bluuebunny/crossref_metadata_2025_split huggingface dataset:
The many colours of chromodomains
Authors: Brehm Alexander , Tufteland Katharina R. , Aasland Rein , Becker Peter B. 
Published: January 2004

AbstractLocal differences in chromatin organisation may profoundly affect the activity of eukaryotic genomes. Regulation at the level of DNA packaging requires the targeting of structural proteins and histone‐modifying enzymes to specific sites and their stable or dynamic interaction with the nucleosomal fiber. The “chromodomain”, a domain shared by many regulators of chromatin structure, has long been suspected to serve as a module mediating chromatin interactions in a variety of different protein contexts. However, recent functional analyses of a number of different chromodomains revealed an unexpected diversity of interaction targets, including histones, DNA and even RNA. The chromodomains of today seem to have evolved from a common ancestral fold to fulfill various functions in different molecular contexts. Combining information gained from recent functional and structural studies of chromodomains with a bioinformatic classification of their structure could lead to the definition of sequence motifs with predictive quality for chromodomain function. BioEssays 26:133–140, 2004. © 2004 Wiley Periodicals, Inc.
Sex determination: insights from the chicken
Authors: Smith Craig A. , Sinclair Andrew H. 
Published: January 2004

AbstractNot all vertebrates share the familiar system of XX:XY sex determination seen in mammals. In the chicken and other birds, sex is determined by a ZZ:ZW sex chromosome system. Gonadal development in the chicken has provided insights into the molecular genetics of vertebrate sex determination and how it has evolved. Such comparative studies show that vertebrate sex‐determining pathways comprise both conserved and divergent elements. The chicken embryo resembles lower vertebrates in that estrogens play a central role in gonadal sex differentiation. However, several genes shown to be critical for mammalian sex determination are also expressed in the chicken, but their expression patterns differ, indicating functional plasticity. While the genetic trigger for sex determination in birds remains unknown, some promising candidate genes have recently emerged. The Z‐linked gene, DMRT1, supports the Z‐dosage model of avian sex determination. Two novel W‐linked genes, ASW and FET1, represent candidate female determinants. BioEssays 26:120–132, 2004. © 2004 Wiley Periodicals, Inc.
The use of animal models in the study of complex disease: all else is never equal or why do so many human studies fail to replicate animal findings?
Authors: Williams Scott M. , Haines Jonathan L. , Moore Jason H. 
Published: January 2004

AbstractThe study of the genetics of complex human disease has met with limited success. Many findings with candidate genes fail to replicate despite seemingly overwhelming physiological data implicating the genes. In contrast, animal model studies of the same genes and disease models usually have more consistent results. We propose that one important reason for this is the ability to control genetic background in animal studies. The fact that controlling genetic background can produce more consistent results suggests that the failure to replicate human findings in the same diseases is due to variation in interacting genes. Hence, the contrasting nature of the findings from the different study designs indicates the importance of non‐additive genetic effects on human disease. We discuss these issues and some methodological approaches that can detect multilocus effects, using hypertension as a model disease. This article contains supplementary material, which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265‐9247/suppmat/index.html. BioEssays 26:170–179, 2004. © 2004 Wiley Periodicals, Inc.
The life and death of sponge cells
Authors: Sipkema Detmer , Snijders Ambrosius P. L. , Schroën Carin G. P. H. , Osinga Ronald , Wijffels René H. 
Published: January 2004

AbstractCell viability is an essential touchstone in the study of the effect of medium components on cell physiology. We developed a flow‐cytometric assay to determine sponge‐cell viability, based on the combined use of fluorescein diacetate (FDA) and propidium iodide (PI). Cell fluorescence measurements based on incubation of cells with FDA or PI resulted in a useful and reproducible estimate of the viability of primary sponge‐cell cultures. We studied the effects of temperature, ammonium, and the fungicide amphotericin B on the viability of a primary‐cell culture from the marine sponge Suberites domuncula using the aforementioned flow‐cytometric assay. S. domuncula cells die rapidly at a temperature of ≥22°C, but they are insensitive to ammonium concentrations of up to 25 mM. Amphotericin B, which is frequently used in sponge‐cell culture media, was found to be toxic to S. domuncula cells. © 2004 Wiley Periodicals, Inc.
Laboratory evolution of cytochrome P450 BM‐3 monooxygenase for organic cosolvents
Authors: Seng Wong Tuck , Arnold Frances H. , Schwaneberg Ulrich 
Published: January 2004

