bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutive Expression of a Nag-Like Dioxygenase Gene through an Internal Promoter in the 2-Chloronitrobenzene Catabolism Gene Cluster of Pseudomonas stutzeri ZWLR2-1
Authors: Gao Yi-Zhou , Liu Hong , Chao Hong-Jun , Zhou Ning-Yi
Published: April 2016

The gene cluster encoding the 2-chloronitrobenzene (2CNB) catabolism pathway in
Pseudomonas stutzeri
ZWLR2-1 is a patchwork assembly of a Nag-like dioxygenase (dioxygenase belonging to the naphthalene dioxygenase NagAaAbAcAd family from
Ralstonia
sp. strain U2) gene cluster and a chlorocatechol catabolism cluster. However, the transcriptional regulator gene usually present in the Nag-like dioxygenase gene cluster is missing, leaving it unclear how this cluster is expressed. The pattern of expression of the 2CNB catabolism cluster was investigated here. The results demonstrate that the expression was constitutive and not induced by its substrate 2CNB or salicylate, the usual inducer of expression in the Nag-like dioxygenase family. Reverse transcription-PCR indicated the presence of at least one transcript containing all the structural genes for 2CNB degradation. Among the three promoters verified in the gene cluster, P1 served as the promoter for the entire catabolism operon, but the internal promoters P2 and P3 also enhanced the transcription of the genes downstream. The P3 promoter, which was not previously defined as a promoter sequence, was the strongest of these three promoters. It drove the expression of
cnbAcAd
encoding the dioxygenase that catalyzes the initial reaction in the 2CNB catabolism pathway. Bioinformatics and mutation analyses suggested that this P3 promoter evolved through the duplication of an 18-bp fragment and introduction of an extra 132-bp fragment.

IMPORTANCE
The release of many synthetic compounds into the environment places selective pressure on bacteria to develop their ability to utilize these chemicals to grow. One of the problems that a bacterium must surmount is to evolve a regulatory device for expression of the corresponding catabolism genes. Considering that 2CNB is a xenobiotic that has existed only since the onset of synthetic chemistry, it may be a good example for studying the molecular mechanisms underlying rapid evolution in regulatory networks for the catabolism of synthetic compounds. The 2CNB utilizer
Pseudomonas stutzeri
ZWLR2-1 in this study has adapted itself to the new pollutant by evolving the always-inducible Nag-like dioxygenase into a constitutively expressed enzyme, and its expression has escaped the influence of salicylate. This may facilitate an understanding of how bacteria can rapidly adapt to the new synthetic compounds by evolving its expression system for key enzymes involved in the degradation of a xenobiotic.
Calcineurin and Calcium Channel CchA Coordinate the Salt Stress Response by Regulating Cytoplasmic Ca
2+
Homeostasis in Aspergillus nidulans
Authors: Wang Sha , Liu Xiao , Qian Hui , Zhang Shizhu , Lu Ling
Published: April 2016

The eukaryotic calcium/calmodulin-dependent protein phosphatase calcineurin is crucial for the environmental adaption of fungi. However, the mechanism of coordinate regulation of the response to salt stress by calcineurin and the high-affinity calcium channel CchA in fungi is not well understood. Here we show that the deletion of
cchA
suppresses the hyphal growth defects caused by the loss of calcineurin under salt stress in
Aspergillus nidulans
. Additionally, the hypersensitivity of the Δ
cnaA
strain to extracellular calcium and cell-wall-damaging agents can be suppressed by
cchA
deletion. Using the calcium-sensitive photoprotein aequorin to monitor the cytoplasmic Ca
2+
concentration ([Ca
2+
]
c
) in living cells, we found that calcineurin negatively regulates CchA on calcium uptake in response to external calcium in normally cultured cells. However, in salt-stress-pretreated cells, loss of either
cnaA
or
cchA
significantly decreased the [Ca
2+
]
c
, but a deficiency in both
cnaA
and
cchA
switches the [Ca
2+
]
c
to the reference strain level, indicating that calcineurin and CchA synergistically coordinate calcium influx under salt stress. Moreover, real-time PCR results showed that the dysfunction of
cchA
in the Δ
cnaA
strain dramatically restored the expression of
enaA
(a major determinant for sodium detoxification), which was abolished in the Δ
cnaA
strain under salt stress. These results suggest that double deficiencies of
cnaA
and
cchA
could bypass the requirement of calcineurin to induce
enaA
expression under salt stress. Finally, YvcA, a member of the transient receptor potential channel (TRPC) protein family of vacuolar Ca
2+
channels, was proven to compensate for calcineurin-CchA in fungal salt stress adaption.

