bluuebunny/crossref_metadata_2025 huggingface dataset:
The Contributions of Economic Anthropology to the Political Economy of Cities
Authors: Koenig Dolores , Matejowsky Ty
Published: January 2015

Urban anthropology's centrality within anthropology and the growing importance of urban areas to global modernity are reflected in the choice of the Society for Economic Anthropology (SEA) to focus its 2012 meeting and this journal volume on the political economy of cities. In this volume, we undertake two tasks. First, we emphasize patterns of urban inequality and political struggle that inform the distribution of economic resources and the ways in which those with fewer resources manipulate and challenge the dominant pattern of resource allocation. Second, we focus on three topical areas of general anthropological interest and contemporary importance: (a) the transformation of urban economies in light of contemporary neoliberalism and how such changes affect the livelihoods of market vendors and less‐affluent urban residents, (b) forms of ancient and contemporary city planning, the political and economic interests behind them, and their subsequent effect on diverse urban communities, and (c) attempts by political leaders and policymakers to control the movement of urban populations and the consequent economic impacts on those forced to move or discouraged from moving. Although the featured articles reflect only a small portion of current work on the political economy of cities, they show clearly that elites working to create cities and urban spaces to their own benefit frequently marginalize and suppress the interests of the poor and working class. However, disadvantaged groups also work in their own interests for tangible benefits and future social mobility.
Unsettling Urban Marketplace Redevelopment in Baguio City, Philippines
Authors: Milgram B. Lynne
Published: January 2015

Urban public marketplaces in Global South cities host a vibrant mix of retail and wholesale trade. Yet local‐to‐national governments increasingly promote sanitized and privatized urban spaces by privileging modern retail outlets (malls and supermarkets) and discouraging “traditional” livelihoods (street vending and market stalls). These political decisions dramatically disrupt the public market trade that has provisioned urbanites for decades. To address this issue, this article analyzes how retailers working in the renowned Baguio City Public Market, northern Philippines, sustain their livelihoods given that Baguio City's first phase of market redevelopment failed to meet their needs (e.g., insufficient store size and banning enterprises). Problematizing legal–illegal work and urban public space use, I argue that public marketers engage everyday and insurgent public space activism to protest their disenfranchisement. Although marketers generally have achieved selected demands, some have benefited more than others. Thus, I suggest that we consider not only marketers' resistance but also the uneven political landscape within which they work—the power differentials among and between marketers and the state. The extent to which variously positioned marketers can realize livelihood rights highlights the unpredictability of civic engagement and “extralegality” when competing ideologies clash over access to urban public space, legal–illegal practice, and appropriate urban provisioning.
The Urban System in the Central Valleys of Oaxaca
Authors: Murphy Arthur D. , Silva Ignacio R. , Morales Rafael R. , Gil Jose L. B. , Segura Jesus J. F.
Published: January 2015

In this article, we explore the nature of the urban system in the Valley of Oaxaca as it has developed in the late 20th century, when Mexico joined the General Agreement on Tariffs and Trade (GATT) (1986) and negotiated the North American Free Trade Agreement (NAFTA) with the United States and Canada (1994, with final aspects of the agreement going into effect in 2008). Both the events exposed Mexico and, by extension, Oaxaca to powerful external economic forces. Global integration significantly altered the urban and regional economic systems in the central valleys of Oaxaca. The conquest of Mexico by Spain in the early 16th century brought Mexico into the global economic system centered in Europe. For most of the five centuries since the arrival of the Spanish, Oaxaca was part of what Immanuel Wallerstein described as the periphery, that is, regions whose primary role in the system was to provide raw goods and labor to core regions such as Mexico City, Madrid, London, and New York. This article describes how the integration of Oaxaca into the world economy that resulted from Mexico's entry into GATT and NAFTA altered the nature of the urban system in the central valleys of Oaxaca. These changes significantly increased the role of Oaxaca City in the extraction of resources from the state into the world economy and increased wealth disparities in the central valleys.
Residential Design Guidelines, Aesthetic Governmentality, and Contested Notions of Southern California Suburban Places
Authors: Lawrence‐Zúñiga Denise
Published: January 2015

Since the 1970s, San Gabriel Valley suburban cities have become a desirable destination for thousands of immigrants from Taiwan, Hong Kong, mainland China, and Southeast Asia, but their remaking of existing residential landscapes has provoked controversy and opposition. At play are two contrasting real estate value regimes: a regional or transnational perspective held by most immigrants and a traditional or preservationist view advocated by long‐term, mostly white residents. This study explores the role of urban planners' use of residential design guidelines to limit and shape home construction practices in four cities. The delineation of common components of “aesthetic governmentality,” including episteme, identities, visibility, techne, and ethos, framed the examination of the guidelines and design review procedures. Analysis reveals the challenges planners and design review boards face implementing regulations based on expert understandings of visual architectural forms. Although initially resistant to such design requirements, immigrants finally complied by hiring design professionals in the same way long‐term residents do.
Design Standards as Urban Planning: From Technical Specification to Community “Look” in Northeast Illinois Suburbs
Authors: Rotenberg Robert
Published: January 2015

Design standards, an urban and municipal branding device that originated as a practice in the United States some two decades ago, have become one of the most powerful place‐making forces currently operating in U.S. suburbs. This article addresses how these standards work to shape development decisions by various stakeholders in localities in Cook County, Illinois. Drawing on observations from several 2010 public architectural review commission hearings in nine different suburbs, I argue that design standards are forward‐looking and ideology‐based practices that are open to negotiation over the short run but ultimately end up shaping the “look” of the community over the long run. Implicit in such strategies is a reliance on an imputed agency of design in the built environment.
The Paved and the Unpaved: Toward a Political Economy of Infrastructure, Mobility, and Urbanization in Haiti
Authors: Yarrington Landon
Published: January 2015

This article argues that an ideological struggle organized around competing Haitian cultural definitions of liberté conditioned the development of Haiti's transport infrastructure from independence in 1804 to the U.S. Occupation of 1915–1934. This definition of liberté was linked to the ideological reproduction of state power by maintaining cultural constructions of people as urban or rural. Using historical sources, an analysis of the institutions, policies, and practices of infrastructure use and development shows that movement itself serves as cultural symbol and site of ideological struggle, as differential access to freedom of movement influences the maintenance of urban and rural classifications. During the colonial period and immediately after independence, the plantation economy neglected transport infrastructure, which helped keep cities small and laborers on plantations. By the mid‐19th century, the plantation economy collapsed, and landowners moved to port cities to enter commerce or politics. Smallholding peasantries emerged in rural areas, but continued lack of transport investment kept them there. Only in the late 19th century did Haitian elites invest in transport infrastructure; this was enhanced by the early‐20th‐century American occupation. Only then did cities begin to grow substantially.
Political Economy of Control: Urban Refugees and the Regulation of Space in Lusaka, Zambia
Authors: Frischkorn Rebecca
Published: January 2015

Although Zambia is routinely praised by the international community for accepting the overwhelming majority of asylum seekers, it attempts to control refugee movement and residency by keeping the majority in refugee camps and settlements and limiting the number allowed in urban areas. However, many refugees continue to live in cities without the required urban residency permits and despite risks of arrest and exploitation. This article examines the efforts of the Zambian government to limit and control its urban refugee population in Lusaka, linking the structure of the global political economy to treatment of refugees. As the Ministry of Home Affairs implements its urban residency policy and registration systems and immigration officers often arbitrarily enforce it through raids on markets and neighborhoods, refugees negotiate the spaces of the city, discovering where to live and move; find work and housing; seek assistance and social services; and become detained, imprisoned, deported, or released. This article further considers not only how power is exercised in this context but also how and why systems of control fail to work effectively or efficiently.
Evaluating hospital performance based on excess cause‐specific incidence
Authors: Van Rompaye Bart , Eriksson Marie , Goetghebeur Els
Published: January 2015

Formal evaluation of hospital performance in specific types of care is becoming an indispensable tool for quality assurance in the health care system. When the prime concern lies in reducing the risk of a cause‐specific event, we propose to evaluate performance in terms of an average excess cumulative incidence, referring to the center's observed patient mix. Its intuitive interpretation helps give meaning to the evaluation results and facilitates the determination of important benchmarks for hospital performance. We apply it to the evaluation of cerebrovascular deaths after stroke in Swedish stroke centers, using data from Riksstroke, the Swedish stroke registry. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Plasmonic Ag@Oxide Nanoprisms for Enhanced Performance of Organic Solar Cells
Authors: Du Peng , Jing Pengtao , Li Di , Cao Yinghui , Liu Zhenyu , Sun Zaicheng
Published: January 2015

Localized surface plasmon resonance (LSPR), light scattering, and lowering the series resistance of noble metal nanoparticles (NPs) provide positive effect on the performance of photovoltaic device. However, the exciton recombination on the noble metal NPs accompanying above influences will deteriorate the performance of device. In this report, surface‐modified Ag@oxide (TiO2 or SiO2) nanoprisms with 1–2 nm shell thickness are developed. The thin film composed of P3HT/Ag@oxides and P3HT:PCBM/Ag@oxides is investigated by absorption, photoluminescence (PL), and transient absorption spectroscopy. The results show a significant absorption, PL enhancement, and long‐lived photogenerated polaron in the P3HT/Ag@TiO2 film, indicating the increase of photogenerated exciton population by LSPR of Ag nanoprisms. In the case of P3HT/Ag nanoprisms, partial PL quench and relatively short‐lived photogenerated polaron are observed. That indicates that the oxides layer can effectively avoid the exciton recombination. When the Ag@oxide nanoprisms are introduced into the active layer of P3HT:PCBM photovoltaic devices, about 31% of power conversion efficiency enhancement is obtained relative to the reference cell. All these results indicate that Ag@oxides can enhance the performance of the cell, at the same time the ultrathin oxide shell prevents from the exciton recombination.
Heterochromatin Protein 1 Alpha (HP1α: CBX5) is a Key Regulator in Differentiation of Endothelial Progenitor Cells to Endothelial Cells
Authors: Maeng Yong-Sun , Kwon Ja Young , Kim Eung Kweon , Kwon Young-Guen
Published: January 2015