AbstractCytochrome P450 BM‐3 (EC 1.14.14.1) catalyzes the hydroxylation and/or epoxidation of a broad range of substrates, including alkanes, alkenes, alcohols, fatty acids, amides, polyaromatic hydrocarbons, and heterocycles. For many of these notoriously water‐insoluble compounds, P450 BM‐3's Km values are in the millimolar range. Polar organic cosolvents are therefore added to increase substrate solubility and achieve high catalytic efficiency. Using P450 BM‐3 as a catalyst for these important transformations requires that we improve its ability to tolerate the cosolvents. By directed evolution, we improved the activity of P450 BM‐3 in the presence of dimethylsulfoxide (DMSO) and tetrahydrofuran (THF), achieving increases in specific activity up to 10‐fold in 2% (v/v) THF and 6‐fold in 25% (v/v) DMSO. The engineered P450 BM‐3's are also significantly more resistant to acetone, acetonitrile, dimethylformamide, and ethanol as cosolvents in the reaction. © 2004 Wiley Periodicals, Inc.
New tools for mass isotopomer data evaluation in 13C flux analysis: Mass isotope correction, data consistency checking, and precursor relationships
Authors: Wahl S.Aljoscha , Dauner Michael , Wiechert Wolfgang 
Published: January 2004

Abstract13C metabolic flux analysis (MFA) is based on carbon‐labeling experiments where a specifically 13C labeled substrate is fed. The labeled carbon atoms distribute over the metabolic network and the label enrichment of certain metabolic pools is measured by using different methods. Recently, MS methods have been dramatically improved—large and precise datasets are now available. MS data has to be preprocessed and corrected for natural stable mass isotopes. In this article we present (1) a new elegant method to correct MS measurement data for natural stable mass isotopes by infinite dimensional matrix calculus and (2) we statistically analyze and discuss a reconstruction of labeling pattern in metabolic precursors from biosynthesis molecules. Moreover, we establish a new method for consistency checking of MS spectra that can be applied for automatic error recognition in high‐throughput flux analysis procedures. Preprocessing the measurement data changes their statistical properties which have to be considered in the subsequent parameter fitting process for 13C MFA. We show that correcting for stable mass isotopes leads to rather small correlations. On the other hand, a direct reconstruction of a precursor labeling pattern from an aromatic amino acid measurement turns out to be critical. Reasonable results are only obtained if additional, independent information about the labeling of at least one precursor is available. A versatile MatLab tool for the rapid correction and consistency checking of MS spectra is presented. Practical examples for the described methods are also given.©2004 Wiley Periodicals, Inc.
Acrylamid — und seine Folgen für die Ernährung und den Chemieunterricht
Authors: Zimmermann Heidi , Kreher Richard P. , Schmidkunz Heinz 
Published: January 2004

AbstractMIT DEM SCHLAGWORT Acrylamid lässt sich der Kontext zur produktgeprägten Lebenswelt einfach herstellen.
Schwieriger ist es, durch Reflektieren und Systematisieren das Verständnis für das strukturelle Konzept und die Reaktivität organischer Verbindungen zu finden und das Ziel zu erreichen, fachliche Kompetenz zu vermitteln sowie Erfahrungs‐ und Handlungsfähigkeit zu entwickeln. Die Anregung zu dieser Übersicht geht auf einen aktuellen Beitrag von W. Hardam [1] zurück.In elementarisierter Form werden zunächst fachliche Probleme und gesundheitliche Gefährdungen beschrieben sowie konkrete Bezüge zu den fachlichen Grundlagen (Namen‐ und Redox‐Reaktionen) aufgezeigt. Im letzten Abschnitt werden didaktische Zusammenhänge mit elementaren Lernstandards aufgezeigt und in einem Internet‐Anhang (Anlagen I‐V) die Perspektiven mit dem aktuellen Stand der Forschung vermittelt.http://www.uni‐dortmund.de
Chemie der Wunderkerze — ein Thema nicht nur in der Weihnachtszeit
Authors: Martin Christina , de Vries Tönjes 
Published: January 2004

