bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammary ductal elongation and myoepithelial migration are regulated by the composition of the extracellular matrix
Authors: NGUYEN‐NGOC K.‐V. , EWALD A.J. 
Published: February 2013

SummaryMammary branching morphogenesis occurs over a period of weeks deep inside an adipocyte‐rich stroma. The adipocytes contain light‐scattering lipid droplets that limit the depth of penetration of visible light. Organotypic culture methods were developed to enable high‐resolution optical monitoring of branching morphogenesis ex vivo. A challenge has been to identify the best culture conditions to model specific developmental events. We recently demonstrated that collagen I induces protrusive invasion in both normal and neoplastic mammary epithelium. In this study, we observed that the abundance of collagen I fibrils correlated strongly with invasive behaviour, even when the collagen I concentration was identical. We found that the extent of fibril assembly was experimentally manipulable by varying the incubation time at 4°C following pH neutralization. We next tested the capacity of collagen I fibrils to induce invasive behaviour when presented in combination with basement membrane proteins (Matrigel). We found that epithelial organoids in mixed gels of collagen I and basement membrane proteins exhibited more extensive branching morphogenesis but did not initiate protrusions into the matrix. Organoids in pure Matrigel produced many small epithelial buds that were bare of myoepithelial cells. Surprisingly, organoids in mixed gels of collagen I and Matrigel produced fewer epithelial buds, the buds elongated further, and the elongating buds remained covered by myoepithelial cells. Our mixed gels therefore provide a more physiologically accurate model of mammary branching morphogenesis. Our results also suggest that changes in the composition of the extracellular matrix could induce migration of epithelial cells past myoepithelial coverage.
Long‐Term Trends in Relative Earnings Mobility
Authors: Schiller Bradley R. , Mukhopadhyay Sankar 
Published: February 2013

ObjectivesThe extent of individual mobility across hierarchical ranks of the income distribution is a critical factor in interpreting the sociopolitical significance of well‐documented increases in cross‐sectional inequality. The objective of this study is to replicate two earlier investigations of mobility, allowing one to discern trends in mobility rates and patterns.MethodsMobility was measured using data from NLSY79 (where NLSY is National Longitudinal Survey of Youth) for the years 1989–2004.ResultsResults show that hierarchical (relative) mobility has remained substantial and pervasive from the 1970s through the 1990s for male workers, with no evidence of any attenuation. In view of the increased distance between (absolute) income ranks, this observation is both surprising and reassuring.ConclusionDespite substantial increase in cross‐sectional inequality, long‐term mobility rates have not changed since the 1960s.
Anaerobic α-Amylase Production and Secretion with Fumarate as the Final Electron Acceptor in Saccharomyces cerevisiae
Authors: Liu Zihe , Österlund Tobias , Hou Jin , Petranovic Dina , Nielsen Jens 
Published: February 2013

ABSTRACT

In this study, we focus on production of heterologous α-amylase in the yeast
Saccharomyces cerevisiae
under anaerobic conditions. We compare the metabolic fluxes and transcriptional regulation under aerobic and anaerobic conditions, with the objective of identifying the final electron acceptor for protein folding under anaerobic conditions. We find that yeast produces more amylase under anaerobic conditions than under aerobic conditions, and we propose a model for electron transfer under anaerobic conditions. According to our model, during protein folding the electrons from the endoplasmic reticulum are transferred to fumarate as the final electron acceptor. This model is supported by findings that the addition of fumarate under anaerobic (but not aerobic) conditions improves cell growth, specifically in the α-amylase-producing strain, in which it is not used as a carbon source. Our results provide a model for the molecular mechanism of anaerobic protein secretion using fumarate as the final electron acceptor, which may allow for further engineering of yeast for improved protein secretion under anaerobic growth conditions.
Role of PelF in Pel Polysaccharide Biosynthesis in Pseudomonas aeruginosa
Authors: Ghafoor Aamir , Jordens Zoe , Rehm Bernd H. A. 
Published: February 2013

