Highly infectious prions are not directly neurotoxic.

abstract：:Down syndrome (DS) is the most common form of intellectual disability. The cognitive alterations in DS are thought to depend on brain regions critical for learning and memory such as the prefrontal cortex (PFC) and the hippocampus (HPC). Neuroimaging studies suggest that increased brain connectivity correlates with lo...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Alemany-González M,Gener T,Nebot P,Vilademunt M,Dierssen M,Puig MV

更新日期：2020-05-26 00:00:00

abstract：:W. D. Hamilton's celebrated formula for the age-specific force of natural selection furnishes predictions for senescent mortality due to mutation accumulation, at the price of reliance on a linear approximation. Applying to Hamilton's setting the full nonlinear demographic model for mutation accumulation recently deve...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Wachter KW,Evans SN,Steinsaltz D

更新日期：2013-06-18 00:00:00

abstract：:We investigate yeast sex chromosome evolution by comparing genome sequences from 16 species in the family Saccharomycetaceae, including data from genera Tetrapisispora, Kazachstania, Naumovozyma, and Torulaspora. We show that although most yeast species contain a mating-type (MAT) locus and silent HML and HMR loci str...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Gordon JL,Armisén D,Proux-Wéra E,ÓhÉigeartaigh SS,Byrne KP,Wolfe KH

更新日期：2011-12-13 00:00:00

abstract：:Death of pancreatic β cells is a pathological hallmark of type 1 diabetes (T1D). However, the molecular mechanisms of β cell death and its regulation are poorly understood. Here we describe a unique regulatory pathway of β cell death that comprises microRNA-21, its target tumor suppressor PDCD4, and its upstream trans...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Ruan Q,Wang T,Kameswaran V,Wei Q,Johnson DS,Matschinsky F,Shi W,Chen YH

更新日期：2011-07-19 00:00:00

abstract：:Ion channel proteins control ionic flux across biological membranes through conformational changes in their transmembrane pores. An exponentially increasing number of channel structures captured in different conformational states are now being determined; however, these newly resolved structures are commonly classifie...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rao S,Klesse G,Stansfeld PJ,Tucker SJ,Sansom MSP

更新日期：2019-07-09 00:00:00

abstract：:Full-length 66-kDa estrogen receptor alpha (ERalpha) stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal domain and AF-2 in the ligand binding domain. Another physiologically expressed 46-kDa ERalpha isoform lacks the N-terminal A/B domains and is consequently devoid of ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Billon-Galés A,Fontaine C,Filipe C,Douin-Echinard V,Fouque MJ,Flouriot G,Gourdy P,Lenfant F,Laurell H,Krust A,Chambon P,Arnal JF

更新日期：2009-02-10 00:00:00

abstract：:Natural antimicrobial peptides (AMPs) provide prototypes for the design of unconventional antimicrobial agents. Existing bulk assays measure AMP activity but do not provide details of the growth-halting mechanism. We use fluorescence microscopy to directly observe the attack of the human antimicrobial peptide LL-37 on...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Sochacki KA,Barns KJ,Bucki R,Weisshaar JC

更新日期：2011-04-19 00:00:00

abstract：:Transfer of organelle DNA into the nuclear genome has been significant in eukaryotic evolution, because it appears to be the origin of many nuclear genes. Most studies on organelle DNA transfer have been restricted to evolutionary events but experimental systems recently became available to monitor the process in real...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Huang CY,Ayliffe MA,Timmis JN

更新日期：2004-06-29 00:00:00

abstract：:A potential new approach for gene therapy against human immunodeficiency virus type 1 (HIV-1) infection is the design of a nonstructural gene-based virion-specific inhibitory molecule that is packaged with virus to destroy its infectivity. We tested this approach for HIV-1 by using Vpx, a virion-associated protein of ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Matsuda Z,Yu X,Yu QC,Lee TH,Essex M

更新日期：1993-04-15 00:00:00

abstract：:Clostridium botulinum neurotoxins (BoNTs), the most potent toxins known, disrupt neurotransmission through proteolysis of proteins involved in neuroexocytosis. The light chains of BoNTs are unique zinc proteases that have stringent substrate specificity and require exceptionally long substrates. We have determined the...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Segelke B,Knapp M,Kadkhodayan S,Balhorn R,Rupp B

