bluuebunny/crossref_metadata_2025 huggingface dataset:
We're Number Two! Beta Cities and the Cultural Economy
Authors: Rekers Josephine V
Published: September 2012

Given that not every city can be an alpha city in today's global urban hierarchy, what options do beta cities such as Toronto or Chicago realistically have in the cultural economy? Put differently, if cultural capitals such as New York, London, Paris, and Tokyo play critically important roles in certifying and establishing new trends in theatre, fashion, and other cultural industries, how can beta cities compete? Recent research suggests that the spatial distribution of cultural industries strongly resembles one of urban hierarchy, where the institutions and infrastructure that support the production and diffusion of new products are largely concentrated in only a few world cities. The implication of this hierarchy is that there is a clearly defined top tier that lower ranked, beta, cities look to for inspiration as they seek to improve their standing. Comparative case studies of musical theatre scenes in Toronto and New York provide insights into an alternative functional perspective on urban hierarchies and the complementarities among cities. This approach makes a distinction between development and diffusion activities, thereby recognizing opportunities for beta cities as important sites for experimentation and innovation, supported by attributes that could be seen as unique (and localized) strengths in an increasingly global cultural economy.
The Influence of School Choice Policy on Active School Commuting: A Case Study of a Middle-Sized School District in Oregon
Authors: Yang Yizhao , Abbott Steve , Schlossberg Marc
Published: September 2012

School choice policy has implications for school travel as it allows students to attend schools farther from their residence than their neighborhood schools. This paper uses a case study from Oregon to investigate how school choice affects parents' school travel decision making and the degree to which school choice affects children's walking or biking to school. The research shows that school choice is associated with lengthened school travel distance and parents' greater willingness to drive their children to school even within a short distance. The research suggests that school choice could hinder the effectiveness of such programs as Safe Routes to School.
Justifying Business Responses to Climate Change: Discursive Strategies of Similarity and Difference
Authors: Nyberg Daniel , Wright Christopher
Published: September 2012

Despite increasing interest in corporate environmentalism, less attention has been directed to how corporations justify and defend their initiatives in this area. This is important in understanding how corporate environmentalism is legitimized in the face of crises, such as climate change, and the ongoing criticism of corporations' deleterious impacts upon the environment. Based on qualitative data from Australian corporations, we illustrate how organizations and managers employ a range of justifications for their activities in order to meet criticism and challenges. We identify different discursive legitimation strategies that are used by managers to deal with conflicts between justifications, and argue that this framework has broader implications in understanding the arguments that underpin social conflict over environmental sustainability.
Projected Futures: The Political Matter of UK Higher Activity Radioactive Waste
Authors: Gregson Nicky
Published: September 2012

This paper identifies, and works from, the technoconceptual as a site of intervention for a politics of stuff. Its case is radioactive waste: specifically, UK higher activity wastes (HAW) and the policy future of a UK Deep Geological Disposal Facility (DGF). The paper proceeds through three steps. It charts, first, the unravelling of HAW as onto-politics through the democratisation of technoscience, showing that, as the gap between stuff and politics has opened, HAW's future in a DGF has become the preserve of science—technical discourses (currently geology and engineered design). Secondly, it joins with the undone-science traditions of STS (science, technology, and society), to critique existing technoscientific conceptualisations of a DGF and to anticipate a future in which a DGF is abandoned. Third, and in response to abandonment, it proposes a different future for a DGF. This starts from thinking radioactive waste as ‘thing power’ but argues that, for a DGF to be materialised in ways that forge attachments with publics, requires a turn to material culture. More broadly, the paper argues that furthering ontopolitics requires keeping the demos alive to stuff's vitality. This means engaging in political settlements of technoscientific controversies; with old, or established, technologies, and ‘cold’ politics; and in politics as practised.
Participatory Approaches to Land Policy Reform in Zambia: Potentials and Challenges
Authors: Ng'ombe Austine , Keivani Ramin , Stubbs Michael , Mattingly Michael
Published: September 2012

The subject of participation is now at the core of many contemporary development debates. This is promoted within the emerging context of moving away from ‘government’ to ‘governance’ as stakeholders are increasingly getting frustrated by governments' continued application of the mundane Decide, Announce, and Defend (DAD) approaches to policy making. However, despite the voluminous amount of literature on participation, there is little scholarly work on whether or how communities, particularly those in rural and periurban locations, participate in land policy processes. This paper examines the extent to which Zambia's land policy process is participatory on the part of rural/periurban communities. The paper argues that despite its potential, genuine participation of rural communities in land policy processes in Zambia is constrained by cultural/social norms that defer the views of rural communities to those of their traditional rulers. On the other hand, periurban communities are excluded from the participatory agenda by the dynamics surrounding struggles over land and proceeds accruing from land transactions. The implication of these findings is that, since participatory requirements/expectations of rural communities may not necessarily be similar to those of periurban communities, there is need to explore the potential of designing ‘bespoke’ policies that would accommodate the needs of the individual communities.
Tolerance to Commuting in Urban Household Location Choice: Evidence from the Paris Metropolitan Area
Authors: Korsu Emre
Published: September 2012

Many social scientists consider improvements in urban travel facilities during the last decades of the 20th century to have significantly weakened proximity constraints, and therefore think that home—workplace proximity is no longer a major factor in household location choice. They believe that better transport conditions give households more freedom in selecting their homes and workplaces, regardless of the distance separating these two locations. It is argued that this point of view underestimates the costs of daily commuting (which remain an increasing function of trip length), and consequently overestimates households' tolerance to commuting. The author's aim is to measure how much weight households give to home—workplace proximity in actual location choices. With the aid of survey data from the Paris-Île-de-France metropolitan area, two values are estimated: (i) the share of home and workplace changes (observed between 1991 and 2002) which either bring home and workplace closer to each other or keep these two places close to each other, and (ii) the ‘life expectancy’ of job—residence combinations which impose long-distance commutes.
Population Mobility in Regeneration Areas: Trends, Drivers, and Implications; Evidence from England's New Deal for Communities Programme
Authors: Pearson Sarah , Lawless Paul
Published: September 2012

The nature, extent, and impact of residential mobility have attracted considerable interest. Little of this work has explored relationships between mobility and outcomes for area-based regeneration schemes. England's New Deal for Communities (NDC) Programme marks a departure from previous regeneration programmes in terms of levels of funding and time span. Evidence suggests that between 2002 and 2006 the thirty-nine NDC areas were subject to complex patterns of mobility, the most important drivers of which were age and tenure. Residents moving out of NDC areas did so for housing and environmental reasons and were less disadvantaged than those who stayed. Those moving into the areas during this period were not more disadvantaged than existing residents. Although there are associations between mobility and outcome change, these are not as strong as might be anticipated and their implications for area-based regeneration policy appear relatively marginal.
A review of recent advances in risk analysis for wildfire management
Authors: Miller Carol , Ager Alan A.
Published: September 2012

Risk analysis evolved out of the need to make decisions concerning highly stochastic events, and is well suited to analyse the timing, location and potential effects of wildfires. Over the past 10 years, the application of risk analysis to wildland fire management has seen steady growth with new risk-based analytical tools that support a wide range of fire and fuels management planning scales from individual incidents to national, strategic interagency programs. After a brief review of the three components of fire risk – likelihood, intensity and effects – this paper reviews recent advances in quantifying and integrating these individual components of fire risk. We also review recent advances in addressing temporal dynamics of fire risk and spatial optimisation of fuels management activities. Risk analysis approaches have become increasingly quantitative and sophisticated but remain quite disparate. We suggest several necessary and fruitful directions for future research and development in wildfire risk analysis.
Behavioural observations and use of burrow systems by an endangered Australian arid-zone lizard, Slater's skink (Liopholis slateri)
Authors: Fenner Aaron L. , Pavey Chris R. , Bull C. Michael
Published: September 2012

The endangered Slater’s skink (Liopholis slateri) is restricted to the river floodplain habitat of central Australia. It is an obligate burrower and creates complex, multientrance burrow systems in the mound of soil that builds up around the base of some shrubs and small trees. We provide detailed information about the behaviour and use of the burrow systems by Slater’s skink. The behaviour of lizards remained consistent over the four months (October–January) of the study, and lizards performed almost all of their daily activities around their burrow/mound systems. Lizards also showed signs of sociality, as pairs of lizards were observed to share occupancy of single burrow systems over extended periods, and demonstrated a high level of tolerance to conspecifics. This study emphasises the importance of the burrow systems for the daily life of this lizard and suggests that conservation measures should focus on ensuring that the lizards have a reliable supply of stable and suitable burrows in their preferred habitat.
Experimental Evaluation of Adult Spring Chinook Salmon Radio-Tagged during the Late Stages of Spawning Migration
Authors: Corbett Stephen C. , Moser Mary L. , Dittman Andrew H.
Published: September 2012

We conducted an experiment to assess the effects of radio- tagging on adult spring Chinook salmon Oncorhynchus tshawytscha during the late stages of their spawning migration. Fish were captured at Roza Dam, Yakima River, Washington (river kilometer 208). Each fish had a radio tag inserted into the stomach via the esophagus and was then transported to a raceway and held for 50 d to assess survival. In the same raceway we also held a control group that was handled but not tagged and a group with externally attached transmitters. Survival of fish with gastrically implanted radio tags was low (10%), while 70% of controls and 90% of fish with externally mounted tags survived to the end of the experiment. Postmortem dissections revealed that after implantation, some radio tags had migrated from the stomach position to the posterior digestive tract and peritoneum. Fish from all treatments exhibited some level of tissue degeneration of the gastrointestinal tract. Gastric implantation should be used with caution, particularly for fish at vulnerable life stages. For spring Chinook salmon in the Columbia River basin, tagging with gastric implants should be conducted early in the freshwater migration to improve survival and reduce tag effects.

