Evolution by leaps : gene duplication in bacteria

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biology Direct 4 (2009): 46, doi:10.1186/1745-6150-4-46.Sequence related families of genes and proteins are common in bacterial genomes. In Escherichia coli they constitute over half of the genome. The presence of families and superfamilies of proteins suggest a history of gene duplication and divergence during evolution. Genome encoded protein families, their size and functional composition, reflect metabolic potentials of the organisms they are found in. Comparing protein families of different organisms give insight into functional differences and similarities. Equivalent enzyme families with metabolic functions were selected from the genomes of four experimentally characterized bacteria belonging to separate genera. Both similarities and differences were detected in the protein family memberships, with more similarities being detected among the more closely related organisms. Protein family memberships reflected known metabolic characteristics of the organisms. Differences in divergence of functionally characterized enzyme family members accounted for characteristics of taxa known to differ in those biochemical properties and capabilities. While some members of the gene families will have been acquired by lateral exchange and other former family members will have been lost over time, duplication and divergence of genes and functions appear to have been a significant contributor to the functional diversity of today’s microbes. Protein families seem likely to have arisen during evolution by gene duplication and divergence where the gene copies that have been retained are the variants that have led to distinct bacterial physiologies and taxa. Thus divergence of the duplicate enzymes has been a major process in the generation of different kinds of bacteria.This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-08ER64511

Understanding the Solar Sources of In Situ Observations

The solar wind can, to a good approximation be described as a two‐component flow with fast, tenuous, quiescent flow emanating from coronal holes, and slow, dense and variable flow associated with the boundary between open and closed magnetic fields. In spite of its simplicity, this picture naturally produces a range of complex heliospheric phenomena, including the presence, location, and orientation of corotating interaction regions and their associated shocks. In this study, we apply a two‐step mapping technique, incorporating a magnetohydrodynamic model of the solar corona, to bring in situ observations from Ulysses, WIND, and ACE back to the solar surface in an effort to determine some intrinsic properties of the quasi‐steady solar wind. In particular, we find that a “layer” of ∼35,000 km exists between the Coronal Hole Boundary (CHB) and the fast solar wind, where the wind is slow and variable. We also derive a velocity gradient within large polar coronal holes (that were present during Ulysses’ rapid latitude scan) as a function of distance from the CHB. We find that v = 713 km/s + 3.2 d, where d is the angular distance from the CHB boundary in degrees. © 2003 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87654/2/79_1.pd

Proof of Concept of the use of Advanced Computational Accident Scenario Modeling for Safety Margin Economic Evaluation

The goal of this project was to pave the way for more data-driven decision making when considering safety within Nuclear Engineering by proving the concept of new and innovative accident scenario modeling techniques for the analysis of the economics of nuclear safety margins. To do this, a simple, if extremely detailed, cost-benefit analysis of potential nuclear power plant upgrades related to safety was performed. In this analysis, the cost of the upgrade was the direct monetary cost of implementing the upgrade. The benefit of the upgrade was the Risk avoided by implementing it, where Risk is the probability the upgrade will prevent or mitigate a radionuclide release, multiplied by the economic consequences of the unprevented or unmitigated radionuclide release. Offsite economic consequences have been found to scale largely linearly with the magnitude of the radionuclide release. To find the probability of a nuclear power plant upgrade preventing or mitigating a radionuclide release, Monte Carlo sampling of accident scenario stochastic parameters was used. By taking advantage of modern super computing capabilities to account for randomness within accident scenarios, a more in-depth and detailed view of safety was attained than is possible with older, more binary approaches. By mapping out the ‘failure space’ comprised by all possible combinations of stochastic parameters that lead to radionuclide release in an accident scenario, both with and without an upgrade, the average impact of the change was analyzed. Finally, comparing the costs and benefits of various potential power plant upgrades, the most cost-effective ways of improving nuclear safety were discerned

Thomas H. Riley Jr. Correspondence

Entries include brief biographical information, a lengthy typed biography on Brunswick Savings Institution, Inc., Brunswick, Maine, stationery, and a letter of receipt for several copies of the booklet Mutual Savings Banks

