Abstract：
:Mitochondrial dysfunction is implicated in the pathophysiology of Parkinson's disease (PD), a common age-associated neurodegenerative disease characterized by intraneuronal inclusions (Lewy bodies) and progressive degeneration of the nigrostriatal dopamine (DA) system. It has recently been demonstrated that midbrain DA neurons of PD patients and elderly humans contain high levels of somatic mtDNA mutations, which may impair respiratory chain function. However, clinical studies have not established whether the respiratory chain deficiency is a primary abnormality leading to inclusion formation and DA neuron death, or whether generalized metabolic abnormalities within the degenerating DA neurons cause secondary damage to mitochondria. We have used a reverse genetic approach to investigate this question and created conditional knockout mice (termed MitoPark mice), with disruption of the gene for mitochondrial transcription factor A (Tfam) in DA neurons. The knockout mice have reduced mtDNA expression and respiratory chain deficiency in midbrain DA neurons, which, in turn, leads to a parkinsonism phenotype with adult onset of slowly progressive impairment of motor function accompanied by formation of intraneuronal inclusions and dopamine nerve cell death. Confocal and electron microscopy show that the inclusions contain both mitochondrial protein and membrane components. These experiments demonstrate that respiratory chain dysfunction in DA neurons may be of pathophysiological importance in PD.
journal_name
Proc Natl Acad Sci U S Aauthors
Ekstrand MI,Terzioglu M,Galter D,Zhu S,Hofstetter C,Lindqvist E,Thams S,Bergstrand A,Hansson FS,Trifunovic A,Hoffer B,Cullheim S,Mohammed AH,Olson L,Larsson NGdoi
10.1073/pnas.0605208103subject
Has Abstractpub_date
2007-01-23 00:00:00pages
1325-30issue
4eissn
0027-8424issn
1091-6490pii
0605208103journal_volume
104pub_type
杂志文章abstract：:Methane emissions in the Arctic are important, and may be contributing to global warming. While methane emission rates from Arctic lakes are well documented, methods are needed to quantify the relative contribution of active layer groundwater to the overall lake methane budget. Here we report measurements of natural t...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1417392112
更新日期：2015-03-24 00:00:00
abstract：:Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, α-ketoacids, and α-hydroxyacids originating from amino acid metabolism as well as polyketide-deri...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1204232109
更新日期：2012-05-29 00:00:00
abstract：:Atomic level characterization of proteins and other macromolecules in the living cell is challenging. Recent advances in NMR instrumentation and methods, however, have enabled in-cell studies with prospects for multidimensional spectral characterization of individual macromolecular components. We present NMR data on t...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0811130106
更新日期：2009-03-31 00:00:00
abstract：:What drives scientists' position taking on matters where empirical answers are unavailable or contradictory? We examined the contentious debate on whether to limit experiments involving the creation of potentially pandemic pathogens. Hundreds of scientists, including Nobel laureates, have signed petitions on the debat...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1613580114
更新日期：2017-06-13 00:00:00
abstract：:Let t --> gamma(t) be a homogeneous curve in R(n). For suitable f, define [unk](f)(x) = sup(h > 0)|(1/h) [unk](0) (h)f(x - gamma(t)) dt|. Then parallel[unk](f) parallel(p)
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.73.7.2176
更新日期：1976-07-01 00:00:00
abstract：:The cytochrome bc1 and related complexes are essential energy-conserving components of mitochondrial and bacterial electron transport chains. They orchestrate a complex sequence of electron and proton transfer reactions resulting in the oxidation of quinol, the reduction of a mobile electron carrier, and the transloca...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0702621104
更新日期：2007-05-08 00:00:00
abstract：:Previous studies have shown that binding of interleukin 1 (IL-1) to its receptor and intracellular processing of the IL-1/IL-1 receptor complex appear to be different in B- and T-lymphocyte cell lines. In this study we used a B-lymphoid cell line, 70Z/3, and T-lymphoid cell line, EL-4 6.1 C10, to explore further the d...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.86.20.8034
更新日期：1989-10-01 00:00:00