AbstractDAS VERSTÄNDNIS von Redox‐Reaktionen gehört zu den wesentlichen Inhalten des Chemieunterrichts. Dabei wird in der Regel zunächst die Reaktion von Metallen mit verschiedenen Metalloxiden betrachtet, um daraus als strukturierendes Prinzip die Redox‐Reihe der Metalle zu entwickeln. Im weiteren Verlauf werden dann auch Nichtmetalle bzw. Nichtmetalloxide wie z.B. Wasser oder Kohlenstoffdioxid in diese Reihe integriert.Im folgenden Beitrag möchten wir eine Unterrichtskonzeption vorstellen, in der Wunderkerzen als motivierender Ausgangspunkt für die vertiefende Betrachtung von Redox‐Reaktionen dienen. Es wird gezeigt, dass Wunderkerzen, vielfach entgegen den Erwartungen der Schüler, auch in sauerstofffreier Atmosphäre brennen. Man kann aus ihnen sogar eine „Fackel”︁ bauen, die unter Wasser weiter brennt. Darüber hinaus lassen sich beim herkömmlichen Abbrennen von Wunderkerzen an der Luft im Schülerexperiment zahlreiche Reaktionsprodukte nachweisen, u.a. auch emittierte nitrose Gase. In diesem Zusammenhang wird über potenzielle Gesundheitsgefahren aufgeklärt und auch experimentell gezeigt, dass das Abbrennen von Wunderkerzen auf Kuchen nicht unbedingt ein „Leckerbissen”︁ ist. In einigen Klassen der Oberstufe ist diese Konzeption bereits praktisch erprobt worden, so dass Schüleräußerungen in diesem Beitrag aufgegriffen werden.
Alkaloide — ein Unterrichtsthema mit historischen, chemischen und präventiven Bezügen
Authors: Yilmaz Ayhan , Uludağ Nesimi , Morgil Fatma Inci 
Published: January 2004

AbstractDAS ZIEL DER VORLIEGENDEN ARBEIT ist es, die chemischen Eigenschaften von Alkaloiden wie Nikotin, Morphin, Kokain sowie Koffein und die Beeinträchtigung der Gesundheit durch den Konsum dieser Stoffe darzustellen. Es ist bekannt, dass diese Alkaloide eine große Bedeutung in der Gesellschaft haben, da sie legal oder auch illegal konsumiert und dass sie meist als Substanzen verstanden werden, die den Menschen in eine heitere Stimmung bzw. in einen Rausch versetzen. Es ist daher von enormer Bedeutung, dass die Schüler und die Erwachsenen unterschiedlichen Bildungsgrades in dieser Hinsicht aufgeklärt bzw. unterrichtet werden. Wir haben diskutiert, wie dieses Thema im Unterricht der Sekundarstufe in unserem Heimatland behandelt werden kann. Ferner haben wir diesbezüglich Unterrichtsbücher untersucht und Schulexperimente für die Schüler vorgeschlagen. Weiterhin wurden Zahlen von Abhängigen aus der Türkei, Europa und Amerika verglichen, die der Alkaloide konsumieren. Daraus geht hervor, dass die Zahlen in den letzten Jahren gefährlich angestiegen sind.
Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinoma
Authors: Hartman Anne‐Renee , Daniel Bruce L. , Kurian Allison W. , Mills Meredith A. , Nowels Kent W. , Dirbas Frederick M. , Kingham Kerry E. , Chun Nicki M. , Herfkens Robert J. , Ford James M. , Plevritis Sylvia K. 
Published: January 2004

