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Author: Andersson, D.R.; Bjornsson, E.; Bergquist, F.; Nissbrandt, H.

Description: Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.

Title: Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors

Subject headings: Analysis of Variance; Animals; Area Under Curve; Brain Injuries/chemically induced/*pathology; Chromatography, High Pressure Liquid/methods; Dendrites/drug effects/metabolism; Disease Models, Animal; Dopamine/*metabolism; Dose-Response Relationship, Drug; Electrochemistry/methods; Female; Functional Laterality; Mecamylamine/pharmacology; Microdialysis/methods; Motor Activity/drug effects/*physiology; Muscarinic Antagonists/pharmacology; Nicotinic Antagonists/pharmacology; Oxidopamine; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic/*physiology; Rotarod Performance Test/methods; Scopolamine Hydrobromide/pharmacology; Substantia Nigra/drug effects/*metabolism/pathology; gamma-Aminobutyric Acid/metabolism

Year: 2010

Publication: Experimental Neurology

Volume: 221

Issue: 1

Pages: 251-259

Full text: http://www.sciencedirect.com/science/article/pii/S0014488609004695

Cited by: https://scholar.google.com/scholar?cites=17842742823817933995&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0014-4886

ISBN:
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Author: Angarne-Lindberg, T.; Wadsby, M.

Description: The children who experienced their parents' divorce when the divorce rate in Sweden had begun to grow to higher levels than in preceding decades are today adults. The aim of this study was to investigate if adults who had experienced parental divorce 15 years before the time of our study, differed in mental health from those with continuously married parents, taking into account life events other than the divorce. Instruments used were the Symptom Checklist (SCL-90) measuring mental health and the Life Event questionnaire capturing the number and experience of occurred events. Forty-eight persons, who were 7-18 years old when their parents divorced, constituted the divorce group, and 48 persons matched on age, sex and growth environment formed the study groups. The SCL-90 showed a limited difference between the groups, but not concerning total mental health. A main finding was a difference with regard to sex and age; women aged 22-27 in the divorce group displayed poorer mental health than other participants in both groups. The results from the Life Event questionnaire showed that the divorce group had experienced a significantly larger number of events, and more life events were described as negative with difficult adjustment. A regression analysis showed a significant relation between the SCL-90, Global Severity Index and life events experienced as negative with difficult adjustment, divorce events excluded, but not with the divorce itself. It seems highly desirable to pay more attention than has thus far been paid to girls with experience of childhood divorce at age 7-12.

Title: Fifteen years after parental divorce: mental health and experienced life-events

Subject headings: *Adaptation, Psychological; Adjustment Disorders/*diagnosis/epidemiology/psychology; Adolescent; Adult; Adult Children/*psychology; Age Factors; Child; Child, Preschool; Cross-Sectional Studies; Divorce/*psychology; Female; Humans; Infant; *Life Change Events; Longitudinal Studies; Male; Middle Aged; Risk Factors; Sweden; Young Adult

Year: 2009

Publication: Nordic Journal of Psychiatry

Volume: 63

Issue: 1

Pages: 32-43

Full text: http://informahealthcare.com/doi/abs/10.1080/08039480802098386

Cited by: https://scholar.google.com/scholar?cites=12625920844990297388&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0803-9488

ISBN:
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Author: Anisimov, O.A.; Nelson, F.E.

Description: The proportion of the Earth's land area underlain by permafrost, currently about 25%, is expected to contract substantially in response to climatic warming. Maps of permafrost distribution in the northern hemisphere were generated using three general circulation models and an empirical paleoreconstruction, all scaled to a 2°C global warming, in conjunction with a permafrost model that has successfully replicated the arrangement of contemporary permafrost zones in several high-latitude regions. The simulations indicate a 25–44% reduction in the total area occupied by equilibrium permafrost. Conditions specified by the climate models result in a poleward (north-northeast) displacement of all permafrost zones. The continuous permafrost zone was most severely impacted in the simulations, with reductions in its areal extent ranging from 29% to 67%. The permafrost model was also used to hindcast the distribution of permafrost in Russia during the Holocene climatic optimum and Eemian interglacial. Agreement of modeled results with mappings based on independent criteria confirm the motel's effectiveness.

Title: Permafrost distribution in the Northern Hemisphere under scenarios of climatic change

Subject headings: Permafrost; Paleoreconstruction

Year: 1996

Publication: Global and Planetary Change

Volume: 14

Issue: 1-2

Pages: 59-72

Full text: http://www.sciencedirect.com/science/article/pii/0921818196000021

Cited by: https://scholar.google.com/scholar?cites=11431167765771197832&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0921-8181

ISBN:
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Author: Ansaldo, A.I.; Marcotte, K.; Scherer, L.; Raboyeau, G.

Description: Given the increasing number of bilinguals around the world, bilingual aphasia has become a hot topic in the field of clinical and theoretical research in communication sciences. The aim of this article is to provide data-driven cues for intervention with bilingual aphasia. First, the impact of a number of factors considered to influence second language processing will be discussed with reference to neurolinguistic and neuroimaging data. The discussion will then move to bilingual aphasia. Specifically, we shall describe the recovery patterns following bilingual aphasia, and discuss the issues of pathological mixing and switching. The literature and clinical evidence will provide the framework for a discussion of data-driven cues for intervention with bilingual aphasia.

Title: Language therapy and bilingual aphasia: Clinical implications of psycholinguistic and neuroimaging research

Subject headings: Bilingual aphasia; Therapy; Data-driven

Year: 2008

Publication: Journal of Neurolinguistics

Volume: 21

Issue: 6

Pages: 539-557

Full text: http://linkinghub.elsevier.com/retrieve/pii/S0911604408000146

Cited by: https://scholar.google.com/scholar?cites=16887109263387767858&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0911-6044

ISBN:
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Author: Arai, L.

Description: Geographic variation in teenage pregnancy is attributable to social and cultural, as well as demographic, factors. In some communities and social networks early childbearing may be acceptable, or even normative. It is these places that are the focus of policy initiatives. This paper reports the findings of a qualitative study of neighbourhood and peer influences on the transition from pregnancy to fertility among 15 young mothers in three English locations. Data were also collected from nine local health workers. The findings show that, from the mothers' perspective, there was no evidence that peers influenced behaviour. However, the data did suggest that early childbearing might be normative in some communities.

Title: Peer and neighbourhood influences on teenage pregnancy and fertility: qualitative findings from research in English communities

Subject headings: Abortion, Induced/utilization; Adolescent; Adult; Attitude to Health/*ethnology; Birth Rate; England; Female; Geography; Humans; Interviews as Topic; Mothers/education/psychology; *Peer Group; Pregnancy; Pregnancy in Adolescence/*ethnology/psychology; Qualitative Research; Residence Characteristics/*classification; *Social Class; *Social Conformity; Social Values/ethnology; Socioeconomic Factors

Year: 2007

Publication: Health & Place

Volume: 13

Issue: 1

Pages: 87-98

Full text: http://www.sciencedirect.com/science/article/pii/S135382920500081X

Cited by: https://scholar.google.com/scholar?cites=9610889022705437681&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 1353-8292

ISBN:
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Author: Ardiel, E.L.; Rankin, C.H.

Description: As self-fertilizing nematodes, Caenorhabditis elegans do not normally come to mind when one thinks of social animals. However, their reproductive mode is optimized for rapid population growth, and although they do not form structured societies, conspecifics are an important source of sensory input. A pheromone signal underlies multiple complex behaviors, including diapause, male-mating, and aggregation. The use of C. elegans in sociogenetics research allows for the analysis of social interactions at the level of genes, circuits, and behaviors. This chapter describes natural polymorphisms in mab-23, plg-1, npr-1, and glb-5 as they relate to two C. elegans social behaviors: male-mating and aggregation.

Title: C. elegans: social interactions in a "nonsocial" animal

Subject headings: Animals; Behavior, Animal; Caenorhabditis elegans/genetics/*physiology; Caenorhabditis elegans Proteins/genetics; Ecosystem; Female; Genetics, Behavioral; Male; Pheromones/physiology; Social Behavior

Year: 2009

Publication: Advances in Genetics

Volume: 68

Issue:

Pages: 1-22

Full text: http://www.sciencedirect.com/science/article/pii/S0065266009680019

Cited by: https://scholar.google.com/scholar?cites=10191182788969714134&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0065-2660

ISBN:
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Author: Arena, G.; Cisse, M.Y.; Pyrdziak, S.; Chatre, L.; Riscal, R.; Fuentes, M.; Arnold, J.J.; Kastner, M.; Gayte, L.; Bertrand-Gaday, C.; Nay, K.; Angebault-Prouteau, C.; Murray, K.; Chabi, B.; Koechlin-Ramonatxo, C.; Orsetti, B.; Vincent, C.; Casas, F.; Marine, J.-C.; Etienne-Manneville, S.; Bernex, F.; Lombes, A.; Cameron, C.E.; Dubouchaud, H.; Ricchetti, M.; Linares, L.K.; Le Cam, L.

Description: Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria to control respiration and mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on respiratory complex I activity and enhancing mitochondrial ROS production. Recruitment of MDM2 to mitochondria increases during oxidative stress and hypoxia. Accordingly, mice lacking MDM2 in skeletal muscles exhibit higher MT-ND6 levels, enhanced complex I activity, and increased muscular endurance in mild hypoxic conditions. Furthermore, increased mitochondrial MDM2 levels enhance the migratory and invasive properties of cancer cells. Collectively, these data uncover a previously unsuspected function of the MDM2 oncoprotein in mitochondria that play critical roles in skeletal muscle physiology and may contribute to tumor progression.

Subject Headings: Mdm2; Mt-Nd6; hypoxia; migration; mitochondria; respiratory complex I

Title: Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53

Subject headings:

Year: 2018

Publication: Molecular Cell

Volume: 69

Issue: 4

Pages: 594-609.e8

Full text: https://www.sciencedirect.com/science/article/pii/S1097276518300522

Cited by: https://scholar.google.com/scholar?cites=17835177264043819980&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 1097-2765

ISBN:
Details

Author: Arias, H.R.

Description: Nicotinic acetylcholine receptors (AChRs) are one of the best characterized ion channels from the Cys-loop receptor superfamily. The study of acetylcholine binding proteins and prokaryotic ion channels from different species has been paramount for the understanding of the structure-function relationship of the Cys-loop receptor superfamily. AChR function can be modulated by different ligand types. The neurotransmitter ACh and other agonists trigger conformational changes in the receptor, finally opening the intrinsic cation channel. The so-called gating process couples ligand binding, located at the extracellular portion, to the opening of the ion channel, located at the transmembrane region. After agonist activation, in the prolonged presence of agonists, the AChR becomes desensitized. Competitive antagonists overlap the agonist-binding sites inhibiting the pharmacological action of agonists. Positive allosteric modulators (PAMs) do not bind to the orthostetic binding sites but allosterically enhance the activity elicited by agonists by increasing the gating process (type I) and/or by decreasing desensitization (type II). Instead, negative allosteric modulators (NAMs) produce the opposite effects. Interestingly, this negative effect is similar to that found for another class of allosteric drugs, that is, noncompetitive antagonists (NCAs). However, the main difference between both categories of drugs is based on their distinct binding site locations. Although both NAMs and NCAs do not bind to the agonist sites, NACs bind to sites located in the ion channel, whereas NAMs bind to nonluminal sites. However, this classification is less clear for NAMs interacting at the extracellular-transmembrane interface where the ion channel mouth might be involved. Interestingly, PAMs and NAMs might be developed as potential medications for the treatment of several diseases involving AChRs, including dementia-, skin-, and immunological-related diseases, drug addiction, and cancer. More exciting is the potential combination of specific agonists with specific PAMs. However, we are still in the beginning of understanding how these compounds act and how these drugs can be used therapeutically.

Title: Positive and negative modulation of nicotinic receptors

Subject headings: Acetylcholine/chemistry/physiology; Allosteric Regulation; Allosteric Site/genetics; Animals; Cholinergic Antagonists/*pharmacology/therapeutic use; Crystallography, X-Ray; Humans; Ion Channel Gating/drug effects; Mice; Nicotinic Agonists/*pharmacology/therapeutic use; Protein Structure, Tertiary; Receptors, Nicotinic/*chemistry/*physiology; Structure-Activity Relationship

Year: 2010

Publication: Advances in Protein Chemistry and Structural Biology

Volume: 80

Issue:

Pages: 153-203

Full text: http://europepmc.org/abstract/med/21109220

Cited by: https://scholar.google.com/scholar?cites=17321345494457981812&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 1876-1623

ISBN:
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Author: Arias-Carrion, O.; Palomero-Rivero, M.; Millan-Aldaco, D.; Haro, R.; Drucker-Colin, R.; Murillo-Rodriguez, E.

Description: Clinical studies have indicated that the primary pharmacological activity of modafinil (MOD) is inducing wakefulness; however, the brain targets that underlie its wake-promoting activity have not been described. In the present study, we show that MOD injected into sleep-wake related brain areas promoted alertness. If administered (10, 20, or 30 mug/1 muL) into either anterior hypothalamus (AH) or pedunculopontine tegmental nucleus (PPTg) at 08:00, 12:00 or 16:00 h, MOD enhanced wakefulness whereas diminished slow wave sleep as well as rapid eye movement sleep. In addition, microinjection of MOD (10, 20, or 30 mug/1 muL) either into AH or PPTg after total sleep deprivation prevented the sleep rebound. Taken together, these observations suggest that AH and PPTg play a key role in the wake-inducing effects of MOD and encourage further experimentation to draw a possible mechanism of action.

Title: Infusion of modafinil into anterior hypothalamus or pedunculopontine tegmental nucleus at different time-points enhances waking and blocks the expression of recovery sleep in rats after sleep deprivation

Subject headings: Analysis of Variance; Animals; Benzhydryl Compounds/pharmacology/*therapeutic use; Central Nervous System Stimulants/pharmacology/*therapeutic use; Electroencephalography; Hypothalamus, Anterior/*drug effects; Microinjections; Pedunculopontine Tegmental Nucleus/*drug effects; Rats; Sleep/*drug effects; Sleep Deprivation/*drug therapy; Wakefulness/*drug effects

Year: 2011

Publication: Experimental Neurology

Volume: 229

Issue: 2

Pages: 358-363

Full text: http://www.sciencedirect.com/science/article/pii/S0014488611000689

Cited by: https://scholar.google.com/scholar?cites=7715940667362334084&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0014-4886

ISBN:
Details

Author: Arimoto-Kobayashi, S.; Sakata, H.; Mitsu, K.; Tanoue, H.

Description: We discovered the directly acting mutagenicity of the tobacco-specific nitrosamine, 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), with UVA light (320-400nm) in Ames bacteria and phage M13mp2 in the absence of metabolic activation. We have investigated the spectrum of mutations caused by UVA-activated NNK. The majority (57%) of induced sequence changes were comprised of GC to CG, GC to TA and GC to AT. This suggested that modification of guanine residues was responsible for these mutations. Hence, we explored the formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) and O(6)-methylguanine (O(6)meG) in the DNA. When calf thymus DNA was treated with NNK and UVA, the amount of 8-oxodG/dG and O(6)meG/G in the DNA increased up to 20-fold and 100-fold, respectively, compared with the untreated control. DNA strand breaks were observed following NNK and UVA treatment, and the strand breaks were suppressed in the presence of scavengers for oxygen and NO radical. The formation of NO was also observed in NNK solutions irradiated with UVA. We analyzed the photodynamic spectrum of mutation induction, 8-oxodG formation and NO formation using monochromatic radiation. The patterns of the action spectra were comparable to the absorption spectrum of NNK. We conclude that NNK may act as a photosensitizer in response to UVA to produce NO and other oxidative and alkylative intermediates following the formation of 8-oxodG and O(6)meG in DNA, which may lead to mutations and DNA strand breaks.

Title: A possible photosensitizer: Tobacco-specific nitrosamine, 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), induced mutations, DNA strand breaks and oxidative and methylative damage with UVA

Subject headings: Base Sequence; DNA Breaks; DNA Methylation--drug effects, radiation effects; Dose-Response Relationship, Drug; Models, Biological; Molecular Sequence Data; Mutation; Nitrosamines--toxicity; Oxidative Stress--drug effects, radiation effects; Photosensitizing Agents--toxicity; Salmonella typhimurium; Tobacco--chemistry; Ultraviolet Rays--adverse effects

Year: 2007

Publication: Mutation Research

Volume: 632

Issue: 1-2

Pages: 111-120

Full text: http://www.sciencedirect.com/science/article/pii/S1383571807001337

Cited by: https://scholar.google.com/scholar?cites=14425975319166951369&as_sdt=1000005&sciodt=0,16&hl=en

Format: Journal Article

ISSN: 0027-5107

ISBN:





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