abstract：:Arginine is an amino acid that serves as a substrate for nitric oxide synthase and arginase. As such, arginine has the potential to influence diverse fundamental processes in the lung. Here we report that the arginine transport protein, cationic amino acid transporter (CAT)2, has a critical role in regulating lung inf...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0605478103
更新日期：2006-10-03 00:00:00
abstract：:A comprehensive mapping of interactions among Epstein-Barr virus (EBV) proteins and interactions of EBV proteins with human proteins should provide specific hypotheses and a broad perspective on EBV strategies for replication and persistence. Interactions of EBV proteins with each other and with human proteins were as...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0702332104
更新日期：2007-05-01 00:00:00
abstract：:The calcium, calmodulin-dependent phosphatase calcineurin, regulates growth and gene expression of striated muscles. The activity of calcineurin is modulated by a family of cofactors, referred to as modulatory calcineurin-interacting proteins (MCIPs). In the heart, the MCIP1 gene is activated by calcineurin and has be...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0308723101
更新日期：2004-03-02 00:00:00
abstract：:During the developmental process of the Gram-negative soil bacterium Myxococcus xanthus, vegetatively growing rod cells differentiate to ultimately become metabolically quiescent and environmentally resistant myxospores encased within fruiting bodies. This program, initiated by nutrient deprivation, is propagated by b...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0506969102
更新日期：2005-10-04 00:00:00
abstract：:Despite the importance of tryptophan (Trp) radicals in biology, very few radicals have been trapped and characterized in a physiologically meaningful context. Here we demonstrate that the diheme enzyme MauG uses Trp radical chemistry to catalyze formation of a Trp-derived tryptophan tryptophylquinone cofactor on its s...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1215011110
更新日期：2013-03-19 00:00:00
abstract：:Two continuous-suspension lymphocyte lines were isolated from the spleen and fibrosarcoma of a New Zealand Black female mouse. A C-type virus with a density of 1.16 g x cm(-3), 70S RNA, and RNA-directed DNA polymerase activity was isolated. The virus was infectious for NRK, NZB, (NZB x NZW)F(1), and (NZW x NZW)F(1) em...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.69.10.2965
更新日期：1972-10-01 00:00:00
abstract：:Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. One area of interest is the development of new immune adjuvants. Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can induce production of a wide variety o...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.94.20.10833
更新日期：1997-09-30 00:00:00
abstract：:Notwithstanding important advances in the context of single-variant pathogenicity identification, novel breakthroughs in discerning the origins of many rare diseases require methods able to identify more complex genetic models. We present here the Variant Combinations Pathogenicity Predictor (VarCoPP), a machine-learn...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1815601116
更新日期：2019-06-11 00:00:00
abstract：:Prader-Willi syndrome (PWS) and Angelman syndrome (AS) result from the loss of function of imprinted genes in human chromosome 15q11-q13. The central part of mouse chromosome 7 is homologous to human 15q11-q13, with conservation of both gene order and imprinted features. We report here the characterization of a transg...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.96.16.9258
更新日期：1999-08-03 00:00:00
abstract：:Fluorescence in situ hybridization (FISH) resolution has advanced because newer techniques use increasingly decondensed chromatin. FISH cannot analyze restriction enzyme cutting sites due to limitations of the hybridization and detection technologies. The RecA-assisted restriction endonuclease (RARE) technique cleaves...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.92.1.165
更新日期：1995-01-03 00:00:00
abstract：:The genome of a thermophilic fungus, Thermomyces lanuginosus, contains a tandemly arranged cluster of sequences that are approximately equal to 50% homologous with the cytoplasmic 5S RNA and that are selectable by hybridization techniques. Unlike typical pseudogenes, these sequences are not truncated; rather, they bea...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.81.6.1768
更新日期：1984-03-01 00:00:00
abstract：:The 24 nucleotides comprising the carbohydrate-recognition domain of Maackia amurensis hemagglutinin (MAH) cDNA were randomly mutated. The mutant lectins were expressed as glutathione-S-transferase fusion proteins in Escherichia coli and 16 clones were randomly chosen. Although all of 16 recombinant lectins reacted st...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.041621998
更新日期：2001-02-27 00:00:00
abstract：:A careful review of the literature in political science and neighboring social science disciplines shows that prevailing assumptions in the international development policy community about improved governance as a principal mechanism to reduce poverty in Africa rests more on faith than science. Conventional policy mod...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0700696104
更新日期：2007-10-23 00:00:00
abstract：:Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable prec...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1918296117
更新日期：2020-03-17 00:00:00
abstract：:The diradical form of thiol-activated neocarzinostatin chromophore resides in the minor groove of DNA, where it has access to hydrogen atoms at the C-5', C-1', and C-4' positions of deoxyribose on each strand. In a dodecamer oligodeoxyribonucleotide containing the sequence AGC.GCT, a bistranded lesion staggered two nu...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.89.15.6706
更新日期：1992-08-01 00:00:00
abstract：:A census of the biomass on Earth is key for understanding the structure and dynamics of the biosphere. However, a global, quantitative view of how the biomass of different taxa compare with one another is still lacking. Here, we assemble the overall biomass composition of the biosphere, establishing a census of the ≈5...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1711842115
更新日期：2018-06-19 00:00:00
abstract：:August-Copenhagen-Irish (ACI) rats are unique in that the ovary-intact females develop high incidence of mammary cancers induced solely by hormones upon prolonged exposure to high levels of estrogen alone. Studies have also shown that such prolonged exposure to high-dose estrogen results in human-like aneuploid mammar...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0710535105
更新日期：2008-03-04 00:00:00
abstract：:During oxygenic photosynthesis in cyanobacteria and chloroplasts of plants and eukaryotic algae, conversion of light energy to biologically useful chemical energy occurs in the specialized thylakoid membranes. Light-induced charge separation at the reaction centers of photosystems I and II, two multisubunit pigment-pr...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.241503898
更新日期：2001-11-06 00:00:00
abstract：:Bacterial proteins often localize to distinct sites within the cell, but the primary cues that dictate localization are largely unknown. Recent evidence has shown that positive membrane curvature can serve as a cue for localization of a peripheral membrane protein. Here we report that localization of the peripheral me...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0906851106
更新日期：2009-08-11 00:00:00
abstract：:Two issues long debated among Pacific and American prehistorians are (i) whether there was a pre-Columbian introduction of chicken (Gallus gallus) to the Americas and (ii) whether Polynesian contact with South America might be identified archaeologically, through the recovery of remains of unquestionable Polynesian or...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 历史文章,杂志文章
doi：10.1073/pnas.0703993104
更新日期：2007-06-19 00:00:00
abstract：:The AAA-ATPase thyroid hormone receptor interacting protein 13 (TRIP13), jointly with the Mad2-binding protein p31(comet), promotes the inactivation of the mitotic (spindle assembly) checkpoint by disassembling the mitotic checkpoint complex (MCC). This checkpoint system ensures the accuracy of chromosome segregation ...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1515358112
更新日期：2015-09-15 00:00:00
abstract：:Although they lie at the conceptual core of a wide range of scientific questions, the notions of irregular or "random" arrangement and the process of randomization itself have never been unambiguously defined. Algorithmic implementation of these concepts requires a combinatorial, rather than a probability-theoretic, f...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.95.4.1363
更新日期：1998-02-17 00:00:00
abstract：:The heterodimeric Elongin BC complex has been shown to interact in vitro and in cells with a conserved BC-box motif found in an increasing number of proteins including RNA polymerase II elongation factor Elongin A, suppressor of cytokine signaling (SOCS)-box proteins, and the von Hippel-Lindau tumor suppressor protein...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.162424199
更新日期：2002-08-06 00:00:00
