357 research outputs found
Geographic variation, null hypotheses, and subspecies limits in the California Gnatcatcher: A response to McCormack and Maley
No full textWe interpreted the results of nuclear DNA sequencing to be inconsistent with the recognition of California Gnatcatcher (Polioptila californica) subspecies. McCormack and Maley (2015) suggested that our data did support 2 taxa, one of which was P. c. californica, listed as Threatened under the Endangered Species Act (ESA). We summarize here how 2 sets of researchers with access to the same data reached different conclusions by including different analyses. We included the southern subspecies’ boundary from the taxonomy of Atwood (1991), the taxonomic basis for the ESA listing, which resulted in an Analysis of Molecular Variance that provided no support for subspecies. In contrast, using a novel taxonomic hypothesis without precedent in the literature, McCormack and Maley (2015) found statistically significant FST values for 2 loci, which they suggested supports P. c. californica. We propose that our mitochondrial and nuclear data had sufficient power to capture geographical structure at either the phylogenetic (monophyly) or traditional ‘‘75% rule’’ level. McCormack and Maley (2015) suggested that finding an absence of population structure was a ‘‘negative result,’’ whereas we consider it to be the null hypothesis for a species with gene flow and no geographical barriers. We interpret the unstructured mtDNA and nuclear DNA trees, the STRUCTURE analysis supporting one group, the identification of just 26% (and not 75%) of individuals of P. c. californica with the most diagnostic nuclear locus, the overall GST that suggests that over 98% of the variation is explained by nontaxonomic sources, and the lack of evidence of ecological differentiation to indicate that P. c. californica is not a valid subspecies. McCormack and Maley (2015) suggest that statistically significant differences at 2 loci that explained ,6% of the genetic variation, and previous morphological data, support recognition of P. c. californica. If ornithology continues to recognize subspecies, these different standards should be reconciled
Thymidylate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil.
No full textDifferent 5-fluorouracil (5-FU) schedules and/or biochemical modulators may result in different mechanisms of cytotoxicity, potentially affecting the correlation between thymidylate synthase (TS) expression and the clinical response to the fluoropyrimidine.TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 124 patients homogeneously treated in a series of clinical trials at our institutions with: (A) leucovorin (LV)-modulated infusional 5-FU (n = 48); (B) LV-modulated bolus 5-FU (n = 41); (C) methotrexate (MTX)-modulated bolus 5-FU (n = 35).A statistically significant correlation between TS levels and the clinical response was observed with the regimens involving continuous infusion and/or LV modulation (response rate in patients with low and high TS: 66\% versus 24\%, P = 0.003, and 50\% versus 0\%, P = 0.0001, in group A and B, respectively). Conversely, TS levels failed to predict the clinical response within the group of patients treated with MTX-modulated bolus 5-FU (response rate 21\% versus 13\%, P = 0.50, with low and high TS, respectively). Consistently, the median time to progression/overall survival time in patients with low and high TS were 9 versus 6 months/19 versus 14 months (P = 0.009/0.035, group A), 8 versus 2 months/12 versus 6 months (P = 0.002/0.0006, group B) and 3 versus 2 months/12 versus 13 months (P = 0.14/0.74, group C).The correlation between intratumoral TS levels and the clinical response to 5-FU depends strongly on the schedule of administration/biochemical modulators that are used in different 5-FU regimens. These data strengthen the notion that different 5-FU schedules have different mechanisms of cytotoxicity
Barker, Mary (Death, 1875-03-05)
No full textAddress: 6 Brown St.Age at death: 42 yrsPg 206/90/1875/F W M/Germany/Dr. P. Maley/Coroner/J. Schreiber/St. John'sOriginal record filed in drawer labeled 'BARD-BARRETT'
Tissue engineering of a tracheal substitute
No full textLectin histochemistry and scanning electron microscopy (SEM) was used to assess the growth and characterise the differentiation of human respiratory epithelial cells (REC) cultured on two biomaterial scaffolds. The first scaffold, based on a hyaluronic acid derivative, was observed to be non-adhesive for REC. This lack of adhesion was found to be unrelated to the presence of the hyaluronic acid binding domain on the surface of isolated REC. The other scaffold, consisting of equine collagen, was observed to encourage REC spreading and adhesion. Positive Ulex Europaeus agglutinin (UEA) lectin staining of this preparation indicated the presence of ciliated REC on the scaffold surface. However, the marked decrease in peanut agglutinin (PNA) positive staining, relative to that of control cultures and native tissue, indicates a dedifferentiation of the secretory cells in monolayer. SEM analysis of REC cultured on the collagen scaffold confirmed the presence of ciliated cells thereby validating the UEA positive staining. The presence of both established and developing cilia was also verified. This indicates that collagen biomaterials are appropriate for the tissue engineering of REC. Furthermore, that UEA and PNA staining is a useful tool in the characterisation of cells cultured on biomaterials, therefore helpful in identifying biomaterials that are suitable for specific tissue engineering purposes.
