Improving Phrap-Based Assembly of the Rat Using “Reliable” Overlaps

The assembly methods used for whole-genome shotgun (WGS) data have a major impact on the quality of resulting draft genomes. We present a novel algorithm to generate a set of “reliable” overlaps based on identifying repeat k-mers. To demonstrate the benefits of using reliable overlaps, we have created a version of the Phrap assembly program that uses only overlaps from a specific list. We call this version PhrapUMD. Integrating PhrapUMD and our “reliable-overlap” algorithm with the Baylor College of Medicine assembler, Atlas, we assemble the BACs from the Rattus norvegicus genome project. Starting with the same data as the Nov. 2002 Atlas assembly, we compare our results and the Atlas assembly to the 4.3 Mb of rat sequence in the 21 BACs that have been finished. Our version of the draft assembly of the 21 BACs increases the coverage of finished sequence from 93.4% to 96.3%, while simultaneously reducing the base error rate from 4.5 to 1.1 errors per 10,000 bases. There are a number of ways of assessing the relative merits of assemblies when the finished sequence is available. If one views the overall quality of an assembly as proportional to the inverse of the product of the error rate and sequence missed, then the assembly presented here is seven times better. The UMD Overlapper with options for reliable overlaps is available from the authors at http://www.genome.umd.edu. We also provide the changes to the Phrap source code enabling it to use only the reliable overlaps

Reproductive output, foraging destinations, and isotopic niche of olive ridley and loggerhead sea turtles, and their hybrids, in Brazil

Hybridization is a fundamental evolutionary and ecological process with significant conservation ramifications. Sea turtle hybridization occurs at unusually high frequencies along the northeastern coast of Brazil. To better understand the process, we studied the reproductive output, migration patterns (through satellite telemetry), and isotopic niches of loggerhead turtles Caretta caretta and olive ridley turtles Lepidochelys olivacea and their hybrids. We classified 154 nesting females as loggerhead (n = 91), olive ridley (n = 38), or hybrid (n = 25) based on mitochondrial and nuclear DNA. Further, we compared nesting female morphological data and reproductive parameters (clutch size, emergence success, hatchling production, incubation period) of 405 nests among hybrids and parental species. We found no significant differences among the 3 groups when hatchling production was corrected for female body size, indicating that hybrids and parental species produce similar numbers of hatchlings per clutch. Satellite tracking of 8 post-nesting hybrid females revealed shared foraging grounds with both parental species, as well as neritic migrations between foraging and nesting areas similar to those previously reported for loggerheads and olive ridleys. Analyses of 13C and 15N isotope values (n = 69) further confirmed this pattern, as hybrid isotopic niches overlapped extensively with both parental species. Thus, given the similarities presented between hybrids and their parental species in reproductive, ecological, and behavioral characteristics, we conclude that these hybrids may persist along with other sea turtle nesting populations in the area, with research and conservation implications. © The authors 2021. Open Access under Creative Commons by Attribution Licence. Use, distribution and reproduction are unrestricted. Authors and original publication must be credited

Adolescents’ responses to the promotion and flavouring of e-cigarettes

Objectives The purpose of the study is to examine adolescents’ awareness of e-cigarette marketing and investigate the impact of e-cigarette flavour descriptors on perceptions of product harm and user image. Methods Data come from the 2014 Youth Tobacco Policy Survey, a cross-sectional in-home survey conducted with 11–16 year olds across the UK (n = 1205). Adolescents’ awareness of e-cigarette promotion, brands, and flavours was assessed. Perceptions of product harm, and likely user of four examples of e-cigarette flavours was also examined. Results Some participants had tried e-cigarettes (12 %) but regular use was low (2 %) and confined to adolescents who had also smoked tobacco. Most were aware of at least one promotional channel (82 %) and that e-cigarettes came in different flavours (69 %). Brand awareness was low. E-cigarettes were perceived as harmful (M = 3.54, SD = 1.19) but this was moderated by product flavours. Fruit and sweet flavours were perceived as more likely to be tried by young never smokers than adult smokers trying to quit (p < 0.001). Conclusions There is a need to monitor the impact of future market and regulatory change on youth uptake and perceptions of e-cigarettes

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

Standard setting: Comparison of two methods

BACKGROUND: The outcome of assessments is determined by the standard-setting method used. There is a wide range of standard – setting methods and the two used most extensively in undergraduate medical education in the UK are the norm-reference and the criterion-reference methods. The aims of the study were to compare these two standard-setting methods for a multiple-choice question examination and to estimate the test-retest and inter-rater reliability of the modified Angoff method. METHODS: The norm – reference method of standard -setting (mean minus 1 SD) was applied to the 'raw' scores of 78 4th-year medical students on a multiple-choice examination (MCQ). Two panels of raters also set the standard using the modified Angoff method for the same multiple-choice question paper on two occasions (6 months apart). We compared the pass/fail rates derived from the norm reference and the Angoff methods and also assessed the test-retest and inter-rater reliability of the modified Angoff method. RESULTS: The pass rate with the norm-reference method was 85% (66/78) and that by the Angoff method was 100% (78 out of 78). The percentage agreement between Angoff method and norm-reference was 78% (95% CI 69% – 87%). The modified Angoff method had an inter-rater reliability of 0.81 – 0.82 and a test-retest reliability of 0.59–0.74. CONCLUSION: There were significant differences in the outcomes of these two standard-setting methods, as shown by the difference in the proportion of candidates that passed and failed the assessment. The modified Angoff method was found to have good inter-rater reliability and moderate test-retest reliability

Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

Development of Upper Body Coordination During Sitting in Typically Developing Infants

Our goal was to determine how the actions of the thorax and the pelvis are organized and coordinated to achieve independent sitting posture in typically developing infants. The participants were 10 typically developing infants who were evaluated longitudinally from first onset of sitting until sitting independence. Each infant underwent nine testing sessions. The first session included motor evaluation with the Peabody test. The other eight sessions occurred over a period of 4 mo where sitting behavior was evaluated by angular kinematics of the thorax and the pelvis. A physical therapist evaluated sitting behavior in each session and categorized it according to five stages. The phasing relationship of the thorax and the pelvis was calculated and evaluated longitudinally using a one-way analysis of variance. With development, the infants progressed from an in-phase (moving in the same direction) to an out-of-phase (moving in an opposite direction) coordinative relationship between the thorax and the pelvis segments. This change was significant for both sagittal and frontal planes of motion. Clinically, this relationship is important because it provides a method to quantify infant sitting postural development, and can be used to assess efficacy of early interventions for pediatric populations with developmental motor delays

The Enduring Hypoxic Response of Mycobacterium tuberculosis

deletion mutant. mutant. for long-term bacteriostasis in the face of oxygen deprivation