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{"title"=>"Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ", "type"=>"journal", "authors"=>[{"first_name"=>"Daniel", "last_name"=>"Lucas", "scopus_author_id"=>"7202026071"}, {"first_name"=>"José M.", "last_name"=>"Delgado-García", "scopus_author_id"=>"7005221472"}, {"first_name"=>"Beatriz", "last_name"=>"Escudero", "scopus_author_id"=>"6603545862"}, {"first_name"=>"Carmen", "last_name"=>"Albo", "scopus_author_id"=>"7004298140"}, {"first_name"=>"Ana", "last_name"=>"Aza", "scopus_author_id"=>"55541539100"}, {"first_name"=>"Rebeca", "last_name"=>"Acín-Pérez", "scopus_author_id"=>"6508070569"}, {"first_name"=>"Yaima", "last_name"=>"Torres", "scopus_author_id"=>"55543760500"}, {"first_name"=>"Paz", "last_name"=>"Moreno", "scopus_author_id"=>"55545562400"}, {"first_name"=>"José Antonio", "last_name"=>"Enríquez", "scopus_author_id"=>"7005261315"}, {"first_name"=>"Enrique", "last_name"=>"Samper", "scopus_author_id"=>"57093804800"}, {"first_name"=>"Luis", "last_name"=>"Blanco", "scopus_author_id"=>"7103149544"}, {"first_name"=>"Alfonso", "last_name"=>"Fairén", "scopus_author_id"=>"7003799257"}, {"first_name"=>"Antonio", "last_name"=>"Bernad", "scopus_author_id"=>"7003851628"}, {"first_name"=>"Agnès", "last_name"=>"Gruart", "scopus_author_id"=>"7004080075"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84871910142", "sgr"=>"84871910142", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0053243", "pmid"=>"23301049", "pui"=>"368044664"}, "id"=>"f85e995b-1a84-32c0-9b6c-f93890a84b0e", "abstract"=>"A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/-) mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/-) mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.", "link"=>"http://www.mendeley.com/research/increased-learning-brain-longterm-potentiation-aged-mice-lacking-dna-polymerase-%CE%BC-1", "reader_count"=>19, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Ph. D. Student"=>4, "Student > Master"=>4, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>3, "Chemistry"=>1, "Psychology"=>1, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Japan"=>1, "Portugal"=>1, "Spain"=>1}, "group_count"=>0}

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• http://doi.org/10.1016/j.arr.2013.10.002
• http://doi.org/10.1016/j.dnarep.2017.04.001
• http://doi.org/10.1002/ajmg.b.32533
• http://doi.org/10.1038/srep25928
• http://doi.org/10.1126/sciadv.aaw6671
• http://doi.org/10.1371/journal.pone.0093074
• http://doi.org/10.1073/pnas.1505805112
• http://doi.org/10.2478/s13380-013-0115-4
• http://doi.org/10.1016/j.nlm.2015.04.006

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/6e96e618-b7df-4ac3-b648-e1c5b6256f64", "title"=>"Author summary of the paper", "body"=>"Aging can be defined as the accumulation of physiological changes that are progressive, deleterious, universal and thus far irreversible. Aging damage occurs to molecules (DNA, proteins, lipids), cells, and organs. Damage associated with the aging process increases the probability that diseases of old age will occur. A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in major DNA repair mechanisms mostly result in accelerated aging and reduced brain function, so it is assumed that consequence of progressive damage in genome must play a central role in brain aging. We show that elimination of DNA polymerase mu, a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, although reduces moderately DNA repair, surprisingly, improves brain aging decay. Using associative learning and long-term potentiation experiments, we demonstrate that Polmu-/- mice maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polmu-/- mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. ", "isRemoved"=>false, "created"=>"2013-01-04T14:05:33Z", "lastModified"=>"2013-01-04T14:05:33Z", "creator"=>{"userId"=>"298983"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0053243", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2013-01-04T14:05:33Z", "replies"=>[]}

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• {"id"=>"286960266439188480", "text"=>"Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ: by Daniel Lucas, José... http://t.co/WY8ZDw5X", "created_at"=>"2013-01-03T22:20:33Z", "user"=>"jevives", "user_name"=>"J.Enric Vives", "user_profile_image"=>"http://a0.twimg.com/profile_images/2944594294/1c6f25b27a5c8aac05fb2483e21b4837_normal.jpeg"}
• {"id"=>"286960268473417729", "text"=>"Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ http://t.co/BIb8gFiU", "created_at"=>"2013-01-03T22:20:34Z", "user"=>"TestAllPLoSRSS", "user_name"=>"TestAllPLoSRSS", "user_profile_image"=>"http://a0.twimg.com/sticky/default_profile_images/default_profile_0_normal.png"}
• {"id"=>"287182503410798593", "text"=>"La ausencia de la ADN-polimerasa mu relacionada con el relentizamiento del #enjevecimiento http://t.co/66pJuPlC #neurociencia", "created_at"=>"2013-01-04T13:03:39Z", "user"=>"FoundNeuroSc", "user_name"=>"Fundamentos NeuroSc", "user_profile_image"=>"http://a0.twimg.com/profile_images/2667276910/02228ad941249f8886a4c238ddad3f71_normal.jpeg"}
• {"id"=>"287182996933574656", "text"=>"Lack of DNA polymerase mu related to a delay in #aging http://t.co/66pJuPlC #neuroscience", "created_at"=>"2013-01-04T13:05:36Z", "user"=>"FoundNeuroSc", "user_name"=>"Fundamentos NeuroSc", "user_profile_image"=>"http://a0.twimg.com/profile_images/2667276910/02228ad941249f8886a4c238ddad3f71_normal.jpeg"}
• {"id"=>"287193547139059712", "text"=>"RT @FoundNeuroSc: Lack of DNA polymerase mu related to a delay in #aging http://t.co/66pJuPlC #neuroscience", "created_at"=>"2013-01-04T13:47:32Z", "user"=>"ruth_caballero", "user_name"=>"Ruth Caballero", "user_profile_image"=>"http://a0.twimg.com/profile_images/2797480124/53325e571c5f369453a5c5b06bbd651c_normal.jpeg"}
• {"id"=>"289677035566166016", "text"=>"Descubren cómo ralentizar el envejecimiento cerebral en ratas. http://t.co/wMCu6cQY", "created_at"=>"2013-01-11T10:16:01Z", "user"=>"mila_fuentes", "user_name"=>"mila fuentes", "user_profile_image"=>"http://a0.twimg.com/profile_images/1827272925/Mila-Fuentes-Albero_800x600-150x150_normal.jpg"}
• {"id"=>"289708979293151232", "text"=>"#Longevidad #Cerebro joven!! La ausencia del gen Polu evita la decadencia cognitiva!! Medicina #Antiaging! Via CSIC http://t.co/CoflZrnU", "created_at"=>"2013-01-11T12:22:57Z", "user"=>"RaquelBlascoR", "user_name"=>"Raquel Blasco ", "user_profile_image"=>"http://a0.twimg.com/profile_images/2992580930/344f456053c73cbf5f317f516699a071_normal.jpeg"}
• {"id"=>"295206970540044288", "text"=>"El envejecimiento del cerebro se ralentiza con la ausencia de una polimerasa http://t.co/owa7u00i", "created_at"=>"2013-01-26T16:30:01Z", "user"=>"PorquesNatura", "user_name"=>"Porqués Naturaleza", "user_profile_image"=>"http://a0.twimg.com/profile_images/2034351024/logo_twitter_normal.jpg"}
• {"id"=>"297381605343903744", "text"=>"RT @PorquesNatura: El envejecimiento del cerebro se ralentiza con la ausencia de una polimerasa http://t.co/owa7u00i", "created_at"=>"2013-02-01T16:31:14Z", "user"=>"JCebrino", "user_name"=>"Jesús Cebrino", "user_profile_image"=>"http://a0.twimg.com/profile_images/2780347135/877fff1250e7ff8de51a3b61d5657e4f_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/279731", "https://ndownloader.figshare.com/files/279757", "https://ndownloader.figshare.com/files/279815", "https://ndownloader.figshare.com/files/279858", "https://ndownloader.figshare.com/files/279915", "https://ndownloader.figshare.com/files/279945", "https://ndownloader.figshare.com/files/280031", "https://ndownloader.figshare.com/files/280121", "https://ndownloader.figshare.com/files/280180", "https://ndownloader.figshare.com/files/280249", "https://ndownloader.figshare.com/files/280344", "https://ndownloader.figshare.com/files/280391"], "description"=>"<div><p>A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ^−/− mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ^−/− mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.</p> </div>", "links"=>[], "tags"=>["potentiation", "aged", "mice", "lacking", "dna", "polymerase"], "article_id"=>115148, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.s001", "https://dx.doi.org/10.1371/journal.pone.0053243.s002", "https://dx.doi.org/10.1371/journal.pone.0053243.s003", "https://dx.doi.org/10.1371/journal.pone.0053243.s004", "https://dx.doi.org/10.1371/journal.pone.0053243.s005", "https://dx.doi.org/10.1371/journal.pone.0053243.s006", "https://dx.doi.org/10.1371/journal.pone.0053243.s007", "https://dx.doi.org/10.1371/journal.pone.0053243.s008", "https://dx.doi.org/10.1371/journal.pone.0053243.s009", "https://dx.doi.org/10.1371/journal.pone.0053243.s010", "https://dx.doi.org/10.1371/journal.pone.0053243.s011", "https://dx.doi.org/10.1371/journal.pone.0053243.s012"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Increased_Learning_and_Brain_Long_Term_Potentiation_in_Aged_Mice_Lacking_DNA_Polymerase__/115148", "title"=>"Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-03 01:25:48"}
• {"files"=>["https://ndownloader.figshare.com/files/514558"], "description"=>"<p>(<b>A</b>) Location of recording (left) and stimulating (right) electrodes implanted chronically in the CA1 and CA3 areas respectively. (<b>B</b>) Animals were implanted with electromyographic (EMG) recording electrodes in the orbicularis oculi (O.O.) muscle, and with stimulating electrodes on the supraorbital nerve for presentation of unconditioned (US) stimuli. Conditioned stimulus (CS) consisted of a tone preceding the US by 500 ms. Animals were also implanted with recording (Rec.) electrodes in the CA1 area and with stimulating (St.) electrodes at the ipsilateral Schaffer collaterals. (<b>C</b>) Example of fEPSP evoked at the CA3-CA1 synapse in an 18-month-old Polµ^−/− mouse (1) and eyeblink evoked in the O.O. muscle by the electrical stimulation of the supraorbital nerve (2). (<b>D</b>) The top two traces illustrate the trace conditioning paradigm, and the moment at which a single pulse was presented to Schaffer collaterals (arrow, St. Hipp.). Samples of EMG activity of the O.O. muscle and hippocampal extracellular activity collected from the 9th conditioning session from an animal of each experimental group (1–4). Calibrations in (1) are for all of the records. Note fEPSPs evoked by the pulse presented to Schaffer collaterals (bend arrows).</p>", "links"=>[], "tags"=>["activity-dependent", "synaptic", "changes", "ca3-ca1", "synapse", "eyeblink"], "article_id"=>185032, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_design_for_recording_activity_dependent_synaptic_changes_at_the_CA3_CA1_synapse_during_classical_eyeblink_conditioning_/185032", "title"=>"Experimental design for recording activity-dependent synaptic changes at the CA3-CA1 synapse during classical eyeblink conditioning.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-03 01:23:52"}
• {"files"=>["https://ndownloader.figshare.com/files/514664"], "description"=>"<p>(A, B) Evolution of the fEPSP slope (A) and of the percentage (%) of conditioned responses (CRs, B) for 3-month-old wild-type (black circles) and Polµ^−/− (white circles) mice, during habituation, conditioning, and extinction sessions. At the top are illustrated averaged (n = 5) fEPSPs collected from the 1st and 9th conditioning sessions. (C, D) A similar set of data collected from 18-month-old wild-type (black triangles) and Polµ^−/− (white triangles) animals. Mean % values are followed by ± SEM. Differences in the percentage of CRs between 18-month-old wild-type and Polµ^−/− animals were statistically significant as indicated (*<i>P</i><0.001, two-way ANOVA). Differences in fEPSP slopes are also indicated, expressed as the % change with respect to mean values collected during the last two-habituation sessions (*<i>P</i><0.001, two-way ANOVA).</p>", "links"=>[], "tags"=>["curves", "evoked", "ca3-ca1", "synapse", "aged", "wild-type"], "article_id"=>185137, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Learning_curves_and_evolution_of_the_evoked_field_potential_fEPSP_at_the_CA3_CA1_synapse_for_young_and_aged_Pol_8722_8722_and_wild_type_mice_across_training_/185137", "title"=>"Learning curves and evolution of the evoked field potential (fEPSP) at the CA3-CA1 synapse for young and aged Polµ^−/− and wild-type mice, across training.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-03 01:25:37"}
• {"files"=>["https://ndownloader.figshare.com/files/514871"], "description"=>"<p>(<b>A</b>) LTP induction in representative 3-month-old control (black circles) and Polµ^−/− (white circles) mice. LTP was evoked in CA1 pyramidal cells by HFS of ipsilateral Schaffer collaterals (five 200 Hz, 100 ms trains of pulses at a rate of 1/s. This protocol was presented 6 times in total, at intervals of 1 min). The fEPSP is given as a percentage of the baseline (100%) slope. Records in the inset were collected at the indicated (1–3) times. (<b>B</b>) Mean ± SEM fEPSP values 1–15 min before (baseline), and 15–30 min (1), 105–120 min (2), and 24 h (3) after HFS for 3-month-old control (black bars) and Polµ^−/− (white bars) animals. No significant differences were observed between LTP evoked in these two groups of animals (<i>P</i> = 1, two-way ANOVA). (<b>C, D</b>) A similar set of data collected from 18-month-old wild-type (black triangles and bars) and Polµ^−/− (white triangles and bars) mice. Note that, in contrast with Polµ^−/− mice, 18-month-old controls presented a non-significant increase in fEPSP slopes after the presentation of the HFS protocol (*<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001, two-way ANOVA).</p>", "links"=>[], "tags"=>["potentiation", "evoked", "ca3-ca1", "synapse", "3-", "18-month-old", "wild-type"], "article_id"=>185344, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Long_term_potentiation_LTP_evoked_at_the_CA3_CA1_synapse_in_3_and_18_month_old_Pol_8722_8722_and_wild_type_mice_/185344", "title"=>"Long-term potentiation (LTP) evoked at the CA3-CA1 synapse in 3- and 18-month-old Polµ^−/− and wild-type mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-03 01:29:04"}
• {"files"=>["https://ndownloader.figshare.com/files/515053"], "description"=>"<p>(<b>A, B</b>) Silver staining shows perforant path axons (pp) and mossy fibers forming axon terminals (mt) in the <i>stratum lucidum</i> of CA3 (outlined), in 4-months-old mice. The images do not suggest anatomical differences between wild-type (<b>A</b>) and Polµ^−/− (KO) mice (<b>B</b>). (<b>C – F’</b>) Mossy fiber terminals in CA3 <i>stratum lucidum</i> immunostained for ZnT3 in wild-type (<b>C, E</b>) and Polµ^−/− (<b>D, F</b>) mice, at 4 months (<b>C, D</b>) and 18 months (<b>E, F</b>); map2 immunostaining reveals dendrites of CA3 pyramidal cells. The distribution of the ZnT3⁺ mossy fiber expansions was altered with aging, but no differences occurred between wild-type and Polµ^−/− (KO) mice of each age. CA1, CA3, areas of the hippocampus proper; DG, dentate gyrus; mt, mossy fiber expansions; pp, perforant pathway. Scale bar, A, B: 250 µm; C–F’: 10 µm.</p>", "links"=>[], "tags"=>["changes", "hippocampal", "circuitry"], "article_id"=>185533, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Absence_of_visible_changes_in_hippocampal_circuitry_in_Pol_8722_8722_mice_/185533", "title"=>"Absence of visible changes in hippocampal circuitry in Polµ^−/− mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-03 01:32:13"}
• {"files"=>["https://ndownloader.figshare.com/files/515222"], "description"=>"<p>(<b>A</b>, <b>B, C</b>) Evaluation of 8oxoG bypass repair activity (tolerance) in brain (wild-type vs. Polµ^−/−) extracts, using the indicated labeled-template primer (<b>B</b>). After incubation (30′–1 h, 30°C) with the clarified extracts (10 µg), with the addition of the indicated nucleotides (50 µM) and 1 mM MnCl₂, products were recovered and resolved in 20% PAGE. The scheme (<b>A</b>) illustrates the mobility of the different expected products: the original labeled primer (+15) could appear intact or degraded by endogenous nucleases (degraded products); extended primers appear at positions (+16 or +17) if no ligation with the 5′-flank of the gap has occurred (short-patch repair), and at full-length repaired (or mutated) product (+34) if ligation did occur. (<b>C</b>). Densitometric analysis of full-length repaired (+34) product was carried out, for the reaction using dATP or rATP, and represented relative to the activity yield by wild-type brain extracts using dATP. (<b>D, E</b>) Evaluation of mitochondrial function in whole extracts (Hom) or mitochondrial purified fractions (Mits), in brain and liver of wild-type and Polµ^−/− mice. Several relevant parameters (COX/CS, CII+CIII/CS, and aconitase/CS ratios) were monitored in brain (<b>D</b>) and compared with activity in liver (<b>E</b>). Differences were considered statistically significant at <i>P<</i>0.05. *<i>P</i><0.01; **, <i>P</i><0.001; ***, <i>P</i><0.0001 and ns, non-significant. (<b>F, G, H</b>) qRT-PCR analysis (<b>F</b>) of genes found to be differentially expressed in brain of old Polµ^−/− mice (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053243#pone.0053243.s008\" target=\"_blank\">Figure S8</a>). Evolution of gene expression at different ages (<b>G, H</b>). All qRT-PCR analyses were carried out in triplicate and normalized to (36B4 or β-actin), and represented as the relative level of expression of the indicated gene.</p>", "links"=>[], "tags"=>["mice", "shows", "molecular", "compatible", "delayed", "aging"], "article_id"=>185690, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pol_8722_8722_mice_brain_shows_a_molecular_profile_compatible_with_a_delayed_aging_phenotype_/185690", "title"=>"Polµ^−/− mice brain shows a molecular profile compatible with a delayed aging phenotype.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-03 01:34:50"}
• {"files"=>["https://ndownloader.figshare.com/files/515407"], "description"=>"<p>(<b>A</b>) Hierarchical clustering of the differential mRNA expression between wild-type and Polµ^−/− old (18 months) mice. (<b>B</b>) Schematic representation of the expression network detected using the software Ingenuity. (<b>C</b>) qRT-PCR analysis of genes belonging to the previously described network (<b>B</b>) and others found in DNA expression arrays carried out with brain of acutely treated animals (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053243#pone.0053243.s010\" target=\"_blank\">Figure S10</a>). Black bars denote values for wild-type animals and white bars correspond to Polµ^−/− animals. (<b>D</b>) Circulating levels of IGF1 and GH (ng/mL) were monitored by ELISA in old (21–24 months) animals. (<b>E, F</b>) qRT-PCR expression (<b>E</b>) and immunoconfocal analysis (<b>F</b>) of Igf1 and Igf1R in the hippocampal CA1area from wild-type and Polμ^−/− young adult (4 months) mice. Igf1 immunoreactivity-labeled non-pyramidal cells (short arrows) of <i>stratum oriens</i> (so), <i>stratum pyramidale</i> (sp), and <i>stratum radiatum</i> (sr; not shown); no differences in labeling frequency or labeling intensity were found between Polμ^−/− and wild-type mice. Igf1R-immunostaining delineated cell processes in the stratum radiatum (sr) of Polμ^−/− but not of wild-type mice. As compared with the case of aged mice, unspecific punctate labeling (long arrows) was infrequent in these tissue sections. Slight differences were found, however, in the occurrence of Igf1-immunoreactive cells in the CA1 area of aged mice, and in the expression of Igf1R between young wild-type and Polμ^−/− mice. Scale bar, 25 µm.</p>", "links"=>[], "tags"=>["mice", "presents", "altered", "endocrine"], "article_id"=>185880, "categories"=>["Neuroscience", "Physics", "Medicine", "Biochemistry", "Mental Health", "Biophysics", "Molecular Biology", "Genetics"], "users"=>["Daniel Lucas", "José M. Delgado-García", "Beatriz Escudero", "Carmen Albo", "Ana Aza", "Rebeca Acín-Pérez", "Yaima Torres", "Paz Moreno", "José Antonio Enríquez", "Enrique Samper", "Luis Blanco", "Alfonso Fairén", "Antonio Bernad", "Agnès Gruart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053243.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pol_8722_8722_mice_brain_presents_an_altered_endocrine_network_/185880", "title"=>"Polµ^−/− mice brain presents an altered endocrine network.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-03 01:38:00"}

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Relative Metric

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F1000Prime