bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Cellular Receptor of Clostridium spiroforme Toxin
Authors: Papatheodorou Panagiotis , Wilczek Claudia , Nölke Thilo , Guttenberg Gregor , Hornuss Daniel , Schwan Carsten , Aktories Klaus 
Published: January 2012

ABSTRACT

Clostridium spiroforme
produces the binary actin-ADP-ribosylating toxin CST (
C. spiroforme
toxin), which has been proposed to be responsible for diarrhea, enterocolitis, and eventually death, especially in rabbits. Here we report on the recombinant production of the enzyme component (CSTa) and the binding component (CSTb) of
C. spiroforme
toxin in
Bacillus megaterium
. By using the recombinant toxin components, we show that CST enters target cells via the lipolysis-stimulated lipoprotein receptor (LSR), which has been recently identified as the host cell receptor of the binary toxins
Clostridium difficile
transferase (CDT) and
Clostridium perfringens
iota toxin. Microscopic studies revealed that CST, but not the related
Clostridium botulinum
C2 toxin, colocalized with LSR during toxin uptake and traffic to endosomal compartments. Our findings indicate that CST shares LSR with
C. difficile
CDT and
C. perfringens
iota toxin as a host cell surface receptor.
Peripheral neuropathy: pattern recognition for the pragmatist
Authors: Overell James R 
Published: January 2012

Abstract
Long lists of causes of peripheral neuropathy make peripheral nerve disease a dry and uninspiring subject. A simple scheme based on the answers to just six questions should enable the clinician to recognise characteristic patterns, investigate relevant subgroups appropriately, and identify treatable disorders quickly: which systems are involved? What is the distribution of weakness? What is the nature of the sensory involvement? Is there any evidence of upper motor neuron involvement? What is the temporal evolution? Is there any evidence for a hereditary neuropathy? Standard screening investigations suffice for the common length dependent axonal neuropathies while complex presentations need more detailed investigations targeted to their clinical phenotype.
Quasi-classical trajectory calculation of the chemical reaction Ca + CF3Br
Authors: Xia Wenwen , Yao Li , Zhong Haiyang 
Published: January 2012

The dynamical properties of the product CaBr for the reaction Ca + CF3Br were studied with the quasi-classical trajectory method based on the extended London–Eyring–Polanyi–Sato potential energy surface. In this paper, the results, such as vibrational distribution, reaction cross section, and rotational alignment of the product CaBr, were calculated and the reaction mechanism has been discussed. The peak value of the vibrational distribution is located at around v = 3 when the collision energy equals 0.55 eV. The result obtained in this paper agrees well with the experimental vibrational result. The reaction cross section and the product rotational alignment all decrease with the increasing collision energy, which changes from 0.1 to 1.0 eV.
A quasi-classical trajectory study of the reagent initial rotation quantum state effect on the reaction He + T2+→ HeT+ + T using an improved ab initio potential energy surface
Authors: Zhao Ningjiu , Liu Yufang 
Published: January 2012

In this work, we employed the quasi-classical trajectory (QCT) method to study the vector correlations and the influence of the reagent initial rotational quantum number j for the reaction He + T2+(v = 0, j = 0–3) → HeT+ + T on a new potential energy surface (PES). The PES was improved by Aquilanti co-workers (Chem. Phys. Lett. 2009. 469: 26–30). The polarization-dependent differential cross sections (PDDCSs) and the distributions of P(θr), P([Formula: see text]r), and P(θr, [Formula: see text]r) are presented in this work. The plots of the PDDCSs provide us with abundant information about the distribution of the product angular momentum polarization. The P(θr) is used to describe the correlation between k (the relative velocity of the reagent) and j′ (the product rotational angular momentum). The distribution of dihedral angle P([Formula: see text]r) shows the k–k′–j′ (k′ refers to the relative velocity of the product) correlation. The PDDCS calculations illustrate that the product of this reaction is mainly backward scatter and it has the strongest polarization in the backward and sideways scattering directions. At the same time, the results of the P([Formula: see text]r) demonstrate that the product HeT+tends to be oriented along the positive direction of the y axis and it tends to rotate right-handedly in planes parallel to the scattering plane. Moreover, the distribution of the P(θr) manifests that the product angular momentum is aligned along different directions relative to k. The direction of the product alignment may be perpendicular, opposite, or parallel to k. Moreover, our calculations are independent of the initial rotational quantum number.
Enhanced Apoptosis and Tumor Growth Suppression Elicited by Combination of MEK (Selumetinib) and mTOR Kinase Inhibitors (AZD8055)
Authors: Holt Sarah V. , Logie Armelle , Davies Barry R. , Alferez Denis , Runswick Sarah , Fenton Sarah , Chresta Christine M. , Gu Yi , Zhang Jingchuan , Wu Yi-Long , Wilkinson Robert W. , Guichard Sylvie M. , Smith Paul D. 
Published: January 2012

Abstract
The mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/AKT signaling pathways interact at multiple nodes in cancer, including at mTOR complexes, suggesting an increased likelihood of redundancy and innate resistance to any therapeutic effects of single pathway inhibition. In this study, we investigated the therapeutic effects of combining the MAPK extracellular signal–regulated kinase (MEK)1/2 inhibitor selumetinib (AZD6244) with the dual mTORC1 and mTORC2 inhibitor (AZD8055). Concurrent dosing in nude mouse xenograft models of human lung adenocarcinoma (non–small cell lung cancers) and colorectal carcinoma was well tolerated and produced increased antitumor efficacy relative to the respective monotherapies. Pharmacodynamic analysis documented reciprocal pathway inhibition associated with increased apoptosis and Bim expression in tumor tissue from the combination group, where key genes such as DUSP6 that are under MEK functional control were also modulated. Our work offers a strong rationale to combine selumetinib and AZD8055 in clinical trials as an attractive therapeutic strategy. Cancer Res; 72(7); 1804–13. ©2012 AACR.
Epithelial–Mesenchymal Transition Induced by TNF-α Requires NF-κB–Mediated Transcriptional Upregulation of Twist1
Authors: Li Chia-Wei , Xia Weiya , Huo Longfei , Lim Seung-Oe , Wu Yun , Hsu Jennifer L. , Chao Chi-Hong , Yamaguchi Hirohito , Yang Neng-Kai , Ding Qingqing , Wang Yan , Lai Yun-Ju , LaBaff Adam M. , Wu Ting-Jung , Lin Been-Ren , Yang Muh-Hwa , Hortobagyi Gabriel N. , Hung Mien-Chie 
Published: January 2012

Abstract
Proinflammatory cytokines produced in the tumor microenvironment facilitate tumor development and metastatic progression. In particular, TNF-α promotes cancer invasion and angiogenesis associated with epithelial–mesenchymal transition (EMT); however, the mechanisms underlying its induction of EMT in cancer cells remain unclear. Here we show that EMT and cancer stemness properties induced by chronic treatment with TNF-α are mediated by the upregulation of the transcriptional repressor Twist1. Exposure to TNF-α rapidly induced Twist1 mRNA and protein expression in normal breast epithelial and breast cancer cells. Both IKK-β and NF-κB p65 were required for TNF-α–induced expression of Twist1, suggesting the involvement of canonical NF-κB signaling. In support of this likelihood, we defined a functional NF-κB–binding site in the Twist1 promoter, and overexpression of p65 was sufficient to induce transcriptional upregulation of Twist1 along with EMT in mammary epithelial cells. Conversely, suppressing Twist1 expression abrogated p65-induced cell migration, invasion, EMT, and stemness properties, establishing that Twist1 is required for NF-κB to induce these aggressive phenotypes in breast cancer cells. Taken together, our results establish a signaling axis through which the tumor microenvironment elicits Twist1 expression to promote cancer metastasis. We suggest that targeting NF-κB–mediated Twist1 upregulation may offer an effective a therapeutic strategy for breast cancer treatment. Cancer Res; 72(5); 1290–300. ©2012 AACR.
Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer
Authors: Yoo David S. , Kirkpatrick John P. , Craciunescu Oana , Broadwater Gloria , Peterson Bercedis L. , Carroll Madeline D. , Clough Robert , MacFall James R. , Hoang Jenny , Scher Richard L. , Esclamado Ramon M. , Dunphy Frank R. , Ready Neal E. , Brizel David M. 
Published: January 2012

Abstract
Purpose: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC).
Experimental Design: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT.
Results: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%–100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median Ktrans values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median Ktrans values that decreased during therapy.
Conclusions: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure. Clin Cancer Res; 18(5); 1404–14. ©2012 AACR.
SKI-606, an Src Inhibitor, Reduces Tumor Growth, Invasion, and Distant Metastasis in a Mouse Model of Thyroid Cancer
Authors: Kim Won Gu , Guigon Celine J. , Fozzatti Laura , Park Jeong Won , Lu Changxue , Willingham Mark C. , Cheng Sheue-yann 
Published: January 2012

AbstractPurpose: Src is overexpressed or hyperactivated in a variety of human cancers, including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of an Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (ThrbPV/PVPten+/− mice).Experimental Design: ThrbPV/PVPten+/− mice were treated with SKI-606 or vehicle controls, beginning at 6 weeks of age until the mice succumbed to thyroid cancer. We assessed the effects of SKI-606 on thyroid cancer progression and analyzed the impact of SKI-606 on aberrant Src-mediated signaling.Results: SKI-606 effectively inhibited aberrant activation of Src and its downstream targets to markedly inhibit the growth of thyroid tumor, thereby prolonging the survival of treated mice. While Src inhibition did not induce cell apoptosis, it decreased cell proliferation by affecting the expression of key regulators of cell-cycle progression. Importantly, SKI-606 dramatically prevented dedifferentiation, vascular invasion, and lung metastasis of thyroid cancer cells. These responses were meditated by downregulation of mitogen-activated protein kinase pathways and inhibition of the epithelial–mesenchymal transition.Conclusions: Our findings suggest that Src is critical in the progression of thyroid cancer, making oral SKI-606 a promising treatment strategy for refractory thyroid cancer. Clin Cancer Res; 18(5); 1281–90. ©2012 AACR.
Next Generation Sequencing of Prostate Cancer from a Patient Identifies a Deficiency of Methylthioadenosine Phosphorylase, an Exploitable Tumor Target
Authors: Collins Colin C. , Volik Stanislav V. , Lapuk Anna V. , Wang Yuwei , Gout Peter W. , Wu Chunxiao , Xue Hui , Cheng Hongwei , Haegert Anne , Bell Robert H. , Brahmbhatt Sonal , Anderson Shawn , Fazli Ladan , Hurtado-Coll Antonio , Rubin Mark A. , Demichelis Francesca , Beltran Himisha , Hirst Martin , Marra Marco , Maher Christopher A. , Chinnaiyan Arul M. , Gleave Martin , Bertino Joseph R. , Lubin Martin , Wang Yuzhuo 
Published: January 2012

Abstract
Castrate-resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumor sequencing program, a patient tumor was analyzed using Illumina genome sequencing and a matched renal capsule tumor xenograft was generated. Both tumor and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2, and ARF genes. It is rare for this deletion to occur in primary prostate tumors, yet approximately 10% express decreased levels of methylthioadenosine phosphorylase (MTAP) mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it seems that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient-derived neuroendocrine xenograft growth while protecting the host from 6-thioguanine toxicity. This therapeutic approach can be applied to other MTAP-deficient human cancers as deletion or hypermethylation of the MTAP gene occurs in a broad spectrum of tumors at high frequency. The combination of genome sequencing and patient-derived xenografts can identify candidate therapeutic agents and evaluate them for personalized oncology. Mol Cancer Ther; 11(3); 775–83. ©2012 AACR.
The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA Translation and Stability in Glioblastoma Cells
Authors: Vo Dat T. , Abdelmohsen Kotb , Martindale Jennifer L. , Qiao Mei , Tominaga Kumiko , Burton Tarea L. , Gelfond Jonathan A.L. , Brenner Andrew J. , Patel Vyomesh , Trageser Daniel , Scheffler Björn , Gorospe Myriam , Penalva Luiz O.F. 
Published: January 2012

AbstractMusashi1 (Msi1) is an evolutionarily conserved RNA-binding protein (RBP) that has profound implications in cellular processes such as stem cell maintenance, nervous system development, and tumorigenesis. Msi1 is highly expressed in many cancers, including glioblastoma, whereas in normal tissues, its expression is restricted to stem cells. Unfortunately, the factors that modulate Msi1 expression and trigger high levels in tumors are largely unknown. The Msi1 mRNA has a long 3′ untranslated region (UTR) containing several AU- and U-rich sequences. This type of sequence motif is often targeted by HuR, another important RBP known to be highly expressed in tumor tissue such as glioblastoma and to regulate a variety of cancer-related genes. In this report, we show an interaction between HuR and the Msi1 3′-UTR, resulting in a positive regulation of Msi1 expression. We show that HuR increased MSI1 mRNA stability and promoted its translation. We also present evidence that expression of HuR and Msi1 correlate positively in clinical glioblastoma samples. Finally, we show that inhibition of cell proliferation, increased apoptosis, and changes in cell-cycle profile as a result of silencing HuR are partially rescued when Msi1 is ectopically expressed. In summary, our results suggest that HuR is an important regulator of Msi1 in glioblastoma and that this regulation has important biological consequences during gliomagenesis. Mol Cancer Res; 10(1); 143–55. ©2012 AACR.
Efficacy and Cost of an Exercise Program for Functionally Impaired Older Patients With Heart Failure
Authors: Witham Miles D. , Fulton Roberta L. , Greig Carol A. , Johnston Derek W. , Lang Chim C. , van der Pol Marjon , Boyers Dwayne , Struthers Allan D. , McMurdo Marion E.T. 
Published: January 2012

Background—
Little is known about the optimum way to deliver exercise to older, functionally impaired patients with heart failure. We tested whether an exercise program tailored to the needs of these patients could improve exercise capacity and quality of life or reduce costs to the National Health Service.

Methods and Results—

The study design was a parallel-group, single-blind, randomized controlled trial. Patients aged ≥70 years with symptomatic heart failure and left ventricular systolic dysfunction were randomized to either 24 weeks of exercise training or usual care. Six-minute walk distance was the primary outcome; markers of physical function, quality of life, health status, and daily activity were measured at baseline and 8 and 24 weeks. Carer strain and healthcare costs were also recorded. A total of 107 participants were randomized (mean age, 80 years; men, 72 [67%]). Six-minute walk distance did not improve compared to that of the control group at 8 weeks (−16.9 m; 95% CI, −41.8 to 7.9 m;
P
=0.18) or at 24 weeks (−5.3 m; 95% CI, −32.6 to 22.0 m;
P
=0.70). For secondary outcomes, only the sit-to-stand test improved significantly at 24 weeks (−6.4 s; 95% CI, −12.2 to 0.6 s;
P
=0.03); there was no difference in change for the Minnesota Living With Heart Failure score (0.1 points; 95% CI, −0.9 to 1.1 points;
P
=0.83) at 24 weeks. Carer strain did not decrease at 24 weeks (difference, −0.5 points; 95% CI, −8.3 to 7.3 points;
P
=0.80), and there was no difference in overall healthcare costs.

Conclusions—
This exercise intervention did not improve exercise capacity or quality of life in older patients with heart failure and was not cost saving to the National Health Service.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN51615566.
Classification of Heart Failure in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Rosamond Wayne D , Chang Patricia P. , Baggett Chris , Johnson Anna , Bertoni Alain G. , Shahar Eyal , Deswal Anita , Heiss Gerardo , Chambless Lloyd E. 
Published: January 2012

Background—
Population-based research on heart failure (HF) is hindered by lack of consensus on diagnostic criteria. Framingham (FRM), National Health and Nutrition Examination Survey (NHANES), Modified Boston (MBS), Gothenburg (GTH), and International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) code criteria, do not differentiate acute decompensated heart failure (ADHF) from chronic stable HF. We developed a new classification protocol for identifying ADHF in the Atherosclerosis Risk in Communities (ARIC) Study and compared it with these other schemes.

