bluuebunny/crossref_metadata_2025 huggingface dataset:
Transsexualism
Authors: Gooren Louis J. G.
Published: July 2011

Transsexualism is the condition in which a person with apparently normal somatic sexual differentiation is convinced that he/she is actually a member of the opposite sex. It is associated with an irresistible urge to be hormonally and surgically adapted to that sex. Traditionally transsexualism has been conceptualized as a purely psychological phenomenon, but research on the brains of male-to-female transsexuals has found that the sexual differentiation of the brain—the bed nucleus of the stria terminalis (BSTC) and the hypothalamic uncinate nucleus—had followed a female pattern (1). This finding may lead to a concept of transsexualism as a form of intersex, where the sexual differentiation of the brain (which in mammals also undergoes sexual differentiation) is not consistent with the other variables of sex, such as chromosomal pattern, nature of the gonad and nature of internal/external genitalia. Thus it can be argued that transsexualism is a sexual differentiation disorder.
Androgen misuse and abuse
Authors: Handelsman David J.
Published: July 2011

The Nobel prize-winning identification of testosterone as the mammalian male sex hormone in 1935 was the culmination of an ancient pursuit to learn how the testis was responsible for masculine virility and superior muscular strength. Within two years, testosterone was being used clinically, and within a decade much of the clinical pharmacology and many applications were recognised (1, 2). Given its weighty historical legacy as the archetypal virilizing substance, testosterone was soon being evaluated to boost pharmacologically the muscular size and strength of healthy men beyond physiological development. In the years following the Second World War, the pharmaceutical industry undertook an extensive quest to identify an ‘anabolic steroid’, an androgen without virilizing properties. Although this proved futile, with the search abandoned, the now meaningless term ‘anabolic steroid’, perpetuating a distinction without a difference, has persisted long beyond its scientific obsolescence largely as a journalistic device for sensationalism and demonization (3). Systematic androgen abuse first appears an epidemic, with an epicentre among Eastern European elite athletes, in the mid 1950s (4). This timing coincided with the golden age of steroid pharmacology in the postwar pharmaceutical industry boom years, which produced the oral contraceptive and synthetic glucocorticoids, and with the early years of the Cold War. This fortuitous intersection of industrial means, unscrupulous operators, and political goals shaped the emergence of systematic androgen abuse as a convenient tool by which sociopolitically dysfunctional Eastern bloc countries could gain short-cut ascendancy through symbolic victories over Western political rivals, a challenge quickly reciprocated by athletes and trainers from the advanced noncommunist countries. This bidding war escalated into national sports doping programs operated covertly by Eastern European communist governments. These organized programs of unscrupulous cheating mixed competitive fraudulence with callous ruination of their athletes’ welfare for national political goals. Of these, only the East German program, with its dire consequences for athletes’ health, has so far been fully disclosed (5). Over the next 4 decades, androgen abuse became endemic in countries where the population is sufficiently affluent to support this consumer variant of drug abuse. Once entrenched in the community, androgen abuse spreads beyond elite sports, where it remains as a low level endemic, to nonsporting users with recreational, cosmetic, and occupational motivations for body-building, such as seeking to promote a fearsome muscular image (6).
Male reproductive health
Authors: Gooren Louis J. G.
Published: July 2011

Life expectancy is on average 7 years shorter for men than for women; from birth through senescence, death rates are higher for males than for females (1). Potentially contributing factors are male risk-taking behaviour (accidents, homicide, smoking, alcoholism, high professional and social achievement), less use of medical care, and possibly genetic and endocrine factors. This chapter will address the potential role of sex steroids in the sex disparity in morbidity and mortality. Male and female, and androgens and oestrogens, are usually considered as being antithetical, and sex differences are usually stressed while similarities receive much less attention. However, in both sexes the decline of sex steroid production in old age is associated with osteopenia. and also with an increase in cardiovascular disease. Moreover, the pathophysiology of breast and prostate cancer might show parallels. In reproductive medicine, advances in scientific knowledge and health care have been greater in women than in men. Strategies successful for women might be utilized to promote the health of (ageing) men. It is unfortunate that sex steroids, and particularly androgens, are often perceived as potentially harmful substances rather than being valued for their potentially beneficial actions. Concerning the difference in life expectancy between men and women, an historical comparison between castrati and intact singers in the 15th to 19th centuries demonstrated that both castrati and intact singers at that time had the same life expectancy of around 64 years; this indicates that testosterone deprivation shortly before puberty did not influence longevity. More recent studies show that sociological, lifestyle and professional factors may be of more importance (2).
Molecular genetics and biochemistry of N-acetyltaurine degradation by Cupriavidus necator H16
Authors: Denger Karin , Lehmann Sabine , Cook Alasdair M.
Published: July 2011