The culture of REC at an air liquid interface (ALI) was investigated. Both conventional ALI inserts and the Biofleece scaffold were used. The cells grown the on conventional inserts became multilayered and showed some degree of ciliation after the period of ten days. The cells grown on the Biofleece scaffold became necrotic and died due to nutrient deprivation. The use of ALI culture techniques on scaffold materials needs to be adjusted to allow for sufficient nutrient supply to the cells.
The Biofleece scaffold was found to be suitable for the tissue engineering of cartilage in vitro. Constructs with a cartilage-like morphology were generated with the scaffold after two weeks in culture. The tissue-engineered cartilage was found to contain a higher number of cells and less extracellular matrix (ECM) than the native tissue controls. Suction seeding techniques were used to improve the distribution of cells within the scaffold and thereby increase the overall efficiency of cartilage tissue engineering within the scaffold. Alcian blue (AB) and Papanicolau (PN) stains of the tissue engineered cartilage described two distinct regions within the constructs, namely the developed cartilage-like region and the developing region. The latter is thought to be areas in which the cartilage cells are yet to fully remodel the scaffold material and deposit their own “native” ECM. However, the Biofleece scaffold material was observed to loose 40-50% of its initial volume during the tissue engineering process over a period of two weeks. Thus the degradation of the Biofleece scaffold exceeds the rate of maturation of the cartilage tissue within the scaffold. This rapid biodegradation is most likely a result of matrixmetalloproteinase (MMP), in particular collagenase, production by the maturing chondrocytes. This reduction in size means that the Biofleece scaffold is not an appropriate material for the tissue engineering of a trachea. The optimal biomaterial for the tissue engineering of a trachea would degrade at a rate equal too, or slower than, the time taken for the cells within the scaffold to mature into functional tissue.
The co-culture of REC and chondrocytes was achieved through the use of matrigel as a basement membrane replacement (note that direct growth of REC on cartilage tissue has been observed to be difficult). The co-cultured constructs were not stable because the Biofleece scaffold degrades at a high rate in the presence of both cell types. The constructs were observed to shrink to approximately 35-30% of the original dimensions in a period of 3-7 days. The reason for this accelerated degradation is not known but is most likely the result of severe MMP production by the two cell types when in combination.
It was concluded that the characterisation procedures used in this study (histochemical staining, fluorescent staining and scanning electron microscopy) for both REC and chondrocyte tissue engineered constructs are appropriate for this and further studies. The chondrocyte seeding methodologies in particular are a useful tool for tissue engineering. This study succeeds in many ways to investigate the tissue engineering of a tracheal substitute by detailing how REC and chondrocytes can be cultured on biomaterials and assessed for tissue development. However, the study does not deliver such a viable substitute as an end product. The primary reason for this outcome is the rapid degradation of the Biofleece scaffold materialLectin Histochemie und Elektronenmikroskopie wurden benutzt, um das Wachstum von humanen respiratorischen Epithelzellen (RECs), welche auf zwei Biomaterialien kultiviert wurden, festzusetzen und ihren Differenzierungsgrad zu bestimmen. Das erste Trägermaterial, welches auf einem Hyaluronsäurederivat basiert, ließ keine Anheftung der RECs zu. Diese fehlende Anheftung ließ sich jedoch nicht zurückführen auf das Vorhandensein der Hyaluronsäure bindenden Domaine auf der Oberfläche isolierter RECs. Das andere Trägermaterial, aus Pferdekollagen hergestellt, zeigte dagegen eine verstärkte Teilungsaktivität und Anheftung der REC. Die positive Ulex Europaeus Agglutinin (UEA) Lectin Färbung dieser Proben ließ die Anwesenheit von mit Zilien versehenen RECs auf der Trägerstoffoberfläche vermuten. Darüber hinaus weist das im Vergleich zu Kontrollkulturen und nativem Gewebe deutliche Nachlassen der positiven Peanut Agglutinin–Färbereaktion auf eine Dedifferenzierung der sekretorischen Zellen in der Monolayer-Kultur hin. Die rasterelektronenmikroskopische Untersuchung der auf dem Kollagenbiomaterial kultivierten RECs bestätigte das Auftreten von Zellen mit Zilien und damit auch die Aussagekräftigkeit der positiven UEA–Färbung. Dies zeigt somit, dass Biomaterialien aus Kollagen für das Tissue Engineering von RECs geeignet sind und dass sowohl die UEA–als auch die PNA–Färbung geeignete Methoden zur Charakterisierung von Zellen darstellen, die auf Biomaterialien kultiviert wurden. Somit helfen sie bei der Identifizierung von Biomaterialien für bestimmte Einsatzgebiete im Tissue Engineering.
