bluuebunny/crossref_metadata_2025 huggingface dataset:
Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm
Authors: Methot Stephen P. , Litzler Ludivine C. , Trajtenberg Felipe , Zahn Astrid , Robert Francis , Pelletier Jerry , Buschiazzo Alejandro , Magor Brad G. , Di Noia Javier M.
Published: March 2015

Activation-induced deaminase (AID) initiates mutagenic pathways to diversify the antibody genes during immune responses. The access of AID to the nucleus is limited by CRM1-mediated nuclear export and by an uncharacterized mechanism of cytoplasmic retention. Here, we define a conformational motif in AID that dictates its cytoplasmic retention and demonstrate that the translation elongation factor eukaryotic elongation factor 1 α (eEF1A) is necessary for AID cytoplasmic sequestering. The mechanism is independent of protein synthesis but dependent on a tRNA-free form of eEF1A. Inhibiting eEF1A prevents the interaction with AID, which accumulates in the nucleus and increases class switch recombination as well as chromosomal translocation byproducts. Most AID is associated to unspecified cytoplasmic complexes. We find that the interactions of AID with eEF1A and heat-shock protein 90 kD (HSP90) are inversely correlated. Despite both interactions stabilizing AID, the nature of the AID fractions associated with HSP90 or eEF1A are different, defining two complexes that sequentially produce and store functional AID in the cytoplasm. In addition, nuclear export and cytoplasmic retention cooperate to exclude AID from the nucleus but might not be functionally equivalent. Our results elucidate the molecular basis of AID cytoplasmic retention, define its functional relevance and distinguish it from other mechanisms regulating AID.
BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms
Authors: Hatzi Katerina , Nance J. Philip , Kroenke Mark A. , Bothwell Marcella , Haddad Elias K. , Melnick Ari , Crotty Shane
Published: March 2015

Follicular helper T cells (Tfh cells) are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of BCL6 in Tfh cells have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates. Interestingly, although some BCL6-bound genes possessed BCL6 DNA–binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6-binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology and provide insight into how this master regulator mediates distinct cell context–dependent phenotypes.
A single glycan on IgE is indispensable for initiation of anaphylaxis
Authors: Shade Kai-Ting C. , Platzer Barbara , Washburn Nathaniel , Mani Vinidhra , Bartsch Yannic C. , Conroy Michelle , Pagan Jose D. , Bosques Carlos , Mempel Thorsten R. , Fiebiger Edda , Anthony Robert M.
Published: March 2015

Immunoglobulin ε (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, FcεRI. Subsequent allergen exposure cross-links mast cell–bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (Cε3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to FcεRI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology.
Similarity solutions for the generalized equation of steady transonic gas flow with a singular source
Authors: Bellout Hamid , Vajravelu Kuppalapalle , Van Gorder Robert
Published: March 2015

In this brief paper, we consider the generalized equation of steady transonic gas flow with the addition of a singular source term. While the addition of a source term often destroys self-similarity of such flows, we demonstrate that a self-similar solution can still exist in the case of a singular source. We first reduce the governing nonlinear partial differential equation into an ordinary differential equation for a class of similarity solutions. Then, we study the existence of solutions for this similarity equation. After that, several explicit solution forms are given. In constructing exact solutions analytically, we demonstrate that dual solution branches may exist for some parameter regimes. For those parameter regimes where exact or analytical solutions are not possible, we obtain numerical solutions. The results demonstrate interesting properties of the solutions which warrant further study.
The future of human cerebral cartography: a novel approach
Authors: Frackowiak Richard , Markram Henry
Published: March 2015

Cerebral cartography can be understood in a limited, static, neuroanatomical sense. Temporal information from electrical recordings contributes information on regional interactions adding a functional dimension. Selective tagging and imaging of molecules adds biochemical contributions. Cartographic detail can also be correlated with normal or abnormal psychological or behavioural data. Modern cerebral cartography is assimilating all these elements. Cartographers continue to collect ever more precise data in the hope that general principles of organization will emerge. However, even detailed cartographic data cannot generate knowledge without a multi-scale framework making it possible to relate individual observations and discoveries. We propose that, in the next quarter century, advances in cartography will result in progressively more accurate drafts of a data-led, multi-scale model of human brain structure and function. These blueprints will result from analysis of large volumes of neuroscientific and clinical data, by a process of reconstruction, modelling and simulation. This strategy will capitalize on remarkable recent developments in informatics and computer science and on the existence of much existing, addressable data and prior, though fragmented, knowledge. The models will instantiate principles that govern how the brain is organized at different levels and how different spatio-temporal scales relate to each other in an organ-centred context.
The restless brain: how intrinsic activity organizes brain function
Authors: Raichle Marcus E.
Published: March 2015

Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.
Cerebral cartography and connectomics
Authors: Sporns Olaf
Published: March 2015

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics.
A massively asynchronous, parallel brain
Authors: Zeki Semir
Published: March 2015

Whether the visual brain uses a parallel or a serial, hierarchical, strategy to process visual signals, the end result appears to be that different attributes of the visual scene are perceived asynchronously—with colour leading form (orientation) by 40 ms and direction of motion by about 80 ms. Whatever the neural root of this asynchrony, it creates a problem that has not been properly addressed, namely how visual attributes that are perceived asynchronously over brief time windows after stimulus onset are bound together in the longer term to give us a unified experience of the visual world, in which all attributes are apparently seen in perfect registration. In this review, I suggest that there is no central neural clock in the (visual) brain that synchronizes the activity of different processing systems. More likely, activity in each of the parallel processing-perceptual systems of the visual brain is reset independently, making of the brain a massively asynchronous organ, just like the new generation of more efficient computers promise to be. Given the asynchronous operations of the brain, it is likely that the results of activities in the different processing-perceptual systems are not bound by physiological interactions between cells in the specialized visual areas, but post-perceptually, outside the visual brain.
Bacillus wuyishanensis sp. nov., isolated from rhizosphere soil of a medical plant, Prunella vulgaris
Authors: Liu Bo , Liu Guo-Hong , Sengonca Cetin , Schumann Peter , Che Jian-Mei , Zhu Yu-Jing , Wang Jie-Ping
Published: March 2015

A Gram-staining-positive, rod-shaped, endospore-forming, aerobic bacterium (FJAT-17212T) was isolated from the rhizosphere soil of a medical plant, Prunella vulgaris (common selfheal), on the Wuyishan mountain of China. Isolate FJAT-17212T grew at 10–50 °C (optimum 30 °C), pH 5–11 (optimum pH 7) and with 0–6  % (w/v) NaCl (optimum 2  %). Phylogenetic analyses based on 16S rRNA gene sequences showed that isolate FJAT-17212T was a member of the genus Bacillus and was most closely related to Bacillus galactosidilyticus DSM 15595T (97.3  %). DNA–DNA relatedness between isolate FJAT-17212T and B. galactosidilyticus DSM 15595T was low (35.2  % ± 2.3). The diagnostic diamino acid of the peptidoglycan of isolate FJAT-17212T was meso-diaminopimelic acid and the predominant isoprenoid quinone was MK-7 (80.8  %). The major cellular fatty acids were iso-C15 : 0 (35.7  %), anteiso-C15 : 0 (29.8  %), iso-C14 : 0 (9.9  %) and iso-C16 : 0 (9.9  %) and the DNA G+C content was 39.8  mol%. Phenotypic, chemotaxonomic and genotypic properties clearly indicated that isolate FJAT-17212T represents a novel species within the genus Bacillus, for which the name Bacillus wuyishanensis sp. nov. is proposed. The type strain is FJAT-17212T ( = DSM 27848T = CGMCC 1.12709T).
Flowering time of butterfly nectar food plants is more sensitive to temperature than the timing of butterfly adult flight
Authors: Kharouba Heather M. , Vellend Mark
Published: March 2015

Variation among species in their phenological responses to temperature change suggests that shifts in the relative timing of key life cycle events between interacting species are likely to occur under climate warming. However, it remains difficult to predict the prevalence and magnitude of these shifts given that there have been few comparisons of phenological sensitivities to temperature across interacting species.

Here, we used a broad‐scale approach utilizing collection records to compare the temperature sensitivity of the timing of adult flight in butterflies vs. flowering of their potential nectar food plants (days per °C) across space and time in British Columbia, Canada.

On average, the phenology of both butterflies and plants advanced in response to warmer temperatures. However, the two taxa were differentially sensitive to temperature across space vs. across time, indicating the additional importance of nontemperature cues and/or local adaptation for many species.

Across butterfly–plant associations, flowering time was significantly more sensitive to temperature than the timing of butterfly flight and these sensitivities were not correlated.