Cupriavidus necator H16 (DSM 428), whose genome has been sequenced, was found to degrade N-acetyltaurine as a sole source of carbon and energy for growth. Utilization of the compound was quantitative. The degradative pathway involved an inducible N-acetyltaurine amidohydrolase (NaaS), which catalysed the cleavage of N-acetyltaurine to acetate and taurine. The degradation of the latter compound is via an inducible, degradative pathway that involves taurine dehydrogenase [EC 1.4.2.–], sulfoacetaldehyde acetyltransferase [EC 2.3.3.15], phosphotransacetylase [EC 2.4.1.8], a sulfite exporter [TC 9.A.29.2.1] and sulfite dehydrogenase [EC 1.8.2.1]. Induction of the expression of representative gene products, encoded by at least four gene clusters, was confirmed biochemically. The acetate released by NaaS was activated to acetyl-CoA by an inducible acetate–CoA ligase [EC 6.2.1.1]. NaaS was purified to homogeneity; it had a K
m value of 9.4 mM for N-acetyltaurine, and it contained tightly bound Zn and Fe atoms. The denatured enzyme has a molecular mass of about 61 kDa (determined by SDS-PAGE) and the native enzyme was apparently monomeric. Peptide-mass fingerprinting identified the locus tag as H16_B0868 in a five-gene cluster, naaROPST (H16_B0865–H16_B0869). The cluster presumably encodes a LysR-type transcriptional regulator (NaaR), a membrane protein (NaaO), a solute : sodium symporter-family permease [TC 2.A.21] (NaaP), the metal-dependent amidohydrolase (NaaS) and a putative metallochaperone (COG0523) (NaaT). Reverse-transcription PCR indicated that naaOPST were inducibly transcribed.
CopR of Sulfolobus solfataricus represents a novel class of archaeal-specific copper-responsive activators of transcription
Authors: Villafane Aramis , Voskoboynik Yekaterina , Ruhl Ilona , Sannino David , Maezato Yukari , Blum Paul , Bini Elisabetta
Published: July 2011

In trace amounts, copper is essential for the function of key enzymes in prokaryotes and eukaryotes. Organisms have developed sophisticated mechanisms to control the cytosolic level of the metal, manage its toxicity and survive in copper-rich environments. Here we show that theSulfolobusCopR represents a novel class of copper-responsive regulators, unique to the archaeal domain. Furthermore, by disruption of the ORF Sso2652 (copR) of theSulfolobussolfataricusgenome, we demonstrate that the gene encodes a transcriptional activator of the copper-transporting ATPase CopA gene and co-transcribedcopT, encoding a putative copper-binding protein. Disruption resulted in a loss of copper tolerance in twocopR-knockout mutants, while metals such as zinc, cadmium and chromium did not affect their growth. Copper sensitivity in the mutant was linked to insufficient levels of expression of CopA and CopT. The findings were further supported by time-course inductively coupled plasma optical emission spectrometry measurements, whereby continued accumulation of copper in theS. solfataricusmutant was observed. In contrast, copper accumulation in the wild-type stabilized after reaching approximately 6 pg (µg total protein)–1. Complementation of the disrupted mutant with a wild-type copy of thecopRgene restored the wild-type phenotype with respect to the physiological and transcriptional response to copper. These observations, taken together, lead us to propose that CopR is an activator ofcopTandcopAtranscription, and the member of a novel class of copper-responsive regulators.
Post-transcription initiation function of the ubiquitous SAGA complex in tissue-specific gene activation
Authors: Weake Vikki M. , Dyer Jamie O. , Seidel Christopher , Box Andrew , Swanson Selene K. , Peak Allison , Florens Laurence , Washburn Michael P. , Abmayr Susan M. , Workman Jerry L.
Published: July 2011

The Spt–Ada–Gcn5–acetyltransferase (SAGA) complex was discovered from Saccharomyces cerevisiae and has been well characterized as an important transcriptional coactivator that interacts both with sequence-specific transcription factors and the TATA-binding protein TBP. SAGA contains a histone acetyltransferase and a ubiquitin protease. In metazoans, SAGA is essential for development, yet little is known about the function of SAGA in differentiating tissue. We analyzed the composition, interacting proteins, and genomic distribution of SAGA in muscle and neuronal tissue of late stage Drosophila melanogaster embryos. The subunit composition of SAGA was the same in each tissue; however, SAGA was associated with considerably more transcription factors in muscle compared with neurons. Consistent with this finding, SAGA was found to occupy more genes specifically in muscle than in neurons. Strikingly, SAGA occupancy was not limited to enhancers and promoters but primarily colocalized with RNA polymerase II within transcribed sequences. SAGA binding peaks at the site of RNA polymerase pausing at the 5′ end of transcribed sequences. In addition, many tissue-specific SAGA-bound genes required its ubiquitin protease activity for full expression. These data indicate that in metazoans SAGA plays a prominent post-transcription initiation role in tissue-specific gene expression.
A family of ParA-like ATPases promotes cell pole maturation by facilitating polar localization of chemotaxis proteins
Authors: Ringgaard Simon , Schirner Kathrin , Davis Brigid M. , Waldor Matthew K.
Published: July 2011

Stochastic processes are thought to mediate localization of membrane-associated chemotaxis signaling clusters in peritrichous bacteria. Here, we identified a new family of ParA-like ATPases (designated ParC [for partitioning chemotaxis]) encoded within chemotaxis operons of many polar-flagellated γ-proteobacteria that actively promote polar localization of chemotaxis proteins. In Vibrio cholerae, a single ParC focus is found at the flagellated old pole in newborn cells, and later bipolar ParC foci develop as the cell matures. The cell cycle-dependent redistribution of ParC occurs by its release from the old pole and subsequent relocalization at the new pole, consistent with a “diffusion and capture” model for ParC dynamics. Chemotaxis proteins encoded in the same cluster as ParC have a similar unipolar-to-bipolar transition; however, they reach the new pole after the arrival of ParC. Cells lacking ParC exhibit aberrantly localized foci of chemotaxis proteins, reduced chemotaxis, and altered motility, which likely accounts for their enhanced colonization of the proximal small intestine in an animal model of cholera. Collectively, our findings indicate that ParC promotes the efficiency of chemotactic signaling processes. In particular, ParC-facilitated development of a functional chemotaxis apparatus at the new pole readies this site for its development into a functional old pole after cell division.
Gene program-specific regulation of PGC-1α activity
Authors: Schmidt Søren F. , Mandrup Susanne
Published: July 2011

Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 α (PGC-1α) activation coordinates induction of the hepatic fasting response through coactivation of numerous transcription factors and gene programs. In the June 15, 2011, issue of Genes & Development, Lustig and colleagues (pp. 1232–1244) demonstrated that phosphorylation of PGC-1α by the p70 ribosomal protein S6 kinase 1 (S6K1) specifically interfered with the interaction between PGC-1α and HNF4α in liver and blocked the coactivation of the gluconeogenic target genes. This demonstrates how independent fine-tuning of gene programs coregulated by the same coactivator can be obtained.
Nitric oxide directly regulates gene expression during Drosophila development: need some gas to drive into metamorphosis?: Figure 1.
Authors: Yamanaka Naoki , O'Connor Michael B.
Published: July 2011

Nitric oxide (NO) is an important second messenger involved in numerous biological processes, but how it regulates gene expression is not well understood. In this issue of Genes & Development, Cáceres and colleagues (pp. 1476–1485) report a critical requirement of NO as a direct regulator of gene expression through its binding to a heme-containing nuclear receptor in Drosophila. This may be an anciently evolved mechanism to coordinate behavior and metabolism during animal development.
Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication
Authors: Heidel Andrew J. , Lawal Hajara M. , Felder Marius , Schilde Christina , Helps Nicholas R. , Tunggal Budi , Rivero Francisco , John Uwe , Schleicher Michael , Eichinger Ludwig , Platzer Matthias , Noegel Angelika A. , Schaap Pauline , Glöckner Gernot
Published: July 2011

Dictyosteliumdiscoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced the genomes of Dictyostelium fasciculatum (DF) and Polysphondylium pallidum (PP), which represent the early diverging groups 1 and 2, respectively. In contrast to DD, PP and DF have conventional telomere organization and strongly reduced numbers of transposable elements. The number of protein-coding genes is similar between species, but only half of them comprise an identifiable set of orthologous genes. In general, genes involved in primary metabolism, cytoskeletal functions and signal transduction are conserved, while genes involved in secondary metabolism, export, and signal perception underwent large differential gene family expansions. This most likely signifies involvement of the conserved set in core cell and developmental mechanisms, and of the diverged set in niche- and species-specific adaptations for defense and food, mate, and kin selection. Phylogenetic dating using a concatenated data set and extensive loss of synteny indicate that DF, PP, and DD split from their last common ancestor at least 0.6 billion years ago.
A national audit of pollen immunotherapy for children in the United Kingdom: patient selection and programme safety
Authors: Vance G. H. S. , Goldring S. , Warner J. O. , Cox H. , Sihra B. , Hughes S. , Gardner J. , North J. , Roberts G. , Proudfoot C. A. , Clarke A. , Luyt D. K. , Gillies D. , Fox A. T.
Published: July 2011

Background
Specific immunotherapy (SIT) is an effective treatment for grass and/or tree pollen‐induced severe allergic rhinoconjunctivitis. However, there are limited detailed data on the use of immunotherapy in children in the United Kingdom.

Objectives
We audited NHS paediatric practice against current national guidelines to evaluate patient selection, SIT modalities and adverse events (AEs).

Methods
Paediatricians offering pollen SIT were identified through the British Society of Allergy and Clinical Immunology Paediatric Allergy Group (BSACI‐PAG) and the database of SIT providers compiled for the Royal College of Physicians and Royal College of Pathologists 2010 joint working group. Standardized proformas were returned by 12 of 20 centres (60%), including 12 of 14 centres offering subcutaneous immunotherapy (SCIT) (85%).

Results
Three hundred and twenty‐three children, with mean age 11 years at initiation (69% boys), had undergone 528 SIT cycles (SCIT 31%) over 10 years. Fifty‐five percent of all patients had asthma. Among SCIT programmes 24.5% patients had perennial (± seasonal) asthma; 75.6% of asthmatics undertaking SCIT had treatments at BTS/SIGN step 2 or above. AEs occurred frequently (50.4% of all SIT cycles) but were mild. In sublingual immunotherapy (SLIT) treatment, local intraoral immediate reactions were most common (44.9% SLIT cycles), as compared with delayed reactions around the injection site in SCIT (28.3% SCIT cycles). An asthma diagnosis had no impact on the number of cycles with AEs, or the severity reported. Few cycles (2.9%) were discontinued as a result of AE(s).

