Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes

Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.     

Design and characteristics of InGaAs/InP composite-channel HFET's

A design for composite-channel structures consisting of an InGaAs channel and an InP subchannel for use as heterostructure field-effect transistors is presented for the first time. This novel channel structure takes advantage of both the high drift velocity and low impact ionization of InP at high electric fields as well as the high electron mobility of InGaAs at low electric fields. It is shown that the doping density of the InP subchannel is the key parameter to realize the advantages of the composite channel. A very high transconductance of 1.29 S/mm and a current gain cutoff frequency of 68.7 GHz are achieved with 0.6 and 0.7 /spl mu/m gates, respectively. The average velocity of electrons in the composite channel is 2.9/spl times/10/sup 7/ cm/s. The devices have no kink phenomena in their I-V characteristics possibly due to low impact ionization in the InP subchannel.<>     

Transfer of rps19 to the nucleus involves the gain of an RNP-binding motif which may functionally replace RPS13 in Arabidopsis mitochondria

The discovery of disrupted rps19 genes in Arabidopsis mitochondria prompted speculation about the transfer to the nuclear compartment. We here describe the functional gene transfer of rps19 into the nucleus of Arabidopsis. Molecular cloning and sequence analysis of rps19 show that the nuclear gene encodes a long N-terminal extension. Import studies of the precursor protein indicate that only a small part of this extension is cleaved off during import. The larger part of the extension, which shows high similarity to conserved RNA-binding domains of the RNP-CS type, became part of the S19 protein. In the Escherichia coli ribosome S19 forms an RNA-binding complex as heterodimer with S13. By using immuno-analysis and import studies we show that a eubacterial-like S13 protein is absent from Arabidopsis mitochondria, and is not substituted by either a chloroplastic or a cytosolic homologue of this ribosomal protein. We therefore propose that either a highly diverged or missing RPS13 has been functionally replaced by an RNP domain that most likely derived from a glycine-rich RNA-binding protein. These results represent the first case of a functional replacement of a ribosomal protein by a common RNA-binding domain and offer a new view on the flexibility of biological systems in using well-adapted functional domains for different jobs.     

Chromosomal and genomic organization of Ty1-copia-like retrotransposon sequences in the genus Avena

Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitogenesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors with only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors.     

Loss performance of tagged and normal ATM cells at a partiallyshared buffer

The loss performance of tagged and normal ATM cells at a first-in-first-out (FIFO) buffer is studied. The authors show that if a partial buffer sharing mechanism is adopted the loss probability of normal cells can be firmly guaranteed, regardless of the traffic intensity of tagged cells     

Damage of polymers studied by micro-Fourier Transform Raman spectroscopy

Summary The potential of the micro-Fourier Transform Raman tool in examining specific localized regions in polymeric materials with some degree of fluorescence when analyzed by conventional Raman spectroscopy is examined. Analysis of characteristic bands of the vibrational spectra obtained in a small area damaged by a visible and NIR laser beam in commercial Polyethylene Terephthalate (PET) shows a different conformer ratio than that observed in a non irradiated zone.     

Generation of chromosome fragment specific bovine DNA sequences by microdissection and DOP-PCR

Trends in causative organisms and sources of infection were studied in a series of 288 episodes of bacteremia in neutropenic cancer patients observed in a single institution from 1986 to 1993. The incidence of bacteremia increased significantly from 20 episodes per 1000 admissions in 1986 to 50 episodes per 1000 admissions in 1993 (p = 0.00001). Over the study period, a continuous increment in gram-positive bacteremia, which reached 81% of episodes in 1993 (p = 0.000001), was observed. Conversely, the incidence of gram-negative bacteremia remained stable. Coagulase-negative staphylococci and viridans group streptococci were the most commonly isolated pathogens. Bacteremia caused by coagulase-negative staphylococci increased from 3 episodes per 1000 admissions to 19 episodes per 1000 admissions (p = 0.0001), and viridans group streptococci bacteremia increased from 0 episodes per 1000 admissions to 19 episodes per 1000 admissions (p = 0.000001). The upward trend in gram-positive bacteremia appeared to be related to a significant increase in both intravascular catheters (p = 0.003) and oral mucositis (p = 0.003) as sources of infection. Specific strategies to prevent chemotherapy-induced mucositis and catheter-related bacteremia merit further investigations.     

Transmit permission control on spread ALOHA packets in LEOsatellite systems

A transmit permission control method for improving the throughput characteristics of a low Earth orbit (LEO) satellite communication system employing spread-slotted ALOHA multiple-access scheme is proposed. Both nonfading and fading satellite links are considered. The basic idea of the proposed scheme is to decrease the level of interference at each satellite and, hence, to increase the probability of packet success, by prohibiting the packet transmission from the users with relatively high propagation loss to their connecting satellites. It is shown that the method has the ability to improve the throughput performance in heavy traffic loads and the peak value of the throughput, significantly. It is also shown that the average delay performance of the system employing the proposed scheme is superior to that of the conventional system at heavy traffic loads     

The master curve and the constitutive equation for creep deformation and fracture for Cr-Mo-V steel throughout smooth,notched and precracked specimens

It has been shown experimentally that the master curve for creep deformation versus the ratio of time to fracture time, can be obtained for smooth, notched and precracked specimens of Cr-Mo-V steel, a high-temperature ductile material. A simple unified constitutive equation, i.e. a master curve equation, has been proposed. It is suggested that there is some correlation between the creep deformation fracture curve and the creep damage size master curve. Although the range of the applicability of methodology might be rather limited, the development of this concept is needed for improved long-term creep lives and for other creep ductile materials.     

KGa-priderite and related compound for the selective reduction of nitrogen monoxide with propylene

The catalytic activity of KGa-priderite, K_1.6Ga_1.6Ti_6.4O₁₆, and its related compound KGa₈Ga₉Ti₁₅O₅₆ was investigated for the selective reduction of nitrogen monoxide (NO) with propylene (C₃H₆) in the presence of high oxygen concentrations. The KGa-priderite showed significant activity during this reaction, but the related compound showed only a little activity. These compounds are quite different from the conventional catalysts for NO_x selective reduction and are characterized by the fact that their properties are free from the effects of solid acidity and support metals. This difference was attributable to the NO desorption rate at the surface of these compounds. It has become clear that the KGa-priderite catalyst remarkably adsorbed NO, and it is suggested that the amount of NO adsorbed and the amount of catalytic activity are able to be increased by the design of priderite structure.