bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-atomic resolution structural model of the yeast 26S proteasome
Authors: Beck Florian , Unverdorben Pia , Bohn Stefan , Schweitzer Andreas , Pfeifer Günter , Sakata Eri , Nickell Stephan , Plitzko Jürgen M. , Villa Elizabeth , Baumeister Wolfgang , Förster Friedrich
Published: August 2012

The 26S proteasome operates at the executive end of the ubiquitin-proteasome pathway. Here, we present a cryo-EM structure of the
Saccharomyces cerevisiae
26S proteasome at a resolution of 7.4 Å or 6.7 Å (Fourier-Shell Correlation of 0.5 or 0.3, respectively). We used this map in conjunction with molecular dynamics-based flexible fitting to build a near-atomic resolution model of the holocomplex. The quality of the map allowed us to assign α-helices, the predominant secondary structure element of the regulatory particle subunits, throughout the entire map. We were able to determine the architecture of the Rpn8/Rpn11 heterodimer, which had hitherto remained elusive. The MPN domain of Rpn11 is positioned directly above the AAA-ATPase N-ring suggesting that Rpn11 deubiquitylates substrates immediately following commitment and prior to their unfolding by the AAA-ATPase module. The MPN domain of Rpn11 dimerizes with that of Rpn8 and the C-termini of both subunits form long helices, which are integral parts of a coiled-coil module. Together with the C-terminal helices of the six PCI-domain subunits they form a very large coiled-coil bundle, which appears to serve as a flexible anchoring device for all the lid subunits.
Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase
Authors: Owen Joshua L. , Zhang Yuanyuan , Bae Soo-Han , Farooqi Midhat S. , Liang Guosheng , Hammer Robert E. , Goldstein Joseph L. , Brown Michael S.
Published: August 2012

Insulin activates sterol regulatory element-binding protein-1c (SREBP-1c) in liver, thereby increasing fatty acid and triglyceride synthesis. We created a line of transgenic rats that produce epitope-tagged human SREBP-1c in liver under control of the constitutive apolipoprotein E promoter/enhancer. This system allows us to dissect the pathway by which insulin stimulates SREBP-1c processing without interference by the insulin-mediated increase in SREBP-1c mRNA. Rats are used because freshly isolated rat hepatocytes respond much more robustly to insulin than do mouse hepatocytes. The data reveal that insulin-mediated stimulation of SREBP-1c processing requires the mechanistic target of rapamycin complex 1 (mTORC1), which also is required for insulin-mediated SREBP-1c mRNA induction. However, in contrast to mRNA induction, insulin stimulation of SREBP-1c processing is blocked by an inhibitor of p70 S6-kinase. The data indicate that the pathways for insulin enhancement of SREBP-1c mRNA and proteolytic processing diverge after mTORC1. Stimulation of processing requires the mTORC1 target p70 S6-kinase, whereas induction of mRNA bypasses this enzyme. Insulin stimulation of both processes is blocked by glucagon. The transgenic rat system will be useful in further defining the molecular mechanism for insulin stimulation of lipid synthesis in liver in normal and diabetic states.
Evidence for the role of cognitive resources in flavour–flavour evaluative conditioning
Authors: Davies Sarah R. , El-Deredy Wael , Zandstra Elizabeth H. , Blanchette Isabelle
Published: August 2012

One way that dis/likes are formed is through evaluative conditioning (EC). In two experiments we investigated the role of cognitive resources in flavour–flavour conditioning. Both experiments employed an EC procedure in which three novel flavoured conditioned stimuli (CSs) were consumed. One was consumed with a pleasant unconditioned stimulus (US; CS+ sugar), one with an aversive US (CS+ saline), and a third with plain water (CS–). Half of participants in each experiment performed a cognitive load task during conditioning. We measured EC using self-reported measures of liking (Experiments 1 and 2) and an indirect measure of liking: drink pick-up latency (Experiment 2). In both experiments, differential EC was observed in the no cognitive load condition but not in the cognitive load condition. This pattern of results was observed in self-reported measures of liking as well as in the drink pick-up latency data. Results from both experiments show that EC occurs only when there are sufficient cognitive resources available. The fact that this was observed using both self-reported and indirect measures suggests that insufficient cognitive resources affect learning itself rather than merely obstructing reporting.
Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity
Authors: Mahuzier Alexia , Gaudé Helori-Mael , Grampa Valentina , Anselme Isabelle , Silbermann Flora , Leroux-Berger Margot , Delacour Delphine , Ezan Jerome , Montcouquiol Mireille , Saunier Sophie , Schneider-Maunoury Sylvie , Vesque Christine
Published: August 2012

Cilia are at the core of planar polarity cellular events in many systems. However, the molecular mechanisms by which they influence the polarization process are unclear. Here, we identify the function of the ciliopathy protein Rpgrip1l in planar polarity. In the mouse cochlea and in the zebrafish floor plate, Rpgrip1l was required for positioning the basal body along the planar polarity axis. Rpgrip1l was also essential for stabilizing dishevelled at the cilium base in the zebrafish floor plate and in mammalian renal cells. In rescue experiments, we showed that in the zebrafish floor plate the function of Rpgrip1l in planar polarity was mediated by dishevelled stabilization. In cultured cells, Rpgrip1l participated in a complex with inversin and nephrocystin-4, two ciliopathy proteins known to target dishevelled to the proteasome, and, in this complex, Rpgrip1l prevented dishevelled degradation. We thus uncover a ciliopathy protein complex that finely tunes dishevelled levels, thereby modulating planar cell polarity processes.
Cancer immunoediting by the innate immune system in the absence of adaptive immunity
Authors: O’Sullivan Timothy , Saddawi-Konefka Robert , Vermi William , Koebel Catherine M. , Arthur Cora , White J. Michael , Uppaluri Ravi , Andrews Daniel M. , Ngiow Shin Foong , Teng Michele W.L. , Smyth Mark J. , Schreiber Robert D. , Bui Jack D.
Published: August 2012

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.
Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice
Authors: Fournier Emilie M. , Velez Maria-Gabriela , Leahy Katelyn , Swanson Cristina L. , Rubtsov Anatoly V. , Torres Raul M. , Pelanda Roberta
Published: August 2012

Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG+ cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-κ B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-κ B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-κ B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG+ cells is partly dependent on Fas inactivation. Furthermore, dual-κ B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity.
Quantifying dielectrophoretic nanoparticle response to amplitude modulated input signal
Authors: Bakewell D J , Chichenkov A
Published: August 2012

A new experimental system and theoretical model have been developed to systematically quantify and analyse the movement of nanoparticles subjected to continuously pulsed, or amplitude modulated, dielectrophoretic (DEP) input signal. Modulation DEP-induced concentration fluctuations of fluorescently labelled 0.5 µm and 1.0 µm diameter latex nanospheres, localized near castellated electrode edges, were quantified using real-time fluorescence microscope dielectrophoretic spectroscopy. Experimental measurements show that the fluorescence fluctuations decrease as the modulation frequency increases—in agreement with model predictions. The modulation frequency was varied from 25 × 10−3 to 25 Hz and the duty-cycle ratios ranged from zero to unity. Two new parameters for characterizing DEP nanoparticle transport are defined: the modulation frequency bandwidth and the optimal duty-cycle ratio. The ‘on/off’ modulation bandwidth, for micrometre scale movement, was measured to be 0.6 Hz and 1.0 Hz for 1.0 µm and 0.5 µm diameter nanospheres, respectively. At these cut-off frequencies very little movement of the nanospheres could be microscopically observed. Optimal fluorescence fluctuations, for modulation frequencies ranging from 0.25 to 1.0 Hz, occurred for duty-cycle ratio values ranging from 0.3 to 0.7—agreeing with theory. The results are useful for automated DEP investigations and associated technologies.
Aucassin, Gauvain, and (Re)Ordering Paris, BnF, fr. 2168
Authors: Simpson James R.
Published: August 2012

This article considers the place of
Aucassin et Nicolette
and
L'Âtre périlleux
in Paris, BnF, fr. 2168. Following on from remarks by Keith Busby, the present study draws on F. W. Bourdillon's edition, which concludes that the manuscript was not originally ordered as it appears at present, but was reorganized during the Middle Ages. The principal change here is that
L'Âtre périlleux
was moved from the centre of the collection to its opening, a reorganization that necessitates some rethinking both of the relations between the texts contained in the compilation and of our sense of its thematic architecture. In addition, this repositioning also, arguably, bears witness to divergent views regarding the place of Gauvain — an object of criticism and ridicule in a variety of romance texts — in the collection itself and in the genre of romance more generally. Accordingly, as part of a wider examination of the complex intertextual and intergeneric relations in fr. 2168, the present study argues that Gauvain's relocation and movement within the collection reads as the material manifestation of anxieties and uncertainties regarding his status and influence as a literary figure, a generic and gender trouble to which
Aucassin et Nicolette
appears as a key witness.
Legacies of the Second World War: Representations of the Theft of Jewish Property in Recent French Crime Fiction
Authors: Hutton Margaret-Anne
Published: August 2012

How can crime be defined in times of war? How does the theft of goods and property from Jews during the Second World War fit into various different discourses — fictional, ethical, legal, historical? Working with a small corpus of five crime fiction texts published between 1999 and 2005, this article explores the highly mediatized issue of the spoliation and plunder of valuables from Jews in France under the Occupation. The crime fiction narrative is revealed to differ significantly from the official French government Mattéoli report on the subject, which equates plunder (
pillage
) with the Nazis and makes minimal mention of French perpetrators. Beyond constituting a supplement (or complement) to the official narrative, the fictional corpus displays a marked concern for intergenerational relations and troubled and troubling aspects of the legacy of the war years. Although all five texts in the corpus offer closure of sorts, a careful reading of the representation of provenance suggests that a concern with cultural heritage, or
patrimoine
, may muddy the ethical waters.
From Homofraternity to Hospitality: Deconstructing the Political with Derrida and the Dardennes
Authors: McMahon Laura
Published: August 2012

This article stages an encounter between the work of contemporary Belgian filmmakers Jean-Pierre and Luc Dardenne and the thinking of the political elaborated by Jacques Derrida. In
La Promesse
(1996) and
Le Fils
(2002) the Dardennes explore issues of responsibility, justice, hospitality, and forgiveness, tracing fragile modes of relationality formed on the ruins of the paternal–filial bond. The article argues that Derrida's interrogation of the homofraternal logic underpinning democracy, and his attendant recasting of the political in terms of the promise, the incalculable, the spectral, and the
démocratie à venir
, offers a fertile framework for reading the deconstruction of the political in these two films and for thinking through the moves made here by cinema beyond the present, beyond ontology, and beyond identification.
Metabolomic Profiling of Children’s Brains Undergoing General Anesthesia with Sevoflurane and Propofol
Authors: Jacob Zvi , Li Haifang , Makaryus Rany , Zhang Shaonan , Reinsel Ruth , Lee Hedok , Feng Tian , Rothman Douglas L. , Benveniste Helene
Published: August 2012

Background

We recently applied proton magnetic resonance spectroscopy (HMRS) to investigate metabolic consequences of general anesthesia in the rodent brain, and discovered that isoflurane anesthesia was characterized by higher concentrations of lactate, glutamate, and glucose in comparison with propofol. We hypothesized that the metabolomic differences between an inhalant and intravenous anesthetic observed in the rodent brain could be reproduced in the human brain.

Methods

HMRS-based metabolomic profiling was applied to characterize the cerebral metabolic status of 59 children undergoing magnetic resonance imaging during anesthesia with either sevoflurane or propofol. HMRS scans were acquired in the parietal cortex after approximately 60 min of anesthesia. Upon emergence the children were assessed using the pediatric anesthesia emergence delirium scale.

Results

With sevoflurane anesthesia, the metabolic signature consisted of higher concentrations of lactate and glucose compared with children anesthetized with propofol. Further, a correlation and stepwise regression analysis performed on emergence delirium scores in relation to the metabolic status revealed that lactate and glucose correlated positively and total creatine negatively with the emergence delirium score.

Conclusions

Our results demonstrating higher glucose and lactate with sevoflurane in the human brain compared with propofol could reflect greater neuronal activity with sevofluane resulting in enhanced glutamate-neurotransmitter cycling, increased glycolysis, and lactate shuttling from astrocytes to neurons or mitochondrial dysfunction. Further, the association between emergence delirium and lactate suggests that anesthesia-induced enhanced cortical activity in the unconscious state may interfere with rapid return to "coherent" brain connectivity patterns required for normal cognition upon emergence of anesthesia.
Superiority of Desflurane over Sevoflurane and Isoflurane in the Presence of Pressure-overload Right Ventricle Hypertrophy in Rats
Authors: Blaudszun Grégoire , Morel Denis R.
Published: August 2012

Background

Pulmonary hypertension and associated pressure-overload right ventricular (RV) hypertrophy represent a tremendous challenge for the anesthesiologist, as optimal perioperative management is mandatory. However, the ideal anesthetic agent remains unknown because scientific evidence is lacking.

Methods

Twenty-eight rats were randomly assigned to a control or a monocrotaline group (60 mg kg). Four weeks later, animals were anesthetized, instrumented with a RV conductance catheter, and underwent well-controlled dose-responses to isoflurane, desflurane, and sevoflurane inhalation (minimum alveolar concentrations 0.5, 1.0, 1.5).

Results

Compared with controls, rats injected with monocrotaline presented with RV hypertrophy, increased afterload, and contractility, without change in cardiac output. The ratio of pressures in the right over the left circulation increased. The halogenated volatiles differently altered hemodynamics. Sevoflurane reduced RV contractility (more than 50%) and the right over left pressures ratio increased (from 0.41 ± 0.08 [SD] to 0.82 ± 0.14; P < 0.0001) secondary to profound concomitant systemic vasodilation, demonstrating a critical pressure gradient between right and left circulations. Despite significantly higher RV systolic pressures and afterload, desflurane decreased RV contractility much less (<10%; P < 0.0001 vs. sevoflurane) and maintained the right over left pressures ratio at more favorable values (0.47 ± 0.07; P < 0.0001 vs. sevoflurane). Isoflurane presented intermediate effects.

Conclusion

In the presence of pressure-overload RV hypertrophy, hemodynamics are better preserved under desflurane inhalation, whereas sevoflurane-and to a lesser extent isoflurane-cause large discrepancies on the left and right circulations, raising the right over left pressures ratio to critical levels despite a conserved cardiac output.
Macromolecular Capillary Leakage Is Involved in the Onset of Anaphylactic Hypotension
Authors: Faye Nathalie , Fournier Laure , Balvay Daniel , Thiam Rokhaya , Orliaguet Gilles , Clément Olivier , Dewachter Pascale
Published: August 2012

Background

The role of the hypovolemic component secondary to the microcirculatory changes in the onset of inaugural anaphylactic hypotension remains debated. We investigated the microcirculatory permeability in a model of anaphylactic shock using a fluorescence confocal microscopy imaging system.

Methods

Ovalbumin-sensitized anesthetized Brown Norway rats were randomly allocated into two groups (n = 6/group): control and anaphylaxis, respectively induced by intravenous saline or ovalbumin at time 0 (T0). The mesentery was surgically exposed. Macromolecular fluorescein isothiocyanate-dextran was intravenously injected (T0-5min) allowing in vivo visualization of the mesenteric microvascular network by fluorescence microscopy. After a period of stabilization of the contrast agent concentration, a 5-s movie was recorded to obtain baseline signal intensity. Following T0, 5-s movies were recorded every 30 s for 30 min. Capillary leakage of fluorescein isothiocyanate-dextran was assessed in interstitium and compared between groups. Data are expressed as mean ± SD.

Results

Following anaphylactic shock onset, an early, progressive, and global signal intensity increase over time was detected in the interstitium. Mean index leakage differed between control and anaphylaxis (respectively 20 ± 11 vs. 170 ± 127%; P < 0.0001), starting at 2 min after shock onset and progressively increasing. Index leakage correlated with the drop in arterial blood pressure until T0 + 10 min (r = -0.75, P = 0.0001).

Conclusions

During anaphylaxis, interstitial capillary leakage occurs within minutes after shock onset. Compared with controls, the mesenteric microcirculation showed at least 8-fold-increased macromolecular capillary leakage. The inflammation-induced microcirculatory changes with subsequent intravascular fluid transfer might be involved in the onset of the inaugural hypotension during anaphylactic shock.
Nasopharyngeal suctioning does not produce a salivary cortisol reaction in preterm infants
Authors: Ivars Katrin , Nelson Nina , Finnström Orvar , Mörelius Evalotte
Published: August 2012

Aim:  To investigate whether nasopharyngeal suctioning produces a physiological and behavioural stress reaction in preterm infants and if a possible reaction can be dampened by sweet solution.

Methods:  Eleven preterm infants were randomly assigned to receive either 30% oral glucose or nothing prior to morning nasopharyngeal suctioning; the procedure was reversed in the afternoon. The study included a total of 44 samples from preterm infants evaluated with salivary cortisol, pain score (Visual Analogue Scale), heart rate, oxygen saturation and recovery time through the Newborn Individualized Developmental Care and Assessment Program. For reference, 44 samples from eleven full‐term infants were evaluated for salivary cortisol.

Results:  Regardless of whether or not preterm infants received glucose before nasopharyngeal suctioning, no statistically significant difference was found in salivary cortisol reactivity, pain score, heart rate, oxygen saturation or recovery time. Nor were any statistically significant differences between salivary cortisol baseline and response values found in full‐term infants after nasopharyngeal suctioning.

Conclusion:  In the present setting, nasopharyngeal suctioning was not stressful enough to increase salivary cortisol or pain score. Oral glucose did not alter salivary cortisol levels.
DNA methylation analysis of ALOX12 and GSTM1 in acute myeloid leukaemia identifies prognostically significant groups
Authors: Ohgami Robert S. , Ma Lisa , Ren Li , Weinberg Olga K. , Seetharam Mahesh , Gotlib Jason R. , Arber Daniel A.
Published: August 2012

To determine the role of DNA methylation in the progression of acute myeloid leukaemia (AML), we analysed the methylation status of ALOX12, GSTM1, HS3ST2 and FZD9 in 127 AML patients. Aberrant methylation of ALOX12 was associated with the subcategory AML with myelodysplasia‐related changes (P = 0·0439) and specifically with megakaryocytic dysplasia (P = 0·0003). An association between HS3ST2 and AML patients with favourable cytogenetic risk was identified (P = 0·0469). In univariate and multivariate analysis, methylation of GSTM1 was associated with worse overall survival (OS) and disease‐free survival (DFS), with hazard ratios of 2·57 and 1·86, respectively. Furthermore, the significance of methylation of GSTM1 in predicting poor prognosis was maintained within the subcategories of AML not otherwise specified (NOS), AML with intermediate cytogenetic risk and normal karyotype AML. Finally, patients with both GSTM1 and ALOX12 methylated, demonstrated worse outcomes when all AML patients were assessed (OS; P = 0·000411) as well as within AML NOS (DFS; P = 0·0023), AML with intermediate cytogenetic risk (OS; P = 0·0104) and normal karyotype AML (OS; P = 0·00636). This study implicates methylation of specific genes in the classification and prognostication of AML and suggests that the morphological feature of multilineage dysplasia may be a surrogate marker of gene methylation in at least a subset of AML cases.
Emerging pathogens and their implications for the blood supply and transfusion transmitted infections
Authors: Dodd Roger Y.
Published: August 2012