Conclusions and Clinical Relevance
Pollen SIT is available across England, though small numbers of children are being treated. Current national guidelines to exclude asthmatic children in SIT programmes are not being adhered to by most specialist paediatric allergy centres. SCIT and SLIT has been well tolerated. Review of patient selection criteria is needed and may allow greater use of this therapeutic option in appropriate clinical settings.

Cite this as: G. H. S. Vance, S. Goldring, J. O. Warner, H. Cox, B. Sihra, S. Hughes, J. Gardner, J. North, G. Roberts, C. A. Proudfoot, A. Clarke, D. K. Luyt, D. Gillies and A. T. Fox, Clinical & Experimental Allergy, 2011 (41) 1313–1323.
Mechanisms of immunotherapy to aeroallergens
Authors: Shamji M. H. , Durham S. R.
Published: July 2011

Allergen immunotherapy is allergen‐specific, allergen dose‐ and time‐dependent and is associated with long‐term clinical and immunological tolerance that persists for years after discontinuation. Successful immunotherapy is accompanied by the suppression of numbers of T‐helper 2 (Th2) effector cells, eosinophils, basophils, c‐kit+mast cells and neutrophils infiltration in target organs, induction of IL‐10 and/or TGF‐β+Treg cells and increases in ‘protective’ non‐inflammatory blocking antibodies, particularly IgG4 and IgA2 subclasses with inhibitory activity. These events are accompanied by a reduction and/or a redirection of underlying antigen‐specific Th2‐type T cell‐driven hypersensitivity to the allergen(s) used for therapy. This suppression occurs within weeks or months as a consequence of the appearance of a population of regulatory T cells that exert their effects by mechanisms involving cell–cell contact, but also by the release of cytokines such as IL‐10 (increases IgG4) and TGF‐β (increases specific IgA). The more delayed‐in‐time appearance of antigen‐specific T‐helper 1 responses and alternative mechanisms such as Th2 cell anergy and/or apoptosis may also be involved. The mechanisms of sublingual immunotherapy are similar to those following a subcutaneous administration of allergen, whereas it is likely that additional events following antigen presentation in the sublingual mucosa and regional lymph nodes are involved. These insights have resulted in novel approaches and portend future biomarkers that may be surrogate or predictive of the clinical response to treatment.

Cite this as: M. H. Shamji and S. R. Durham, Clinical & Experimental Allergy, 2011 (41) 1235–1246.
The NLRP3 inflammasome in health and disease: the good, the bad and the ugly
Authors: Menu P , Vince J E
Published: July 2011

While interleukin (IL)-1β plays an important role in combating the invading pathogen as part of the innate immune response, its dysregulation is responsible for a number of autoinflammatory disorders. Large IL-1β activating platforms, known as inflammasomes, can assemble in response to the detection of endogenous host and pathogen-associated danger molecules. Formation of these protein complexes results in the autocatalysis and activation of caspase-1, which processes precursor IL-1β into its secreted biologically active form. Inflammasome and IL-1β activity is required to efficiently control viral, bacterial and fungal pathogen infections. Conversely, excess IL-1β activity contributes to human disease, and its inhibition has proved therapeutically beneficial in the treatment of a spectrum of serious, yet relatively rare, heritable inflammasomopathies. Recently, inflammasome function has been implicated in more common human conditions, such as gout, type II diabetes and cancer. This raises the possibility that anti-IL-1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammasome activity.
Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus
Authors: Chen S , Akbar S M F , Abe M , Hiasa Y , Onji M
Published: July 2011

The immunosuppressive state of tumour-bearing hosts is attributable, at least in part, to myeloid-derived suppressor cells (MDSC). However, the role of MDSC in physiological conditions and diseases other than cancer has not been addressed. As the liver is a tolerogenic organ, the present study attempted to localize and assess functions of hepatic MDSC in a normal liver and in a murine model of chronic hepatitis B virus (HBV) infection. MDSC was identified in the liver of normal mice and HBV transgenic mice (TM) as CD11b+ Gr1+ cells by dual-colour flow cytometry. Highly purified populations of MDSC and their subtypes were isolated by fluorescence-activated cell sorting. The functions of MDSC and their subtypes were evaluated in allogenic mixed lymphocyte reaction (MLR) and hepatitis B surface antigen (HBsAg)-specific T cell proliferation assays. Normal mice-derived liver MDSC, but not other myeloid cells (CD11b+ Gr1−), suppressed T cell proliferation in allogenic MLR in a dose-dependent manner. Alteration of T cell antigens and impaired interferon-γ production seems to be related to MDSC-induced immunosuppression. In HBV TM, the frequencies of liver MDSC were about twice those of normal mice liver (13·6 ± 3·2% versus 6·05 ± 1·21%, n = 5, P < 0·05). Liver-derived MDSC from HBV TM also suppressed proliferative capacities of allogenic T cells and HBsAg-specific lymphocytes. Liver MDSC may have a critical role in maintaining homeostasis during physiological conditions. As liver MDSC had immunosuppressive functions in HBV TM, they may be a target of immune therapy in chronic HBV infection.
Listeria monocytogenes cell invasion: a new role for cofilin in co‐ordinating actin dynamics and membrane lipids
Authors: Bamburg James R.
Published: July 2011

