Specificity of the E. coli LysR-Type Transcriptional Regulators

Families of paralogous oligomeric proteins are common in biology. How the specificity of assembly evolves is a fundamental question of biology. The LysR-Type Transcriptional Regulators (LTTR) form perhaps the largest family of transcriptional regulators in bacteria. Because genomes often encode many LTTR family members, it is assumed that many distinct homooligomers are formed simultaneously in the same cell without interfering with each other's activities, suggesting specificity in the interactions. However, this assumption has not been systematically tested.A negative-dominant assay with λcI repressor fusions was used to evaluate the assembly of the LTTRs in E. coli K-12. Thioredoxin (Trx)-LTTR fusions were used to challenge the homooligomeric interactions of λcI-LTTR fusions. Eight cI-LTTR fusions were challenged with twenty-eight Trx fusions. LTTRs could be divided into three classes based on their interactions with other LTTRs.Multimerization of LTTRs in E. coli K-12 is mostly specific. However, under the conditions of the assay, many LTTRs interact with more than one noncognate partner. The physiological significance and physical basis for these interactions are not known

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

Conjugative Plasmids of Neisseria gonorrhoeae

Many clinical isolates of the human pathogen Neisseria gonorrhoeae contain conjugative plasmids. The host range of these plasmids is limited to Neisseria species, but presence of a tetracycline (tetM) determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. Previously plasmids with different backbones (Dutch and American type backbones) and with and without different tetM determinants (Dutch and American type tetM determinants) have been identified. Within the isolates tested, all plasmids with American or Dutch type tetM determinants contained a Dutch type plasmid backbone. This demonstrated that tetM determinants should not be used to differentiate between conjugal plasmid backbones. The nucleotide sequences of conjugative plasmids with Dutch type plasmid backbones either not containing the tetM determinant (pEP5233) or containing Dutch (pEP5289) or American (pEP5050) type tetM determinants were determined. Analysis of the backbone sequences showed that they belong to a novel IncP1 subfamily divergent from the IncP1α, β, γ, δ and ε subfamilies. The tetM determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The presence of the toxin and antitoxin on different plasmids might explain why the host range of this IncP1 plasmid is limited to Neisseria species. The isolated plasmids conjugated efficiently between N. gonorrhoeae strains, but did not enhance transfer of a genetic marker

Parameter selection for and implementation of a web-based decision-support tool to predict extubation outcome in premature infants

BACKGROUND: Approximately 30% of intubated preterm infants with respiratory distress syndrome (RDS) will fail attempted extubation, requiring reintubation and mechanical ventilation. Although ventilator technology and monitoring of premature infants have improved over time, optimal extubation remains challenging. Furthermore, extubation decisions for premature infants require complex informational processing, techniques implicitly learned through clinical practice. Computer-aided decision-support tools would benefit inexperienced clinicians, especially during peak neonatal intensive care unit (NICU) census. METHODS: A five-step procedure was developed to identify predictive variables. Clinical expert (CE) thought processes comprised one model. Variables from that model were used to develop two mathematical models for the decision-support tool: an artificial neural network (ANN) and a multivariate logistic regression model (MLR). The ranking of the variables in the three models was compared using the Wilcoxon Signed Rank Test. The best performing model was used in a web-based decision-support tool with a user interface implemented in Hypertext Markup Language (HTML) and the mathematical model employing the ANN. RESULTS: CEs identified 51 potentially predictive variables for extubation decisions for an infant on mechanical ventilation. Comparisons of the three models showed a significant difference between the ANN and the CE (p = 0.0006). Of the original 51 potentially predictive variables, the 13 most predictive variables were used to develop an ANN as a web-based decision-tool. The ANN processes user-provided data and returns the prediction 0–1 score and a novelty index. The user then selects the most appropriate threshold for categorizing the prediction as a success or failure. Furthermore, the novelty index, indicating the similarity of the test case to the training case, allows the user to assess the confidence level of the prediction with regard to how much the new data differ from the data originally used for the development of the prediction tool. CONCLUSION: State-of-the-art, machine-learning methods can be employed for the development of sophisticated tools to aid clinicians' decisions. We identified numerous variables considered relevant for extubation decisions for mechanically ventilated premature infants with RDS. We then developed a web-based decision-support tool for clinicians which can be made widely available and potentially improve patient care world wide

Effects of climate and snow depth on Bromus tectorum population dynamics at high elevation

