Hidden breakpoints in genome alignments

During the course of evolution, an organism's genome can undergo changes that affect the large-scale structure of the genome. These changes include gene gain, loss, duplication, chromosome fusion, fission, and rearrangement. When gene gain and loss occurs in addition to other types of rearrangement, breakpoints of rearrangement can exist that are only detectable by comparison of three or more genomes. An arbitrarily large number of these "hidden" breakpoints can exist among genomes that exhibit no rearrangements in pairwise comparisons. We present an extension of the multichromosomal breakpoint median problem to genomes that have undergone gene gain and loss. We then demonstrate that the median distance among three genomes can be used to calculate a lower bound on the number of hidden breakpoints present. We provide an implementation of this calculation including the median distance, along with some practical improvements on the time complexity of the underlying algorithm. We apply our approach to measure the abundance of hidden breakpoints in simulated data sets under a wide range of evolutionary scenarios. We demonstrate that in simulations the hidden breakpoint counts depend strongly on relative rates of inversion and gene gain/loss. Finally we apply current multiple genome aligners to the simulated genomes, and show that all aligners introduce a high degree of error in hidden breakpoint counts, and that this error grows with evolutionary distance in the simulation. Our results suggest that hidden breakpoint error may be pervasive in genome alignments.Comment: 13 pages, 4 figure

Priming of Grasping Muscles When Viewing a Safety Handle is Diminished With Age

Merely viewing objects within reachable space can activate motor cortical networks and potentiate movement. This holds potential value for smooth interaction with objects in our surroundings, and could offer an advantage for quickly generating targeted hand movements (e.g. grasping a support rail to maintain stability). The present study investigated if viewing a wall-mounted safety handle resulted in automatic activation of motor cortical networks, and if this effect changes with age. Twenty-five young adults (18–30 years) and seventeen older adults (65+ years) were included in this study. Single-pulse, transcranial magnetic stimulation was applied over the motor cortical hand representation of young and older adults shortly after they viewed a safety handle within reaching distance. Between trials, vision was occluded and the environment was unpredictably altered to reveal either a safety handle, or no handle (i.e. covered). Modulation of intrinsic hand muscle activity was evident in young adults when viewing a handle, and this was selective in terms of both the muscles activated and the time at which it emerged. By contrast, older adults failed to show any changes when viewing the safety handle. Specifically, the presence of a handle increased corticospinal activity in hand muscles of young adults when TMS was applied 120 ms after opening the goggles (p = .014), but not in the older adults (p \u3e .954). The fact that the visual priming observed in younger adults was absent in older adults suggests that aging may diminish the ability to quickly put our visual world into automatic motor terms

Electronic Transport Properties or Ensembles of Perylene-Substituted Poly-isocyanopeptide Arrays

Contains fulltext : 72261.pdf (publisher's version ) (Closed access)9 p

Effects of comorbid cardiovascular disease and diabetes on hand osteoarthritis, pain, and functional state transitions: The Johnston county osteoarthritis project

Objective. The purpose of this study is to examine the course of hand osteoarthritis (HOA) and its relationship with cardiovascular disease (CVD) and diabetes (DM). Methods. Data were collected at 3 timepoints from 845 Johnston County Osteoarthritis Project participants (two-thirds women, one-third African Americans, mean age 60 yrs) with and without HOA, CVD, or DM. A diagnosis of radiographic HOA (rHOA) required a Kellgren-Lawrence severity grade of ≥ 2 in at least 3 joints in each hand. A 4-state progressive model included transitions based on rHOA and pain or function as defined using the Australian/Canadian HOA Index (AUSCAN). Markov multistate models estimated HR (aHR) and 95% CI for associations between DM or CVD and specific state transitions, adjusting for baseline and time-varying covariates. Results. Participants with DM (vs those without DM) were more likely to experience worsening pain with rHOA. Individuals who had or developed CVD (vs those who did not) were significantly less likely to experience symptomatic improvement, regardless of rHOA status. Those with DM or CVD (vs those without these comorbidities) were less likely to experience improvement in function, although this was statistically significant only for those with DM and no rHOA. Conclusion. Overall, having or developing DM and/or CVD reduced the likelihood of symptomatic and functional improvement over time, suggesting an effect of comorbid CVD and DM on the clinical and radiographic course of HOA. Additional studies are needed to confirm these findings