As the ability to control the differentiation of endothelial stem/progenitor cells (EPCs) into vascular endothelial cell lineages could be useful for promoting neovascularization, it is important to obtain a deeper understanding of the epigenetic mechanisms that regulate EPC differentiation and neovascularization. Heterochromatin protein 1α (HP1α) is known to be involved in the epigenetic regulation of gene silencing. However, recent reports demonstrate that HP1α can also activate gene expression during cell differentiation. In this study, microarray analysis revealed that HP1α expression was induced during EPC differentiation and is associated with the expression of outgrowing endothelial cell (OEC)-specific protein markers. To explore the role of HP1α in the differentiation of EPCs to OECs, its expression was knocked-down or over-expressed in differentiating EPCs. Overexpression of HP1α promoted the differentiation and angiogenic activity of EPCs in vitro and in vivo, whereas knockdown of HP1α led to a defect in OEC migration, tube formation, and angiogenic sprouting activity. Gene expression profiling showed increased expression of angiogenic genes, including NOTCH1, cadherin-5, and angiopoietin-like-2, and decreased expression of progenitor cell marker genes, including CD133, CXCR4, and C-KIT, in HP1α-overexpressing EPCs. Also, increased HP1α at an early stage of EPC differentiation may regulate angiogenic gene transcription by interacting with chromatin that modifies epigenetic factors such as the methyl-CpG binding domain, Polycomb group ring finger 2, and DNA methyltransferases. Our findings demonstrate, for the first time, that HP1α plays an important role in the differentiation and angiogenic function of EPCs by regulating endothelial gene expression. Stem Cells  2015;33:1512–1522
Twist1 and Snail Link Hedgehog Signaling to Tumor-Initiating Cell-Like Properties and Acquired Chemoresistance Independently of ABC Transporters
Authors: Kong Ying , Peng Yuanqiu , Liu Yuan , Xin Hong , Zhan Xia , Tan Wenfu
Published: January 2015

The Hedgehog (Hh) signaling pathway has been implicated in acquired chemoresistance. However, it remains unclear whether and how the Hh pathway may maintain the chemoresistant phenotype by controlling the tumor-initiating cell-like properties of acquired chemoresistant cancer cells. In this study, using well-established acquired chemoresistant cancer cells and chemosensitive KB cancer cells with artificially elevated Hh pathway activity, we found that Hh pathway activity may transcriptionally control the expression of twist1 and snail, thereby maintaining the tumor-initiating cell-like properties and consequently the chemoresistant phenotype. Meanwhile, we obtained direct evidence that twist1, which may amplify Hh signaling activity and plays an essential role in limb development, is a direct transcriptional target of Gli, similar to snail. We further observed that the expression of ATP-binding cassette (ABC) transporters was dispensable for the chemoresistance mediated by twist1 and snail. Collectively, these findings demonstrate that twist1, together with snail, links the Hh pathway to the tumor-initiating cell-like properties of chemoresistant cells. This consequently promotes chemoresistance independently of ABC transporters, thereby contributing to future development of strategies for combating chemoresistance through Hh pathway interference. Furthermore, our finding that twist1 is a direct target of the transcription factor Gli improves the interpretation of the association between twist1 and the Hh pathway and the nature of the signaling transduction of the Hh pathway. Stem Cells  2015;33:1063–1074
The impact of atmospheric stability on the near‐surface wind over sea in storm conditions
Authors: Baas P. , Bosveld F. C. , Burgers G.
Published: January 2015

We study the influence of boundary layer stability on the near‐surface wind speed, especially for high‐wind conditions. An analysis of the wind speed ratio between two vertical levels observed at tall masts in the North Sea and The Netherlands demonstrates that over sea non‐neutral conditions commonly occur, even when the 10 m wind speed is 7 Bft or higher (at least 13.9 ms−1). Over land, stability conditions are always close to neutral for these strong wind conditions. This is because over land, large vertical temperature differences are rare in these conditions. An analysis of 30 years of station data shows that even in storm conditions the ratio of the 10 m wind speed between sea and land depends systematically on the difference between the air temperature and the sea surface temperature. The observational results are reproduced by HARMONIE, a state‐of‐the‐art Numerical Weather Prediction model, although the impact of stability is smaller than in the observations. A model sensitivity analysis for a severe storm shows that the near‐surface wind speed over sea can vary by 10% depending on the difference between the air temperature and the sea surface temperature. The results presented in this study indicate that even in conditions that are usually classified as ‘(near) neutral’, small variations in stability may have a significant impact on the wind profile. They also indicate that for high wind speeds, the sea‐to‐land wind speed ratio is dominated by the stability over sea as in these conditions the stability over land is close to neutral. Copyright © 2015 John Wiley & Sons, Ltd.
Recent advances in nanotechnology for diabetes treatment
Authors: DiSanto Rocco Michael , Subramanian Vinayak , Gu Zhen
Published: January 2015

Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to ‘closed‐loop’ insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels (BGLs). ‘Closing the loop’ between BGL measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. WIREs Nanomed Nanobiotechnol 2015, 7:548–564. doi: 10.1002/wnan.1329

This article is categorized under:

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
The Role of Fracture Reduction and Plate Position in the Aetiology of Flexor Pollicis Longus Tendon Rupture after Volar Plate Fixation of Distal Radius Fractures
Authors: Selvan David R. , Machin David G. , Perry Daniel , Simpson Claire , Thorpe Phillipa , Brown Daniel J.
Published: January 2015

Background

Flexor pollicis longus (FPL) rupture has been described as complication following volar plating for distal radius fractures. It has been hypothesised that this is due to plate prominence. The aim of the study was to investigate the relationship between sub-optimal plate position and fracture reduction on plate prominence.

Methods

Plate prominence was measured in two experimental models. In the first, the effect of plate position was investigated using 18 fresh frozen cadavers with prominence being measured using a micrometer. In the second study, the effect of fracture reduction on plate prominence was investigated using similar methodology with simulated mal-reductions on dry bone models.

Results

The results of the first study showed a significant increase in lift-off for three plates (DVR, Synthes Universal and Acu-Loc), if the plates were moved distally or proximally from the anatomical position. Similar increases in prominence were also seen with rotational mal-positions. The results of the second study showed a statistically significant effect on plate prominence for even a 5° mal-reduction ( p=0.001) with worsening lift-off with increasing mal-reduction. These changes are significantly different from baseline and also significantly different to the lift-off recorded with mal-reductions 5° better and worse. Mal-reductions also necessitate more proximal placement of the plate to avoid screw penetration of the articular surface, and each 5° increment is significantly different from baseline.

Conclusions

The results show a statistically and clinically significant effect of both plate position and fracture reduction on plate prominence and support the theory that both contribute to the aetiology of post-operative FPL rupture.
The sensitivity to change over time of the Amsterdam IADL Questionnaire©
Authors: Koster Naomi , Knol Dirk L. , Uitdehaag Bernard M.J. , Scheltens Philip , Sikkes Sietske A.M.
Published: January 2015

Introduction

This study aimed to investigate the sensitivity to change over time of a new informant‐based instrument to assess instrumental activities of daily living (IADL) during the course of dementia: the Amsterdam IADL Questionnaire© (A‐IADL‐Q).

Methods

Participants (n = 102) were patients and their informants who visited the Alzheimer Center of the VU University Medical Center. Linear mixed models with random effects were used to relate longitudinal change on the A‐IADL‐Q to diagnosis and to longitudinal change in cognitive measures.

Results

We found longitudinal change on the A‐IADL‐Q to differ between diagnosis (P = .003), with dementia patients showing the fastest rate of decline (P < .001). In addition, we found longitudinal change on the A‐IADL‐Q to be related to longitudinal change in cognitive measures (global cognition: P < .001; memory: P = .024; executive functioning: P = .028).

Discussion

Findings indicate the A‐IADL‐Q is sensitive to change over time in IADL functioning and can be used in evaluating treatment effects and assessing individual disease progress.
Spectral modelling of high Reynolds number unstably stratified homogeneous turbulence
Authors: Burlot A. , Gréa B.-J. , Godeferd F. S. , Cambon C. , Griffond J.
Published: January 2015

We study unconfined homogeneous turbulence with a destabilizing background density gradient in the Boussinesq approximation. Starting from initial isotropic turbulence, the buoyancy force induces a transient phase toward a self-similar regime accompanied by a rapid growth of kinetic energy and Reynolds number, along with the development of anisotropic structures in the flow in the direction of gravity. We model this with a two-point statistical approach using an axisymmetric eddy-damped quasi-normal Markovian (EDQNM) closure that includes buoyancy production. The model is able to match direct numerical simulations (DNS) in a parametric study showing the effect of initial Froude number and mixing intensity on the development of the flow. We further improve the model by including the stratification timescale in the characteristic relaxation time for triple correlations in the closure. It permits the computation of the long-term evolution of unstably stratified turbulence at high Reynolds number. This agrees with recent theoretical predictions concerning the self-similar dynamics and brings new insight into the spectral energy distribution and anisotropy of the flow.
Maternal depression, stress and feeding styles: towards a framework for theory and research in child obesity
Authors: El-Behadli Ana F. , Sharp Carla , Hughes Sheryl O. , Obasi Ezemenari M. , Nicklas Theresa A.
Published: January 2015