ABSTRACT

Pseudomonas aeruginosa
produces three exopolysaccharides, Psl, Pel, and alginate, that play vital roles in biofilm formation. Pel is a glucose-rich, cellulose-like exopolysaccharide. The essential Pel biosynthesis proteins are encoded by seven genes,
pelA
to
pelG
. Bioinformatics analysis suggests that PelF is a cytosolic glycosyltransferase. Here, experimental evidence was provided to support this PelF function. A UDP-glucose dehydrogenase-based assay was developed to quantify UDP-glucose. UDP-glucose was proposed as the substrate for PelF. The isogenic
pelF
deletion mutant accumulated 1.8 times more UDP-glucose in its cytosol than the wild type. This suggested that PelF, which was found localized in the cystosol, uses UDP-glucose as substrate. Additionally,
in vitro
experiments confirmed that PelF uses UDP-glucose as substrate. To analyze the functional roles of conserved residues in PelF, site-directed mutagenesis was performed. The presence of the EX
7
E motif is characteristic for various glycosyltransferase families, and in PelF, E405/E413 are the conserved residues in this motif. Replacement of E405 with A resulted in a reduction of PelF activity to 30.35% ± 3.15% (mean ± standard deviation) of the wild-type level, whereas replacement of the second E, E413, with A did not produce a significant change in the activity of PelF. Moreover, replacement of both E residues did not result in a loss of PelF function, but replacement of the conserved R325 or K330 with A resulted in a complete loss of PelF activity. Overall, our data show that PelF is a soluble glycosyltransferase that uses UDP-glucose as the substrate for Pel synthesis and that conserved residues R325 and K330 are important for the activity of PelF.
FK506 Maturation Involves a Cytochrome P450 Protein-Catalyzed Four-Electron C-9 Oxidation in Parallel with a C-31O-Methylation
Authors: Chen Dandan , Zhang Lihan , Pang Bo , Chen Jing , Xu Zhinan , Abe Ikuro , Liu Wen 
Published: February 2013

ABSTRACTFK506, structurally similar to FK520 and rapamycin, is an α-keto amide bonding-containing, macrolide natural product that exhibits potent immunosuppressive activity and moderate antifungal activity. FK506 biosynthesis requires a hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) system to construct the skeleton of the macrolide. The mechanism for tailoring this macrolide to furnish FK506 remains poorly understood. In this study, we report a maturation paradigm common for FK506, FK520, and rapamycin, by characterizing two conserved regiospecific, post-PKS-NRPS modifications in an FK506-producingStreptomyces tsukubaensisstrain. A cytochrome P450 protein, FkbD, catalyzes a less common, four-electron oxidation at C-9 to give a rarely found α-keto amide group, whereas a methyltransferase, FkbM, is responsible forO-methylation at C-31 to afford a methoxy group. Both FkbD and FkbM are highly tolerant in their substrate choice; therefore, the order of FkbD- and FkbM-catalyzed reactions is interchangeable in the FK506 biosynthetic pathway. Inactivation offkbDproduced a new intermediate, 9-deoxo-FK506, which displayed antifungal activity lower than that of FK506. Taking previously reported bioassay results regarding the intermediates 9-deoxo-31-O-demethyl-FK506 and 31-O-demethyl-FK506 into account, it is clear that the modifications catalyzed by FkbD and FkbM are of importance to reach the full biological activity of FK506 by forming a key structure motif that is necessary for interaction of the molecule with the receptor and, subsequently, the downstream intracellular responses.
Disulfide Bond Oxidoreductase DsbA2 of Legionella pneumophila Exhibits Protein Disulfide Isomerase Activity
Authors: Kpadeh Zegbeh Z. , Jameson-Lee Max , Yeh Anthony J. , Chertihin Olga , Shumilin Igor A. , Dey Rafik , Day Shandra R. , Hoffman Paul S. 
Published: February 2013

