Biomedical subjects

W Li

Publications and source records attributed to W Li.

At least 361 records · Page 20Linked to original sources

PubMed2000

The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf.

Caenorhabditis elegans sur-8 encodes a positive regulator of Ras signaling. We investigated the mechanism by which the human Sur-8 homolog can positively regulate Ras-MAP kinase signaling in mammalian cells. Sur-8 expression enhances Ras- or EGF-induced Raf and ERK activation but has no effect on ERK activation induced by active Raf or MEK. Furthermore, Sur-8 expression does not increase AKT or JNK activation. Sur-8 interacts with Ras and Raf and is able to form a ternary complex with the two proteins. Thus, Sur-8 may function as a scaffold that enhances Ras-MAP kinase signal transduction by facilitating the interaction between Ras and Raf.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Rab geranylgeranyl transferase alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet synthesis.

Few molecular events important to platelet biogenesis have been identified. Mice homozygous for the spontaneous, recessive mutation gunmetal (gm) have prolonged bleeding, thrombocytopenia, and reduced platelet alpha- and delta-granule contents. Here we show by positional cloning that gm results from a G-->A substitution mutation in a splice acceptor site within the alpha-subunit of Rab geranylgeranyl transferase (Rabggta), an enzyme that attaches geranylgeranyl groups to Rab proteins. Most Rabggta mRNAs from gm tissues skipped exon 1 and lacked a start codon. Rabggta protein and Rab geranylgeranyl transferase (GGTase) activity were reduced 4-fold in gm platelets. Geranylgeranylation and membrane association of Rab27, a Rab GGTase substrate, were significantly decreased in gm platelets. These findings indicate that geranylgeranylation of Rab GTPases is critical for hemostasis. Rab GGTase inhibition may represent a new treatment for thrombocytosis and clotting disorders.

Alkyl and Aryl Transferases↗

PubMed2000

Defective cleavage of membrane bound TGFalpha leads to enhanced activation of the EGF receptor in malignant cells.

Transforming growth factor alpha (TGFalpha) is widely expressed in malignant as well as normal cells and is involved in regulating cell growth and differentiation. Although processing of TGFalpha has been extensively studied in normal cells, there is little information regarding TGFalpha cleavage in malignant cells. Therefore, we compared the processing of TGFalpha in two human colon carcinoma cell lines. We found that there was a defective cleavage pattern for the TGFalpha precursor resulting in retention of partially processed TGFalpha on the cell surface of both the HCT116a2alphaS3 and CBS4alphaS2 cell lines. This raised the possibility that signaling from the resulting defective cleavage species could differ from that of soluble TGFalpha. The membrane-associated TGFalpha induced higher phosphorylation of EGFR on the cell surface of adjacent cells than equivalent levels of mature TGFalpha. The interaction of membrane bound TGFalpha precursor with the EGFR caused a slower internalization of activated EGFR relative to the internalization of the soluble TGFalpha/EGFR complexes. In addition, the tethered TGFalpha was resistant to the ability of protein-tyrosine phosphatases (PTPs) to reduce EGFR tyrosine phosphorylation, also contributing to higher activation of EGFR. The enhanced activation of EGFR by the tethered form of TGFalpha was reflected by higher activation of Grb2, SHC and Erk downstream mediators of EGF receptor signaling. The higher activation of EGFR by membrane tethered TGFalpha indicates that defective TGFalpha processing provides a mechanism whereby malignant cells can obtain a growth advantage over normal cells.

Cell Membrane↗

PubMed2000

Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1.

Mucin1 (MUC1) is expressed ubiquitously on breast cancer cells and is a potential target for the generation of cytotoxic T cells for vaccination against breast cancer. Thus far studies of the immunogenicity of MUC1 have used peptides from the variable number of tandem repeat (VNTR); mice so immunised can generate strong cellular and antibody responses to the VNTR of human MUC1. We now demonstrate that significant CTL and CTLp can be induced to other regions of MUC1. Using the whole native MUC1 molecule, the human milk fat globule membrane antigen (HMFG) linked to mannan, cytotoxic T cell precursors (CTLp) can be generated in BALB/c, C57BL/6, transgenic HLA-A*0201/K(b) and double transgenic HLA-A*0201/K(b)xhuman MUC1 (A2 K(b)MUC1) mice. By immunising with HMFG and testing selectively on (a) extracellular (non-VNTR); (b) VNTR and (c) intracellular peptides, it was shown that all three regions generated effective CTL. Further, the CTL responses to non-VNTR peptides were as strong as those generated to the VNTR. Epitope prediction algorithms were not particularly helpful to describe CTL epitopes: overlapping peptides had to be synthesised and tested to find the epitopes. Thus, for CTL generation, the whole HMFG molecule is a powerful immunogen when linked to mannan, especially as multiple peptide epitopes for presentation by many Class I molecules are contained within the one molecule. Furthermore, Class I restricted MUC1 CTL were generated in double transgenic A2 K(b)MUC1 mice by immunising with mannan-native mucin (HMFG), suggesting that tolerance to MUC1 can be overcome with mannan-HMFG.