Des weiteren wurde die Kultivierung von RECs auf einem Air liquid interface (ALI) untersucht, wobei sowohl der konventionelle ALI–Einsatz als auch das Biovliesmaterial zum Einsatz kamen. Dabei wuchsen die Zellen auf dem konventionellen Einsatz in Multilayern und zeigten nach einem Zeitraum von 10 Tagen einen bestimmten Anteil an Ziliierung. Die Zellen auf dem Biovlies dagegen wurden nekrotisch und gingen schließlich an Nahrungsmangel ein. Deshalb muss der Einsatz von ALI–Kulturtechniken bei Trägermaterialien dementsprechend modifiziert werden, dass eine ausreichende Versorgung der Zellen mit Nährstoffen gewährleistet ist.
Für das in vitro–Tissue Engineering von Knorpel erwies sich das Biovlies jedoch als geeignet. Mit ihm konnten nach zwei Wochen Kulturzeit Konstrukte mit einer knorpelähnlichen Morphologie erzeugt werden. Dabei zeigte sich, dass der Tissue Engineering–Knorpel eine höhere Zellzahl bei reduzierter extrazellulärer Matrix (ECM) aufwies als vergleichbares natives Kontrollgewebe. Dabei wurden Saugtechniken benutzt, um die Verteilung der Zellen im Trägerstoff zu verbessern. Die Alzian – Blau – Färbung (AB) und Papanicolau – Färbung (PN) zeigten bei dem Tissue Engineering–Knorpel zwei unterschiedliche Regionen innerhalb des Konstrukts, nämlich eine knorpelähnliche bereits entwickelte Region und eine sich entwickelnde Region. Bei letzterer dürfte es sich wohl um Gebiete handeln, in denen Zellen noch im Begriff sind, den Trägerstoff vollends umzubauen und ihre eigene „native“ ECM abzulagern. Nichtsdestoweniger büßte das Biovlies während des Tissue Engineering Prozesses über einen Zeitraum von zwei Wochen annähernd 40-50 % seines anfänglichen Volumens ein. Somit übersteigt das Ausmaß der Degradation des Biovlieses das des Heranreifens von Knorpelgewebe in dem Trägermaterial. Diese schnelle Biodegradation ist am ehesten das Ergebnis der Aktivität von Matrixmetalloproteinasen (MMP), insbesondere der Kollagenase, welche von reifenden Chondrozyten produziert wird. Diese Schrumpfung bedeutet also, dass das Biovlies kein geeignetes Material für das Tissue Engineering der Trachea darstellt. Denn ein optimales Biomaterial für das Tissue Engineering der Trachea sollte sich innerhalb derselben Zeit bzw. über einen längeren Zeitraum hinweg abbauen, als innerhalb desjenigen, den die sich in dem Trägermaterial befindlichen Zellen benötigen, um zu funktionalem Gewebe heranzureifen.
Durch den Einsatz von Matrigel als Ersatz für die Basalmembran konnte eine Kokultur aus RECs und Chondrozyten etabliert werden (wobei anzumerken ist, dass sich direktes Wachstum von RECs auf Knorpelgewebe als problematisch erweist). Die Konstrukte aus Kokulturen waren nicht stabil, da das Biovlies in Anwesenheit beider Zelltypen hochgradig abgebaut wird. Innerhalb von 3–7 Tagen schrumpften die Konstrukte auf ca. 35–50 % ihrer Ausgangsgröße zusammen. Der Grund für diesen beschleunigten Abbau ist unbekannt, jedoch ist am ehesten eine ausgeprägte Produktion von MMP durch die beiden Zellarten anzunehmen, sobald diese in Kombination vorliegen.