AbstractBACKGROUNDIntensive screening is an alternative to prophylactic mastectomy in women at high risk for developing breast carcinoma. The current article reports preliminary results from a screening protocol using high‐quality magnetic resonance imaging (MRI), ductal lavage (DL), clinical breast examination, and mammography to identify early malignancy and high‐risk lesions in women at increased genetic risk of breast carcinoma.METHODSWomen with inherited BRCA1 or BRCA2 mutations or women with a > 10% risk of developing breast carcinoma at 10 years, as estimated by the Claus model, were eligible. Patients were accrued from September 2001 to May 2003. Enrolled patients underwent biannual clinical breast examinations and annual mammography, breast MRI, and DL.RESULTSForty‐one women underwent an initial screen. Fifteen of 41 enrolled women (36.6%) either had undergone previous bilateral oophorectomy and/or were on tamoxifen at the time of the initial screen. One patient who was a BRCA1 carrier had high‐grade ductal carcinoma in situ (DCIS) that was screen detected by MRI but that was missed on mammography. High‐risk lesions that were screen detected by MRI in three women included radial scars and atypical lobular hyperplasia. DL detected seven women with cellular atypia, including one woman who had a normal MRI and mammogram.CONCLUSIONSBreast MRI identified high‐grade DCIS and high‐risk lesions that were missed by mammography. DL detected cytologic atypia in a high‐risk cohort. A larger screening trial is needed to determine which subgroups of high‐risk women will benefit and whether the identification of malignant and high‐risk lesions at an early stage will impact breast carcinoma incidence and mortality. Cancer 2004. © 2004 American Cancer Society.
The relationship of increasing radiotherapy dose to reduced distant metastases and mortality in men with prostate cancer
Authors: Jacob Rojymon , Hanlon Alexandra L. , Horwitz Eric M. , Movsas Benjamin , Uzzo Robert G. , Pollack Alan 
Published: January 2004

AbstractBACKGROUNDThe association of increasing radiotherapy (RT) dose with reduced biochemical failure (BF) is accepted widely. However, there is little direct evidence that dose escalation has an impact on distant metastasis (DM) or overall mortality (OM). These associations were examined in the current study.METHODSThe outcome of 835 patients who were treated at the Fox Chase Cancer Center (Philadelphia, PA) between 1989 and 1997 using 3‐dimensional, conformal RT alone (median dose, 74 Gray [Gy]) was analyzed. Stepwise multivariate Cox proportional hazards regression analyses (MVAs) were performed with RT dose included as a covariate along with log‐transformed initial pretreatment PSA level, Gleason score, palpation T status, age, and year of treatment (YOT), where indicated. To minimize the effect of YOT, an analysis was performed on a subgroup of 363 patients who were treated prior to 1994.RESULTSWith a median follow‐up of 64 months, there were 220 PSA failures, 44 distant metastases, and 162 deaths. In MVA, RT dose (as a continuous variable) was a significant predictor for BF, DM, and OM. When YOT was included as a covariate, it was related strongly to all endpoints, and the correlations of RT dose with DM and OM were lost. When the effect of YOT was minimized by limiting the MVA to patients who were treated prior to 1994, RT dose again emerged as a significant predictor of DM.CONCLUSIONSEscalation of RT dose reduced the rates of BF, DM, and OM significantly in patients with prostate cancer. The inclusion of YOT had a pronounced effect on these correlations that may confound interpretation. Cancer 2004. © 2003 American Cancer Society.
Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence
Authors: Blakely L. Johnetta , Buzdar Aman U. , Lozada Jose A. , Shullaih Samer A. , Hoy Emma , Smith Terry L. , Hortobagyi Gabriel N. 
Published: January 2004

AbstractBACKGROUNDThe goal of the current study was to assess the effect of pregnancy on the subsequent risk of recurrence after treatment for breast carcinoma, adjusting for established prognostic factors.METHODSBetween 1974 and 1998, 383 patients age ≤ 35 years were treated for breast carcinoma with adjuvant chemotherapy at The University of Texas M. D. Anderson Cancer Center (Houston, TX). The median follow‐up period was 13 years. Of these, 13 patients were excluded from analysis, as no history was available regarding pregnancy; 240 (65%) were > 30 years old; 47 (13%) had at least 1 pregnancy after therapy; 32 had full‐ term pregnancies; 10 had spontaneous or elective abortions; 4 had miscarriages; and 1 had a premature delivery. Estrogen receptor (ER) status, lymph node involvement, and disease stage were evaluated as potential risk factors for recurrence. Information on ER status was unavailable for 123 (33%) patients.RESULTSPatients who experienced a pregnancy tended to have earlier‐stage disease (Stage I/II: 80% vs. 73%), fewer positive lymph nodes (< 4: 87% vs. 52%), more ER negativity (68% vs. 58%), and younger age (< 30 years: 57% vs. 32%) than patients who did not. The incidence of disease recurrence was 23% for women who experienced a pregnancy and 54% for women who did not. The hazard ratio (using the multivariate Cox proportional hazards model) for disease recurrence in patients with posttreatment pregnancy was 0.71 (P = 0.4).CONCLUSIONSIn the current study population, pregnancy was not associated with an increased risk of disease recurrence or poorer survival in patients previously treated for breast carcinoma. Cancer 2004. © 2003 American Cancer Society.
Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity
Authors: Muñoz‐Guerra Mario Fernando , Marazuela Eva G. , Martín‐Villar Esther , Quintanilla Miguel , Gamallo Carlos 
Published: January 2004

AbstractBACKGROUNDClinicopathologic data demonstrated that the lymphatic system is the main route for solid tumor metastasis. However, the effect of intratumoral lymphangiogenesis (IL) on prognosis in oral carcinoma is still unknown because, until recently, no reliable markers for lymphatic endothelium were available. The current study analyzed the lymphatic vessels in tumor tissue specimens of patients with primary oral carcinoma using the new marker, PA2.26.METHODSThe authors investigated IL in surgical tissue samples of 61 patients with early‐stage (Stages I–II) oral carcinoma. The tissue specimens were stained for PA2.26 and the correlation between IL and relevant parameters was analyzed by the Pearson chi‐square test. In a univariate analysis using the Kaplan–Meier method, IL was analyzed against survival and disease‐free period. Statistical significance of differences between distributions was studied by the log‐rank test. Clinicopathologic parameters, including IL, were entered in a multivariate analysis to determine independent prognostic significance.RESULTSThirty‐three patients had IL. In the follow‐up, a strong association was found between IL and locoregional recurrence (30.3 % of the patients with IL and 7.1% of the patients without IL). The presence of IL did not correlate significantly with the pT classification, primary location, or tumor differentiation. IL was found to have no influence on overall survival in univariate analysis, but there was significant association between IL and disease‐free survival (P = 0.03). Multivariate analysis revealed IL to be the sole independent factor influencing disease‐free interval (P = 0.02).CONCLUSIONSThese results suggested that IL is associated with locoregional disease recurrence in early‐stage oral carcinoma. The presence of IL was a useful discriminator in predicting the outcome of patients with absence of lymph node metastasis. Cancer 2004. © 2003 American Cancer Society.
High‐dose tamoxifen and sulindac as first‐line treatment for desmoid tumors
Authors: Hansmann Anika , Adolph Claudia , Vogel Tilmann , Unger Andreas , Moeslein Gabriela 
Published: January 2004

AbstractBACKGROUNDDesmoid tumors are mesenchymal nonmetastasizing neoplasms. Although rare in the general population, they are a common extracolonic manifestation of familial adenomatous polyposis (FAP). Because of high tumor recurrence rates, surgery has been less than satisfactory in the treatment of desmoid tumors. In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery.METHODSSince 1992, 25 patients at Heinrich Heine University (Dusseldorf, Germany) were treated with a combination of tamoxifen and sulindac. In the current study, 17 patients with FAP‐associated and 8 patients with sporadic desmoid tumors received 120 mg of tamoxifen and 300 mg of sulindac daily. Every 6 months, the protracted course of desmoid growth was measured by computed tomography and/or magnetic resonance imaging scans. Tumor responses were characterized as progressive disease, stable disease (SD), partial regression (PR), and complete regression (CR).RESULTSOf the group of patients who received tamoxifen and sulindac as a primary treatment, all three patients with sporadic desmoid tumors demonstrated cessation of growth, and 10 of the 13 patients with FAP‐associated tumors achieved either a PR or CR. In the sporadic desmoid tumor group, eight of nine patients developed tumor recurrences after undergoingsurgery at other institutions. Of these, two patients had SD and two patients had a PR to CR.CONCLUSIONSThe patients with desmoid tumors who were managed conservatively with high‐dose tamoxifen and sulindac had the best outcome. Desmoid tumor recurrence after surgery was high and in the FAP‐associated tumor group, therapy with tamoxifen and sulindac was found to be less successful. Based on this experience, the authors recommended high‐dose tamoxifen and sulindac as the primary treatment for patients with FAP‐associated desmoid tumors. However, to our knowledge, the best approach after surgical intervention for patients with sporadic desmoid tumors remains to be determined. Cancer 2004. © 2003 American Cancer Society.