Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Changes in perfusion angiography after IVC filter placement and retrieval

Inferior vena cava (IVC) filters are posited to effect flow dynamics, causing turbulence, vascular remodeling and eventual thrombosis; however, minimal data exists evaluating hemodynamic effects of IVC filters in vivo. The purpose of this study was to determine differences in hemodynamic flow parameters acquired with two-dimension (2D)-perfusion angiography before and after IVC filter placement or retrieval. 2D-perfusion images were reconstructed retrospectively from digital subtraction angiography from a cohort of 37 patients (13F/24M) before and after filter placement (n = 18) or retrieval (n = 23). Average dwell time was 239.5 ± 132.1 days. Changes in the density per pixel per second within a region of interest (ROI) were used to calculate contrast arrival time (AT), time-to-peak (TTP), wash-in-rate (WIR), and mean transit time (MTT). Measurements were obtained superior to, inferior to, and within the filter. Differences in hemodynamic parameters before and after intervention were compared, as well as correlation between parameters versus filter dwell time. A P value with Bonferroni correction of <.004 was considered statistically significant. After placement, there was no difference in any 2D-perfusion variable. After retrieval, ROIs within and inferior to the filter showed a significantly shorter TTP (1.7 vs 1.4 s, P = .004; 1.5 vs 1.3 s, P = .001, respectively) and MTT (1.7 vs 1.4 s, P = .003; 1.5 vs 1.2 s, P = .002, respectively). Difference in variables showed no significant correlation when compared to dwell time. 2D-perfusion angiography is feasible to evaluate hemodynamic effects of IVC filters in vivo. TTP and MTT within and below the filter after retrieval were significantly changed, without apparent correlation to dwell time, suggesting a functional hemodynamic delay secondary to filter presence

Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease.

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson's disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony. Here we demonstrate for the first time that during intra-operative 60 Hz STN DBS, one or more bands of resting state neural synchrony were amplified in the STN in PD. We recorded intra-operative STN resting state local field potentials (LFPs) from twenty-eight STNs in seventeen PD subjects after placement of the DBS lead (model 3389, Medtronic, Inc.) before and during three randomized neurostimulation sets (130 Hz/1.35V, 130 Hz/2V, 60 Hz/2V). During 130 Hz/2V DBS, baseline (no DBS) STN alpha (8-12 Hz) and beta (13-35 Hz) band power decreased (N=14, P < 0.001 for both), whereas during 60 Hz/2V DBS, alpha band and peak frequency power increased (P = 0.012, P = 0.007, respectively). The effect of 60 Hz/2V DBS opposed that of power-equivalent (130 Hz/1.35V) DBS (alpha: P < 0.001, beta: P = 0.006). These results show that intra-operative 60 Hz STN DBS amplified whereas 130 Hz STN DBS attenuated resting state neural synchrony in PD; the effects were frequency-specific. We demonstrate that neurostimulation may be useful as a tool to selectively modulate resting state resonant bands of neural synchrony and to investigate its influence on motor and non-motor behaviors in PD and other neuropsychiatric diseases

Example STN during the different stimulation sets.

<p><b>A</b>, <b>B</b>, <b>C</b>, and <b>D</b> are raw waveforms and spectrograms from the baseline epoch, 130 Hz/2V DBS epoch, 60 Hz/2V DBS epoch, and 130 Hz/1.35V DBS epoch, respectively. Spectrograms are displayed with 99% window overlap. <b>E</b>: Relative PSD traces of the four epochs. Black = baseline; red = 130 Hz/2V; blue = 60 Hz/2V; green = 130 Hz/1.35V. Colored dashed lines represent 95% confidence intervals for each spectrum.</p

Peak detection for all fourteen sides.

<p><b>A</b>—<b>N</b> are absolute PSDs from all fourteen recordings. Black = baseline; red = 60 Hz/2V; dashed = 130 Hz/2V. Arrows indicate where peaks were detected by the algorithm, and the color of an arrow corresponds to its PSD spectrum. Black asterisks on <b>J</b> (one for 60 Hz/2V) and <b>K</b> (two, one for 60 Hz/2V and one for baseline) indicate peaks chosen visually.</p

Change (Δ) in Mean Power with Respect to Baseline.

<p>The total power delivered during 60 Hz/2V DBS was equivalent to that delivered during 130 Hz/1.35V DBS. However, their effects on baseline spectral power were significantly different from each other in both the alpha (P < 0.001) and beta (P = 0.006) bands.</p><p>Change (Δ) in Mean Power with Respect to Baseline.</p