IMPORTANCE
The feedback inhibition relationship between calcineurin and the calcium channel Cch1/Mid1 has been well recognized from yeast. Interestingly, our previous study (S. Wang et al., PLoS One
7:
e46564, 2012,
http://dx.doi.org/10.1371/journal.pone.0046564
) showed that the deletion of
cchA
could suppress the hyphal growth defects caused by the loss of calcineurin under salt stress in
Aspergillus nidulans
. In this study, our findings suggest that fungi are able to develop a unique mechanism for adapting to environmental salt stress. Compared to cells cultured normally, the NaCl-pretreated cells had a remarkable increase in transient [Ca
2+
]
c
. Furthermore, we show that calcineurin and CchA are required to modulate cellular calcium levels and synergistically coordinate calcium influx under salt stress. Finally, YvcA, a member of of the TRPC family of vacuolar Ca
2+
channels, was proven to compensate for calcineurin-CchA in fungal salt stress adaption. The findings in this study provide insights into the complex regulatory links between calcineurin and CchA to maintain cytoplasmic Ca
2+
homeostasis in response to different environments.
An Efficient Method To Generate Gene Deletion Mutants of the Rapamycin-Producing Bacterium Streptomyces iranensis HM 35
Authors: Netzker Tina , Schroeckh Volker , Gregory Matthew A. , Flak Michal , Krespach Mario K. C. , Leadlay Peter F. , Brakhage Axel A.
Published: April 2016

Streptomyces iranensisHM 35 is an alternative rapamycin producer toStreptomyces rapamycinicus. Targeted genetic modification of rapamycin-producing actinomycetes is a powerful tool for the directed production of rapamycin derivatives, and it has also revealed some key features of the molecular biology of rapamycin formation inS. rapamycinicus.The approach depends upon efficient conjugational plasmid transfer fromEscherichia colitoStreptomyces, and the failure of this step has frustrated its application toStreptomyces iranensisHM 35. Here, by systematically optimizing the process of conjugational plasmid transfer, including screening of various media, and by defining optimal temperatures and concentrations of antibiotics and Ca2+ions in the conjugation media, we have achieved exconjugant formation for each of a series of gene deletions inS. iranensisHM 35. Among them wererapK, which generates the starter unit for rapamycin biosynthesis, andhutF, encoding a histidine catabolizing enzyme. The protocol that we have developed may allow efficient generation of targeted gene knockout mutants ofStreptomycesspecies that are genetically difficult to manipulate.

IMPORTANCEThe developed protocol of conjugational plasmid transfer fromEscherichia colitoStreptomyces iranensismay allow efficient generation of targeted gene knockout mutants of other genetically difficult to manipulate, but valuable,Streptomycesspecies.
Metabolic Engineering of the Actinomycete Amycolatopsis sp. Strain ATCC 39116 towards Enhanced Production of Natural Vanillin
Authors: Fleige Christian , Meyer Florian , Steinbüchel Alexander
Published: April 2016

The Gram-positive bacterium
Amycolatopsis
sp. ATCC 39116 is used for the fermentative production of natural vanillin from ferulic acid on an industrial scale. The strain is known for its outstanding tolerance to this toxic product. In order to improve the productivity of the fermentation process, the strain's metabolism was engineered for higher final concentrations and molar yields. Degradation of vanillin could be decreased by more than 90% through deletion of the
vdh
gene, which codes for the central vanillin catabolism enzyme, vanillin dehydrogenase. This mutation resulted in improvement of the final concentration of vanillin by more than 2.2 g/liter, with a molar yield of 80.9%. Further improvement was achieved with constitutive expression of the vanillin anabolism genes
ech
and
fcs
, coding for the enzymes feruloyl-coenzyme A (CoA) synthetase (
fcs
) and enoyl-CoA hydratase/aldolase (
ech
). The transcription of both genes was shown to be induced by ferulic acid, which explains the unwanted adaptation phase in the fermentation process before vanillin was efficiently produced by the wild-type cells. Through the constitutive and enhanced expression of the two genes, the adaptation phase was eliminated and a final vanillin concentration of 19.3 g/liter, with a molar yield of 94.9%, was obtained. Moreover, an even higher final vanillin concentration of 22.3 g/liter was achieved, at the expense of a lower molar yield, by using an improved feeding strategy. This is the highest reported vanillin concentration reached in microbial fermentation processes without extraction of the product. Furthermore, the vanillin was produced almost without by-products, with a molar yield that nearly approached the theoretical maximum.

IMPORTANCE
Much effort has been put into optimization of the biotechnological production of natural vanillin. The demand for this compound is growing due to increased consumer concerns regarding chemically produced food additives. Since this compound is toxic to most organisms, it has proven quite difficult to reach high concentrations and molar yields. This study shows that improvements in the final vanillin concentrations and molar yields can be made through a combination of modification of the fermentation parameters and molecular strain engineering, without the need for methods such as continuous extraction from the fermentation broth. Using this approach, we were able to reach a final vanillin concentration of 22.3 g/liter, which is the highest vanillin concentration reported to date that was generated with
Amycolatopsis
sp. ATCC 39116 without additional extraction of the toxic product.
FDA Escherichia coli Identification (FDA-ECID) Microarray: a Pangenome Molecular Toolbox for Serotyping, Virulence Profiling, Molecular Epidemiology, and Phylogeny
Authors: Patel Isha R. , Gangiredla Jayanthi , Lacher David W. , Mammel Mark K. , Jackson Scott A. , Lampel Keith A. , Elkins Christopher A.
Published: April 2016

Most
Escherichia coli
strains are nonpathogenic. However, for clinical diagnosis and food safety analysis, current identification methods for pathogenic
E. coli
either are time-consuming and/or provide limited information. Here, we utilized a custom DNA microarray with informative genetic features extracted from 368 sequence sets for rapid and high-throughput pathogen identification. The FDA
Escherichia coli
Identification (FDA-ECID) platform contains three sets of molecularly informative features that together stratify strain identification and relatedness. First, 53 known flagellin alleles, 103 alleles of
wzx
and
wzy
, and 5 alleles of
wzm
provide molecular serotyping utility. Second, 41,932 probe sets representing the pan-genome of
E. coli
provide strain-level gene content information. Third, approximately 125,000 single nucleotide polymorphisms (SNPs) of available whole-genome sequences (WGS) were distilled to 9,984 SNPs capable of recapitulating the
E. coli
phylogeny. We analyzed 103 diverse
E. coli
strains with available WGS data, including those associated with past foodborne illnesses, to determine robustness and accuracy. The array was able to accurately identify the molecular O and H serotypes, potentially correcting serological failures and providing better resolution for H-nontypeable/nonmotile phenotypes. In addition, molecular risk assessment was possible with key virulence marker identifications. Epidemiologically, each strain had a unique comparative genomic fingerprint that was extended to an additional 507 food and clinical isolates. Finally, a 99.7% phylogenetic concordance was established between microarray analysis and WGS using SNP-level data for advanced genome typing. Our study demonstrates FDA-ECID as a powerful tool for epidemiology and molecular risk assessment with the capacity to profile the global landscape and diversity of
E. coli
.

IMPORTANCE
This study describes a robust, state-of-the-art platform developed from available whole-genome sequences of
E. coli
and
Shigella
spp. by distilling useful signatures for epidemiology and molecular risk assessment into one assay. The FDA-ECID microarray contains features that enable comprehensive molecular serotyping and virulence profiling along with genome-scale genotyping and SNP analysis. Hence, it is a molecular toolbox that stratifies strain identification and pathogenic potential in the contexts of epidemiology and phylogeny. We applied this tool to strains from food, environmental, and clinical sources, resulting in significantly greater phylogenetic and strain-specific resolution than previously reported for available typing methods.
Impact of health insurance status changes on healthcare utilisation patterns: a longitudinal cohort study in South Korea
Authors: Kim Jae-Hyun , Lee Sang Gyu , Lee Kwang-Soo , Jang Sung-In , Cho Kyung-Hee , Park Eun-Cheol
Published: April 2016

Objectives

The study examined medical care utilisation by health insurance status changes.

Setting

The Korean Welfare Panel Study (KoWePs) was used.

Participants

This study analysed 14 267 participants at baseline (2006).

Interventions

The individuals were categorised into four health insurance status groups: continuous health insurance, change from health insurance to Medical Aid, change from Medical Aid to health insurance, or continuous Medical Aid.

Primary and secondary outcome measures

Three dependent variables were also analysed: days spent in hospital; number of outpatient visits; and hospitalisations per year. Longitudinal data analysis was used to determine whether changes in health insurance status were associated with healthcare utilisation.

Results

The number of outpatient visits per year was 0.1.363 times higher (p<0.0001) in the continuous Medical Aid than in the continuous health insurance group. The number of hospitalisations per year was 1.560 times higher (p<0.001) in new Medical Aid and −0.636 times lower (p<0.001) in new health insurance than in continuous health insurance group. The number of days spent in hospital per year was −0.567 times lower (p=0.021) in the new health insurance than in the continuous health insurance group.

Conclusions

Health insurance beneficiaries with a coverage level lower than Medical Aid showed lower healthcare utilisation, as measured by the number of hospitalisations and days spent in hospital per year.
Towards a standardised informed consent procedure for live donor nephrectomy: the PRINCE (Process of Informed Consent Evaluation) project—study protocol for a nationwide prospective cohort study
Authors: Kortram Kirsten , Spoon Emerentia Q W , Ismail Sohal Y , d'Ancona Frank C H , Christiaans Maarten H L , van Heurn L W Ernest , Hofker H Sijbrand , Hoksbergen Arjan W J , Homan van der Heide Jaap J , Idu Mirza M , Looman Caspar W N , Nurmohamed S Azam , Ringers Jan , Toorop Raechel J , van de Wetering Jacqueline , Ijzermans Jan N M , Dor Frank J M F
Published: April 2016

Introduction

Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence.

Methods and analysis

The PRINCE (Process of Informed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardised format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is disclosed, in which format, etc) and correlation of donor knowledge with surgeons' estimation thereof.

Ethics and dissemination

Approval for this study was obtained from the medical ethical committee of the Erasmus MC, University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has been obtained from the local ethics committees in six participating centres. Approval in the last centre has been sought.

Results

Outcome will be published in a scientific journal.

Trial registration number

NTR5374; Pre-results.
Physical and functional outcomes following multidisciplinary residential rehabilitation for prearthritic hip pain among young active UK military personnel
Authors: Coppack Russell J , Bilzon James L , Wills Andrew K , McCurdie Ian M , Partridge Laura K , Nicol Alastair M , Bennett Alexander N
Published: April 2016

Background

There are no studies describing the clinical outcomes of a residential, multidisciplinary team (MDT) rehabilitation intervention for patients with prearthritic hip pain. The aim of this cohort study was to describe the functional and physical outcomes of multidisciplinary residential rehabilitation for UK military personnel with prearthritic hip pain.

Methods

Participants (N=40) with a mean age of 33 years referred to a specialist residential rehabilitation centre completed a comprehensive multidisciplinary residential intervention. The main outcome measures were mean pain, physical function (modified shuttle test (MST) and Y-balance test), hip range of motion (HROM) and a patient-reported outcome measure (The Copenhagen Hip and Groin Outcome Score, HAGOS). All scores for symptomatic hips were taken at baseline and post-treatment.

Results

There were improvements in the Y-balance test and HROM following rehabilitation. There were significant improvements in mean difference (T1-to-T2) for Y-balance scores (15.8 cm, 95% CI 10.7 to 20.9, p<0.001), HROM (6.5° increase in hip flexion, 95% CI 4.6 to 9.4, p<0.001) and hip internal rotation (4.6°, 95% CI 2.7 to 6.6, p<0.001). Scores for HAGOS, pain, MST and functional activity assessment showed no improvement.

Conclusions

Among UK military personnel with prearthritic hip pain, MDT residential rehabilitation resulted in improvements in a functional Y-balance test, hip flexion and internal rotation. The study suggests short-term benefits across some outcomes for the current UK military approach to MDT residential rehabilitation.
Distinction between contrast staining and hemorrhage after endovascular stroke treatment: one CT is not enough
Authors: Dekeyzer Sven , Nikoubashman Omid , Lutin Bart , De Groote Jeroen , Vancaester Evelien , De Blauwe Sofie , Hemelsoet Dimitri , Wiesmann Martin , Defreyne Luc
Published: April 2016

Background

Postinterventional cerebral hyperdensities (PCHDs) are a common finding after endovascular stroke treatment. There is uncertainty about the extent to which PCHDs correspond to hemorrhage or contrast staining. Our aim was to evaluate the use of PCHD density on immediate postinterventional CT, and PCHD evolution on follow-up CT for differentiating contrast staining from hemorrhage after endovascular treatment.

Methods

We retrospectively reviewed the imaging data of 84 patients who underwent endovascular treatment for acute arterial ischemic stroke in the anterior circulation and who received an immediate postinterventional CT, a follow-up CT within 36 h, and a follow-up MRI within 10 days.

Results

PCHDs were seen in 62 of 84 patients in a total of 130 Alberta Stroke Program Early CT Score (ASPECTS) areas. A specificity of 100% to predict hemorrhage was only seen for PCHDs with densities <40 HU (for ruling hemorrhage out) and ≥140 HU (for ruling hemorrhage in), at the cost of a low sensitivity of 1.1% and 2.4%, respectively. Persisting PCHDs correlated with hemorrhage with a specificity of 93.3% and a sensitivity of 62.5%. When follow-up CT was performed at least 19 h after the first CT, persisting PCHDs correlated with hemorrhage with a specificity of 100% and a sensitivity of 62.5%.

