bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of TCR/CD3 complex CD3ɛ chains of regulatory CD4+ T (Treg) lymphocytes: role in Treg differentiation in vitro and impact on Treg in vivo
Authors: Rojo Jose M , Ojeda Gloria , Acosta Yenny Y , Montes-Casado Maria , Criado Gabriel , Portolés Pilar 
Published: November 2013

ABSTRACTTregs are anergic CD4+CD25+Foxp3+ T lymphocytes exerting active suppression to control immune and autoimmune responses. However, the factors in TCR recognition underlying Treg differentiation are unclear. Based on our previous data, we hypothesized that Treg TCR/CD3 antigen receptor complexes might differ from those of CD4+CD25− Tconv. Expression levels of TCR/CD3, CD3ɛ,ζ chains, or other molecules involved in antigen signaling and the characteristics of CD3ɛ chains were analyzed in thymus or spleen Treg cells from normal mice. Tregs had quantitative and qualitatively distinct TCR/CD3 complexes and CD3ɛ chains. They expressed significantly lower levels of the TCR/CD3 antigen receptor, CD3ɛ chains, TCR-ζ chain, or the CD4 coreceptor than Tconv. Levels of kinases, adaptor molecules involved in TCR signaling, and early downstream activation pathways were also lower in Tregs than in Tconv. Furthermore, TCR/CD3 complexes in Tregs were enriched in CD3ɛ chains conserving their N-terminal, negatively charged amino acid residues; this trait is linked to a higher activation threshold. Transfection of mutant CD3ɛ chains lacking these residues inhibited the differentiation of mature CD4+Foxp3− T lymphocytes into CD4+Foxp3+ Tregs, and differences in CD3ɛ chain recognition by antibodies could be used to enrich for Tregs in vivo. Our results show quantitative and qualitative differences in the TCR/CD3 complex, supporting the hyporesponsive phenotype of Tregs concerning TCR/CD3 signals. These differences might reconcile avidity and flexible threshold models of Treg differentiation and be used to implement therapeutic approaches involving Treg manipulation.
Dispersal, eddies, and the diversity of marine phytoplankton
Authors: Clayton Sophie , Dutkiewicz Stephanie , Jahn Oliver , Follows Michael J. 
Published: November 2013

Lay AbstractPhytoplankton are the “plants” of the ocean; they fix carbon dioxide from the atmosphere and make up the base of the oceanic food chain. Phytoplankton are incredibly diverse, but the reason for their high biodiversity is not well understood. Generally speaking, phytoplankton might be present in a given location either because they are “happy” and able to grow there, or if they are unable to grow there, because they have been transported in from elsewhere (i.e., via dispersal). Previous studies have suggested that “hotspots” of high phytoplankton diversity found in the most dynamic oceanic regions can be explained by dispersal. We explored this question by using a set of computer simulations of phytoplankton ecology coupled to a realistic ocean circulation. We show that dispersal can only partly explain diversity hotspots. The mixing of populations by ocean currents and eddies is important, but a plentiful supply of nutrients and variable environmental conditions also enhance phytoplankton diversity. This work has generated hypotheses that will stimulate new projects to test them in the field.
ModelingMycobacterium tuberculosisearly granuloma formation in experimental human lung tissue
Authors: Parasa Venkata Ramanarao , Rahman Muhammad Jubayer , Ngyuen Hoang Anh Thu , Svensson Mattias , Brighenti Susanna , Lerm Maria 
Published: November 2013

SummaryThe widely used animal models for tuberculosis (TB) display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and display characteristics of human lung tissue including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the Type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.
Synthesis of Highly Conjugated Dinuclear Ru Complexes Bridged by a Novel N2–N3 Ligand and Their Application in Photocatalytic Oxygenation of Sulfides
Authors: Kozawa Kazuyuki , Inagaki Akiko , Akita Munetaka 
Published: November 2013

Abstract
Highly conjugated dinuclear Ru complexes bridged by a novel N2–N3 ligand were synthesized. The dinuclear Ru complexes were active toward photoredox-mediated catalytic sulfide oxygenation via proton-coupled oxidation in neutral conditions. Various control experiments have shown that both dinuclear motif and light are essential for the reaction.
Circulating U2 Small Nuclear RNA Fragments as a Novel Diagnostic Tool for Patients with Epithelial Ovarian Cancer
Authors: Kuhlmann Jan Dominik , Baraniskin Alexander , Hahn Stephan A , Mosel Frank , Bredemeier Maren , Wimberger Pauline , Kimmig Rainer , Kasimir-Bauer Sabine 
Published: November 2013

Abstract

BACKGROUND
Ovarian cancer is the leading cause of death among malignancies in women. Despite advances in treatment, &gt;50% of patients relapse. For disease monitoring, the identification of a blood-based biomarker would be of prime interest. In this regard, noncoding RNAs, such as microRNA (miRNA) or small nuclear RNA (snRNA), have been suggested as biomarkers for noninvasive cancer diagnosis. In the present study, we sought to identify differentially expressed miRNA/snRNA in sera of ovarian cancer patients and investigate their potential to aid in therapy monitoring.

