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Item Open Access Crystal structure and DNA binding activity of a PadR family transcription regulator from hypervirulent Clostridium difficile R20291(2016-10-04) Isom, Catherine E.; Menton, Smita K.; Thomas, Leonard M.; West, Ann H.; Richter-Addo, George B.; Karr, Elizabeth A.Background. Clostridium difficile is a spore-forming obligate anaerobe that can remain viable for extended periods, even in the presence of antibiotics, which contributes to the persistence of this bacterium as a human pathogen during host-to-host transmission and in hospital environments. We examined the structure and function of a gene product with the locus tag CDR20291_0991 (cdPadR1) as part of our broader goal aimed at elucidating transcription regulatory mechanisms involved in virulence and antibiotic resistance of the recently emergent hypervirulent C. difficile strain R20291. cdPadR1 is genomically positioned near genes that are involved in stress response and virulence. In addition, it was previously reported that cdPadR1 and a homologue from the historical C. difficile strain 630 (CD630_1154) were differentially expressed when exposed to stressors, including antibiotics. Results. The crystal structure of cdPadR1 was determined to 1.9 Å resolution, which revealed that it belongs to the PadR-s2 subfamily of PadR transcriptional regulators. cdPadR1 binds its own promoter and other promoter regions from within the C. difficile R20291 genome. DNA binding experiments demonstrated that cdPadR1 binds a region comprised of inverted repeats and an AT-rich core with the predicted specific binding motif, GTACTAT(N2)ATTATA(N)AGTA, within its own promoter that is also present in 200 other regions in the C. difficile R20291 genome. Mutation of the highly conserved W in α4 of the effector binding/oligomerization domain, which is predicted to be involved in multi-drug recognition and dimerization in other PadR-s2 proteins, resulted in alterations of cdPadR1 binding to the predicted binding motif, potentially due to loss of higher order oligomerization. Conclusions. Our results indicate that cdPadR1 binds a region within its own promoter consisting of the binding motif GTACTAT(N2)ATTATA(N)AGTA and seems to associate non-specifically with longer DNA fragments in vitro, which may facilitate promoter and motif searching. This suggests that cdPadR1 acts as a transcriptional auto-regulator, binding specific sites within its own promoter, and is part of a broad gene regulatory network involved, in part, with environmental stress response, antibiotic resistance and virulence.Item Open Access Is extinction forever?(2015) Smith-Patten, Brenda D.; Bridge, Eli S.; Crawford, Priscilla H. C.; Hough, Daniel J.; Kelly, Jeffrey F.; Patten, Michael A.Mistrust of science has seeped into public perception of the most fundamental aspect of conservation—extinction. The term ought to be straightforward, and yet, there is a disconnect between scientific discussion and public views. This is not a mere semantic issue, rather one of communication. Within a population dynamics context, we say that a species went locally extinct, later to document its return. Conveying our findings matters, for when we use local extinction, an essentially nonsensical phrase, rather than extirpation, which is what is meant, then we contribute to, if not create outright, a problem for public understanding of conservation, particularly as local extinction is often shortened to extinction in media sources. The public that receives the message of our research void of context and modifiers comes away with the idea that extinction is not forever or, worse for conservation as a whole, that an extinction crisis has been invented.Item Open Access Mining document, concept, and term associations for effective biomedical retrieval - Introducing MeSH-enhanced retrieval models(2015) Mao, Jin; Mu, Xiangming; Li, GangManually assigned subject terms, such as Medical Subject Headings (MeSH) in the health domain, describe the concepts or topics of a document. Existing information retrieval models do not take full advantage of such information. In this paper, we propose two MeSH-enhanced (ME) retrieval models that integrate the concept layer (i.e. MeSH) into the language modeling framework to improve retrieval performance. The new models quantify associations between documents and their assigned concepts to construct conceptual representations for the documents, and mine associations between concepts and terms to construct generative concept models. The two ME models reconstruct two essential estimation processes of the relevance model (Lavrenko and Croft 2001) by incorporating the document-concept and the concept-term associations. More specifically, in Model 1, language models of the pseudo-feedback documents are enriched by their assigned concepts. In Model 2, concepts that are related to users’ queries are first identified, and then used to reweight the pseudo-feedback documents according to the document-concept associations. Experiments carried out on two standard test collections show that the ME models outperformed the query likelihood model, the relevance model (RM3), and an earlier ME model. A detailed case analysis provides insight into how and why the new models improve/worsen retrieval performance. Implications and limitations of the study are discussed. This study provides new ways to formally incorporate semantic annotations, such as subject terms, into retrieval models. The findings of this study suggest that integrating the concept layer into retrieval models can further improve the performance over the current state-of-the-art models.Item Open Access On the geography of activity: productivity but not temperature constrains discovery rates by ectotherm consumers(2019) Kaspari, Michael; de Beurs, KirstenConsumer activity—the rate that individuals move through and discover items in their environment—can constrain population interactions and ecosystem services. We introduce a model that assumes consumer activity is co‐limited by the abundance and velocity of consumers, which in turn are constrained by two global drivers: net primary productivity (NPP) and environmental temperature, respectively. We test it with data from a recent study showing how arthropod activity decreases with latitude and elevation. The maximum discovery rates (discoveries per day) of these ectotherms increased linearly with NPP and accounted for the observed latitudinal gradient in activity. The mean temperature of the warmest month in contrast had no consistent effect on activity. An ecosystem's NPP, which provides carbon to build individuals and sugars to fuel them, can thus be an important constraint on the activity of its ectotherm consumers.