Received September 30, 2011; accepted June 4, 2012
Characterization of Greater Amberjack Microsatellite Markers in Lesser Amberjacks, Yellowtail Jacks, Almaco Jacks, and Banded Rudderfish
Authors: Renshaw Mark A , Buentello Alejandro , Gold John R
Published: September 2012

Thirty-one microsatellite markers that were previously isolated from and characterized in greater amberjacks Seriola dumerili were assayed for cross-species amplification in four other members of the carangid genus Seriola: the lesser amberjack S. fasciata, yellowtail jack S. lalandi, almaco jack S. rivoliana, and banded rudderfish S. zonata. The number of markers that consistently amplified and were polymorphic ranged from 16 in yellowtail jacks to 25 in lesser amberjacks. The microsatellites characterized in this study will be useful for a variety of applications, including stock structure assessments of wild fish and parentage assignments of farmed fish.
Selective CO Methanation over Ru Catalysts Supported on Nanostructured TiO2 with Different Crystalline Phases and Morphology
Authors: Wang Gui-ying , Gao Yu-xian , Wang Wen-dong , Huang Wei-xin
Published: September 2012

Nanostructured titanium dioxides were synthesized via various post-treatments of titanate nanofibers obtained from titanium precursors by hydrothermal reactions. The microstructures of TiO2 and supported Ru/TiO2 catalysts were characterized with X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray analysis, and nitrogen adsorption isotherms. The phase structure, particle size, morphology, and specific surface area were determined. The supported Ru catalysts were applied for the selective methanation of CO in a hydrogen-rich stream. The results indicated that the Ru catalyst supported on rutile and TiO2-B exhibited higher catalytic performance than the counterpart supported on anatase, which suggested the distinct interaction between Ru nanoparticles and TiO2 resulting from different crystalline phases and morphology.
NetworkView: 3D display and analysis of protein·RNA interaction networks
Authors: Eargle John , Luthey-Schulten Zaida
Published: September 2012

Summary: NetworkView is an application for the display and analysis of protein·RNA interaction networks derived from structure and/or dynamics. These networks typically model individual protein residues and nucleic acid monomers as nodes and their pairwise contacts as edges with associated weights. NetworkView projects the network onto the underlying 3D molecular structure so that visualization and analysis of the network can be coupled to physical and biological properties. NetworkView is implemented as a plugin to the molecular visualization software VMD.

Availability and implementation: NetworkView is included with VMD, which is available at http://www.ks.uiuc.edu/Research/vmd/. Documentation, tutorials and supporting programs are available at http://www.scs.illinois.edu/schulten/software/.

Contact: networkview@scs.illinois.edu
DLRS: gene tree evolution in light of a species tree
Authors: Sjöstrand Joel , Sennblad Bengt , Arvestad Lars , Lagergren Jens
Published: September 2012

Summary: PrIME-DLRS (or colloquially: ‘Delirious’) is a phylogenetic software tool to simultaneously infer and reconcile a gene tree given a species tree. It accounts for duplication and loss events, a relaxed molecular clock and is intended for the study of homologous gene families, for example in a comparative genomics setting involving multiple species. PrIME-DLRS uses a Bayesian MCMC framework, where the input is a known species tree with divergence times and a multiple sequence alignment, and the output is a posterior distribution over gene trees and model parameters.

Availability and implementation: PrIME-DLRS is available for Java SE 6+ under the New BSD License, and JAR files and source code can be downloaded from http://code.google.com/p/jprime/. There is also a slightly older C++ version available as a binary package for Ubuntu, with download instructions at http://prime.sbc.su.se. The C++ source code is available upon request.

Contact:  joel.sjostrand@scilifelab.se or jens.lagergren@scilifelab.se.

Supplementary Information: PrIME-DLRS is based on a sound probabilistic model (Åkerborg et al., 2009) and has been thoroughly validated on synthetic and biological datasets (Supplementary Material online).
Should antidiabetic treatment of type 2 diabetes in patients with heart failure differ from that in patients without?
Authors: Gitt Anselm K. , Halle Martin , Hanefeld Markolf , Kellerer Monika , Marx Nikolaus , Meier Juris J. , Schumm‐Draeger Petra‐Maria , Bramlage Peter , Tschöpe Diethelm
Published: September 2012

Aims

Patients with type 2 diabetes are at high risk for developing heart failure. Evidence‐based treatment recommendations with respect to the specific benefits or possible hazards of antidiabetic treatment are scarce.

Methods and results

In a systematic search we only identified randomized, controlled trials for thiazolidinediones. Further evidence is largely based on subgroup analyses of larger intervention studies in mostly systolic heart failure, on observational studies, or on registries. Acknowledging this lack of data, hyperglycaemia should be treated to appropriate guideline‐recommended targets and hypoglycaemia avoided until this evidence becomes available. Thiazolidinediones should not be used because of an increased event rate in diabetic patients with established heart failure and a large increase in incident heart failure. All other glucose‐lowering strategies might be used in patients with diabetes and heart failure, but specific precautions must be considered.

Conclusions

The documented lack of data calls for specific trials, as diabetes and heart failure as well as their co‐morbidities are highly prevalent and are becoming even more important with an increasing prevalence of obesity and an ageing population.
Normal Changes of Ageing
Authors: Mackenzie Peter
Published: September 2012

At a biological level, normal ageing or ‘senescence’ results in limitation of function, increased risk of disease and ultimately death. The pattern, onset and rate vary between individuals and appear not to be the result of a single overarching mechanism but instead that of a complex interplay between intrinsic and extrinsic factors. As such ‘chronological age’ and ‘biological age’ often widely differ. The effects of the ageing process are becoming more important to consider as each generation passes, due to increased life expectancy and other demographic changes.
Health Promotion in Primary Care
Authors: Simon Chantal
Published: September 2012

Rather than focussing on individuals, health promotion involves whole population of people. It supports personal and social development through providing information, providing education for health and enhancing life skills. By doing so, it increases the options available to people to exercise more control over their own health and their environments and to make choices conducive to health. This article focuses on the links between health promotion and health inequality and the ways in which GPs and the wider primary healthcare team can engage in health promotion activities to benefit their practice population both now and in the future.
Childhood Cancer
Authors: Smith Helin , Phillips Bob
Published: September 2012

Childhood cancers are uncommon, accounting for only 0.5% of all cancers in the UK. Approximately, 1500 children are diagnosed with cancer in the UK every year. Despite it being a rare occurrence, cancer still remains the largest cause of death in the 1–14 year age group, amongst whom it counts for 20% of all deaths. Although most adult cancers affect the lung, breast, bowel and prostate, the majority of childhood cancers are haematological and central nervous system (CNS) tumours. The primary care physician's role is vital across the disease trajectory, requiring them to recognize the signs and symptoms of childhood cancer, understand treatment, provide support to children and families, and finally consider the issues affecting survivors of childhood cancer.
When to Suspect Dementia?
Authors: Cundill Frances
Published: September 2012

Approximately 800 000 people have dementia in the UK and this number is expected to double over the next 30 years. Only 40% of those with dementia receive a formal diagnosis but if dementia is diagnosed early enough, there are lots of things that can be done to help people overcome the problems and to improve their quality of life. The Government has recognised this, and in the past 3 years it has produced a National Dementia Strategy and Prime Minister's Challenge on Dementia with an emphasis on early recognition and diagnosis of dementia. This article aims to highlight when to suspect dementia in primary care and what assessments should be carried out before referral to specialist services.
Photorhabdus luminescens subsp. noenieputensis subsp. nov., a symbiotic bacterium associated with a novel Heterorhabditis species related to Heterorhabditis indica
Authors: Ferreira Tiarin , van Reenen Carol , Pagès Sylvie , Tailliez Patrick , Malan Antoinette P. , Dicks Leon M. T.
Published: September 2012

The bacterial symbiont AM7T, isolated from a novel entomopathogenic nematode species of the genus Heterorhabditis, displays the main phenotypic traits of the genus

Photorhabdus

and is highly pathogenic to Galleria mellonella. Phylogenetic analysis based on a multigene approach (16S rRNA, recA, gyrB, dnaN, gltX and infB) confirmed the classification of isolate AM7T within the species

Photorhabdus luminescens

and revealed its close relatedness to

Photorhabdus luminescens subsp. caribbeanensis

,

P. luminescens subsp. akhurstii

and

P. luminescens subsp. hainanensis

. The five concatenated protein-encoding sequences (4197 nt) of strain AM7T revealed 95.8, 95.4 and 94.9 % nucleotide identity to sequences of

P. luminescens subsp. caribbeanensis

HG29T,

P. luminescens subsp. akhurstii

FRG04T and

P. luminescens subsp. hainanensis

C8404T, respectively. These identity values are less than the threshold of 97 % proposed for classification within one of the existing subspecies of

P. luminescens

. Unlike other strains described for

P. luminescens

, strain AM7T produces acid from adonitol, sorbitol and xylitol, assimilates xylitol and has no lipase activity on medium containing Tween 20 or 60. Strain AM7T is differentiated from

P. luminescens subsp. caribbeanensis

by the assimilation of N-acetylglucosamine and the absence of haemolytic activity. Unlike

P. luminescens subsp. akhurstii

, strain AM7T does not assimilate mannitol, and it is distinguished from

P. luminescens subsp. hainanensis

by the assimilation of trehalose and citrate, the inability to produce indole from tryptophan and the presence of acetoin production and urease activity. Strain AM7T ( = ATCC BAA-2407T  = DSM 25462T) belongs to a novel subspecies, and is proposed as the type strain of Photorhabdus luminescens subsp. noenieputensis sp. nov.
Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation
Authors: Yin Jing-wen , Liang Yan , Park Ji Yeon , Chen Dongrui , Yao Xiao , Xiao Qi , Liu Zhen , Jiang Bo , Fu Yu , Bao Menghan , Huang Yan , Liu Yuting , Yan Jun , Zhu Min-sheng , Yang Zhongzhou , Gao Pingjin , Tian Bin , Li Dangsheng , Wang Gang
Published: September 2012

