Throughout the natural world, organisms have responded to predators, inadequate resources, or inclement conditions by forming ongoing mutually beneficial partnerships--or symbioses--with different ...species. Symbiosis is the foundation for major evolutionary events, such as the emergence of eukaryotes and plant eating among vertebrates, and is also a crucial factor in shaping many ecological communities. The Symbiotic Habit provides an accessible and authoritative introduction to symbiosis, describing how symbioses are established, function, and persist in evolutionary and ecological time. Angela Douglas explains the evolutionary origins and development of symbiosis, and illustrates the principles of symbiosis using a variety of examples of symbiotic relationships as well as nonsymbiotic ones, such as parasitic or fleeting mutualistic associations. Although the reciprocal exchange of benefit is the key feature of symbioses, the benefits are often costly to provide, causing conflict among the partners. Douglas shows how these conflicts can be managed by a single controlling organism that may selectively reward cooperative partners, control partner transmission, and employ recognition mechanisms that discriminate between beneficial and potentially harmful or ineffective partners. The Symbiotic Habit reveals the broad uniformity of symbiotic process across many different symbioses among organisms with diverse evolutionary histories, and demonstrates how symbioses can be used to manage ecosystems, enhance food production, and promote human health.
All insects are colonized by microorganisms on the insect exoskeleton, in the gut and hemocoel, and within insect cells. The insect microbiota is generally different from microorganisms in the ...external environment, including ingested food. Specifically, certain microbial taxa are favored by the conditions and resources in the insect habitat, by their tolerance of insect immunity, and by specific mechanisms for their transmission. The resident microorganisms can promote insect fitness by contributing to nutrition, especially by providing essential amino acids, B vitamins, and, for fungal partners, sterols. Some microorganisms protect their insect hosts against pathogens, parasitoids, and other parasites by synthesizing specific toxins or modifying the insect immune system. Priorities for future research include elucidation of microbial contributions to detoxification, especially of plant allelochemicals in phytophagous insects, and resistance to pathogens; as well as their role in among-insect communication; and the potential value of manipulation of the microbiota to control insect pests.
Drug development has a high attrition rate, with poor pharmacokinetic and safety properties a significant hurdle. Computational approaches may help minimize these risks. We have developed a novel ...approach (pkCSM) which uses graph-based signatures to develop predictive models of central ADMET properties for drug development. pkCSM performs as well or better than current methods. A freely accessible web server (http://structure.bioc.cam.ac.uk/pkcsm), which retains no information submitted to it, provides an integrated platform to rapidly evaluate pharmacokinetic and toxicity properties.
UV Signature Mutations Brash, Douglas E.
Photochemistry and photobiology,
January/February 2015, Letnik:
91, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta‐analysis discusses signatures ...and their proper use. We first distinguish between a mutagen's canonical mutations—deviations from a random distribution of base changes to create a pattern typical of that mutagen—and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the nontranscribed strand or at the 3′ pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non‐UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; UV's nonsignature mutations may cause melanoma BRAF mutations; and the mutagen for sunlight‐related skin neoplasms may vary between continents.
Inverse relationship of canonical mutation patterns and mutation signatures for inferring the mutagen from mutations. Two mutagens are illustrated. A mutagen's canonical mutations deviate from random base changes, establishing a pattern typical for that mutagen. Different mutagens can produce the same canonical mutations (non‐informative mutations). Signature mutations are the subset of canonical mutations that, in addition, are unique to that mutagen and permit inference backward from mutations to mutagen. A mutagen therefore produces signature mutations plus non‐informative mutations. The latter are real and are produced by the mutagen, but are not useful for identifying that mutagen or carcinogen.
Insect pests are responsible for substantial crop losses worldwide through direct damage and transmission of plant diseases, and novel approaches that complement or replace broad-spectrum chemical ...insecticides will facilitate the sustainable intensification of food production in the coming decades. Multiple strategies for improved crop resistance to insect pests, especially strategies relating to plant secondary metabolism and immunity and microbiome science, are becoming available. Recent advances in metabolic engineering of plant secondary chemistry offer the promise of specific toxicity or deterrence to insect pests; improved understanding of plant immunity against insects provides routes to optimize plant defenses against insects; and the microbiomes of insect pests can be exploited, either as a target or as a vehicle for delivery of insecticidal agents. Implementation of these advances will be facilitated by ongoing advances in plant breeding and genetic technologies.
The role of science in policymaking has gained unprecedented stature in the United States, raising questions about the place of science and scientific expertise in the democratic process. Some ...scientists have been given considerable epistemic authority in shaping policy on issues of great moral and cultural significance, and the politicizing of these issues has become highly contentious.
Since World War II, most philosophers of science have purported the concept that science should be "value-free." InScience, Policy and the Value-Free Ideal,Heather E. Douglas argues that such an ideal is neither adequate nor desirable for science. She contends that the moral responsibilities of scientists require the consideration of values even at the heart of science. She lobbies for a new ideal in which values serve an essential function throughout scientific inquiry, but where the role values play is constrained at key points, thus protecting the integrity and objectivity of science. In this vein, Douglas outlines a system for the application of values to guide scientists through points of uncertainty fraught with moral valence.
Following a philosophical analysis of the historical background of science advising and the value-free ideal, Douglas defines how values should-and should not-function in science. She discusses the distinctive direct and indirect roles for values in reasoning, and outlines seven senses of objectivity, showing how each can be employed to determine the reliability of scientific claims. Douglas then uses these philosophical insights to clarify the distinction between junk science and sound science to be used in policymaking. In conclusion, she calls for greater openness on the values utilized in policymaking, and more public participation in the policymaking process, by suggesting various models for effective use of both the public and experts in key risk assessments.
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