Actin reorganization, mediated by the actin dynamizing protein cofilin, is essential for host cell invasion by the intracellular pathogenic bacterium Listeria monocytogenes. During invasion, the InlB bacterial surface ligands closely interact with host cell Met receptors to induce phagocytosis. In this issue of Molecular Microbiology, Han et al., 2011 clearly demonstrate that phospholipase D (PLD)‐dependent production of membrane phosphatidic acid is required for invasion. They further show that the phosphorylated form of cofilin, which is inactive in actin binding, is necessary for the activation of the PLD1 isoform. Although cofilin‐independent PLD2 can also mediate internalization, it is a phospho‐cofilin‐dependent balanced production of phosphatidic acid that is required for optimal Listeria internalization. Cofilin‐dependent membrane lipid remodelling has important implications for cofilin function that go well beyond its direct effects on actin.
Spanish nursing under Franco: reinvention, modernization and repression (1956–1976)
Authors: Miró Margalida , Gastaldo Denise , Nelson Sioban , Gallego Gloria
Published: July 2011

MIRÓ M, GASTALDO D, NELSON S and GALLEGO G. Nursing Inquiry 2012; 19: 270–280  Spanish nursing under Franco: reinvention, modernization and repression (1956–1976)

This article examines Spanish nursing during a critical 20‐year period (1956–76) when, under the dictatorial government of General Franco, nursing became the target of a modernization strategy. In the national standardized system of state‐run schools, the previously distinct nursing and midwifery programmes were merged into a new training programme which created the single professional denomination of ATS–Ayudante Técnico Sanitario (Technical Sanitary Assistant). Under the leadership of medicine, and with the blessing of the Catholic Church and the Sección Femenina (Women’s Section of the Falangist Party), nursing was positioned as feminized and subordinate to medicine, a predominantly male profession in mid‐twentieth century Spain. This article discusses this crucial phase of Spanish nursing history by focusing on one influential historical document (published in 1956), Professional Moral Orientation for the Sanitary Technical Assistants, a nursing textbook on professional morals for first‐year nursing students written by Rosamaria Miranda, a Catholic nun and a trained nurse. Our analysis reveals that gender‐related and technical discourses concerning disciplinary and pastoral power relations presented in this textbook legitimate the core beliefs of Franquism put forward by the politically powerful women’s branch of the ruling Falangist Party in mid‐twentieth century Spain.
Long‐distance geneflow and habitat specificity of the rock‐dwelling coppertail skink, Ctenotus taeniolatus
Authors: DENNISON SIOBHAN , SMITH SHANNON M. , STOW ADAM J.
Published: July 2011

Rock boulders or ‘bush‐rocks’ provide essential habitat for many organisms and there has been interest in rehabilitating areas denuded of rock with artificial substitutes. We examine whether the density and size of bush rock influences the density of the coppertail skink (Ctenotus taeniolatus). The success of habitat rehabilitation is contingent on dispersal of rock‐dwelling organisms into areas that have been remediated. To gauge the likelihood of this we characterize geneflow of coppertail skinks among discrete patches of rocky habitat associated with ridge tops. We genotyped 154 individuals from seven localities at six microsatellite DNA loci and from a subset of these individuals we obtained sequence data from the mitochondrial ND4 region. Our field survey established that lizard density was positively associated with the availability of suitably sized bush‐rock (P < 0.001), highlighting the importance of maintaining this habitat element, or replacing it where it has been lost. Despite the presence of habitat features that might be presumed as barriers to dispersal for coppertail skinks, such as intervening gullies and dense vegetation, our genetic data demonstrated high levels of geneflow among rocky ridge tops. Levels of partitioning estimated by global FST were significant but low for both microsatellite (FST = 0.020) and mitochondrial data (FST = 0.113). Spatial autocorrelation of genotypic similarity supports our conclusion of regular longer‐distance geneflow, and we infer lower levels of dispersal in juveniles than in adults. This study suggests that dispersal of coppertail skinks can be sufficient to naturally colonize areas of restored habitat.
Role of biodiversity in integrated fruit production in eastern North American orchards
Authors: Brown Mark W.
Published: July 2011

Diversifying agricultural ecosystems to enhance biological control is a promising way of promoting sustainable pest management.

In the present study, monoculture apple and peach with standard insecticide treatments were compared with three biodiverse treatments (polyculure, monoculture with companion plants and polyculture with companion plants) with reduced standard insecticide use.

Abundance of insect predators was increased by both the presence of companion plants and extrafloral nectar but parasitism of the leafroller Platynota idaeusalis was not affected.

There were no consistent effects of biodiversity treatment on either tree growth or fruit yield. Insect injury to Empire apple and peach fruit was not consistently affected by the biodiversity treatments. Granny Smith apples were harvested later than Empire and had more fruit injury in the biodiverse treatments than the standard insecticide control.

A reduction in pesticides with added biodiversity proved to be a viable alternative to standard chemical insecticide management for temperate tree fruit. Increases in the natural control of pests resulting from increased plant diversity has promise for reducing the reliance on chemical insecticides for pest suppression.
Long‐term results of permanent urethral stent Memotherm implantation in the management of recurrent bulbar urethral stenosis
Authors: Sertcelik Memduh N. , Bozkurt Ibrahim H. , Yalcinkaya Fatih , Zengin Kursad
Published: July 2011

Study Type – Therapy (case series) Level of Evidence 4

What’s known on the subject? and What does the study add?