The Mediator complex functions as a control center, orchestrating diverse signaling, gene activities, and biological processes. However, how Mediator subunits determine distinct cell fates remains to be fully elucidated. Here, we show that Mediator MED23 controls the cell fate preference that directs differentiation into smooth muscle cells (SMCs) or adipocytes. Med23 deficiency facilitates SMC differentiation but represses adipocyte differentiation from the multipotent mesenchymal stem cells. Gene profiling revealed that the presence or absence of Med23 oppositely regulates two sets of genes: the RhoA/MAL targeted cytoskeleton/SMC genes and the Ras/ELK1 targeted growth/adipogenic genes. Mechanistically, MED23 favors ELK1–SRF binding to SMC gene promoters for repression, whereas the lack of MED23 favors MAL–SRF binding to SMC gene promoters for activation. Remarkably, the effect of MED23 on SMC differentiation can be recapitulated in zebrafish embryogenesis. Collectively, our data demonstrate the dual, opposing roles for MED23 in regulating the cytoskeleton/SMC and growth/adipogenic gene programs, suggesting its “Ying-Yang” function in directing adipogenesis versus SMC differentiation.
Regulation of the Hippo–YAP pathway by protease-activated receptors (PARs)
Authors: Mo Jung-Soon , Yu Fa-Xing , Gong Rui , Brown Joan Heller , Guan Kun-Liang
Published: September 2012

The Hippo signaling pathway plays a crucial role in tissue growth and tumorigenesis. Core components of the Hippo pathway include the MST1/2 and Lats1/2 kinases. Acting downstream from the Hippo pathway are the YAP/TAZ transcription coactivators, which are inhibited through phosphorylation by Lats. However, upstream signals that regulate the Hippo pathway have not been well delineated. Here we report that stimulation of protease-activated receptors (PARs) activates YAP/TAZ by decreasing phosphorylation and increasing nuclear localization. PAR1 acts through G12/13and Rho GTPase to inhibit the Lats1/2 kinase. Our observations establish thrombin as a physiological signal for the Hippo pathway and implicate Hippo–YAP as a key downstream signaling branch of PAR activation.
The transcriptional landscape and mutational profile of lung adenocarcinoma
Authors: Seo Jeong-Sun , Ju Young Seok , Lee Won-Chul , Shin Jong-Yeon , Lee June Koo , Bleazard Thomas , Lee Junho , Jung Yoo Jin , Kim Jung-Oh , Shin Jung-Young , Yu Saet-Byeol , Kim Jihye , Lee Eung-Ryoung , Kang Chang-Hyun , Park In-Kyu , Rhee Hwanseok , Lee Se-Hoon , Kim Jong-Il , Kang Jin-Hyoung , Kim Young Tae
Published: September 2012

All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We found 45 fusion genes, eight of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches.
Involvement of the anterior cingulate cortex in formation, consolidation, and reconsolidation of recent and remote contextual fear memory
Authors: Einarsson Einar Ö. , Nader Karim
Published: September 2012

It has been suggested that memories become more stable and less susceptible to the disruption of reconsolidation over weeks after learning. Here, we test this by targeting the anterior cingulate cortex (ACC) and test its involvement in the formation, consolidation, and reconsolidation of recent and remote contextual fear memory. We found that inhibiting NMDAR-NR2B activity disrupts memory formation, and that infusion of the protein-synthesis inhibitor anisomycin impairs memory consolidation and reconsolidation of recent and remote memory. Our findings demonstrate for the first time that the ACC plays an important role in reconsolidation of contextual fear memory at recent and remote time points.
Impact of the Absence of Stem-Specific β-Glucosidases on Lignin and Monolignols
Authors: Chapelle Aurélie , Morreel Kris , Vanholme Ruben , Le-Bris Philippe , Morin Halima , Lapierre Catherine , Boerjan Wout , Jouanin Lise , Demont-Caulet Nathalie
Published: September 2012

Monolignol glucosides are thought to be implicated in the lignin biosynthesis pathway as storage and/or transportation forms of cinnamyl alcohols between the cytosol and the lignifying cell walls. The hydrolysis of these monolignol glucosides would involve β-glucosidase activities. In Arabidopsis (Arabidopsis thaliana), in vitro studies have shown the affinity of β-GLUCOSIDASE45 (BGLU45) and BGLU46 for monolignol glucosides. BGLU45 and BGLU46 genes are expressed in stems. Immunolocalization experiments showed that BGLU45 and BGLU46 proteins are mainly located in the interfascicular fibers and in the protoxylem, respectively. Knockout mutants for BGLU45 or BGLU46 do not have a lignin-deficient phenotype. Coniferin and syringin could be detected by ultra-performance liquid chromatography-mass spectrometry in Arabidopsis stems. Stems from BGLU45 and BGLU46 mutant lines displayed a significant increase in coniferin content without any change in coniferyl alcohol, whereas no change in syringin content was observed. Other glucosylated compounds of the phenylpropanoid pathway were also deregulated in these mutants, but to a lower extent. By contrast, BGLU47, which is closely related to BGLU45 and BGLU46, is not implicated in either the general phenylpropanoid pathway or in the lignification of stems and roots. These results confirm that the major in vivo substrate of BGLU45 and BGLU46 is coniferin and suggest that monolignol glucosides are the storage form of monolignols in Arabidopsis, but not the direct precursors of lignin.
A Comparative Study of Ethylene Growth Response Kinetics in Eudicots and Monocots Reveals a Role for Gibberellin in Growth Inhibition and Recovery
Authors: Kim Joonyup , Wilson Rebecca L. , Case J. Brett , Binder Brad M.
Published: September 2012

Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa ‘Nipponbare’) seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics.
An irreversible phase transition in 1-n-butylindeno[2,1-c]pyran-3,9-dione
Authors: Batsanov Andrei S. , Howard Judith A. K. , Wu Na , Yang Zhen , Marder Todd B.
Published: September 2012

At ambient temperature, the title compound, C16H14O3, is triclinic, with then-butyl side chain disordered in an out-of-plane orientation. On cooling below 240 K, it converts into a different triclinic phase with an ordered planar conformation and denser packing, which is retained on warming to room temperature. The transition (occasionally) proceeds from single crystal to single crystal.
SPInDel: a multifunctional workbench for species identification using insertion/deletion variants
Authors: Carneiro João , Pereira Filipe , Amorim António
Published: September 2012

The majority of the available methods for the molecular identification of species use pairwise sequence divergences between the query and reference sequences (DNA barcoding). The presence of multiple insertions and deletions (indels) in the target genomic regions is generally regarded as a problem, as it introduces ambiguities in sequence alignments. However, we have recently shown that a high level of species discrimination is attainable in all taxa of life simply by considering the length of hypervariable regions defined by indel variants. Each species is tagged with a numeric profile of fragment lengths—a true numeric barcode. In this study, we describe a multifunctional computational workbench (named SPInDel for SPecies Identification by Insertions/Deletions) to assist researchers using variable‐length DNA sequences, and we demonstrate its applicability in molecular ecology. The SPInDel workbench provides a step‐by‐step environment for the alignment of target sequences, selection of informative hypervariable regions, design of PCR primers and the statistical validation of the species‐identification process. In our test data sets, we were able to discriminate all species from two genera of frogs (Ansonia and Leptobrachium) inhabiting lowland rainforests and mountain regions of South‐East Asia and species from the most common genus of coral reef fishes (Apogon). Our method can complement conventional DNA barcoding systems when indels are common (e.g. in rRNA genes) without the required step of DNA sequencing. The executable files, source code, documentation and test data sets are freely available at http://www.portugene.com/SPInDel/SPInDel_webworkbench.html.
Apoptotic Vascular Smooth Muscle Cell Depletion via BCL2 Family of Proteins in Human Ascending Aortic Aneurysm and Dissection
Authors: Durdu Serkan , Deniz Gunseli C. , Balci Deniz , Zaim Cagin , Dogan Arin , Can Alp , Akcali Kamil C. , Akar Ahmet Ruchan
Published: September 2012

Aims: This study investigates the expression patterns of BCL2 (B‐cell CLL/lymphoma2) family of proteins and the extent of vascular smooth muscle cell (VSMC) apoptosis in thoracic aortic aneurysms (TAA), type‐A aortic dissections (TAD), and nondilated ascending aortic samples. Methods: Aortic wall specimens were obtained from patients undergoing surgical repair for TAA (n = 24), TAD (n = 20), and normal aortic tissues from organ donors (n = 6). The expression pattern of BCL2, BCL2L1 (BCL2‐like1), BAK1 (BCL2‐antagonist/killer1), and BAX (BCL2‐associated X protein) proteins was investigated by immunohistochemistry. Furthermore, colocalization of alpha smooth muscle actin (ACTA2) and caspase3 (CASP3) in aortic VSMCs was analyzed by double‐immunofluorescence staining. Onset of DNA fragmentation was measured by TUNEL assay. Results: Apoptotic index was significantly increased in both TAD group (31.3 ± 17.2, P < 0.001) and TAA group (21.1 ± 12.7, P = 0.001) relative to control aortas (2.0 ± 1.2). Anti‐CASP3 and ACTA2 double‐immunostaining confirmed apoptosis in VSMCs in TAA and TAD groups but not in controls. Proapoptotic BAX expression was significantly elevated in VSMCs of TAA patients, compared with that of controls (OR = 20; P = 0.02; 95% CI, 16–250). In contrast, antiapoptotic BCL2L1 expression was higher in controls compared with that of TAA group (OR = 11.2; P = 0.049; 95% CI, 1.0–123.9). Furthermore, BAX/BCL2 ratio was significantly increased in both TAA (1.2 ± 0.7, P < 0.001) and TAD (0.6 ± 0.4, P = 0.05) groups relative to controls (0.2 ± 0.1, P < 0.001). Conclusions: Apoptotic VSMC depletion in human TAA/TAD is associated with disturbance of the balance between proapoptotic and antiapoptotic members of the BCL2 family proteins, which may have a role in the pathogenesis of vascular remodelling in aortic disease. In light of the future studies, targeting apoptotic pathways in TAA and TAD pathogenesis may provide therapeutic benefits to patients by slowing down the progression and even possibly preventing the TAD.
RhinAsthma Patient Perspective: a short daily asthma and rhinitisQoLassessment
Authors: Braido F. , Baiardini I. , Stagi E. , Scichilone N. , Rossi O. , Lombardi C. , Ridolo E. , Gani F. , Balestracci S. , Girbino G. , Senna G. E. , Bordo A. , Church M. K. , Canonica G. W.
Published: September 2012

Background

The present study aimed to develop a short validated patient‐completed questionnaire, theRhinAsthma Patient Perspective (RAPP), to assess the health‐related quality of life (HRQoL) in patients with asthma and comorbid allergic rhinitis in clinical practice.

