bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Immigration Legislation
Authors: Reimers David
Published: August 2014

Racism and economics account for the first laws directed at Chinese and Japanese. Entering as “picture brides,” Japanese women evaded the Gentlemen’s Agreement of 1907-1908 between the United States and Japan, but by use of the naturalization qualifications in the 1920s, Congress effectively closed the door to Asian immigration. For southern and eastern Europeans, national-origin quotas of the same decade cut their immigration drastically. After 1945, Congress and U.S. presidents relaxed the tight restrictions, and, in 1965, Congress passed the Hart-Celler Act, which created a new and more liberal system that stressed family unification. Major issues in recent years have concerned terrorism and undocumented immigration. Throughout this period, the results of the laws were often unintended, largely because the flow of immediate family members and chain migration were unseen.
Race and U.S. Panethnic Formation
Authors: Espiritu Yen Le
Published: August 2014

Panethnicity refers to the development of bridging organizations and the generalization of solidarity among subgroups that are racialized to be homogeneous by outsiders. This chapter argues that while the formation of a consolidated white identity in the United States is self-motivated and linked to white privilege, panethnicity for people of color is a product of racial categorization and bound up with power relations. As the influx of new immigrants transforms the demographic composition of existing groups such as Asian Americans and Latinos, group members face the challenge of bridging the class, ethnic, and generational chasms dividing the immigrants and the U.S.-born. In all, existing data confirm the plural and ambivalent nature of panethnicity: it is a highly contested terrain on which different groups merge and clash over terms of inclusion but also an effective site from which to forge alliances with other groups both within and across the U.S. borders.
Machine Bosses, Reformers, and the Politics of Ethnic and Minority Incorporation
Authors: Erie Steven P. , Kogan Vladimir
Published: August 2014

Throughout American history, political party organizations have served both as effective forces of political incorporation of newly arriving immigrants and as powerful barriers to fuller representation for minority groups. This chapter examines how urban political leaders and institutions have shaped the political emergence or suppression of ethnic groups from the Civil War era to the early twenty-first century. With particular focus on New York and Chicago, it critically reassesses the conventional paradigm of big-city party bosses as ethnic integrators fashioning and rewarding multiethnic “rainbow coalitions” and of political reformers as defenders of native-born Protestants.
Relationship and Sexual Functioning During Pregnancy and the Postpartum Period
Authors: Lachance-Grzela Mylène
Published: August 2014

There has been much debate among researchers in couple and family psychology on whether and how much the transition to parenthood affects partners’ conjugal life. This chapter provides a literature review aimed at determining what is currently known about relationship functioning and sexual functioning during pregnancy and the postpartum period. Most existing research on the subject reveals that the birth of a first child is associated with a decline in relationship satisfaction and sexual functioning. Recent data from prospective studies suggest that the transition from being a couple to being parents is actually associated with declines in relationship functioning over and above the normative declines reported by couples without children. This chapter examines the impact of individual, relational, and situational factors that have been proposed to explain this decline. Finally, the strengths and limitations of current research are discussed, and future research avenues are considered.
Patient Handoffs: Is Cross Cover or Night Shift Better?
Authors: Higgins Alanna , Brannen Melissa L. , Heiman Heather L. , Adler Mark D.
Published: August 2014

Objectives

Studies show singular handoffs between health care providers to be risky. Few describe sequential handoffs or compare handoffs from different provider types. We investigated the transfer of information across 2 handoffs using a piloted survey instrument. We compared cross-cover (every fourth night call) with dedicated night-shift residents.

Methods

Surveys assessing provider knowledge of hospitalized patients were administered to pediatric residents. Primary teams were surveyed about their handoff upon completion of daytime coverage of a patient. Night-shift or cross-covering residents were surveyed about their handoff of the same patient upon completion of overnight coverage. Pediatric hospitalists rated the consistency of information between the surveys. Absolute difference was calculated between the 2 providers' rating of a patient’s (a) complexity and (b) illness severity. Scores were compared across provider type.

Results

Fifty-nine complete handoff pairs were obtained. Fourteen and 45 handoff surveys were completed by a cross-covering and a night-shift provider, respectively. There was no significant difference in information consistency between primary and night-shift (median, 4.0; interquartile range [IQR], 3–4) versus primary and cross-covering providers (median, 4.0; IQR, 3–4). There was no significant difference in median patient complexity ratings (night shift, 3.0; IQR, 1–5, versus cross cover, 3.5; IQR, 1–5) or illness severity ratings (night shift, 2.0; IQR, 1–4, versus cross-cover, 3.0; IQR, 1–6) when comparing provider types giving a handoff.

Conclusions

We did not find a difference in physicians' transfer of information during 2 handoffs among providers taking traditional call or on night shift. Development of tools to measure handoff consistency is needed.
Racial and Ethnic Disparities in Patient Safety
Authors: Okoroh Juliet Siena , Uribe Erika Flores , Weingart Saul
Published: August 2014

Background

Although there is extensive evidence on disparities in the process and outcomes of health care, data on racial and ethnic disparities in patient safety remain inconclusive in the United States.

Objectives

The aims of this study were to (1) explore differences in reporting race/ethnicity in studies on disparities in patient safety; (2) assess adjustment for socioeconomic status, comorbidity, and disease severity; and (3) make recommendations on the inclusion of race/ethnicity for future studies on adverse events.

Methods

We searched PubMed database (for articles published from 1991 to May 1, 2013) using a predetermined criteria for studies on racial and ethnic disparities in patient safety. Only quantitative studies that used chart review or administrative data for the detection of adverse events were considered for eligibility. Two reviewers independently extracted data on inclusion of race/ethnicity in baseline characteristics and in stratification of outcomes.

Results

A total of 174 studies were initially obtained from the search. Of these, 24 met inclusion criteria and received full-text review. Meta-analysis was not performed because of the methodological and statistical heterogeneity between studies. Eight studies included race/ethnicity in baseline characteristics and adjusted for confounders. Hospital-level variations such teaching status and percentage of minorities served were infrequently analyzed.

Conclusions

To our knowledge, this is the first methodological review of racial/ethnic disparities in patient safety in the United States. The evidence on the existence of disparities in adverse events was mixed. Poor stratification of outcomes by race/ethnicity and consideration of geographic and hospital-level variations explain the inconclusive evidence; variations in the quality of care at hospitals should be considered in studies using national databases.
Determining asymptotically large population sizes in insect swarms
Authors: Puckett James G. , Ouellette Nicholas T.
Published: August 2014

Social animals commonly form aggregates that exhibit emergent collective behaviour, with group dynamics that are distinct from the behaviour of individuals. Simple models can qualitatively reproduce such behaviour, but only with large numbers of individuals. But how rapidly do the collective properties of animal aggregations in nature emerge with group size? Here, we study swarms of
Chironomus riparius
midges and measure how their statistical properties change as a function of the number of participating individuals. Once the swarms contain order 10 individuals, we find that all statistics saturate and the swarms enter an asymptotic regime. The influence of environmental cues on the swarm morphology decays on a similar scale. Our results provide a strong constraint on how rapidly swarm models must produce collective states. But our findings support the feasibility of using swarms as a design template for multi-agent systems, because self-organized states are possible even with few agents.
Effect of interfacial slippage on the near-tip fields of an interface crack between a soft elastomer and a rigid substrate
Authors: Lengyel T. H. , Long Rong , Schiavone P.
Published: August 2014

We consider the role of interfacial slippage in the deformation and stress fields near the tip of a plane interface crack occurring between a compressible hyperelastic material and a rigid substrate. Specifically, we draw comparisons between the two limiting cases of ‘no-slip’ (infinitely high friction) and ‘frictionless’ (zero friction) surfaces by performing corresponding asymptotic analyses in the crack-tip region. Our results indicate that for the no-slip case, when the body is subjected to far-field loading, the crack deforms to a wedge-like shape consistent with experimental observations reported in the literature. Moreover, in this case, the wedge angle is shown to be directly related to ratios of various Cauchy stress components on the bonded surface in the near-tip region. Finite-element simulations reveal that the wedge angle also depends on material compressibility and the far-field loading conditions. By contrast, the analysis of the frictionless case reveals that the crack consistently opens into a smooth parabolic shape with a right wedge angle and near-tip stress field dominated by the normal stress at the surface. The results established here can be used as a basis for the understanding of the role of varying degrees of slippage on interfacial cracks.
Hox gene duplications correlate with posterior heteronomy in scorpions
Authors: Sharma Prashant P. , Schwager Evelyn E. , Extavour Cassandra G. , Wheeler Ward C.
Published: August 2014

The evolutionary success of the largest animal phylum, Arthropoda, has been attributed to tagmatization, the coordinated evolution of adjacent metameres to form morphologically and functionally distinct segmental regions called tagmata. Specification of regional identity is regulated by the Hox genes, of which 10 are inferred to be present in the ancestor of arthropods. With six different posterior segmental identities divided into two tagmata, the bauplan of scorpions is the most heteronomous within Chelicerata. Expression domains of the anterior eight Hox genes are conserved in previously surveyed chelicerates, but it is unknown how Hox genes regionalize the three tagmata of scorpions. Here, we show that the scorpionCentruroides sculpturatushas two paralogues of all Hox genes exceptHox3, suggesting cluster and/or whole genome duplication in this arachnid order. Embryonic anterior expression domain boundaries of each of the last four pairs of Hox genes (two paralogues each ofAntp,Ubx,abd-AandAbd-B) are unique and distinguish segmental groups, such as pectines, book lungs and the characteristic tail, while maintaining spatial collinearity. These distinct expression domains suggest neofunctionalization of Hox gene paralogues subsequent to duplication. Our data reconcile previous understanding of Hox gene function across arthropods with the extreme heteronomy of scorpions.
Contrasting effects of large density changes on relative testes size in fluctuating populations of sympatric vole species
Authors: Klemme Ines , Soulsbury Carl D. , Henttonen Heikki
Published: August 2014

Across species, there is usually a positive relationship between sperm competition level and male reproductive effort on ejaculates, typically measured using relative testes size (RTS). Within populations, demographic and ecological processes may drastically alter the level of sperm competition and thus, potentially affect the evolution of testes size. Here, we use longitudinal records (across 38 years) from wild sympatric Fennoscandian populations of five species of voles to investigate whether RTS responds to natural fluctuations in population density, i.e. variation in sperm competition risk. We show that for some species RTS increases with density. However, our results also show that this relationship can be reversed in populations with large-scale between-year differences in density. Multiple mechanisms are suggested to explain the negative RTS–density relationship, including testes size response to density-dependent species interactions, an evolutionary response to sperm competition levels that is lagged when density fluctuations are over a certain threshold, or differing investment in pre- and post-copulatory competition at different densities. The results emphasize that our understanding of sperm competition in fluctuating environments is still very limited.
Lunar-forming impacts: processes and alternatives
Authors: Canup R. M.
Published: August 2014

The formation of a protolunar disc by a giant impact with the early Earth is discussed, focusing on two classes of impacts: (i) canonical impacts, in which a Mars-sized impactor produces a planet–disc system whose angular momentum is comparable to that in the current Earth and Moon, and (ii) high-angular-momentum impacts, which produce a system whose angular momentum is approximately a factor of 2 larger than that in the current Earth and Moon. In (i), the disc originates primarily from impactor-derived material and thus is expected to have an initial composition distinct from that of the Earth's mantle. In (ii), a hotter, more compact initial disc is produced with a silicate composition that can be nearly identical to that of the silicate Earth. Both scenarios require subsequent processes for consistency with the current Earth and Moon: disc–planet compositional equilibration in the case of (i), or large-scale angular momentum loss during capture of the newly formed Moon into the evection resonance with the Sun in the case of (ii).
Isotopes as tracers of the sources of the lunar material and processes of lunar origin
Authors: Pahlevan Kaveh
Published: August 2014

Ever since the Apollo programme, isotopic abundances have been used as tracers to study lunar formation, in particular to study the sources of the lunar material. In the past decade, increasingly precise isotopic data have been reported that give strong indications that the Moon and the Earth's mantle have a common heritage. To reconcile these observations with the origin of the Moon via the collision of two distinct planetary bodies, it has been proposed (i) that the Earth–Moon system underwent convective mixing into a single isotopic reservoir during the approximately 103year molten disc epoch after the giant impact but before lunar accretion, or (ii) that a high angular momentum impact injected a silicate disc into orbit sourced directly from the mantle of the proto-Earth and the impacting planet in the right proportions to match the isotopic observations. Recently, it has also become recognized that liquid–vapour fractionation in the energetic aftermath of the giant impact is capable of generating measurable mass-dependent isotopic offsets between the silicate Earth and Moon, rendering isotopic measurements sensitive not only to the sources of the lunar material, but also to the processes accompanying lunar origin. Here, we review the isotopic evidence that the silicate–Earth–Moon system represents a single planetary reservoir. We then discuss the development of new isotopic tracers sensitive to processes in the melt–vapour lunar disc and how theoretical calculations of their behaviour and sample observations can constrain scenarios of post-impact evolution in the earliest history of the Earth–Moon system.
Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli
Authors: Jovanovic Goran , Mehta Parul , Ying Liming , Buck Martin
Published: August 2014

All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that inEscherichia colithe low-order oligomeric PspA regulatory complex associates with cardiolipin-rich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization.
Monophasic expression of FliC by Salmonella 4,[5],12:i:- DT193 does not alter its pathogenicity during infection of porcine intestinal epithelial cells
Authors: Crayford Georgina , Coombes Janine L. , Humphrey Tom J. , Wigley Paul
Published: August 2014

Non-typhoidal serotypes ofSalmonella entericaremain important food-borne pathogens worldwide and the frequent emergence of epidemic strains in food-producing animals is a risk to public health. In recent years,Salmonella4,[5],12:i:- isolates, expressing only phase 1 (FliC) of the two flagellar antigens, have emerged and increased in prevalence worldwide. In Europe, the majority of 4,[5],12:i:- isolates belong to phage types DT193 and DT120 ofSalmonellaTyphimurium and pigs have been identified as the reservoir species. In this study we investigated the ability of pig-derived monophasic (4,[5],12:i:-) and biphasic DT193 isolates to invade a porcine intestinal epithelial cell line (IPEC-1) and activate TLR-5, IL-8 and caspases. We found that the 4,[5],12:i:- isolates exhibited comparable adhesion and invasion to that of the virulentS. Typhimurium isolate 4/74, suggesting that these strains could be capable of colonizing the small intestine of pigsin vivo. Infection with 4,[5],12:i:- and biphasic DT193 isolates resulted in approximately the same level of TLR-5 (a flagellin receptor) and IL-8 (a proinflammatory chemokine) mRNA upregulation. The monophasic variants also elicited similar levels of caspase activation and cytotoxicity to the phase-variable DT193 isolates. These findings suggest that failure of 4,[5],12:i:- DT193 isolates to express a second phase of flagellar antigen (FljB) is unlikely to hamper their pathogenicity during colonization of the porcine intestinal tract.
A codon model of nucleotide substitution with selection on synonymous codon usage
Authors: Kubatko Laura , Shah Premal , Herbei Radu , Gilchrist Michael A.
Published: August 2014

The quality of phylogenetic inference made from protein-coding genes depends, in part, on the realism with which the codon substitution process is modeled. Here we propose a new mechanistic model that combines the standard M0 substitution model of Yang (1997) with a simplified model from Gilchrist (2007) that includes selection on synonymous substitutions as a function of codon-specific nonsense error rates. We tested the newly proposed model by applying it to 104 protein-coding genes in brewer’s yeast, and compared the fit of the new model to the standard M0 model and to the mutation-selection model of Yang and Nielsen (2008) using the AIC. Our new model provided significantly better fit in approximately 85% of the cases considered for the basic M0 model and in approximately 25% of the cases for the M0 model with estimated codon frequencies, but only in a few cases when the mutation-selection model was considered. However, our model includes a parameter that can be interpreted as a measure of the rate of protein production, and the estimates of this parameter were highly correlated with an independent measure of protein production for the yeast genes considered here. Finally, we found that in some cases the new model led to the preference of a different phylogeny for a subset of the genes considered, indicating that substitution model choice may have an impact on the estimated phylogeny.
Pollen-Specific Activation of Arabidopsis Retrogenes Is Associated with Global Transcriptional Reprogramming
Authors: Abdelsamad Ahmed , Pecinka Ales
Published: August 2014

Duplications allow for gene functional diversification and accelerate genome evolution. Occasionally, the transposon amplification machinery reverse transcribes the mRNA of a gene, integrates it into the genome, and forms an RNA-duplicated copy: the retrogene. Although retrogenes have been found in plants, their biology and evolution are poorly understood. Here, we identified 251 (216 novel) retrogenes in Arabidopsis thaliana, corresponding to 1% of protein-coding genes. Arabidopsis retrogenes are derived from ubiquitously transcribed parents and reside in gene-rich chromosomal regions. Approximately 25% of retrogenes are cotranscribed with their parents and 3% with head-to-head oriented neighbors. This suggests transcription by novel promoters for 72% of Arabidopsis retrogenes. Many retrogenes reach their transcription maximum in pollen, the tissue analogous to animal spermatocytes, where upregulation of retrogenes has been found previously. This implies an evolutionarily conserved mechanism leading to this transcription pattern of RNA-duplicated genes. During transcriptional repression, retrogenes are depleted of permissive chromatin marks without an obvious enrichment for repressive modifications. However, this pattern is common to many other pollen-transcribed genes independent of their evolutionary origin. Hence, retroposition plays a role in plant genome evolution, and the developmental transcription pattern of retrogenes suggests an analogous regulation of RNA-duplicated genes in plants and animals.
Crystal structure of 7-bromo-4-oxo-4H-chromene-3-carbaldehyde
Authors: Ishikawa Yoshinobu
Published: August 2014

In the title compound, C10H5BrO3, a brominated 3-formylchromone derivative, all atoms are essentially coplanar (r.m.s. = 0.0631 Å for the non-H atoms), with the largest deviation from the least-squares plane [0.215 (3) Å] being for the formyl O atom. In the crystal, molecules are linked into tapes through C—H...O hydrogen bonds and these tapes are assembled by stacking interactions [centroid–centroid distance between the pyran rings = 3.858 (3) Å] to form supramolecular layers that stack along thecaxis.
Does dexmedetomidine have a cardiac protective effect during non‐cardiac surgery? A randomised controlled trial
Authors: Xu Lili , Hu Zhiyong , Shen Jianjun , McQuillan Patrick M
Published: August 2014

This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non‐cardiac surgery. This study was a prospective, randomized, double‐blind trial. Eighty patients having CHD were scheduled for elective hip‐replacement surgery and randomly allocated to receive a loading dose of 1 μg/kg dexmedetomidine followed by a 0.2 μg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, rate–pressure product and changes in ST‐T segment on the electrocardiogram were recorded every 5 min during surgery. Serum creatine kinase‐MB (CK‐MB), cardiac troponin I (cTnI), glycogen phosphorylase BB (GP‐BB), interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α protein levels were determined preoperatively, at the end of surgery and 12 and 24 h after surgery. The improvement rate of myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%, respectively; P < 0.05). In addition, the Dex group had lower serum CK‐MB, IL‐6, cTnI and GP‐BB concentrations than the control group (P < 0.05). There was no significance difference in TNF‐α between the two groups (P > 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non‐cardiac surgery.
How Do Land Takings Affect Political Trust in Rural China?
Authors: Cui Ernan , Tao Ran , Warner Travis J. , Yang Dali L.
Published: August 2014

While China's ruling Communist Party has benefited from a reservoir of political trust engendered by more than three decades of rapid economic growth, it is confronted with rising social tensions and the prospect of instability. The number of mass incidents, which is a key measure of instability, has risen enormously, and a major source of such incidents stems from local governments taking land from farmers, often at below-market prices. This article draws upon data from two surveys to assess the political trust implications of land takings. It is found that, as expected, land takings are associated with a decline in political trust. However, the decline affects trust in local authorities only and leaves the central government largely unscathed. Nonetheless, the gap between villagers' trust in central and local authorities is not unalloyed good news for the regime and has major implications for policy implementation and governance.
The ‘reach’ of employee participation in decision‐making: exploring theAristotelian roots of workplace democracy
Authors: Timming Andrew R.
Published: August 2014

This article examines the ‘reach’, or the distribution, of employee participation in decision‐making (PDM) within organisations. It makes a unique contribution to the wider employee voice literature by asking what types of employees have a ‘say’ in strategic decision‐making and, in similar vein, what types of employees are denied participation, and why. In order to answer this under‐investigated research question, the article presents anAristotelian analysis of the concept of citizenship in the ‘best regime’. In the light of this analysis, the article concludes that some groups of employees are excluded fromPDMon the basis of a perceived lack of ‘excellence’.
Effects of phylogenetic reconstruction method on the robustness of species delimitation using single‐locus data
Authors: Tang Cuong Q. , Humphreys Aelys M. , Fontaneto Diego , Barraclough Timothy G.
Published: August 2014

Coalescent‐based species delimitation methods combine population genetic and phylogenetic theory to provide an objective means for delineating evolutionarily significant units of diversity. The generalised mixed Yule coalescent (GMYC) and the Poisson tree process (PTP) are methods that use ultrametric (GMYC or PTP) or non‐ultrametric (PTP) gene trees as input, intended for use mostly with single‐locus data such as DNA barcodes.

Here, we assess how robust the GMYC and PTP are to different phylogenetic reconstruction and branch smoothing methods. We reconstruct over 400 ultrametric trees using up to 30 different combinations of phylogenetic and smoothing methods and perform over 2000 separate species delimitation analyses across 16 empirical data sets. We then assess how variable diversity estimates are, in terms of richness and identity, with respect to species delimitation, phylogenetic and smoothing methods.

The PTP method generally generates diversity estimates that are more robust to different phylogenetic methods. The GMYC is more sensitive, but provides consistent estimates for BEAST trees. The lower consistency of GMYC estimates is likely a result of differences among gene trees introduced by the smoothing step. Unresolved nodes (real anomalies or methodological artefacts) affect both GMYC and PTP estimates, but have a greater effect on GMYC estimates. Branch smoothing is a difficult step and perhaps an underappreciated source of bias that may be widespread among studies of diversity and diversification.

Nevertheless, careful choice of phylogenetic method does produce equivalent PTP and GMYC diversity estimates. We recommend simultaneous use of the PTP model with any model‐based gene tree (e.g. RAxML) and GMYC approaches with BEAST trees for obtaining species hypotheses.
Exome sequencing of three cases of familial exceptional longevity
Authors: Cash Timothy P. , Pita Guillermo , Domínguez Orlando , Alonso Maria R. , Moreno Leticia T. , Borrás Consuelo , Rodríguez‐Mañas Leocadio , Santiago Catalina , Garatachea Nuria , Lucia Alejandro , Avellana Juan A. , Viña Jose , González‐Neira Anna , Serrano Manuel
Published: August 2014

Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co‐segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long‐lived siblings (probands ≥ 103 years and at least one sibling ≥ 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function. Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Interestingly, APOB is a component of lipoprotein particles together with APOE, and variants in the genes encoding these two proteins have been previously associated with human longevity. Analysis of nonfamilial EL cases showed a trend, without reaching statistical significance, toward enrichment of APOB RFVs. We have also identified candidate longevity genes shared between two families (5–13) or within individual families (66–156 genes). Some of these genes have been previously linked to longevity in model organisms, such as PPARGC1A, NRG1, RAD52, RAD51, NCOR1, and ADCY5 genes. This work provides an initial catalog of genes that could contribute to exceptional familial longevity.
Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor vismodegib (GDC‐0449)
Authors: Meani Rowena E , Lim Shueh‐Wen , Chang Anne Lynn S , Kelly John W
Published: August 2014

Vismodegib (GDC‐0449, Genentech, USA), a small molecule inhibitor of the Hedgehog signalling pathway, has potent anti‐tumour activity in advanced basal cell carcinoma (BCC). We report a case of a 67‐year‐old Australian man with metastatic BCC including pulmonary disease with malignant effusion who showed a dramatic complete response to vismodegib but subsequently experienced a recurrence of pulmonary disease, indicative of chemoresistance to vismodegib. This case is the first to illustrate chemoresistance in a patient with metastatic BCC, and demonstrates the need for closely monitoring metastatic BCC patients even after an apparently complete response.
Perineal outcome and the risk of pelvic floor dysfunction: A cohort study of primiparous women
Authors: Rikard‐Bell Joan , Iyer Jay , Rane Ajay
Published: August 2014

Background

Pelvic floor dysfunction (PFD) is the most common complication of childbirth. Assumptions have been made that perineal trauma increases the risk of PFD compared to an intact perineum, however the evidence for this is lacking. The aim of this study was to explore the relationship between perineal outcome and postpartum PFD.

Materials and Methods

Prospective cohort study design, with a self‐reported quality of life (QOL) questionnaire mailed to all primiparous women with a non‐instrumental delivery at The Townsville Hospital between 2011 and 2012 (n = 766). ANOVA was used to compare how the symptoms of PFD affect QOL in women with an intact perineum, episiotomy or spontaneous tear.

Results

Seventy‐nine percent of the population had perineal injury; 60% had a spontaneous tear and 19% had an episiotomy. Ninety‐seven percent of women who completed the questionnaire (n = 196) complained of PFD symptoms. Women with episiotomy had the best QOL, reporting the lowest levels of urinary dysfunction (statistically significant). No differences between the groups were found for symptoms of bowel, prolapse or sexual dysfunction.

Conclusions

This study shows a relationship between perineal outcome and PFD and suggests that an episiotomy is associated with the least morbidity due to symptoms of urinary incontinence. Additional large‐scale prospective research is required to further investigate and delineate the impact of childbirth on PFD.
Globalising higher education in and through urban spaces: Higher education projects, international student mobilities and trans‐local connections in Seoul
Authors: Collins Francis
Published: August 2014

This paper explores the connections between universities and cities in a moment of heightened emphasis on international student mobilities and globalising processes in Asian higher education. In particular, I seek to draw attention to the contingent assembly of the urban and its role in globalising higher education by highlighting the ways in which urban spaces draw together different sorts of trans‐local connections and flows. To explore this approach, I discuss the globalisation of higher education in South Korea, and the significance of Seoul in these processes through a focus on two leading universities – Korea University and Seoul National University. To highlight the importance of trans‐local connections in the urban dimensions of higher education, I discuss the generation of desires to be mobile in imaginations of Seoul as a destination for higher education, student experiences of situated learning in place and the articulation of student mobilities into career pathways with Korean transnational firms. From this perspective urban spaces need to be understood as much more than just the geographical backdrop to the globalisation of higher education. Rather, cities like Seoul are the spaces through which connections are being forged around knowledge production, international migration and trans‐local economic practices.
Researching controversial and sensitive issues: using visual vignettes to explore farmers' attitudes towards the control of bovine tuberculosis in England
Authors: Naylor Rhiannon , Maye Damian , Ilbery Brian , Enticott Gareth , Kirwan James
Published: August 2014

This paper addresses the potential difficulties associated with researching controversial and/or sensitive issues. Drawing on the findings from in‐depth interviews with farmers, the paper provides a reflexive commentary on the use of visual vignettes to explore farmers' attitudes towards the control of bovine tuberculosis in England – currently a highly controversial subject. Five short video clips were shown to interviewees to prompt discussions about different aspects of disease control, including methods to vaccinate and cull badgers. Visual vignettes have not been used widely outside the fields of health and social care. The method is used here to encourage interviewees to discuss sensitive issues related to badger control, including their trust in various stakeholders involved in the management of bovine tuberculosis, their own knowledge and understanding about disease control, and their attitudes towards control methods. The results suggest that visual vignettes have a number of advantages that could benefit research in human geography and the wider social sciences.
Spermatogenic ultrastructure in the anomalodesmatan bivalve Myochama anomioides (Mollusca: Myochamidae) – does the nucleus help position the ‘temporary’ acrosome?
Authors: Healy John M. , Mikkelsen Paula M. , Bieler Rüdiger
Published: August 2014