ABSTRACTThe extracytoplasmic assembly of the Dot/Icm type IVb secretion system (T4SS) ofLegionella pneumophilais dependent on correct disulfide bond (DSB) formation catalyzed by a novel and essential disulfide bond oxidoreductase DsbA2 and not by DsbA1, a second nonessential DSB oxidoreductase. DsbA2, which is widely distributed in the microbial world, is phylogenetically distinct from the canonical DsbA oxidase and the DsbC protein disulfide isomerase (PDI)/reductase ofEscherichia coli. Here we show that the extended N-terminal amino acid sequence of DsbA2 (relative to DsbA proteins) contains a highly conserved 27-amino-acid dimerization domain enabling the protein to form a homodimer. Complementation tests withE. colimutants established thatL. pneumophila dsbA1, but not thedsbA2strain, restored motility to adsbAmutant. In a protein-folding PDI detector assay, thedsbA2strain, but not thedsbA1strain, complemented adsbCmutant ofE. coli. Deletion of the dimerization domain sequences from DsbA2 produced the monomer (DsbA2N), which no longer exhibited PDI activity but complemented theE. coli dsbAmutant. PDI activity was demonstratedin vitrofor DsbA2 but not DsbA1 in a nitrocefin-based mutant TEM β-lactamase folding assay. In an insulin reduction assay, DsbA2N activity was intermediate between those of DsbA2 and DsbA1. InL. pneumophila, DsbA2 was maintained as a mixture of thiol and disulfide forms, while inE. coli, DsbA2 was present as the reduced thiol. Our studies suggest that DsbA2 is a naturally occurring bifunctional disulfide bond oxidoreductase that may be uniquely suited to the majority of intracellular bacterial pathogens expressing T4SSs as well as in many slow-growing soil and aquatic bacteria.
DNA-Damaging Agents Induce the RecA-Independent Homologous Recombination Functions of Integrating Conjugative Elements of the SXT/R391 Family
Authors: Garriss Geneviève , Poulin-Laprade Dominic , Burrus Vincent 
Published: February 2013

ABSTRACTIntegrating conjugative elements (ICEs) of the SXT/R391 family are major contributors to the spread of antibiotic resistance genes. These elements also catalyze their own diversity by promoting inter-ICE recombination through the action of the RecA-independent homologous recombination system that they encode. Here, we report that expression of this recombination system, which consists of the single-stranded DNA annealing protein Bet and the exonuclease Exo, is induced by DNA-damaging agents via ICE-encoded transcriptional regulators. We show that thebetandexogenes are part of a large polycistronic transcript that contains many conserved ICE genes that are not involved in the main integration/excision and conjugative transfer processes. We show that although the recombination genes are highly transcribed, their translation is subject to additional strong regulatory mechanisms. We also show that an ICE-encoded putative single-stranded DNA binding protein (Ssb) limits hybrid ICE formation. Finally, a thoroughin silicoanalysis reveals that orthologues of Bet and Exo are widely distributed in bacterial strains belonging to very distantly related bacterial species and are carried by various mobile genetic elements. Phylogenetic analyses suggest that the annealing proteins and exonucleases that compose these systems sometimes have different evolutionary origins, underscoring the strong selective pressure to maintain the functionality of these unrelated cooperating proteins.
Downregulation of the Novel Tumor Suppressor DIRAS1 Predicts Poor Prognosis in Esophageal Squamous Cell Carcinoma
Authors: Zhu Ying-Hui , Fu Li , Chen Leilei , Qin Yan-Ru , Liu Haibo , Xie Fajun , Zeng Tingting , Dong Sui-Sui , Li Jiangchao , Li Yan , Dai Yongdong , Xie Dan , Guan Xin-Yuan 
Published: February 2013

Abstract
Loss of chromosome 19p is one of the most frequent allelic imbalances in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes within this region. In this study, we investigated a role in ESCCs for a candidate tumor suppressor gene located at 19p13.3, the Ras-like small GTPase DIRAS1. Downregulation of DIRAS1 occurred in approximately 50% of primary ESCCs where it was associated significantly with advanced clinical stage, lymph node metastasis, and poor overall survival. LOH and promoter methylation analyses suggested that loss of DIRAS1 expression was mediated by epigenetic mechanisms. Functional studies established that ectopic re-expression of DIRAS1 in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation. Mechanistic investigations suggested that DIRAS1 acted through extracellular signal–regulated kinase (ERK1/2; MAPK3/1) and p38 mitogen-activated protein kinase (MAPK; MAPK14) signaling to trigger BAD Ser112 dephosphorylation and matrix metalloproteinase (MMP)2/9 transcriptional inactivation to promote apoptosis and inhibit metastasis, respectively. Taken together, our results revealed that DIRAS1 has a pivotal function in ESCC pathogenesis, with possible use as a biomarker and intervention point for new therapeutic strategies. Cancer Res; 73(7); 2298–309. ©2013 AACR.
Drug–Gene Modeling in Pediatric T-Cell Acute Lymphoblastic Leukemia Highlights Importance of 6-Mercaptopurine for Outcome
Authors: Beesley Alex H. , Firth Martin J. , Anderson Denise , Samuels Amy L. , Ford Jette , Kees Ursula R. 
Published: February 2013

Abstract
Patients relapsing with T-cell acute lymphoblastic leukemia (T-ALL) face a dismal outcome. The aim of this study was to identify new markers of drug resistance and clinical response in T-ALL. We measured gene expression and drug sensitivity in 15 pediatric T-ALL cell lines to find signatures predictive of resistance to 10 agents used in therapy. These were used to generate a model for outcome prediction in patient cohorts using microarray data from diagnosis specimens. In three independent T-ALL cohorts, the 10-drug model was able to accurately identify patient outcome, indicating that the in vitro–derived drug–gene profiles were clinically relevant. Importantly, predictions of outcome within each cohort were linked to distinct drugs, suggesting that different mechanisms contribute to relapse. Sulfite oxidase (SUOX) expression and the drug-transporter ABCC1 (MRP1) were linked to thiopurine sensitivity, suggesting novel pathways for targeting resistance. This study advances our understanding of drug resistance in T-ALL and provides new markers for patient stratification. The results suggest potential benefit from the earlier use of 6-mercaptopurine in T-ALL therapy or the development of adjuvants that may sensitize blasts to this drug. The methodology developed in this study could be applied to other cancers to achieve patient stratification at the time of diagnosis. Cancer Res; 73(9); 2749–59. ©2013 AACR.
Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells
Authors: Walker Brian A. , Wardell Christopher P. , Johnson David C. , Kaiser Martin F. , Begum Dil B. , Dahir Nasrin B. , Ross Fiona M. , Davies Faith E. , Gonzalez David , Morgan Gareth J. 
Published: February 2013

Key Points
IGH translocations in myeloma can occur through at least 5 mechanisms. t(11;14) and t(14;20) DH-JH rearrangement-mediated translocations occur indicating these appear to occur in a pregerminal center cell.
Exploring factors influencing asthma control and asthma-specific health-related quality of life among children
Authors: Gandhi Pranav K , Kenzik Kelly M , Thompson Lindsay A , DeWalt Darren A , Revicki Dennis A , Shenkman Elizabeth A , Huang I-Chan 
Published: February 2013

Abstract

Background
Little is known about factors contributing to children’s asthma control status and health-related quality of life (HRQoL). The study objectives were to assess the relationship between asthma control and asthma-specific HRQoL in asthmatic children, and to examine the extent to which parental health literacy, perceived self-efficacy with patient-physician interaction, and satisfaction with shared decision-making (SDM) contribute to children’s asthma control and asthma-specific HRQoL.

Methods
This cross-sectional study utilized data collected from a sample of asthmatic children (n = 160) aged 8–17 years and their parents (n = 160) who visited a university medical center. Asthma-specific HRQoL was self-reported by children using the National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Asthma Impact Scale. Satisfaction with SDM, perceived self-efficacy with patient-physician interaction, parental health literacy, and asthma control were reported by parents using standardized measures. Structural equation modeling (SEM) was performed to test the hypothesized pathways.

Results
Path analysis revealed that children with better asthma control reported higher asthma-specific HRQoL (β = 0.4, P < 0.001). Parents with higher health literacy and greater perceived self-efficacy with patient-physician interactions were associated with higher satisfaction with SDM (β = 0.38, P < 0.05; β = 0.58, P < 0.001, respectively). Greater satisfaction with SDM was in turn associated with better asthma control (β = −0.26, P < 0.01).

Conclusion
Children’s asthma control status influenced their asthma-specific HRQoL. However, parental factors such as perceived self-efficacy with patient-physician interaction and satisfaction with shared decision-making indirectly influenced children’s asthma control status and asthma-specific HRQoL.
Babesia microti:an unusual travel-related disease
Authors: Poisnel Elodie , Ebbo Mikael , Berda-Haddad Yael , Faucher Benoit , Bernit Emmanuelle , Carcy Bernard , Piarroux Renaud , Harlé Jean-Robert , Schleinitz Nicolas 
Published: February 2013

Abstract

Background
Human babesiosis is a rare tick-borne infectious disease. The clinical presentation ranges from an asymptomatic form to a life threatening infection with severe hemolysis. Human babesiosis due to Babesia microti is the most common and is endemic in North America.

Case presentation
We report a European patient with severe pancytopenia and reactive hemophagocytosis related to a Babesia microti infection. Babesia infection was acquired during a travel in the USA.

Conclusion
Babesiosis should be considered in patients who traveled in endemic areas, especially North America for the most common agent Babesia microti.
Desmoid tumor of posterior cruciate ligament of the knee: a case report
Authors: Ling Wang , Kedong Song , Hong Wang , Weiguo Zhang , Decheng Lv 
Published: February 2013

Abstract

Background
Desmoid tumor is a rare type of cancer that develops in the tissues that form tendons and ligaments. These tumors, also called aggressive fibromatosis, are considered benign with no metastatic potential. They may invade nearby tissues and organs, however, and can be difficult to control. Desmoid tumor in the posterior cruciate ligament (PCL) of the knee has never been described in the literature.

Case presentation
A 49-year-old man presented with a 2-month history of posteromedial knee dull pain and decreased range of motion of the knee. He was diagnosed desmoid tumor of posterior cruciate ligament of the knee by intraoperative biopsy, and underwent successful PCL resection and reconstruction by Four-strand semitendinosus and gracilis tendon autograft arthroscopically, and fortunately five years after operation, there were no clues as to recurrence of the tumor examined by Magnetic Resonance Imaging (MRI).

Conclusion
Desmoid tumor is characterized by infiltrative growth and a tendency towards recurrence,as this tumor entity is rare, data giving evidence based recommendations for the optimal treatment algorithm for this disease is lacking. At present there is no definite and effective method of treatment. However, early detection of the tumor play an important role, MRI is now the most important method for the detection of tumor extent, which facilitates the treatment choice as well as the prediction of prognosis. In our case, we followed-up the patient five years postoperatively by MRI and got a good result.
A framework for scientific advice on health: EuSANH’s principles and guidelines
Authors: Sarría-Santamera Antonio , Schoten Eert J , Coenen Theodora MM , Gunning-Schepers Louise J , Pauwels André , Allander Susanne V , Wysocki Miroslaw J , Ciutan Marius , Segovia Carlos 
Published: February 2013

Abstract

Background
Society expects politicians to make sound decisions by bringing the best evidence to bear on the health problems in question. Performing this task requires access to independent sources of sound scientific advice. The European Science Advisory Network for Health (EuSANH) is a network of national science advisory bodies in Europe which are active in the field of health and provide independent scientific advice to their authorities. The EuSANH addressed this question in a European project.

Methods
Guidelines and principles for producing sound advice have been formulated after international comparative evaluations and extensive discussions among participants of the EuSANH-ISA project with input from international experts.

Results
A framework for scientific advice on health has been produced.

Conclusions
This framework will ensure a uniform approach and thus opens possibilities for collaboration between science advisory bodies.
Mechanism of Thiol–Disulfide Exchange Reactions between DsbA and DsbB over a Wide pH Range
Authors: Yazawa Kenjiro , Furusawa Hiroyuki , Okahata Yoshio 
Published: February 2013

Abstract
We performed the transient kinetics of the oxidation reaction between DsbASH,SH and DsbBS–S,S–S embedded in supported lipid bilayers immobilized on a 27-MHz quartz-crystal microbalance, under various pH conditions, in order to investigate the pH-adaptability mechanism of the Dsb system. The obtained kinetic parameters indicated that two pairs of cysteine residues in DsbBS–S,S–S were important for both the stability of the DsbA–DsbB intermediate and the oxidation of DsbA over a wide pH range.
Relation between Audit Effort and Financial Report Misstatements: Evidence from Quarterly and Annual Restatements
Authors: Lobo Gerald J. , Zhao Yuping 
Published: February 2013

ABSTRACT
We identify two research design issues that explain the inconsistency between the theoretically predicted negative relation between audit effort and misstatements (measured using restatements) and empirical findings. First, auditor risk adjustment behavior induces an upward bias in the association between audit effort and restatements. Second, the theoretical prediction applies only to audited financial reports (i.e., annual reports) and not to unaudited reports (i.e., interim quarterly reports). Comingling restatements of audited with unaudited reports introduces an additional upward bias in the association between audit effort and restatements. After correcting for these two sources of bias, we find a robust negative association between audit effort and annual report restatements.
JEL Classification: M49.
Data Availability: Data used in this study are available from public sources.