Milroy reported 84% success at a mean of 4.5 years follow‐up by usage of a permanently implantable “urolume” spent in 1993. Memotherm was developed later, especially for urologic use. Our study is one of the largest in this urea, with a high number of patients and a long follow‐up period.

OBJECTIVE

• To evaluate the effectiveness and long‐term results of permanent urethral stent (Memotherm) implantation in the treatment of recurrent bulbar urethral stricture.

PATIENTS AND METHODS

• In all, 47 patients with a history of previous unsuccessful treatment for bulbar urethral stricture were treated using Memotherm bulbar urethral stents between 1998 and 2002.

• Long‐term follow‐up data was analysed and discussed.

RESULTS

• At the end of the 7‐year period 37 of 47 patients (78.7%) had been treated successfully.

• Post‐micturition dribbling incontinence lasting up to 3 months after stent placement occurred in 32 (68.1%) patients, but this was reduced to only seven patients (14.9%) by the 7‐year follow‐up.

• There was stress incontinence of various severities in nine (19.2%) patients at the 1‐year follow‐up. These patients were those who had stenosed urethral segments adjacent to the external sphincter. At the long‐term follow‐up <10% of the patients had stress incontinence complaints.

CONCLUSION

• Memotherm is a good treatment option in patients with recurrent bulbar urethral stricture of any cause.
Combined p53 and MDM2 biomarker analysis shows a unique pattern of expression associated with poor prognosis in patients with renal cell carcinoma undergoing radical nephrectomy
Authors: Noon Aidan P. , Polański Radosław , El‐Fert Ashraf Y. , Kalirai Helen , Shawki Howida , Campbell Fiona , Dodson Andy , Eccles Richard M. , Lloyd Bryony H. , Sibson David R. , Coupland Sarah E. , Lake Sarah L. , Parsons Keith , Vlatković Nikolina , Boyd Mark T.
Published: July 2011

What's known on the subject? and What does the study add?

Unlike most other cancers mutations of the p53 gene (TP53), typically indicated by increased p53 expression, are rare in renal cell carcinomas (RCC) and there is no evidence that mutation of TP53 is associated with outcome or treatment response. However, whilst TP53 mutations are not linked with outcome, p53 expression is as we show here.

Our study is the first to demonstrate simultaneously that patients with increased p53 expression (significantly associated with MDM2 expression), have reduced disease specific survival even though the expressed p53 is rarely mutated.

We therefore identify increased expression of wild‐type p53 and MDM2 in RCC as targets for future therapeutic approaches.

OBJECTIVE

To resolve much debated issues surrounding p53 function, expression and mutation in renal cell carcinoma (RCC), we performed the first study to simultaneously determine p53/MDM2 expression, TP53 mutational status (in p53‐positive patients) and outcome in RCC.

PATIENTS AND METHODS

In total, 90 specimens obtained from patients with RCC, who were treated by radical nephrectomy, were analyzed by immunohistochemistry for p53 and MDM2 on a tissue microarray, and p53 was functionally and genetically analyzed in p53 positive samples.

Outcome analysis was by the Kaplan–Meier method and univariate analysis was used to identify variables for subsequent multivariate analysis of correlations between clinical parameters and biomarker expression.

RESULTS

Up‐regulation of p53 in RCC is strongly linked with MDM2 up‐regulation (P < 0.001).

Increased coexpression of p53 and MDM2 identifies those patients with a significantly reduced disease‐specific survival by univariate (P= 0.036) and Cox multiple regression analysis (P= 0.027; relative risk, 3.20).

Functional (i.e. functional analysis of separated alleles in yeast) and genetic analysis of tumours with increased p53 expression shows that most patients (86%) retain wild‐type p53.

CONCLUSIONS

Coexpression of p53/MDM2 identifies a subset of patients with poor prognosis, despite all of them having organ‐confined disease.

Up‐regulated p53 is typically wild‐type and thus provides a mechanistic explanation for the association between p53 and MDM2 expression: up‐regulated wild‐type p53 likely promotes the observed MDM2 coexpression.

The results obtained in the present study suggest that the p53 pathway is altered in a tissue/disease‐specific manner and that therapeutic strategies targeting this pathway should be investigated to determine whether the tumour suppressive function of p53 can be rescued in RCC.
Characterizing homologues of crop domestication genes in poorly described wild relatives by high‐throughput sequencing of whole genomes
Authors: Malory Sylvia , Shapter Frances M. , Elphinstone Martin S. , Chivers Ian H. , Henry Robert J.
Published: July 2011

