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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:

Publication year: 2018

Journal or book title: Molecular Cell

Volume: 69

Issue: 4

Pages: 594-609.e8

Find the full text : https://www.sciencedirect.com/science/article/pii/S1097276518300522

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Type: Journal Article

Serial number: 2278

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

Publication year: 2010

Journal or book title: Advances in Protein Chemistry and Structural Biology

Volume: 80

Issue:

Pages: 153-203

Find the full text : http://europepmc.org/abstract/med/21109220

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Type: Journal Article

Serial number: 1886

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

Publication year: 2011

Journal or book title: Experimental Neurology

Volume: 229

Issue: 2

Pages: 358-363

Find the full text : http://www.sciencedirect.com/science/article/pii/S0014488611000689

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Type: Journal Article

Serial number: 330

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

Publication year: 2007

Journal or book title: Mutation Research

Volume: 632

Issue: 1-2

Pages: 111-120

Find the full text : http://www.sciencedirect.com/science/article/pii/S1383571807001337

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Type: Journal Article

Serial number: 86

ISSN: 0027-5107

ISBN:
Details

Author: Armstrong-Brown, J.; Eng, E.; Hammond, W.P.; Zimmer, C.; Bowling, J.M.

Description: Physical inactivity is one of the factors contributing to disproportionate disease rates among older African Americans. Previous literature indicates that older African Americans are more likely to live in racially segregated neighborhoods and that racial residential segregation is associated with limited opportunities for physical activity. A cross-sectional mixed methods study was conducted guided by the concept of therapeutic landscapes. Multilevel regression analyses demonstrated that racial residential segregation was associated with more minutes of physical activity and greater odds of meeting physical activity recommendations. Qualitative interviews revealed the following physical activity related themes: aging of the neighborhood, knowing your neighbors, feeling of safety, and neighborhood racial identity. Perceptions of social cohesion enhanced participants' physical activity, offering a plausible explanation to the higher rates of physical activity found in this population. Understanding how social cohesion operates within racially segregated neighborhoods can help to inform the design of effective interventions for this population.

Title: Redefining racial residential segregation and its association with physical activity among African Americans 50 years and older: a mixed methods approach

Subject headings: African Americans/*statistics & numerical data; Age Factors; Aged; Attitude to Health/*ethnology; Cross-Sectional Studies; Exercise/*physiology; Female; Geography; Humans; Interviews as Topic; Life Style; Male; Middle Aged; Motor Activity/*physiology; Multivariate Analysis; Racism/ethnology/*statistics & numerical data; Regression Analysis; Risk Assessment; Sex Factors; Time Factors; United States

Publication year: 2015

Journal or book title: Journal of Aging and Physical Activity

Volume: 23

Issue: 2

Pages: 237-246

Find the full text : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900142/

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Type: Journal Article

Serial number: 1292

ISSN: 1063-8652

ISBN:
Details

Author: Arnold, H.J.; Feldman, D.C.

Description: The susceptibility to social desirability response bias of four alternative methods of measuring the importance of job and organizational characteristics is examined. Data were collected from 86 graduate management students. Results support the hypothesis that the explicitly stated subjective weight methodologies are more likely to evoke a social desirability response bias than is the inferred objective weight method.

Subject Headings: Social Desirability; Response Bias; Self-report; Choice situations

Keywords: Social Desirability Response Bias in Self-Report Choice Situations

Title: Social Desirability Response Bias in Self-Report Choice Situations

Subject headings:

Publication year: 1981

Journal or book title: Academy of Management Journal

Volume: 24

Issue: 2

Pages: 377-385

Find the full text : https://www.jstor.org/stable/pdf/255848.pdf

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Type: Journal Article

Serial number: 2540

ISSN: 0001-4273

ISBN:
Details

Author: Aro, H.M.; Palosaari, U.K.

Description: In a long-term study of the effects of divorce, children in a Finnish town who had completed questionnaires in school at age 16 were followed up with postal questionnaires at age 22. Depression in young adulthood was found to be slightly more common among children from divorced families. In addition, the life trajectories of children in divorced families revealed more stressful paths and more distress in both adolescence and young adulthood.

Title: Parental divorce, adolescence, and transition to young adulthood: a follow-up study

Subject headings: Achievement; Adaptation, Psychological; Adolescent; *Adolescent Psychology; Adult; Cohort Studies; Depression/psychology; Divorce/*psychology; Female; Follow-Up Studies; Humans; Interpersonal Relations; Male; *Personality Development; Self Concept; Social Adjustment; Somatoform Disorders/psychology

Publication year: 1992

Journal or book title: The American Journal of Orthopsychiatry

Volume: 62

Issue: 3

Pages: 421-429

Find the full text : http://onlinelibrary.wiley.com/doi/10.1037/h0079342/abstract

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Type: Journal Article

Serial number: 279

ISSN: 0002-9432

ISBN:
Details

Author: Arolfo, M.P.; Brioni, J.D.

Description: The effect of diazepam (0.3, 1.0, and 3.0 mg/kg) on the acquisition and retention of place learning was evaluated. The analysis of escape latencies indicates that 1.0 and 3.0 mg/kg diazepam significantly impaired the retention of spatial information. When a free swim trial was carried out only control animals showed spatial bias to the target quadrant. The absence of spatial bias in the group that received 0.3 mg/kg suggests that the amnesic effect of diazepam can be seen at doses similar to or even lower than the anxiolytic ones, and that the GABA/benzodiazepine receptor complex is highly sensitive to the cognitive impairment induced by diazepam in spatial tasks.

Title: Diazepam impairs place learning in the Morris water maze

Subject headings: Animals; Diazepam/*pharmacology; Discrimination Learning/*drug effects; Dose-Response Relationship, Drug; Escape Reaction/*drug effects; Male; Mental Recall/drug effects; Orientation/*drug effects; Rats; Rats, Inbred Strains; Reaction Time/drug effects; Retention (Psychology)/*drug effects

Publication year: 1991

Journal or book title: Behavioral and Neural Biology

Volume: 55

Issue: 1

Pages: 131-136

Find the full text : http://www.sciencedirect.com/science/article/pii/016310479180133Y

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Type: Journal Article

Serial number: 249

ISSN: 0163-1047

ISBN:
Details

Author: Aronson, J.; Fried, C.B.; Good, C.

Description: African American college students tend to obtain lower grades than their White counterparts, even when they enter college with equivalent test scores. Past research suggests that negative stereotypes impugning Black students' intellectual abilities play a role in this underperformance. Awareness of these stereotypes can psychologically threaten African Americans, a phenomenon known as "stereotype threat" (Steele & Aronson, 1995), which can in turn provoke responses that impair both academic performance and psychological engagement with academics. An experiment was performed to test a method of helping students resist these responses to stereotype threat. Specifically, students in the experimental condition of the experiment were encouraged to see intelligence "the object of the stereotype" as a malleable rather than fixed capacity. This mind-set was predicted to make students' performances less vulnerable to stereotype threat and help them maintain their psychological engagement with academics, both of which could help boost their college grades. Results were consistent with predictions. The African American students (and, to some degree, the White students) encouraged to view intelligence as malleable reported greater enjoyment of the academic process, greater academic engagement, and obtained higher grade point averages than their counterparts in two control groups.

Title: Reducing the Effects of Stereotype Threat on African American College Students by Shaping Theories of Intelligence

Subject headings: African American; College students; Stereotypes; Stereotype threat; Academic performance; Grades

Publication year: 2002

Journal or book title: Journal of Experimental Social Psychology

Volume: 38

Issue: 2

Pages: 113-125

Find the full text : http://steinhardt.nyu.edu/scmsAdmin/uploads/004/308/Aronson%20Fried%20%20Good.pdf

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Type: Journal Article

Serial number: 1186

ISSN: 0022-1031

ISBN:
Details

Author: Arp, W.J.

Description: While photosynthesis of C3 plants is stimulated by an increase in the atmospheric CO2 concentration, photosynthetic capacity is often reduced after long‐term exposure to elevated CO2. This reduction appears to be brought about by end product inhibition, resulting from an imbalance in the supply and demand of carbohydrates. A review of the literature revealed that the reduction of photosynthetic capacity in elevated CO2 was most pronounced when the increased supply of carbohydrates was combined with small sink size. The volume of pots in which plants were grown affected the sink size by restricting root growth. While plants grown in small pots had a reduced photosynthetic capacity, plants grown in the field showed no reduction or an increase in this capacity. Pot volume also determined the effect of elevated CO2 on the root/shoot ratio: the root/shoot ratio increased when root growth was not restricted and decreased in plants grown in small pots. The data presented in this paper suggest that plants growing in the field will maintain a high photosynthetic capacity as the atmospheric CO2 level continues to rise.

Subject Headings: elevated carbon dioxide: photosynthetic acclimation

Keywords: Effects of source-sink relations on photosynthetic acclimation to elevated CO2

Title: Effects of source-sink relations on photosynthetic acclimation to elevated CO2

Subject headings:

Publication year: 1991

Journal or book title: Plant, Cell and Environment

Volume: 14

Issue: 8

Pages: 869-875

Find the full text : https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-3040.1991.tb01450.x

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Type: Journal Article

Serial number: 2696

ISSN: 0140-7791

ISBN:





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