Women, men and coronary heart disease: a review of the qualitative literature

Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

A comparative study of the electrochemical properties of vitamin B-6 related compounds at physiological pH

A comparative study of vitamin B6 group and related compounds in buffered solutions using electrochemical techniques has been performed at neutral pH. Irreversible bi- or tetra-electronic processes are observed for these substances, and the electron transfer coefficient (αn) calculated. It was concluded that either the first or second electron transfer were the rate determining step of the electrode process. The diffusion coefficient of these substances was calculated and the values given follow an inverse tendency to the molecular size. For aldehydes the values obtained were corrected of the hydration reaction. It is important to remark that catalytic waves were reported for the first time for these compounds. Using a model involving the nitrogen of the basic structure the kinetic constants were calculated for most of them

Comorbid conditions and the transition among states of hip osteoarthritis and symptoms in a community-based study: A multi-state time-to-event model approach

Background: We examined the association of three common chronic conditions (obesity, diabetes mellitus [DM], and cardiovascular disease [CVD]) with transitions among states of hip osteoarthritis (HOA). Methods: This longitudinal analysis used data from the Johnston County Osteoarthritis Project (JoCo OA, n = 3857), a community-based study in North Carolina, USA, with 18.4 ± 1.5 years of follow-up. Transitions across the following states were modeled: development of radiographic HOA (rHOA; Kellgren-Lawrence grade [KLG] of< 2); development of hip symptoms (self-reported hip pain, aching, or stiffness on most days) or symptomatic HOA (sxHOA; rHOA and symptoms in the same hip), and resolution of symptoms. Obesity (body mass index ≥ 30 kg/m2) and self-reported DM and CVD were the time-dependent comorbid conditions of interest. Markov multi-state models were used to estimate adjusted hazard ratios and 95% confidence intervals to describe the associations between the conditions and HOA states. Results: The sample included 33% African Americans, 39% men, with a mean (SD) age of 62.2 (9.8) years; the frequencies of the comorbidities increased substantially over time. When considered individually, obesity was associated with incident hip symptoms, while CVD and DM were associated with reduced symptom resolution. For those with > 1 comorbidity, the likelihood of incident sxHOA increased, while that of symptom resolution significantly decreased. When stratified by sex, the association between obesity and incident symptoms was only seen in women; among men with DM versus men without, there was a significant (~ 75%) reduction in symptom resolution in those with rHOA. When stratified by race, African Americans with DM, versus those without, were much more likely to develop sxHOA. Conclusions: Comorbid chronic conditions are common in individuals with OA, and these conditions have a significant impact on the persistence and progression of HOA. OA management decisions, both pharmacologic and non-pharmacologic, should include considerations of the inter-relationships between OA and common comorbidities such as DM and CVD

Associations of Comorbid Conditions and Transitions Across States of Knee Osteoarthritis in a Community-Based Cohort

Objective: To examine relationships between knee osteoarthritis (KOA) and obesity, diabetes mellitus (DM), and cardiovascular disease (CVD). Methods: Associations of time-dependent obesity, DM, and CVD with KOA transition states over approximately 18 years were examined among 4093 participants from a community-based cohort. Transition states were 1) no knee symptoms and no radiographic KOA (rKOA; Kellgren-Lawrence grade ≥2 in at least one knee), 2) asymptomatic rKOA, 3) knee symptoms only, 4) symptomatic rKOA (sxKOA; rKOA and symptoms in same knee). Markov multistate models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for associations between comorbid conditions and transitions across states, adjusting for baseline age, sex, race, education, enrollment cohort, birth year, and time-dependent knee injury history. Results: At baseline, 40% of participants had obesity, 13% had DM, and 22% had CVD (mean age = 61 years; 34% Black; 37% male). Compared with those without obesity, those with obesity had a higher hazard of worsening from no rKOA/no symptoms to asymptomatic rKOA (aHR = 1.7; 95% CI = 1.3-2.2) and from knee symptoms to sxKOA (aHR = 1.7; 95% CI = 1.3-2.3), as well as a lower hazard of symptom resolution from sxKOA to asymptomatic rKOA (aHR = 0.5 [95% = CI 0.4-0.7]). Compared with those without CVD, those with CVD had a higher hazard of worsening from no rKOA/symptoms to knee symptoms (aHR = 1.5; 95% CI = 1.1-2.1). DM was not associated with transitions of rKOA. Conclusion: Prevention of obesity and CVD may limit the development or worsening of rKOA and symptoms

