@article{8021, abstract = {Most excitatory inputs in the mammalian brain are made on dendritic spines, rather than on dendritic shafts. Spines compartmentalize calcium, and this biochemical isolation can underlie input-specific synaptic plasticity, providing a raison d'etre for spines. However, recent results indicate that the spine can experience a membrane potential different from that in the parent dendrite, as though the spine neck electrically isolated the spine. Here we use two-photon calcium imaging of mouse neocortical pyramidal neurons to analyze the correlation between the morphologies of spines activated under minimal synaptic stimulation and the excitatory postsynaptic potentials they generate. We find that excitatory postsynaptic potential amplitudes are inversely correlated with spine neck lengths. Furthermore, a spike timing-dependent plasticity protocol, in which two-photon glutamate uncaging over a spine is paired with postsynaptic spikes, produces rapid shrinkage of the spine neck and concomitant increases in the amplitude of the evoked spine potentials. Using numerical simulations, we explore the parameter regimes for the spine neck resistance and synaptic conductance changes necessary to explain our observations. Our data, directly correlating synaptic and morphological plasticity, imply that long-necked spines have small or negligible somatic voltage contributions, but that, upon synaptic stimulation paired with postsynaptic activity, they can shorten their necks and increase synaptic efficacy, thus changing the input/output gain of pyramidal neurons. }, author = {Araya, R. and Vogels, Tim P and Yuste, R.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {28}, pages = {E2895--E2904}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Activity-dependent dendritic spine neck changes are correlated with synaptic strength}}, doi = {10.1073/pnas.1321869111}, volume = {111}, year = {2014}, } @article{9479, abstract = {Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved AAA-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48ANPL4 complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction.}, author = {Mérai, Zsuzsanna and Chumak, Nina and García-Aguilar, Marcelina and Hsieh, Tzung-Fu and Nishimura, Toshiro and Schoft, Vera K. and Bindics, János and Ślusarz, Lucyna and Arnoux, Stéphanie and Opravil, Susanne and Mechtler, Karl and Zilberman, Daniel and Fischer, Robert L. and Tamaru, Hisashi}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {45}, pages = {16166--16171}, publisher = {National Academy of Sciences}, title = {{The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes}}, doi = {10.1073/pnas.1418564111}, volume = {111}, year = {2014}, } @article{17990, abstract = {Molecular junctions formed using the scanning-tunneling-microscope–based break-junction technique (STM-BJ) have provided unique insight into charge transport at the nanoscale. In most prior work, the same metal, typically Au, Pt, or Ag, is used for both tip and substrate. For such noble metal electrodes, the density of electronic states is approximately constant within a narrow energy window relevant to charge transport. Here, we form molecular junctions using the STM-BJ technique, with an Au metal tip and a microfabricated graphite substrate, and measure the conductance of a series of graphite/amine-terminated oligophenyl/Au molecular junctions. The remarkable mechanical strength of graphite and the single-crystal properties of our substrates allow measurements over few thousand junctions without any change in the surface properties. We show that conductance decays exponentially with molecular backbone length with a decay constant that is essentially the same as that for measurements with two Au electrodes. More importantly, despite the inherent symmetry of the oligophenylamines, we observe rectification in these junctions. State-of-art ab initio conductance calculations are in good agreement with experiment, and explain the rectification. We show that the highly energy-dependent graphite density of states contributes variations in transmission that, when coupled with an asymmetric voltage drop across the junction, leads to the observed rectification. Together, our measurements and calculations show how functionality may emerge from hybrid molecular-scale devices purposefully designed with different electrodes beyond the so-called “wide band limit,” opening up the possibility of assembling molecular junctions with dissimilar electrodes using layered 2D materials.}, author = {Kim, Taekyeong and Liu, Zhen-Fei and Lee, Chulho and Neaton, Jeffrey B. and Venkataraman, Latha}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {30}, pages = {10928--10932}, publisher = {National Academy of Sciences}, title = {{Charge transport and rectification in molecular junctions formed with carbon-based electrodes}}, doi = {10.1073/pnas.1406926111}, volume = {111}, year = {2014}, } @article{927, abstract = {Morphogenesis during embryo development requires the coordination of mechanical forces to generate the macroscopic shapes of organs. We propose a minimal theoretical model, based on cell adhesion and actomyosin contractility, which describes the various shapes of epithelial cells and the bending and buckling of epithelial sheets, as well as the relative stability of cellular tubes and spheres. We show that, to understand these processes, a full 3D description of the cells is needed, but that simple scaling laws can still be derived. The morphologies observed in vivo can be understood as stable points of mechanical equations and the transitions between them are either continuous or discontinuous. We then focus on epithelial sheet bending, a ubiquitous morphogenetic process. We calculate the curvature of an epithelium as a function of actin belt tension as well as of cell-cell and and cell-substrate tension. The model allows for a comparison of the relative stabilities of spherical or cylindrical cellular structures (acini or tubes). Finally, we propose a unique type of buckling instability of epithelia, driven by a flattening of individual cell shapes, and discuss experimental tests to verify our predictions.}, author = {Hannezo, Edouard B and Prost, Jacques and Joanny, Jean}, issn = {1091-6490}, journal = {PNAS}, number = {1}, pages = {27 -- 32}, publisher = {National Academy of Sciences}, title = {{Theory of epithelial sheet morphology in three dimensions}}, doi = {10.1073/pnas.1312076111}, volume = {111}, year = {2014}, } @article{809, abstract = {The assembly of HIV-1 is mediated by oligomerization of the major structural polyprotein, Gag, into a hexameric protein lattice at the plasma membrane of the infected cell. This leads to budding and release of progeny immature virus particles. Subsequent proteolytic cleavage of Gag triggers rearrangement of the particles to form mature infectious virions. Obtaining a structural model of the assembled lattice of Gag within immature virus particles is necessary to understand the interactions that mediate assembly of HIV-1 particles in the infected cell, and to describe the substrate that is subsequently cleaved by the viral protease. An 8-Å resolution structure of an immature virus-like tubular array assembled from a Gag-derived protein of the related retrovirus Mason-Pfizer monkey virus (M-PMV) has previously been reported, and a model for the arrangement of the HIV-1 capsid (CA) domains has been generated based on homology to this structure. Here we have assembled tubular arrays of a HIV-1 Gag-derived protein with an immature-like arrangement of the C-terminal CA domains and have solved their structure by using hybrid cryo-EM and tomography analysis. The structure reveals the arrangement of the C-terminal domain of CA within an immature-like HIV-1 Gag lattice, and provides, to our knowledge, the first high-resolution view of the region immediately downstream of CA, which is essential for assembly, and is significantly different from the respective region in M-PMV. Our results reveal a hollow column of density for this region in HIV-1 that is compatible with the presence of a six-helix bundle at this position.}, author = {Bharata, Tanmay and Menendez, Luis and Hagena, Wim and Luxd, Vanda and Igonete, Sebastien and Schorba, Martin and Schur, Florian and Kraüsslich, Hans and Briggsa, John}, issn = {1091-6490}, journal = {PNAS}, number = {22}, pages = {8233 -- 8238}, publisher = {National Academy of Sciences}, title = {{Cryo electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly}}, doi = {10.1073/pnas.1401455111}, volume = {111}, year = {2014}, } @article{6133, abstract = {cGMP signaling is widespread in the nervous system. However, it has proved difficult to visualize and genetically probe endogenously evoked cGMP dynamics in neurons in vivo. Here, we combine cGMP and Ca2+ biosensors to image and dissect a cGMP signaling network in a Caenorhabditis elegans oxygen-sensing neuron. We show that a rise in O2 can evoke a tonic increase in cGMP that requires an atypical O2-binding soluble guanylate cyclase and that is sustained until oxygen levels fall. Increased cGMP leads to a sustained Ca2+ response in the neuron that depends on cGMP-gated ion channels. Elevated levels of cGMP and Ca2+ stimulate competing negative feedback loops that shape cGMP dynamics. Ca2+-dependent