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Activity Leads (activity + lead)

Distribution by Scientific Domains

Life Sciences	45%
Medical Sciences	36%

Selected Abstracts

Spontaneous electrical activity and dendritic spine size in mature cerebellar Purkinje cells

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005
Robin J. Harvey
Abstract Previous experiments have shown that in the mature cerebellum both blocking of spontaneous electrical activity and destruction of the climbing fibres by a lesion of the inferior olive have a similar profound effect on the spine distribution on the proximal dendrites of the Purkinje cells. Many new spines develop that are largely innervated by parallel fibers. Here we show that blocking electrical activity leads to a significant decrease in size of the spines on the branchlets. We have also compared the size of the spines of the proximal dendritic domain that appear during activity block and after an inferior olive lesion. In this region also, the spines in the absence of activity are significantly smaller. In the proximal dendritic domain, the new spines that develop in the absence of activity are innervated by parallel fibers and are not significantly different in size from those of the branchlets, although they are shorter. Thus, the spontaneous activity of the cerebellar cortex is necessary not only to maintain the physiological spine distribution profile in the Purkinje cell dendritic tree, but also acts as a signal that prevents spines from shrinking. [source]

Aggresome formation by anti-Ras intracellular scFv fragments

FEBS JOURNAL, Issue 2 2001
The fate of the antigen, antibody complex
Diverting the antigen from its normal intracellular location to other compartments in an antibody-mediated way represents a mode of action for intracellular antibodies [Cardinale, A., Lener, M., Messina, S., Cattaneo, A. & Biocca, S. (1998) FEBS Lett.,439, 197,202; Lener, M., Horn, I.R., Cardinale, A., Messina, S., Nielsen, U.B., Rybak, S.M., Hoogenboom, H.R., Cattaneo, A. & Biocca, S. (2000) Eur J Biochem.267, 1196,205]. In the case of p21Ras, the sequestration of the antigen in aggregated structures in the cytoplasm of transfected cells leads to the inhibition of its biological function. We have further investigated the intracellular fate of the antigen,antibody complex by analyzing the effect of proteasome inhibitors on the formation and the intracellular localization of the aggregates. Overexpression of anti-Ras scFv fragments or inhibition of proteasomes activity leads to the formation of large perinuclear aggresomes formed of ubiquitinated-scFv fragments in which p21Ras is sequestered and degraded in an antibody-mediated way. Disruption of microtubules by nocodazole completely abrogates the accumulation of scFv fragments in a single aggresome and induces the dispersion of these structures in the periphery of the cell. Cotransfection of the GFP-scFv with a myc-tagged ubiquitin and colocalization with specific anti-proteasome antibodies indicate the recruitment of exogenous ubiquitin and proteasomes to the newly formed aggresomes. Taken together these results suggest that the intracellular antigen,antibody complex is naturally addressed to the ubiquitin,proteasome pathway and that the mechanism of ubiquitination does not inhibit the antibody binding properties and the capacity to block the antigen function. [source]

New tricks of an old molecule: lifespan regulation by p53

AGING CELL, Issue 5 2006
Johannes H. Bauer
Summary As guardian of the genome the tumor suppressor p53 controls a crucial point in protection from cellular damage and response to stressors. Activation of p53 can have beneficial (DNA repair) or detrimental (apoptosis) consequences for individual cells. In either case activation of p53 is thought to safeguard the organism at large from the deleterious effects of various stresses. Recent data suggest that the function of p53 might also play a role in the regulation of organismal lifespan. Increased p53 activity leads to lifespan shortening in mice, while apparent reduction of p53 activity in flies leads to lifespan extension. Although the mechanism by which p53 regulates lifespan remains to be determined, these findings highlight the possibility that careful manipulation of p53 activity during adult life may result in beneficial effects on healthy lifespan. [source]

Extensive phage dynamics in Staphylococcus aureus contributes to adaptation to the human host during infection

MOLECULAR MICROBIOLOGY, Issue 6 2006
Christiane Goerke
Summary Bacteriophages serve as a driving force in microbial evolution, adaptation to new environments and the pathogenesis of human bacterial infections. In Staphylococcus aureus phages encoding immune evasion molecules (SAK, SCIN, CHIPS), which integrate specifically into the ,-haemolysin (Hlb) gene, are widely distributed. When comparing S. aureus strain collections from infectious and colonizing situations we could detect a translocation of sak -encoding phages to atypical genomic integration sites in the bacterium only in the disease-related isolates. Additionally, significantly more Hlb producing strains were detected in the infectious strain collection. Extensive phage dynamics (intragenomic translocation, duplication, transfer between hosts, recombination events) during infection was shown by analysing cocolonizing and consecutive isolates of patients. This activity leads to the splitting of the strain population into various subfractions exhibiting different virulence potentials (Hlb-production and/or production of immune evasion molecules). Thus, phage-inducing conditions and strong selection for survival of the bacterial host after phage movement are typical for the infectious situation. Further in vitro characterization of phages revealed that: (i) SAK is encoded not only on serogroup F phages showing a conserved tropism for hlb but also on serogroup B phages which always integrate in a distinct intergenic region, (ii) the level of sak transcription correlates to phage inducibility but is independent of the phage localization in the chromosome, and (iii) phages can be stabilized extra-chromosomally during their life cycle. [source]

Tobacco Mg protoporphyrin IX methyltransferase is involved in inverse activation of Mg porphyrin and protoheme synthesis

THE PLANT JOURNAL, Issue 2 2005
Ali E. Alawady
Summary Protoporphyrin, a metabolic intermediate of tetrapyrrole biosynthesis, is metabolized by Mg chelatase and ferrochelatase and is directed into the Mg-branch for chlorophyll synthesis and in the Fe-branch for protoheme synthesis respectively. Regulation of the enzyme activities at the beginning of this branchpoint ensures accurate partition of protoporphyrin, but is still not entirely understood. Transgenic tobacco plants were generated that express antisense or sense RNA for inhibited and excessive expression of Mg protoporphyrin methyltransferase (MgPMT) respectively. This enzyme accepts Mg protoporphyrin from Mg chelatase and catalyses the transfer of a methyl group to the carboxyl group of the C13-propionate side chain. Low MgPMT activity is correlated with reduced Mg chelatase activity and a low synthesis rate of 5-aminolevulinate, but with enhanced ferrochelatase activity. In contrast, high MgPMT activity leads to inverse activity profiles: high activities of Mg chelatase and for 5-aminolevulinate synthesis, but reduced activity of ferrochelatase, indicating a direct influence of MgPMT in combination with Mg chelatase on the metabolic flux of ALA and the distribution of protoporphyrin into the branched pathway. The modified enzyme activities in tetrapyrrole biosynthesis in the transgenic plants can be explained with changes of certain corresponding mRNA contents: increased 5-aminolevulinate synthesis and Mg chelatase activity correlate with enhanced transcript levels of the HemA, Gsa, and CHLH gene encoding glutamyl-tRNA reductase, glutamate-1-semialdehyde aminotransferase and a Mg chelatase subunit respectively. It is proposed that reduced and increased MgPMT activity in chloroplasts is communicated to the cytoplasm for modulating transcriptional activities of regulatory enzymes of the pathway. [source]

Severe gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase

ARTHRITIS & RHEUMATISM, Issue 7 2009
Hang-Korng Ea
A deficiency in hypoxanthine guanine phosphoribosyltransferase (HPRT) activity leads to overproduction of uric acid. According to the degree of enzymatic deficiency, a large spectrum of neurologic features can also be observed, ranging from mild or no neurologic involvement to complete Lesch-Nyhan disease. Herein, we describe a patient with hyperuricemia, juvenile-onset gouty arthritis, nephrolithiasis, and mild neurologic symptoms, attributed to a newly identified variant of the hprt gene, c.596T>G, resulting in the amino acid change p.F199C. Residual HPRT activity (8%) protected against severe neurologic involvement in this patient. Modeling of the mutated protein was used to predict the mechanisms that led to partial enzymatic activity. Careful neurologic examination is warranted in juvenile and middle-aged patients with gout, in order to detect mild symptoms that may lead to a diagnosis of HPRT deficiency. [source]

Risk factors for damage in childhood-onset systemic lupus erythematosus: Cumulative disease activity and medication use predict disease damage

ARTHRITIS & RHEUMATISM, Issue 2 2002
Hermine I. Brunner
Objective The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index measures damage in adult patients with systemic lupus erythematosus (SLE), but its usefulness in patients with childhood-onset SLE has not been examined. This study was conducted to evaluate the sensibility of the SLICC/ACR Damage Index, to investigate how cumulative disease activity is related to damage in childhood-onset SLE, and to identify other risk factors for damage in childhood-onset SLE. Methods Disease activity and damage in 66 patients with newly diagnosed childhood-onset SLE were assessed retrospectively, and information on potential risk factors for damage (age, race, sex, medications, duration of disease, hypertension, body mass index, antiphospholipid antibodies, kidney disease, acute thrombocytopenia) was obtained. In addition, a group of physicians was surveyed to establish the sensibility of the SLICC/ACR Damage Index in childhood-onset SLE. Results The SLICC/ACR Damage Index was found to have face, content, and construct validity when used in children. The mean SLICC/ACR Damage Index score of the patients was 1.76 (mean followup 3.3 years). Cumulative disease activity over time was the single best predictor of damage (R2 = 0.30). Other, possibly important risk factors for damage were corticosteroid treatment, the presence of antiphospholipid antibodies, and acute thrombocytopenia. It was determined that immunosuppressive agents may be protective. Conclusion The SLICC/ACR Damage Index, though useful in childhood-onset SLE, may benefit from the introduction of weightings and redefinition of some of the items. Ongoing disease activity leads to disease damage, and treatment should be prompt. Prolonged use of high-dose corticosteroids may further increase damage, but use of immunosuppressive agents may protect against disease damage; this latter finding may have potential implications for the treatment of childhood-onset SLE and deserves further study. The relationship between disease activity and concomitant use of medication also requires further investigation. [source]

The Impact of Day-Trading on Volatility and Liquidity,

ASIA-PACIFIC JOURNAL OF FINANCIAL STUDIES, Issue 2 2009
Jay M. Chung
Abstract We examine day-trading activities for 540 stocks traded on the Korea Stock Exchange using transactions data for the period from 1999 to 2000. Our cross-sectional analysis reveals that day-traders prefer lower-priced, more liquid, and more volatile stocks. By estimating various bivariate VAR models using minute-by-minute data, we find that greater day-trading activity leads to greater return volatility and that the impact of a day-trading shock dissipates gradually within an hour. Past return volatility also positively affects future day-trading activity. We also find that past day-trading activity negatively affects bid-ask spreads, and past bid-ask spreads negatively affect future day-trading activity. Finally, we find that day-traders use short-term contrarian strategies and their order imbalance affects future returns positively. This result is consistent with a cyclical behavior of day-traders who concentrate their buy or sell trades at the bottom or peak of the short-term price cycles, respectively. [source]

Cross-linked envelopes in nail plate in lamellar ichthyosis

BRITISH JOURNAL OF DERMATOLOGY, Issue 5 2003
R.H. Rice
Summary Background Corneocytes of the nail plate, like those of the stratum corneum, generate cornified envelopes (CEs) of cross-linked protein that can be visualized readily after removal of non-cross-linked protein by detergent extraction. Defective CE formation occurs in epidermal scale and hair in transglutaminase 1 (TGM1)-negative lamellar ichthyosis (LI) and has been proposed as a diagnostic aid for this syndrome. Objectives (i) To ascertain whether TGM1 is important for CE formation in nail; (ii) to characterize CE abnormalities occurring in LI that may be distinguished from other types of inherited ichthyosis when nail samples are subjected to detergent extraction; and (iii) to evaluate the utility of nails as a diagnostic aid for LI. Methods Nail samples were provided by nine patients previously classified as having TGM1-negative LI, four with other types of ichthyotic conditions and six normal controls. Samples were extracted extensively in sodium dodecyl sulphate under reducing conditions and examined by light and electron microscopy. Results After extraction, defective CE cross-linking was visualized in epidermal corneocytes from seven of nine patients exhibiting TGM1-negative LI, whereas nail samples from patients with the other syndromes were normal. The defects in CE structure resembled those recently reported for LI scale, although in some cases residual CE and CE-associated structures were present. Conclusions Despite the paucity of clinical nail symptoms in LI, TGM1 activity is important for generation of normal CE in nail plate, consistent with its importance in protein cross-linking in interfollicular epidermis and hair. Lack of this activity leads to a strikingly aberrant appearance of CE in LI nail after detergent extraction that is evident ultrastructurally in a large majority of cases. Nail envelopes therefore could provide a useful diagnostic tool in distinguishing LI from other ichthyoses with overlapping clinical features. [source]

Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003
Takae Ibuki
We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance. Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol ,l,1 h,1) or saline (IT-S: 1 ,l h,1) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg,1) or saline (IP-S: 3 ml kg,1) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured. Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine+IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine+i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups. For the IT-M+IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment. Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups. The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection. The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance. British Journal of Pharmacology (2003) 138, 689,697. doi:10.1038/sj.bjp.0705102 [source]

Alteration of NF-,B activity leads to mitochondrial apoptosis after infection with pathological prion protein

CELLULAR MICROBIOLOGY, Issue 9 2007
Soizic Bourteele
Summary Nuclear factor kappa B (NF-,B) is a key regulator of the immune response, but in almost the same manner it is involved in induction of inflammation, proliferation and regulation of apoptosis. In the central nervous system activated NF-,B plays a neuroprotective role. While in some neurodegenerative disorders the role of NF-,B is well characterized, there is poor knowledge on the role of NF-,B in prion disease. We found binding but no transcriptional activity of the transcription factor in vitro. Characterizing the mechanism of cell death after infection with pathological prion protein increased caspase-9 and caspase-3 activity was detected and the lack of NF-,B activity resulted in the inability to activate target genes that usually play an important role in neuroprotection. Additionally, we investigated the role of NF-,B after prion infection of Nfkb1,/,, Nfkb2,/, and Bcl3,/, mice and central nervous system-specific p65-deleted mice revealing an accelerated prion disease in NF-,B2- and Bcl-3-deficient mice, which is in line with a reduced neuroprotective activity in prion infection. Based on our findings, we propose a model whereby the alteration of NF-,B activity at the early stages of infection with pathological prion protein leads to neuronal cell death mediated by mitochondrial apoptosis. [source]