techniques for garnering otherwise hard‐to‐access self‐perceptions and associations of people with ID. Implications are discussed for practice and research.
Regulation of Progestin Receptor Expression in the Developing Rat Brain by a Dopamine D1 Receptor Antagonist
Authors: Olesen K. M. , Auger C. J. , Auger A. P.
Published: June 2007

Steroid receptors within the developing brain influence a variety of cellular processes that endure into adulthood, altering both behaviour and physiology. Therefore, it is important to understand how steroid receptor expression is regulated during early brain development. Most studies indicate that oestradiol, by acting upon oestrogen receptors, increases the expression of progestin receptors in the developing brain. We have recently observed an additional mechanism by which dopamine can increase the expression of progestin receptors in developing female rat brain. That is, we found that a dopamine D1 receptor agonist can further increase progestin receptor expression by activating oestrogen receptors in a ligand‐independent manner within restricted areas of female brain; however, it is unclear whether dopamine D1 receptors are involved in the normally occurring expression of progestin receptors in developing male and female brain. To investigate this, we examined whether a dopamine D1 receptor antagonist can disrupt the normal developmental expression of progestin receptors in both male and female rat brain. We report that treatment with a dopamine D1 receptor antagonist reduces progestin receptor expression within some, but not all, regions of the developing rat brain in a sex‐specific manner. Some of the current findings also suggest that dopamine might be acting to prevent sex differences in progestin receptor expression in some areas while contributing to a sex difference in other areas.
Peroxisome Proliferator‐Activated Receptor γ in the Human Pituitary Gland: Expression and Splicing Pattern in Adenomas Versus Normal Pituitary
Authors: Occhi G. , Albiger N. , Berlucchi S. , Gardiman M. , Scanarini M. , Scienza R. , Fassina A. , Mantero F. , Scaroni C.
Published: June 2007

Pituitary adenomas are slow‐growing tumours arising within the pituitary gland. If secreting, they give rise to well‐known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator‐activated receptor γ (PPARγ), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARγ in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real‐time polymerase chain reaction, PPARγ was expressed as much in adrenocorticotrophic hormone (ACTH)‐secreting and ACTH‐silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARγ detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARγ expression in approximately one‐half of analysed samples. The intra‐ and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARγ‐ligand treatment. Moreover, the higher level of PPARγ expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.
Corticosteroids, 11β‐Hydroxysteroid Dehydrogenase Isozymes and the Rabbit Choroid Plexus
Authors: Sinclair A. J. , Onyimba C. U. , Khosla P. , Vijapurapu N. , Tomlinson J. W. , Burdon M. A. , Stewart P. M. , Murray P. I. , Walker E. A. , Rauz S.
Published: June 2007

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain. The balance between CSF production and drainage, in part, facilitates a normal intracranial pressure. The secretion of Na+ and anions by the CP creates an osmotic gradient driving water into the ventricles. This is opposite to classical Na+ transporting tissues, such as the kidney, where Na+ and water reabsorption is mediated by 11β‐hydroxysteroid dehydrogenase type 2 that protects the mineralocorticoid receptor by abrogating active cortisol to inactive cortisone. In the human ocular ciliary epithelium, Na+ and water secretion is dependent on a novel mediator of ciliary epithelial Na+ transport, 11β‐HSD type 1 (11β‐HSD1), that generates intraocular cortisol. In a mechanism analogous to that of the embryologically related ocular ciliary epithelium, we propose that autocrine regulation of intracranial cortisol is dependent on 11β‐HSD1 expression in the CP epithelial cells. By conducting immunolocalisation studies on brains from New Zealand White Albino rabbits, we defined the expression of 11β‐HSD1 in the secretory CP epithelial cells. Enzyme assays performed on intact rabbit CP whole tissue explants confirmed predominant 11β‐HSD1 activity, generating cortisol that was inhibited by glycyrrhetinic acid (an 11β‐HSD inhibitor). Using the real time‐polymerase chain reaction, rabbit CP tissue was found to express levels of 11β‐HSD1, glucocorticoid receptor α and serum and glucocorticoid‐regulated kinase 1 mRNA comparable to that expressed in rabbit ocular ciliary body, thereby highlighting the similarity between these two tissues. Furthermore, an enzyme‐linked immunosorbent assay of rabbit CSF revealed a median cortisol concentration of 1.7 nmol/l (range 1.4–4.3 nmol/l, n = 9). Our data have identified a functional 11β‐HSD1 within the CP, mediating intracranial cortisol bioavailability. Expression of 11β‐HSD1 may be fundamental in the regulation of CSF secretion and the local generation of cortisol may represent a pathophysiological mechanism underlying cortisol‐dependent neuroendocrine diseases.
Fossorial but widespread: the phylogeography of the common spadefoot toad (Pelobates fuscus), and the role of the Po Valley as a major source of genetic variability
Authors: CROTTINI ANGELICA , ANDREONE FRANCO , KOSUCH JOACHIM , BORKIN LEO J. , LITVINCHUK SPARTAK N. , EGGERT CHRISTOPHE , VEITH MICHAEL
Published: June 2007