negative feedback loops, including activation of phosphodiesterase-1 (PDE-1), dampen the rise of cGMP. A different negative feedback loop, mediated by phosphodiesterase-2 (PDE-2) and stimulated by cGMP-dependent kinase (PKG), unexpectedly promotes cGMP accumulation following a rise in O2, apparently by keeping in check gating of cGMP channels and limiting activation of Ca2+-dependent negative feedback loops. Simultaneous imaging of Ca2+ and cGMP suggests that cGMP levels can rise close to cGMP channels while falling elsewhere. O2-evoked cGMP and Ca2+ responses are highly reproducible when the same neuron in an individual animal is stimulated repeatedly, suggesting that cGMP transduction has high intrinsic reliability. However, responses vary substantially across individuals, despite animals being genetically identical and similarly reared. This variability may reflect stochastic differences in expression of cGMP signaling components. Our work provides in vivo insights into the architecture of neuronal cGMP signaling.}, author = {Couto, A. and Oda, S. and Nikolaev, V. O. and Soltesz, Z. and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {35}, pages = {E3301--E3310}, publisher = {Proceedings of the National Academy of Sciences}, title = {{In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor}}, doi = {10.1073/pnas.1217428110}, volume = {110}, year = {2013}, } @article{9481, abstract = {Arabidopsis thaliana endosperm, a transient tissue that nourishes the embryo, exhibits extensive localized DNA demethylation on maternally inherited chromosomes. Demethylation mediates parent-of-origin–specific (imprinted) gene expression but is apparently unnecessary for the extensive accumulation of maternally biased small RNA (sRNA) molecules detected in seeds. Endosperm DNA in the distantly related monocots rice and maize is likewise locally hypomethylated, but whether this hypomethylation is generally parent-of-origin specific is unknown. Imprinted expression of sRNA also remains uninvestigated in monocot seeds. Here, we report high-coverage sequencing of the Kitaake rice cultivar that enabled us to show that localized hypomethylation in rice endosperm occurs solely on the maternal genome, preferring regions of high DNA accessibility. Maternally expressed imprinted genes are enriched for hypomethylation at putative promoter regions and transcriptional termini and paternally expressed genes at promoters and gene bodies, mirroring our recent results in A. thaliana. However, unlike in A. thaliana, rice endosperm sRNA populations are dominated by specific strong sRNA-producing loci, and imprinted 24-nt sRNAs are expressed from both parental genomes and correlate with hypomethylation. Overlaps between imprinted sRNA loci and imprinted genes expressed from opposite alleles suggest that sRNAs may regulate genomic imprinting. Whereas sRNAs in seedling tissues primarily originate from small class II (cut-and-paste) transposable elements, those in endosperm are more uniformly derived, including sequences from other transposon classes, as well as genic and intergenic regions. Our data indicate that the endosperm exhibits a unique pattern of sRNA expression and suggest that localized hypomethylation of maternal endosperm DNA is conserved in flowering plants.}, author = {Rodrigues, Jessica A. and Ruan, Randy and Nishimura, Toshiro and Sharma, Manoj K. and Sharma, Rita and Ronald, Pamela C and Fischer, Robert L. and Zilberman, Daniel}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {19}, pages = {7934--7939}, publisher = {National Academy of Sciences}, title = {{Imprinted expression of genes and small RNA is associated with localized hypomethylation of the maternal genome in rice endosperm}}, doi = {10.1073/pnas.1306164110}, volume = {110}, year = {2013}, } @article{14305, abstract = {Understanding the mechanism of protein folding requires a detailed knowledge of the structural properties of the barriers separating unfolded from native conformations. The S-peptide from ribonuclease S forms its α-helical structure only upon binding to the folded S-protein. We characterized the transition state for this binding-induced folding reaction at high resolution by determining the effect of site-specific backbone thioxylation and side-chain modifications on the kinetics and thermodynamics of the reaction, which allows us to monitor formation of backbone hydrogen bonds and side-chain interactions in the transition state. The experiments reveal that α-helical structure in the S-peptide is absent in the transition state of binding. Recognition between the unfolded S-peptide and the S-protein is mediated by loosely packed hydrophobic side-chain interactions in two well defined regions on the S-peptide. Close packing and helix formation occurs rapidly after binding. Introducing hydrophobic residues at positions outside the recognition region can drastically slow down association.}, author = {Bachmann, Annett and Wildemann, Dirk and Praetorius, Florian M and Fischer, Gunter and Kiefhaber, Thomas}, issn = {1091-6490}, journal = {PNAS}, keywords = {Multidisciplinary}, number = {10}, pages = {3952--3957}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Mapping backbone and side-chain interactions in the transition state of a coupled protein folding and binding reaction}}, doi = {10.1073/pnas.1012668108}, volume = {108}, year = {2011}, } @article{6137, abstract = {Variation in food quality and abundance requires animals to decide whether to stay on a poor food patch or leave in search of better food. An important question in behavioral ecology asks when is it optimal for an animal to leave a food patch it is depleting. Although optimal foraging is central to evolutionary success, the neural and molecular mechanisms underlying it are poorly understood. Here we investigate the neuronal basis for adaptive food-leaving behavior in response to resource depletion in Caenorhabditis elegans, and identify several of the signaling pathways involved. The ASE neurons, previously implicated in salt chemoattraction, promote food-leaving behavior via a cGMP pathway as food becomes limited. High ambient O2 promotes food-leaving via the O2-sensing neurons AQR, PQR, and URX. Ectopic activation of these neurons using channelrhodopsin is sufficient to induce high food-leaving behavior. In contrast, the neuropeptide receptor NPR-1, which regulates social behavior on food, acts in the ASE neurons, the nociceptive ASH neurons, and in the RMG interneuron to repress food-leaving. Finally, we show that neuroendocrine signaling by TGF-β/DAF-7 and neuronal insulin signaling are necessary for adaptive food-leaving behavior. We suggest that animals integrate information about their nutritional state with ambient oxygen and gustatory stimuli to formulate optimal foraging strategies.}, author = {Milward, K. and Busch, K. E. and Murphy, R. J. and de Bono, Mario and Olofsson, B.}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {51}, pages = {20672--20677}, publisher = {National Academy of Sciences}, title = {{Neuronal and molecular substrates for optimal foraging in Caenorhabditis elegans}}, doi = {10.1073/pnas.1106134109}, volume = {108}, year = {2011}, } @article{9483, abstract = {Imprinted genes are expressed primarily or exclusively from either the maternal or paternal allele, a phenomenon that occurs in flowering plants and mammals. Flowering plant imprinted gene expression has been described primarily in endosperm, a terminal nutritive tissue consumed by the embryo during seed development or after germination. Imprinted expression in Arabidopsis thaliana endosperm is orchestrated by differences in cytosine DNA methylation between the paternal and maternal genomes as well as by Polycomb group proteins. Currently, only 11 imprinted A. thaliana genes are known. Here, we use extensive sequencing of cDNA libraries to identify 9 paternally expressed and 34 maternally expressed imprinted genes in A. thaliana endosperm that are regulated by the DNA-demethylating glycosylase DEMETER, the DNA methyltransferase MET1, and/or the core Polycomb group protein FIE. These genes encode transcription factors, proteins involved in hormone signaling, components of the ubiquitin protein degradation pathway, regulators of histone and DNA methylation, and small RNA pathway proteins. We also identify maternally expressed genes that may be regulated by unknown mechanisms or deposited from maternal tissues. We did not detect any imprinted genes in the embryo. Our results show that imprinted gene expression is an extensive mechanistically complex phenomenon that likely affects multiple aspects of seed development.}, author = {Hsieh, Tzung-Fu and Shin, Juhyun and Uzawa, Rie and Silva, Pedro and Cohen, Stephanie and Bauer, Matthew J. and Hashimoto, Meryl and Kirkbride, Ryan C. and Harada, John J. and Zilberman, Daniel and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {5}, pages = {1755--1762}, publisher = {National Academy of Sciences}, title = {{Regulation of imprinted gene expression in Arabidopsis endosperm}}, doi = {10.1073/pnas.1019273108}, volume = {108}, year = {2011}, } @article{9485, abstract = {Cytosine methylation silences transposable elements in plants, vertebrates, and fungi but also regulates gene expression. Plant methylation is catalyzed by three families of enzymes, each with a preferred sequence context: CG, CHG (H = A, C, or T), and CHH, with CHH methylation targeted by the RNAi pathway. Arabidopsis thaliana endosperm, a placenta-like tissue that nourishes the embryo, is globally hypomethylated in the CG context while retaining high non-CG methylation. Global methylation dynamics in seeds of cereal crops that provide the bulk of human nutrition remain unknown. Here, we show that rice endosperm DNA is hypomethylated in all sequence contexts. Non-CG methylation is reduced evenly across the genome, whereas CG hypomethylation is localized. CHH methylation of small transposable elements is increased in embryos, suggesting that endosperm demethylation enhances transposon silencing. Genes preferentially expressed in endosperm, including those coding for major storage proteins and starch synthesizing enzymes, are frequently hypomethylated in endosperm, indicating that DNA methylation is a crucial regulator of rice endosperm biogenesis. Our data show that genome-wide reshaping of seed DNA methylation is conserved among angiosperms and has a profound effect on gene expression in cereal crops.}, author = {Zemach, Assaf and Kim, M. Yvonne and Silva, Pedro and Rodrigues, Jessica A. and Dotson, Bradley and Brooks, Matthew D. and Zilberman, Daniel}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {43}, pages = {18729--18734}, publisher = {National Academy of Sciences}, title = {{Local DNA hypomethylation activates genes in rice endosperm}}, doi = {10.1073/pnas.1009695107}, volume = {107}, year = {2010}, } @article{6146, abstract = {Homeostasis of internal carbon dioxide (CO2) and oxygen (O2) levels is fundamental to all animals. Here we examine the CO2 response of the nematode Caenorhabditis elegans. This species inhabits rotting material, which typically has a broad CO2 concentration range. We show that well fed C. elegans avoid CO2 levels above 0.5%. Animals can respond to both absolute CO2 concentrations and changes in CO2 levels within seconds. Responses to CO2 do not reflect avoidance of acid pH but appear to define a new sensory response. Sensation of CO2 is promoted by the cGMP-gated ion channel subunits TAX-2 and TAX-4, but other pathways are also important. Robust CO2 avoidance in well fed animals requires inhibition of the DAF-16 forkhead transcription factor by the insulin-like receptor DAF-2. Starvation, which activates DAF-16, strongly suppresses CO2 avoidance. Exposure to hypoxia (<1% O2) also suppresses CO2 avoidance via activation of the hypoxia-inducible transcription factor HIF-1. The npr-1 215V allele of the naturally polymorphic neuropeptide receptor npr-1, besides inhibiting avoidance of high ambient O2 in feeding C. elegans, also promotes avoidance of high CO2. C. elegans integrates competing O2 and CO2 sensory inputs so that one response dominates. Food and allelic variation at NPR-1 regulate which response prevails. Our results suggest that multiple sensory inputs are coordinated by C. elegans to generate different coherent foraging strategies.}, author = {Bretscher, A. J. and Busch, K. E. and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {23}, pages = {8044--8049}, publisher = {Proceedings of the National Academy of Sciences}, title = {{A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans}}, doi = {10.1073/pnas.0707607105}, volume = {105}, year = {2008}, } @article{3740, abstract = {In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be possible to transmit much more than just one regulatory bit. Realizing this optimal information capacity would require that the dynamic range of TF concentrations used by the cell, the input/output relation of the regulatory module, and the noise in gene expression satisfy certain matching relations, which we derive. These results provide parameter-free, quantitative predictions connecting independently measurable quantities. Although we have considered only the simplified problem of a single gene responding to a single TF, we find that these predictions are in surprisingly good agreement with recent experiments on the Bicoid/Hunchback system in the early Drosophila embryo and that this system achieves approximately 90% of its theoretical maximum information transmission.}, author = {Tkacik, Gasper and Callan, Curtis and Bialek, William}, issn = {1091-6490}, journal = {PNAS}, number = {34}, pages = {12265 -- 12270}, publisher = {National Academy of Sciences}, title = {{Information flow and optimization in transcriptional regulation}}, doi = {10.1073/pnas.0806077105}, volume = {105}, year = {2008}, } @article{3827, abstract = {Previous studies revealed that synaptotagmin 1 is the major Ca(2+) sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca(2+) sensor at hippocampal inhibitory synapses has not been determined. To address the functional role of synaptotagmin 1 at identified inhibitory terminals, we made paired recordings from synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As expected, genetic elimination of synaptotagmin 1 abolished synchronous transmitter release at excitatory GC-BC synapses. However, synchronous release at inhibitory BC-GC synapses was maintained. Quantitative analysis revealed that elimination of synaptotagmin 1 reduced release probability and depression but maintained the synchrony of transmitter release at BC-GC synapses. Elimination of synaptotagmin 1 also increased the frequency of both miniature excitatory postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic currents (recorded in GCs), consistent with a clamping function of synaptotagmin 1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription quantitative PCR analysis revealed that single BCs coexpressed multiple synaptotagmin isoforms, including synaptotagmin 1-5, 7, and 11-13. Our results indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not absolutely required for synchronous release at inhibitory BC-GC synapses. Thus, alternative fast Ca(2+) sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.}, author = {Kerr, Angharad and Reisinger, Ellen and Jonas, Peter M}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {40}, pages = {15581 -- 6}, publisher = {National Academy of Sciences}, title = {{Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses}}, doi = {10.1073/pnas.0800621105}, volume = {105}, year = {2008}, } @article{13425, abstract = {Nanoparticles (NPs) decorated with ligands combining photoswitchable dipoles and covalent cross-linkers can be assembled by light into organized, three-dimensional suprastructures of various types and sizes. NPs covered with only few photoactive ligands form metastable crystals that can be assembled and disassembled “on demand” by using light of different wavelengths. For higher surface concentrations, self-assembly is irreversible, and the NPs organize into permanently cross-linked structures including robust supracrystals and plastic spherical aggregates.}, author = {Klajn, Rafal and Bishop, Kyle J. M. and Grzybowski, Bartosz A.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {25}, pages = {10305--10309}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Light-controlled self-assembly of reversible and irreversible nanoparticle suprastructures}}, doi = {10.1073/pnas.0611371104}, volume = {104}, year = {2007}, } @article{8483, abstract = {Atom-resolved real-time studies of kinetic processes in proteins have been hampered in the past by the lack of experimental techniques that yield sufficient temporal and atomic resolution. Here we present band-selective optimized flip-angle short transient (SOFAST) real-time 2D NMR spectroscopy, a method that allows simultaneous observation of reaction kinetics for a large number of nuclear sites along the polypeptide chain of a protein with an unprecedented time resolution of a few seconds. SOFAST real-time 2D NMR spectroscopy combines fast NMR data acquisition techniques with rapid sample mixing inside the NMR magnet to initiate the kinetic event. We demonstrate the use of SOFAST real-time 2D NMR to monitor the conformational transition of α-lactalbumin from a molten globular to the native state for a large number of amide sites along the polypeptide chain. The kinetic behavior observed for the disappearance of the molten globule and the appearance of the native state is monoexponential and uniform along the polypeptide chain. This observation confirms previous findings that a single transition state ensemble controls folding of α-lactalbumin from the molten globule to the native state. In a second application, the spontaneous unfolding of native ubiquitin under nondenaturing conditions is characterized by amide hydrogen exchange rate constants measured at high pH by using SOFAST real-time 2D NMR. Our data reveal that ubiquitin unfolds in a gradual manner with distinct unfolding regimes.}, author = {Schanda, Paul and Forge, V. and Brutscher, B.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {27}, pages = {11257--11262}, publisher = {National Academy of Sciences}, title = {{Protein folding and unfolding studied at atomic resolution by fast two-dimensional NMR spectroscopy}}, doi = {10.1073/pnas.0702069104}, volume = {104}, year = {2007}, } @article{9487, abstract = {Cytosine DNA methylation is considered to be a stable epigenetic mark, but active demethylation has been observed in both plants and animals. In Arabidopsis thaliana, DNA glycosylases of the DEMETER (DME) family remove methylcytosines from DNA. Demethylation by DME is necessary for genomic imprinting, and demethylation by a related protein, REPRESSOR OF SILENCING1, prevents gene silencing in a transgenic background. However, the extent and function of demethylation by DEMETER-LIKE (DML) proteins in WT plants is not known. Using genome-tiling microarrays, we mapped DNA methylation in mutant and WT plants and identified 179 loci actively demethylated by DML enzymes. Mutations in DML genes lead to locus-specific DNA hypermethylation. Reintroducing WT DML genes restores most loci to the normal pattern of methylation, although at some loci, hypermethylated epialleles persist. Of loci demethylated by DML enzymes, >80% are near or overlap genes. Genic demethylation by DML enzymes primarily occurs at the 5′ and 3′ ends, a pattern opposite to the overall distribution of WT DNA methylation. Our results show that demethylation by DML DNA glycosylases edits the patterns of DNA methylation within the Arabidopsis genome to protect genes from potentially deleterious methylation.}, author = {Penterman, Jon and Zilberman, Daniel and Huh, Jin Hoe and Ballinger, Tracy and Henikoff, Steven and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {16}, pages = {6752--6757}, publisher = {National Academy of Sciences}, title = {{DNA demethylation in the Arabidopsis genome}}, doi = {10.1073/pnas.0701861104}, volume = {104}, year = {2007}, } @article{18370, abstract = {An efficient algorithm for isometry-invariant matching of surfaces is presented. The key idea is computing the minimum-distortion mapping between two surfaces. For this purpose, we introduce the generalized multidimensional scaling, a computationally efficient continuous optimization algorithm for finding the least distortion embedding of one surface into another. The generalized multidimensional scaling algorithm allows for both full and partial surface matching. As an example, it is applied to the problem of expression-invariant three-dimensional face recognition.}, author = {Bronstein, Alexander and Bronstein, Michael M. and Kimmel, Ron}, issn = {1091-6490}, journal = {PNAS}, number = {5}, pages = {1168--1172}, publisher = {National Academy of Sciences}, title = {{Generalized multidimensional scaling: A framework for isometry-invariant partial surface matching}}, doi = {10.1073/pnas.0508601103}, volume = {103}, year = {2006}, } @article{11877, abstract = {The World Wide Web provides a unprecedented opportunity to automatically analyze a large sample of interests and activity in the world. We discuss methods for extracting knowledge from the web by randomly sampling and analyzing hosts and pages, and by analyzing the link structure of the web and how links accumulate over time. A variety of interesting and valuable information can be extracted, such as the distribution of web pages over domains, the distribution of interest in different areas, communities related to different topics, the nature of competition in different categories of sites, and the degree of communication between different communities or countries.}, author = {Henzinger, Monika H and Lawrence, Steve}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {suppl_1}, pages = {5186--5191}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Extracting knowledge from the World Wide Web}}, doi = {10.1073/pnas.0307528100}, volume = {101}, year = {2004}, } @article{3543, abstract = {Both neocortical and hippocampal networks organize the firing patterns of their neurons by prominent oscillations during sleep, but the functional role of these rhythms is not well understood. Here, we show a robust correlation of neuronal discharges between the somatosensory cortex and hippocampus on both slow and fine time scales in the mouse and rat. Neuronal bursts in deep cortical layers, associated with sleep spindles and delta waves/slow rhythm, effectively triggered hippocampal discharges related to fast (ripple) oscillations. We hypothesize that oscillation-mediated temporal links coordinate specific information transfer between neocortical and hippocampal cell assemblies. Such a neocortical-hippocampal interplay may be important for memory consolidation.}, author = {Sirota, Anton and Csicsvari, Jozsef L and Buhl, Derek and Buzsáki, György}, issn = {1091-6490}, journal = {PNAS}, number = {4}, pages = {2065 -- 2069}, publisher = {National Academy of Sciences}, title = {{Communication between neocortex and hippocampus during sleep in rodents}}, doi = {10.1073/pnas.0437938100}, volume = {100}, year = {2003}, }