Amino Acid Sequence↗

PubMed2000

A soluble and air-stable organic semiconductor with high electron mobility

Electronic devices based on organic semiconductors offer an attractive alternative to conventional inorganic devices due to potentially lower costs, simpler packaging and compatibility with flexible substrates. As is the case for silicon-based microelectronics, the use of complementary logic elements-requiring n- and p-type semiconductors whose majority charge carriers are electrons and holes, respectively-is expected to be crucial to achieving low-power, high-speed performance. Similarly, the electron-segregating domains of photovoltaic assemblies require both n- and p-type semiconductors. Stable organic p-type semiconductors are known, but practically useful n-type semiconductor materials have proved difficult to develop, reflecting the unfavourable electrochemical properties of known, electron-demanding polymers. Although high electron mobilities have been obtained for organic materials, these values are usually obtained for single crystals at low temperatures, whereas practically useful field-effect transistors (FETs) will have to be made of polycrystalline films that remain functional at room temperature. A few organic n-type semiconductors that can be used in FETs are known, but these suffer from low electron mobility, poor stability in air and/or demanding processing conditions. Here we report a crystallographically engineered naphthalenetetracarboxylic diimide derivative that allows us to fabricate solution-cast n-channel FETs with promising performance at ambient conditions. By integrating our n-channel FETs with solution-deposited p-channel FETs, we are able to produce a complementary inverter circuit whose active layers are deposited entirely from the liquid phase. We expect that other complementary circuit designs can be realized by this approach as well.

Journal Article↗

PubMed2000

Ribozyme ablation demonstrates that the cardiac subtype of the voltage-sensitive calcium channel is the molecular transducer of 1, 25-dihydroxyvitamin D(3)-stimulated calcium influx in osteoblastic cells.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) stimulates transmembrane influx of Ca(2+) through L-type voltage-sensitive Ca(2+) channels (VSCCs) in ROS 17/2.8 osteoblastic cells. Ca(2+) influx modulates osteoblastic activities including matrix deposition, hormone responsiveness, and Ca(2+)-dependent signaling. 1, 25(OH)(2)D(3) also regulates transcript levels encoding VSCCs. L-type VSCCs are multisubunit complexes composed of a central pore-forming alpha(1) subunit and four additional subunits. The alpha(1) subunit is encoded by one gene in a multimember family, defining tissue-specific subtypes. Osteoblasts synthesize two splice variants of the alpha(1C) cardiac VSCC subtype; however, the molecular identity of the 1,25(OH)(2)D(3)-regulated VSCC remained unknown. We created a ribozyme specifically cleaving alpha(1C) mRNA. To increase target ablation efficiency, the ribozyme was inserted into U1 small nuclear RNA (snRNA) by engineering the U1 snRNA expression cassette, conferring the ribozyme transcript with stabilizing stem-loops at both sides and the Sm binding site that facilitates localization into nucleoplasm. After transfection of ROS 17/2.8 cells with U1 ribozyme-encoding vector, stable clonal cells were selected in which the expression of alpha(1C) transcript and protein were strikingly reduced. Ca(2+) influx assays in ribozyme transfectants showed selective attenuation of depolarization and 1, 25(OH)(2)D(3)-regulated Ca(2+) responses. We conclude that the cardiac subtype of the L-type VSCC is the transducer of stimulated Ca(2+) influx in ROS 17/2.8 osteoblastic cells.

Alternative Splicing↗

PubMed2000

A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements?