Pelobates fuscus is a fossorial amphibian that inhabits much of the European plain areas. To unveil traces of expansion and contraction events of the species’ range, we sequenced 702 bp of the mitochondrial cytochrome b gene. To infer the population history we applied phylogeographical methods, such as nested clade phylogeographical analysis (NCPA), and used summary statistics to analyse population structure under a neutral model of evolution. Populations were assigned to different drainage systems and we tested hypotheses of explicit refugial models using information from analysis of molecular variance, nucleotide diversity, effective population size estimation, NCPA, mismatch distribution and Bayesian dating. Coalescent simulations were used as post hoc tests for plausibility of derived or a priori assumed biogeographical hypotheses. Our combination of all approaches enabled the reconstruction of the colonization history and phylogeography of P. fuscus and confirmed a previous assumption of the existence of two major genetic lineages within P. fuscus. Using the Afro‐European vicariance of Pelobates cultripes and Pelobates varaldii and applying Bayesian dating we estimated the divergence of these phylogeographical lineages to the Pliocene. We suggest the existence of three different glacial refugia: (i) the area between the Caspian and Black Seas as the origin for the expansion of the ‘eastern lineage’; (ii) the Danube system as a centre of diversity for part of the ‘western lineage’; (iii) the Po Valley, the largest centre of genetic variability. This fits the hypothesis that climatic fluctuation was a key event for differentiation processes in P. fuscus.
Testing hypotheses of population structuring in the Northeast Atlantic Ocean and Mediterranean Sea using the common cuttlefish Sepia officinalis
Authors: PÉREZ‐LOSADA MARCOS , NOLTE MARK J. , CRANDALL KEITH A. , SHAW PAUL W.
Published: June 2007

Population structuring in species inhabiting marine environments such as the Northeast Atlantic Ocean (NEA) and Mediterranean Sea (MS) has usually been explained based on past and present physical barriers to gene flow and isolation by distance (IBD). Here, we examined the relative importance of these factors on population structuring of the common cuttlefish Sepia officinalis by using methods of phylogenetic inference and hypothesis testing coupled with coalescent and classical population genetic parameter estimation. Individuals from 10 Atlantic and 15 Mediterranean sites were sequenced for 659 bp of the mitochondrial COI gene (259 sequences). IBD seems to be the main factor driving present and past genetic structuring of Sepia populations across the NEA–MS, both at large and small geographical scales. Such an evolutionary process agrees well with some of the biological features characterizing this cuttlefish species (short migrations, nektobenthic habit, benthic eggs hatching directly to benthic juveniles). Despite the many barriers to migration/gene flow suggested in the NEA–MS region, genetic population fragmentation due to past isolation of water masses (Pleistocene; 0.56 million years ago) and/or present‐day oceanographic currents was only detected between the Aegean‐Ionian and western Mediterranean Seas. Restricted gene flow associated with the Almería‐Oran hydrographic front was also suggested between southern and eastern Spanish populations. Distinct population boundaries could not be clearly determined, except for the Aegean‐Ionian stock. Two Atlantic and five Mediterranean samples showed evidence of current decline in genetic diversity, which may indicate over‐exploitation of Sepia in both marine regions.