bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Replication Checkpoint Signaling Depends on a Rad53–Dbf4 N-Terminal Interaction in Saccharomyces cerevisiae
Authors: Chen Ying-Chou , Kenworthy Jessica , Gabrielse Carrie , Hänni Christine , Zegerman Philip , Weinreich Michael 
Published: April 2013

Abstract
Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) are essential to initiate DNA replication at individual origins. During replication stress, the S-phase checkpoint inhibits the DDK- and CDK-dependent activation of late replication origins. Rad53 kinase is a central effector of the replication checkpoint and both binds to and phosphorylates Dbf4 to prevent late-origin firing. The molecular basis for the Rad53–Dbf4 physical interaction is not clear but occurs through the Dbf4 N terminus. Here we found that both Rad53 FHA1 and FHA2 domains, which specifically recognize phospho-threonine (pT), interacted with Dbf4 through an N-terminal sequence and an adjacent BRCT domain. Purified Rad53 FHA1 domain (but not FHA2) bound to a pT Dbf4 peptide in vitro, suggesting a possible phospho-threonine-dependent interaction between FHA1 and Dbf4. The Dbf4–Rad53 interaction is governed by multiple contacts that are separable from the Cdc5- and Msa1-binding sites in the Dbf4 N terminus. Importantly, abrogation of the Rad53–Dbf4 physical interaction blocked Dbf4 phosphorylation and allowed late-origin firing during replication checkpoint activation. This indicated that Rad53 must stably bind to Dbf4 to regulate its activity.
Reactive Oxygen Species Homeostasis and Virulence of the Fungal PathogenCryptococcus neoformansRequires an Intact Proline Catabolism Pathway
Authors: Lee I Russel , Lui Edmund Y L , Chow Eve W L , Arras Samantha D M , Morrow Carl A , Fraser James A 
Published: April 2013

AbstractDegradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. The two-step oxidation of proline is catalyzed by proline oxidase and Δ1-pyrroline-5-carboxylate (P5C) dehydrogenase, which produce P5C and glutamate, respectively. In animal and plant cells, impairment of P5C dehydrogenase activity results in P5C-proline cycling when exogenous proline is supplied via the actions of proline oxidase and P5C reductase (the enzyme that converts P5C to proline). This proline is oxidized by the proline oxidase-FAD complex that delivers electrons to the electron transport chain and to O2, leading to mitochondrial reactive oxygen species (ROS) overproduction. Coupled activity of proline oxidase and P5C dehydrogenase is therefore important for maintaining ROS homeostasis. In the genome of the fungal pathogen Cryptococcus neoformans, there are two paralogs (PUT1 and PUT5) that encode proline oxidases and a single ortholog (PUT2) that encodes P5C dehydrogenase. Transcription of all three catabolic genes is inducible by the presence of proline. However, through the creation of deletion mutants, only Put5 and Put2 were found to be required for proline utilization. The put2Δ mutant also generates excessive mitochondrial superoxide when exposed to proline. Intracellular accumulation of ROS is a critical feature of cell death; consistent with this fact, the put2Δ mutant exhibits a slight, general growth defect. Furthermore, Put2 is required for optimal production of the major cryptococcal virulence factors. During murine infection, the put2Δ mutant was discovered to be avirulent; this is the first report highlighting the importance of P5C dehydrogenase in enabling pathogenesis of a microorganism.
Bulk Segregant Analysis of an Induced Floral Mutant Identifies aMIXTA-Like R2R3MYBControlling Nectar Guide Formation inMimulus lewisii
Authors: Yuan Yao-Wu , Sagawa Janelle M , Di Stilio Verónica S , Bradshaw H D 
Published: April 2013

AbstractThe genetic and developmental basis of many ecologically important floral traits (e.g., carotenoid pigmentation, corolla tube structure, nectar volume, pistil and stamen length) remains poorly understood. Here we analyze a chemically induced floral mutant of Mimulus lewisii through bulk segregant analysis and transgenic experiments and identify a MIXTA-like R2R3 MYB gene that controls nectar guide formation in M. lewisii flowers, which involves epidermal cell development and carotenoid pigmentation.
Effect of Type 1 Diabetes on Carotid Structure and Function in Adolescents and Young Adults
Authors: Urbina Elaine M. , Dabelea Dana , D’Agostino Ralph B. , Shah Amy S. , Dolan Lawrence M. , Hamman Richard F. , Daniels Stephen R. , Marcovina Santica , Wadwa R. Paul 
Published: April 2013

OBJECTIVE
Type 1 diabetes mellitus causes increased carotid intima-media thickness (IMT) in adults. We evaluated IMT in young subjects with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Participants with type 1 diabetes (N = 402) were matched to controls (N = 206) by age, sex, and race or ethnicity. Anthropometric and laboratory values, blood pressure, and IMT were measured. ANCOVA was used to assess differences controlling for demographic risk factors, cardiovascular risk factors, and HbA1c.

RESULTS
Subjects were 18.9 ± 3.3 years old (50% male, 82.7% non-Hispanic white). Youth with type 1 diabetes had thicker bulb IMT, which remained significantly different after adjustment for demographics and cardiovascular risk factors. Age, sex, adiposity, and systolic blood pressure were consistent significant determinants of IMT. Adjustment for HbA1c eliminated the difference, suggesting the difference was attributable to poor glycemic control.

CONCLUSIONS
Carotid IMT may be increased in youth with type 1 diabetes at high risk for cardiovascular disease. Better control of diabetes may be essential in preventing progression of atherosclerosis.
Effect of Insulin Glargine and n-3FA on Carotid Intima-Media Thickness in People With Dysglycemia at High Risk for Cardiovascular Events
Authors: Lonn Eva M. , Bosch Jackie , Diaz Rafael , Lopez-Jaramillo Patricio , Ramachandran Ambady , Hâncu Nicolae , Hanefeld Markolf , Krum Henry , Ryden Lars , Smith Sandra , McQueen Matthew J. , Dyal Leanne , Yusuf Salim , Gerstein Hertzel C. ,   for the GRACE and ORIGIN Investigators
Published: April 2013

OBJECTIVE
To evaluate the effects of insulin glargine and n-3 polyunsaturated fatty acid (n-3FA) supplements on carotid intima-media thickness (CIMT).

RESEARCH DESIGN AND METHODS
We enrolled 1,184 people with cardiovascular (CV) disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes in a randomized multicenter 2 × 2 factorial design trial. Participants received open-label insulin glargine (targeting fasting glucose levels ≤5.3 mmol/L [95 mg/dL]) or standard glycemic care and double-blind therapy with a 1-g capsule of n-3FA or placebo. The primary trial outcome was the annualized rate of change in maximum CIMT for the common carotid, bifurcation, and internal carotid artery segments. Secondary outcomes were the annualized rates of change in maximum CIMT for the common carotid and the common carotid plus bifurcation, respectively. Baseline followed by annual ultrasounds were obtained during a median follow-up of 4.9 years.

RESULTS
Compared with standard care, insulin glargine reduced the primary CIMT outcome, but the difference was not statistically significant (difference = 0.0030 ± 0.0021 mm/year; P = 0.145) and significantly reduced the secondary CIMT outcomes (differences of 0.0033 ± 0.0017 mm/year [P = 0.049] and 0.0045 ± 0.0021 mm/year [P = 0.032], respectively). There were no differences in the primary and secondary outcomes between the n-3FA supplement and placebo groups.

CONCLUSIONS
In people with CV disease and/or CV risk factors and dysglycemia, insulin glargine used to target normoglycemia modestly reduced CIMT progression, whereas daily supplementation with n-3FA had no effect on CIMT progression.
Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine
Authors: Riddle Matthew C. , Forst Thomas , Aronson Ronnie , Sauque-Reyna Leobardo , Souhami Elisabeth , Silvestre Louise , Ping Lin , Rosenstock Julio 
Published: April 2013

OBJECTIVEWhen oral therapy for type 2 diabetes is ineffective, adding basal insulin improves glycemic control. However, when glycated hemoglobin (HbA1c) remains elevated because of postprandial hyperglycemia, the next therapeutic step is controversial. We examined the efficacy and safety of lixisenatide in patients with HbA1c still elevated after initiation of insulin glargine.RESEARCH DESIGN AND METHODSThis double-blind, parallel-group trial enrolled patients with HbA1c 7–10% despite oral therapy. Insulin glargine was added and systematically titrated during a 12-week run-in, after which candidates with fasting glucose ≤7.8 mmol/L and HbA1c 7–9% were randomized to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued. The primary end point was HbA1c change after randomization.RESULTSThe randomized population (n = 446) had mean diabetes duration of 9.2 years, BMI 31.8 kg/m2, and daily glargine dosage of 44 units. HbA1c had decreased during run-in from 8.6 to 7.6%; adding lixisenatide further reduced HbA1c by 0.71 vs. 0.40% with placebo (least squares mean difference, –0.32%; 95% CI, –0.46 to –0.17; P &lt; 0.0001). More participants attained HbA1c &lt;7% with lixisenatide (56 vs. 39%; P &lt; 0.0001). Lixisenatide reduced plasma glucose 2 h after a standardized breakfast (difference vs. placebo –3.2 mmol/L; P &lt; 0.0001) and had a favorable effect on body weight (difference vs. placebo –0.89 kg; P = 0.0012). Nausea, vomiting, and symptomatic hypoglycemia &lt;3.3 mmol/L were more common with lixisenatide.CONCLUSIONSAdding lixisenatide to insulin glargine improved overall and postprandial hyperglycemia and deserves consideration as an alternative to prandial insulin for patients not reaching HbA1c goals with recently initiated basal insulin.
Glucagon-Like Peptide 1 Reduces Endothelial Dysfunction, Inflammation, and Oxidative Stress Induced by Both Hyperglycemia and Hypoglycemia in Type 1 Diabetes
Authors: Ceriello Antonio , Novials Anna , Ortega Emilio , Canivell Silvia , La Sala Lucia , Pujadas Gemma , Esposito Katherine , Giugliano Dario , Genovese Stefano 
Published: April 2013

OBJECTIVE
Hyperglycemia and hypoglycemia currently are considered risk factors for cardiovascular disease in type 1diabetes. Both acute hyperglycemia and hypoglycemia induce endothelial dysfunction and inflammation, raising the oxidative stress. Glucagon-like peptide 1 (GLP-1) has antioxidant properties, and evidence suggests that it protects endothelial function.

RESEARCH DESIGN AND METHODS
The effect of both acute hyperglycemia and acute hypoglycemia in type 1 diabetes, with or without the simultaneous infusion of GLP-1, on oxidative stress (plasma nitrotyrosine and plasma 8-iso prostaglandin F2alpha), inflammation (soluble intercellular adhesion molecule-1 and interleukin-6), and endothelial dysfunction has been evaluated.

RESULTS
Both hyperglycemia and hypoglycemia acutely induced oxidative stress, inflammation, and endothelial dysfunction. GLP-1 significantly counterbalanced these effects.

CONCLUSIONS
These results suggest a protective effect of GLP-1 during both hypoglycemia and hyperglycemia in type 1 diabetes.
Low-Carbohydrate Diet for the Treatment of Gestational Diabetes Mellitus
Authors: Moreno-Castilla Cristina , Hernandez Marta , Bergua Merce , Alvarez Maria C. , Arce Maria A. , Rodriguez Karen , Martinez-Alonso Montserrat , Iglesias Montserrat , Mateu Magdalena , Santos Maria D. , Pacheco Linda R. , Blasco Yolanda , Martin Eva , Balsells Nuria , Aranda Nuria , Mauricio Didac 
Published: April 2013

OBJECTIVE
Medical nutrition therapy based on the control of the amount and distribution of carbohydrates (CHO) is the initial treatment for gestational diabetes mellitus (GDM), but there is a need for randomized controlled trials comparing different dietary strategies. The purpose of this study was to test the hypothesis that a low-CHO diet for the treatment of GDM would lead to a lower rate of insulin treatment with similar pregnancy outcomes compared with a control diet.

RESEARCH DESIGN AND METHODS
A total of 152 women with GDM were included in this open, randomized controlled trial and assigned to follow either a diet with low-CHO content (40% of the total diet energy content as CHO) or a control diet (55% of the total diet energy content as CHO). CHO intake was assessed by 3-day food records. The main pregnancy outcomes were also assessed.

RESULTS
The rate of women requiring insulin was not significantly different between the treatment groups (low CHO 54.7% vs. control 54.7%; P = 1). Daily food records confirmed a difference in the amount of CHO consumed between the groups (P = 0.0001). No differences were found in the obstetric and perinatal outcomes between the treatment groups.

CONCLUSIONS
Treatment of women with GDM using a low-CHO diet did not reduce the number of women needing insulin and produced similar pregnancy outcomes. In GDM, CHO amount (40 vs. 55% of calories) did not influence insulin need or pregnancy outcomes.
Variational iteration method — a promising technique for constructing equivalent integral equations of fractional order
Authors: Wang Yi-Hong , Wu Guo-Cheng , Baleanu Dumitru 
Published: April 2013

Abstract
The variational iteration method is newly used to construct various integral equations of fractional order. Some iterative schemes are proposed which fully use the method and the predictor-corrector approach. The fractional Bagley-Torvik equation is then illustrated as an example of multi-order and the results show the efficiency of the variational iteration method’s new role.
The Lady Gregory Letters To G. B. Shaw
Authors: Murphy Daniel 
Published: April 2013