Joint hypermobility is not positively associated with prevalent multiple joint osteoarthritis: A cross-sectional study of older adults

Background: This cross-sectional study evaluated associations of joint hypermobility and multiple joint osteoarthritis (MJOA) in a community-based cohort of adults 45+ years of age. Methods: MJOA and joint hypermobility data were from 1677 participants (mean age 69 years, 68% women) who completed research clinic visits during 2003-2010. Prevalent MJOA was defined in four ways. Radiographic OA (rOA) was defined as Kellgren-Lawrence (KL) > 2 at any included study joint; symptomatic OA (sxOA) required both symptoms and rOA in a joint. Joint hypermobility was defined as a Beighton score of > 4. Separate logistic regression models were used to estimate odds ratios (OR) between joint hypermobility and each MJOA definition, adjusting for age, sex, race, body mass index, and baseline visit. Results: In this cohort, 4% had Beighton score > 4 and 63% met any definition of MJOA. Joint hypermobility was associated with significantly lower odds of radiographic and symptomatic MJOA-1 (multiple joint OA-definition 1: involvement of > 1 IP (interphalangeal) nodes and > 2 sites of hip, knee, and spine; 74 and 58% lower, respectively). However, for the other MJOA definitions (i.e., MJOA-2:involvement of > 2 IP joints, > 1 carpometacarpal [CMC] joints, and knee or hip sites; MJOA-3: involvement of > 5 joint sites from among distal interphalangeal, proximal interphalangeal, CMC, hip, knee, or spine sites; and MJOA-4:involvement of > 2 lower body sites (hip, knee, or spine), there were no statistically significant associations. For associations between site-specific hypermobility and any MJOA definition, most adjusted ORs were less than one, but few were statistically significant. Conclusions: Overall, joint hypermobility was not positively associated with any definition of prevalent MJOA in this cohort, and an inverse association existed with one definition of MJOA. Longitudinal studies are needed to determine the contribution of hypermobility to the incidence and progression of MJOA outcomes

Relationship of joint hypermobility with low Back pain and lumbar spine osteoarthritis

Background: Chronic low back pain (cLBP) affects millions of Americans and costs billions. Studies suggest a link between cLBP and joint hypermobility. Methods: We conducted cross-sectional primary analyses of joint hypermobility and cLBP, lumbar spine osteoarthritis (OA), and lumbar facet joint OA (FOA) in 3 large studies - the Generalized Osteoarthritis Study, Genetics of Generalized Osteoarthritis Study, and Johnston County Osteoarthritis Project (total n = 5072). Associations of joint hypermobility and Beighton trunk flexion with cLBP and lumbar OA were estimated using separate adjusted logistic regression models. Adjusted pooled odds ratios (pORs) and 95% confidence intervals (CIs) were then summarized - using random effect univariate, multivariate crude, and adjusted models - and heterogeneity was determined (I 2 statistic). Results: In univariate models, hypermobility was associated with symptomatic FOA (pOR = 0.64 [95% CI 0.44, 0.93]) but this result was not found in the multivariate models. In multivariate adjusted models, hypermobility was not significantly associated with cLBP and lumbar OA, but trunk flexion was inversely associated with cLBP (pOR = 0.40 [95% 0.26, 0.62]), spine OA (pOR = 0.66 [95% CI 0.50, 0.87]), symptomatic spine OA (pOR = 0.39 [95% CI 0.28, 0.53]), and symptomatic FOA (pOR = 0.53 [95% CI 0.37, 0.77]). Generally, between-study heterogeneity was moderate-high. Conclusions: Hypermobility was not associated with cLBP or lumbar OA. The inverse association of trunk flexion with cLBP and lumbar OA may indicate a role for a flexible spine in avoiding or managing these conditions. © 2019 The Author(s)