The role of the response–outcome association in the nature of inhibitory Pavlovian-instrumental transfer in rats

2020 ◽  
pp. 174702182096304
Author(s):  
Lindsay J Kemp ◽  
Laura H Corbit
Keyword(s):  
Specific Effect ◽  
Choice Test ◽  
Training Phase ◽  
Inhibitory Effects ◽  
Multiple Outcomes ◽  
Reward Seeking ◽  
Specific Manner ◽  
Single Response ◽  
Feature Negative

Inhibitory stimuli can reduce animals’ reward seeking in an outcome-specific manner or outcome-general manner. However, we do not understand the factors that determine which of these effects are produced. To address this, we carried out three experiments which examined whether instrumental training with one or multiple outcomes determined the nature of subsequently observed Pavlovian-instrumental transfer (PIT). Rats underwent Pavlovian training to produce inhibitors and excitors for two outcomes using a feature-negative procedure. In Experiment 1, these stimuli were tested for their effects on a single response trained with one of those outcomes in a PIT procedure. Here, stimuli trained as inhibitors and excitors were found to produce outcome-general effects on reward seeking (in addition to an outcome-specific effect for excitors). In Experiment 2, we trained two responses, one for each of the Pavlovian outcomes, and tested the effect of the stimuli on each response individually. This design also produced outcome-general inhibitory and excitatory PIT effects. Experiment 3 followed the procedure of Experiment 2, except for implementation of a shorter Pavlovian training phase and an additional choice test, where both responses were concurrently available. This procedure produced putative inhibitory effects that were also outcome-general. However, outcome-specific excitatory effects were observed, indicating that the general inhibitory results may not be attributable to the duration of Pavlovian training. Overall, this study suggests that variations in the number of response–outcome contingencies experienced by animals do not readily determine the specificity of putative inhibitors.

scholarly journals Berry-Derived Polyphenols in Cardiovascular Pathologies: Mechanisms of Disease and the Role of Diet and Sex

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 387
Author(s):  
Rami S. Najjar ◽  
Casey G. Turner ◽  
Brett J. Wong ◽  
Rafaela G. Feresin
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Vascular Remodeling ◽  
Specific Effect ◽  
Biological Sex ◽  
Treatment And Prevention ◽  
Specific Manner ◽  
Cardiovascular Pathologies ◽  
Polyphenolic Profile

Cardiovascular disease (CVD) prevalence, pathogenesis, and manifestation is differentially influenced by biological sex. Berry polyphenols target several signaling pathways pertinent to CVD development, including inflammation, oxidative stress, and cardiac and vascular remodeling, and there are innate differences in these pathways that also vary by sex. There is limited research systematically investigating sex differences in berry polyphenol effects on these pathways, but there are fundamental findings at this time that suggest a sex-specific effect. This review will detail mechanisms within these pathological pathways, how they differ by sex, and how they may be individually targeted by berry polyphenols in a sex-specific manner. Because of the substantial polyphenolic profile of berries, berry consumption represents a promising interventional tool in the treatment and prevention of CVD in both sexes, but the mechanisms in which they function within each sex may vary.

scholarly journals A Role for Histone H2B During Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1375-1387
Author(s):  
Emmanuelle M D Martini ◽  
Scott Keeney ◽  
Mary Ann Osley
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Chromatin Structure ◽  
Specific Effect ◽  
Cell Killing ◽  
Cyclobutane Pyrimidine Dimers ◽  
Histone H2b ◽  
Uv Sensitivity ◽  
Pyrimidine Dimers

Abstract To investigate the role of the nucleosome during repair of DNA damage in yeast, we screened for histone H2B mutants that were sensitive to UV irradiation. We have isolated a new mutant, htb1-3, that shows preferential sensitivity to UV-C. There is no detectable difference in bulk chromatin structure or in the number of UV-induced cis-syn cyclobutane pyrimidine dimers (CPD) between HTB1 and htb1-3 strains. These results suggest a specific effect of this histone H2B mutation in UV-induced DNA repair processes rather than a global effect on chromatin structure. We analyzed the UV sensitivity of double mutants that contained the htb1-3 mutation and mutations in genes from each of the three epistasis groups of RAD genes. The htb1-3 mutation enhanced UV-induced cell killing in rad1Δ and rad52Δ mutants but not in rad6Δ or rad18Δ mutants, which are defective in postreplicational DNA repair (PRR). When combined with other mutations that affect PRR, the histone mutation increased the UV sensitivity of strains with defects in either the error-prone (rev1Δ) or error-free (rad30Δ) branches of PRR, but did not enhance the UV sensitivity of a strain with a rad5Δ mutation. When combined with a ubc13Δ mutation, which is also epistatic with rad5Δ, the htb1-3 mutation enhanced UV-induced cell killing. These results suggest that histone H2B acts in a novel RAD5-dependent branch of PRR.

scholarly journals An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Thao Thi Thanh Nguyen ◽  
Masato Shingyoji ◽  
Michiko Hanazono ◽  
Boya Zhong ◽  
Takao Morinaga ◽  
...  
Keyword(s):  
Wild Type ◽  
Inhibitory Effects ◽  
Cytotoxic Effects ◽  
P53 Expression ◽  
Nuclear Factor I ◽  
Infected Cells ◽  
Wild Type P53 ◽  
Mdm2 Inhibitor ◽  
P16 Expression

AbstractA majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.

scholarly journals Seed Gamma Irradiation of Arabidopsis thaliana ABA-Mutant Lines Alters Germination and Does Not Inhibit the Photosynthetic Efficiency of Juvenile Plants

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582097924
Author(s):  
Darya Babina ◽  
Marina Podobed ◽  
Ekaterina Bondarenko ◽  
Elizaveta Kazakova ◽  
Sofia Bitarishvili ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Growth Response ◽  
Dose Range ◽  
Fine Tuning ◽  
Plant Tolerance ◽  
Inhibitory Effects ◽  
Γ Irradiation ◽  
Photosynthetic Responses ◽  
Mutant Lines

Plant growth response to γ-irradiation includes stimulating or inhibitory effects depending on plant species, dose applied, stage of ontogeny and other factors. Previous studies showed that responses to irradiation could depend on ABA accumulation and signaling. To elucidate the role of ABA in growth and photosynthetic responses to irradiation, lines Col-8, abi3-8 and aba3 -1 of Arabidopsis thaliana were used. Seeds were γ-irradiated using 60Co in the dose range 50-150 Gy. It was revealed that the dose of 150 Gy affected germination parameters of aba3 -1 and Col-8 lines, while abi3-8 line was the most resistant to the studied doses and even showed faster germination at early hours after γ-irradiation at 50 Gy. These results suggest that susceptibility to ABA is probably more important for growth response to γ-irradiation than ABA synthesis. The photosynthetic functioning of 16-day-old plants mainly was not disturbed by γ-irradiation of seeds, and no indication of photosystem II photoinhibition was noticed, revealing the robustness of the photosynthetic system of A. thaliana. Glutathione peroxidase activity and ABA concentrations in plant tissues were not affected in the studied dose range. These results contribute to the understanding of germination and photosynthesis fine-tuning and of mechanisms of plant tolerance to ionizing radiation.

scholarly journals Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 493
Author(s):  
 Chung-Yu Chen ◽  
Chien-Rung Chen ◽  
Chiao-Nan Chen ◽  
Paulus S. Wang ◽  
Toby Mündel ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Prostaglandin F2α ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Steroidogenic Enzyme ◽  
Estradiol Secretion ◽  
Basal Release ◽  
Ca2 Channels

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females.

scholarly journals Group size and aquatic vegetation modulates male preferences for female shoals in wild zebrafish, Danio rerio

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aditya Ghoshal ◽  
Anuradha Bhat
Keyword(s):  
Group Size ◽  
Aquatic Vegetation ◽  
Natural Habitat ◽  
Ecological Factors ◽  
Choice Test ◽  
Female Group ◽  
Aquatic Flora ◽  
In The Wild ◽  
The Individual

AbstractShoaling decisions in the wild are determined by a combination of innate preferences of the individual along with the interplay of multiple ecological factors. In their natural habitat as well as in the laboratory, zebrafish is a shoaling fish. Here, we investigate the role of group size and associated vegetation in shaping shoaling preferences of wild male zebrafish. We studied the association preference of males to groups of female shoals in a multi-choice test design. We found that males made greater proportion of visits to an 8-female group compared to 2 and 4-female groups. However, males spent similar proportions of time across the three female-containing groups. When artificial vegetation was incorporated along with female number as an additional factor, we found that males prefer high and moderately vegetated patches compared to low or no-vegetation groups, irrespective of the number of females in these patches. Based on experiments using a novel multi-choice design, our results show that preference for group size can change due to interaction of two separate factors. This work is a first attempt to understand the role of aquatic flora in determining shoaling preferences in zebrafish, using an experimental paradigm consisting of a gradation in female and vegetation densities.

scholarly journals Role of DegQ in differential stability of flagellin subunits in Vibrio vulnificus

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
You-Chul Jung ◽  
Mi-Ae Lee ◽  
Han-Shin Kim ◽  
Kyu-Ho Lee
Keyword(s):  
Life Cycle ◽  
Biofilm Formation ◽  
Vibrio Vulnificus ◽  
Differential Regulation ◽  
Specific Manner ◽  
Associated Proteins ◽  
Differential Stability ◽  
Methionine Residues

AbstractBiofilm formation of Vibrio vulnificus is initiated by adherence of flagellated cells to surfaces, and then flagellum-driven motility is not necessary during biofilm maturation. Once matured biofilms are constructed, cells become flagellated and swim to disperse from biofilms. As a consequence, timely regulations of the flagellar components’ expression are crucial to complete a biofilm life-cycle. In this study, we demonstrated that flagellins’ production is regulated in a biofilm stage-specific manner, via activities of a protease DegQ and a chaperone FlaJ. Among four flagellin subunits for V. vulnificus filament, FlaC had the highest affinities to hook-associated proteins, and is critical for maturating flagellum, showed the least susceptibility to DegQ due to the presence of methionine residues in its DegQ-sensitive domains, ND1 and CD0. Therefore, differential regulation by DegQ and FlaJ controls the cytoplasmic stability of flagellins, which further determines the motility-dependent, stage-specific development of biofilms.

scholarly journals Inhibitory effects of Yangzheng Xiaoji on angiogenesis and the role of the focal adhesion kinase pathway

2012 ◽  
Vol 41 (5) ◽  
pp. 1635-1642 ◽  
Author(s):  
WEN G. JIANG ◽  
LIN YE ◽  
KE JI ◽  
NATASHA FREWER ◽  
JIAFU JI ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Inhibitory Effects ◽  
Kinase Pathway

scholarly journals Az ösztrogénmetabolom biológiai és klinikai jelentősége lokális folyamatokban

2017 ◽  
Vol 158 (24) ◽  
pp. 929-937
Author(s):  
Krisztián Kovács ◽  
Barna Vásárhelyi ◽  
Katalin Mészáros ◽  
Attila Patócs ◽  
Gellért Karvaly
Keyword(s):  
Biological Activity ◽  
Clinical Significance ◽  
Physiological Role ◽  
Tissue Homeostasis ◽  
Diagnostic Significance ◽  
Peripheral Tissues ◽  
Breakdown Process ◽  
Specific Manner ◽  
Related Compounds

Abstract: Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929–937.

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