Frequency modulation of ERK activation dynamics rewires cell fate.

Transient versus sustained ERK MAP kinase (MAPK) activation dynamics induce proliferation versus differentiation in response to epidermal (EGF) or nerve (NGF) growth factors in PC-12 cells. Duration of ERK activation has therefore been proposed to specify cell fate decisions. Using a biosensor to measure ERK activation dynamics in single living cells reveals that sustained EGF/NGF application leads to a heterogeneous mix of transient and sustained ERK activation dynamics in distinct cells of the population, different than the population average. EGF biases toward transient, while NGF biases toward sustained ERK activation responses. In contrast, pulsed growth factor application can repeatedly and homogeneously trigger ERK activity transients across the cell population. These datasets enable mathematical modeling to reveal salient features inherent to the MAPK network. Ultimately, this predicts pulsed growth factor stimulation regimes that can bypass the typical feedback activation to rewire the system toward cell differentiation irrespective of growth factor identity.

Shulamit an Ancient Love-Drama. Known as the "Song of Songs," and attributed to Solomon, King of Israel

Gershon Katz

Mabel Love, Brustbild

Signatur des Originals: S 36/F09136

Love in a Village. : Mrs. Billington in Rosetta.

Signatur des Originals: S 36/G00008

Fate and effects of drilling wastes in a shallow estuarine mesocosm

To address concerns expressed about the possible effect of drilling mud discharges on shallow, low-energy estuarine ecosystems, a 12 month study was designed to detect alterations in water quality and sediment geochemistry. Each drilling mud used in the study and sediments from the study site were analyzed in the laboratory for chemical and physical characteristics. Potential water quality impacts were simulated by the EPA-COE elutriation test procedure. Mud toxicity was measured by acute and chronic bioassays with Mysidopsis bahia, Mercenaria mercenaria, and Nereis virens.^ For the field study, a relatively pristine, shallow (1.2 m) estuary (Christmas Bay, TX) without any drilling activity for the last 30 years was chosen for the study site. After a three month baseline study, three stations were selected. Station 1 was an external control. At each treatment station (2, 3), mesocosms were constructed to enclose a 3.5 m$\sp3$ water column. Each treatment station included an internal control site also. Each in situ mesocosm, except the controls, was successively dosed at a mesocosm-specific dose (1:100; 1:1,000; or 1:10,000 v/v) with 4 field collected drilling muds (spud, nondispersed, lightly-treated, and heavily-treated lignosulfonate) in sequential order over 1.5 months. Twenty-four hours after each dose, water exchange was allowed until the next treatment. Station 3 was destroyed by a winter storm. After the last treatment, the enclosures were removed and the remaining sites monitored for 6 months. One additional site was similarly dosed (1:100 v/v) with clean dredged sediment from Christmas Bay for comparison between dredged sediments and drilling muds.^ Results of the analysis of the water samples and field measurements showed that water quality was impacted during the discharges, primarily at the highest dose (1:100 v/v), but that elevated levels of C, Cr (T,F), Cr$\sp{+3}$ (T, F), N, Pb, and Zn returned to ambient levels before the end of the 24 hour exposure period or immediately after water exchange was allowed (Al, Ba(T), Chlorophyll ABC, SS, %T). Barium, from the barite, was used as a geochemical tracer in the sediments to confirm estimated doses by mass balance calculations. Barium reached a maximum of 166x background levels at the high dose mesocosm. Barium levels returned to ambient or only slightly elevated levels at the end of the 6 month monitoring period due to sediment deposition, resuspension, and bioturbation. QA/QC results using blind samples consisting of lab standards and spiked samples for both water and sediment matrices were within acceptable coefficients of variation.^ In order to avoid impacts on water quality and sediment geochemistry in a shallow estuarine ecosystem, this study concluded that a minimal dilution of 1:1,000 (v/v) would be required in addition to existing regulatory constraints. ^

THE CHLOREX TREATABILITY STUDY: ENVIRONMENTAL FATE IN FACULTATIVE ANAEROBIC AND AEROBIC WASTE STABILIZATION PONDS (BIODEGRADATION, VOLATILIZATION, SORPTION, PRIORITY POLLUTANTS)

