Direct Detection and Sequencing of Damaged DNA Bases

Products of various forms of DNA damage have been implicated in a variety of important biological processes, such as aging, neurodegenerative diseases, and cancer. Therefore, there exists great interest to develop methods for interrogating damaged DNA in the context of sequencing. Here, we demonstrate that single-molecule, real-time (SMRT®) DNA sequencing can directly detect damaged DNA bases in the DNA template - as a by-product of the sequencing method - through an analysis of the DNA polymerase kinetics that are altered by the presence of a modified base. We demonstrate the sequencing of several DNA templates containing products of DNA damage, including 8-oxoguanine, 8-oxoadenine, O6-methylguanine, 1-methyladenine, O4-methylthymine, 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxymethyluracil, or thymine dimers, and show that these base modifications can be readily detected with single-modification resolution and DNA strand specificity. We characterize the distinct kinetic signatures generated by these DNA base modifications

Reconstructing gravitational wave signals from binary black hole mergers with minimal assumptions

We present a systematic comparison of the binary black hole (BBH) signal waveform reconstructed by two independent and complementary approaches used in LIGO and Virgo source inference: a template-based analysis, and a morphology-independent analysis. We apply the two approaches to real events and to two sets of simulated observations made by adding simulated BBH signals to LIGO and Virgo detector noise. The first set is representative of the 10 BBH events in the first Gravitational Wave Transient Catalog (GWTC-1). The second set is constructed from a population of BBH systems with total mass and signal strength in the ranges that ground based detectors are typically sensitive. We find that the reconstruction quality of the GWTC-1 events is consistent with the results of both sets of simulated signals. We also demonstrate a simulated case where the presence of a mismodelled effect in the observed signal, namely higher order modes, can be identified through the morphology-independent analysis. This study is relevant for currently progressing and future observational runs by LIGO and Virgo

The BayesWave analysis pipeline in the era of gravitational wave observations

We describe updates and improvements to the BayesWave gravitational wave transient analysis pipeline, and provide examples of how the algorithm is used to analyze data from ground-based gravitational wave detectors. BayesWave models gravitational wave signals in a morphology-independent manner through a sum of frame functions, such as Morlet-Gabor wavelets or chirplets. BayesWave models the instrument noise using a combination of a parametrized Gaussian noise component and non-stationary and non-Gaussian noise transients. Both the signal model and noise model employ trans-dimensional sampling, with the complexity of the model adapting to the requirements of the data. The flexibility of the algorithm makes it suitable for a variety of analyses, including reconstructing generic unmodeled signals; cross checks against modeled analyses for compact binaries; as well as separating coherent signals from incoherent instrumental noise transients (glitches). The BayesWave model has been extended to account for gravitational wave signals with generic polarization content and the simultaneous presence of signals and glitches in the data. We describe updates in the BayesWave prior distributions, sampling proposals, and burn-in stage that provide significantly improved sampling efficiency. We present standard review checks indicating the robustness and convergence of the BayesWave trans-dimensional sampler

Three-Dimensional Kinematics of Hummingbird Flight

Hummingbirds are specialized for hovering flight, and substantial research has explored this behavior. Forward flight is also important to hummingbirds, but the manner in which they perform forward flight is not well documented. Previous research suggests that hummingbirds increase flight velocity by simultaneously tilting their body angle and stroke-plane angle of the wings, without varying wingbeat frequency and upstroke: downstroke span ratio. We hypothesized that other wing kinematics besides stroke-plane angle would vary in hummingbirds. To test this, we used synchronized highspeed (500·Hz) video cameras and measured the threedimensional wing and body kinematics of rufous hummingbirds (Selasphorus rufus, 3·g, N=5) as they flew at velocities of 0–12·m·s–1 in a wind tunnel. Consistent with earlier research, the angles of the body and the stroke plane changed with velocity, and the effect of velocity on wingbeat frequency was not significant. However, hummingbirds significantly altered other wing kinematics including chord angle, angle of attack, anatomical strokeplane angle relative to their body, percent of wingbeat in downstroke, wingbeat amplitude, angular velocity of the wing, wingspan at mid-downstroke, and span ratio of the wingtips and wrists. This variation in bird-centered kinematics led to significant effects of flight velocity on the angle of attack of the wing and the area and angles of the global stroke planes during downstroke and upstroke. We provide new evidence that the paths of the wingtips and wrists change gradually but consistently with velocity, as in other bird species that possess pointed wings. Although hummingbirds flex their wings slightly at the wrist during upstroke, their average wingtip–span ratio of 93% revealed that they have kinematically ‘rigid’ wings compared with other avian species

Posturography using the Wii Balance Board. A feasibility study with healthy adults and adults post-stroke

