Structural changes of tumor necrosis factor alpha associated with membrane insertion and channel formation.

Low pH enhances tumor necrosis factor alpha (TNF)-induced cytolysis of cancer cells and TNF-membrane interactions that include binding, insertion, and ion-channel formation. We have also found that TNF increases Na+ influx in cells. Here, we examined the structural features of the TNF-membrane interaction pathway that lead to channel formation. Fluorometric studies link TNF's acid-enhanced membrane interactions to rapid but reversible acquisition of hydrophobic surface properties. Intramembranous photolabeling shows that (i) protonation of TNF promotes membrane insertion, (ii) the physical state of the target bilayer affects the kinetics and efficiency of TNF insertion, and (iii) binding and insertion of TNF are two distinct events. Acidification relaxes the trimeric structure of soluble TNF so that the cryptic carboxyl termini, centrally located at the base of the trimer cone, become susceptible to carboxypeptidase Y. After membrane insertion, TNF exhibits a trimeric configuration in which the carboxyl termini are no longer exposed; however, the proximal salt-bridged Lys-11 residues as well as regional surface amino acids (Glu-23, Arg-32, and Arg-44) are notably more accessible to proteases. The sequenced cleavage products bear the membrane-restricted photoreactive probe, proof that surface-cleaved TNF has an intramembranous disposition. In summary, the trimer's structural plasticity is a major determinant of its channel-forming ability. Channel formation occurs when cracked or partially splayed trimers bind and penetrate the bilayer. Reannealing leads to a slightly relaxed trimeric structure. The directionality of bilayer penetration conforms with x-ray data showing that receptor binding to the monomer interfaces of TNF poises the tip of the trimeric cone directly above the target cell membrane.

Japanese American Biracial Adolescents and Identity Formation

The purpose of the current paper is to examine the racial identity development of Japanese American biracial adolescents. A review of the literature revealed critical factors as it relates to Japanese American biracial adolescents and their identity formation. Ethnic identity, adolescent developmental stage, environmental ethnic socialization processes used to facilitate identity development, and the resulting psychological adjustment were the major issues identified in the literature. Educators, counselors and other mental health professionals must begin to understand their development if the needs of this population are to be met in the future. A case study of a biracial Japanese American teen was included to heighten the understanding of the identity development of biracial individuals. Findings indicate that biracial children who are raised to identify with both sides of their ethnic heritage are not suffering from negative psychological consequences (e.g. guilt, anger, isolation) but, instead, gain a "healthier" sense of self. Implications for clinicians are discussed in terms of how therapists can be responsive to the unique needs of biracial adolescents.

Testing diagnostics of nuclear activity and star formation in galaxies at z > 1

We present some of the first science data with the new Keck/MOSFIRE instrument to test the effectiveness of different AGN/SF diagnostics at z ~ 1.5. MOSFIRE spectra were obtained in three H-band multi-slit masks in the GOODS-S field, resulting in 2 hr exposures of 36 emission-line galaxies. We compare X-ray data with the traditional emission-line ratio diagnostics and the alternative mass-excitation and color-excitation diagrams, combining new MOSFIRE infrared data with previous HST/WFC3 infrared spectra (from the 3D-HST survey) and multiwavelength photometry. We demonstrate that a high [O III]/Hβ ratio is insufficient as an active galactic nucleus (AGN) indicator at z > 1. For the four X-ray-detected galaxies, the classic diagnostics ([O III]/Hβ versus [N II]/Hα and [S II]/Hα) remain consistent with X-ray AGN/SF classification. The X-ray data also suggest that "composite" galaxies (with intermediate AGN/SF classification) host bona fide AGNs. Nearly ~2/3 of the z ~ 1.5 emission-line galaxies have nuclear activity detected by either X-rays or the classic diagnostics. Compared to the X-ray and line ratio classifications, the mass-excitation method remains effective at z > 1, but we show that the color-excitation method requires a new calibration to successfully identify AGNs at these redshifts.

Common origin for surface reconstruction and the formation of chains of metal atoms

During the fracture of nanocontacts gold spontaneously forms freely suspended chains of atoms, which is not observed for the isoelectronic noble metals Ag and Cu. Au also differs from Ag and Cu in forming reconstructions at its low-index surfaces. Using mechanically controllable break junctions we show that all the 5d metals that show similar reconstructions (Ir, Pt, and Au) also form chains of atoms, while both properties are absent in the 4d neighbor elements (Rh, Pd, and Ag), indicating a common origin for these two phenomena. A competition between s and d bonding is proposed as an explanation.

Sub-Cellular Localization and Complex Formation by Aminoacyl-tRNA Synthetases in Cyanobacteria: Evidence for Interaction of Membrane-Anchored ValRS with ATP Synthase

tRNAs are charged with cognate amino acids by aminoacyl-tRNA synthetases (aaRSs) and subsequently delivered to the ribosome to be used as substrates for gene translation. Whether aminoacyl-tRNAs are channeled to the ribosome by transit within translational complexes that avoid their diffusion in the cytoplasm is a matter of intense investigation in organisms of the three domains of life. In the cyanobacterium Anabaena sp. PCC 7120, the valyl-tRNA synthetase (ValRS) is anchored to thylakoid membranes by means of the CAAD domain. We have investigated whether in this organism ValRS could act as a hub for the nucleation of a translational complex by attracting other aaRSs to the membranes. Out of the 20 aaRSs, only ValRS was found to localize in thylakoid membranes whereas the other enzymes occupied the soluble portion of the cytoplasm. To investigate the basis for this asymmetric distribution of aaRSs, a global search for proteins interacting with the 20 aaRSs was conducted. The interaction between ValRS and the FoF1 ATP synthase complex here reported is of utmost interest and suggests a functional link between elements of the gene translation and energy production machineries.

Private pensions and capital formation /

Mode of access: Internet.

Base surge and cloud formation /

"Prepared for the U.S. Atomic Energy Commission."

The church of the first three centuries: or, Notices of the lives and opinions of some of the early Fathers, with special reference to the doctrine of the Trinity; illustrating its late origin and gradual formation.

Mode of access: Internet.

Secondary market for commercial business loans : hearing before the Subcommittee on Economic Growth and Credit Formation of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, One Hundred Third Congress, first session, March 9, 1993.

Mode of access: Internet.

Secondary market for commercial business loans : hearing before the Subcommittee on Economic Growth and Credit Formation of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, One Hundred Third Congress, first session, April 21, 1993.

Mode of access: Internet.

Secondary market for commercial business loans : hearing before the Subcommittee on Economic Growth and Credit Formation of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, One Hundred Third Congress, first session, February 16, 1993.

Mode of access: Internet.

H.R. 2600, the Business, Commercial, and Community Development Secondary Market Development Act : hearing before the Subcommittee on Economic Growth and Credit Formation of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, One Hundred Third Congress, first session, October 7, 1993.

Mode of access: Internet.