Thirty-eight-negative kinase 1 (TNK1) facilitates TNFalpha-induced apoptosis by blocking NF-kappaB activation.

Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor alpha (TNFalpha)-induced apoptosis by selectively inhibiting TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB). TNK1 has no effect on NF-kappaB DNA binding or the composition of the NF-kappaB complex; however, the kinase markedly prevents TNFalpha-induced NF-kappaB transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFalpha signaling and therefore cell death.

Evidence for radiosensitizing by gliotoxin in HL-60 cells: implications for a role of NF-kappaB independent mechanisms.

Radioresistance markedly impairs the efficacy of tumor radiotherapy and may involve antiapoptotic signal transduction pathways that prevent radiation-induced cell death. A common cellular response to genotoxic stress induced by radiation is the activation of the nuclear factor kappa B (NF-kappaB). NF-kappaB activation in turn can lead to an inhibition of radiation-induced apoptotic cell death. Thus, inhibition of NF-kappaB activation is commonly regarded as an important strategy to abolish radioresistance. Among other compounds, the fungal metabolite gliotoxin (GT) has been reported to be a highly selective inhibitor of NF-kappaB activation. Indeed, low doses of GT were sufficient to significantly enhance radiation-induced apoptosis in HL-60 cells. However, this effect turned out to be largely independent of NF-kappaB activation since radiation of HL-60 cells with clinically relevant doses of radiation induced only a marginal increase in NF-kappaB activity, and selective inhibition of NF-kappaB by SN50 did not result in a marked enhancement of GT-induced apoptosis. GT induced activation of JNKs, cytochrome c release from the mitochondria and potently stimulated the caspase cascade inducing cleavage of caspases -9, -8, -7 and -3. Furthermore, cleavage of the antiapoptotic protein X-linked IAP and downregulation of the G2/M-specific IAP-family member survivin were observed during GT-induced apoptosis. Finally, the radiation-induced G2/M arrest was markedly reduced in GT-treated cells most likely due to the rapid induction of apoptosis. Our data demonstrate that various other pathways apart from the NF-kappaB signaling complex can sensitize tumor cells to radiation and propose a novel mechanism for radiosensitization by GT, the interference with the G2/M checkpoint that is important for repair of radiation-induced DNA damage in p53-deficient tumor cells.

Molecular cloning and characterization of the human protein kinase D2. A novel member of the protein kinase D family of serine threonine kinases.

We have isolated the full-length cDNA of a novel human serine threonine protein kinase gene. The deduced protein sequence contains two cysteine-rich motifs at the N terminus, a pleckstrin homology domain, and a catalytic domain containing all the characteristic sequence motifs of serine protein kinases. It exhibits the strongest homology to the serine threonine protein kinases PKD/PKCmicro and PKCnu, particularly in the duplex zinc finger-like cysteine-rich motif, in the pleckstrin homology domain and in the protein kinase domain. In contrast, it shows only a low degree of sequence similarity to other members of the PKC family. Therefore, the new protein has been termed protein kinase D2 (PKD2). The mRNA of PKD2 is widely expressed in human and murine tissues. It encodes a protein with a molecular mass of 105 kDa in SDS-polyacrylamide gel electrophoresis, which is expressed in various human cell lines, including HL60 cells, which do not express PKCmicro. In vivo phorbol ester binding studies demonstrated a concentration-dependent binding of [(3)H]phorbol 12,13-dibutyrate to PKD2. The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of PKD2 in a synergistic fashion. Phorbol esters also stimulated autophosphorylation of PKD2 in intact cells. PKD2 activated by phorbol esters efficiently phosphorylated the exogenous substrate histone H1. In addition, we could identify the C-terminal Ser(876) residue as an in vivo phosphorylation site within PKD2. Phosphorylation of Ser(876) of PKD2 correlated with the activation status of the kinase. Finally, gastrin was found to be a physiological activator of PKD2 in human AGS-B cells stably transfected with the CCK(B)/gastrin receptor. Thus, PKD2 is a novel phorbol ester- and growth factor-stimulated protein kinase.

Optimal strategies for sending information through A quantum channel

Quantum states can be used to encode the information contained in a direction, i.e., in a unit vector. We present the best encoding procedure when the quantum state is made up of N spins (qubits). We find that the quality of this optimal procedure, which we quantify in terms of the fidelity, depends solely on the dimension of the encoding space. We also investigate the use of spatial rotations on a quantum state, which provide a natural and less demanding encoding. In this case we prove that the fidelity is directly related to the largest zeros of the Legendre and Jacobi polynomials. We also discuss our results in terms of the information gain.

Characterization of a subfamily of related winged helix genes, XFD-12/12'/12" (XFLIP), during Xenopus embryogenesis.

