scholarly journals Hit and run versus long-term activation of PARP-1 by its different domains fine-tunes nuclear processes

2019 ◽  
Vol 116 (20) ◽  
pp. 9941-9946 ◽  
Author(s):  
Colin Thomas ◽  
Yingbiao Ji ◽  
Chao Wu ◽  
Haily Datz ◽  
Cody Boyle ◽  
...  
Keyword(s):  
Specific Binding ◽  
Histone H4 ◽  
Short Term ◽  
Terminal Domain ◽  
Specific Binding Sites ◽  
Hit And Run ◽  
Nuclear Processes ◽  
Parp 1 ◽  
Continuous Accumulation

Poly(ADP-ribose) polymerase 1 (PARP-1) is a multidomain multifunctional nuclear enzyme involved in the regulation of the chromatin structure and transcription. PARP-1 consists of three functional domains: the N-terminal DNA-binding domain (DBD) containing three zinc fingers, the automodification domain (A), and the C-terminal domain, which includes the protein interacting WGR domain (W) and the catalytic (Cat) subdomain responsible for the poly(ADP ribosyl)ating reaction. The mechanisms coordinating the functions of these domains and determining the positioning of PARP-1 in chromatin remain unknown. Using multiple deletional isoforms of PARP-1, lacking one or another of its three domains, as well as consisting of only one of those domains, we demonstrate that different functions of PARP-1 are coordinated by interactions among these domains and their targets. Interaction between the DBD and damaged DNA leads to a short-term binding and activation of PARP-1. This “hit and run” activation of PARP-1 initiates the DNA repair pathway at a specific point. The long-term chromatin loosening required to sustain transcription takes place when the C-terminal domain of PARP-1 binds to chromatin by interacting with histone H4 in the nucleosome. This long-term activation of PARP-1 results in a continuous accumulation of pADPr, which maintains chromatin in the loosened state around a certain locus so that the transcription machinery has continuous access to DNA. Cooperation between the DBD and C-terminal domain occurs in response to heat shock (HS), allowing PARP-1 to scan chromatin for specific binding sites.

Effects of pH Changes on Zinc Uptake by Chlamydomonas variabilis Grown in Batch Culture

1986 ◽  
Vol 43 (3) ◽  
pp. 687-693 ◽  
Author(s):  
Gail I. Harrison ◽  
Peter G. C. Campbell ◽  
André Tessier
Keyword(s):  
Specific Binding ◽  
Physiological State ◽  
Growth Conditions ◽  
Growth Stages ◽  
Short Term ◽  
Ph Changes ◽  
Specific Binding Sites ◽  
Zn Concentration ◽  
Effects Of Ph ◽  
Ph Range

The effects of changes in H+ activity on the adsorption and intracellular accumulation of Zn by Chlamydomonas variabilis Dangeard have been studied over the pH range 7–5. Other experimental variables included the dissolved free Zn concentration, [Zn2+]b, the antecedent growth conditions (pH of the growth medium = 7, 6, or 5), and the physiological state of the harvested cells. After short-term incubations with 65Zn, algal cells were collected and the concentrations of EDTA-extractable Zn ([Zn]a ~ surface-bound Zn) and nonextractable Zn ([Zn]c ~ transported Zn) were determined. Values for [Zn]a and the flux (F) of Zn across the cell membrane decreased with increasing culture age, but cells harvested at comparable growth stages behaved similarly in the subsequent short-term incubations with Zn, irrespective of their original growth pH. In the incubation solutions, however, pH changes did affect both [Zn]a and F. At constant [Zn2+]b, a decrease in pH from 7 to 5 led to lower values of [Zn]a (~70%), suggesting either a pH-induced change in algal surface potential or a competition between H+ and Zn2+ for specific binding sites at the cell surface; a concomitant decrease in Zn flux (50–65%) was noted. The decrease in pH from 7 to 5 also had the effect of minimizing the dependence of Zn flux on the Zn2+ concentration. Two Zn transport mechanisms may coexist in C. variabilis cells, one involving a diffusion pathway sensitive to pH changes in the range 7–5 and the other a high-affinity porter system operative at both pH 7 and pH 5. These results suggest that the net effect of lake acidification may well be a decrease in the overall bioavailability of Zn to algae.

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 710-727
Author(s):  
Beula M. Magimairaj ◽  
Naveen K. Nagaraj ◽  
Alexander V. Sergeev ◽  
Natalie J. Benafield
Keyword(s):  
Auditory Processing ◽  
Short Term Memory ◽  
Group Differences ◽  
Long Term Memory ◽  
Short Term ◽  
Significant Group ◽  
Term Memory ◽  
Memory And Attention ◽  
Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

Abstract #283 Diabetes Increases Short-Term but not Long-Term Risk of Fracture: A Community-Based Study

2019 ◽  
Vol 25 ◽  
pp. 114
Author(s):  
Alyssa Dufour ◽  
Setareh Williams ◽  
Richard Weiss ◽  
Elizabeth Samelson
Keyword(s):  
Short Term ◽  
Community Based ◽  
Risk Of Fracture

Abstract #238: Improved Short Term and Long Term Outcomes of Early Insulin Initiation in Type 2 Diabetes Over 10 Years

2017 ◽  
Vol 23 ◽  
pp. 50
Author(s):  
Jothydev Kesavadev ◽  
Shashank Joshi ◽  
Banshi Saboo ◽  
Hemant Thacker ◽  
Arun Shankar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Initiation ◽  
Long Term Outcomes ◽  
Short Term

Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽  
2019 ◽  
Vol 48 (4) ◽  
pp. 321-329
Author(s):  
Mariya Kronlage ◽  
Erwin Blessing ◽  
Oliver J. Müller ◽  
Britta Heilmeier ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Limb Ischemia ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Short Term ◽  
Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

Intraindividual Variability and Stability of Affect and Well-Being

GeroPsych ◽  
2013 ◽  
Vol 26 (3) ◽  
pp. 185-199 ◽  
Author(s):  
Christina Röcke ◽  
Annette Brose
Keyword(s):  
Age Differences ◽  
Well Being ◽  
Subjective Well Being ◽  
Emotional Experiences ◽  
Short Term ◽  
Regulatory Processes ◽  
Functional Implications ◽  
Methodological Approaches ◽  
Underlying Processes

Whereas subjective well-being remains relatively stable across adulthood, emotional experiences show remarkable short-term variability, with younger and older adults differing in both amount and correlates. Repeatedly assessed affect data captures both the dynamics and stability as well as stabilization that may indicate emotion-regulatory processes. The article reviews (1) research approaches to intraindividual affect variability, (2) functional implications of affect variability, and (3) age differences in affect variability. Based on this review, we discuss how the broader literature on emotional aging can be better integrated with theories and concepts of intraindividual affect variability by using appropriate methodological approaches. Finally, we show how a better understanding of affect variability and its underlying processes could contribute to the long-term stabilization of well-being in old age.

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