更新日期：2004-05-04 00:00:00

abstract：:Signaling through the Toll receptor is required for dorsal/ventral polarity in Drosophila embryos, and also plays an evolutionarily conserved role in the immune response. Upon ligand binding, Toll appears to multimerize and activate the associated kinase, Pelle. However, the immediate downstream targets of Pelle have ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Shen B,Liu H,Skolnik EY,Manley JL

更新日期：2001-07-17 00:00:00

abstract：:Restenosis, a process characterized in part by excessive smooth muscle cell (SMC) proliferation in areas of vascular injury, occurs in up to 50% of patients undergoing balloon angioplasty. In an effort to develop a treatment strategy for restenosis, we constructed a replication-deficient recombinant adenovirus (AdMLP....

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Guzman RJ,Hirschowitz EA,Brody SL,Crystal RG,Epstein SE,Finkel T

更新日期：1994-10-25 00:00:00

abstract：:Using a comprehensive transcriptome analysis, a Z chromosome-linked chicken homolog of hemogen (cHEMGN) was identified and shown to be specifically involved in testis differentiation in early chicken embryos. Hemogen [Hemgn in mice, EDAG (erythroid differentiation-associated gene protein) in humans] was recently chara...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Nakata T,Ishiguro M,Aduma N,Izumi H,Kuroiwa A

更新日期：2013-02-26 00:00:00

abstract：:Inducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3' region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using tw...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Vaeth M,Gogishvili T,Bopp T,Klein M,Berberich-Siebelt F,Gattenloehner S,Avots A,Sparwasser T,Grebe N,Schmitt E,Hünig T,Serfling E,Bodor J

更新日期：2011-02-08 00:00:00

abstract：:The capacity of a so-called male recombination (MR) chromosome in Drosophila melanogaster to generate mutations at 14 X-chromosome loci specifying visible phenotypes was investigated. Appreciable increases in mutation were found at three loci y, sn, and ras. Tests of represnetative mutants generated at each locus esta...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Green MM

更新日期：1977-08-01 00:00:00

abstract：:P-glycoprotein is an ATP-binding cassette multidrug transporter that actively transports chemically diverse substrates across the lipid bilayer. The precise molecular mechanism underlying transport is not fully understood. Here, we present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from Cyanidi...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kodan A,Yamaguchi T,Nakatsu T,Sakiyama K,Hipolito CJ,Fujioka A,Hirokane R,Ikeguchi K,Watanabe B,Hiratake J,Kimura Y,Suga H,Ueda K,Kato H

更新日期：2014-03-18 00:00:00

abstract：:The versatility of CRISPR-Cas endonucleases as a tool for biomedical research has led to diverse applications in gene editing, programmable transcriptional control, and nucleic acid detection. Most CRISPR-Cas systems, however, suffer from off-target effects and unpredictable nonspecific binding that negatively impact ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Specht DA,Xu Y,Lambert G

更新日期：2020-05-26 00:00:00

abstract：:The tumor suppressor protein p53 plays a crucial role in coordinating cellular processes, such as cell cycle arrest, apoptosis, and senescence. The nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a homophilic adhesion molecule and involved in nerve regeneration. Interestingly, Ninj1 is found to be overexpressed i...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Cho SJ,Rossi A,Jung YS,Yan W,Liu G,Zhang J,Zhang M,Chen X

更新日期：2013-06-04 00:00:00

abstract：:Both activated and resting CD4(+) T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin alpha(4)beta(7) (alpha(4)beta(7)), the gut mucosal homing receptor. We find that alpha(4)beta(7)(high) C...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Cicala C,Martinelli E,McNally JP,Goode DJ,Gopaul R,Hiatt J,Jelicic K,Kottilil S,Macleod K,O'Shea A,Patel N,Van Ryk D,Wei D,Pascuccio M,Yi L,McKinnon L,Izulla P,Kimani J,Kaul R,Fauci AS,Arthos J

更新日期：2009-12-08 00:00:00

abstract：:We describe a quantum mechanics/molecular mechanics investigation of the guanidinoacetate methyltransferase catalyzed reaction, which shows that proton transfer from guanidinoacetate (GAA) to Asp-134 and methyl transfer from S-adenosyl-L-methionine (AdoMet) to GAA are concerted. By self-consistent-charge density funct...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Zhang X,Bruice TC

更新日期：2006-10-31 00:00:00

abstract：:In everyday life, a macroscopic valve is a device with a movable control element that regulates the flow of gases or liquids by blocking and opening passageways. Construction of such a device on the nanoscale level requires (i) suitably proportioned movable control elements, (ii) a method for operating them on demand,...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Nguyen TD,Tseng HR,Celestre PC,Flood AH,Liu Y,Stoddart JF,Zink JI

更新日期：2005-07-19 00:00:00

abstract：:Iron-sulfur clusters function as cofactors of a wide range of proteins, with diverse molecular roles in both prokaryotic and eukaryotic cells. Dedicated machineries assemble the clusters and deliver them to the final acceptor molecules in a tightly regulated process. In the prototypical Gram-negative bacterium Escheri...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Santos JA,Alonso-García N,Macedo-Ribeiro S,Pereira PJ

更新日期：2014-06-03 00:00:00

abstract：:We report direct evidence for the existence of an iron(IV)-hydroxide. Resonance Raman measurements on chloroperoxidase compound II (CPO-II) reveal an isotope ((18)O and (2)H)-sensitive band at nu(Fe-O) = 565 cm(-1). Preparation of CPO-II in H(2)O using H(2)(18)O(2) results in a red-shift of 22 cm(-1), while preparatio...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Stone KL,Behan RK,Green MT

更新日期：2006-08-15 00:00:00

abstract：:Phosphorylation of purified microtubule-associated proteins (MAPs) inhibits the rate and extent of MAP-stimulated microtubule assembly. The extent of microtubule assembly is reduced as a result of a decrease in the fraction of tubulin polymerized, without a significant change in the critical protein concentration. The...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Jameson L,Caplow M

更新日期：1981-06-01 00:00:00

abstract：:Type-1 reactions (T1R) are pathological inflammatory episodes and main contributors to nerve damage in leprosy. Here, we evaluate the genewise enrichment of rare protein-altering variants in 7 genes where common variants were previously associated with T1R. We selected 474 Vietnamese leprosy patients of which 237 were...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Fava VM,Xu YZ,Lettre G,Van Thuc N,Orlova M,Thai VH,Tao S,Croteau N,Eldeeb MA,MacDougall EJ,Cambri G,Lahiri R,Adams L,Fon EA,Trempe JF,Cobat A,Alcaïs A,Abel L,Schurr E

更新日期：2019-07-30 00:00:00

abstract：:Changes in the expression of Hox genes have been widely linked to the evolution of animal body plans, but functional demonstrations of this relationship have been impeded by the lack of suitable model organisms. A classic case study involves the repeated evolution of specialized feeding appendages, called maxillipeds,...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Pavlopoulos A,Kontarakis Z,Liubicich DM,Serano JM,Akam M,Patel NH,Averof M

更新日期：2009-08-18 00:00:00

abstract：:Electrophysiological and activity-dependent gene expression studies of birdsong have contributed to the understanding of the neural representation of natural sounds. However, we have limited knowledge about the overall spatial topography of song representation in the avian brain. Here, we adapt the noninvasive functio...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Voss HU,Tabelow K,Polzehl J,Tchernichovski O,Maul KK,Salgado-Commissariat D,Ballon D,Helekar SA

更新日期：2007-06-19 00:00:00

abstract：:Frogs (Anura) are one of the most diverse groups of vertebrates and comprise nearly 90% of living amphibian species. Their worldwide distribution and diverse biology make them well-suited for assessing fundamental questions in evolution, ecology, and conservation. However, despite their scientific importance, the evol...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Feng YJ,Blackburn DC,Liang D,Hillis DM,Wake DB,Cannatella DC,Zhang P

更新日期：2017-07-18 00:00:00

abstract：:The roles of glycosylation and protein synthesis in the maintenance of insulin receptor levels and turnover rates in 3T3-L1 adipocytes were investigated. The heavy isotope density-shift technique was employed to determine the effects of inhibitors of these processes on the rates of synthesis and degradation of cellula...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Reed BC,Ronnett GV,Lane MD

更新日期：1981-05-01 00:00:00

abstract：:What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Thompson-Schill SL,Swick D,Farah MJ,D'Esposito M,Kan IP,Knight RT

更新日期：1998-12-22 00:00:00