Methods and Results—
A sample of 1180 hospitalizations with a patient address in 4 study communities and eligible discharge codes were selected. After assessing whether the chart contained evidence of possible HF signs, 705 were fully abstracted. Two independent reviewers classified each case as ADHF, chronic stable HF, or no HF, using ARIC classification guidelines. Fifty-nine percent of cases met ARIC criteria for ADHF and 13.9% and 27.1% were classified as chronic stable HF or no HF, respectively. Among events classified as HF by FRM criteria, 68.4% were validated as ADHF, 9.6% as chronic stable HF, and 21.9% as no HF. However, 92.5% of hospitalizations with a primary ICD-9-CM 428 “heart failure” code were validated as ADHF. Sensitivities of comparison criteria to classify ADHF ranged from 38–95%, positive predictive values from 62–92%, and specificities from 19–96%.

Conclusions—
Although comparison criteria for classifying HF were moderately sensitive in identifying ADHF, specificity varied when applied to a randomly selected set of suspected HF hospitalizations in the community.
The 2008 Global Crisis and the East Asian Developmental States Shifts of Export-Driven Strategies
Authors: Petropoulos Sotiris 
Published: January 2012

AbstractThe 2008 crisis affected all regions across the globe. East Asia appeared one of the regions best positioned to overcome its impact because of the resilience of strong developmental states. The crisis has raised the question of whether the East Asian economic growth model is too dependent on high export performance. The sharp decline of private consumption in the OECD economies in 2008–2009 has affected continued economic success in East Asia. Now the challenge for East Asian developmental states is to search for a new economic strategy moving away from extreme dependence on exports.This imperative was first acknowledged by China, which has initiated an ambitious support package to stimulate domestic demand and private consumption, relying less exclusively on global foreign markets. Thus China has provided new and more accessible markets to its ASEAN neighbours, with the potential to substitute declining import capacity in Europe, Japan and the USA.A structural consequence of the global crisis indicates an acceleration in the rise of East Asia's economic integration. However, this new facilitation of export benefits for the ASEAN countries may delay or hinder long-term needed reforms to raise domestic living standards and wealth redistribution across Southeast Asia.
Industrialization of Seed Production: Implications for Agriculture in India
Authors: Mallick Sambit , Ejnavarzala Haribabu , Reddy B. Bhoopathi 
Published: January 2012

Abstract
From the sociology of science perspective, this paper attempts to trace the shifts in the knowledge and its application in the context of seed production—the central input in agriculture. The paper argues that the seed production, which was once in the hands of farming communities, has become industrialized with the advent of hybrid seeds. The hybrid seed production, based on phenotypic knowledge of the plants, marks the first phase of the industrialization of seed and the genetically modified seed, based on genotypic knowledge of the plants, marks the beginning of another phase in the industrialization of seed production. This paper draws attention to controversies over genetically modified seed based on economic, social, environmental considerations. This paper also discusses the implications of these developments and the changes in the institutional arrangements that govern the production and use of the seed, as these developments have profound implications for Indian agriculture and agrarian relations.
Obesity in Europe: The Strategy of the European Union from a Public Health Law Perspective
Authors: Faeh Andrea 
Published: January 2012

Abstract
In 2007 the European Commission published a White Paper on a “Strategy on nutrition, overweight and obesity”, proposing measures to impede the current trend towards a steady gain in weight by Union citizens. In this article, these ideas are discussed critically in the light of the competences of the Union and from a public health law perspective, in order to scrutinise the effectiveness of the measures and to identify shortcomings in the White Paper. One focus of this article will be European food legislation, as food is one of the leading causes of people being overweight or obese.