[EN] Background: Posturography systems that incorporate force platforms are considered to assess balance and postural control with greater sensitivity and objectivity than conventional clinical tests. The Wii Balance Board (WBB) system has been shown to have similar performance characteristics as other force platforms, but with lower cost and size. Objectives: To determine the validity and reliability of a freely available WBB-based posturography system that combined the WBB with several traditional balance assessments, and to assess the performance of a cohort of stroke individuals with respect to healthy individuals. Methods: Healthy subjects and individuals with stroke were recruited. Both groups were assessed using the WBB-based posturography system. Individuals with stroke were also assessed using a laboratory grade posturography system and a battery of clinical tests to determine the concurrent validity of the system. A group of subjects were assessed twice with the WBB-based system to determine its reliability. Results: A total of 144 healthy individuals and 53 individuals with stroke participated in the study. Concurrent validity with another posturography system was moderate to high. Correlations with clinical scales were consistent with previous research. The reliability of the system was excellent in almost all measures. In addition, the system successfully characterized individuals with stroke with respect to the healthy population. Conclusions: The WBB-based posturography system exhibited excellent psychometric properties and sensitivity for identifying balance performance of individuals with stroke in comparison with healthy subjects, which supports feasibility of the system as a clinical tool. (C) 2015 Elsevier B.V. All rights reserved.This study was funded by project NeuroVR (TIN2013-44741-R) of the Ministerio de Economia y Competitividad (Madrid, Spain).Llorens Rodríguez, R.; Grau Latorre, J.; Noe, E.; Keshner, EA. (2015). Posturography using the Wii Balance Board. A feasibility study with healthy adults and adults post-stroke. Gait and Posture. 43:228-232. https://doi.org/10.1016/j.gaitpost.2015.10.002S2282324

Discovery of tissue-specific exons using comprehensive human exon microarrays

Comprehensive exon microarrays with a simple intra-gene normalization algorithm were used to detect human tissue-specific alternative splicing events, suggesting significant expression outside of known exons and well annotated genes and a high frequency of alternative splicing events

Characterizing the efficacy of methods to subtract terrestrial transient noise near gravitational wave events and the effects on parameter estimation

We investigate the impact of transient noise artifacts, or {\it glitches}, on gravitational wave inference, and the efficacy of data cleaning procedures in recovering unbiased source properties. Due to their time-frequency morphology, broadband glitches demonstrate moderate to significant biasing of posterior distributions away from true values. In contrast, narrowband glitches have negligible biasing effects owing to distinct signal and glitch morphologies. We inject simulated binary black hole signals into data containing three common glitch types from past LIGO-Virgo observing runs, and reconstruct both signal and glitch waveforms using {\tt BayesWave}, a wavelet-based Bayesian analysis. We apply the standard LIGO-Virgo-KAGRA deglitching procedure to the detector data - we subtract the glitch waveform estimated by the joint {\tt BayesWave} inference before performing parameter estimation with detailed compact binary waveform models. We find that this deglitching effectively mitigates bias from broadband glitches, with posterior peaks aligning with true values post deglitching. This provides a baseline validation of existing techniques, while demonstrating waveform reconstruction improvements to the Bayesian algorithm for robust astrophysical characterization in glitch-prone detector data.Comment: 22 pages, 17 figure

Affy exon tissues: exon levels in normal tissues in human, mouse and rat

Summary: Most genes in human, mouse and rat produce more than one transcript isoform. The Affymetrix Exon Array is a tool for studying the many processes that regulate RNA production, with separate probesets measuring RNA levels at known and putative exons. For insights on how exons levels vary between normal tissues, we constructed the Affy Exon Tissues track from tissue data published by Affymetrix. This track reports exon probeset intensities as log ratios relative to median values across the dataset and renders them as colored heat maps, to yield quick visual identification of exons with intensities that vary between normal tissues

Unusual Intron Conservation near Tissue-Regulated Exons Found by Splicing Microarrays

Alternative splicing contributes to both gene regulation and protein diversity. To discover broad relationships between regulation of alternative splicing and sequence conservation, we applied a systems approach, using oligonucleotide microarrays designed to capture splicing information across the mouse genome. In a set of 22 adult tissues, we observe differential expression of RNA containing at least two alternative splice junctions for about 40% of the 6,216 alternative events we could detect. Statistical comparisons identify 171 cassette exons whose inclusion or skipping is different in brain relative to other tissues and another 28 exons whose splicing is different in muscle. A subset of these exons is associated with unusual blocks of intron sequence whose conservation in vertebrates rivals that of protein-coding exons. By focusing on sets of exons with similar regulatory patterns, we have identified new sequence motifs implicated in brain and muscle splicing regulation. Of note is a motif that is strikingly similar to the branchpoint consensus but is located downstream of the 5′ splice site of exons included in muscle. Analysis of three paralogous membrane-associated guanylate kinase genes reveals that each contains a paralogous tissue-regulated exon with a similar tissue inclusion pattern. While the intron sequences flanking these exons remain highly conserved among mammalian orthologs, the paralogous flanking intron sequences have diverged considerably, suggesting unusually complex evolution of the regulation of alternative splicing in multigene families