bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long Pentraxin-3 Inhibits FGF8b-Dependent Angiogenesis and Growth of Steroid Hormone–Regulated Tumors
Authors: Leali Daria , Alessi Patrizia , Coltrini Daniela , Ronca Roberto , Corsini Michela , Nardo Giorgia , Indraccolo Stefano , Presta Marco 
Published: July 2011

Abstract
Fibroblast growth factor-8b (FGF8b) exerts nonredundant autocrine/paracrine functions in steroid hormone–regulated tumors. Previous observations had shown that the soluble pattern recognition receptor long pentraxin-3 (PTX3) is a natural selective antagonist for a restricted number of FGF family members, inhibiting FGF2 but not FGF1 and FGF4 activity. Here, we assessed the capacity of PTX3 to antagonize FGF8b and to inhibit the vascularization and growth of steroid hormone–regulated tumors. Surface plasmon resonance analysis shows that PTX3 binds FGF8b with high affinity (Kd = 30–90 nmol/L). As a consequence, PTX3 prevents the binding of FGF8b to its receptors, inhibits FGF8b-driven ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells, and suppresses FGF8b-induced neovascularization in vivo. Also, PTX3 inhibits dihydrotestosterone (DHT)- and FGF8b-driven proliferation of androgen-regulated Shionogi 115 (S115) mouse breast tumor cells. Furthermore, DHT-treated, PTX3 overexpressing hPTX3_S115 cell transfectants show a reduced proliferation rate in vitro and a limited angiogenic activity in the chick embryo chorioallantoic membrane and murine s.c. Matrigel plug assays. Accordingly, hPTX3_S115 cells show a dramatic decrease of their tumorigenic activity when grafted in immunodeficient male mice. These results identify PTX3 as a novel FGF8b antagonist endowed with antiangiogenic and antineoplastic activity with possible implications for the therapy of hormonal tumors. Mol Cancer Ther; 10(9); 1600–10. ©2011 AACR.
Potent, Selective Inhibitors of Fibroblast Growth Factor Receptor Define Fibroblast Growth Factor Dependence in Preclinical Cancer Models
Authors: Squires Matthew , Ward George , Saxty Gordan , Berdini Valerio , Cleasby Anne , King Peter , Angibaud Patrick , Perera Tim , Fazal Lynsey , Ross Douglas , Jones Charlotte Griffiths , Madin Andrew , Benning Rajdeep K. , Vickerstaffe Emma , O'Brien Alistair , Frederickson Martyn , Reader Michael , Hamlett Christopher , Batey Michael A. , Rich Sharna , Carr Maria , Miller Darcey , Feltell Ruth , Thiru Abarna , Bethell Susanne , Devine Lindsay A. , Graham Brent L. , Pike Andrew , Cosme Jose , Lewis Edward J. , Freyne Eddy , Lyons John , Irving Julie , Murray Christopher , Newell David R. , Thompson Neil T. 
Published: July 2011

Abstract
We describe here the identification and characterization of 2 novel inhibitors of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases. The compounds exhibit selective inhibition of FGFR over the closely related VEGFR2 receptor in cell lines and in vivo. The pharmacologic profile of these inhibitors was defined using a panel of human tumor cell lines characterized for specific mutations, amplifications, or translocations known to activate one of the four FGFR receptor isoforms. This pharmacology defines a profile for inhibitors that are likely to be of use in clinical settings in disease types where FGFR is shown to play an important role. Mol Cancer Ther; 10(9); 1542–52. ©2011 AACR.
Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency
Authors: Dickinson Rachel Emma , Griffin Helen , Bigley Venetia , Reynard Louise N. , Hussain Rafiqul , Haniffa Muzlifah , Lakey Jeremy H. , Rahman Thahira , Wang Xiao-Nong , McGovern Naomi , Pagan Sarah , Cookson Sharon , McDonald David , Chua Ignatius , Wallis Jonathan , Cant Andrew , Wright Michael , Keavney Bernard , Chinnery Patrick F. , Loughlin John , Hambleton Sophie , Santibanez-Koref Mauro , Collin Matthew 
Published: July 2011

Abstract
The human syndrome of dendritic cell, monocyte, B and natural killer lymphoid deficiency presents as a sporadic or autosomal dominant trait causing susceptibility to mycobacterial and other infections, predisposition to myelodysplasia and leukemia, and, in some cases, pulmonary alveolar proteinosis. Seeking a genetic cause, we sequenced the exomes of 4 unrelated persons, 3 with sporadic disease, looking for novel, heterozygous, and probably deleterious variants. A number of genes harbored novel variants in person, but only one gene, GATA2, was mutated in all 4 persons. Each person harbored a different mutation, but all were predicted to be highly deleterious and to cause loss or mutation of the C-terminal zinc finger domain. Because GATA2 is the only common mutated gene in 4 unrelated persons, it is highly probable to be the cause of dendritic cell, monocyte, B, and natural killer lymphoid deficiency. This disorder therefore constitutes a new genetic form of heritable immunodeficiency and leukemic transformation.
Active Machine Learning for Consideration Heuristics
Authors: Dzyabura Daria , Hauser John R. 
Published: July 2011

We develop and test an active-machine-learning method to select questions adaptively when consumers use heuristic decision rules. The method tailors priors to each consumer based on a “configurator.” Subsequent questions maximize information about the decision heuristics (minimize expected posterior entropy). To update posteriors after each question, we approximate the posterior with a variational distribution and use belief propagation (iterative loops of Bayes updating). The method runs sufficiently fast to select new queries in under a second and provides significantly and substantially more information per question than existing methods based on random, market-based, or orthogonal-design questions. Synthetic data experiments demonstrate that adaptive questions provide close-to-optimal information and outperform existing methods even when there are response errors or “bad” priors. The basic algorithm focuses on conjunctive or disjunctive rules, but we demonstrate generalizations to more complex heuristics and to the use of previous-respondent data to improve consumer-specific priors. We illustrate the algorithm empirically in a Web-based survey conducted by an American automotive manufacturer to study vehicle consideration (872 respondents, 53 feature levels). Adaptive questions outperform market-based questions when estimating heuristic decision rules. Heuristic decision rules predict validation decisions better than compensatory rules.
The Labor Illusion: How Operational Transparency Increases Perceived Value
Authors: Buell Ryan W. , Norton Michael I. 
Published: July 2011

Aubiquitous feature of even the fastest self-service technology transactions is the wait. Conventional wisdom and operations theory suggest that the longer people wait, the less satisfied they become; we demonstrate that because of what we term the labor illusion, when websites engage in operational transparency by signaling that they are exerting effort, people can actually prefer websites with longer waits to those that return instantaneous results—even when those results are identical. In five experiments that simulate service experiences in the domains of online travel and online dating, we demonstrate the impact of the labor illusion on service value perceptions, demonstrate that perceptions of service provider effort induce feelings of reciprocity that together mediate the link between operational transparency and increased valuation, and explore boundary conditions and alternative explanations. This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors. This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors.
Predictors of Survival and Causes of Death in Japanese Patients with Systemic Sclerosis
Authors: HASHIMOTO ATSUSHI , TEJIMA SATOKO , TONO TOSHIHIRO , SUZUKI MAIKO , TANAKA SUMIAKI , MATSUI TOSHIHIRO , TOHMA SHIGETO , ENDO HIRAHITO , HIROHATA SHUNSEI 
Published: July 2011

Objective.To clarify the mortality rates, causes of death, and contributing clinical factors in Japanese patients with systemic sclerosis (SSc).Methods.A cohort of 405 patients with SSc, who attended our institution during the period 1973 to 2008, was retrospectively analyzed until the end of 2009. Clinical data were obtained from medical records or autopsy reports.Results.The 405 patients with SSc consisted of 310 (76.5%) survivors, 86 (21.2%) who died, and 9 who were lost to followup. Diffuse cutaneous SSc and involvement of organs other than the gastrointestinal tract were more frequent in patients who died, and were associated with a worse prognosis according to Kaplan-Meier analysis. Female sex, limited cutaneous SSc, anticentromere antibody (ACA), and overlap with Sjögren’s syndrome (SS) were factors favoring a better prognosis, while overlap with myositis contributed to a poor prognosis. The overall 10-year survival rate was 88%. The patients with SSc had a significantly higher mortality than the general population (standardized mortality ratio 2.76), but the patients with ACA or overlapping SS did not. The most common causes of death were unknown ones including sudden death, followed by malignancy and infection. In patients with pulmonary arterial hypertension, sudden death was the most common cause of mortality.Conclusion.The overall mortality rate of patients with SSc was higher than that of the general population, probably because of poor prognostic factors including organ involvement. These factors should be carefully monitored during followup.
Altered JS‐2 expression in colorectal cancers and its clinical pathological relevance
Authors: Lam Alfred King-Yin , Gopalan Vinod , Nassiri Mohammad Reza , Kasim Kais , Dissanayake Jayampathy , Tang Johnny Chuek-On , Smith Robert Anthony 
Published: July 2011