Wild crop relatives represent a source of novel alleles for crop genetic improvement. Screening biodiversity for useful or diverse gene homologues has often been based upon the amplification of targeted genes using available sequence information to design primers that amplify the target gene region across species. The crucial requirement of this approach is the presence of sequences with sufficient conservation across species to allow for the design of universal primers. This approach is often not successful with diverse organisms or highly variable genes. Massively parallel sequencing (MPS) can quickly produce large amounts of sequence data and provides a viable option for characterizing homologues of known genes in poorly described genomes. MPS of genomic DNA was used to obtain species‐specific sequence information for 18 rice genes related to domestication characteristics in a wild relative of rice, Microlaena stipoides. Species‐specific primers were available for 16 genes compared with 12 genes using the universal primer method. The use of species‐specific primers had the potential to cover 92% of the sequence of these genes, while traditional universal primers could only be designed to cover 80%. A total of 24 species‐specific primer pairs were used to amplify gene homologues, and 11 primer pairs were successful in capturing six gene homologues. The 23 million, 36‐base pair (bp) paired end reads, equated to an average of 2X genome coverage, facilitated the successful amplification and sequencing of six target gene homologues, illustrating an important approach to the discovery of useful genes in wild crop relatives.
Onset‐Nucleus Sharing and the Acquisition of Second Language Codas: A Stochastic Optimality Theoretic Account*
Authors: Cardoso Walcir
Published: July 2011

Abstract. The study provides a stochastic optimality theoretic account for the acquisition of word‐final voiceless stops (codas) in the developing grammar of Brazilian Portuguese (BP) speakers learning English as a second language (L2). Following a variationist methodology for data collection and analysis of learner speech, the study focuses on Onset‐Nucleus Sharing (ONS), a developmental phenomenon found in intermediate stages of L2 acquisition, phonetically manifested as aspiration. This phonetic behavior is interpreted to be an instantiation of ONS, wherein the potential coda syllabifies as an onset and, in order to be licensed, some of its features spread (via aspiration) into the following empty nucleus in order to optimize the syllable shape of the emerging grammar.
BODIES, BURIALS AND AGEING: ACCESSING THE TEMPORALITY OF OLD AGE IN PREHISTORIC SOCIETIES
Authors: APPLEBY J.E.P.
Published: July 2011

There has been little attempt within archaeology to understand the social meanings specifically attached to old age, or the implications of the social construction of old age for the reconstruction of prehistoric social formations. This stems partly from the low social value placed upon the elderly in modern societies, which makes us tend to view them as irrelevant, and partly from the difficulty of accurately ageing the skeletons of older individuals, which can make them appear invisible in the archaeological record.

A case study from the Traisental of Lower Austria is used to illustrate how the changing meanings of old age are recoverable from archaeological cemetery assemblages. Analysis of material culture patterning is combined with assessment of different forms of bodily degeneration to identify changes over time in the way that old age was socially recognized and the possibility that different kinds of bodily infirmity had very different social implications.
EPISCOPAL GROUPS IN HISPANIA
Authors: GURT I ESPARRAGUERA JOSEP M. , RAMOS ISABEL SÁNCHEZ
Published: July 2011

This study considers the most important Christian architectural complex in the Late Antique city, which at the same time came to be seen as a fundamental point of reference for the ecclesiastical structure of the surrounding territory. Taking the current state of research on episcopal groups in Hispania as its starting point, this paper aims to reach a series of conclusions as regards their location, spatial evolution and the total area they occupied, as well as their internal distribution. In addition, the continuing difficulties involved in archaeologically defining the presence of these religious complexes in the majority of episcopal sees created in Hispania during this period are discussed.
Political objectives and privatization decisions
Authors: Szentpéteri Ádám , Telegdy Álmos
Published: July 2011

In early Romanian privatization a group of firms was explicitly banned from privatization. We use this institutional feature to test which factors contributed to the selection of firms for long‐term state ownership, and find that politicians sheltered from privatization large and inefficient firms which paid low wages and had high overdue payments. These results are consistent with minimization of employment losses, even if efficiency enhancement of privatization had to be sacrificed. We conjecture that the unfavourable economic conditions bringing large employment losses motivated Romanian politicians to fear the possible negative employment effects of privatization.
Vocabulary size and depth of word knowledge in adult‐onset second language acquisition
Authors: Hellman Andrea B.
Published: July 2011

This study investigated whether adult‐onset second language (L2) learners achieve native level vocabulary after decades of immersion. Vocabulary tests were given to three groups of participants: highly successful adult‐onset learners of English, monolingual English speakers, and bilingual native speakers of English. Overall, the native speakers outperformed the non‐native speakers; however, the rate of native like achievement was remarkably high among the successful adult‐onset learners, which indicated that native level L2 vocabulary size and depth of word knowledge were attainable in adulthood. Factors that correlated with native level L2 vocabulary were: childhood caregivers' education, verbal ability and literacy in the native language, and interest in word learning and daily reading. The findings suggest that the lexicon may be the potentially most successful area of adult‐onset L2 learning.

Olyan felnőttkori angol nyelvtanulók szókincsét vizsgáltuk, akik több évtizedig amerikai angol nyelvterületen tartózkodtak és az angol nyelvet sikeresen elsajátították. A felnőttkori angol nyelvtanulókat két kontroll csoporttal hasonlítottuk össze szókincsfelmérő tetszek alapján: egy nyelven beszélő amerikai angol anyanyelvűekkel és több nyelven beszélő amerikai angol anyanyelvűekkel. Mindent összevetve, az angol anyanyelvű kontroll csoportok magasabb eredményt értek el. Ennek ellenére meglepően magas volt a sikeres felnőttkori nyelvtanuló mintacsoportban azoknak az aránya, akik anyanyelvi szintű angol szókincset értek el, ami arra utal, hogy egy idegennyelv szókincse felnőttkorban is elsajátítható anyanyelvi szinten. Regressziópróba három összetett faktort hozott statisztikai összefüggésbe az anyanyelvi szintű idegennyelvi szókinccsel azoknak a felnőttkori nyelvtanulóknak a körében, akik több évtizedig nyelvterületen tartózkodtak: (1) szüleik/nevelőik iskolai végzettsége, (2) magyar anyanyelvi kézségük és írás‐olvasás tudásszintjük, (3) érdeklődésük a szókincsfejlesztés és a mindennapi olvasás iránt. Az eredmény azt jelzi, hogy a szókincs nagysága és mélysége a felnőttkori nyelvelsajátítás potenciálisan legsikeresebb területe.
Grammar and meaning in early adult foreign language instruction
Authors: Scheffler Paweł
Published: July 2011

There are at present two general views on implementing second/foreign language instruction. First, we can start from meaning and communication, assuming that grammar will ‘take care of itself’ with only a little help from the teacher. Second, we can start from grammar, assuming that communicative ability will follow from subsequent practice. The present article examines the key arguments for the meaning‐first approach and two specific proposals for its implementation. It is then argued that such an approach is not appropriate for adult foreign language instruction, in which grammar should be taught and practised systematically from the initial stages of the process.

Istnieją obecnie dwa poglądy na realizację nauczania języka obcego/drugiego. Po pierwsze, możemy rozpocząć proces nauczania od komunikacji i nacisku na znaczenie form językowych, przyjmując, że kompetencja gramatyczna wykształci się sama z niewielką pomocą nauczyciela. Po drugie, możemy rozpocząć od nauczania gramatyki, zakładając, że umiejętność komunikacji będzie konsekwencjąćwiczeń komunikacyjnych. Niniejszy artykuł omawia główne argumenty za pierwszym z wymienionych podejść i dwa modele jego realizacji. Następnie autor przedstawia argumenty, według których podejście to nie jest odpowiednie dla dorosłych uczących się języka obcego. W takim przypadku, gramatyka powinna być nauczana systematycznie od początkowego etapu nauki.
Language policy mistakes in Singapore: Governance, expertise and the deliberation of language ideologies
Authors: Wee Lionel
Published: July 2011

An admission of a language policy mistake from the Singapore government is a rare occurrence. In recent years, there have been two such admissions. This paper discusses these policy mistakes, and focuses on the contributions that language experts might be able to make to the process of policy construction. It is argued that language experts should not be restricted in their ability to contribute to the process of policy formulation, particularly if deeply entrenched ideologies about language are to be subjected to careful scrutiny. The paper concludes by considering deliberative polls, which provide one practical design where experts and non‐experts can engage in an informed discussion about specific policy recommendations.
Provision of Fluoride Varnish to Medicaid‐Enrolled Children by Physicians: The Massachusetts Experience
Authors: Isong Inyang A. , Silk Hugh , Rao Sowmya R. , Perrin James M. , Savageau Judith A. , Donelan Karen
Published: July 2011

Objectives. To evaluate the impact of a 2008 Medicaid policy in Massachusetts (MA), regarding reimbursing physicians for providing fluoride varnish (FV) to eligible children in medical settings.

Data Source. Survey of a sample of primary care physicians in MA.

Study Design. Cross‐sectional survey of a sample of physicians who provide care to MassHealth (MA Medicaid) enrolled‐children. Dependent variables: history of completed preventive dental skills training, and FV provision. Independent variables: oral health knowledge, FV‐attitudes, and physician and practice characteristics.

Principal Findings. Overall, 19 percent of respondents had completed the training required to be eligible to bill for FV provision. Only 5 percent of physicians were providing FV. Most respondents (63 percent) were not familiar with the new policy, and only 25 percent felt that FV should be provided during well‐child visits. Most physicians (60 percent) did not feel that the reimbursement rate of U.S.$26/application was sufficient; 17 percent said that they would not provide FV, regardless of payment. Most common barriers to FV provision were a lack of time and logistical challenges.

Conclusions. Our findings suggest that simply reimbursing physicians for FV provision is insufficient to ensure provider participation. Success of this policy will likely require addressing several barriers identified.
Health Systems' Responsiveness and Its Characteristics: A Cross‐Country Comparative Analysis
Authors: Robone Silvana , Rice Nigel , Smith Peter C.
Published: July 2011

Objectives. Responsiveness has been identified as one of the intrinsic goals of health care systems. Little is known, however, about its determinants. Our objective is to investigate the potential country‐level drivers of health system responsiveness.

Data Source. Data on responsiveness are taken from the World Health Survey. Information on country‐level characteristics is obtained from a variety of sources including the United Nations Development Program (UNDP).

Study Design. A two‐step procedure. First, using survey data we derive a country‐level measure of system responsiveness purged of differences in individual reporting behavior. Secondly, we run cross‐sectional country‐level regressions of responsiveness on potential drivers.

Principal Findings. Health care expenditures per capita are positively associated with responsiveness, after controlling for the influence of potential confounding factors. Aspects of responsiveness are also associated with public sector spending (negatively) and educational development (positively).

Conclusions. From a policy perspective, improvements in responsiveness may require higher spending levels. The expansion of nonpublic sector provision, perhaps in the form of increased patient choice, may also serve to improve responsiveness. However, these inferences are tentative and require further study.