Conclusions

There are no density thresholds for PCHDs that allow predicting the absence or presence of hemorrhage with 100% specificity and acceptable sensitivity. A CT scan performed at least 19–24 h after endovascular therapy is the only reliable method to differentiate contrast staining from hemorrhage.
Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells
Authors: Thangjam Gagan S. , Birmpas Charalampos , Barabutis Nektarios , Gregory Betsy W. , Clemens Mary Ann , Newton Joseph R. , Fulton David , Catravas John D.
Published: April 2016

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation.
27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells
Authors: Hashimoto Yuichiro , Sugiura Hisatoshi , Togo Shinsaku , Koarai Akira , Abe Kyoko , Yamada Mitsuhiro , Ichikawa Tomohiro , Kikuchi Takashi , Numakura Tadahisa , Onodera Katsuhiro , Tanaka Rie , Sato Kei , Yanagisawa Satoru , Okazaki Tatsuma , Tamada Tsutomu , Kikuchi Toshiaki , Hoshikawa Yasushi , Okada Yoshinori , Ichinose Masakazu
Published: April 2016

Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells. Localization of senescence-associated proteins and sterol 27-hydroxylase was investigated in the lungs of COPD patients by immunohistochemical staining. To evaluate whether 27-OHC accelerates cellular senescence, lung resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated tissue repair were investigated in the 27-OHC-treated cells. Expression of senescence-associated proteins was significantly enhanced in lung fibroblasts of COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly upregulated in lung fibroblasts and alveolar macrophages in these patients. Treatment with the concentration of 27-OHC detected in COPD airways significantly augmented expression of senescence-associated proteins and senescence-associated β-galactosidase activity, and delayed cell growth through the prostaglandin E2-reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue repair function. Fibroblasts from lungs of COPD patients showed accelerated senescence and were more susceptible to 27-OHC-induced cellular senescence compared with those of healthy subjects. In conclusion, 27-OHC accelerates cellular senescence in lung resident cells and may play a pivotal role in cellular senescence in COPD.
Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation
Authors: Hung Amos C. , Lo Steven , Hou Ming-Feng , Lee Yi-Chen , Tsai Chun-Hao , Chen Yuan-Yin , Liu Wangta , Su Yu-Han , Lo Yi-Hsuan , Wang Chie-Hong , Wu Shiou-Chen , Hsieh Ya-Ching , Hu Stephen Chu-Sung , Tai Ming-Hong , Wang Yun-Ming , Yuan Shyng-Shiou F.
Published: April 2016

Purpose: Visfatin is an adipocytokine involved in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings.

Experimental Design: Associations of serum visfatin with clinicopathologic characteristics and patient survival were assessed with Cox regression models and Kaplan–Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were used to inhibit c-Abl and STAT3 activation, respectively.

Results: Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatin-promoted in vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was observed in zebrafish xenografted with visfatin-pretreated breast cancer cells. Tumor growth and lung metastasis occurred in visfatin-administered mice xenografted with breast cancer cells. Tail vein–injected mice with visfatin-pretreated breast cancer cells showed increased lung metastasis, which was suppressed by imatinib.

Conclusions: Serum visfatin levels in breast cancer patients reveal potential prognostic values, and our findings that visfatin promoted breast cancer through activation of c-Abl and STAT3 may provide an important molecular basis for future design of targeted therapies that take into account different serum visfatin levels in breast cancer. Clin Cancer Res; 22(17); 4478–90. ©2016 AACR.
How Cinderella Became a Queen
Authors: Delmestri Giuseppe , Greenwood Royston
Published: April 2016

Using a case study of the Italian spirit grappa, we examine status recategorization—the vertical extension and reclassification of an entire market category. Grappa was historically a low-status product, but in the 1970s one regional distiller took steps that led to a radical break from its traditional image, so that in just over a decade high-quality grappa became an exemplar of cultured Italian lifestyle and held a market position in the same class as cognac and whisky. We use this context to articulate “theorization by allusion,” which occurs through three mechanisms: category detachment—distancing a social object from its existing category; category emulation—presenting that object so that it hints at the practices of a high-status category; and category sublimation—shifting from local, field-specific references to broader, societal-level frames. This novel theorization is particularly appropriate for explaining change from low to high status because it avoids resistance to and contestation of such change (by customers, media, and other sources) as a result of status imperatives, which may be especially strong in mature fields. Unlike prior studies that have examined the status of organizations within a category, ours foregrounds shifts in the status and social meaning of a market category itself.
Drawing Upon Lessons Learned
Authors: Swanson Julie Dingle
Published: April 2016

Javits Gifted and Talented Education Program has provided a wealth of knowledge on culturally and linguistically diverse (CLD) gifted learners and how to support teachers in their work with CLD students. This study examined five impactful Javits projects through qualitative inquiry centered on how innovative practice takes root or not. Using grounded theory tradition, examination of Javits project participation enabled insight into how educators act and react to innovation as well as their perceptions of CLD student impacts. Data sources (documents, conversations with principal investigators, and interviews with 14 educators) provide evidence for what sustains effective, research-based practices and explores continued student benefits. Major findings are (a) context matters in sustaining innovation, (b) powerful curriculum and instruction can transform teaching and teachers, and (c) student impacts continue. Data point to leadership as an underlying element in sustaining innovation. Leaders ensure that innovation extends from broad-based goals; they develop innovation through scale-up and involvement of others; they purposefully track results. Growing effective approaches is critical to access and opportunity and CLD-gifted learners’ talent development.
The Effect of US Troop Deployments on Human Rights
Authors: Bell Sam R. , Clay K. Chad , Martinez Machain Carla
Published: April 2016

US noninvasion troops deployed abroad often try to promote greater respect for human rights in the host country. The host country, having an incentive to retain the troop presence, may choose to comply with these requests. We argue that this effect will not be at play in states with high security salience for the United States (US) (for which the US may not be able to credibly threaten to remove the troops). In these cases, US deployments will provide the leader with security from both internal and external threats that is independent of the local population’s support for the leader. Host state leaders thus become less reliant on (and potentially less responsive to) their local populations, which in turn may lead to increased human rights violations. In this article, we use data on both US troop deployments abroad and on human rights violations to test these arguments from 1982 to 2005.
Walking the Line
Authors: Prasad Monica , Hoffman Steve G. , Bezila Kieran
Published: April 2016

Over one-third of the white working class in America vote for Republicans. Some scholars argue that these voters support Republican economic policies, while others argue that these voters’ preferences on cultural and moral issues override their economic preferences. We draw on in-depth interviews with 120 white working-class voters to defend a broadly “economic” interpretation: for this segment of voters, moral and cultural appeals have an economic dimension, because these voters believe certain moral behaviors will help them prosper economically. Even the very word “conservative” is understood as referencing not respect for tradition generally, but avoidance of debt and excessive consumption specifically. For many respondents, the need to focus on morality and personal responsibility as a means of prospering economically—what we call “walking the line”—accords with the rhetoric they associate with Republicans. Deindustrialization may have heightened the appeal of this rhetoric.
Comparison of state estimation techniques for nonlinear hybrid systems
Authors: Zhou Gan , Biswas Gautam , Zhang Wenfeng , Zhao Qi , Feng Wenquan
Published: April 2016

Modern real-world engineering systems exhibit complex hybrid behaviors, which are composed of continuous nonlinear plant dynamics interspersed with discrete mode switching. State estimation of hybrid systems for accurate and timely online monitoring and diagnosis applications is a difficult task. A number of different methods have been proposed, and we develop a conceptual framework to perform a comparative study of four different hybrid state estimation algorithms in this paper: (1) the switched extended Kalman filter; (2) focused hybrid estimation; (3) multiple-modal particle filtering; and (4) the one-step look-ahead particle filtering. The conceptual comparison is followed by an empirical evaluation, where we study the effectiveness of these algorithms in tracking the behaviors of a Reverse Osmosis Subsystem of an Advanced Water Recovery System that was developed at the NASA Johnson Space Center. We discuss our results, which show the strengths and weaknesses of each of these algorithms, and propose topics for further research into this important problem.
Popper, Objectification, and the Problem of the Public Sphere
Authors: Shearmur Jeremy
Published: April 2016

Shearmur argues for the importance of Popper’s ideas about World 3, and against the idea that they should be re-interpreted in social terms. However, he also argues for the importance of Popper’s ideas about methodological rules—and that these may be given a partially social interpretation. The content of our ideas may in consequence differ from what we take it to be, as a consequence of our institutions and practices operating as methodological rules. He also explores related ideas about the interplay between World 3 and social factors in connection with Darnton’s ideas about the book and work that has built on it, and related issues about the public sphere and the problem of effective deliberative feedback on public policy.
Popper’s Theory of World 3 and the Evolution of the Internet
Authors: Backes Peter
Published: April 2016

While developing his theory of world 3, Popper rejects two claims made by Plato: first, that the inhabitants of world 3, ideas, are a source of ultimate explanation, a divine revelation of truth, and second, that these ideas are unchanging. I will rehabilitate the second claim. Man does not construct world 3 by creating his theories (as Popper claims), nor is it a source of ultimate truth (as Plato claims). Instead, world 3 is discovered by man, and it destroys some of his theories: destructive Platonism. I discuss the impact of the modified position on the Grundlagenstreit in mathematics, taking into account Gillies’s constructive Aristotelianism. I then turn to the philosophy of computers and discuss how destructive Platonism relates to computers and the Internet. In particular, I criticize Popper’s claim that computers are nothing but elaborate pens as too pessimistic and incautious, and the fashionable “singularity” theory (von Neumann, Ulam, Vinge, Kurzwell, Hawking) as too optimistic and at the same time too fatalistic. In my closing remarks, as an antidote against both views, I provide a more modest and reasonable (although, of course, very wild) speculation about the ultimate goal and meaning of life.
Phonological Transfer as a Forerunner of Merger in Upstate New York
Authors: Dinkin Aaron J.
Published: April 2016

Herold (1990) discusses three mechanisms by which phonemic merger can take place: expansion, approximation, and transfer. A fourth possibility Herold touches on but does not explore might be called phonological transfer: as in (lexical) transfer, words move abruptly from one phonemic class to another; but rather than one lexeme at a time being transferred, all words of a particular phonological class move simultaneously. This paper provides evidence that phonological transfer is playing a role in the movement toward merger of /o/ (as in lot) and /oh/ (as in thought) in Upstate New York. Words containing (olF)—i.e., historical /o/ followed by /l/ plus a labiovelar, as in golf and revolve—are produced with /oh/ rather than /o/ in 74 percent of tokens; this use of /oh/ is increasing in apparent time. Many speakers using /oh/ in (olF) words have an otherwise clear phonemic distinction between /o/ and /oh/; however, the geographic distribution of this phonological transfer is correlated with other indices of progress toward the low back merger. This indicates that phonological transfer can be regarded here as an early sign of merger in progress, and that a single merger can proceed by two mechanisms simultaneously (here, approximation and phonological transfer).
Emplacing Risks in the City: Class, Politics, Risk, and the Built Environment of Women’s Residential Clubs, 1896-1917
Authors: Bartram Robin
Published: April 2016

Residential clubs for women in Progressive Era urban America offered protection against risks in the city. This article is an investigation into the relationship between perceptions of risk, built environments, class, and political ideology at two such clubs in Chicago. I merge theories of risk with Bourdieu’s notions of fields, symbolic violence, and symbolic labor to establish two new concepts: risk ideology and risk emplacement. Risk ideologies are sets of ideas about what and where is dangerous. Risk emplacement is the process through which social actors align risk ideologies with certain places and places with particular risks. I argue that these concepts address a general concern in urban history: how built environments organize populations and how aesthetic concerns are distinct from—yet often work to reproduce—class and political ideologies.
Glazed balconies as passive greenhouse systems – Potential of their use in Poland
Authors: Grudzińska Magdalena
Published: April 2016

The paper discusses the possibilities of using passive greenhouse systems, such as glazed balconies, in an example residential building. The analyses were carried out for five localities in Poland, different in terms of external air temperature and insolation. Typical meteorological years were used as the source of climatic data needed in calculations. Two types of balcony’s casing were evaluated, with high and low thermal insulating properties. Demand for heating and cooling in a flat was determined with the use of dynamic computer simulations, and the outcomes were compared with the energy performance of a flat with an open balcony. Additionally, the number of hours with the internal operative temperature exceeding 26℃ was taken as a measure of overheating the apartment when natural airing by opening windows was included in simulations. The calculations showed diversification in the effectiveness of greenhouse systems resulting from climatic conditions, and allowed areas which are the most suitable for the passive use of solar radiation to be identified.

Practical application: Analyses present energy savings in a typical dwelling achieved thanks to glazed balconies, and allow to choose the most efficient type of balcony’s envelope taking into account the heating and cooling demand, and the risk of overheating. The results are diversified in respect of building’s location, showing the areas of Poland where the passive use of solar energy would be most beneficial. The calculations may become the basis for further economical evaluation of greenhouse systems effectiveness.
Looking Out From the Top
Authors: Blader Steven L. , Shirako Aiwa , Chen Ya-Ru
Published: April 2016

The impact of hierarchical rank on perspective taking is both practically and theoretically important, prompting considerable research attention to this issue. However, prior research has primarily examined how power affects perspective taking, and has neglected to investigate the impact of status (i.e., the respect and esteem that an individual holds in the eyes of others). Yet status represents a distinct and ubiquitous basis of hierarchical differentiation, one that may profoundly affect perspective taking. The current research addresses this gap, theorizing and testing the prediction that high status enhances perspective taking, in contrast to prior research that has generally found that high power diminishes perspective taking. Five studies, examining various forms of perspective taking across diverse paradigms, provide converging evidence that status and power exert differential effects on perspective taking. Moreover, these studies provide insight regarding the distinction between status and power, as well as the distinct psychology associated with status.
Are the Powerful Really Blind to the Feelings of Others? How Hierarchical Concerns Shape Attention to Emotions
Authors: Stamkou Eftychia , van Kleef Gerben A. , Fischer Agneta H. , Kret Mariska E.
Published: April 2016

