Causal protein-signaling networks derived from multiparameter single-cell data     

Sachs K  Perez O  Pe'er D  Lauffenburger DA  Nolan GP 《Science (New York, N.Y.)》2005,308(5721):523-529

Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the ordering of connections between pathway components, wherein Bayesian network computational methods automatically elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.  相似文献   

Constraints on neon and argon isotopic fractionation in solar wind     

Meshik A  Mabry J  Hohenberg C  Marrocchi Y  Pravdivtseva O  Burnett D  Olinger C  Wiens R  Reisenfeld D  Allton J  McNamara K  Stansbery E  Jurewicz AJ 《Science (New York, N.Y.)》2007,318(5849):433-435

To evaluate the isotopic composition of the solar nebula from which the planets formed, the relation between isotopes measured in the solar wind and on the Sun's surface needs to be known. The Genesis Discovery mission returned independent samples of three types of solar wind produced by different solar processes that provide a check on possible isotopic variations, or fractionation, between the solar-wind and solar-surface material. At a high level of precision, we observed no significant inter-regime differences in 20Ne/22Ne or 36Ar/38Ar values. For 20Ne/22Ne, the difference between low- and high-speed wind components is 0.24 +/- 0.37%; for 36Ar/38Ar, it is 0.11 +/- 0.26%. Our measured 36Ar/38Ar ratio in the solar wind of 5.501 +/- 0.005 is 3.42 +/- 0.09% higher than that of the terrestrial atmosphere, which may reflect atmospheric losses early in Earth's history.  相似文献   

The convergence of synthetic organic and polymer chemistries     

Hawker CJ  Wooley KL 《Science (New York, N.Y.)》2005,309(5738):1200-1205

Several recent conceptual advances, which take advantage of the design criteria and practical techniques of molecular-level control in organic chemistry, allow preparation of well-defined polymers and nanostructured materials. Two trends are clear: the realization that synthesis of complex macromolecules poses major challenges and opportunities and the expectation that such materials will exhibit distinctive properties and functions. Polymer synthesis methods now being developed will yield well-defined synthetic macromolecules that are capable of mimicking many of the features of proteins (for example, three-dimensional folded structure) and other natural materials. These macromolecules have far-reaching potential for the study of molecular-level behavior at interfaces, in thin films, and in solution, while also enabling the development of encapsulation, drug-delivery, and nanoscale-patterning technologies.  相似文献   

A delicate balance in Amazonia     

Bruna EM  Kainer KA 《Science (New York, N.Y.)》2005,307(5712):1044-5; author reply 1044-5

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Block copolymer assembly via kinetic control     

Cui H  Chen Z  Zhong S  Wooley KL  Pochan DJ 《Science (New York, N.Y.)》2007,317(5838):647-650

Block copolymers consist of two or more chemically different polymer segments, or blocks, connected by a covalent linkage. In solution, amphiphilic blocks can self-assemble as a result of energetic repulsion effects between blocks. The degree of repulsion, the lengths of the block segments, and the selectivity of the solvent primarily control the resultant assembled morphology. In an ideal situation, one would like to be able to alter the morphology that forms without having to change the chemistry of the block copolymer. Through the kinetic manipulation of charged, amphiphilic block copolymers in solution, we are able to generate different nanoscale structures with simple block copolymer chemistry. The technique relies on divalent organic counter ions and solvent mixtures to drive the organization of the block copolymers down specific pathways into complex one-dimensional structures. Block copolymers are increasingly used as templating materials; thus, the ability to control the formation of specific patterns and structures is of growing interest and applicability.  相似文献   

Secondary siRNAs result from unprimed RNA synthesis and form a distinct class   总被引：1，自引：0，他引：1  

Sijen T  Steiner FA  Thijssen KL  Plasterk RH 《Science (New York, N.Y.)》2007,315(5809):244-247

In Caenorhabditis elegans, an effective RNA interference (RNAi) response requires the production of secondary short interfering RNAs (siRNAs) by RNA-directed RNA polymerases (RdRPs). We cloned secondary siRNAs from transgenic C. elegans lines expressing a single 22-nucleotide primary siRNA. Several secondary siRNAs start a few nucleotides downstream of the primary siRNA, indicating that non-RISC (RNA-induced silencing complex)-cleaved mRNAs are substrates for secondary siRNA production. In lines expressing primary siRNAs with single-nucleotide mismatches, secondary siRNAs do not carry the mismatch but contain the nucleotide complementary to the mRNA. We infer that RdRPs perform unprimed RNA synthesis. Secondary siRNAs are only of antisense polarity, carry 5' di- or triphosphates, and are only in the minority associated with RDE-1, the RNAi-specific Argonaute protein. Therefore, secondary siRNAs represent a distinct class of small RNAs. Their biogenesis depends on RdRPs, and we propose that each secondary siRNA is an individual RdRP product.  相似文献   

Retraction     

Davis ST  Benson BG  Bramson HN  Chapman DE  Dickerson SH  Dold KM  Eberwein DJ  Edelstein M  Frye SV  Gampe RT  Grifffen RJ  Harris PA  Hassell AM  Holmes WD  Hunter RN  Knick VB  Lackey K  Lovejoy B  Luzzio MJ  Murray D  Parker P  Rocque WJ  Shewchuk-Chapman L  Veal JM  Walker DH  Kuyper LF 《Science (New York, N.Y.)》2002,298(5602):2327

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Radioactive elements on Mercury's surface from MESSENGER: implications for the planet's formation and evolution     

Peplowski PN  Evans LG  Hauck SA  McCoy TJ  Boynton WV  Gillis-Davis JJ  Ebel DS  Goldsten JO  Hamara DK  Lawrence DJ  McNutt RL  Nittler LR  Solomon SC  Rhodes EA  Sprague AL  Starr RD  Stockstill-Cahill KR 《Science (New York, N.Y.)》2011,333(6051):1850-1852

The MESSENGER Gamma-Ray Spectrometer measured the average surface abundances of the radioactive elements potassium (K, 1150 ± 220 parts per million), thorium (Th, 220 ± 60 parts per billion), and uranium (U, 90 ± 20 parts per billion) in Mercury's northern hemisphere. The abundance of the moderately volatile element K, relative to Th and U, is inconsistent with physical models for the formation of Mercury requiring extreme heating of the planet or its precursor materials, and supports formation from volatile-containing material comparable to chondritic meteorites. Abundances of K, Th, and U indicate that internal heat production has declined substantially since Mercury's formation, consistent with widespread volcanism shortly after the end of late heavy bombardment 3.8 billion years ago and limited, isolated volcanic activity since.  相似文献   

Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum     

Bendall SC  Simonds EF  Qiu P  Amir el-AD  Krutzik PO  Finck R  Bruggner RV  Melamed R  Trejo A  Ornatsky OI  Balderas RS  Plevritis SK  Sachs K  Pe'er D  Tanner SD  Nolan GP 《Science (New York, N.Y.)》2011,332(6030):687-696

Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell "mass cytometry" to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, DNA content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.  相似文献   

Conserved eukaryotic fusogens can fuse viral envelopes to cells     

Avinoam O  Fridman K  Valansi C  Abutbul I  Zeev-Ben-Mordehai T  Maurer UE  Sapir A  Danino D  Grünewald K  White JM  Podbilewicz B 《Science (New York, N.Y.)》2011,332(6029):589-592

Caenorhabditis elegans proteins AFF-1 and EFF-1 [C. elegans fusion family (CeFF) proteins] are essential for developmental cell-to-cell fusion and can merge insect cells. To study the structure and function of AFF-1, we constructed vesicular stomatitis virus (VSV) displaying AFF-1 on the viral envelope, substituting the native fusogen VSV glycoprotein. Electron microscopy and tomography revealed that AFF-1 formed distinct supercomplexes resembling pentameric and hexameric "flowers" on pseudoviruses. Viruses carrying AFF-1 infected mammalian cells only when CeFFs were on the target cell surface. Furthermore, we identified fusion family (FF) proteins within and beyond nematodes, and divergent members from the human parasitic nematode Trichinella spiralis and the chordate Branchiostoma floridae could also fuse mammalian cells. Thus, FF proteins are part of an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle.  相似文献