Insgesamt lässt sich sagen, dass die Methoden zur Zell- und Gewebecharakterisierung, welche in dieser Studie benutzt wurden (histochemische Färbungen, Fluoreszenzfärbung und Elektronenmikroskopie) sowohl für mit RECs als auch mit Chondrozyten hergestellte Konstrukte für die vorliegende Arbeit als auch zukünftige Studien als geeignet anzusehen sind. Diese Studie hat in vielerlei Hinsicht erfolgreich das Tissue Engineering einer Luftröhre untersuchen können, indem sie im Detail aufzeigt, wie RECs und Chondrozyten auf Biomaterialien kultiviert und für das Tissue Engineering eingesetzt werden können. Trotzdem kann diese Arbeit kein einsetzbares Ersatzmaterial als Endprodukt liefern. Der Hauptgrund für dieses Ergebnis ist in erster Linie in dem schnellen Abbau des Biovlieses als Trägermaterial zu sehen
McGuire, Mich. (Death, 1876-02-19)
No full textAddress: 7 Rice St.Age at death: 6 yrsPg 105/1876/486/M W S/City/Dr. P. Maley Coroner/Sullivan/St. Joseph'sOriginal record filed in drawer labeled 'MCGRATH-MCLAUGHLIN'
Wrapped in the Strong Arms of the Union: Shakespeare and King James
No full textBackground. Acute phase protein production is a hallmark of severe burns. We wondered whether anabolic treatment with oxandrolone would affect these proteins.Methods. Thirty-five children with greater than or equal to40% total body surface area burns were randomized to receive either placebo or oxandrolone (0.1 mg/kg by mouth twice daily) from postoperative day 5 to 1 year postburn. Levels of constitutive proteins and acute phase proteins were measured at admission, at discharge; and at 6, 9, and 12 months after burn. Total albumin supplementation and hepatic transaminases were also assessed.Results. Constitutive proteins such as albumin, prealbumin, and retinol-binding protein levels increased (p < 0.05), and acute phase proteins such as alpha(1)-acid glycoprotein, C3 complement, alpha(2)-macroglobulin, and fibrinogen levels significantly decreased in the oxandrolone group compared with placebo (p < 0.05). Albumin supplementation during the acute hospitalization was reduced in the oxandrolone group. Hepatic transaminases remained within normal levels.Conclusion:. Treatment with oxandrolone in severe burns significantly increases constitutive protein and reduces acute phase protein levels.</p
A new method to accurately identify single nucleotide variants using small FFPE breast samples
No full textMost tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches
Reciprocity in corporate cultures : a radical behavioral perspective
No full textThis paper discusses the radical behavioral concept of reciprocity as it applies to contemporary business. First, the origins and explanations of reciprocity are delineated, followed by descriptions and examples of how this psychological concept might be applied to corporate cultures. Next, the benefits of reciprocity for business are discussed, with a concluding section on what this paper has accomplished, and what areas warrant further research. The perspective taken by the author is consonant with the approach to human behavior posited by B. F. Skinner; i.e. radical behaviorism.Psychology, Department o
Holocene changes in African vegetation: Tradeoff between climate and water availability
No full textAlthough past climate change is well documented in West Africa through instrumental records, modeling activities, and paleo-data, little is known about regional-scale ecosystem vulnerability and long-term impacts of climate on plant distribution and biodiversity. Here we use paleohydrological and paleobotanical data to discuss the relation between available surface water, monsoon rainfall and vegetation distribution in West Africa during the Holocene. The individual patterns of plant migration or community shifts in latitude are explained by differences among tolerance limits of species to rainfall amount and seasonality. Using the probability density function methodology, we show here that the widespread development of lakes, wetlands and rivers at the time of the "Green Sahara" played an additional role in forming a network of topographically defined water availability, allowing for tropical plants to migrate north from 15 to 24° N (reached ca. 9 cal ka BP). The analysis of the spatio-temporal changes in biodiversity, through both pollen occurrence and richness, shows that the core of the tropical rainbelt associated with the Intertropical Convergence Zone was centered at 15-20° N during the early Holocene wet period, with comparatively drier/more seasonal climate conditions south of 15° N. © 2014 Author(s)
Approaching Cancer Evolution from Different Angles
No full textDr Francesca Ciccarelli (The Francis Crick Institute, UK) and Dr James De Gregori (University of Colorado, USA) interview 3 top scientists in clinical (Dr Charles Swanton, The Francis Crick Institute, UK), molecular (Dr Kornelia Polyak, Dana-Farber Cancer Institute, USA), and evolutionary cancer research (Dr Carlo Maley, Arizona State University, USA) to discuss the current status of knowledge, the challenges, and the opportunities to move the field forward.</p
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