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171.
Multiplication of Rous sarcoma virus and morphological conversion of chicken embryo fibroblasts are mediated by a DNA provirus. The role of the provirus in induction of morphological conversion has been shown by experiments of light inactivation of bromodeoxyuridine (BUdR)-sensitized proviral DNA. In the experiments reported here, inactivation of focus formation by BUdR and light could be obtained in cells in which the ability to produce virus has become resistant to X irradiation. This property is considered here to reflect the integrated state of the provirus. These experiments indicate that the role of proviral DNA extends beyond induction of morphological conversion and that an intact provirus is required for the maintenance of the transformed state. These experiments also indicate that no irreversible process leading to morphological conversion is initiated by a nonintegrated or by an integrated provirus.  相似文献   
172.
Although it is generally recognized that global biodiversity is declining, few studies have examined long‐term changes in multiple biodiversity dimensions simultaneously. In this study, we quantified and compared temporal changes in the abundance, taxonomic diversity, functional diversity, and phylogenetic diversity of bird assemblages, using roadside monitoring data of the North American Breeding Bird Survey from 1971 to 2010. We calculated 12 abundance and diversity metrics based on 5‐year average abundances of 519 species for each of 768 monitoring routes. We did this for all bird species together as well as for four subgroups based on breeding habitat affinity (grassland, woodland, wetland, and shrubland breeders). The majority of the biodiversity metrics increased or remained constant over the study period, whereas the overall abundance of birds showed a pronounced decrease, primarily driven by declines of the most abundant species. These results highlight how stable or even increasing metrics of taxonomic, functional, or phylogenetic diversity may occur in parallel with substantial losses of individuals. We further found that patterns of change differed among the species subgroups, with both abundance and diversity increasing for woodland birds and decreasing for grassland breeders. The contrasting changes between abundance and diversity and among the breeding habitat groups underscore the relevance of a multifaceted approach to measuring biodiversity change. Our findings further stress the importance of monitoring the overall abundance of individuals in addition to metrics of taxonomic, functional, or phylogenetic diversity, thus confirming the importance of population abundance as an essential biodiversity variable.  相似文献   
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The polymerization of hemoglobin-derived ferric-protoporphyrin IX [Fe(III)PPIX] to inert hemozoin (malaria pigment) is a crucial and unique process for intraerythrocytic plasmodia to prevent heme toxicity and thus a good target for new antimalarials. Quinoline drugs, i.e., chloroquine, and non-iron porphyrins have been shown to block polymerization by forming electronic pi-pi interactions with heme monomers. Here, we report the identification of ferrous-protoporphyrin IX [Fe(II)PPIX] as a novel endogenous anti-malarial. Fe(II)PPIX molecules, released from the proteolysis of hemoglobin, are first oxidized and then polymerized to hemozoin. We obtained Fe(II)PPIX on preparative scale by electrochemical reduction of Fe(III)PPIX, and the reaction was monitored by cyclic voltammetry. Polymerization assays at acidic pH were conducted with the resulting Fe(II)PPIX using a spectrophotometric microassay of heme polymerization adapted to anaerobic conditions and the products characterized by infrared spectroscopy. Fe(II)PPIX (a) did not polymerize and (b) produced a dose-dependent inhibition of Fe(III)PPIX polymerization (IC(50) = 0.4 molar equiv). Moreover, Fe(II)PPIX produced by chemical reduction with thiol-containing compounds gave similar results: a dose-dependent inhibition of heme polymerization was observed using either L-cysteine, N-acetylcysteine, or DL-homocysteine, but not with L-cystine. Cyclic voltammetry confirmed that the inhibition of heme polymerization was due to the Fe(II)PPIX molecules generated by the thiol-mediated reduction of Fe(III)PPIX. These results point to Fe(II)PPIX as a potential endogenous antimalarial and to Fe(III)PPIX reduction as a potential new pharmacological target.  相似文献   
176.
Effect of genotype and season on gynogenesis efficiency in Gerbera   总被引:5,自引:0,他引:5  
The effects of season, genotype and their interaction on haploid production were evaluated on four genotypes responsive to gynogenesis. Naked mature unfertilised ovules, collected from April to October, were cultivated on modified MS basal medium plus 0.88 μM 6-benzyladenine and 0.57 μM indol-3-acetic acid. After 30–60 days, recovered calli were transferred to a MS basal medium with 8.8 μM BA and 0.57 μM IAA for regeneration. Genotype and season of ovule collection substantially interact in the recovery of haploid calli. Between the four genotypes analysed, two gave more calli in the spring, one in the autumn and the fourth showed only weak differences between seasons. Shoot recovery depended upon both the season of ovule collection and the genotype but no significant interaction was shown by our data. The ability to produce haploid callus is not predictive for efficient shoot regeneration. This revised version was published online in June 2006 with corrections to the Cover Date.  相似文献   
177.