Pax-6 encodes a transcription factor that is important in the development of eye and CNS. Identification of Pax-6 target genes is crucial for understanding the gene regulatory network in these developmental processes. Using an in-vitro approach of cyclic amplification of the protein binding sequences (CAPBS), we isolated a PAX6 binding sequence from a human single-copy (sc) DNA library. Characterization of this PAX6 binding sequence revealed a 15bp region (hGCalpha1BLs5) that is sufficient for PAX6 specific binding. From a homology search in the GenBank, we found that an hGCalpha1BLs5-like Pax-6 binding site exists in 21 genes (16 from rodent), 15 of which were shown to be able to bind Pax-6 in vitro. Interestingly, some of these sites occur in B1 repetitive elements. Although hGCalpha1BLs5 is highly similar to a region in B1 repetitive elements, PAX6 does not bind to the consensus sequence in B1. However, a single-step mutation in some B1 elements can lead to a gain of function for PAX6 binding. This experimental evidence and phylogenetic analysis raise an interesting speculation for the coevolution between PAX6 regulation and repeat elements. Since a (Pax-6-binding) null B1 element can be re-activated by even a single-step mutation, it has the potential to recruit gene targets for Pax-6 if it is inserted into the regulatory region, and therefore may play a role for evolutionary modification of Pax-6 regulation.

Animals↗

PubMed2000

Induction of cell death by the lysosomotropic detergent MSDH.

Controlled lysosomal rupture was initiated in lysosome-rich, macrophage-like cells by the synthetic lysosomotropic detergent, O-methyl-serine dodecylamide hydrochloride (MSDH). When MSDH was applied at low concentrations, resulting in partial lysosomal rupture, activation of pro-caspase-3-like proteases and apoptosis followed after some hours. Early during apoptosis, but clearly secondary to lysosomal destabilization, the mitochondrial transmembrane potential declined. At high concentrations, MSDH caused extensive lysosomal rupture and necrosis. It is suggested that lysosomal proteases, if released to the cytosol, may cause apoptosis directly by pro-caspase activation and/or indirectly by mitochondrial attack with ensuing discharge of pro-apoptotic factors.

Amides↗

PubMed2000

Expression of the RNA-binding protein TIAR is increased in neurons after ischemic cerebral injury.

T-cell restricted intracellular antigen-related protein (TIAR) is an RNA recognition motif-type RNA-binding protein that has been implicated in the apoptotic death of T-lymphocytes and retinal pigment epithelial cells. Western blots prepared with a monoclonal antibody against TIAR showed expression in normal rat hippocampus, and induction by 15 min of global cerebral ischemia. This increased expression was evident at 8 hr after ischemia and maximal at 24 hr, whereas expression at 72 hr was reduced below basal levels. Expression of TIAR protein was also increased in parietal cortex 6 and 24 hr after 90 min of focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion, as well as in cultured cortical neurons and astroglia after exposure to hypoxia in vitro. Immunocytochemistry showed that increased expression of TIAR occurred mainly in the CA1 sector of hippocampus 24 hr after global ischemia, and in cortical and striatal neurons 24 hr after 20 or 90 min of focal ischemia. Double-labeling studies showed that TIAR protein expression was co-localized with DNA damage in neuronal cells. The findings suggest that TIAR may be involved in neuronal cell death after cerebral ischemic injury.

Animals↗

PubMed2000

Effects of neutral sphingomyelinase on phenylephrine-induced vasoconstriction and Ca(2+) mobilization in rat aortic smooth muscle.

The sphingomyelin pathway is now recognized as an important signal transduction system regulating various cellular functions, in which activation of a neutral sphingomyelinase induced by various extracellular stimulants results in selective degradation of sphingomyelin, yielding bioactive lipid intermediates, ceramides and phosphorylcholine. In the present study, our emphasis has been to examine the effects of exogenous Mg(2+)-dependent neutral sphingomyelinase, in physiological and pathophysiological magnesium concentrations, on phenylephrine-induced vasomotor tone and on intracellular free Ca(2+)([Ca(2+)](i)) mobilization in vitro. Neutral sphingomyelinase (0.001-0.1 U/ml), alone, did not elicit any significant changes in either basal tension or resting levels of [Ca(2+)](i) in rat aortic smooth muscle; similar results were obtained with phosphorylcholine. However, neutral sphingomyelinase (0.001-0.1 U/ml) and C(2)-ceramide or ceramide-1-phosphate, but not phosphorylcholine, attenuated phenylephrine-induced contractions, in isolated rat aortic rings, in a concentration-related manner. The addition of extracellular magnesium in different concentrations (0, 0.3, 1.2, 2.4 mM) modulated the neutral sphingomyelinase-vasorelaxant action in a concentration-dependent manner. Neutral sphingomyelinase-evoked relaxation was only partially endothelium-dependent. Nitric oxide synthase inhibitors, N(G)-nitro-L-arginine (L-NNA) and L-N(G)-monomethyl-arginine (L-NMMA), an inhibitor of prostanoid synthesis (indomethacin), and pharmacologic amine antagonists, such as atropine, diphenhydramine, cimetidine, propranolol, and methysergide as well as an opiate antagonist, naloxone, all failed to attenuate or interfere with the vasorelaxant responses of neutral sphingomyelinase. Three different inhibitors of protein kinase C (i.e., staurosporine, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) or bisindolylmaleimide I), when used over a wide concentration range, also failed to interfere with the neutral sphingomyelinase-induced relaxations. Neutral sphingomyelinase inhibited the elevations in [Ca(2+)](i) in cultured rat aortic smooth muscle cells caused by phenylephrine. Our results suggest that a Mg(2+)-dependent sphingomyelin signaling pathway may play an important regulatory role in arterial wall tone.