Abstract
JS‐2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS‐2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS‐2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS‐2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non‐neoplastic tissues) using real‐time polymerase chain reaction. JS‐2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS‐2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS‐2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS‐2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS‐2 expression than non‐mucinous adenocarcinoma (p = 0.02). Early T‐stage cancers appear to have higher JS‐2 copy number and lower expression of JS‐2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS‐2 than the benign colorectal cell line. JS‐2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS‐2 was found to be related to location, pathological subtypes and staging of colorectal cancer.
Rapid-Viability PCR Method for Detection of Live, Virulent Bacillus anthracis in Environmental Samples
Authors: Létant Sonia E. , Murphy Gloria A. , Alfaro Teneile M. , Avila Julie R. , Kane Staci R. , Raber Ellen , Bunt Thomas M. , Shah Sanjiv R. 
Published: July 2011

ABSTRACT

In the event of a biothreat agent release, hundreds of samples would need to be rapidly processed to characterize the extent of contamination and determine the efficacy of remediation activities. Current biological agent identification and viability determination methods are both labor- and time-intensive such that turnaround time for confirmed results is typically several days. In order to alleviate this issue, automated, high-throughput sample processing methods were developed in which real-time PCR analysis is conducted on samples before and after incubation. The method, referred to as rapid-viability (RV)-PCR, uses the change in cycle threshold after incubation to detect the presence of live organisms. In this article, we report a novel RV-PCR method for detection of live, virulent
Bacillus anthracis
, in which the incubation time was reduced from 14 h to 9 h, bringing the total turnaround time for results below 15 h. The method incorporates a magnetic bead-based DNA extraction and purification step prior to PCR analysis, as well as specific real-time PCR assays for the
B. anthracis
chromosome and pXO1 and pXO2 plasmids. A single laboratory verification of the optimized method applied to the detection of virulent
B. anthracis
in environmental samples was conducted and showed a detection level of 10 to 99 CFU/sample with both manual and automated RV-PCR methods in the presence of various challenges. Experiments exploring the relationship between the incubation time and the limit of detection suggest that the method could be further shortened by an additional 2 to 3 h for relatively clean samples.
Global Biogeography and Quantitative Seasonal Dynamics of Gemmatimonadetes in Soil
Authors: DeBruyn Jennifer M. , Nixon Lauren T. , Fawaz Mariam N. , Johnson Amy M. , Radosevich Mark 
Published: July 2011

ABSTRACT

Bacteria belonging to phylum
Gemmatimonadetes
comprise approximately 2% of soil bacterial communities. However, little is known of their ecology due to a lack of cultured representation. Here we present evidence from biogeographical analyses and seasonal quantification of
Gemmatimonadetes
in soils, which suggests an adaptation to low soil moisture.
Distinct Microbial Communities within the Endosphere and Rhizosphere of Populus deltoides Roots across Contrasting Soil Types
Authors: Gottel Neil R. , Castro Hector F. , Kerley Marilyn , Yang Zamin , Pelletier Dale A. , Podar Mircea , Karpinets Tatiana , Uberbacher Ed , Tuskan Gerald A. , Vilgalys Rytas , Doktycz Mitchel J. , Schadt Christopher W. 
Published: July 2011

