Phasing and climate forcing potential of the Millennium Eruption of Mt. Baekdu.

The Millennium Eruption of Mt. Baekdu, one of the largest volcanic eruptions in the Common Era, initiated in late 946. It remains uncertain whether its two main compositional phases, rhyolite and trachyte, were expelled in a single eruption or in two. Investigations based on proximal and medial ash have not resolved this question, prompting us to turn to high-resolution ice-core evidence. Here, we report a suite of glaciochemical and tephra analyses of a Greenlandic ice core, identifying the transition from rhyolitic to trachytic tephra with corresponding spikes in insoluble particle fallout. By modeling annual snow accumulation, we estimate an interval of one to two months between these spikes, which approximates the hiatus between two eruptive phases. Additionally, negligible sulfur mass-independent fractionation, near-synchroneity between particle and sulfate deposition, and peak sulfur fallout in winter all indicate an ephemeral aerosol veil. These factors limited the climate forcing potential of the Millennium Eruption.

The potential of a niacinamide dominated cosmeceutical formulation on fibroblast activity and wound healing in vitro.

Knowledge on the intrinsic mechanisms involved in wound healing provides opportunity for various therapeutic strategies. The manipulation of dermal fibroblast proliferation and differentiation might prove to beneficially augment wound healing. This study evaluated the combined effects of niacinamide, L-carnosine, hesperidin and Biofactor HSP(®) on fibroblast activity. The effects on fibroblast collagen production, cellular proliferation, migration and terminal differentiation were assessed. In addition, the authors determined the effects on in vitro wound healing. The optimal concentrations of actives were determined in vitro. Testing parameters included microscopic morphological cell analysis, cell viability and proliferation determination, calorimetric collagen detection and in vitro wound healing dynamics. Results show that 0·31 mg/ml niacinamide, 0·10 mg/ml L-carnosine, 0·05 mg/ml hesperidin and 5·18 µg/ml Biofactor HSP® proved optimal in vitro. The results show that fibroblast collagen synthesis was increased alongside with cellular migration and proliferation.

Tres problemas conceptuales en torno al estudio de la libertad en psicoanálisis: Sujeto, causa y responsabilidad / Three conceptual issues around the study of freedom in psychoanalysis: Subject, cause and responsibility

En este artículo se esbozan los principales interrogantes a desplegar durante el proyecto de investigación UBACyT 2012-2014: "La libertad en psicoanálisis. Su incidencia en la concepción de sujeto y la causalidad en la obra de J. Lacan. Consecuencias clínicas y éticas”. Con el objetivo de ubicar el valor conceptual que la noción de “libertad” presenta a lo largo de la obra de J. Lacan, se desarrollará: 1) La libertad a partir de la diferencia que es posible situar en Freud entre determinismo y causalidad, cuestionando las series complementarias 2) La libertad a partir de la subversión del sujeto en J. Lacan 3) La libertad en relación a la noción de responsabilidad en tanto atribución y 4) Los modos en que la cultura occidental ha desentrañado la problemática relación entre determinación y libertad desde la antigüedad a la modernidad que puedan tener alguna relación con los modos en que el psicoanálisis se plantea esta problemática.

Tres problemas conceptuales en torno al estudio de la libertad en psicoanálisis: Sujeto, causa y responsabilidad / Three conceptual issues around the study of freedom in psychoanalysis: Subject, cause and responsibility

En este artículo se esbozan los principales interrogantes a desplegar durante el proyecto de investigación UBACyT 2012-2014: "La libertad en psicoanálisis. Su incidencia en la concepción de sujeto y la causalidad en la obra de J. Lacan. Consecuencias clínicas y éticasö. Con el objetivo de ubicar el valor conceptual que la noción de ôlibertadö presenta a lo largo de la obra de J. Lacan, se desarrollará: 1) La libertad a partir de la diferencia que es posible situar en Freud entre determinismo y causalidad, cuestionando las series complementarias 2) La libertad a partir de la subversión del sujeto en J. Lacan 3) La libertad en relación a la noción de responsabilidad en tanto atribución y 4) Los modos en que la cultura occidental ha desentrañado la problemática relación entre determinación y libertad desde la antig³edad a la modernidad que puedan tener alguna relación con los modos en que el psicoanálisis se plantea esta problemática.(AU)

El estadio del espejo y la constitución del yo en la enseñanza de Jacques Lacan: incidencias en la práctica analítica / The mirror stage and the constitution of the ego in Jacques Lacan teaching: its influence in analytic practice

El presente trabajo propone localizar algunas consecuencias clínicas que se desprenden de las diversas conceptualizaciones del estadio del espejo y de la constitución del yo, en distintos momentos de la obra de J. Lacan. En particular, recortaremos tres períodos de dicha conceptualización: el de sus antecedentes, entre los años 1936 y 1953, período en el que se acentúa la dimensión imaginaria en la constitución del yo; un segundo momento, a partir de 1953 y hasta 1962, en el que se enfatiza el registro simbólico; y un tercer momento, entre 1962 y 1965, en el que Lacan comienza a destacar el modo en que opera lo real en la constitución del yo, en su articulación con el concepto de objeto a.

