Los vínculos de intercambio entre el noreste de Africa y el Levante (ca.3400 - 3000 a.C.)

El estudio de los vínculos entre distintas comunidades generó diversos modelos teóricos e interpretaciones que fueron desarrollados para el estudio de las relaciones de intercambio existentes entre las poblaciones antiguas. En general, estas posturas teóricas se pueden diferenciar entre las que se concentran específicamente en los vínculos de intercambio establecidos entre distintas comunidades y diferentes áreas, y las que analizan el efecto de ellos en los procesos internos de una comunidad. En este trabajo nos enfocamos en el primer aspecto, ya que nuestro objeto es abordar las relaciones de intercambio existentes desde la Alta Nubia hasta el Levante, atravesando Baja Nubia, Alto Egipto y Bajo Egipto durante el período que se extiende desde el 3400 a.C al 3000 a.C., aplicando la teoría sistema-mundo y los análisis de los sistemas-mundo

Los vínculos de intercambio entre el noreste de Africa y el Levante (ca.3400 - 3000 a.C.)

El estudio de los vínculos entre distintas comunidades generó diversos modelos teóricos e interpretaciones que fueron desarrollados para el estudio de las relaciones de intercambio existentes entre las poblaciones antiguas. En general, estas posturas teóricas se pueden diferenciar entre las que se concentran específicamente en los vínculos de intercambio establecidos entre distintas comunidades y diferentes áreas, y las que analizan el efecto de ellos en los procesos internos de una comunidad. En este trabajo nos enfocamos en el primer aspecto, ya que nuestro objeto es abordar las relaciones de intercambio existentes desde la Alta Nubia hasta el Levante, atravesando Baja Nubia, Alto Egipto y Bajo Egipto durante el período que se extiende desde el 3400 a.C al 3000 a.C., aplicando la teoría sistema-mundo y los análisis de los sistemas-mundo

Los vínculos de intercambio entre el noreste de Africa y el Levante (ca.3400 - 3000 a.C.)

El estudio de los vínculos entre distintas comunidades generó diversos modelos teóricos e interpretaciones que fueron desarrollados para el estudio de las relaciones de intercambio existentes entre las poblaciones antiguas. En general, estas posturas teóricas se pueden diferenciar entre las que se concentran específicamente en los vínculos de intercambio establecidos entre distintas comunidades y diferentes áreas, y las que analizan el efecto de ellos en los procesos internos de una comunidad. En este trabajo nos enfocamos en el primer aspecto, ya que nuestro objeto es abordar las relaciones de intercambio existentes desde la Alta Nubia hasta el Levante, atravesando Baja Nubia, Alto Egipto y Bajo Egipto durante el período que se extiende desde el 3400 a.C al 3000 a.C., aplicando la teoría sistema-mundo y los análisis de los sistemas-mundo

Direct interaction of Gβγ with a C-terminal Gβγ-binding domain of the Ca2+ channel α1 subunit is responsible for channel inhibition by G protein-coupled receptors

Several classes of voltage-gated Ca2+ channels (VGCCs) are inhibited by G proteins activated by receptors for neurotransmitters and neuromodulatory peptides. Evidence has accumulated to indicate that for non-L-type Ca2+ channels the executing arm of the activated G protein is its βγ dimer (Gβγ). We report below the existence of two Gβγ-binding sites on the A-, B-, and E-type α1 subunits that form non-L-type Ca2+ channels. One, reported previously, is in loop 1 connecting transmembrane domains I and II. The second is located approximately in the middle of the ca. 600-aa-long C-terminal tails. Both Gβγ-binding regions also bind the Ca2+ channel β subunit (CCβ), which, when overexpressed, interferes with inhibition by activated G proteins. Replacement in α1E of loop 1 with that of the G protein-insensitive and Gβγ-binding-negative loop 1 of α1C did not abolish inhibition by G proteins, but the exchange of the α1E C terminus with that of α1C did. This and properties of α1E C-terminal truncations indicated that the Gβγ-binding site mediating the inhibition of Ca2+ channel activity is the one in the C terminus. Binding of Gβγ to this site was inhibited by an α1-binding domain of CCβ, thus providing an explanation for the functional antagonism existing between CCβ and G protein inhibition. The data do not support proposals that Gβγ inhibits α1 function by interacting with the site located in the loop I–II linker. These results define the molecular mechanism by which presynaptic G protein-coupled receptors inhibit neurotransmission.

Sp1 phosphorylation regulates inducible expression of platelet-derived growth factor B-chain gene via atypical protein kinase C-ζ

Platelet-derived growth factor (PDGF) is a broadly expressed mitogenic and chemotactic factor with diverse roles in a number of physiologic and pathologic settings. The zinc finger transcription factors Sp1, Sp3 and Egr-1 bind to overlapping elements in the proximal PDGF B-chain promoter and activate transcription of this gene. The anthracycline nogalamycin has previously been reported to inhibit the capacity of Egr-1 to bind DNA in vitro. Here we used electrophoretic mobility shift assays to show that nogalamycin added to cells in culture did not alter the interaction of Egr-1 with the PDGF-B promoter. Instead, it enhanced the capacity of Sp1 to bind DNA. Nogalamycin increased PDGF-B mRNA expression at the level of transcription, which was abrogated by mutation of the Sp1 binding site in the PDGF-B promoter or overexpression of mutant Sp1. Rather than increasing total levels of Sp1, nogalamycin altered the phosphorylation state of the transcription factor. Overexpression of dominant-negative PKC-ζ blocked nogalamycin-inducible Sp1 phosphorylation and PDGF-B promoter-dependent expression. Nogalamycin stimulated the phosphorylation of PKC-ζ (on residue Thr410). These findings demonstrate for the first time that PKC-ζ and Sp1 phosphorylation mediate the inducible expression of this growth factor.

Triplex targeting of human PDGF-B (c-sis, proto-oncogene) promoter specifically inhibits factors binding and PDGF-B transcription

Human c-sis/PDGF-B proto-oncogene has been shown to be overexpressed in a large percentage of human tumor cells establishing a growth-promoting, autocrine growth circuit. Triplex forming oligonucleotides (TFOs) can recognize and bind sequences in duplex DNA, and have received considerable attention because of their potential for targeting specific genomic sites. The c-sis/PDGF-B promoter contains a unique homopurine/homopyrimidine sequence (SIS proximal element, SPE), which is crucial for binding nuclear factors that provoke transcription. In order to develop specific transcriptional inhibitors of the human c-sis/PDGF-B proto-oncogene, 20 potential TFOs targeting part or all of the SPE were screened by gel mobility analysis. DNase I footprinting shows that the TFOs we designed can form a sequence-specific triplex with the target. Protein binding assays demonstrate that triplex formation inhibits nuclear factors binding the c-sis/PDGF-B promoter. Both transient and stable transfection experiments demonstrate that the transcriptional activity of the promoter is considerably inhibited by the TFOs. We propose that TFOs represent a therapeutic potential to specifically diminish the expression of c-sis/PDGF-B proto-oncogene in various pathologic settings where constitutive expression of this gene has been observed.

Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP.

Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).

A B C of gothic architecture /

Includes index.

Sumerian mythology, a study of spiritual and literary achievement in the third millennium, B.C.

Frontispiece accompanied by leaf with descriptive letterpress.

Zenon papyri; business papers of the third century B.C. dealing with Palestine and Egypt,

Vol. 2 cite as: P.Col. IV