THE SECOND LETTER IN THE FOLLOWING SELECTION is characteristic of the relationship between Lady Gregory and G. B. Shaw—it is a request for advice. Shaw was frequently asked about theater matters, for, as Lady Gregory once pointed out, she could not go to the Author's League, since, as the owner of a theater, she was considered the author's legitimate enemy. Problems were constantly cropping up—money matters, salaries for author and actor, audience hostility, and the need for new plays. It was this need for plays, perhaps, that first involved Shaw with what has become known as the Irish Renaissance. The Abbey patent restricted the theater "to exhibit plays in the Irish or English language written by Irish writers on Irish subjects, or such dramatic works of foreign authors as would tend to interest the public in the higher works of dramatic art .... "The small repertory company assembled by the Fay brothers precluded any ambitious undertaking; moreover, there was no tradition in Ireland for the kind of plays the theater needed. Yeats asked Shaw for help, and he responded with John Bull's Other Island.
Ibsen's Wild Duck
Authors: Mueller Janel 
Published: April 2013

WHEN IBSEN MAILED THE MANUSCRIPT OF The Wild Duck to his publisher in September 1884, he noted in his covering letter that the method of the new play gave it a place apart in his work. He would say no more, he added; the critics would find enough to squabble about and interpret. Ibsen's prediction has proved abundantly correct. Although some have found novelty in its mixture of tragedy and farce, in its involved, equivocal exposition, or in its notoriously squalid setting, most have agreed that the novelty of The Wild Duck is in its structure. As the title alerts us to see, the play is built around the wild duck which, though it remains unglimpsed by the audience, becomes the most instrumental element in the drama. Ibsen uses it to bring out the nature and relations of the characters and to point the way to our understanding of the course of events. In fact, his choice of title is our best clue to the meaning of his teasing remarks, for The Wild Duck all but ensures recognition of the peculiar concentric arrangement of the play.
Six Characters: Pirandello's Last Tape
Authors: Kennedy Andrew 
Published: April 2013

THERE CAN BE LITTLE DOUBT that Pirandello's Six Characters in Search of An Author owes its continued hold on our imagination-and its power as theatre-to the successful fusion of two orders of experience: the pain of role-playing in any life, and the painful limitations of dramatic art, particularly the crisis of post-Ibsen naturalism. The way Pirandello achieves this fusion is familiar enough and can be restated as follows. The imagined but prematurely abandoned 'characters,' who come to claim performance on the stage, feel themselves caught in the false fixity of a few moments of action; so they hope to be shown, to be re-created in the precise sense, through a different and compensating fixity: the Grecian urn perfectedness of art. But the completion and rehearsal of an unfinished play is not at all like the Grecian urn; on the contrary, it brings back the flux of life and inchoate creation, and the characters have to suffer again an awareness that exceeds their role. In effect, they react to this openness by wanting to choose the kind of play that suits them. And the two most articulate characters-the Father and the Stepmother-are torn by a desire for seemingly conflicting types of play: they want absolute fidelity to every naturalistic detail (the yellow plush of Madame Pace's sofa) while also wanting to go beyond this reduced play to express their essential inwardness: they want to be chorus, and they want to mean more than their fixed actions and words.
Riot, Revolution, And The Weavers
Authors: Dobie Ann 
Published: April 2013

GERHART HAUPTMANN HOLDS THE LONELY DISTINCTION of being a playwright who is anthologized and taught with some frequency but who, with equal frequency, is criticized and dismissed as minor, dated, and inconsistent. Indeed, The Weavers, his most significant play, is often found in textbooks for courses in modern drama with a notable critic such as John Gassner calling it repetitious and criticizing Hauptmann for not fully developing the characters. Gassner even comments that the actions of the weavers contribute nothing to "an intelligent treatment of modern realities." In general, critical opinion is reluctant to abandon Hauptmann completely to the once popular-then taught-now forgotten category to which many writers are discarded. On the other hand, the superficial and generalized analyses done of his work fail to reveal reasons for continuing to read, study, or produce his plays. Upon reading much of the Hauptmann study of the past few years one is led to wonder what all the enthusiasm could ever have been about. But upon reading Hauptmann himself, the old excitement returns and one wonders what the sneering was all about. In light of the revolutionary aspects of the present day, The Weavers is a surprisingly current and socially relevant play. Revolution, a word used only a decade ago with some sense of superiority when referring to the governments of South America, is today a term pondered, condemned, and celebrated by America's taxi-drivers, intellectuals, and teen-agers. If heretofore Hauptmann's play has been read with a degree of misunderstanding and apathy, the events of this decade, and more particularly the past election year, bring today's reader to the play with experiences which heighten and clarify its passion and its simplicity.
Book Reviews
Authors: Adler Jacob , Ziegler Carl , Johnson Walter , Carpenter Fredrick , Falk Signi , Erickson John , Miller Jordan , Brandon James 
Published: April 2013

Milton Levin, Noel Coward, reviewed by Jacob H. Adler John M. Spalek, Ernst Toller And His Critics, reviewed by Carl Ziegler Egil Tornqvist, Drama Och Teater, reviewed by Walter Johnson Tifno Tiusanen, O'Neill's Scenic Images, reviewed by Frederic I. Carpenter Robert E. Gard, Theatre In America: Appraisal And Challenge, reviewed by Signi Falk . Anthony N. Zahareas ed., Ramon Del Valle-Inclan: An Appraisal Of His Life And Works, reviewed by John D. Erickson Louis Sheaffer, O'Neill: Son And Playwright, reviewed by Jordan Y. Miller James L. Peacock, Rites Of Modernization: Symbolic And Social Aspects Of Indonesian Proletarian Drama, reviewed by James R. Brandon
Arthur Miller And The Meaning Of Tragedy
Authors: Martin Robert 
Published: April 2013

(Interview by Robert A. Martin) R.M. In earlier essays and statements you have said that tragedy reflects certain qualities, and I take it that when you wrote All My Sons, Death of a Salesman, The Crucible, and A View from the Bridge, tragedy was a definable quality to you. For example, "Tragedy makes us aware of what the character might have been"; "Tragedy is the consequence of a man's total compulsion to evaluate himself justly"; and later, in the "Preface" to the Collected Plays, you said, "The less capable a man is of walking away from the central conflict of a play, the closer he approaches the tragic existence."
The Theater Of Buero Vallejo 1949-1969
Authors: Giuliano William 
Published: April 2013

ANTONIO BUERO VALLEJO, AFTER TWENTY YEARS of continued success, is generally considered Spain's most important contemporary dramatist. He has confounded those critics who have affirmed that the Spanish theatrical public would not support a serious dramatist, that is, one whose aim was not primarily to entertain his audience. Since the now historic success. of Historia de una escalera (Story of a Staircase) in 1949 flung open the doors of a career as playwright to him, Buero, unlike other popular dramatists, has written slowly and carefully, having had produced only thirteen full-length plays and one one-act play. One or two others remain unproduced, while another has been recently published. It would not be amiss at this time to take an overall view of the work of this author who has added a new dimension to contemporary Spanish drama, to examine his works in order to see which are the dominant themes and ideas that have won approval from critics and public alike.
The Divina Commedia As Model And Anti-Model For The Investigation By Peter Weiss
Authors: Salloch Erika 
Published: April 2013

CRITICAL REACTION TO DOCUMENTARY THEATER and particularly to Peter Weiss's The Investigation, has been predominantly negative. "Never was an author less important," is one theme of the criticism. The Investigation is, to date, the most extreme case of the genre of documntary theater because its text follows so closely the documents of the trial in Frankfurt and other published reports on the history of Auschwitz. This paper will not deal with the content of the play, but only with its form, in order to reveal its artistic structure. Its structure as creative effort does not spring from the writer's free imagination, but from the effort to imagine-literally to have the image before his eyes-of the things, the events, and the men of Auschwitz. Just as a collage artist does not manufacture the parts of his composition, the newspaper clippings and the rags, but uses what he finds, so Weiss forms his play from existing elements.
Book Reviews
Authors: Sprinchorn Evert , Parkin Andrew , Loney Glen , Orel Harold , Arestad Sverre , Salmon Eric , Albert Sidney 
Published: April 2013

Martin Lamm, August Strindberg, reviewed by Evert Sprinchorn John Rees Moore, Masks Of Love And Death: Yeats As Dramatist, reviewed by Andrew Parkin Gerald Weales, Clifford Odets: Playwright, reviewed by Glen Loney Harold Orel, Letters To Molly, John Millington Synge To Maire O'Neill 1906-1909, reviewed by Harold Orel Orley I. Holtan, Mythic Patterns In Ibsen's Last Plays, reviewed by Sverre Arestad Dan H. Laurence ed., The Bodley Head Bernard Shaw: Collected Plays And Their Prefaces, reviewed by Eric Salmon Stanley Weintraub, Journey To Heartbreak: The Crucible Years Of Bernard Shaw 1914-18, reviewed by Sidney P. Albert