ABSTRACT

The root-rhizosphere interface of
Populus
is the nexus of a variety of associations between bacteria, fungi, and the host plant and an ideal model for studying interactions between plants and microorganisms. However, such studies have generally been confined to greenhouse and plantation systems. Here we analyze microbial communities from the root endophytic and rhizospheric habitats of
Populus deltoides
in mature natural trees from both upland and bottomland sites in central Tennessee. Community profiling utilized 454 pyrosequencing with separate primers targeting the V4 region for bacterial 16S rRNA and the D1/D2 region for fungal 28S rRNA genes. Rhizosphere bacteria were dominated by
Acidobacteria
(31%) and
Alphaproteobacteria
(30%), whereas most endophytes were from the
Gammaproteobacteria
(54%) as well as
Alphaproteobacteria
(23%). A single
Pseudomonas
-like operational taxonomic unit (OTU) accounted for 34% of endophytic bacterial sequences. Endophytic bacterial richness was also highly variable and 10-fold lower than in rhizosphere samples originating from the same roots. Fungal rhizosphere and endophyte samples had approximately equal amounts of the
Pezizomycotina
(40%), while the
Agaricomycotina
were more abundant in the rhizosphere (34%) than endosphere (17%). Both fungal and bacterial rhizosphere samples were highly clustered compared to the more variable endophyte samples in a UniFrac principal coordinates analysis, regardless of upland or bottomland site origin. Hierarchical clustering of OTU relative abundance patterns also showed that the most abundant bacterial and fungal OTUs tended to be dominant in either the endophyte or rhizosphere samples but not both. Together, these findings demonstrate that root endophytic communities are distinct assemblages rather than opportunistic subsets of the rhizosphere.
Distinct Cell Surface Appendages Produced by Sinorhizobium fredii USDA257 and S. fredii USDA191, Cultivar-Specific and Nonspecific Symbionts of Soybean
Authors: Krishnan Hari B. , Natarajan Savithiry S. , Kim Won-Seok 
Published: July 2011

ABSTRACT

Sinorhizobium fredii
USDA257 and
S. fredii
USDA191 are fast-growing rhizobia that form nitrogen-fixing nodules on soybean roots. In contrast to USDA191, USDA257 exhibits cultivar specificity and can form nodules only on primitive soybean cultivars. In response to flavonoids released from soybean roots, these two rhizobia secrete
n
odulation
o
uter
p
roteins (Nop) to the extracellular milieu through a type III secretion system. In spite of the fact that Nops are known to regulate legume nodulation in a host-specific manner, very little is known about the differences in the compositions of Nops and surface appendages elaborated by USDA191 and USDA257. In this study we compared the Nop profiles of USDA191 and USDA257 by one-dimensional (1D) and 2D gel electrophoresis and identified several of these proteins by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and liquid chromatography-tandem MS (LC-MS/MS). Examination of the surface appendages elaborated by these two strains of soybean symbionts by transmission electron microscopy revealed distinct differences in their morphologies. Even though the flagella produced by USDA191 and USDA257 were similar in their morphologies, they differed in their flagellin composition. USDA257 pili resembled long thin filaments, while USDA191 pili were short, rod shaped, and much thinner than the flagella. 2D gel electrophoresis of pilus-like appendages of USDA191 and USDA257 followed by mass spectrometry resulted in the identification of several of the Nops along with some proteins previously undetected in these strains. Some of the newly identified proteins show homology to putative zinc protease and a LabA-like protein from
Bradyrhizobium
sp. ORS278, fimbrial type 4 assembly proteins from
Ralstonia solanacearum
, and the type III effector Hrp-dependent protein from
Rhizobium leguminosarum
bv.
trifolii
.
A Fail-Safe Mechanism in the Septal Ring Assembly Pathway Generated by the Sequential Recruitment of Cell Separation Amidases and Their Activators
Authors: Peters Nick T. , Dinh Thuy , Bernhardt Thomas G. 
Published: July 2011

ABSTRACT

During cytokinesis in
Escherichia coli
, the peptidoglycan (PG) layer produced by the divisome must be split to promote cell separation. Septal PG splitting is mediated by the amidases: AmiA, AmiB, and AmiC. To efficiently hydrolyze PG, the amidases must be activated by LytM domain factors. EnvC specifically activates AmiA and AmiB, while NlpD specifically activates AmiC. Here, we used an exportable, superfolding variant of green fluorescent protein (GFP) to demonstrate that AmiB, like its paralog AmiC, is recruited to the division site by an N-terminal targeting domain. The results of colocalization experiments indicate that EnvC is recruited to the division site well before its cognate amidase AmiB. Moreover, we show that EnvC and AmiB have differential FtsN requirements for their localization. EnvC accumulates at division sites independently of this essential division protein, whereas AmiB localization is FtsN dependent. Interestingly, we also report that AmiB and EnvC are recruited to division sites independently of one another. The same is also true for AmiC and NlpD. However, unlike EnvC, we find that NlpD shares an FtsN-dependent localization with its cognate amidase. Importantly, when septal PG synthesis is blocked by cephalexin, both EnvC and NlpD are recruited to septal rings, whereas the amidases fail to localize. Our results thus suggest that the order in which cell separation amidases and their activators localize to the septal ring relative to other components serves as a fail-safe mechanism to ensure that septal PG synthesis precedes the expected burst of PG hydrolysis at the division site, accompanied by amidase recruitment.
Overexpression of Cloned
RhsA
Sequences Perturbs the Cellular Translational Machinery in Escherichia coli
Authors: Aggarwal Kunal , Lee Kelvin H. 
Published: July 2011

ABSTRACT

RhsA
is a member of the multigene
Rhs
family and consists of a complex genetic sequence. This sequence consists of several distinct components, including a GC-rich core (core open reading frame [ORF]), an AT-rich extension (ext-a1) of the core ORF and an AT-rich region following the core extension (dsORF-a1). The functions of
RhsA
and the different distinct components, which can include open reading frames, are not well understood. Here, we study the effect of overexpression of the ext-a1 sequence and the ext-a1 3′ region, which includes a partial sequence of dsORF-a1, on
Escherichia coli
cells. Cells expressing these sequences show reduced cell growth and cell viability. The expression of these sequences dramatically affects different components of the transcription and translation machinery. Transcriptomic analysis reveals an increase in the expression of genes involved in transcription, RNA processing, and nucleotide biosynthesis and metabolism and a decrease in the expression of amino acid biosynthesis genes and transfer RNAs. Further, expression of the above-mentioned
RhsA
components increases ribosomal gene expression, as well as rRNA and ribosome abundance. Proteomic analysis reveals an overall reduction of protein expression at the genome-wide level in cells expressing the above-mentioned
RhsA
components. Based on these observations, we suspect a translation product of ext-a1 affects different regulatory mechanisms that control rRNA synthesis.
Sources of spiritual well-being in advanced cancer
Authors: Lo Christopher , Zimmermann Camilla , Gagliese Lucia , Li Madeline , Rodin Gary 
Published: July 2011

ObjectiveTo test a conceptual model of sources of spiritual well-being in patients facing life-limiting disease.DesignCross-sectional survey.SettingPrincess Margaret Hospital, Toronto, Canada.Participants747 patients with stage IV gastrointestinal, breast, genitourinary or gynaecological cancer, or stage IIIA, IIIB or IV lung cancer, recruited from 2002 to 2008.Main outcome measureSpiritual well-being as assessed by the FACIT-Sp-12.ResultsUsing structural equation modelling, spiritual well-being was specified as being predicted by religiosity, self-esteem, social relatedness and the physical burden of disease. The model had a good fit, Comparative Fit Index=0.96, Non-normed Fit Index=0.94, Root Mean Square Error of Approximation=0.057. Standardised path coefficients relating each factor to spiritual well-being were as follows: religiosity 0.50, social relatedness 0.28, self-esteem 0.26 and physical burden −0.11.ConclusionsThe authors confirmed our theoretical model in which spiritual well-being is positively associated with religiosity, self-esteem and social relatedness, and is negatively associated with physical suffering. Our findings support a multidimensional approach to spiritual well-being that addresses not only religious issues, but also pain and symptom control, and the potentially damaging effects of advanced disease on self-worth and close relationships. The spiritually informed clinical encounter may be one in which sufficient time and opportunity for reflection are afforded to consider illness trajectories and treatment decisions in the context of religious beliefs and personal values, self-worth, support systems and concerns about dependency.