Amplification of acetylcholine-binding catenanes from dynamic combinatorial libraries     

Lam RT  Belenguer A  Roberts SL  Naumann C  Jarrosson T  Otto S  Sanders JK 《Science (New York, N.Y.)》2005,308(5722):667-669

Directed chemical synthesis can produce a vast range of molecular structures, but the intended product must be known at the outset. In contrast, evolution in nature can lead to efficient receptors and catalysts whose structures defy prediction. To access such unpredictable structures, we prepared dynamic combinatorial libraries in which reversibly binding building blocks assemble around a receptor target. We selected for an acetylcholine receptor by adding the neurotransmitter to solutions of dipeptide hydrazones [proline-phenylalanine or proline-(cyclohexyl)alanine], which reversibly combine through hydrazone linkages. At thermodynamic equilibrium, the dominant receptor structure was an elaborate [2]-catenane consisting of two interlocked macrocyclic trimers. This complex receptor with a 100 nM affinity for acetylcholine could be isolated on a preparative scale in 67% yield.  相似文献   

Extreme reversed sexual dichromatism in a bird without sex role reversal     

Heinsohn R  Legge S  Endler JA 《Science (New York, N.Y.)》2005,309(5734):617-619

Brilliant plumage is typical of male birds, reflecting differential enhancement of male traits when females are the limiting sex. Brighter females are thought to evolve exclusively in response to sex role reversal. The striking reversed plumage dichromatism of Eclectus roratus parrots does not fit this pattern. We quantify plumage color in this species and show that very different selection pressures are acting on males and females. Male plumage reflects a compromise between the conflicting requirements for camouflage from predators while foraging and conspicuousness during display. Females are liberated from the need for camouflage but compete for rare nest hollows.  相似文献   

A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A     

Cruz-Migoni A  Hautbergue GM  Artymiuk PJ  Baker PJ  Bokori-Brown M  Chang CT  Dickman MJ  Essex-Lopresti A  Harding SV  Mahadi NM  Marshall LE  Mobbs GW  Mohamed R  Nathan S  Ngugi SA  Ong C  Ooi WF  Partridge LJ  Phillips HL  Raih MF  Ruzheinikov S  Sarkar-Tyson M  Sedelnikova SE  Smither SJ  Tan P  Titball RW  Wilson SA  Rice DW 《Science (New York, N.Y.)》2011,334(6057):821-824

The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1.  相似文献   

Ordered and dynamic assembly of single spliceosomes     

Hoskins AA  Friedman LJ  Gallagher SS  Crawford DJ  Anderson EG  Wombacher R  Ramirez N  Cornish VW  Gelles J  Moore MJ 《Science (New York, N.Y.)》2011,331(6022):1289-1295

The spliceosome is the complex macromolecular machine responsible for removing introns from precursors to messenger RNAs (pre-mRNAs). We combined yeast genetic engineering, chemical biology, and multiwavelength fluorescence microscopy to follow assembly of single spliceosomes in real time in whole-cell extracts. We find that individual spliceosomal subcomplexes associate with pre-mRNA sequentially via an ordered pathway to yield functional spliceosomes and that association of every subcomplex is reversible. Further, early subcomplex binding events do not fully commit a pre-mRNA to splicing; rather, commitment increases as assembly proceeds. These findings have important implications for the regulation of alternative splicing. This experimental strategy should prove widely useful for mechanistic analysis of other macromolecular machines in environments approaching the complexity of living cells.  相似文献   

Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery     

Pal-Bhadra M  Leibovitch BA  Gandhi SG  Rao M  Bhadra U  Birchler JA  Elgin SC 《Science (New York, N.Y.)》2004,303(5658):669-672

Genes normally resident in euchromatic domains are silenced when packaged into heterochromatin, as exemplified in Drosophila melanogaster by position effect variegation (PEV). Loss-of-function mutations resulting in suppression of PEV have identified critical components of heterochromatin, including proteins HP1, HP2, and histone H3 lysine 9 methyltransferase. Here, we demonstrate that this silencing is dependent on the RNA interference machinery, using tandem mini-white arrays and white transgenes in heterochromatin to show loss of silencing as a result of mutations in piwi, aubergine, or spindle-E (homeless), which encode RNAi components. These mutations result in reduction of H3 Lys9 methylation and delocalization of HP1 and HP2, most dramatically in spindle-E mutants.  相似文献   

Beyond noise mitigation: managing soundscapes as common-pool resources     

Sarah L. Dumyahn  Bryan C. Pijanowski 《Landscape Ecology》2011,26(9):1311-1326

The extent of noise and its impacts continues to grow globally indicating a different approach from regulating individual noise sources is needed. We pose the argument that soundscapes, or the acoustic environment, should be managed as a common-pool resource (CPR). Using CPR theory, we argue that soundscapes possess key features of CPRs: (1) multiple soundscape users, (2) difficulty of exclusion, and (3) subtractability and degradation. Using Ostrom’s Social-Ecological Systems (SES) framework, we describe the main elements of soundscapes to consider for their sustainable management. In order to assess noise issues and challenges in managing national park soundscapes, we conducted interviews with U.S. National Park Service managers at parks identified as having air tour overflight impacts. While most managers indicated that aircraft overflights posed the most serious impacts to park resources and visitor experiences, the park units also experienced several other types of noise impacts including traffic on park roads, park maintenance operations, and different types of motorized recreational vehicles. Addressing single sources of noise is necessary, as is the case with air tour overflights, but we argue that a more comprehensive approach is needed to protect park soundscapes. From this study several SES framework variables emerged that need to be addressed for sustainable management, such as the lack of clear soundscape boundaries, availability of acoustic monitoring and data, and the number and types of soundscape users. Based on CPR theory and using the SES framework, the challenges and a potential new approach for sustainable management are discussed.  相似文献   

Anthocyanin characterization utilizing liquid chromatography combined with advanced mass spectrometric detection     

Steimer S  Sjöberg PJ 《Journal of agricultural and food chemistry》2011,59(7):2988-2996

Anthocyanins are naturally occurring polyphenolic plant pigments. To analyze the anthocyanin content of samples, rapid and reliable methods for separation and detection are needed. In this work an LC-DAD-ESI-MS/MS instrument was used to develop a new tandem MS data acquisition strategy for anthocyanin characterization which was subsequently compared to more conventional measurements. It has been shown that the newly developed strategy, multiple reaction monitoring-initiated anthocyanin characterization (MIAC), can successfully be used in anthocyanin analysis and has various advantages compared to some more traditional measurements, such as enhanced selectivity, better signal-to-noise ratio and simplified data evaluation. Furthermore, the number of relevant MS/MS data increased significantly with the MIAC method compared with a more common information dependent MS experiment strategy.  相似文献   

Competencies: a cure for pre-med curriculum     

Anderson WA  Amasino RM  Ares M  Banerjee U  Bartel B  Corces VG  Drennan CL  Elgin SC  Epstein IR  Fanning E  Guillette LJ  Handelsman J  Hatfull GF  Hoy RR  Kelley D  Leinwand LA  Losick R  Lu Y  Lynn DG  Neuhauser C  O'Dowd DK  Olivera T  Pevzner P  Richards-Kortum RR  Rine J  Sah RL  Strobel SA  Walker GC  Walt DR  Warner IM  Wessler S  Willard HF  Zare RN 《Science (New York, N.Y.)》2011,334(6057):760-761

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A decision-analytic approach to the optimal allocation of resources for endangered species consultation     

Sarah J. Converse  Kevin J. Shelley  Steve Morey  Jeffrey Chan  Andrea LaTier  Carolyn Scafidi  Deborah T. Crouse  Michael C. Runge 《Biological conservation》2011,(1):319-329

The resources available to support conservation work, whether time or money, are limited. Decision makers need methods to help them identify the optimal allocation of limited resources to meet conservation goals, and decision analysis is uniquely suited to assist with the development of such methods. In recent years, a number of case studies have been described that examine optimal conservation decisions under fiscal constraints; here we develop methods to look at other types of constraints, including limited staff and regulatory deadlines. In the US, Section Seven consultation, an important component of protection under the federal Endangered Species Act, requires that federal agencies overseeing projects consult with federal biologists to avoid jeopardizing species. A benefit of consultation is negotiation of project modifications that lessen impacts on species, so staff time allocated to consultation supports conservation. However, some offices have experienced declining staff, potentially reducing the efficacy of consultation. This is true of the US Fish and Wildlife Service’s Washington Fish and Wildlife Office (WFWO) and its consultation work on federally-threatened bull trout (Salvelinus confluentus). To improve effectiveness, WFWO managers needed a tool to help allocate this work to maximize conservation benefits. We used a decision-analytic approach to score projects based on the value of staff time investment, and then identified an optimal decision rule for how scored projects would be allocated across bins, where projects in different bins received different time investments. We found that, given current staff, the optimal decision rule placed 80% of informal consultations (those where expected effects are beneficial, insignificant, or discountable) in a short bin where they would be completed without negotiating changes. The remaining 20% would be placed in a long bin, warranting an investment of seven days, including time for negotiation. For formal consultations (those where expected effects are significant), 82% of projects would be placed in a long bin, with an average time investment of 15 days. The WFWO is using this decision-support tool to help allocate staff time. Because workload allocation decisions are iterative, we describe a monitoring plan designed to increase the tool’s efficacy over time. This work has general application beyond Section Seven consultation, in that it provides a framework for efficient investment of staff time in conservation when such time is limited and when regulatory deadlines prevent an unconstrained approach.  相似文献   

The fate of Amazonian forest fragments: A 32-year investigation   总被引：2，自引：0，他引：2  

William F. Laurance  José L.C. Camargo  Regina C.C. Luizão  Susan G. Laurance  Stuart L. Pimm  Emilio M. Bruna  Philip C. Stouffer  G. Bruce Williamson  Julieta Benítez-Malvido  Heraldo L. Vasconcelos  Kyle S. Van Houtan  Charles E. Zartman  Sarah A. Boyle  Raphael K. Didham  Ana Andrade  Thomas E. Lovejoy 《Biological conservation》2011,(1):56-67

We synthesize findings to date from the world’s largest and longest-running experimental study of habitat fragmentation, located in central Amazonia. Over the past 32 years, Amazonian forest fragments ranging from 1 to 100 ha have experienced a wide array of ecological changes. Edge effects have been a dominant driver of fragment dynamics, strongly affecting forest microclimate, tree mortality, carbon storage, fauna, and other aspects of fragment ecology. However, edge-effect intensity varies markedly in space and time, and is influenced by factors such as edge age, the number of nearby edges, and the adjoining matrix of modified vegetation surrounding fragments. In our study area, the matrix has changed markedly over the course of the study (evolving from large cattle pastures to mosaics of abandoned pasture and regrowth forest) and this in turn has strongly influenced fragment dynamics and faunal persistence. Rare weather events, especially windstorms and droughts, have further altered fragment ecology. In general, populations and communities of species in fragments are hyperdynamic relative to nearby intact forest. Some edge and fragment-isolation effects have declined with a partial recovery of secondary forests around fragments, but other changes, such as altered patterns of tree recruitment, are ongoing. Fragments are highly sensitive to external vicissitudes, and even small changes in local land-management practices may drive fragmented ecosystems in markedly different directions. The effects of fragmentation are likely to interact synergistically with other anthropogenic threats such as logging, hunting, and especially fire, creating an even greater peril for the Amazonian biota.  相似文献