The efficacy of waste stabilization lagoons for the treatment of five priority pollutants and two widely used commercial compounds was evaluated in laboratory model ponds. Three ponds were designed to simulate a primary anaerobic lagoon, a secondary facultative lagoon, and a tertiary aerobic lagoon. Biodegradation, volatilization, and sorption losses were quantified for bis(2-chloroethyl) ether, benzene, toluene, naphthalene, phenanthrene, ethylene glycol, and ethylene glycol monoethyl ether. A statistical model using a log normal transformation indicated biodegradation of bis(2-chloroethyl) ether followed first-order kinetics. Additionally, multiple regression analysis indicated biochemical oxygen demand was the water quality variable most highly correlated with bis(2-chloroethyl) ether effluent concentration. ^

Functional analysis of the sea urchin {\it orthodenticle\/} -related gene, {\it SPOTX\/}, in aboral ectoderm-specific gene activation and aboral ectoderm cell fate specification

An important question in developmental biology is how embryonic cell types are derived from a fertilized egg. To address this question, this thesis investigates the mechanisms by which the aboral ectoderm-specific Spec2a gene is spatially and temporally regulated during sea urchin embryogenesis. The Spec2a gene of the sea urchin Strongylocentratus purpuratus has served as a valuable maker to understand the basis of lineage-specific gene activation and the role of transcription factors in cell fate specification. The hypothesis is that transcription factors responsible for cell type-specific gene activation are key components in the initial cell specification step. The Spec2a gene, which encodes a small cytosolic calcium-binding protein, is expressed exclusively in aboral ectoderm cell lineages. The 1516-bp control region of the Spec2a gene contains a 188-bp enhancer element required for temporal activation and aboral ectoderm/mesenchyme cell expression, while an unidentified element upstream of the enhancer represses expression in mesenchyme cells. Using an enhancer activation assay, combined with site-directed mutagenesis, I showed that three TAATCC/T sites within the enhancer are responsible for enhancer activity. Mutagenizing these sites and a fourth one just upstream abolished all activity from the Spec2a control region. A 77-bp DNA fragment from the Spec2a enhancer containing two of the TAATCC/T sites is sufficient for aboral ectoderm/mesenchyme cell expression. A cDNA encoding SpOtx, an orthodenticle-related protein, was cloned from S. purpuratus and shown to bind with high affinity to the TAATCC/T sequences within the Spec2a control region. SpOtx transcripts were found initially in all cells of the cleaving embryo, but they gradually became restricted to oral ectoderm and endoderm cells, suggesting that SpOtx might play a role in the initial temporal activation of the Spec2a gene and most likely has additional functions in the developing embryo. To reveal the broader biological functions of SpOtx, I injected SpOtx mRNA into living sea urchin eggs to determine what effects overexpressing the SpOtx protein might have on embryo development. SpOtx mRNA-injected embryos displayed dramatic alterations in development. Instead of developing into pluteus larvae with 15 different cell types, uniform epithelia balls were formed. These balls consisted of a thin layer of squamous cells with short cilia highly reminiscent of aboral ectoderm. Immunohistochemical staining and RT-PCR demonstrated that the SpOtx-injected embryoids expressed aboral ectoderm markers uniformly, but showed very weak or no expression of markers for non-aboral ectoderm cell types. These data strongly suggested that overexpression of SpOtx redirected the normal fate of non-aboral ectoderm cells to that of aboral ectoderm. These results show that SpOtx is involved in aboral ectoderm differentiation by activating aboral ectoderm-specific genes and that modulating its expression can lead to changes in cell fate. ^

Integrated Data Sets of the EU FP5 Research Project ORFOIS: Origin and fate of biogenic particle fluxes in the ocean and their interactions with atmospheric CO2 concentrations as well as the marine sediment

For a reliable simulation of the time and space dependent CO2 redistribution between ocean and atmosphere an appropriate time dependent simulation of particle dynamics processes is essential but has not been carried out so far. The major difficulties were the lack of suitable modules for particle dynamics and early diagenesis (in order to close the carbon and nutrient budget) in ocean general circulation models, and the lack of an understanding of biogeochemical processes, such as the partial dissolution of calcareous particles in oversaturated water. The main target of ORFOIS was to fill in this gap in our knowledge and prediction capability infrastructure. This goal has been achieved step by step. At first comprehensive data bases (already existing data) of observations of relevance for the three major types of biogenic particles, organic carbon (POC), calcium carbonate (CaCO3), and biogenic silica (BSi or opal), as well as for refractory particles of terrestrial origin were collated and made publicly available.