Spermatogenic ultrastructure in the marine bivalve mollusc Myochama anomioides (Myochamidae) is described and contrasted with other bivalves, especially other euheterodonts. Small (0.1 μm diameter), primary proacrosomal vesicles produced in spermatocytes give rise to much larger (0.4 μm diameter) secondary proacrosomal vesicles in early spermatids, which in turn form the dished‐shaped, definitive acrosomal vesicle (diameter 1.0 μm) of later spermatids. The acrosomal vesicle acquires a deposit of subacrosomal material and comes to lie close to or in contact with the plasma membrane. The acrosomal complex (acrosomal vesicle + subacrosomal material) initially positions itself at the apex of the condensing, fibrous nucleus (the so‐called temporary acrosome position), but subsequently begins to move posteriorly. The condensing nucleus becomes markedly folded so that its apex is posteriorly orientated towards the migrating acrosomal complex and the midpiece (mitochondria and centrioles). The close spatial relationship of nuclear apex to acrosomal complex during this folding strongly suggests that acrosomal migration in M. anomioides is assisted, at least in part, by movement of the late spermatid nucleus. Similar nuclear folding has previously been demonstrated in an early stage of fertilization in another anomalodesmatan (Laternula limicola) raising the possibility that one event might be a reversal of the other.
ASC, a Bioactive Steroidal Saponin from Ophitopogin japonicas, Inhibits Angiogenesis through Interruption of Src Tyrosine Kinase‐dependent Matrix Metalloproteinase Pathway
Authors: Zeng Ke‐Wu , Song Fang‐Jiao , Li Ning , Dong Xin , Jiang Yong , Tu Peng‐Fei
Published: August 2014

As angiogenesis is an important target for antitumour drugs, the agents that inhibit angiogenesis may help reduce the use of chemotherapy by blocking tumour blood supply. In this study, we investigated a potent angiogenesis inhibitor, ASC, a steroidal saponin compound, which has been purified from Ophitopogin japonicus (L.f) Ker.‐Gawl. Our observations showed that ASC significantly suppressed human umbilical vein endothelial cell (HUVECs) growth both in vitro and in vivo. This may be resulted from the G2/M cell cycle arrest effects of ASC. Moreover, ASC inhibited HUVECs invasion and tube formation processes, which were associated with endothelial cells remodelling. A mechanism study indicated that ASC down‐regulated the expression of Src tyrosine kinase, further leading to the blockage of Akt‐dependent matrix metalloproteinases (mainly for MMP‐9) signalling pathway, which was functionally associated with angiogenic blood vessels. Finally, ASC significantly inhibited angiogenesis and MMPs/VEGF expression in the subcutaneously injected matrigel in C57/BL mice. These findings suggest that ASC might be a potential drug candidate in anti‐angiogenesis and anticancer therapies.
Different Effects of Cabergoline and Bromocriptine on Metabolic and Cardiovascular Risk Factors in Patients with Elevated Prolactin Levels
Authors: Krysiak Robert , Okopien Bogusław
Published: August 2014

Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine‐resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin‐like growth factor‐1 (IGF‐1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2‐hr post‐challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA‐IR), and circulating levels of IGF‐1, free fatty acids (FFA), uric acid, high‐sensitivity C‐reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25‐hydroxyvitamin D. With the exception of a reduction in HOMA‐IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2‐hr post‐challenge plasma glucose levels, HOMA‐IR, as well as circulating levels of IGF‐1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25‐hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine.
Group typicality, group loyalty and cognitive development
Authors: Patterson Meagan M.
Published: August 2014

Over the course of childhood, children's thinking about social groups changes in a variety of ways. Developmental Subjective Group Dynamics (DSGD) theory emphasizes children's understanding of the importance of conforming to group norms. Abrams et al.'s study, which uses DSGD theory as a framework, demonstrates the social cognitive skills underlying young elementary school children's thinking about group norms. Future research on children's thinking about groups and group norms should explore additional elements of this topic, including aspects of typicality beyond loyalty.
Preliminary characterisation of nanotubes connecting T‐cells and their use by HIV‐1
Authors: Lachambre Simon , Chopard Christophe , Beaumelle Bruno
Published: August 2014

Background Information

Cells, especially those of the immune system, can form long and thin connections termed tunnelling nanotubes (TNTs). These structures can reach >100 µm in length and, in T‐cells, contain actin but no tubulin and are not open ended. T‐cell TNTs were found to form following cell contact and to enable the transfer of HIV‐1 from an infected‐ to a connected‐T‐cell. TNTs are poorly characterised at molecular level.

Results

We found Rab11 and tetraspanins, especially CD81, all along T‐cells TNTs, whereas Rab4 and Rab35 were absent from these structures. Regarding actin cytoskeleton regulators, Exo70, N‐WASP and especially ezrin accumulated at the level of the TNT tip that contacts the connected cell. Phosphoinositides such as PI(4,5)P2 were also concentrated at this level together with HIV‐1 Gag. Gag spots on cells and TNTs were essentially immobile, and likely correspond to area of Gag multimerisation for budding to form virus‐like particles. Mobility of PHPLCδ, a specific probe for PI(4,5)P2, was reduced > threefold at the level of TNT basis or tip compared with the cell body.

Conclusion

Our study identified the TNT tip as an active zone of actin cytoskeleton reorganisation with the presence of ezrin, Exo70, N‐WASP and PI(4,5)P2. The latter is also known to enable HIV‑1 Gag recruitment for viral budding, and the presence of Gag at this level, contacting the connected cell, indicates that the TNT tip is also a favourite place for HIV‐1 assembly and budding.
Structural basis for constitutive activity and agonist‐induced activation of the enteroendocrine fat sensor GPR119
Authors: Engelstoft M S , Norn C , Hauge M , Holliday N D , Elster L , Lehmann J , Jones R M , Frimurer T M , Schwartz T W
Published: August 2014

Background and Purpose

GPR119 is a Gαs‐coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2‐monoacylglycerol. GPR119 stimulates enteroendocrine hormone and insulin secretion. But despite massive drug discovery efforts in the field, very little is known about the basic molecular pharmacology of GPR119.

Experimental Approach

GPR119 receptor signalling was studied in transfected cells. Mutational mapping (30 mutations in 23 positions) was performed on residues required for ligand‐independent and agonist‐induced GPR119 activation (AR231453 and OEA). Novel Rosetta‐based receptor modelling was applied, using a composite template approach with segments from different X‐ray structures and fully flexible ligand docking.

Key Results

The increased signalling induced by increasing the cell surface expression of GPR119 in the absence of agonist and the inhibitory effect of two synthetic inverse agonists demonstrated that GRP119 signals with a high degree of constitutive activity through the Gαs pathway. The mutational maps for AR231453 and OEA were very similar and, surprisingly, also similar to the mutational map for residues affecting the constitutive signalling – albeit with key differences. Surprisingly, almost all residues in extracellular loop‐2b were important for the constitutive activity. The molecular modelling and docking demonstrated that AR231453 binds in a ‘vertical’ pocket in between mutational hits reaching from the centre of the receptor out to extracellular loop‐2b.

Conclusions and Implications

The high constitutive activity of GPR119 should be taken into account in future drug discovery efforts, which can now be guided by the detailed knowledge of the physiochemical properties of the extended ligand‐binding pocket.
Anti‐tumor activity of WK88‐1, a novel geldanamycin derivative, in gefitinib‐resistant non‐small cell lung cancers with Met amplification
Authors: Jang Won‐Jun , Jung Sung‐Keun , Kang Jong‐Soon , Jeong Joo‐Won , Bae Moon‐Kyoung , Joo Sang Hoon , Park Gyu Hwan , Kundu Joydeb K. , Hong Young‐Soo , Jeong Chul‐Ho
Published: August 2014

Although epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) have been introduced for the treatment of non‐small cell lung cancer (NSCLC), the emergence of secondary T790M mutation in EGFR or amplification of the Met proto‐oncogene restrain the clinical success of EGFR‐TKIs. Since heat shock protein‐90 (Hsp90) stabilizes various oncoproteins including EGFR and c‐Met, the inhibition of Hsp90 activity appears as a rational strategy to develop anticancer drugs. Despite preclinical efficacy of geldanamycin‐anasamycin (GA)‐derivatives containing benzoquinone moiety as Hsp90 inhibitors, the hepatotoxicity of these GA‐derivatives restricts their therapeutic benefit. We have prepared WK‐88 series of GA‐derivatives, which lack the benzoquinone moiety. In this study, we have examined the anticancer effects of WK88‐1 in Met‐amplified‐ and gefitinib‐resistant (HCC827GR) NSCLC cells and its parental HCC827 cells. Treatment with WK88‐1 reduced the cell viability in both HCC827 and HCC827GR cells, which was associated with marked decrease in the constitutive expression of Hsp90 client proteins, such as EGFR, ErbB2, ErbB3, Met and Akt. Moreover, WK88‐1 attenuated phosphorylation of these Hsp90 client proteins and reduced the anchorage‐independent growth of HCC827GR cells. Administration of WK88‐1 did not cause hepatotoxicity in animals and significantly reduced the growth of HCC827GR cells xenograft tumors in nude mice. Our study provides evidence that ErbB3 might be a client for Hsp90 in Met‐amplified NSCLCs. In conclusion, we demonstrate that inhibition of Hsp90 dampens the activation of EGFR‐ or c‐Met‐mediated survival of Met‐amplified NSCLCs and that WK88‐1 as a Hsp90 inhibitor alleviates gefitinib resistance in HCC827GR cells.