Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele

Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.     

Nutritional Aspects of Dissimilatory Sulfate Reduction in the Human Large Intestine

In contrast to other anaerobic ecosystems, such as marine and estuarine sediments, there is a lack of information on the nutritional requirements of human gut sulfate-reducing bacteria (SRB). Various substrates stimulated sulfate reduction in mixed culture, including short-chain fatty acids and other organic acids, alcohols, and amino acids (but not sugars or aromatic compounds). However, the use of sodium molybdate as a specific inhibitor of sulfate reduction caused an accumulation of ethanol and malonate only, and reduced the rate of utilization of lactate. This indicates the importance of these electron donors for sulfate reduction. Since ethanol and lactate are primarily utilized by members of the Desulfovibrio genus, the results suggest a physiologically important role for this group.  Experiments with two strains of Desulfovibrio desulfuricans isolated from human feces demonstrated that both were able to reduce sulfite, thiosulfate or nitrate in the absence of sulfate. In addition, one strain (DsvUC1) was able to grow by fermentative metabolism, although the second strain (DsvFD1) showed more restricted fermentative growth. The data indicate that desulfovibrios are ecologically the most significant group of SRB in the human colon, and that colonic isolates belonging to this genus are versatile, in terms of both the electron acceptors and donors that they are able to utilize. Received: 24 March 1997 / Accepted: 10 June 1997     

Intensity-Corrected Dual-Echo Echo-Planar Imaging (DE-EPI) for Improved Pediatric Brain Diffusion Imaging

Here we investigate the utility of a dual-echo Echo-Planar Imaging (DE-EPI) Diffusion Weighted Imaging (DWI) approach to improve lesion conspicuity in pediatric imaging. This method delivers two ‘echo images’ for one diffusion-preparation period. We also demonstrate how the echoes can be utilized to remove transmit/receive coil-induced and static magnetic field intensity modulations on both echo images, which often mimic pathology and thereby pose diagnostic challenges. DE-EPI DWI data were acquired in 18 pediatric patients with abnormal diffusion lesions, and 46 pediatric patient controls at 3T. Echo1 [TE = 45ms] and Echo2 [TE = 86ms] were corrected for signal intensity variation across the images by exploiting the images equivalent coil-sensitivity and susceptibility-induced modulations. Two neuroradiologists independently reviewed Echo1 and Echo2 and their intensity-corrected variants (cEcho1 and cEcho2) on a 7-point Likert scale, with grading on lesion conspicuity diagnostic confidence. The apparent diffusion coefficient (ADC) map from Echo1 was used to validate presence of true pathology. Echo2 was unanimously favored over Echo1 for its sensitivity for detecting acute brain injury, with a mean respective lesion conspicuity of 5.7/4.4 (p < 0.005) and diagnostic confidence of 5.1/4.3 (p = 0.025). cEcho2 was rated higher than cEcho1, with a mean respective lesion conspicuity of 5.5/4.3 (p < 0.005) and diagnostic confidence of 5.4/4.4 (p < 0.005). cEcho2 was favored over all echoes for its diagnostic reliability, particularly in regions close to the head coil. This work concludes that DE-EPI DWI is a useful alternative to conventional single-echo EPI DWI, whereby Echo2 and cEcho2 allows for improved lesion detection and overall higher diagnostic confidence.     

Densitometry from digitized images of X-radiographs: Methodology for measurement of coral skeletal density

Skeletons of massive coral colonies contain annual density bands that are revealed by X-radiography of slices cut along growth axes. These bands allow measurement of skeletal growth parameters such as annual extension rate and annual calcification rate. Such measurements have been important in understanding coral growth, in assessing environmental impacts and in recovering proxy environmental information. Measurements of coral calcification rate from annual density banding require measurements of skeletal density along tracks across skeletal slices and, until now, such density measurements have depended upon specialized and expensive equipment. Here, we describe a straightforward, inexpensive and accurate technique for measuring skeletal density from digitized images of X-radiographs of coral skeletal slices. An aragonitic step-wedge was included in each X-radiograph of a coral slice together with two aluminium bars positioned along the anode-cathode axis. Optical density was measured along tracks across the X-ray images of these different objects. The aragonite step-wedge provided a standard for converting optical density to skeletal density. The aluminium bars were used to correct for the heel effect—a variation in the intensity of the X-ray beam along the anode-cathode axis that would, otherwise, introduce large errors into measurements of skeletal density. Exposure was found to vary from X-radiographs to X-radiograph, necessitating the inclusion of the calibration standards in each X-radiograph of a coral slice. Results obtained using this technique compared well with results obtained by direct gamma densitometry of skeletal slices.     

Contraction properties and motor nucleus morphology of the two heads of the cat flexor carpi ulnaris muscle

Previous studies have examined the isometric contraction properties of the two heads of the cat flexor carpi ulnaris acting as a single unit. In this study, the contraction properties and fiber architecture of each head of the flexor carpi ulnaris were determined separately and related to previous reports on the histochemical characteristics of this muscle. The morphology of retrograde-labeled motor nuclei for the two heads of the muscle was also examined. The humeral head had a significantly longer contraction time (48 msec) than the ulnar head (36 msec) as well as a significantly lower tetanic fusion frequency (28 Hz vs. 35 Hz). The maximum tetanic tension per gram of muscle tissue was 71% greater in the ulnar head. Motoneurons of the flexor carpi ulnaris formed a column 12 mm long and 0.5 mm wide in the center of the ventral grey in spinal segments C8 and T1. The ulnar head had alpha-motoneurons with greater soma diameters than those in the humeral head. The smaller soma diameter, slower contraction time, and weaker contraction in the humeral head correlate with the preponderance of oxidative-metabolic muscle fiber types found in the humeral head by other workers. These correlations suggest that the humeral head plays a major role in maintaining a sustained antigravity tension that prevents the wrist from buckling during standing.