The threat of infection by conventional transfusion‐transmitted agents has been essentially eliminated from the blood supply in developed countries, thus focusing attention on the potential risk from emerging infections. Over recent years, actions have been taken to manage a number of such risks to blood safety. These illustrate the inherent variability of the agents concerned and of the measures needed to define and control the risk.
HLA‐DQ strikes again: Genome‐wide association study further confirms HLA‐DQ in the diagnosis of asthma among adults
Authors: Lasky‐Su J. , Himes B. E. , Raby B. A. , Klanderman B. J. , Sylvia J. Senter , Lange C. , Melen E. , Martinez F. D. , Israel E. , Gauderman J. , Gilliland F. , Sleiman P. , Hakonarson H. , Celedón J. C. , Soto‐Quiros M. , Avila L. , Lima J. J. , Irvin C. G. , Peters S. P. , Boushey H. , Chinchilli V. M. , Mauger D. , Tantisira K. , Weiss S. T. ,   and for the SHARP investigators
Published: August 2012

Background

Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL3, PDE4D, HLA‐DQ, and TLE4) via genome‐wide association studies.

Objective

To identify genetic variants associated with asthma affection status using genome‐wide association data.

Methods

We describe results from a genome‐wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms (SNPs).

Result

The genome‐wide association study resulted in the prioritization of 33 variants for immediate follow‐up in a multi‐staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA‐DQA1 (chromosome 6p21.3) was associated with asthma in adults (P‐value = 2.2E‐08) with consistent evidence in the more heterogeneous group of adults and children (P‐value = 1.0E‐04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations.

Conclusion

Overall, our findings further replicate the HLA‐DQ region in the pathogenesis of asthma. HLA‐DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA‐DRA, HLA‐DQB1 and HLA‐DQA2.
Efficacy of IGF‐based growth hormone (GH) dosing in nonGH‐deficient (nonGHD) short stature children with low IGF‐I is not related to basal IGF‐I levels
Authors: Cohen Pinchas , Rogol Alan D. , Weng Wayne , Kappelgaard Anne‐Marie , Rosenfeld Ron G. , Germak John ,   The American Norditropin Study Group
Published: August 2012

Objective

Weight‐based GH dosing is the standard for treating children with short stature. The current study validates the usefulness of IGF‐based GH dosing for GH therapy in nonGH‐deficient (nonGHD) children and its relationship with pretreatment serum IGF‐I concentration.

Design and Patients

In this twelve‐month, open‐label, randomized controlled study, 151 nonGHD (based on GH‐stimulation tests), prepubertal children with short stature and IGF‐I levels ≤ 33rd percentile [–0·44 standard deviation score (SDS)] were randomly assigned to receive GH (dose based on IGF‐I titration algorithm; n = 114) or to observation (n = 37). GH dose (initially 40 μg/kg/d) was adjusted every 3 months to achieve an IGF‐I SDS in the upper normal range (66–99th percentile).

Measurements and Results

In treated children, mean height SDS (HSDS) increased from −2·5 at baseline to −1·7 at 12 months and mean IGF‐I SDS increased from −1·7 to 0·1. These parameters remained unchanged in untreated children. There was no relationship between change in HSDS (ΔHSDS) and degree of IGF‐I deficiency at baseline. No safety problems were observed. Both groups had a similar advance in bone age. At the end of study, ΔHSDS in treated children showed a positive correlation with IGF‐I SDS, but not with GH dose [mean 59 μg/kg/d (range 29–92)], basal IGF‐I SDS or 1‐month IGF parameters.

Conclusions

In nonGHD subjects with short stature and serum IGF‐I concentrations within and below the lower third of normal, adjusting GH dose to achieve an IGF‐I level in the upper normal range resulted in a significant increase in HSDS, regardless of basal IGF‐I levels.
Effect of platelet‐rich plasma on bone healing of fresh frozen bone allograft in mandibular defects: a histomorphometric study in dogs
Authors: Messora Michel R. , Nagata Maria J. H. , Pola Natália M. , de Campos Natália , Fucini Stephen E. , Furlaneto Flávia A. C.
Published: August 2012

Objective

This study histologically analyzed the healing of fresh frozen bone allograft (FFBA) with or without platelet‐rich plasma (PRP) in bony defects surgically created in the mandible of dogs.

Material and methods

Bilateral resection defects were surgically created on the inferior border of the mandible in 10 dogs. The defects were randomly divided into three groups: C (the defect was filled by blood clot only), FFBA (the defect was filled with particulate FFBA), and FFBA/PRP (the defect was filled with particulate FFBA combined with PRP). The animals were euthanized at 12 weeks post‐surgery. Histomorphometric and histological analyses were performed. Data were statistically analyzed using Friedman test and Dunn test (P < 0.05).

Results

Group FFBA/PRP presented a statistically greater mineralized bone area and a smaller marrow bone area than Groups FFBA and C.