Methods

A provisionalRAPPquestionnaire was formed from candidate items identified through retrospective analysis of 333RHINASTHMAquestionnaires. This was then tested on 150 asthma patients with allergic rhinitis.

Results

Psychometric analyses identified eight items fitting a unidimensional model to formRAPP. Internal consistency (Cronbach's alpha coefficient > 0.8) and agreement withRHINASTHMA(r = −0.31,P = 0.0001) were excellent. Criterion, discriminant, and convergent validity were good. Reliability in 47 stable patients was very good (intra‐class and concordance correlation coefficients were 0.90 and 0.89, respectively). Responsiveness in 103 patients with health improvement or deterioration was significantly associated with changes inGlobalRatingScale (r = −0.4965,P < 0.01),RhinitisVisualAnalogueScale (r = 0.5722,P < 0.01) and asthma control test (r = −0.6483,P < 0.01). Minimal clinical difference in the analyzed population was 2.

Conclusion

RhinAsthma Patient Perspective is a simple eight‐question questionnaire with good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardizedHRQoLmeasurement in patients with asthma and comorbid allergic rhinitis in clinical practice.
IgE detection to α/β/γ‐gliadin and its clinical relevance in wheat‐dependent exercise‐induced anaphylaxis
Authors: Hofmann S. C. , Fischer J. , Eriksson C. , Bengtsson Gref O. , Biedermann T. , Jakob T.
Published: September 2012

Wheat‐dependent exercise‐induced anaphylaxis (WDEIA) is characterized by anaphylactic reactions after wheat ingestion and physical exercise. IgE antibodies to recombinant ω5‐gliadin are detectable in a majority of WDEIA patients, but other wheat allergens may also play a role in elicitation of WDEIA. Here, we performed a comprehensive analysis of IgE reactivity to different wheat proteins in 17 patients with confirmed WDEIA by ImmunoCAP research prototypes and a semi‐quantitative microarray immunoassay with α/β/γ‐gliadin, high‐molecular‐weight (HMW) glutenin, alpha‐amylase inhibitor (AAI) dimer, and wheat lipid transfer protein (LTP). By ImmunoCAP, IgE to recombinant ω5‐gliadin was detectable in 14/17 patients (82%), to α/β/γ‐gliadin in 82% including the three patients lacking IgE to ω5‐gliadin, and to HMW glutenin in 59%. The microarray revealed specifically γ‐gliadin as the second most important allergen. These results demonstrate the additional diagnostic value of α/β‐ and γ‐gliadin in particular in ω5‐gliadin‐negative patients in the diagnosis of WDEIA.
The impact of vitamin D on pregnancy: a systematic review
Authors: CHRISTESEN HENRIK T. , FALKENBERG TINE , LAMONT RONALD F. , JØRGENSEN JAN S.
Published: September 2012

Hypovitaminosis D is common in pregnancy. To systematically review the evidence on vitamin D‐dependent pregnancy outcomes, PubMed and Embase were searched for randomized control trials, cohort and case–control studies. In randomized control trials (n = 7), larger doses of vitamin D resulted in higher 25‐hydroxylated vitamin D (25OHD) levels (n = 6), increased maternal weight gain (n = 1), and fewer classical vitamin D deficiency symptoms (n = 1). In observational studies (n = 32), lower vitamin D intake, or low 25OHD‐levels, were associated with adverse fertility parameters (n = 2), preeclampsia (n = 5), gestational diabetes or higher blood glucose (n = 6), bacterial vaginosis (n = 4), primary cesarean section (n = 1), none (n = 3) or a few days’ (n = 2) shorter gestation, and postpartum depression (n = 1). Studies with few participants having low 25OHD did not identify an association to preeclampsia (n = 5) or gestational diabetes (n = 2). Increased odds of pregnancy‐associated breast cancer with 25OHD >25.8 nmol/L were observed (n = 1). In conclusion, an effect of vitamin D on several pregnancy outcomes is suggested.
Assessment of circulatory adjustments during underwater apnoea in elite divers by means of a portable device
Authors: Tocco F. , Marongiu E. , Pinna M. , Roberto S. , Pusceddu M. , Angius L. , Migliaccio G. , Milia R. , Concu A. , Crisafulli A.
Published: September 2012

Aim

Considering that sympathetic activation is induced by exercise, it is reasonable to assume that hemodynamic adjustments to exercise act in opposition to those elicited by the diving response. However, cardiovascular measurements have never been performed during underwater dynamic apnoea (DA), and this hypothesis remains speculative.