The whole cell biological conversion of naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene by the E. coli JM109(pPS1778) recombinant strain carrying the naphthalene dioxygenase and regulatory genes cloned from Pseudomonas fluorescens N3 in micellar systems has been investigated using biochemical and chemico-physical techniques. Reverse and direct micellar systems have been tested. Non-ionic surfactants (Tween and Triton X series) were found not to inhibit either the growth of the bacteria and the expression of the hydroxylating dioxygenase enzyme in such systems and were utilized in order to speed up the naphthalene conversion by increasing its solubility and also its bioavailability. The phase behavior of the direct micellar system was characterized through light scattering and other chemico-physical techniques. Further addition of isopropyl-palmitate 1–2% v/v to the micellar systems resulted in an increase of the apparent substrate concentration in solution and particularly its bioavailability thus allowing faster catalytic conversions resulting in an increase in productivity for the process. Since the cis-dihydrodiols are acquiring considerable potential as chiral pool synthons in asymmetric synthesis for a variety of industrial processes, possible applications for efficient small and large-scale production of such compounds are discussed.  相似文献   
178.
Evolving in sync with the computation revolution over the past 30 years, computational biology has emerged as a mature scientific field. While the field has made major contributions toward improving scientific knowledge and human health, individual computational biology practitioners at various institutions often languish in career development. As optimistic biologists passionate about the future of our field, we propose solutions for both eager and reluctant individual scientists, institutions, publishers, funding agencies, and educators to fully embrace computational biology. We believe that in order to pave the way for the next generation of discoveries, we need to improve recognition for computational biologists and better align pathways of career success with pathways of scientific progress. With 10 outlined steps, we call on all adjacent fields to move away from the traditional individual, single-discipline investigator research model and embrace multidisciplinary, data-driven, team science.

Do you want to attract computational biologists to your project or to your department? Despite the major contributions of computational biology, those attempting to bridge the interdisciplinary gap often languish in career advancement, publication, and grant review. Here, sixteen computational biologists around the globe present "A field guide to cultivating computational biology," focusing on solutions.

Biology in the digital era requires computation and collaboration. A modern research project may include multiple model systems, use multiple assay technologies, collect varying data types, and require complex computational strategies, which together make effective design and execution difficult or impossible for any individual scientist. While some labs, institutions, funding bodies, publishers, and other educators have already embraced a team science model in computational biology and thrived [17], others who have not yet fully adopted it risk severely lagging behind the cutting edge. We propose a general solution: “deep integration” between biology and the computational sciences. Many different collaborative models can yield deep integration, and different problems require different approaches (Fig 1).Open in a separate windowFig 1Supporting interdisciplinary team science will accelerate biological discoveries.Scientists who have little exposure to different fields build silos, in which they perform science without external input. To solve hard problems and to extend your impact, collaborate with diverse scientists, communicate effectively, recognize the importance of core facilities, and embrace research parasitism. In biologically focused parasitism, wet lab biologists use existing computational tools to solve problems; in computationally focused parasitism, primarily dry lab biologists analyze publicly available data. Both strategies maximize the use and societal benefit of scientific data.In this article, we define computational science extremely broadly to include all quantitative approaches such as computer science, statistics, machine learning, and mathematics. We also define biology broadly, including any scientific inquiry pertaining to life and its many complications. A harmonious deep integration between biology and computer science requires action—we outline 10 immediate calls to action in this article and aim our speech directly at individual scientists, institutions, funding agencies, and publishers in an attempt to shift perspectives and enable action toward accepting and embracing computational biology as a mature, necessary, and inevitable discipline (Box 1).Box 1. Ten calls to action for individual scientists, funding bodies, publishers, and institutions to cultivate computational biology. Many actions require increased funding support, while others require a perspective shift. For those actions that require funding, we believe convincing the community of need is the first step toward agencies and systems allocating sufficient support
  1. Respect collaborators’ specific research interests and motivationsProblem: Researchers face conflicts when their goals do not align with collaborators. For example, projects with routine analyses provide little benefit for computational biologists.Solution: Explicit discussion about interests/expertise/goals at project onset.Opportunity: Clearly defined expectations identify gaps, provide commitment to mutual benefit.
  2. Seek necessary input during project design and throughout the project life cycleProblem: Modern research projects require multiple experts spanning the project’s complexity.Solution: Engage complementary scientists with necessary expertise throughout the entire project life cycle.Opportunity: Better designed and controlled studies with higher likelihood for success.
  3. Provide and preserve budgets for computational biologists’ workProblem: The perception that analysis is “free” leads to collaborator budget cuts.Solution: When budget cuts are necessary, ensure that they are spread evenly.Opportunity: More accurate, reproducible, and trustworthy computational analyses.
  4. Downplay publication author order as an evaluation metric for computational biologistsProblem: Computational biologist roles on publications are poorly understood and undervalued.Solution: Journals provide more equitable opportunities, funding bodies and institutions improve understanding of the importance of team science, scientists educate each other.Opportunity: Engage more computational biologist collaborators, provide opportunities for more high-impact work.
  5. Value software as an academic productProblem: Software is relatively undervalued and can end up poorly maintained and supported, wasting the time put into its creation.Solution: Scientists cite software, and funding bodies provide more software funding opportunities.Opportunity: More high-quality maintainable biology software will save time, reduce reimplementation, and increase analysis reproducibility.
  6. Establish academic structures and review panels that specifically reward team scienceProblem: Current mechanisms do not consistently reward multidisciplinary work.Solution: Separate evaluation structures to better align peer review to reward indicators of team science.Opportunity: More collaboration to attack complex multidisciplinary problems.
  7. Develop and reward cross-disciplinary training and mentoringProblem: Academic labs and institutions are often insufficiently equipped to provide training to tackle the next generation of biological problems, which require computational skills.Solution: Create better training programs aligned to necessary on-the-job skills with an emphasis on communication, encourage wet/dry co-mentorship, and engage younger students to pursue computational biology.Opportunity: Interdisciplinary students uncover important insights in their own data.
  8. Support computing and experimental infrastructure to empower computational biologistsProblem: Individual computational labs often fund suboptimal cluster computing systems and lack access to data generation facilities.Solution: Institutions can support centralized compute and engage core facilities to provide data services.Opportunity: Time and cost savings for often overlooked administrative tasks.
  9. Provide incentives and mechanisms to share open data to empower discovery through reanalysisProblem: Data are often siloed and have untapped potential.Solution: Provide institutional data storage with standardized identifiers and provide separate funding mechanisms and publishing venues for data reuse.Opportunity: Foster new breed of researchers, “research parasites,” who will integrate multimodal data and enhance mechanistic insights.
  10. Consider infrastructural, ethical, and cultural barriers to clinical data accessProblem: Identifiable health data, which include sensitive information that must be kept hidden, are distributed and disorganized, and thus underutilized.Solution: Leadership must enforce policies to share deidentifiable data with interoperable metadata identifiers.Opportunity: Derive new insights from multimodal data integration and build datasets with increased power to make biological discoveries.
  相似文献   
179.
Habitat richness, that is, the diversity of ecosystem types, is a complex, spatially explicit aspect of biodiversity, which is affected by bioclimatic, geographic, and anthropogenic variables. The distribution of habitat types is a key component for understanding broad‐scale biodiversity and for developing conservation strategies. We used data on the distribution of European Union (EU) habitats to answer the following questions: (i) how do bioclimatic, geographic, and anthropogenic variables affect habitat richness? (ii) Which of those factors is the most important? (iii) How do interactions among these variables influence habitat richness and which combinations produce the strongest interactions? The distribution maps of 222 terrestrial habitat types as defined by the Natura 2000 network were used to calculate habitat richness for the 10 km × 10 km EU grid map. We then investigated how environmental variables affect habitat richness, using generalized linear models, generalized additive models, and boosted regression trees. The main factors associated with habitat richness were geographic variables, with negative relationships observed for both latitude and longitude, and a positive relationship for terrain ruggedness. Bioclimatic variables played a secondary role, with habitat richness increasing slightly with annual mean temperature and overall annual precipitation. We also found an interaction between anthropogenic variables, with the combination of increased landscape fragmentation and increased population density strongly decreasing habitat richness. This is the first attempt to disentangle spatial patterns of habitat richness at the continental scale, as a key tool for protecting biodiversity. The number of European habitats is related to geography more than climate and human pressure, reflecting a major component of biogeographical patterns similar to the drivers observed at the species level. The interaction between anthropogenic variables highlights the need for coordinated, continental‐scale management plans for biodiversity conservation.  相似文献   
180.
Current information on pancreatic islet sulfonylurea receptors has been obtained with laboratory animal pancreatic β cells or stable β-cell lines. In the present study, we evaluated the properties of sulfonylurea receptors of human islets of Langherans, prepared by collagenase digestion and density-gradient purification. The binding characterisitics of labeled glibenclamide to pancreatic islet membrane preparations were analyzed, displacement studies with several oral hypoglycemic agents were performed, and these latter compounds were tested as for their insulinotropic action on intact human islets. [3H]glibenclamide saturable binding was shown to be linear at ≤0.25 mg/ml protein; it was both temperature and time dependent. Scatchard analysis of the equilibrium binding data at 25°C indicated the presence of a single class of saturable, high-affinity binding sites with a Kd value of 1.0 ± 0.07 nM and a Bmax value of 657 ± 48 fmol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested: glibenclamide = glimepiride > tolbutamide > chlorpropamide ≫ metformin. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds. J. Cell. Biochem. 71:182–188, 1998. © 1998 Wiley-Liss, Inc.  相似文献   
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