The fork head domain family of genes defines a growing group of proteins that serve important regulatory functions in pattern-forming events of both invertebrates and vertebrates. Here we add three closely related, novel members to this family in Xenopus laevis, termed XFD-12, XFD-12' and XFD-12". All three genes reveal indistinguishable expression patterns during Xenopus embryogenesis. During gastrulation, XFD-12 type transcripts are detected exclusively in the superficial layer of cells within the Spemann organizer territory. In the open neural plate, XFD-12 type expression defines a row of cells located along the dorsal midline and destined to become the floor plate of the neural tube. After closure of the neural tube, XFD-12 type encoding mRNAs are only detected in the tailtip and a small area located at the midbrain/hindbrain boundary. Within the Spemann organizer and in the floor plate area, expression of XFD-12 type genes is only partially overlapping with XFD-1 expression.

Revascularizaciones y reimplantes mayores de miembros: Siete años de experiencia / Major limb revascularizations and replantations: a seven-year experience

El objetivo de la presente comunicación es presentar nuestra experiencia de los últimos siete años en revascularizaciones y reimplantes mayores de los miembros. Hemos llevado a cabo un total de 28 procedimientos, 25 en miembros superiores y 3 en miembros inferiores, con un porcentaje de éxito del 78,57 por ciento. Del total de casos encontramos que los resultados fueron excelentes o muy buenos en 18 (64,27 por ciento). Las indicaciones para estos procedimientos incluyeron casi todas las amputaciones traumáticas, excepto aquellas que presentaban gran atrición tisular o aplastamiento y pacientes con otras lesiones acompañantes de gravedad o patologías preexistentes. La edad no constituyó una limitación. Severa atrición o arrancamiento fueron las causas de los fracasos en 6 casos. Se concluye que los reimplantes y revasculaciones de los miembros son procedimientos con una metodología reglada y cuyo éxito se encuentra ligado a la estricta observancia de la misma, al desarrollo y perfeccionamiento de las técnicas microquirúrgicas y al entrenamiento constante del equipo de profesionales interviniente. Asimismo se hace mención al papel primordial de la rehabilitación, a los efectos de obtener no sólo miembros viables sino funcionalmente útiles

Tram desepidermizado con complejo areola pezón / Deepidermized TRAM flap with areolar nipple complex

La reconstrucción mamaria en el tratamiento de las secuelas de mastectomías es un desafío, para lo cual contamos con una gran calidad y cantidad de intervenciones quirúrgicas. El objetivo de este trabajos es mostrar el resultado logrado utilizando la técnica de TRAM desepidermizado con complejo areola pezón. Se relatan los factores a considerar en la indicación quirúrgica y la técnica operatoria. Se destaca la superioridad estética y la seguridad a largo plazo del tejido autógenos utilizado, cuya cantidad y calidad es manifiesta

Revascularizaciones y reimplantes mayores de miembros: Siete años de experiencia / Major limb revascularizations and replantations: a seven-year experience

El objetivo de la presente comunicación es presentar nuestra experiencia de los últimos siete años en revascularizaciones y reimplantes mayores de los miembros. Hemos llevado a cabo un total de 28 procedimientos, 25 en miembros superiores y 3 en miembros inferiores, con un porcentaje de éxito del 78,57 por ciento. Del total de casos encontramos que los resultados fueron excelentes o muy buenos en 18 (64,27 por ciento). Las indicaciones para estos procedimientos incluyeron casi todas las amputaciones traumáticas, excepto aquellas que presentaban gran atrición tisular o aplastamiento y pacientes con otras lesiones acompañantes de gravedad o patologías preexistentes. La edad no constituyó una limitación. Severa atrición o arrancamiento fueron las causas de los fracasos en 6 casos. Se concluye que los reimplantes y revasculaciones de los miembros son procedimientos con una metodología reglada y cuyo éxito se encuentra ligado a la estricta observancia de la misma, al desarrollo y perfeccionamiento de las técnicas microquirúrgicas y al entrenamiento constante del equipo de profesionales interviniente. Asimismo se hace mención al papel primordial de la rehabilitación, a los efectos de obtener no sólo miembros viables sino funcionalmente útiles

Tram desepidermizado con complejo areola pezón / Deepidermized TRAM flap with areolar nipple complex

La reconstrucción mamaria en el tratamiento de las secuelas de mastectomías es un desafío, para lo cual contamos con una gran calidad y cantidad de intervenciones quirúrgicas. El objetivo de este trabajos es mostrar el resultado logrado utilizando la técnica de TRAM desepidermizado con complejo areola pezón. Se relatan los factores a considerar en la indicación quirúrgica y la técnica operatoria. Se destaca la superioridad estética y la seguridad a largo plazo del tejido autógenos utilizado, cuya cantidad y calidad es manifiesta