This paper proposes to locate some clinical consequences arising from the different conceptualizations of the mirror stage and the constitution of the ego at different times of the work of J. Lacan. In particular, we will cut three periods in such conceptualizations: their record, between 1936 and 1953, which emphasizes the imaginary dimension in the constitution of the ego, a second stage, from 1953 until 1962, that emphasizes the symbolic register, and a third time, between 1962 and 1965, in which Lacan begins to highlight how the real register operates in the constitution of the self, in its articulation with the concept of object a.

El estadio del espejo y la constitución del yo en la enseñanza de Jacques Lacan: incidencias en la práctica analítica / The mirror stage and the constitution of the ego in Jacques Lacan teaching: its influence in analytic practice

El presente trabajo propone localizar algunas consecuencias clínicas que se desprenden de las diversas conceptualizaciones del estadio del espejo y de la constitución del yo, en distintos momentos de la obra de J. Lacan. En particular, recortaremos tres períodos de dicha conceptualización: el de sus antecedentes, entre los años 1936 y 1953, período en el que se acentúa la dimensión imaginaria en la constitución del yo; un segundo momento, a partir de 1953 y hasta 1962, en el que se enfatiza el registro simbólico; y un tercer momento, entre 1962 y 1965, en el que Lacan comienza a destacar el modo en que opera lo real en la constitución del yo, en su articulación con el concepto de objeto a.(AU)

This paper proposes to locate some clinical consequences arising from the different conceptualizations of the mirror stage and the constitution of the ego at different times of the work of J. Lacan. In particular, we will cut three periods in such conceptualizations: their record, between 1936 and 1953, which emphasizes the imaginary dimension in the constitution of the ego, a second stage, from 1953 until 1962, that emphasizes the symbolic register, and a third time, between 1962 and 1965, in which Lacan begins to highlight how the real register operates in the constitution of the self, in its articulation with the concept of object a. (AU)

Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation.

p90 ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-activated protein kinase, but its biological functions are not well understood. We have now identified the first small-molecule, RSK-specific inhibitor, which we isolated from the tropical plant Forsteronia refracta. We have named this novel inhibitor SL0101. SL0101 shows remarkable specificity for RSK. The major determinant of SL0101-binding specificity is the unique ATP-interacting sequence in the amino-terminal kinase domain of RSK. SL0101 inhibits proliferation of the human breast cancer cell line MCF-7, producing a cell cycle block in G(1) phase with an efficacy paralleling its ability to inhibit RSK in intact cells. RNA interference of RSK expression confirmed that RSK regulates MCF-7 proliferation. Interestingly, SL0101 does not alter proliferation of a normal human breast cell line MCF-10A, although SL0101 inhibits RSK in these cells. We show that RSK is overexpressed in approximately 50% of human breast cancer tissue samples, suggesting that regulation of RSK has been compromised. Thus, we show that RSK has an unexpected role in proliferation of transformed cells and may be a useful new target for chemotherapeutic agents. SL0101 will provide a powerful new tool to dissect the molecular functions of RSK in cancer cells.

Mechanisms of autoinhibition in cyclic nucleotide-dependent protein kinases.

Cyclic AMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) are autoinhibited through multiple interactions between their respective regulatory and catalytic domains. A large portion of this autoinhibition occurs through interactions between residues within the catalytic domain and those within either a substrate-like sequence (-RRXSX-) or pseudosubstrate sequence (-RRXAX-) in the regulatory domains. These contacts effectively inhibit catalysis by blocking substrate binding. Particularly important contacts involve the P-2, P-3, and P+1 residues where either serine, which is potentially autophosphorylated, or alanine occupies the P0 position. The primary sequence is apparently less important for autoinhibition in PKGs than in PKAs, and a conserved serine at P+2 in PKGs is important for autoinhibitory contacts. Elements outside the substrate-related sequences also contribute to autoinhibition in both PKA and PKG. For example, synthetic peptides with relatively short pseudosubstrate sequences are weak inhibitors; while heat-denatured RII subunit does not inhibit catalytic subunit, it is still rapidly autophosphorylated; and truncated PKGs lacking the substrate-like sequence are still partially autoinhibited. Thus, capacity for autoinhibition of PKA or PKG is provided by contacts involving direct interactions with the catalytic site and by contacts that stabilize an inactive conformation.