Circularity in Louise Erdrich's Love medicine

La estructura circular en la novela Love Medicine, de Louise Erdrich, enmarca a los personajes y a los temas principales, e involucra al lector en un interesante proceso de decodificación del texto. Los personajes buscan su identidad y se reconcilian con el pasado (dos temas fundamentales) mientras que el lector adopta un rol activo en el proceso de establecer conexiones con el fin de construir el mundo de la novela.

Roma de amor y muerte : Eros y Thánatos en tres poetas latinos (Horacio, Virgilio, Propercio)

¿De qué modos se vinculan Eros y Thánatos en la poesía latina clásica? Catulo había fijado una primera expresión de tal vínculo. Los poetas del círculo de Mecenas, cada uno a su modo, renuevan el tema. Horacio intenta moderar el miedo a la muerte y el afán amoroso. Virgilio, por su parte, en sus versos sobre Orfeo y Eurídice, nos ofrece otra cifra del enigma: ni el mayor poeta y amante pudo rescatar de la oscuridad a su amada; pero la poesía con que cante su dolor sobrevivirá a la muerte de ambos. Propercio, finalmente, expresa la constante cercanía de amor y muerte; amar es sentir el fondo de la humana fragilidad. Sin embargo, no piensa él meramente en una perduración literaria; afirma que “son algo los manes", pues su amada Cintia, ya muerta, lo ha visitado. “Aun cruza las riberas del Hado un gran amor."

Los héroes han muerto : La revisión de la tragedia de Séneca en "Phaedras Love", de Sarah Kane

La literatura, como ya lo afirmaba Gérard Genette, no es nada más ni nada menos que un palimpsesto. Toda creación literaria se inscribe irremediablemente en una tradición y retoma temas o conflictos ya enunciados por otras obras anteriores. Podríamos decir que existen aspectos de la condición humana que serán revisitados una y otra vez sin caer en la repetición, que presentan aún "mucha tela por cortar" y que se resignifican en los diferentes contextos sociohistóricos en que son planteados. Los mitos griegos han sido durante siglos un material particularmente rico y explotado por diferentes autores. Es el caso del mito de Fedra, cuyo primer antecedente del que nos queda evidencia es la tragedia Hipólito de Eurípides (del siglo V a.C., de la cual existieron dos versiones pero sólo se conserva una), reescrito (siguiendo el concepto romano de aemulatio) en Fedra por el romano Séneca casi cinco siglos más tarde y del que se han producido hasta el día de hoy gran cantidad de versiones. Una de estas es la obra de Sarah Kane, Phaedra's Love. El presente trabajo es un análisis de dicha obra como ejemplo de la narrativa del teatro británico in-yer-face de finales del siglo XX. Una obra cruda que incomoda al lector espectador y echa por tierra con las instituciones, los valores enunciados y lo sagrado de las sociedades modernas

Los héroes han muerto : La revisión de la tragedia de Séneca en "Phaedras Love", de Sarah Kane

La literatura, como ya lo afirmaba Gérard Genette, no es nada más ni nada menos que un palimpsesto. Toda creación literaria se inscribe irremediablemente en una tradición y retoma temas o conflictos ya enunciados por otras obras anteriores. Podríamos decir que existen aspectos de la condición humana que serán revisitados una y otra vez sin caer en la repetición, que presentan aún "mucha tela por cortar" y que se resignifican en los diferentes contextos sociohistóricos en que son planteados. Los mitos griegos han sido durante siglos un material particularmente rico y explotado por diferentes autores. Es el caso del mito de Fedra, cuyo primer antecedente del que nos queda evidencia es la tragedia Hipólito de Eurípides (del siglo V a.C., de la cual existieron dos versiones pero sólo se conserva una), reescrito (siguiendo el concepto romano de aemulatio) en Fedra por el romano Séneca casi cinco siglos más tarde y del que se han producido hasta el día de hoy gran cantidad de versiones. Una de estas es la obra de Sarah Kane, Phaedra's Love. El presente trabajo es un análisis de dicha obra como ejemplo de la narrativa del teatro británico in-yer-face de finales del siglo XX. Una obra cruda que incomoda al lector espectador y echa por tierra con las instituciones, los valores enunciados y lo sagrado de las sociedades modernas