Against the background of rising rates of obesity in children and adults in the USA, and modest effect sizes for obesity interventions, the aim of the present narrative review paper is to extend the UNICEF care model to focus on childhood obesity and its associated risks with an emphasis on the emotional climate of the parent–child relationship within the family. Specifically, we extended the UNICEF model by applying the systems approach to childhood obesity and by combining previously unintegrated sets of literature across multiple disciplines including developmental psychology, clinical psychology and nutrition. Specifically, we modified the extended care model by explicitly integrating new linkages (i.e. parental feeding styles, stress, depression and mother's own eating behaviour) that have been found to be associated with the development of children's eating behaviours and risk of childhood obesity. These new linkages are based on studies that were not incorporated into the original UNICEF model, but suggest important implications for childhood obesity. In all, this narrative review offers important advancements to the scientific understanding of familial influences on children's eating behaviours and childhood obesity.
Impact of nutrition on ageing the process. Bridging the Gap: the animal perspective
Authors: Butterwick Richard F.
Published: January 2015

In pets, as in humans, there is increasing interest in interventions that promote ‘health and well-being’ into later life and extend these beyond their current limits. The purpose of this review was to assess the relevance of current knowledge of ageing in humans, described in a companion paper, as well as reviewing recent research on ageing in pet populations. The role of diet and other factors that influence the ageing process and ultimately lifespan in pets are highlighted in this review; in addition, future opportunities and challenges to further our understanding of the ageing process in pets are identified. Advancing knowledge of the fundamental biology of ageing will be key for the development and evaluation of strategies that extend both the quality and the quantity of lifespan in human and pet populations.
MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies
Authors: Choudhary G S , Al-harbi S , Mazumder S , Hill B T , Smith M R , Bodo J , Hsi E D , Almasan A
Published: January 2015

Overexpression of anti-apoptotic BCL-2 family members is a hallmark of many lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) that can be targeted with small molecule inhibitors. ABT-199 is a rationally designed BCL-2 homology (BH)-3 mimetic that specifically binds to BCL-2, but not to MCL-1 and BCL-xL. Although the thrombocytopenia that occurs with navitoclax treatment has not been a problem with ABT-199, clinical trials in CLL could benefit by lowering the ABT-199 concentration through targeting other survival pathways. In this study, we investigated the mechanisms of resistance that develops to ABT-199 therapy by generating ABT-199-resistant (ABT199-R) cell lines via chronic exposure of NHL cell lines to ABT-199. Acquired resistance resulted in substantial AKT activation and upregulation of MCL-1 and BCL-xL levels that sequestered BIM. ABT199-R cells exhibited increased MCL-1 stability and failed to activate BAX in response to ABT-199. The ABT-199 acquired and inherent resistant cells were sensitized to treatment with ABT-199 by inhibitors of the PI3K, AKT, and mTOR pathways, NVP-BEZ235 and GS-1101. NVP-BEZ235, a dual inhibitor of p-AKT and mTOR, reduced MCL-1 levels causing BIM release from MCL-1 and BCL-xL, thus leading to cell death by BAX activation. The PI3Kδ inhibitor GS-1101 (idelalisib) downregulated MCL-1 and sensitized ABT199-R cells through AKT-mediated BAX activation. A genetic approach, through siRNA-mediated down-regulation of AKT, MCL-1, and BCL-xL, significantly decreased cell survival, demonstrating the importance of these cell survival factors for ABT-199 resistance. Our findings suggest a novel mechanism that modulates the expression and activity of pro-survival proteins to confer treatment resistance that could be exploited by a rational combination therapeutic regimen that could be effective for treating lymphoid malignancies.
PKR downregulation prevents neurodegeneration and β-amyloid production in a thiamine-deficient model
Authors: Mouton-Liger F , Rebillat A-S , Gourmaud S , Paquet C , Leguen A , Dumurgier J , Bernadelli P , Taupin V , Pradier L , Rooney T , Hugon J
Published: January 2015

Brain thiamine homeostasis has an important role in energy metabolism and displays reduced activity in Alzheimer’s disease (AD). Thiamine deficiency (TD) induces regionally specific neuronal death in the animal and human brains associated with a mild chronic impairment of oxidative metabolism. These features make the TD model amenable to investigate the cellular mechanisms of neurodegeneration. Once activated by various cellular stresses, including oxidative stress, PKR acts as a pro-apoptotic kinase and negatively controls the protein translation leading to an increase of BACE1 translation. In this study, we used a mouse TD model to assess the involvement of PKR in neuronal death and the molecular mechanisms of AD. Our results showed that the TD model activates the PKR-eIF2α pathway, increases the BACE1 expression levels of Aβ in specific thalamus nuclei and induces motor deficits and neurodegeneration. These effects are reversed by PKR downregulation (using a specific inhibitor or in PKR knockout mice).
Phosphorylation of the translation initiation factor eIF2α at serine 51 determines the cell fate decisions of Akt in response to oxidative stress
Authors: Rajesh K , Krishnamoorthy J , Kazimierczak U , Tenkerian C , Papadakis A I , Wang S , Huang S , Koromilas A E
Published: January 2015

Phosphorylation of the α subunit of the translation initiation factor eIF2 at serine 51 (eIF2αP) is a master regulator of cell adaptation to various forms of stress with implications in antitumor treatments with chemotherapeutic drugs. Herein, we demonstrate that genetic loss of the eIF2α kinases PERK and GCN2 or impaired eIF2αP by genetic means renders immortalized mouse fibroblasts as well as human tumor cells increasingly susceptible to death by oxidative stress. We also show that eIF2αP facilitates Akt activation in cells subjected to oxidative insults. However, whereas Akt activation has a pro-survival role in eIF2αP-proficient cells, the lesser amount of activated Akt in eIF2αP-deficient cells promotes death. At the molecular level, we demonstrate that eIF2αP acts through an ATF4-independent mechanism to control Akt activity via the regulation of mTORC1. Specifically, eIF2αP downregulates mTORC1 activity, which in turn relieves the feedback inhibition of PI3K resulting in the upregulation of the mTORC2-Akt arm. Inhibition of mTORC1 by rapamycin restores Akt activity in eIF2αP-deficient cells but renders them highly susceptible to Akt-mediated death by oxidative stress. Our data demonstrate that eIF2αP acts as a molecular switch that dictates either cell survival or death by activated Akt in response to oxidative stress. Hence, we propose that inactivation of eIF2αP may be a suitable approach to unleash the killing power of Akt in tumor cells treated with pro-oxidant drugs.
Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling
Authors: Secq V , Leca J , Bressy C , Guillaumond F , Skrobuk P , Nigri J , Lac S , Lavaut M-N , Bui T-t , Thakur A K , Callizot N , Steinschneider R , Berthezene P , Dusetti N , Ouaissi M , Moutardier V , Calvo E , Bousquet C , Garcia S , Bidaut G , Vasseur S , Iovanna J L , Tomasini R
Published: January 2015

Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of cancer, with few therapeutic options. Evidence supports an implication of the intratumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within the pathophysiology and clinical course of PDA, through tumor recurrence and neuropathic pain, remains unknown, neglecting a putative, therapeutic window. Here, we report that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and we highlight factors such as ‘SLIT2’ (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA. We showed that ‘CAF-secreted SLIT2’ increases neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell migration/proliferation by modulating N-cadherin/β-catenin signaling. Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural connection. Finally, we revealed that SLIT2 expression and CAFs are correlated with neural remodeling within human and mouse PDA. All together, our data demonstrate the implication of CAFs, through the secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of the stromal/neural compartment connection with SLIT2/ROBO inhibitors for the treatment of pancreatic cancer recurrence and pain.
Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax)
Authors: Leverson J D , Zhang H , Chen J , Tahir S K , Phillips D C , Xue J , Nimmer P , Jin S , Smith M , Xiao Y , Kovar P , Tanaka A , Bruncko M , Sheppard G S , Wang L , Gierke S , Kategaya L , Anderson D J , Wong C , Eastham-Anderson J , Ludlam M J C , Sampath D , Fairbrother W J , Wertz I , Rosenberg S H , Tse C , Elmore S W , Souers A J
Published: January 2015

The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein–protein interactions, and therefore designing small molecules potent enough to inhibit MCL-1 in cells has proven extremely challenging. Here, we describe a series of indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to MCL-1 selectively and with sufficient affinity to disrupt MCL-1–BIM complexes in living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL inhibitor navitoclax to kill a variety of cancer cell lines. This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity. It also demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of MCL-1 and the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the treatment of cancer.
NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by β-lapachone
Authors: Moore Z , Chakrabarti G , Luo X , Ali A , Hu Z , Fattah F J , Vemireddy R , DeBerardinis R J , Brekken R A , Boothman D A
Published: January 2015

Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (e.g., FK866) target the most active pathway of NAD+ synthesis in tumor cells, but lack tumor-selectivity for use as a single agent. Reducing NAD+ pools by inhibiting NAMPT primed pancreatic ductal adenocarcinoma (PDA) cells for poly(ADP ribose) polymerase (PARP1)-dependent cell death induced by the targeted cancer therapeutic, β-lapachone (β-lap, ARQ761), independent of poly(ADP ribose) (PAR) accumulation. β-Lap is bioactivated by NADPH:quinone oxidoreductase 1 (NQO1) in a futile redox cycle that consumes oxygen and generates high levels of reactive oxygen species (ROS) that cause extensive DNA damage and rapid PARP1-mediated NAD+ consumption. Synergy with FK866+β-lap was tumor-selective, only occurring in NQO1-overexpressing cancer cells, which is noted in a majority (∼85%) of PDA cases. This treatment strategy simultaneously decreases NAD+ synthesis while increasing NAD+ consumption, reducing required doses and treatment times for both drugs and increasing potency. These complementary mechanisms caused profound NAD(P)+ depletion and inhibited glycolysis, driving down adenosine triphosphate levels and preventing recovery normally observed with either agent alone. Cancer cells died through an ROS-induced, μ-calpain-mediated programmed cell death process that kills independent of caspase activation and is not driven by PAR accumulation, which we call NAD+-Keresis. Non-overlapping specificities of FK866 for PDA tumors that rely heavily on NAMPT-catalyzed NAD+ synthesis and β-lap for cancer cells with elevated NQO1 levels affords high tumor-selectivity. The concept of reducing NAD+ pools in cancer cells to sensitize them to ROS-mediated cell death by β-lap is a novel strategy with potential application for pancreatic and other types of NQO1+ solid tumors.
Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma
Authors: Singer E , Judkins J , Salomonis N , Matlaf L , Soteropoulos P , McAllister S , Soroceanu L
Published: January 2015

Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN–MES transition. This ‘reprogramming’ of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.
Insulin-like growth factor-1 endues monocytes with immune suppressive ability to inhibit inflammation in the intestine
Authors: Ge Rong-Ti , Mo Li-Hua , Wu Ruijin , Liu Jiang-Qi , Zhang Huan-Ping , Liu Zhigang , Liu Zhanju , Yang Ping-Chang
Published: January 2015

The pathogenesis of some chronic inflammation such as inflammatory bowel disease is unclear. Insulin-like growth factor-1 (IGF1) has active immune regulatory capability. This study aims to investigate into the mechanism by which IGF1 modulates the monocyte (Mo) properties to inhibit immune inflammation in the intestine. In this study, the production of IGF1 by intestinal epithelial cells was evaluated by real time RT-PCR and Western blotting. Mos were analyzed by flow cytometry. A mouse colitis model was created with trinitrobenzene sulfonic acid. The results showed that mouse IECs produced IGF1, which could be up regulated by exposure to CpG-ODN (CpG-oligodeoxynueleotides) in the culture. Culture the CpG-ODN-primed IEC cells and Mos or exposure of Mos to IGF1 in the culture induced the Mos to express IL-10. The IGF1-primed Mos showed the immune suppressive effect on inhibiting the immune inflammation in the mouse colon. In conclusion, the IGF1-primed Mos are capable of suppressing immune inflammation in the intestine.
Superior radiation-resistant nanoengineered austenitic 304L stainless steel for applications in extreme radiation environments
Authors: Sun C. , Zheng S. , Wei C. C. , Wu Y. , Shao L. , Yang Y. , Hartwig K. T. , Maloy S. A. , Zinkle S. J. , Allen T. R. , Wang H. , Zhang X.
Published: January 2015

Nuclear energy provides more than 10% of electrical power internationally and the increasing engagement of nuclear energy is essential to meet the rapid worldwide increase in energy demand. A paramount challenge in the development of advanced nuclear reactors is the discovery of advanced structural materials that can endure extreme environments, such as severe neutron irradiation damage at high temperatures. It has been known for decades that high dose radiation can introduce significant void swelling accompanied by precipitation in austenitic stainless steel (SS). Here we report, however, that through nanoengineering, ultra-fine grained (UFG) 304L SS with an average grain size of ~100 nm, can withstand Fe ion irradiation at 500°C to 80 displacements-per-atom (dpa) with moderate grain coarsening. Compared to coarse grained (CG) counterparts, swelling resistance of UFG SS is improved by nearly an order of magnitude and swelling rate is reduced by a factor of 5. M23C6 precipitates, abundant in irradiated CG SS, are largely absent in UFG SS. This study provides a nanoengineering approach to design and discover radiation tolerant metallic materials for applications in extreme radiation environments.
Development of a hierarchical double application of crisp cluster validity indices: a proof-of-concept study for automated FTIR spectral histology
Authors: Nguyen Thi Nguyet Que , Jeannesson Pierre , Groh Audrey , Guenot Dominique , Gobinet Cyril
Published: January 2015

The hierarchical double application of crisp cluster validity indices for automated spectral histology of a normal human colon.
Gold nanoparticles as a colorimetric probe for the determination of N-acetyl-l-cysteine in biological samples and pharmaceutical formulations
Authors: Rastegarzadeh Saadat , Hashemi Fatemeh
Published: January 2015

In this study, gold nanoparticles (AuNPs) have been synthesised using ascorbic acid as a reducing agent and employed in the design of anin situcolorimetric probe for the spectrophotometric detection ofN-acetyl-l-cysteine (NAC).
Colorimetric detection of melamine based on the size effect of AuNPs
Authors: Paul Ida Evangeline , Rajeshwari A. , Prathna T. C. , Raichur Ashok M. , Chandrasekaran N. , Mukherjee Amitava
Published: January 2015

A simple colorimetric detection of melamine was studied using 15 nm (AuNPs-I), 30 nm (AuNPs-II), and 40 nm (AuNPs-III) citrate-capped gold nanoparticles (AuNPs).
Determination of total chromium in tea samples by suspension dispersive solid phase extraction combined with silver nanoparticles and using flame atomic absorption spectrometry
Authors: Xiong Wei , Cheng Chunsheng , Yang Yaling
Published: January 2015

A method to separate and preconcentrate trace levels of chromium using silver nanoparticle (Ag NP) technology and suspension dispersive solid phase extraction is proposed.
Catalytic antioxidant therapy by metallodrugs: lessons from metallocorroles
Authors: Haber Adi , Gross Zeev
Published: January 2015

This article provides a perspective on the utility of metal-based catalytic antioxidants for disease prevention or treatment, with focus on their mode of action and its dependence (DCA) or independence (ICA) on the involvement of cofactors.
Water/alcohol soluble conjugated polymers for the interface engineering of highly efficient polymer light-emitting diodes and polymer solar cells
Authors: Hu Zhicheng , Zhang Kai , Huang Fei , Cao Yong
Published: January 2015

This review provides a summary of the recent developments and applications of water/alcohol soluble conjugated polymers in highly efficient polymer light-emitting diodes and polymer solar cells.
DNA-aptamer gating membranes
Authors: Schäfer Thomas , Özalp Veli Cengiz
Published: January 2015

This report describes a membrane barrier whose permeability is modulated through the recognition of a small-molecule target, adenosine triphosphate (ATP), by a DNA-aptamer.
Homolytic H2 cleavage by a mercury-bridged Ni(i) pincer complex [{(PNP)Ni}2{μ-Hg}]
Authors: Kreye Markus , Freytag Matthias , Jones Peter G. , Williard Paul G. , Bernskoetter Wesley H. , Walter Marc D.
Published: January 2015

The Hg-bridged (PNP)Ni-complex acts as a synthon for Ni(i) and homolytically cleaves H2 to yield [(PNP)NiH].
Versatile polyiodopyrazoles: synthesis and biocidal promise
Authors: Chand Deepak , Shreeve Jean'ne M.
Published: January 2015

An efficient synthetic route provides ready access to polyiodopyrazoles, including 3,4,5-triiodopyrazole; further introduction of the diiodo-methyl group increases the iodine concentration which gives rise to anti bioagent detonation products I2 and HI, making these iodo compounds promising candidates as ingredients in agent defeat weapons (ADWs).
Hyperosmotic polydixylitol for crossing the blood brain barrier and efficient nucleic acid delivery
Authors: Garg P. , Pandey S. , Seonwoo Hoon , Yeom Seungmin , Choung Yun-Hoon , Cho Chong-Su , Choung Pill-Hoon , Hoon Chung Jong
Published: January 2015

We report that the incorporation of a hyperosmotic molecule, dixylitol, into the backbone of a delivery vector can enhance its blood brain barrier transmigration.
Ultrafast liquid water transport through graphene-based nanochannels measured by isotope labelling
Authors: Sun Pengzhan , Liu He , Wang Kunlin , Zhong Minlin , Wu Dehai , Zhu Hongwei
Published: January 2015

Liquid water can afford an ultrafast permeation through graphene-based nanochannels under no external hydrostatic pressure.
Regioselective oxidative Pd-catalysed coupling of alkylboronic acids with pyridin-2-yl-substituted heterocycles
Authors: Wippich Julian , Schnapperelle Ingo , Bach Thorsten
Published: January 2015

A total of 19 alkylated heterocycles (thiophenes, benzo-thiophenes, pyrroles, furans) were prepared (36–99% yield) from the respective pyridin-2-yl-substituted precursors employing alkylboronic acids as the alkylating reagents in an oxidative (Ag2CO3 and 2,6-dimethyl-1,4-benzoquinone as oxidants) Pd-catalysed coupling reaction.
Associative chemosensing by fluorescent macrocycle–dye complexes – a versatile enzyme assay platform beyond indicator displacement
Authors: Biedermann Frank , Hathazi Denisa , Nau Werner M.
Published: January 2015

Enzymatic reactions of aromatic substrates can be monitored by fluorescence with μM sensitivity in real time by using self-assembled fluorescent receptors.
Rational molecular designs for drastic acceleration of the color-fading speed of photochromic naphthopyrans
Authors: Arai Katsutoshi , Kobayashi Yoichi , Abe Jiro
Published: January 2015

We report rational molecular designs for acceleration of the color-fading speed of photochromic 3H-naphthopyrans.