Invasive plants are thought to be especially capable of range shifts or expansion in response to climate change due to high dispersal and colonization abilities. Although highly invasive throughout the Intermountain West, the presence and impact of the grass Bromus tectorum has been limited at higher elevations in the eastern Sierra Nevada, potentially due to extreme wintertime conditions. However, climate models project an upward elevational shift of climate regimes in the Sierra Nevada that could favor B. tectorum expansion. This research specifically examined the effects of experimental snow depth manipulations and interannual climate variability over 5 years on B. tectorum populations at high elevation (2,175 m). Experimentally-increased snow depth had an effect on phenology and biomass, but no effect on individual fecundity. Instead an experimentally-increased snowpack inhibited population growth in 1 year by reducing seedling emergence and early survival. A similar negative effect of increased snow was observed 2 years later. However, a strong negative effect on B. tectorum was also associated with a naturally low-snow winter, when seedling emergence was reduced by 86%. Across 5 years, winters with greater snow cover and a slower accumulation of degree-days coincided with higher B. tectorum seedling density and population growth. Thus, we observed negative effects associated with both experimentally-increased and naturally-decreased snowpacks. It is likely that the effect of snow at high elevation is nonlinear and differs from lower elevations where wintertime germination can be favorable. Additionally, we observed a doubling of population size in 1 year, which is alarming at this elevation

Both male and female identity influence variation in male signalling effort

<p>Abstract</p> <p>Background</p> <p>Male sexual displays play an important role in sexual selection by affecting reproductive success. However, for such displays to be useful for female mate choice, courtship should vary more among than within individual males. In this regard, a potentially important source of within male variation is adjustment of male courtship effort in response to female traits. Accordingly, we set out to dissect sources of variation in male courtship effort in a fish, the desert goby (<it>Chlamydogobius eremius</it>). We did so by designing an experiment that allowed simultaneous estimation of within and between male variation in courtship, while also assessing the importance of the males and females as sources of courtship variation.</p> <p>Results</p> <p>Although males adjusted their courtship depending on the identity of the female (a potentially important source of within-male variation), among-male differences were considerably greater. In addition, male courtship effort towards a pair of females was highly repeatable over a short time frame.</p> <p>Conclusion</p> <p>Despite the plasticity in male courtship effort, courtship displays had the potential to reliably convey information about the male to mate-searching females. Our experiment therefore underscores the importance of addressing the different sources contributing to variation in the expression of sexually-selected traits.</p

Rationale and design: telepsychology service delivery for depressed elderly veterans

<p>Abstract</p> <p>Background</p> <p>Older adults who live in rural areas experience significant disparities in health status and access to mental health care. "Telepsychology," (also referred to as "telepsychiatry," or "telemental health") represents a potential strategy towards addressing this longstanding problem. Older adults may benefit from telepsychology due to its: (1) utility to address existing problematic access to care for rural residents; (2) capacity to reduce stigma associated with traditional mental health care; and (3) utility to overcome significant age-related problems in ambulation and transportation. Moreover, preliminary evidence indicates that telepsychiatry programs are often less expensive for patients, and reduce travel time, travel costs, and time off from work. Thus, telepsychology may provide a cost-efficient solution to access-to-care problems in rural areas.</p> <p>Methods</p> <p>We describe an ongoing four-year prospective, randomized clinical trial comparing the effectiveness of an empirically supported treatment for major depressive disorder, Behavioral Activation, delivered either via in-home videoconferencing technology ("Telepsychology") or traditional face-to-face services ("Same-Room"). Our hypothesis is that in-homeTelepsychology service delivery will be equally effective as the traditional mode (Same-Room). Two-hundred twenty-four (224) male and female elderly participants will be administered protocol-driven individual Behavioral Activation therapy for depression over an 8-week period; and subjects will be followed for 12-months to ascertain longer-term effects of the treatment on three outcomes domains: (1) clinical outcomes (symptom severity, social functioning); (2) process variables (patient satisfaction, treatment credibility, attendance, adherence, dropout); and (3) economic outcomes (cost and resource use).</p> <p>Discussion</p> <p>Results from the proposed study will provide important insight into whether telepsychology service delivery is as effective as the traditional mode of service delivery, defined in terms of clinical, process, and economic outcomes, for elderly patients with depression residing in rural areas without adequate access to mental health services.</p> <p>Trial registration</p> <p>National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00324701).</p

Production and characterization of murine models of classic and intermediate maple syrup urine disease

BACKGROUND: Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency. Current treatments are not satisfactory and require new approaches to combat this disease. A major hurdle in developing new treatments has been the lack of a suitable animal model. METHODS: To create a murine model of classic MSUD, we used gene targeting and embryonic stem cell technologies to create a mouse line that lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To create a murine model of intermediate MSUD, we used transgenic technology to express a human E2 cDNA on the knockout background. Mice of both models were characterized at the molecular, biochemical, and whole animal levels. RESULTS: By disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we created a gene knockout mouse model of classic MSUD. The homozygous knockout mice lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and had a 3-fold increase in circulating branched-chain amino acids. These metabolic derangements resulted in neonatal lethality. Transgenic expression of a human E2 cDNA in the liver of the E2 knockout animals produced a model of intermediate MSUD. Branched-chain keto acid dehydrogenase activity was 5–6% of normal and was sufficient to allow survival, but was insufficient to normalize circulating branched-chain amino acids levels, which were intermediate between wildtype and the classic MSUD mouse model. CONCLUSION: These mice represent important animal models that closely approximate the phenotype of humans with the classic and intermediate forms of MSUD. These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease