Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation

Recent studies indicate that Caenorhabditis elegans CED-4 interacts with and promotes the activation of the death protease CED-3, and that this activation is inhibited by CED-9. Here we show that a mammalian homolog of CED-4, Apaf-1, can associate with several death proteases, including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. The interaction with caspase-9 was mediated by the N-terminal CED-4-like domain of Apaf-1. Expression of Apaf-1 enhanced the killing activity of caspase-9 that required the CED-4-like domain of Apaf-1. Furthermore, Apaf-1 promoted the processing and activation of caspase-9 in vivo. Bcl-XL, an antiapoptotic member of the Bcl-2 family, was shown to physically interact with Apaf-1 and caspase-9 in mammalian cells. The association of Apaf-1 with Bcl-XL was mediated through both its CED-4-like domain and the C-terminal domain containing WD-40 repeats. Expression of Bcl-XL inhibited the association of Apaf-1 with caspase-9 in mammalian cells. Significantly, recombinant Bcl-XL purified from Escherichia coli or insect cells inhibited Apaf-1-dependent processing of caspase-9. Furthermore, Bcl-XL failed to inhibit caspase-9 processing mediated by a constitutively active Apaf-1 mutant, suggesting that Bcl-XL regulates caspase-9 through Apaf-1. These experiments demonstrate that Bcl-XL associates with caspase-9 and Apaf-1, and show that Bcl-XL inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans.

Revista moderna : Anno 1, n. 6 (20 setembro 1897)

Impressa em papel couché. De acordo com Ana Luiza Martins em sua obra "Revistas em revista": "A Revista Moderna, impressa em Paris, em 1897, introduzia o que havia de mais avançado em periodismo, primando por elaboradas reportagens, coberturas de acontecimentos marcantes do tempo, geralmente ilustradas com desenhos tomados a partir dos acontecimentos, não se furtando ao sensacionalismo em voga."

Synthesis and in vivo murine evaluation of Na4[1-(1′-B10H9)-6-SHB10H8] as a potential agent for boron neutron capture therapy

Reaction of the normal isomer of [B20H18]2− and the protected thiol anion, [SC(O)OC(CH3)3]−, produces an unexpected isomer of [B20H17SC(O)OC(CH3)3]4− directly and in good yield. The isomer produced under mild conditions is characterized by an apical–apical boron atom intercage connection as well as the location of the thiol substituent on an equatorial belt adjacent to the terminal boron apex. Although the formation of this isomer from nucleophilic attack of the normal isomer of [B20H18]2− has not been reported previously, the isomeric assignment has been unambiguously confirmed by one-dimensional and two-dimensional 11B NMR spectroscopy. Deprotection of the thiol substituent under acidic conditions produces a protonated intermediate, [B20H18SH]3−, which can be deprotonated with a suitable base to yield the desired product, [B20H17SH]4−. The sodium salt of the resulting [B20H17SH]4− ion has been encapsulated in small, unilamellar liposomes, which are capable of delivering their contents selectively to tumors in vivo, and investigated as a potential agent for boron neutron capture therapy. The biodistribution of boron was determined after intravenous injection of the liposomal suspension into BALB/c mice bearing EMT6 mammary adenocarcinoma. At low injected doses, the tumor boron concentration increased throughout the time-course experiment, resulting in a maximum observed boron concentration of 46.7 μg of B per g of tumor at 48 h and a tumor to blood boron ratio of 7.7. The boron concentration obtained in the tumor corresponds to 22.2% injected dose (i.d.) per g of tissue, a value analogous to the most promising polyhedral borane anions investigated for liposomal delivery and subsequent application in boron neutron capture therapy.

Synthesis and spectroscopic characterization of site-specific 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine oligodeoxyribonucleotide adducts

The aim of the present study is to determine the chemical structure and conformation of DNA adducts formed by incubation of the bioactive form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-acetoxy-PhIP, with a single-stranded 11mer oligodeoxyribonucleotide. Using conditions optimized to give the C8-dG-PhIP adduct as the major product, sufficient material was synthesized for NMR solution structure determination. The NMR data indicate that in duplex DNA this adduct exists in equilibrium between two different conformational states. In the main conformer, the covalently bound PhIP molecule intercalates in the helix, whilst in the minor conformation the PhIP ligand is probably solvent exposed. In addition to the C8-dG-PhIP adduct, at least eight polar adducts are found after reaction of N-acetoxy-PhIP with the oligonucleotide. Three of these were purified for further characterization and shown to exhibit lowest energy UV absorption bands in the range 342–347 nm, confirming the presence of PhIP or PhIP derivative. Accurate mass determination of two of the polar adducts by negative ion MALDI-TOF MS revealed ions consistent with a spirobisguanidino-PhIP derivative and a ring-opened adduct. The third adduct, which has the same mass as the C8-dG-PhIP oligonucleotide adduct, may contain PhIP bound to the N2 position of guanine.

Rotten Symbol Mongering: Scapegoating in Post-9/11 American War Literature

A rhetorical approach to the fiction of war offers an appropriate vehicle by which one may encounter and interrogate such literature and the cultural metanarratives that exist therein. My project is a critical analysis—one that relies heavily upon Kenneth Burke’s dramatistic method and his concepts of scapegoating, the comic corrective, and hierarchical psychosis—of three war novels published in 2012 (The Yellow Birds by Kevin Powers, FOBBIT by David Abrams, and Billy Lynn’s Long Halftime Walk by Ben Fountain). This analysis assumes a rhetorical screen in order to subvert and redirect the grand narratives the United States perpetuates in art form whenever it goes to war. Kenneth Burke’s concept of ad bellum purificandum (the purification of war) sought to bridge the gap between war experience and the discourse that it creates in both art and criticism. My work extends that project. I examine the symbolic incongruity of convenient symbols that migrate from war to war (“Geronimo” was used as code for Osama bin Laden’s death during the S.E.A.L team raid; “Indian Country” stands for any dangerous land in Iraq; hajji is this generation’s epithet for the enemy other). Such an examination can weaken our cultural “symbol mongering,” to borrow a phrase from Walker Percy. These three books, examined according to Burke’s methodology, exhibit a wide range of approaches to the soldier’s tale. Notably, however, whether they refigure the grand narratives of modern culture or recast the common redemptive war narrative into more complex representations, this examination shows how one can grasp, contend, and transcend the metanarrative of the typical, redemptive war story.

Russia's Clandestine War against the United States: The Resurrection of the KGB and Russian Organized Crime Post 9/11

As American leadership has narrowly focused on fighting global terror in Iraq and Afghanistan, the modern version of the KGB, now known as the FSB, has been conducting continuous clandestine warfare operations against the United States. These warfare operations include strategic economic and political partnerships with anti-American entities worldwide and direct embedding of double agents in the US intelligence community. This paper investigates the role of Russia's cultural history leading to the merger of the Russian Federal Security Service (FSB) and Russian Organized Crime (ROC). This paper concludes that the FSB is the most pervasive security threat to the United States and that employing Russian native and heritage speakers of Russian in the US intelligence community compromises US national security.

Quitclaim, 1745/6 February 11

Handwritten quitclaim by Benjamin Fuller and Hannah Fuller as beneficiaries of the estate of Benjamin Wadsworth, acknowledging payment by Andrew Bordman.

Quitclaim, 1745/6 February 11

Handwritten quitclaim by Timothy Tolman and Elizabeth Tolman as beneficiaries of the estate of Benjamin Wadsworth, acknowledging payment by Andrew Bordman.