Assessing the Accuracy of Ancestral Protein Reconstruction Methods

The phylogenetic inference of ancestral protein sequences is a powerful technique for the study of molecular evolution, but any conclusions drawn from such studies are only as good as the accuracy of the reconstruction method. Every inference method leads to errors in the ancestral protein sequence, resulting in potentially misleading estimates of the ancestral protein's properties. To assess the accuracy of ancestral protein reconstruction methods, we performed computational population evolution simulations featuring near-neutral evolution under purifying selection, speciation, and divergence using an off-lattice protein model where fitness depends on the ability to be stable in a specified target structure. We were thus able to compare the thermodynamic properties of the true ancestral sequences with the properties of “ancestral sequences” inferred by maximum parsimony, maximum likelihood, and Bayesian methods. Surprisingly, we found that methods such as maximum parsimony and maximum likelihood that reconstruct a “best guess” amino acid at each position overestimate thermostability, while a Bayesian method that sometimes chooses less-probable residues from the posterior probability distribution does not. Maximum likelihood and maximum parsimony apparently tend to eliminate variants at a position that are slightly detrimental to structural stability simply because such detrimental variants are less frequent. Other properties of ancestral proteins might be similarly overestimated. This suggests that ancestral reconstruction studies require greater care to come to credible conclusions regarding functional evolution. Inferred functional patterns that mimic reconstruction bias should be reevaluated

Lower survival after coronary artery bypass in patients who had atrial fibrillation missed by widely used definitions

OBJECTIVE: To investigate the impact of limiting the definition of post-coronary artery bypass graft (CABG) atrial fibrillation (AF) to AF/flutter requiring treatment-as in the Society of Thoracic Surgeons\u27 (STS) database- on the association with survival. PATIENTS AND METHODS: We assessed in-hospital incidence of post-CABG AF in 7110 consecutive isolated patients with CABG without preoperative AF at 4 hospitals (January 1, 2004 to December 31, 2010). Patients with ≥1 episode of post-CABG AF detected via continuous in-hospital electrocardiogram (ECG)/telemetry monitoring documented by physicians were assigned to the following: Group 1, identified as having post-CABG AF in STS data and Group 2, not identified as having post-CABG AF in STS data. Patients without documented post-CABG AF constituted Group 3. Survival was compared via a Cox model, adjusted for STS risk of mortality and accounting for site differences. RESULTS: Over 7 years\u27 follow-up, 16.0% (295 of 1841) of Group 1, 18.7% (79 of 422) of Group 2, and 7.9% (382 of 4847) of Group 3 died. Group 2 had a significantly greater adjusted risk of death than both Group 1 (hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.02 to 1.33) and Group 3 (HR: 1.94; 95% CI, 1.69 to 2.22). CONCLUSIONS: The statistically significant 16% higher risk of death for patients with AF post-CABG missed vs captured in STS data suggests treatment and postdischarge management should be investigated for differences. The historical misclassification of missed patients as experiencing no AF in the STS data weakens the ability to observe differences in risk between patients with and without post-CABG AF. Therefore, STS data should not be used for research examining post-CABG AF

Evaluation of Sample Design and Estimation Methods for Great Lakes Angler Surveys

The waters of the Great Lakes support outstanding recreational fishing opportunities. Total catch and effort estimates obtained from on‐site angler surveys are essential for the management of the recreational fisheries. However, quality of angler survey estimates can be greatly affected by the survey design and estimation approaches used. Using Monte Carlo simulation techniques, we evaluated the effects of two potential sources of bias (disproportional sampling of angler trips and subsampling of the fishing day) on two catch estimators: (1) a multiple‐day estimator that ignores day effects and pools the angler trip data over a multiple‐day period, and (2) a daily estimator that treats the trip data in each day separately. When catch rates are constant among different time periods of the fishing day, the daily estimator produces total catch estimates with little bias, whereas the multiple‐day estimator is prone to bias caused by disproportional sampling of angler trips. When catch rates vary among different periods of a fishing day, the daily estimator produces biased estimates of total catch when the fishing day is subsampled, whereas the multiple‐day estimator is less affected by the variation in daily time‐period catch rates and subsampling of fishing days. Quality of total catch and effort estimates, in terms of root mean square error and coverage probability of confidence intervals, is poor when the number of days sampled each month is low and fishing days are subsampled.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141929/1/tafs0234.pd

Traces of violence: Representing the atrocities of war

This article explores the relationships between war and representation through the use of visual images, and takes a cue from the French cultural theorist Paul Virilio, who has written extensively on the militarization of vision in ways that have yet to be fully recognized in criminology. It then outlines some of the disputes surrounding documentary photography, not least since one of the main factors driving the development of the medium was the desire to record warfare, before turning to recent efforts to reconfigure the violence of representation by focusing on what has been termed ‘aftermath photography’, where practitioners deliberately adopt an anti-reportage position, slowing down the image-making process and arriving well after the decisive moment. This more contemplative strategy challenges the oversimplification of much photojournalism and the article concludes by reflecting on how military-turned-consumer technologies are structuring our everyday lives in more and more pervasive ways

Digital image analysis using video microscopy of human-derived prostate cancer vs normal prostate organoids to assess migratory behavior on extracellular matrix proteins

The advent of perpetuating living organoids derived from patient tissue is a promising avenue for cancer research but is limited by difficulties with precise characterization. In this brief communication, we demonstrate via time-lapse imaging distinct phenotypes of prostate organoids derived from patient material– without confirmation of cellular identity. We show that organoids derived from histologically normal tissue more readily spread on a physiologic extracellular matrix (ECM) than on pathologic ECM (p<0.0001), while tumor-derived organoids spread equally on either substrate (p=0.2406). This study is an important proof-of-concept to defer precise characterization of organoids and still glean information into disease pathology

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe