Main Menu (Mobile)- Block

Main Menu - Block

custom | custom

Search Results

filters_region_cap | custom

Filter

facetapi-Q2b17qCsTdECvJIqZJgYMaGsr8vANl1n | block

Associated Lab

facetapi-W9JlIB1X0bjs93n1Alu3wHJQTTgDCBGe | block
facetapi-61yz1V0li8B1bixrCWxdAe2aYiEXdhd0 | block
facetapi-PV5lg7xuz68EAY8eakJzrcmwtdGEnxR0 | block
general_search_page-panel_pane_1 | views_panes

2432 Janelia Publications

Showing 2151-2160 of 2432 results
10/01/12 | Super-resolution using sparse representations over learned dictionaries: reconstruction of brain structure using electron microscopy.
Hu T, Nunez-Iglesias J, Vitaladevuni S, Scheffer L, Xu S, Bolorizadeh M, Hess H, Fetter R, Chklovskii D
arXiv.org . 2012 Oct:

A central problem in neuroscience is reconstructing neuronal circuits on the synapse level. Due to a wide range of scales in brain architecture such reconstruction requires imaging that is both high-resolution and high-throughput. Existing electron microscopy (EM) techniques possess required resolution in the lateral plane and either high-throughput or high depth resolution but not both. Here, we exploit recent advances in unsupervised learning and signal processing to obtain high depth-resolution EM images computationally without sacrificing throughput. First, we show that the brain tissue can be represented as a sparse linear combination of localized basis functions that are learned using high-resolution datasets. We then develop compressive sensing-inspired techniques that can reconstruct the brain tissue from very few (typically 5) tomographic views of each section. This enables tracing of neuronal processes and, hence, high throughput reconstruction of neural circuits on the level of individual synapses.

View Publication Page
01/01/12 | The Pfam protein families database.
Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, Heger A, Holm L, Sonnhammer EL, Sean R. Eddy , Bateman A, Finn RD
Nucleic acids research. 2012 Jan;40:D290-301. doi: 10.1093/nar/gkr1065

Pfam is a widely used database of protein families, currently containing more than 13,000 manually curated protein families as of release 26.0. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/). Here, we report on changes that have occurred since our 2010 NAR paper (release 24.0). Over the last 2 years, we have generated 1840 new families and increased coverage of the UniProt Knowledgebase (UniProtKB) to nearly 80%. Notably, we have taken the step of opening up the annotation of our families to the Wikipedia community, by linking Pfam families to relevant Wikipedia pages and encouraging the Pfam and Wikipedia communities to improve and expand those pages. We continue to improve the Pfam website and add new visualizations, such as the ’sunburst’ representation of taxonomic distribution of families. In this work we additionally address two topics that will be of particular interest to the Pfam community. First, we explain the definition and use of family-specific, manually curated gathering thresholds. Second, we discuss some of the features of domains of unknown function (also known as DUFs), which constitute a rapidly growing class of families within Pfam.

View Publication Page
01/01/12 | Use of a Drosophila genome-wide conserved sequence database to identify functionally related cis-regulatory enhancers.
Brody T, Yavatkar AS, Kuzin A, Kundu M, Tyson LJ, Ross J, Lin T, Lee C, Awasaki T, Lee T, Odenwald WF
Developmental Dynamics: An Official Publication of the American Association of Anatomists. 2012 Jan;241:169-89. doi: 10.1002/dvdy.22728

Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs.

View Publication Page
Magee Lab
12/22/11 | Observations on clustered synaptic plasticity and highly structured input patterns.
Magee JC
Neuron. 2011 Dec 22;72(6):887-8. doi: 10.1016/j.neuron.2011.12.009

In this issue of Neuron, Makino and Malinow and Kleindienst et al. present evidence of a behaviorally induced form of synaptic plasticity that would encourage the development of fine-scale structured input patterns and the binding of features within single neurons.

View Publication Page
12/16/11 | Synthesis of rhodamines from fluoresceins using Pd-catalyzed C-N cross-coupling.
Grimm JB, Lavis LD
Organic Letters. 2011 Dec 16;13(24):6354-7. doi: 10.1021/ol202618t

A unified, convenient, and efficient strategy for the preparation of rhodamines and N,N’-diacylated rhodamines has been developed. Fluorescein ditriflates were found to undergo palladium-catalyzed C-N cross-coupling with amines, amides, carbamates, and other nitrogen nucleophiles to provide direct access to known and novel rhodamine derivatives, including fluorescent dyes, quenchers, and latent fluorophores.

View Publication Page
12/12/11 | The BTB/POZ zinc finger protein Broad-Z3 promotes dendritic outgrowth during metamorphic remodeling of the peripheral stretch receptor dbd.
Scott JA, Williams DW, Truman JW
Neural Development. 2011 Dec 12;6:39. doi: 10.1186/1749-8104-6-39

Various members of the family of BTB/POZ zinc-finger transcription factors influence patterns of dendritic branching. One such member, Broad, is notable because its BrZ3 isoform is widely expressed in Drosophila in immature neurons around the time of arbor outgrowth. We used the metamorphic remodeling of an identified sensory neuron, the dorsal bipolar dendrite sensory neuron (dbd), to examine the effects of BrZ3 expression on the extent and pattern of dendrite growth during metamorphosis.

View Publication Page
Eddy/Rivas Lab
12/07/11 | Phosphorylation at the interface.
Davis FP
Structure . 2011 Dec 7;19:1726-7. doi: 10.1016/j.str.2011.11.006

Proteomic studies have identified thousands of eukaryotic phosphorylation sites (phosphosites), but few are functionally characterized. Nishi et al., in this issue of Structure, characterize phosphosites at protein-protein interfaces and estimate the effect of their phosphorylation on interaction affinity, by combining proteomics data with protein structures.

View Publication Page
Looger LabSchreiter Lab
12/02/11 | Structure of the escherichia coli phosphonate binding protein PhnD and rationally optimized phosphonate biosensors.
Alicea I, Marvin JS, Miklos AE, Ellington AD, Looger LL, Schreiter ER
Journal of Molecular Biology. 2011 Dec 2;414(3):356-69. doi: 10.1016/j.jmb.2011.09.047

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by \~{}70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins.

View Publication Page
12/01/11 | A critical role of mitochondrial phosphatase Ptpmt1 in embryogenesis reveals a mitochondrial metabolic stress-induced differentiation checkpoint in embryonic stem cells.
Shen J, Liu X, Yu W, Liu J, Nibbelink MG, Guo C, Finkel T, Qu C
Molecular and Cellular Biology. 2011 Dec;31:4902-16. doi: 10.1128/MCB.05629-11

Mitochondria are highly dynamic organelles that play multiple roles in cells. How mitochondria cooperatively modulate embryonic stem (ES) cell function during development is not fully understood. Global disruption of Ptpmt1, a mitochondrial Pten-like phosphatidylinositol phosphate (PIP) phosphatase, resulted in developmental arrest and postimplantation lethality. Ptpmt1(-/-) blastocysts failed to outgrow, and inner-cell-mass cells failed to thrive. Depletion of Ptpmt1 in conditional knockout ES cells decreased proliferation without affecting energy homeostasis or cell survival. Differentiation of Ptpmt1-depleted ES cells was essentially blocked. This was accompanied by upregulation of cyclin-dependent kinase inhibitors and a significant cell cycle delay. Reintroduction of wild-type but not of catalytically deficient Ptpmt1 C132S or truncated Ptpmt1 lacking the mitochondrial localization signal restored the differentiation capabilities of Ptpmt1 knockout ES cells. Intriguingly, Ptpmt1 is specifically important for stem cells, as ablation of Ptpmt1 in differentiated embryonic fibroblasts did not disturb cellular function. Further analyses demonstrated that oxygen consumption of Ptpmt1-depleted cells was decreased, while glycolysis was concomitantly enhanced. In addition, mitochondrial fusion/dynamics were compromised in Ptpmt1 knockout cells due to accumulation of PIPs. These studies, while establishing a crucial role for Ptpmt1 phosphatase in embryogenesis, reveal a mitochondrial metabolic stress-activated checkpoint in the control of ES cell differentiation.

View Publication Page
12/01/11 | Advances in the chemistry of small molecule fluorescent probes.
Wysocki LM, Lavis LD
Current Opinion in Chemical Biology. 2011 Dec;15(6):752-9. doi: 10.1016/j.cbpa.2011.10.013

Small molecule fluorophores are essential tools for chemical biology. A benefit of synthetic dyes is the ability to employ chemical approaches to control the properties and direct the position of the fluorophore. Applying modern synthetic organic chemistry strategies enables efficient tailoring of the chemical structure to obtain probes for specific biological experiments. Chemistry can also be used to activate fluorophores; new fluorogenic enzyme substrates and photoactivatable compounds with improved properties have been prepared that facilitate advanced imaging experiments with low background fluorescence. Finally, chemical reactions in live cells can be used to direct the spatial distribution of the fluorophore, allowing labeling of defined cellular regions with synthetic dyes.

View Publication Page