Paying attention to others’ emotions is essential to successful social interactions. Integrating social-functional approaches to emotion with theorizing on the reciprocal nature of power, we propose that attention to others’ emotions depends on concerns over one’s power position and the social signal conveyed by the emotion. Others’ anger signals attack—information relevant to high-power individuals who are concerned about the legitimacy or suitability of their position. On the contrary, others’ fear signals vulnerability—information relevant to low-power individuals who are concerned about their unfair treatment within an illegitimate hierarchy. Accordingly, when power roles were illegitimately assigned or mismatched with one’s trait power, leaders were faster at detecting the appearance of anger (Studies 1 and 2), slower at judging the disappearance of anger (Study 2), and more accurate in recognizing subordinates’ anger, whereas subordinates were more accurate in recognizing leaders’ fear (Study 3). Implications for theorizing about emotion and social hierarchy are discussed.
Attachment insecurity and perceived importance of relational features
Authors: Ren Dongning , Arriaga Ximena B. , Mahan Elizabeth R.
Published: April 2016

Chronic attachment insecurity can affect the outlook people have on relationships. This research examines how attachment insecurity relates to perceived importance of various features in a romantic relationship (e.g., intimacy, independence). Consistent with predictions, the results from Studies 1–3 ( N1 = 53, N2 = 226, N3 = 196) revealed that greater attachment anxiety was associated with ranking intimacy higher in importance and independence lower, whereas attachment avoidance was associated with ranking independence higher, intimacy, and trust lower. Study 4 ( N4 = 175) further showed that insecure participants recognized that some of their priorities are unique to themselves and not shared by others. Additionally, they did not perceive their current relationships as having more of the relational features they prioritized. Insecure individuals thus have unique relational priorities, which may direct their romantic judgments and decisions.
The influence of the impedance function on gravity-based pedestrian accessibility measures: A comparative analysis
Authors: Vale David S , Pereira Mauro
Published: April 2016

Pedestrian accessibility has been growing in importance as an urban planning objective. Assessing it with gravity-based or potential accessibility measures requires the selection of an impedance function in order to reflect the friction of distance. The choice of impedance function is crucial to pedestrian accessibility assessment due to the level of spatial data detail required and also because perceived distances differ from physical distances. Here, we measure and compare 20 gravity-based measures, varying the impedance function and associated parameters. Correlation analysis revealed a significant and strong correlation between the measures. Factor analysis extracted two groups of measures, differing mainly in their maximum cutoff travel distance, i.e. the distance at which the impedance function reaches zero. Spatial analysis revealed that all measures produce similar spatial results in terms of identifying high and low accessibility locations but different values for medium accessibility locations. Places located at between 200 and 400 m from an opportunity are especially sensitive to the impedance function used. We promote a cumulative–Gaussian approach to measure pedestrian accessibility, as it explicitly includes the travel tolerance concept and we found it to be the most robust measure in terms of data variability.
Processing nonnative consonant clusters in the classroom: Perception and production of phonetic detail
Authors: Davidson Lisa , Wilson Colin
Published: April 2016

Recent research has shown that speakers are sensitive to non-contrastive phonetic detail present in nonnative speech (e.g. Escudero et al. 2012; Wilson et al. 2014). Difficulties in interpreting and implementing unfamiliar phonetic variation can lead nonnative speakers to modify second language forms by vowel epenthesis and other changes. These difficulties may be exacerbated in the classroom, as previous studies have found that classroom acoustics have a detrimental effect on listeners’ ability to identify nonnative sounds and words (e.g. Takata and Nábělek, 1990). Here we compare the effects of two acoustic environments – a sound booth and a classroom – on English speakers’ ability to process and produce unfamiliar consonant sequences in an immediate shadowing task. A number of acoustic–phonetic properties were manipulated to create variants of word-initial obstruent–obstruent and obstruent–nasal clusters. The acoustic manipulations significantly affected English speakers’ correct productions and detailed error patterns in both the sound booth and the classroom, suggesting that the relevant acoustic detail is not substantially degraded by classroom acoustics. However, differences in the response patterns in the two environments indicate that the classroom setting does affect how speakers interpret nonnative phonetic detail for the purpose of determining their production targets.