Conclusions

The use of PRP improved the incorporation of FFBA, increasing the density of newly formed bone at 12 weeks post‐surgery.
Targeting the vascular endothelial growth factor in hematologic malignancies
Authors: Paesler Julian , Gehrke Iris , Poll‐Wolbeck Simon Jonas , Kreuzer Karl‐Anton
Published: August 2012

There exists increasing evidence that apart from solid tumors, angiogenic growth factors also play important roles in the development and/or maintenance of hematolymphoid malignancies. Thus, in these cancers, angiogenesis and bone marrow microvessel density often correlate with prognosis and disease burden. Several reports speculated on the role of angiogenesis and the resulting possible therapeutic options in hematologic malignancies. The most prominent angiogenic factor, vascular endothelial growth factor (VEGF), is expressed in a number of established leukemic cell lines as well as in freshly isolated human leukemias and lymphomas, and several human leukemias express VEGF receptor 1 and/or VEGF receptor 2. VEGF/VEGF‐receptor interactions are also involved in proliferation, migration, and survival of leukemic cells by autocrine and paracrine mechanisms. As a consequence, a possible drugable effect by inhibiting VEGF signaling in different hematologic malignancies has been discussed. This review focuses on angiogenesis‐independent effects of VEGF on survival and proliferation of leukemic or lymphoma cells and on possible therapeutic approaches using anti‐VEGF/VEGF‐receptor therapies to inhibit proliferation or induce apoptosis of malignant cells in hematologic diseases.
Estimating recreational harvest using interview‐based recall survey: implication of recalling in weight or numbers
Authors: Sparrevohn C. R.
Published: August 2012

For many overfished marine stocks, recreational fishing continues even though recovery plans are implemented and commercial landings regulated. In such cases, unbiased and precise estimates of recreational harvest are important for successful management. Harvest estimation often relies on interviewed‐based surveys where fishers are asked to recall harvest within a given timeframe. However, the importance of whether fishers are requested to provide figures in weight or number is unresolved. Therefore, a recall survey aiming at estimating recreational harvest was designed, such that respondents could report harvest using either weight or numbers. It was found that: (1) a preference for reporting in numbers dominated; (2) reported mean individual weight of fish caught, differed between units preferences; and (3) when an estimate of total harvest in weight are calculated, these difference could result in a substantial bias through the conversion from numbers to weight. Based upon these results it is recommended that recreational harvest should be requested in numbers and not weight.
Differential Expression of Human Beta Defensin 2 and 3 in Gastric Mucosa of Helicobacter pylori‐Infected Individuals
Authors: Bauer Bianca , Wex Thomas , Kuester Doerthe , Meyer Thomas , Malfertheiner Peter
Published: August 2012

Background

Antimicrobial peptides are key players of initial innate immune responses to human pathogens. Two major representatives, the human beta defensin 2 and 3 (hBD2 and hBD3), are both known to be regulated by, and to affect viability of, Helicobacter pylori. Previously, it was demonstrated in vitro that H. pylori actively abrogates hBD3 expression during prolonged infections. Here, we comprehensively assessed hBD2 and hBD3 expression ex vivo in the gastric mucosa of healthy individuals.

Materials and Methods

Twenty volunteers (H. pylori positive and H. pylori negative: n = 10) were enrolled. Helicobacter pylori‐positive subjects underwent eradication therapy and repeated the protocol. Expression of both defensins was assessed by quantitative RT‐PCR and ELISA, and correlated with histopathologic degree of gastritis.

Results

hBD2 and hBD3 were found to be ubiquitously expressed in all three groups. In general, hBD2 levels were elevated in relation to H. pylori infection (up to 40‐fold). This upregulation correlated with degree of gastritis in corpus and antrum. In contrast, hBD3 protein levels were significantly decreased, while corresponding mRNA amounts remained unchanged. Eradication therapy led to normalization of mucosal hBD2 expression, while hBD3 expression demonstrated high interindividual variations among individuals.

Conclusions

Both defensins are ubiquitously but differentially expressed in gastric mucosa in relation to H. pylori infection. Ex vivo data support the notion that H. pylori infection is associated with reduced hBD3 expression in chronic active gastritis.
PHYLOGENETIC ANALYSIS OF THE MALE ONTOGENETIC PROGRAM IN AQUATIC AND TERRESTRIAL MONOCOTYLEDONS
Authors: BLACKMORE S. , MCCONCHIE C. A. , KNOX R. B.
Published: August 2012

Abstract—

The male program of ontogeny in flowering plants encompasses the events from meiosis of microsporocytes to fertilization. Three main sequences are discussed; the deposition of cell walls, changes in cytoplasmic organelles, and the program of nuclear divisions leading to the formation of two sperm cells and a vegetative cell in each pollen grain. Variations in these ontogenetic sequences are particularly apparent in the monocotyledons, which exhibit diversity in pollen morphology, wall structure, and mode of pollination. The male program of development has been compared in selected terrestrial monocotyledons belonging to the Liliaceae and Gramineae and aquatic members of the Cymodoceaceae, Najadaceae, and Zannichelliaceae. A total of 26 characters from the male program are discussed and then used to construct a cladogram derived only from developmental data for the five species. The polarity of only a few of the character transformations has been determined directly by observation of developmental sequences; most have been interpreted by outgroup analysis.
Web‐based alcohol intervention for Māori university students: double‐blind, multi‐site randomized controlled trial
Authors: Kypri Kypros , McCambridge Jim , Vater Tina , Bowe Steven J. , Saunders John B. , Cunningham John A. , Horton Nicholas J.
Published: August 2012

Aims

Like many indigenous peoples, New Zealand Māori bear a heavy burden of alcohol‐related harm relative to their non‐indigenous compatriots, and disparities are greatest among young adults. We tested the effectiveness of web‐based alcohol screening and brief intervention (e‐SBI) for reducing hazardous drinking among Māori university students.

Design

Parallel, double‐blind, multi‐site, randomized controlled trial.

Setting

Seven of New Zealand's eight universities.

Participants

In April 2010, we sent e‐mail invitations to all 6697 17–24‐year‐old Māori students to complete a brief web questionnaire including the Alcohol Use Disorders Identification Test (AUDIT)‐C, a screening tool for hazardous and harmful drinking. Those screening positive were computer randomized to: <10 minutes of web‐based alcohol assessment and personalized feedback (intervention) or screening alone (control).

Measurements

We conducted a fully automated 5‐month follow‐up assessment with observers and participants blinded to study hypotheses, design and intervention delivery. Pre‐determined primary outcomes were: (i) frequency of drinking, (ii) amount consumed per typical drinking occasion, (iii) overall volume of alcohol consumed and (iv) academic problems.

Findings

Of the participants, 1789 were hazardous or harmful drinkers (AUDIT‐C ≥ 4) and were randomized: 850 to control, 939 to intervention. Follow‐up assessments were completed by 682 controls (80%) and 733 intervention group members (78%). Relative to controls, participants receiving intervention drank less often [RR = 0.89; 95% confidence interval (CI): 0.82–0.97], less per drinking occasion (RR = 0.92; 95% CI: 0.84–1.00), less overall (RR = 0.78; 95% CI: 0.69–0.89) and had fewer academic problems (RR = 0.81; 95% CI: 0.69–0.95).

Conclusions

Web‐based screening and brief intervention reduced hazardous and harmful drinking among non‐help‐seeking Māori students in a large‐scale pragmatic trial. The study has wider implications for behavioural intervention in the important but neglected area of indigenous health.
The task of taking care of children: methodological perspectives and empirical implications
Authors: Andenaes Agnes
Published: August 2012

Methods are not neutral instruments but construct the phenomena under investigation and convey meaning about what is important. This paper explores a methodological framework to investigate parental care for children. As part of the results, the following characteristics of how parents take care of their children are presented: continuous responsibility; predictable routines that are adjusted to the child; and interpretations and negotiations about developmental goals. The argument is that methodological approaches that analyse larger temporal units of contextualized practices as presented by the participants themselves open up for more context‐sensitive knowledge about the task of taking care of children. Thus, the understanding of the process of development is widened and specified in a way that may be useful for fields of practice where developmental psychology is ‘at work’.
A prospective study of human papillomavirus (HPV) testing to resolve uncertainty in colposcopy
Authors: Bowring J. , Albrow R. , Fisher A. , Downey G. , Cullimore J. , Patnick J. , Walker P. G. , Kitchener H. C.
Published: August 2012

J. Bowring, R. Albrow, A. Fisher, G. Downey, J. Cullimore, J. Patnick, P.G. Walker and H.C. Kitchener  A prospective study of human papillomavirus (HPV) testing to resolve uncertainty in colposcopy

Objective:  UK colposcopy services are seeing increased workloads, a large proportion of which are follow‐up appointments. The English Cervical Screening Programme HPV Special Interest Group identified five subcategories of colposcopy clinic patients who often require prolonged follow‐up regimes for low‐grade abnormalities. Human papillomavirus (HPV) testing has a high negative predictive value, meaning that HPV‐negative women are at very low risk of underlying disease. Our objectives were to quantify the number of HPV‐negative women in each study subcategory and to evaluate the number who could potentially be discharged from colposcopy on the basis of their results.

Methods:  Four colposcopy clinics prospectively identified women according to five categories over 12 months. All women underwent cytological testing and high‐risk HPV (hrHPV) testing using the Hybrid Capture 2 test. Management outcomes and decisions based on a knowledge of the HPV status were recorded.

Results:  Data available on 755 women showed that 422/755 (55.9%) and 260/755 (34.4%) had persistent cervical intraepithelial neoplasia grade 1 (CIN1) (Category 1) or a minor abnormality following treatment (Category 2), respectively. In Categories 1 and 2, 51.7% and 60.2%, respectively, were hrHPV negative. The rates with biopsies of CIN2 or worse (CIN2+) across the two categories were 3/355 (0.8%) and 21/291 (7.0%) for hrHPV‐negative and hrHPV‐positive women, respectively.

Conclusion:  The incorporation of hrHPV testing within organized cervical screening programmes has been widely accepted. hrHPV testing for the clinical scenarios outlined in this study detects women who are hrHPV negative and therefore at low risk of underlying disease, potentially reducing anxiety and inconvenience for women and costs to colposcopy services.
Cutin and suberin biomarkers as tracers for the turnover of shoot and root derived organic matter along a chronosequence of Ecuadorian pasture soils
Authors: Hamer U. , Rumpel C. , Dignac M.‐F.
Published: August 2012

Forest‐to‐pasture conversion has been reported to increase soil organic matter (SOM) in mineral topsoils in the tropical mountain rainforest region of south Ecuador, with subsequent decreases following pasture abandonment. Until now the mechanisms behind these changes have not been fully understood. To elucidate their varied preservation patterns, we analysed root‐ and shoot‐derived organic matter and assessed their contribution to the formation of SOM in topsoils (0–5 cm) on a chronosequence of pastures (Setaria sphacelata (Schumach.); C4) established after slash and burn of the natural forest (diverse C3 plant species) and an abandoned pasture site invaded by bracken fern (Pteridium arachnoideum (Kaulf.) Maxon.; C3). Cutin and suberin biomarkers of the two plant species (grass and bracken) and of forest litter were identified after saponification and their contribution to SOM was studied by compound‐specific stable carbon isotope analyses. Our results showed specific root and shoot biomarkers for the two plant species and for forest litter, which often did not correspond to the classification of root‐versus shoot‐specific monomers reported in the literature. This illustrates the importance of direct biomarker determination rather than using results from studies with different plants. Shoot‐ as well as root‐derived OM of forest and grass origin contributed to the stable SOM pool with decadal turnover times. Forest‐derived monomers contributed more to the stable SOM pool compared with grass‐derived monomers. ω‐hydroxy carboxylic acids and α,ω‐alkanedioic acids of forest origin may have been stabilized in these tropical soils by bonding to soil minerals. Rapid degradation of grass‐derived lipids from the same compound classes suggests a saturation of the mineral binding capacity. In pasture soils, the accumulation of SOM was mainly driven by large inputs of root OM. The accumulated SOM during pasture use is, however, lost rapidly after abandonment.
A systematic review of risk factors during first year of life for early childhood caries
Authors: Leong Pamela Margaret , Gussy Mark Gregory , Barrow Su‐Yan L. , de Silva‐Sanigorski Andrea , Waters Elizabeth
Published: August 2012

Background

Early childhood caries (ECC) describes dental caries affecting children aged 0–71 months. Current research suggests ECC has important aetiological bases during the first year of life. Gaps in knowledge about disease progression prevent the effective and early identification of ‘at risk’ children.

Aim

To conduct a systematic review of research studies focusing on (a) acquisition and colonization of oral bacteria and ECC and (b) risk and/or protective factors in infants aged 0–12 months.

Design

Ovid Medline and Embase databases (1996–2011) were searched for RCT, longitudinal, cross‐sectional and qualitative studies. Two investigators undertook a quality assessment for risk of bias.

Results

Inclusion criteria were met for (a) by four papers and for (b) by 13 papers; five papers were rated medium or high quality. Bacterial acquisition/colonization and modifying factor interrelationships were identified, but their role in the caries process was not clarified. Key risk indicators were infant feeding practices (nine papers), maternal circumstances and oral health (6) and infant‐related oral health behaviours (4).

Conclusion

This review confirmed that factors occurring during the first year of life affect ECC experience. Despite heterogeneity, findings indicated maternal factors influence bacterial acquisition, whereas colonization was mediated by oral health behaviours and practices and feeding habits.
Epidemiology of malaria in the Papua New Guinean highlands
Authors: Betuela Inoni , Maraga Seri , Hetzel Manuel W. , Tandrapah Tony , Sie Albert , Yala Simon , Kundi Julius , Siba Peter , Reeder John C. , Mueller Ivo
Published: August 2012

Objectives  To conduct an in‐depth investigation of the epidemiology of malaria in the Papua New Guinea (PNG) highlands and provide a basis for evidence‐based planning and monitoring of intensified malaria control activities.

Methods  Between December 2000 and July 2005, 153 household‐based, rapid malaria population surveys were conducted in 112 villages throughout the central PNG highlands. The presence of malaria infections was determined by light microscopy and risk factors assessed using a structured questionnaire. The combined dataset from all individually published surveys was reanalysed.

Results  The prevalence of malaria infections in the different surveys ranged from 0.0% to 41.8% (median 4.3%) in non‐epidemic surveys and 6.6% to 63.2% (median 21.2%, P < 0.001) during epidemics. Plasmodium falciparum was the predominant infection below 1400 m and during epidemics, Plasmodium vivax at altitudes >1600 m. Outside epidemics, prevalence decreased significantly with altitude, was reduced in people using bed nets [odds ratio (OR) = 0.8, P < 0.001] but increased in those sleeping in garden houses (OR = 1.34, P < 0.001) and travelling to highly endemic lowlands (OR = 1.80, P < 0.001). Below 1400 m, malaria was a significant source of febrile illness. At higher altitudes, malaria was only a significant source of febrile illness during epidemic outbreaks, but asymptomatic malaria infections were common in non‐epidemic times.

Conclusions  Malaria is once again endemic throughout the PNG highlands in areas below 1400–1500 m of altitude with a significant risk of seasonal malaria outbreaks in most area between 1400–1650 m. Ongoing control efforts are likely to result in a substantial reduction in malaria transmission and may even result in local elimination of malaria in higher lying areas.