Methods

Data concerning heart rate (HR), stroke volume (SV) and cardiac output (CO) during static apnoea (SA) and DA were collected from 12 elite divers by means of an impedance cardiograph adapted to the underwater environment. Mean arterial pressure (MBP), systemic vascular resistance (SVR) and arterial oxygen saturation (SaO2) were also assessed. Five trials were performed by the divers: head‐out immersion during normal breathing (test A); 3 min of SA immersed at the surface (B) and at 3 m depth (C); DA till exhaustion immersed at the surface (D) and at 3 m depth (E).

Results

Both B and C conditions led to bradycardia (−17%) compared to A and also induced a decrement in SV (−8%) and in CO (−25%), while MBP was maintained because of an increase in SVR. A significant MBP increment (+11%) was detected only during tests D and E, when a SaO2 drop was also present, whereas HR, SV and CO remained unchanged.

Conclusion

We concluded that typical diving response was present only during SA, while sympathetic activation was induced by exercise during DA, which partially obscured the effects of the diving response.
ESCRT‐II's involvement in HIV‐1 genomic RNA trafficking and assembly
Authors: Ghoujal Bashar , Milev Miroslav P. , Ajamian Lara , Abel Karen , Mouland Andrew J.
Published: September 2012

Background information

Several host proteins play crucial roles in the HIV‐1 replication cycle. The endosomal sorting complex required for transport (ESCRT) exemplifies a large, multi‐component host machinery that is required by HIV‐1 for viral budding. ESCRT promotes the inward budding of vesicles from the membranes of late endosomes to generate multi‐vesicular bodies. However, HIV‐1 co‐opts the ESCRT to enable outwards budding of virus particles from the plasma membrane, a phenomenon that is topologically similar to multi‐vesicular body biogenesis. A role for ESCRTII in mRNA trafficking has been established in Drosophila in which the ESCRT‐II components, Vps22 and Vps36, promote the localisation of the bicoid mRNA in the fertilised egg. This is achieved via specific interactions with the Staufen protein. In this work, we investigated a possible implication of ESCRT‐II in the HIV‐1 replication cycle.

Results

Co‐immunoprecipitation analyses and live cell tri‐molecular fluorescence complementation assays revealed that interactions between EAP30 and Gag and another between EAP30 and Staufen1 occur in mammalian cells. We then depleted EAP30 (the orthologue for Vps22) by siRNA to target ESCRT‐II in HIV‐1 expressing cells. This treatment disrupted ESCRT‐II function and leads to the degradation of the two other ESCRT‐II complex proteins, EAP45 and EAP20, as well as the associated Rab7‐interacting lysosomal protein. The depletion of EAP30 led to dramatically reduced viral structural protein Gag and virus production levels, without any effect on viral RNA levels. On the contrary, the overexpression of EAP30 led to a several‐fold increase in virus production. Unexpec‐tedly, siRNA‐mediated depletion of EAP30 led to a block to HIV‐1 genomic RNA trafficking and resulted in the accumulation of genomic RNA in the nucleus and juxtanuclear domains.

Conclusions

Our data provide the first evidence that the Staufen1–ESCRT‐II interaction is evolutionarily conserved from lower to higher eukaryotes and reveal a novel role for EAP30 in the control of HIV‐1 RNA trafficking and gene expression.
Conformational Adaptation Drives Potent, Selective and Durable Inhibition of the Human Protein Methyltransferase DOT1L
Authors: Basavapathruni Aravind , Jin Lei , Daigle Scott R. , Majer Christina R. A. , Therkelsen Carly A. , Wigle Tim J. , Kuntz Kevin W. , Chesworth Richard , Pollock Roy M. , Scott Margaret P. , Moyer Mikel P. , Richon Victoria M. , Copeland Robert A. , Olhava Edward J.
Published: September 2012

DOT1L is the human protein methyltransferase responsible for catalyzing the methylation of histone H3 on lysine 79 (H3K79). The ectopic activity of DOT1L, associated with the chromosomal translocation that is a universal hallmark of MLL‐rearranged leukemia, is a required driver of leukemogenesis in this malignancy. Here, we present studies on the structure–activity relationship of aminonucleoside‐based DOT1L inhibitors. Within this series, we find that improvements in target enzyme affinity and selectivity are driven entirely by diminution of the dissociation rate constant for the enzyme–inhibitor complex, leading to long residence times for the binary complex. The biochemical Ki and residence times measured for these inhibitors correlate well with their effects on intracellular H3K79 methylation and MLL‐rearranged leukemic cell killing. Crystallographic studies reveal a conformational adaptation mechanism associated with high‐affinity inhibitor binding and prolonged residence time; these studies also suggest that conformational adaptation likewise plays a critical role in natural ligand interactions with the enzyme, hence, facilitating enzyme turnover. These results provide critical insights into the role of conformational adaptation in the enzymatic mechanism of catalysis and in pharmacologic intervention for DOT1L and other members of this enzyme class.