METHODS
miRNA/snRNA abundance was investigated in serum (n = 10) by microarray analysis and validated in an extended serum set (n = 119) by reverse-transcription quantitative PCR.

RESULTS
Abundance of U2-1 snRNA fragment (RNU2-1f) was significantly increased in sera of ovarian cancer patients (P &lt; 0.0001) and paralleled International Federation of Gynecology and Obstetrics stage as well as residual tumor burden after surgery (P &lt; 0.0001 and P = 0.011, respectively). Moreover, for patients with suboptimal debulking, preoperative RNU2-1f concentration was associated with radiographic response after chemotherapy and with platinum resistance (P = 0.0088 and P = 0.0015, respectively). Interestingly, according to the RNU2-1f abundance dynamics, persistent RNU2-1f positivity before surgery and after chemotherapy identified a subgroup of patients with high risk of recurrence and poor prognosis.

CONCLUSIONS
This is the first report to suggest that a circulating snRNA can serve as an auxiliary diagnostic tool for monitoring tumor dynamics in ovarian cancer. Our results provide a rationale to further investigate whether this high-risk patient group may benefit from additional therapies that are directly applied after chemotherapy.
Supporting the creative industries: The rationale for an exchange of thinking between the art and business schools
Authors: Kearney Gemma , Harris Paul 
Published: November 2013

Abstract
Increasing interest in the concept of the ‘Creative Industries’ with emphasis upon the ‘industry’ aspect, presents questions as to how Art Schools can best prepare students. Indeed the industrial aspect encourages consideration of business and entrepreneurship and by adopting a conceptual approach to draw together different strands of literature from art, design, business and entrepreneurship research, this article explores the issues and challenges in supporting students in a creative context. Areas where an exchange of thinking could occur between the Art and Business Schools are identified and where the cross-fertilization of ideas and teaching practices could offer new methods to support students to engage in the Creative Industries. Barriers remain in teaching entrepreneurship, but viewing it as a process, utilizing the Theory of Effectuation and drawing attention to the prevalence of entrepreneurial teams proffers insights.
The mechanics of managing the Cultural and Creative Industry ParkCultural and Creative Industry Park in National Taiwan University of Arts
Authors: Huang Mei-Hsien 
Published: November 2013

Abstract
In response to the trend of creative economy and in support of the national education policy of university-industry links and the mission of cultivating talents, National Taiwan University of Arts established the first Cultural and Creative Industry Park in Taiwan in 2007. This also qualifies National Taiwan University of Arts as the only university affiliated with a cultural and creative park in Taiwan. This paper aims to explore the mechanics of managing the Cultural and Creative Industry ParkCultural and Creative Industry Park in National Taiwan University of Arts. Through document analysis this article reveals the six operational characteristics of this park, including renovating the old paper mill factory, planning the multifunctional space, inviting excellent cultural and creative manufacturers to station in, establishing a specialized management unit, utilizing university academic and administrative resources, and striving for the government subsidy and industry reward. There are five objectives of the operational content of the Cultural and Creative Industry ParkCultural and Creative Industry Park, including teaching and internship, consultation for starting an enterprise, research innovation, industry incubation, and life aesthetics promotion. Finally, the paper points out three concerns regarding current operations.
Reviews
Authors: Carrier David , Haanstra Folkert , Schönau Diederik 
Published: November 2013

Abstract
World Art: An Introduction to the Art in Artefacts, Ben Burt (2013) London and New York: Bloomsbury Academic, 272 pp., ISBN: 978-1-84788-943-0, p/bk, $29.95, £17.99
Zeichnen: Wahrnehmen, Verarbeiten, Darstellen. Empirische Untersuchungen Zur Ermittlung Räumlich-Visueller Kompetenzen IM Kunstunterricht, Edith Glaser-Henzer, Ludwig Diehl, Luitgard Diehl Ott, Georg Peez (2012) München: Kopaed, 201 pp., ISBN: 978-3-86736-133-0, p/bk, €18.80
Künstlerische Kunstpädagogik. Ein Diskurs Zur Künstlerischen Bildung, Carl-Peter Buschkühle (ed.) (2012) Oberhausen: Athena Verlag, 482 pp., ISBN: 978-3-89896-514-9, p/bk, €29.50
Implicating SCF Complexes in Organogenesis in Caenorhabditis elegans
Authors: Polley Stanley R G , Kuzmanov Aleksandra , Kuang Jujiao , Karpel Jonathan , Lažetić Vladimir , Karina Evguenia I , Veo Bethany L , Fay David S 
Published: November 2013

Abstract
Development of the Caenorhabditis elegans foregut (pharynx) is regulated by a network of proteins that includes the Retinoblastoma protein (pRb) ortholog LIN-35; the ubiquitin pathway components UBC-18 and ARI-1; and PHA-1, a cytoplasmic protein. Loss of pha-1 activity impairs pharyngeal development and body morphogenesis, leading to embryonic arrest. We have used a genetic suppressor approach to dissect this complex pathway. The lethality of pha-1 mutants is suppressed by loss-of-function mutations in sup-35/ztf-21 and sup-37/ztf-12, which encode Zn-finger proteins, and by mutations in sup-36. Here we show that sup-36 encodes a divergent Skp1 family member that binds to several F-box proteins and the microtubule-associated protein PLT-1/τ. Like SUP-35, SUP-36 levels were negatively regulated by UBC-18–ARI-1. We also found that SUP-35 and SUP-37 physically associated and that SUP-35 could bind microtubules. Thus, SUP-35, SUP-36, and SUP-37 may function within a pathway or complex that includes cytoskeletal components. Additionally, SUP-36 may regulate the subcellular localization of SUP-35 during embryogenesis. We carried out a genome-wide RNAi screen to identify additional regulators of this network and identified 39 genes, most of which are associated with transcriptional regulation. Twenty-three of these genes acted via the LIN-35 pathway. In addition, several S-phase kinase-associated protein (Skp)1–Cullin–F-Box (SCF) components were identified, further implicating SCF complexes as part of the greater network controlling pharyngeal development.
Recombination and Annealing Pathways Compete for Substrates in Making rrn Duplications in Salmonella enterica
Authors: Reams Andrew B , Kofoid Eric , Duleba Natalie , Roth John R 
Published: November 2013

Abstract
Tandem genetic duplications arise frequently between the seven directly repeated 5.5-kb rrn loci that encode ribosomal RNAs in Salmonella enterica. The closest rrn genes, rrnB and rrnE, flank a 40-kb region that includes the purHD operon. Duplications of purHD arise by exchanges between rrn loci and form at a high rate (10−3/cell/division) that remains high in strains blocked for early steps in recombination (recA, recB, and/or recF), but drops 30-fold in mutants blocked for later Holliday junction resolution (ruvC recG). The duplication defect of a ruvC recG mutant was fully corrected by an added mutation in any one of the recA, recB, or recF genes. To explain these results, we propose that early recombination defects activate an alternative single-strand annealing pathway for duplication formation. In wild-type cells, rrn duplications form primarily by the action of RecFORA on single-strand gaps. Double-strand breaks cannot initiate rrn duplications because rrn loci lack Chi sites, which are essential for recombination between two separated rrn sequences. A recA or recF mutation allows unrepaired gaps to accumulate such that different rrn loci can provide single-strand rrn sequences that lack the RecA coating that normally inhibits annealing. A recB mutation activates annealing by allowing double-strand ends within rrn to avoid digestion by RecBCD and provide a new source of rrn ends for use in annealing. The equivalent high rates of rrn duplication by recombination and annealing pathways may reflect a limiting economy of gaps and breaks arising in heavily transcribed, palindrome-rich rrn sequences.
General Triallelic Frequency Spectrum Under Demographic Models with Variable Population Size
Authors: Jenkins Paul A , Mueller Jonas W , Song Yun S 
Published: November 2013

Abstract
It is becoming routine to obtain data sets on DNA sequence variation across several thousands of chromosomes, providing unprecedented opportunity to infer the underlying biological and demographic forces. Such data make it vital to study summary statistics that offer enough compression to be tractable, while preserving a great deal of information. One well-studied summary is the site frequency spectrum—the empirical distribution, across segregating sites, of the sample frequency of the derived allele. However, most previous theoretical work has assumed that each site has experienced at most one mutation event in its genealogical history, which becomes less tenable for very large sample sizes. In this work we obtain, in closed form, the predicted frequency spectrum of a site that has experienced at most two mutation events, under very general assumptions about the distribution of branch lengths in the underlying coalescent tree. Among other applications, we obtain the frequency spectrum of a triallelic site in a model of historically varying population size. We demonstrate the utility of our formulas in two settings: First, we show that triallelic sites are more sensitive to the parameters of a population that has experienced historical growth, suggesting that they will have use if they can be incorporated into demographic inference. Second, we investigate a recently proposed alternative mechanism of mutation in which the two derived alleles of a triallelic site are created simultaneously within a single individual, and we develop a test to determine whether it is responsible for the excess of triallelic sites in the human genome.
Estimation of the Spontaneous Mutation Rate per Nucleotide Site in aDrosophila melanogasterFull-Sib Family
Authors: Keightley Peter D , Ness Rob W , Halligan Daniel L , Haddrill Penelope R 
Published: November 2013