A solar wind coronal origin study from SOHO/UVCS and ACE/SWICS joint analysis

The solar wind ionic charge composition is a powerful tool to distinguish between the slow wind and the coronal-hole associated fast wind. The solar wind heavy ions are believed to be “frozen-in” within 5 solar radii of the Sun which falls right in the range of SOHO/UVCS coronal observations. We present a joint analysis from SOHO/UVCS and ACE/SWICS which attempts to establish observational evidence of the coronal origin of the solar wind. To connect the solar wind with its coronal origin, we adopt a 3-D MHD model as a guide to link the solar wind at 1 AU to structures in the inner corona. We relate in-situ measured properties of the solar wind (elemental abundances and charge state distributions) with remotely sensed signatures in the corona, namely outflow velocity, electron temperature and elemental abundance. © 2001 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87584/2/133_1.pd

Recent applications of a single quadrupole mass spectrometer in 11C, 18F and radiometal chemistry

Mass spectrometry (MS) has longstanding applications in radiochemistry laboratories, stemming from carbon-dating. However, research on the development of radiotracers for molecular imaging with either positron emission tomography (PET) or single photon emission computed tomography has yet to take full advantage of MS. This inertia has been attributed to the relatively low concentrations of radiopharmaceutical formulations and lack of access to the required MS equipment due to the high costs for purchase and maintenance of specialized MS systems. To date, single quadrupole (SQ)-MS coupled to liquid chromatography (LC) systems is the main form of MS that has been used in radiochemistry laboratories. These LC–MS systems are primarily used for assessing the chemical purity of radiolabeling precursor or standard molecules but also have applications in the determination of metabolites. Herein, we highlight personal experiences using a compact SQ-MS in our PET radiochemistry laboratories, to monitor the small amounts of carrier observed in most radiotracer preparations, even at high molar activities. The use of a SQ-MS in the observation of the low mass associated with non-radioactive species which are formed along with the radiotracer from the trace amounts of carrier found is demonstrated. Herein, we describe a pre-concentration system to detect dilute radiopharmaceutical formulations and metabolite analyses by SQ-MS. Selected examples where SQ-MS was critical for optimization of radiochemical reactions and for unequivocal characterization of radiotracers are showcased. We also illustrate examples where SQ-MS can be applied in identification of radiometal complexes and development of a new purification methodology for Pd-catalyzed radiofluorination reactions, shedding light on the identity of metal complexes present in the labelling solution

Weekly observations of online survey metadata obtained through home computer use allow for detection of changes in everyday cognition before transition to mild cognitive impairment

IntroductionSubtle changes in instrumental activities of daily living often accompany the onset of mild cognitive impairment (MCI) but are difficult to measure using conventional tests.MethodsWeekly online survey metadata metrics, annual neuropsychological tests, and an instrumental activity of daily living questionnaire were examined in 110 healthy older adults with intact cognition (mean age = 85 years) followed up for up to 3.6 years; 29 transitioned to MCI during study follow‐up.ResultsIn the baseline period, incident MCI participants completed their weekly surveys 1.4 hours later in the day than stable cognitively intact participants, P = .03, d = 0.47. Significant associations were found between earlier survey start time of day and higher memory (r = −0.34; P < .001) and visuospatial test scores (r = −0.37; P < .0001). Longitudinally, incident MCI participants showed an increase in survey completion time by 3 seconds per month for more than the year before diagnosis compared with stable cognitively intact participants (β = 0.12, SE = 0.04, t = 2.8; P = .006).DiscussionWeekly online survey metadata allowed for detection of changes in everyday cognition before transition to MCI.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152601/1/alzjjalz201707756.pd

Multivariate meta-analysis of individual participant data helped externally validate the performance and implementation of a prediction model

Objectives Our aim was to improve meta-analysis methods for summarizing a prediction model's performance when individual participant data are available from multiple studies for external validation. Study Design and Setting We suggest multivariate meta-analysis for jointly synthesizing calibration and discrimination performance, while accounting for their correlation. The approach estimates a prediction model's average performance, the heterogeneity in performance across populations, and the probability of "good" performance in new populations. This allows different implementation strategies (e.g., recalibration) to be compared. Application is made to a diagnostic model for deep vein thrombosis (DVT) and a prognostic model for breast cancer mortality. Results In both examples, multivariate meta-analysis reveals that calibration performance is excellent on average but highly heterogeneous across populations unless the model's intercept (baseline hazard) is recalibrated. For the cancer model, the probability of "good" performance (defined by C statistic ≥ 0.7 and calibration slope between 0.9 and 1.1) in a new population was 0.67 with recalibration but 0.22 without recalibration. For the DVT model, even with recalibration, there was only a 0.03 probability of "good" performance. Conclusion Multivariate meta-analysis can be used to externally validate a prediction model's calibration and discrimination performance across multiple populations and to evaluate different implementation strategies

Criteria for the diagnosis of corticobasal degeneration

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed