| 1. |
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| 2. |
- Baker, Maggie, et al.
(författare)
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Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:44, s. 11769-11774
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Tidskriftsartikel (refereegranskat)abstract
- Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.
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| 3. |
- Fahlke, Claudia, 1964, et al.
(författare)
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Platelet monoamine oxidase activity in a nonhuman primate model of type 2 excessive alcohol consumption
- 2002
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 159, s. 2107-2109
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Low platelet monoamine oxidase (MAO) activity is associated with "type 2 alcoholism." MAO activity is also affected by cigarette smoking. Since most alcoholics are smokers, it is difficult to evaluate the possible effect of platelet MAO activity on alcoholism independently of the effects of smoking, The authors investigated the relationship between platelet MAO activity and excessive alcohol consumption in rhesus macaques. Method: Platelet MAO activity and CSF metabolite concentrations were measured. The authors also investigated level of voluntary alcohol intake and social dominance rank. Results: Subjects with low platelet MAO activity consumed alcohol to excess, had low CSF 5-hydroxyindoleacetic acid concentrations, and were less competent socially. Conclusions: These findings show that nonhuman primates that exhibit type 2-like alcohol features display low platelet MAO activity and support the notion that platelet MAO activity is a biologic marker for central serotonergic activity. The results also challenge the hypothesis that low platelet MAO activity in type 2 alcoholism is simply an artifact of smoking.
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| 4. |
- Fahlke, Claudia, 1964, et al.
(författare)
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Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates
- 2000
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 24, s. 644-650
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates. Methods: Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions. Results: The social separation challenge increased infant plasma cortisol concentrations, with peerreared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively. Conclusions: These findings suggest that early rearing experiences, such as! adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.
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| 5. |
- Niskanen, A. J., et al.
(författare)
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Miniature tunnel oxide electrodes on silicon for aqueous hot electron electrochemistry and electrochemiluminecscence studies
- 2007
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Ingår i: Transducers '07 & Eurosensors Xxi, Digest of Technical Papers, Vols 1 and 2. - 9781424408412
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Bokkapitel (populärvet., debatt m.m.)abstract
- The basic principles of cathodic hot electron-induced electrochemiluminescence (HECL) and hot electron (HE) injection into aqueous electrolyte solution are shortly discussed. The applicability of miniaturized oxide-coated silicon electrodes as working electrodes in detection of electrochemiluminescent labels by HECL is studied. In addition, the fabrication processes of these tunnel oxide electrodes are described, and an immunoassay is used as an example of a real bioaffinity assay carried out using oxide-coated silicon electrodes.
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| 6. |
- Schwandt, Melanie L., et al.
(författare)
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Gene-Environment Interactions and Response to Social Intrusion in Male and Female Rhesus Macaques
- 2010
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 67:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat. Methods: Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated. Results: Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing. Conclusions: Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.
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| 7. |
- Dowling, Nicki A., et al.
(författare)
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The Development of Empirically Derived Australian Low-Risk Gambling Limits
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- This study derived a set of Australian low-risk gambling limits and explored the relative and absolute risk associated with exceeding these limits. Secondary analysis of population-representative Tasmanian and Australian Capital Territory (ACT) cross-sectional (11,597 respondents) and longitudinal studies (2027 respondents) was conducted. Balancing sensitivity and specificity, the limits were: gambling frequency of 20-30 times per year; gambling expenditure of AUD $380-$615 per year (USD $240-$388 per year); gambling expenditure comprising 0.83-1.68% of gross personal income; and two types of gambling activities per year. All limits, except number of activities, predicted subsequent harm, with limits related to gambling expenditure consistently the best-performing. Exceeding the limits generally conferred a higher degree of relative and absolute risk, with gamblers exceeding the limits being 3-20 times more likely to experience harm than those who do not, and having a 5-17% risk of experiencing harm. Only 7-12% of gamblers exceeding the limits actually experienced harm. Gambling consumption lower than the limits also conferred a considerable amount of harm. Using a relative risk method, this study derived similar limits from disparate Australian states and territories. These limits can serve as working guidelines for the consideration of researchers, clinicians, and policy makers, but need to be subject to further rigorous empirical investigation.
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| 8. |
- Dowling, N. A., et al.
(författare)
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The Identification of Low-risk Gambling Limits for Specific Gambling Activities
- 2022
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Ingår i: Journal of Gambling Studies. - : Springer Science and Business Media LLC. - 1050-5350 .- 1573-3602. ; 38:2, s. 559-590
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Tidskriftsartikel (refereegranskat)abstract
- An emerging literature has identified optimal low-risk gambling limits in an effort to reduce gambling-related harm. Concerns have, however, been raised about the construction of aggregate low-risk limits that are applied to all gambling activities and there is support from gambling experts and the general public in Australia for the identification of low-risk limits for specific gambling activities. The study's aim was to identify and evaluate a set of empirically-based activity-specific limits (gambling frequency, gambling expenditure, gambling expenditure as a proportion of gross personal income, session expenditure, session duration) in a secondary analysis of Social and Economic Impact Studies of Gambling in Tasmania and the 2014 Survey on Gambling, Health and Wellbeing in the ACT. Balancing sensitivity and specificity, limits were identified for all gambling activities: EGMs (10 times per year, AUD$300/year, 0.63-1.04% of personal income, AUD$35 per session, 40 min/session), horse/dog racing (0.55% of personal income), instant scratch tickets (AUD$45/year), lotteries (0.45% of personal income), keno (4-13 times/year, AUD$45-$160/year), casino table games (AUD$345/year, 0.36-0.76% of personal income), bingo (AUD$150/year, 0.49% of personal income, AUD$17/session, 90 min/session), and sports/other event betting (14 times/year, AUD$400/year, 0.55-0.86% of personal income). These limits were exceeded by one-quarter to one-half of gamblers on these specific activities and were generally good predictors of gambling-related harm in subgroups of gamblers participating in these gambling activities and in the overall gambling sample. The limits provide gamblers, regulators, prevention workers, and researchers with simple rules of thumb in prevention efforts to reduce gambling-related harm in specific contexts.
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| 9. |
- Jaervinen, Elina, et al.
(författare)
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Cultured lymphocytes' mitochondrial genome integrity is not altered by cladribine
- 2023
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Ingår i: Clinical and Experimental Immunology. - 0009-9104 .- 1365-2249. ; 214:3, s. 304-313
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Tidskriftsartikel (refereegranskat)abstract
- Cladribine tablets are a treatment for multiple sclerosis with effects on lymphocytes, yet its mode of action has not been fully established. Here, we analyzed the effects of cladribine on mitochondrial DNA integrity in lymphocytes. We treated cultured human T-cell lines (CCRF-CEM and Jurkat) with varying concentrations of cladribine to mimic the slow cell depletion observed in treated patients. The CCRF-CEM was more susceptible to cladribine than Jurkat cells. In both cells, mitochondrial protein synthesis, mitochondrial DNA copy number, and mitochondrial cytochrome-c oxidase-I mRNA mutagenesis was not affected by cladribine, while caspase-3 cleavage was detected in Jurkat cells at 100 nM concentration. Cladribine treatment at concentrations up to 10 nM in CCRF-CEM and 100 nM in Jurkat cells did not induce significant increase in mitochondrial DNA mutations. Peripheral blood mononuclear cells from eight multiple sclerosis patients and four controls were cultured with or without an effective dose of cladribine (5 nM). However, we did not find any differences in mitochondrial DNA somatic mutations in lymphocyte subpopulations (CD4+, CD8+, and CD19+) between treated versus nontreated cells. The overall mutation rate was similar in patients and controls. When different lymphocyte subpopulations were compared, greater mitochondrial DNA mutation levels were detected in CD8+ (P = 0.014) and CD4+ (P = 0.038) as compared to CD19+ cells, these differences were independent of cladribine treatment. We conclude that T cells have more detectable mitochondrial DNA mutations than B cells, and cladribine has no detectable mutagenic effect on lymphocyte mitochondrial genome nor does it impair mitochondrial function in human T-cell lines. Cultured leukemic human T-cell lines and cultured ex vivo human peripheral mononuclear cells from patients with multiple sclerosis and controls were treated with cladribine in vitro . In the T-cell lines mitochondrial protein synthesis, DNA copy number and mutagenesis were not affected by cladribine. In the ex vivo lymphocyte subpopulations (CD4+, CD8+, and CD19+), there were no significant differences in mitochondrial DNA mutations between treated versus nontreated cells. Graphical Abstract
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| 10. |
- Lindell, S. G., et al.
(författare)
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Intermittent Access to Ethanol Induces Escalated Alcohol Consumption in Primates
- 2017
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Ingår i: Journal of addictive behaviors, therapy and rehabilitation. - : SciTechnol. - 2324-9005. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process.
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| 11. |
- Long, Maeve, et al.
(författare)
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DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion
- 2022
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 41
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Tidskriftsartikel (refereegranskat)abstract
- Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated with deferiprone, a therapeutic iron chelator that stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling of lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurred several hours before mitochondrial clearance, with lipid droplets bordering mitochondria upon iron chelation. We demonstrate that DGAT1 inhibition restricts mitophagy in vitro, with impaired lysosomal homeostasis and cell viability. Importantly, genetic depletion of DGAT1 in vivo significantly impaired neuronal mitophagy and locomotor function in Drosophila. Our data define iron depletion as a potent signal that rapidly reshapes metabolism and establishes an unexpected synergy between lipid homeostasis and mitophagy that safeguards cell and tissue integrity.
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| 12. |
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| 13. |
- Simpson, Elizabeth A, et al.
(författare)
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Comments: Animal studies help clarify misunderstandings about neonatal imitation (vol. 40, articelID e400, 2017)
- 2017
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Ingår i: Behavioral and Brain Sciences. - : Cambridge University Press. - 0140-525X .- 1469-1825. ; 40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Empirical studies are incompatible with the proposal that neonatal imitation is arousal driven or declining with age. Nonhuman primate studies reveal a functioning brain mirror system from birth, developmental continuity in imitation and later sociability, and the malleability of neonatal imitation, shaped by the early environment. A narrow focus on arousal effects and reflexes may grossly underestimate neonatal capacities.
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| 14. |
- Vähätalo, Mervi, et al.
(författare)
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Institutional logics and efficiency pressures in public organizations : what about the healthcare sector?
- 2018
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Ingår i: Paper presented at the 25th Annual EurOMA Conference, Budapest, Hungary, June 24-26, 2018. ; , s. 1-8
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Konferensbidrag (refereegranskat)abstract
- This study describes the current state of public sector logic from the perspective of healthcare professionals. More than 1500 healthcare professionals answered the survey concerning the way in which values, decision making and aims appear in the public sector. Healthcare professionals felt that the essential value in the public sector is still the respect for human life. However, they also argued that good care has become subordinate to financial values. In the current age of austerity, improving efficiency in the public sector is inevitable. However, it shouldn’t be done by jeopardizing professionals’ ability to work according to their professional logic.
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| 15. |
- Wargelius, Hanna-Linn, et al.
(författare)
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Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.
- 2010
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Ingår i: Upsala journal of medical sciences. - : Uppsala Medical Society. - 2000-1967 .- 0300-9734. ; 115:1, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.
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