AbstractWe employed deep genome sequencing of two parents and 12 of their offspring to estimate the mutation rate per site per generation in a full-sib family of Drosophila melanogaster recently sampled from a natural population. Sites that were homozygous for the same allele in the parents and heterozygous in one or more offspring were categorized as candidate mutations and subjected to detailed analysis. In 1.23 × 109 callable sites from 12 individuals, we confirmed six single nucleotide mutations. We estimated the false negative rate in the experiment by generating synthetic mutations using the empirical distributions of numbers of nonreference bases at heterozygous sites in the offspring. The proportion of synthetic mutations at callable sites that we failed to detect was &lt;1%, implying that the false negative rate was extremely low. Our estimate of the point mutation rate is 2.8 × 10−9 (95% confidence interval = 1.0 × 10−9 − 6.1 × 10−9) per site per generation, which is at the low end of the range of previous estimates, and suggests an effective population size for the species of ∼1.4 × 106. At one site, point mutations were present in two individuals, indicating that there had been a premeiotic mutation cluster, although surprisingly one individual had a G→A transition and the other a G→T transversion, possibly associated with error-prone mismatch repair. We also detected three short deletion mutations and no insertions, giving a deletion mutation rate of 1.2 × 10−9 (95% confidence interval = 0.7 × 10−9 − 11 × 10−9).
HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer
Authors: Verma Sunil , Joy Anil A. , Rayson Daniel , McLeod Deanna , Brezden-Masley Christine , Boileau Jean-François , Gelmon Karen A. 
Published: November 2013

AbstractUntreated human epidermal growth factor receptor-2 (HER-2)-positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER-2-directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER-2-positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER-2-directed therapy has had on disease outcomes, some patients with HER-2-positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER-2-directed therapy in patients with HER-2-positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER-2-positive ABC outcomes.
Where are You Watching? Patterns of Visual Exploration in the Ultimatum Game
Authors: Villani Daniela , Massaro Davide , Castelli Ilaria , Marchetti Antonella 
Published: November 2013

The study aimed to advance the traditional issue of identifying decision strategy by analyzing the information
processing in terms of visual exploration patterns. Twenty-seven participants played as responders in a computerized version
of Ultimatum Game with an anonymous virtual partner.
Responders tended to reject unfair offers, probably due to their taste for fairness and to the unidentifiability of the other
player that reduced the willingness to cooperate. Furthermore, according to the evolutionary approach, participants focused
their attention more at themselves than at the partner. Among the three type of offers – hyperfair, fair and unfair –
mid-value offers, such as fair ones, required more number of fixations and fixations duration, related to the more complex
cognitive and reasoning processes involved.
Implications of this study could be applied in decisional settings with anonymous partners, such as those online, with future
studies confirming the results found and integrating them through other process tracing methodologies.
Cross-Linking as an Adjuvant Treatment for Tectonic Corneal Lamellar Graft Preparation
Authors: Kymionis George D. , Plaka Argyro D. , Diakonis Vasilios F. , Grentzelos Michael A. , Kontadakis Georgios A. , Mersinoglou Andreana C. , Detorakis Efstathios T. , Topouzis Fotis 
Published: November 2013

Purpose:
To describe a new surgical approach for the tectonic reconstruction of the anterior ocular segment and the management of scleral and conjuctival melting.

Methods:
Case series of patients demonstrating anterior segment anomalies, such as scleral and conjunctival melting. The anterior stromal part of a pre-cut corneal graft for Descemet’s stripping automated endothelial keratoplasty (DSAEK) was cross-linked with riboflavin and ultraviolet A irradiation and was used to cover scleral (scleral melting in a patient with necrotizing scleritis, one case) and conjuctival (dehiscence of the conjunctiva in patients with anti-glaucomatous valve exposure, two cases) areas. The endothelial part of all corneal grafts was used for DSAEK in patients with need of corneal endothelial transplantation.

Results:
Repair of scleral and conjuctival melting was successful in all cases. No intra- or post- operative complications occured. Visual acuity of all patients remained stable during the follow up period. One year postoperatively the corneal graft remained in place and no signs of inflammation were evident, while all grafts were epithelialized.

Conclusions:
The use of cross-linked corneal graft for the tectonic reconstruction of the anterior ocular segment represents an adequate surgical approach for the management of scleral and conjuctival melting; while, at the same time it offers the advantage of using one corneal graft for two recipients.