Our results indicate that warming‐driven shifts in the relative timing of life cycle events between butterflies and plants are likely to be prevalent, but that predicting the magnitude and direction of such changes in particular cases is going to require detailed, fine‐scale data.
Drawing with a camera? Ethnographic film and transformative anthropology
Authors: Grimshaw Anna , Ravetz Amanda
Published: March 2015

Drawing has emerged as a recent focus of anthropological attention. Writers such as Ingold and Taussig have argued for its significance as a special kind of knowledge practice, linking it to a broader re‐imagining of the anthropological project itself. Underpinning their approach is an opposition between the pencil and the camera, between ‘making’ and ‘taking’, between restrictive and generative modes of inquiry. This essay challenges this assumption, arguing that these elements in drawing and filmmaking exist in a dialectical rather than a polarized relationship. It highlights particular insights that follow from a dialogue between written and film‐based anthropologies and links them to broader debates within the discipline – for example, debates about ways of knowing, skilled practice, improvisation and the imagination, and anthropology as a form of image‐making practice.
Accountability and the academy: producing knowledge about the human dimensions of climate change
Authors: Hall Elizabeth F. , Sanders Todd
Published: March 2015

Calls for accountability and ‘impactful’ research are fundamentally reshaping the academy, giving rise to a large, critical scholarship on neoliberal regimes of accountability and their pernicious effects. But these calls also animate other institutional forms and practices that have received less critical attention. These include new forms of science that promise accountability through interdisciplinarity, collaborating with stakeholders, and addressing real‐world problems. This article considers one example of such accountable science: human dimensions of climate change field research. This research endeavour has produced surprising results, including the uncritical adoption of controversial Euro‐American ideas about traditional Others. In exploring how this has come about, the article considers how theoretical and disciplinary diversity are managed within this arena, and the organizing logics that enable climate sciences and scientists to work together. We ultimately argue that accountable science – like other neoliberal modes of accountability – can produce outcomes for which no one can be held to account.
Mojave desert tortoise (Gopherus agassizii) thermal ecology and reproductive success along a rainfall cline
Authors: SIEG Annette E. , GAMBONE Megan M. , WALLACE Bryan P. , CLUSELLA‐TRULLAS Susana , SPOTILA James R. , AVERY Harold W.
Published: March 2015

Desert resource environments (e.g. microclimates, food) are tied to limited, highly localized rainfall regimes which generate microgeographic variation in the life histories of inhabitants. Typically, enhanced growth rates, reproduction and survivorship are observed in response to increased resource availability in a variety of desert plants and short‐lived animals. We examined the thermal ecology and reproduction of US federally threatened Mojave desert tortoises (Gopherus agassizii), long‐lived and large‐bodied ectotherms, at opposite ends of a 250‐m elevation‐related rainfall cline within Ivanpah Valley in the eastern Mojave Desert, California, USA. Biophysical operative environments in both the upper‐elevation, “Cima,” and the lower‐elevation, “Pumphouse,” plots corresponded with daily and seasonal patterns of incident solar radiation. Cima received 22% more rainfall and contained greater perennial vegetative cover, which conferred 5°C‐cooler daytime shaded temperatures. In a monitored average rainfall year, Cima tortoises had longer potential activity periods by up to several hours and greater ephemeral forage. Enhanced resource availability in Cima was associated with larger‐bodied females producing larger eggs, while still producing the same number of eggs as Pumphouse females. However, reproductive success was lower in Cima because 90% of eggs were depredated versus 11% in Pumphouse, indicating that predatory interactions produced counter‐gradient variation in reproductive success across the rainfall cline. Land‐use impacts on deserts (e.g. solar energy generation) are increasing rapidly, and conservation strategies designed to protect and recover threatened desert inhabitants, such as desert tortoises, should incorporate these strong ecosystem‐level responses to regional resource variation in assessments of habitat for prospective development and mitigation efforts.
Induction of lcc2 expression and activity by Agaricus bisporus provides defence against Trichoderma aggressivum toxic extracts
Authors: Sjaarda Calvin P. , Abubaker Kamal S. , Castle Alan J.
Published: March 2015

Laccases are used by fungi for several functions including defence responses to stresses associated with attack by other fungi. Laccase activity changes and the induction of two laccase genes, lcc1 and lcc2, in Agaricus bisporus were measured in response to toxic extracts of medium in which Trichoderma aggressivum, the cause of green mould disease, was grown. A strain of A. bisporus that shows resistance to the extracts showed higher basal levels and greater enzymatic activity after extract exposure than did a sensitive strain. Furthermore, pre‐incubation of T. aggressivum extract with laccases reduced toxicity. Faster induction and greater numbers of lcc2 transcripts in response to the extract were noted in the resistant strain than in the sensitive strain. The timing and increase in lcc2 transcript abundance mirrored changes in total laccase activity. No correlation between resistance and lcc1 transcription was apparent. Transcript abundance in transformants with a siRNA construct homologous to both genes varied widely. A strong negative correlation between transcript abundance and sensitivity of the transformant to toxic extract was observed in plate assays. These results indicated that laccase activity and in particular that encoded by lcc2 contributes to toxin metabolism and by extension green mould disease resistance.
Evaluation of Rhizoctonia zeae as a potential biological control option for fungal root diseases of sugar beet
Authors: Webb K.M. , Harveson R.M. , West M.S.
Published: March 2015

Several common root diseases routinely damage sugar beet in Nebraska and other production areas of the Central High Plains, and it is becoming more common to find fields infested simultaneously with multiple pathogens. Owing to the shortage of available fungicides for economic management of soilborne diseases, alternative techniques such as biological control are increasingly being sought for disease management. Over the last several years, unidentified, sterile fungi have been isolated in conjunction with pathogens from infected sugar beet roots and seedlings. At least two promising isolates have been identified from in vitro assays that inhibit the radial growth of multiple sugar beet root pathogens, including Rhizoctonia solani, Fusarium oxysporum f. sp. betae, Phoma betae and Pythium aphanidermatum. Based on morphological and molecular characterisation, two isolates, ‘Hall’ and ‘R47’, were putatively identified as Rhizoctonia zeae. In vitro pathogenicity testing indicated that these isolates were not pathogens of sugar beet. Both isolates were compared with the well‐established biological control fungus Laetisaria arvalis and tested as potential treatments in a field naturally infested with multiple sugar beet root diseases. Data indicated that these fungi provided some level of protection against a complex of soilborne diseases and suggest that these isolates could have a potential fit in an integrative management strategy for several sugar beet root diseases.
Atopic dermatitis from adolescence to adulthood in the TOACS cohort: prevalence, persistence and comorbidities
Authors: Mortz C. G. , Andersen K. E. , Dellgren C. , Barington T. , Bindslev‐Jensen C.
Published: March 2015

Background

While much is known about childhood atopic dermatitis, little is known about persistence of atopic dermatitis into adult life. We report, to our knowledge for the first time, the clinical course of atopic dermatitis in an unselected cohort of adolescents followed into adulthood.

Methods

The course of atopic dermatitis from adolescence to adulthood was studied prospectively in a cohort of unselected 8th‐grade schoolchildren established in 1995 and followed up in 2010 with questionnaire and clinical examination.

Results

The lifetime prevalence of atopic dermatitis was high (34.1%), and a considerable number of adults still suffered from atopic dermatitis evaluated both by questionnaire (17.1%) and clinical examination (10.0%). Persistent atopic dermatitis was found in 50% of those diagnosed in school age, and persistent atopic dermatitis was significantly associated with early onset, childhood allergic rhinitis and hand eczema. A close association was also found with allergic contact dermatitis and increased specific IgE to Malassezia furfur, but not with filaggrin gene defect.

Conclusion

Persistence of atopic dermatitis in adulthood is common and affects quality of life. Persistent atopic dermatitis is particularly prevalent in those with early onset, allergic rhinitis and hand eczema in childhood. It is important to recognizing atopic dermatitis as a common and disabling disease not only in children but also in adults.
The rs6060566 of the reactive oxygen species modulator 1 (Romo‐1) gene affects Romo‐1 expression and the development of diabetic retinopathy in Caucasians with type 2 diabetes
Authors: Petrovic Mojca Globocnik , Kruzliak Peter , Petrovic Daniel
Published: March 2015

Purpose

The aim of this study was to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (Romo‐1) gene in the development of diabetic retinopathy (DR) in Caucasians with type 2 diabetes (T2DM). Moreover, another aim was to investigate the effect of Romo‐1 genotypes on Romo‐1 expression in fibrovascular membranes from patients with proliferative DR.

Methods

A total of 806 subjects with T2DM were enrolled in cross‐sectional case–control study: 278 patients with DR and 528 subjects without clinical signs of DR. Genetical analysis was performed in 806 subjects with T2DM. Moreover, immunohistochemical analysis of 40 fibrovascular membranes of patients with proliferative DR was performed. The number of positive (labelled) cells per area – numerical areal density of the Romo‐1‐positive cells (the number of positive cells/mm2) – was calculated.

Results

A significantly higher frequency of the CC genotype of the rs6060566 polymorphism of the Romo‐1 gene was found in subjects with T2DM with DR compared to those without DR (odds ratio=3.3, 95% confidence interval=1.1–8.8; p = 0.024). Moreover, the Romo‐1 C allele was found to effect Romo‐1 expression in fibrovascular membranes of patients with proliferative DR.

Conclusions

The rs6060566 polymorphism of the Romo‐1 gene was found to be an independent risk factor for DR in Caucasians with T2DM. Moreover, the rs6060566 is most probably functional and its effect might be mediated through the increased expression of Romo‐1 in the retina.
Intrabronchial Microdialysis: Effects of Probe Localization on Tissue Trauma and Drug Penetration into the Pulmonary Epithelial Lining Fluid
Authors: Rottbøll Lisa Amanda Holm , Skovgaard Kerstin , Barington Kristiane , Jensen Henrik Elvang , Friis Christian
Published: March 2015

Recent intrabronchial microdialysis data indicate that the respiratory epithelium is highly permeable to drugs. Of concern is whether intrabronchial microdialysis disrupts the integrity of the respiratory epithelium and thereby alters drug penetration into the pulmonary epithelial lining fluid (PELF). The objective of this study was to investigate the effect of intrabronchial microdialysis on the integrity of the bronchial epithelium. Microdialysis sampling in PELF in proximal (n = 4) and distal bronchi (n = 4) was performed after intravenous inulin and florfenicol administration in anaesthetized pigs. Inulin was used as a marker molecule of permeability of the epithelium, and florfenicol was used as test drug. Bronchial tissue was examined by histopathology (distal and proximal bronchi) and gene expression analysis (RT‐qPCR, proximal bronchi) at the termination of the experiment (6.5 hr). The microdialysis probe caused overt tissue trauma in distal bronchi, whereas no histopathological lesions were observed in proximal bronchi. A moderate up‐regulation of the pro‐inflammatory cytokinesIL1B,IL6 and acute‐phase reactant serum amyloidAwas seen in proximal bronchi surrounding the microdialysis probes suggesting initiation of an inflammatory response. The observed up‐regulation is considered to have limited impact on drug penetration during short‐term studies. Inulin penetrated the respiratory epithelium in both proximal and distal bronchi without any correlation to histopathological lesions. Likewise, florfenicol penetration into PELF was unaffected by bronchial histopathology. However, this independency of pathology on drug penetration may not be valid for other antibiotics. We conclude that short‐term microdialysis drug quantification can be performed in proximal bronchi without disruption of tissue integrity.
Nephrectomy for benign disease in the UK: results from the British Association of Urological Surgeons nephrectomy database
Authors: Zelhof Bachar , McIntyre Iain G. , Fowler Sarah M. , Napier‐Hemy Richard D. , Burke Daniel M. , Grey Ben R. ,   the British Association of Urological Surgeons
Published: March 2015

Objective

To summarize the practice of UK urologists with regard to nephrectomy for benign disease, documenting the indications, procedural techniques and outcomes.

Methods

All patients undergoing nephrectomy for a benign condition in 2012 were identified from the British Association of Urological Surgeons (BAUS) nephrectomy database. Recorded variables included the technique of surgery, the type of minimally invasive procedure, operating time, blood loss, transfusion rate, conversion rate, intra‐ and postoperative complications and mortality rate. Cases were also sub‐analysed according to their pathologies to determine the differences in complication rate between stone disease, pyelonephritis, non‐functioning kidney and other benign lesions. To contextualize procedural complexity, the simple nephrectomy data were compared with those obtained from the BAUS stage T1 radical nephrectomy audit.

Results

A total of 1 093 nephrectomies were performed (537 non‐functioning kidneys, 142 stone disease, 129 nephrectomies secondary to pyelonephritis and 285 cases with other benign conditions). Of these, 76% were performed laparoscopically. Blood loss >500 mL was noted in 74 cases with a 4.8% blood transfusion rate. The intra‐ and postoperative complication rates were 5.2 and 11.9%, respectively. Of the 847 minimally invasive procedures, the conversion rate was 5.9%. Patients with stone disease have the highest intra‐ and postoperative complications (9.9 and 23.9%, respectively) compared with other benign pathologies. The total number of T1 radical nephrectomies performed was 1 095. In comparison with T1 radical nephrectomy, simple nephrectomy carries an increased risk of conversion to an open procedure (1.8 times), a higher rate of blood transfusion (4.8 vs 2.8%), and a higher risk of intra‐ and postoperative complications (5.2 vs 3.7% and 11.9 vs 10%, respectively).

Conclusion

The present study reports the largest series of nephrectomies performed for benign disease and the resultant data now support the bespoke preoperative counselling of patients. Furthermore, it confirms the commonly held view that simple nephrectomy can be more difficult than its radical counterpart. The authors suggest that the term ‘simple nephrectomy’ is changed to ‘benign nephrectomy’.
LC‐MS/MS‐based method for long‐term steroid profiling in human scalp hair
Authors: Noppe Gerard , de Rijke Yolanda B. , Dorst Kristien , van den Akker Erica L. T. , van Rossum Elisabeth F. C.
Published: March 2015

Background

Liquid chromatography–tandem mass spectrometry (LC‐MS/MS) is the method of choice for quantification of steroids. Human scalp hair provides the possibility to measure long‐term retrospective steroid concentrations, which is especially useful for steroids with large time‐dependent fluctuations in concentration, such as the glucocorticoid cortisol.

Aim

We set up and validated a LC‐MS/MS‐based method for long‐term steroid profiling, quantifying cortisol, cortisone, testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS) and 17‐α‐hydroxyprogesterone (17OHP).

Method

Hair locks were cut from the posterior vertex of healthy male and female volunteers and washed in isopropanol. Steroids were extracted using methanol, and extract was cleaned up by solid‐phase extraction and measured on a Waters XEVO‐TQ‐S LC‐MS/MS. Lower limit of quantification, precision, matrix interference and intra‐individual variation were determined.

Results

The functional sensitivity of our steroid analysis was <1·3, <9·3, 2·3, <1·3, <15·9, 1·87 pg/mg hair for cortisol, cortisone, testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), and 17OHP, respectively. Measured over a 9‐month period, the inter‐run CVs were below 16% for all steroids. Intra‐individual coefficients of variation were below 15% for all steroids, except 17OHP (19·7%).

Conclusion

The authors present a LC‐MS/MS‐based method for long‐term steroid profiling in human scalp hair, potentially providing novel insights by a multitude of clinical and research applications in the field of endocrinology.
Psychological aspects of hyperandrogenic states in late adolescent and young women
Authors: Guidi Jenny , Gambineri Alessandra , Zanotti Laura , Fanelli Flaminia , Fava Giovanni A. , Pasquali Renato
Published: March 2015

Objective

The psychosocial implications of polycystic ovary syndrome (PCOS) phenotypes have been investigated in different patient populations, but little attention was paid to adolescent and young women. The aim of this study was to evaluate the psychosocial correlates of PCOS and other hyperandrogenic states in a population of late adolescent and young females and to provide a psychological characterization of specific clinical hyperandrogenic phenotypes.

Design

This was a cross‐sectional study.

Patients

High school female students, aged 16–19 years.

Measurements

The study protocol was designed with three possible levels of participation characterized by an increased level of commitment. For the specific purposes of this investigation, we focused on the subsamples of students whose clinical state was assessed by medical examination (n = 835) and for whom additional laboratory tests were available (n = 394). Psychological evaluation encompassed psychological distress, levels of stress, well‐being, illness behaviour and quality of life (as measured by the Symptom Questionnaire, the Psychosocial Index and the Psychological Well‐Being scales).

Results

Significantly higher levels of psychological distress and impaired well‐being and quality of life were found among late adolescent and young women with isolated clinical hyperandrogenism compared to their normal counterparts. Furthermore, females with PCOS showed significantly greater hostility/irritability compared to healthy control subjects.

Conclusions

These findings highlight the importance of early recognizing and adequately managing psychological distress in such patients.
Clinical characteristics of polycystic ovary syndrome: investigating differences in White and South Asian women
Authors: Mani Hamidreza , Davies Melanie J. , Bodicoat Danielle H. , Levy Miles J. , Gray Laura J. , Howlett Trevor A. , Khunti Kamlesh
Published: March 2015

Objective

To understand the phenotypic presentation of women with polycystic ovary syndrome (PCOS) of different ethnicities and at different ages.

Design

Cross‐sectional, retrospective data analysis (1988 – 2009).

Setting

Specialist clinic in a University Hospital, Leicestershire, UK.

Participants

Women with PCOS, n = 1310 (mean age 26·2 years), 70·9% White and 29·1% South Asian (SA) attending a speciality clinic in Leicester UK.

Main Outcomes measures

Clinical and demographic characteristics of women with PCOS including age at first clinic appointment, signs and symptoms, body mass index (BMI) and blood pressure (BP).

Results

Compared to White women, the SA were younger (24·3 vs 27·1 years, P < 0·001), less likely to smoke (3·7% vs 17·9% P < 0·001) and had a higher prevalence of acanthosis nigricans (AN) (16·8% vs 3·1% P < 0·001), type 2 diabetes (T2DM) (8·1% vs 5·6%, P < 0·01) and hirsutism (88·5% vs 77·4%, P < 0·001), with lower systolic (126·5 vs 133·0 mmHg, P < 0·001), diastolic BP (71·8 vs 75·1 mmHg P = 0·008) and BMI (29·3 vs 31·5 kg/m2 P = 0·002). Differences in body weight remained when participants were classified as obese, overweight and normal according to ethnicity‐specific cut‐off points (P = 0·048). In both ethnicities, those aged ≥30 years old had higher rates of obesity, T2DM, hypertension and infertility, and less acne, and oligomenorrhoea. Obesity was associated with increased T2DM, AN, systolic/diastolic BP, hirsutism and infertility.

Conclusion

The phenotypic and metabolic presentations of women with PCOS appear to be significantly different depending on ethnicity, obesity and age. This has implications for management strategies in these groups.
Life history traits and phenotypic selection among sunflower crop–wild hybrids and their wild counterpart: implications for crop allele introgression
Authors: Kost Matthew A. , Alexander Helen M. , Jason Emry D. , Mercer Kristin L.
Published: March 2015

Hybridization produces strong evolutionary forces. In hybrid zones, selection can differentially occur on traits and selection intensities may differ among hybrid generations. Understanding these dynamics in crop–wild hybrid zones can clarify crop‐like traits likely to introgress into wild populations and the particular hybrid generations through which introgression proceeds. In a field experiment with four crop–wild hybridHelianthus annuus(sunflower) cross types, we measured growth and life history traits and performed phenotypic selection analysis on early season traits to ascertain the likelihood, and routes, of crop allele introgression into wild sunflower populations. All cross types overwintered, emerged in the spring, and survived until flowering, indicating no early life history barriers to crop allele introgression. While selection indirectly favored earlier seedling emergence and taller early season seedlings, direct selection only favored greater early season leaf length. Further, there was cross type variation in the intensity of selection operating on leaf length. Thus, introgression of multiple early season crop‐like traits, due to direct selection for greater early season leaf length, should not be impeded by any cross type and may proceed at different rates among generations. In sum, alleles underlying early season sunflower crop‐like traits are likely to introgress into wild sunflower populations.
Irbesartan, an angiotensin II receptor antagonist, with selective PPAR‐gamma‐modulating activity improves function and structure of chemotherapy‐damaged ovaries in rats
Authors: Abdel‐Raheem Ihab T. , Omran Gamal A. , Katary Mohamed Alaa
Published: March 2015

Cyclophosphamide (CYP) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP induces granulosa cell apoptosis and oxidative stress. Irbesartan (IRB) is a unique ARB with a peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) agonistic activity. As PPAR‐ɣ activation exerts anti‐inflammatory effects and reduces ROS production, IRB may further reduce inflammatory chemokine expression and suppress apoptotic cell death. Therefore, this study aimed to evaluate the effects of IRB on the development of CYP‐induced ovarian damage. Rats were divided into four groups: control group, IRB group (100 mg/kg, orally), CYP group (100 mg/kg, i.p. single injection), and IRB+CYP group (IRB administered 9 days before and 6 days after CYP administration). Rats sacrificed on day 16 of experiment; estradiol (E2), FSH, and TNF‐α levels were estimated in serum. Reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase‐3 activities, myeloperoxidase (MPO), and IL‐10 levels were determined in ovarian tissues. Protein expressions of p53, caspase‐3, Ki‐67, and Rad‐51 were estimated by immunohistochemical and Western blot techniques. CYP produced ovarian damage as indicated from the decline in serum E2; elevation in FSH; unbalance in tissue oxidative stress parameters; increase in MPO, TNF‐α levels, caspase‐3 activity/expression, p53, and Rad‐51 expression; and decrease in IL‐10 contents, without effect on Ki‐67. On the other hand, IRB, significantly reduced the toxic effects of CYP as indicted from normalization of E2, FSH, oxidative stress, apoptotic, and inflammatory mediators. These data were further supported by histopathological studies. Thus, co‐administration of IRB may be promising in alleviating the ovarian toxic effects of CYP.
The Homestay in Intensive Language Study Abroad: Social Networks, Language Socialization, and Developing Intercultural Competence
Authors: Shiri Sonia
Published: March 2015

This study investigated the composition of the social network that the homestay offers learners in an intensive summer Arabic language program in diglossic and multilingual Tunisia and examined the types of language socialization as well as the overall linguistic and intercultural competence such opportunities present. The study specifically investigated patterns of student interaction with members of the host families and explored the degree to which students took advantage of this rich learning environment. A survey was completed by 73 students upon their return to the United States at the end of the summers of 2010–2012. Results showed that, although the social network often involved extended family members, the host mother remained the primary locus of interaction. Data also showed that the homestay offered a breadth and depth of experiences that affected students' linguistic, sociolinguistic, and cultural gains and that, postprogram, students maintained their connection to this social network via social media.
A High‐Leverage Language Teaching Practice: Leading an Open‐Ended Group Discussion
Authors: Kearney Erin
Published: March 2015

In response to calls for more practice‐based teacher education, this study investigated the way in which two high‐performing novice world language teachers, one in Spanish and one in Latin, implemented a high‐leverage teaching practice, leading an open‐ended group discussion. Observational data revealed a number of constituent micro‐practices. The article offers examples illustrating the way in which the practice was achieved and also captures the impact of such practices on classroom discourse. Findings provide an initial basis upon which continued research on high‐leverage teaching practices in the world language education context can be pursued.
Complications associated with central venous access device in children with haemophilia: a nationwide multicentre study in Finland
Authors: Vepsäläinen K. , Lassila R. , Arola M. , Lähteenmäki P. , Möttönen M. , Mäkipernaa A. , Riikonen P.
Published: March 2015

Children with haemophilia require venous access for regular infusion of coagulation factors. A central venous access device (CVAD) ensures long‐term access but associates with infectious and non‐infectious complications with proposed risk factors of young age at initial CVAD implantation and presence of an inhibitor. Our aim was to evaluate the incidence and risk factors for complications associated with CVAD usage in a retrospective nationwide multicentre study in five Finnish Paediatric Haemophilia Treatment Centers. Our study investigated 106 CVADs in 58 patients with 137 971 CVAD days. The median access survival was 1159 CVAD days, and most often a malfunction led to CVAD removal after a long survival (median of 1640 CVAD days). We detected a very low bloodstream infection rate (0.12/1000 CVAD days). The presence of neutralizing inhibitor was a significant risk factor for infection. Heparin vs. saline flushing did not influence the CVAD outcome. We detected a lower infection rate than previously reported, although 90% of the patients were very young (<2 years) at first insertion (median age = 1.02 year). Port access was frequent after initial implantation: six patients (10%) used the port daily for immune tolerance induction therapy and 74% at least twice weekly for prophylaxis. Young age did not increase the risk of infections, as 59% of the CVAD‐related infections were recorded in children over 6 years of age. Our national experience confirms the safety of prophylactic factor concentrate administration via ports even in very young children.
Distinct expression patterns of Toll‐like receptor 7 in tumour cells and fibroblast‐like cells in oral squamous cell carcinoma
Authors: Ni Yan Hong , Ding Liang , Zhang Dong Ya , Hou Ya Yi , Huang Xiaofeng , Hu Qingang
Published: March 2015

Aims

Toll‐like receptor (TLR)‐7 agonists have been used in cancer immunotherapy, but tumour heterogeneity means that TLR‐7 activity is variable in different components of the tumour microenvironment and the characteristics of TLR‐7 in oral squamous cell carcinoma (OSCC) are unclear.

Methods and results

Twenty healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR‐7 and showed up‐regulated expression during carcinogenesis. Moreover, patients with high expression of TLR‐7 in tumour cells (TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR‐7 in stroma fibroblast‐like cells (FLCs) had low tumour stage, no lymph node metastasis (LNM) and better prognosis. Furthermore, Ki‐67, CD3, CD4, CD8 and forkhead box protein 3 (FoxP3)+ tumour‐infiltrated lymphocytes were assessed and we found that TLR‐7high TCs were infiltrated by fewer CD3+CD4+ but more FoxP3+ lymphocytes. Importantly, patients with TLR‐7lowTCs and TLR‐7highFLCs had less FoxP3+ lymphocyte infiltration and longer survival time than those with TLR‐7highTCs/TLR‐7lowFLCs, although TLR‐7 was not an independent prognostic factor for OSCC.

Conclusions

The low expression of TLR‐7 in tumour and high expression of TLR‐7 in stroma predict a good clinical outcome for OSCC patients, and stroma FLCs might be amenable to immunotherapy by a TLR‐7 agonist.
Platelet‐derived growth factor receptor β (PDGFRβ) immunohistochemistry highlights activated bone marrow stroma and is potentially predictive for fibrosis progression in prefibrotic myeloproliferative neoplasia
Authors: Méhes Gábor , Tzankov Alexandar , Hebeda Konnie , Anagnostopoulos Ioannis , Krenács László , Bedekovics Judit
Published: March 2015

Aims

Myelofibrosis is the result of aberrant stromal activity which is determined routinely by reticulin staining in bone marrow biopsies. As matrix fibres are the product of activated fibroblasts, we analysed fibre accumulation compared to stromal cell activity during myelofibrosis progression using the fibroblast activation marker platelet‐derived growth factor receptor β (PDGFRβ) by immunohistochemistry.

Methods and results

Initial and follow‐up bone marrow biopsies from 84 patients with myeloproliferative neoplasia, including 55 cases with primary myelofibrosis, were evaluated from five haematopathology centres. The stromal mass was measured by conventional reticulin staining [myelofibrosis (MF) grade, 0–3] and PDGFRβ‐positive cells using a novel PDGFRβ scoring system (0–3). Results were correlated for prediction of progression. The MF grade and the PDGFRβ score showed excellent correlation (Spearman's r = 0.83, P < 0.0001). Elevated PDGFRβ scores (higher than MF‐grade) predicted myelofibrosis progression in total with 43% sensitivity and 57% specificity, and short‐term (within 1 year) progression with 82% sensitivity and 53% specificity. Progression of prefibrotic disease to manifest myelofibrosis could be forecast with 90% sensitivity and 75% specificity.

Conclusion

PDGFRβ highlights stromal cell activation in marrow fibrosis, which is closely related to matrix accumulation, indicating a direct clinical impact especially in prefibrotic myeloproliferative disorders.