Animals↗

PubMed2000

Supramolecular steric effects as the means of making reactive carbon radicals persistent. Quantitative characterization of the external surface of MFI zeolites through a persistent radical probe and a langmuir adsorption isotherm

The photochemistry of tetraphenylacetone (1) adsorbed on the external surface of a MFI zeolite (the sodium form of LZ-105) has been investigated in combination with computational chemistry, surface area measurements, EPR analysis, and classical adsorption isotherms. All of the methods are consistent with a supramolecular structural model in which 1 is first adsorbed strongly through intercalation of a single benzene ring into a hole on the LZ-105 external surface (site I) followed by a weaker binding to the external framework between the holes (site II) until a monolayer of 1 is formed. From both computational and surface area measurements, it is estimated that the site I holes on the external surface will be filled at ca. 0.3-0.5 wt %/wt loading of 1/LZ-105, which corresponds to 6.5 x 10(18) (ca. 10(-)(5) mol) of holes or molecules of 1 adsorbed in holes per gram of zeolite. The supramolecular composition of ca. 0.3-0.5% of 1 on LZ-105 characterizes a "break point" for the photochemistry and the EPR measurements, since it represents the value for saturation of the site I holes with 1. These conclusions are supported quantitatively by experimental isotherms of the adsorption of 1 on LZ-105. Photolysis of 1 intercalated in the site I holes causes fragmentation into two isomeric supramolecular diphenylmethyl (DPM) radicals, one (DMP)(in) which is adsorbed into the internal surface and becomes strongly persistent (half-life of many weeks) and the other (DMP)(ex) which diffuses on the external surface and rapidly dimerizes (less than a few minutes) to produce the radical-radical combination product tetraphenylethane (2). Photolysis of 1 adsorbed on the solid external surface produces two supramolecularly equivalent DPM radicals (DMP)(ex) that diffuse on the external surface and rapidly dimerize to produce 2, and do not produce persistent DPM radicals.

Journal Article↗

PubMed2000

Regulation of double-strand break-induced mammalian homologous recombination by UBL1, a RAD51-interacting protein.

Mammalian RAD51 protein plays essential roles in DNA homologous recombination, DNA repair and cell proliferation. RAD51 activities are regulated by its associated proteins. It was previously reported that a ubiquitin-like protein, UBL1, associates with RAD51 in the yeast two-hybrid system. One function of UBL1 is to covalently conjugate with target proteins and thus modify their function. In the present study we found that non-conjugated UBL1 forms a complex with RAD51 and RAD52 proteins in human cells. Overexpression of UBL1 down-regulates DNA double-strand break-induced homologous recombination in CHO cells and reduces cellular resistance to ionizing radiation in HT1080 cells. With or without overexpressed UBL1, most homologous recombination products arise by gene conversion. However, overexpression of UBL1 reduces the fraction of bidirectional gene conversion tracts. Overexpression of a mutant UBL1 that is incapable of being conjugated retains the ability to inhibit homologous recombination. These results suggest a regulatory role for UBL1 in homologous recombination.

Animals↗

PubMed2000

Regulation of Jak2 tyrosine kinase by protein kinase C during macrophage differentiation of IL-3-dependent myeloid progenitor cells.

Differentiation of macrophages from myeloid progenitor cells depends on a discrete balance between cell growth, survival, and differentiation signals. Interleukin-3 (IL-3) supports the growth and survival of myeloid progenitor cells through the activation of Jak2 tyrosine kinase, and macrophage differentiation has been shown to be regulated by protein kinase C (PKC). During terminal differentiation of macrophages, the cells lose their mitogenic response to IL-3 and undergo growth arrest, but the underlying signaling mechanisms have remained elusive. Here we show that in IL-3-dependent 32D myeloid progenitor cells, the differentiation-inducing PKC isoforms PKC-alpha and PKC-delta specifically caused rapid inhibition of IL-3-induced tyrosine phosphorylation. The target for this inhibition was Jak2, and the activation of PKC by 12-O-tetradecanoyl-phorbol-13-acetate treatment also abrogated IL-3-induced tyrosine phosphorylation of Jak2 in Ba/F3 cells. The mechanism of this regulation was investigated in 32D and COS7 cells, and the inhibition of Jak2 required catalytic activity of PKC-delta and involved the phosphorylation of Jak2 on serine and threonine residues by the associated PKC-delta. Furthermore, PKC-delta inhibited the in vitro catalytic activity of Jak2, indicating that Jak2 was a direct target for PKC-delta. In 32D cells, the inhibition of Jak2 either by PKC-delta, tyrosine kinase inhibitor AG490, or IL-3 deprivation caused a similar growth arrest. Reversal of PKC-delta-mediated inhibition by the overexpression of Jak2 promoted apoptosis in differentiating 32D cells. These results demonstrate a PKC-mediated negative regulatory mechanism of cytokine signaling and Jak2, and they suggest that it serves to integrate growth-promoting and differentiation signals during macrophage differentiation. (Blood. 2000;95:1626-1632)

Animals↗

PubMed2000

Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis.

Induction of wild-type p53 in mouse fibroblasts causes cell cycle arrest at the G(1) phase, whereas coexpression of p53 and the protooncogene c-myc induces apoptosis. Although p53 transcriptional activity generally is required for both pathways, the molecular components mediating p53-dependent apoptosis are not well understood. To identify factors that could mediate p53-induced cell death, we used a comparative RNA differential display procedure. We have identified Pw1/Peg3 as a gene product induced during p53/c-myc-mediated apoptosis. Pw1/Peg3 is not induced during p53-mediated G(1) growth arrest nor by c-myc alone. Although it is not clear whether the induction of Pw1/Peg3 depends on p53 activity, we show that Pw1/Peg3 interacts with a p53-inducible gene product Siah1a. We demonstrate that coexpression of Pw1/Peg3 with Siah1a induces apoptosis independently of p53 whereas expression of Pw1/Peg3 or Siah1a separately has no effect on cell death. These data suggest that Siah1a and Pw1/Peg3 cooperate in the p53-mediated cell death pathway. Furthermore, we show that inhibiting Pw1/Peg3 activity blocks p53-induced apoptosis. The observation that Pw1/Peg3 is necessary for the p53 apoptotic response suggests a pivotal role for this gene in determining cell death versus survival.

3T3 Cells↗

PubMed2000

mag-1, a homolog of Drosophila mago nashi, regulates hermaphrodite germ-line sex determination in Caenorhabditis elegans.

The Caenorhabditis elegans gene mag-1 can substitute functionally for its homolog mago nashi in Drosophila and is predicted to encode a protein that exhibits 80% identity and 88% similarity to Mago nashi (P. A. Newmark et al., 1997, Development 120, 3197-3207). We have used RNA-mediated interference (RNAi) to analyze the phenotypic consequences of impairing mag-1 function in C. elegans. We show here that mag-1(RNAi) causes masculinization of the germ line (Mog phenotype) in RNA-injected hermaphrodites, suggesting that mag-1 is involved in hermaphrodite germ-line sex determination. Epistasis analysis shows that ectopic sperm production caused by mag-1(RNAi) is prevented by loss-of-function (lf) mutations in fog-2, gld-1, fem-1, fem-2, fem-3, and fog-1, all of which cause germ-line feminization in XX hermaphrodites, but not by a her-1(lf) mutation which causes germ-line feminization only in XO males. These results suggest that mag-1 interacts with the fog, fem, and gld genes and acts independently of her-1. We propose that mag-1 normally allows oogenesis by inhibiting function of one or more of these masculinizing genes, which act during the fourth larval stage to promote transient sperm production in the hermaphrodite germ line. When the Mog phenotype is suppressed by a fog-2(lf) mutation, mag-1(RNAi) also causes lethality in the progeny embryos of RNA-injected, mated hermaphrodites, suggesting an essential role for mag-1 during embryogenesis. The defective embryos arrest during morphogenesis with an apparent elongation defect. The distribution pattern of a JAM-1::GFP reporter, which is localized to boundaries of hypodermal cells, shows that hypodermis is disorganized in these embryos. The temporal expression pattern of the mag-1 gene prior to and during morphogenesis appears to be consistent with an essential role of mag-1 in embryonic hypodermal organization and elongation.

Animals↗

PubMed2000

rtPA intravenous thrombolysis in anterior choroidal artery territory stroke.

OBJECTIVE: To study the possible specific response to recombinant tissue plasminogen activator (rtPA) thrombolysis of anterior choroidal artery (AChA) stroke. BACKGROUND: Outcome and response after rtPA thrombolysis are possibly better in small-vessel infarcts, but a specific study of AChA stroke has not yet been performed. METHODS: The authors proposed an open trial of IV rtPA within 7 hours in patients age 20 and 81 years with all types of internal carotid artery territory stroke if the baseline Scandinavian Stroke Scale (SSS) score was less than 48. A dose of rtPA 0.8 mg/kg was infused over 90 minutes. Of 114 consecutive patients, 9 patients (7.9%) exhibited hypodensity in the AChA territory on day 1 brain CT. RESULTS: Seven of nine patients with AChA infarct had a primary early recovery within 6 hours after the initiation of rtPA infusion. In addition, recovery was complete in five patients and partial in two patients. No intracerebral hematoma was observed. Three patients had a "reinfarct syndrome" at 12, 25, and 48 hours respectively. However, in the two latter patients treated with IV heparin, the deficit disappeared again with the increase of heparin dose in one patient and disappeared spontaneously in the other patient. The overall outcome at day 90 was six total recoveries in nine patients (66%). Patients with a final good outcome had a slight "unstructured" hypodensity in the AChA territory on day 1 brain CT, whereas patients with a bad outcome had the classic "structured" hypodensity of AChA territory stroke. CONCLUSION: These data support a specific quick response of AChA territory stroke to IV rtPA thrombolysis, probably due to the small size of the artery and of the "clot." The high frequency of the reinfarct syndrome is a clinical fact that is difficult to explain. Efficient heparin treatment after 24 hours may control the reinfarct syndrome in some patients.

Aged↗

PubMed2000

Bcl-w expression is increased in brain regions affected by focal cerebral ischemia in the rat.

Proteins of the bcl-2 family are important regulators of apoptosis in many tissues of the embryo and adult and may play a role in cell death following stroke. The recently isolated bcl-w gene encodes a pro-survival member of the bcl-2 family, which is widely expressed. However, it is not known whether bcl-w plays a role in determining cell survival after cerebral ischemia. Using Western blot analysis and immunocytochemistry, regional bcl-w protein expression was studied in rat brain 2, 6, 24 and 72 h following 20 min temporary middle cerebral artery occlusion (MCAO). Focal cerebral ischemia increased bcl-w protein expression within the caudate putamen and parietal cortex, as well as causing milder increases within frontal cortex. Immunocytochemically bcl-w was expressed within neurons (frontal and parietal cortex) and glia (caudate putamen) 24 h after MCAO. These data suggest that bcl-w could play a role in determining cell survival after cerebral ischemia.

Animals↗

PubMed2000

Large-scale complementary integrated circuits based on organic transistors

Thin-film transistors based on molecular and polymeric organic materials have been proposed for a number of applications, such as displays and radio-frequency identification tags. The main factors motivating investigations of organic transistors are their lower cost and simpler packaging, relative to conventional inorganic electronics, and their compatibility with flexible substrates. In most digital circuitry, minimal power dissipation and stability of performance against transistor parameter variations are crucial. In silicon-based microelectronics, these are achieved through the use of complementary logic-which incorporates both p- and n-type transistors-and it is therefore reasonable to suppose that adoption of such an approach with organic semiconductors will similarly result in reduced power dissipation, improved noise margins and greater operational stability. Complementary inverters and ring oscillators have already been reported. Here we show that such an approach can realize much larger scales of integration (in the present case, up to 864 transistors per circuit) and operation speeds of approximately 1 kHz in clocked sequential complementary circuits.

Journal Article↗