A guide to best practices for Gene Ontology (GO) manual annotation.

The Gene Ontology Consortium (GOC) is a community-based bioinformatics project that classifies gene product function through the use of structured controlled vocabularies. A fundamental application of the Gene Ontology (GO) is in the creation of gene product annotations, evidence-based associations between GO definitions and experimental or sequence-based analysis. Currently, the GOC disseminates 126 million annotations covering >374,000 species including all the kingdoms of life. This number includes two classes of GO annotations: those created manually by experienced biocurators reviewing the literature or by examination of biological data (1.1 million annotations covering 2226 species) and those generated computationally via automated methods. As manual annotations are often used to propagate functional predictions between related proteins within and between genomes, it is critical to provide accurate consistent manual annotations. Toward this goal, we present here the conventions defined by the GOC for the creation of manual annotation. This guide represents the best practices for manual annotation as established by the GOC project over the past 12 years. We hope this guide will encourage research communities to annotate gene products of their interest to enhance the corpus of GO annotations available to all. DATABASE URL: http://www.geneontology.org

MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1

Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects. However, the transcriptional pathways controlling AHF development and their roles in congenital heart defects remain incompletely elucidated. Here, we inactivated the gene encoding the transcription factor MEF2C in the AHF in mice. Loss of Mef2c function in the AHF results in a spectrum of outflow tract alignment defects ranging from overriding aorta to double-outlet right ventricle and dextro-transposition of the great arteries. We identify Tdgf1, which encodes a Nodal co-receptor (also known as Cripto), as a direct transcriptional target of MEF2C in the outflow tract via an AHFrestricted Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1 genes are associated with congenital heart defects in humans. Thus, these studies establish a direct transcriptional pathway between the core cardiac transcription factor MEF2C and the human congenital heart disease gene TDGF1. Moreover, we found a range of outflow tract alignment defects resulting from a single genetic lesion, supporting the idea that AHF-derived outflow tract alignment defects may constitute an embryological spectrum rather than distinct anomalies

Flattened Stirling Permutations

Recall that a Stirling permutation is a permutation on the multiset $\{1,1,2,2,\ldots,n,n\}$ such that any numbers appearing between repeated values of $i$ must be greater than $i$. We call a Stirling permutation ``flattened'' if the leading terms of maximal chains of ascents (called runs) are in weakly increasing order. Our main result establishes a bijection between flattened Stirling permutations and type $B$ set partitions of $\{0,\pm1,\pm2,\ldots,\pm (n-1)\}$, which are known to be enumerated by the Dowling numbers, and we give an independent proof of this fact. We also determine the maximal number of runs for any flattened Stirling permutation, and we enumerate flattened Stirling permutations with a small number of runs or with two runs of equal length. We conclude with some conjectures and generalizations worthy of future investigation.Comment: 15 pages, 1 figure, 2 tabl

Use of the Adult Myopathy Assessment Tool as a predictor of functional abilities in people with multiple sclerosis

Background: People with multiple sclerosis (PwMS) are at greater risk for decreased muscle performance which may lead to decreased functional abilities. The Kurtzke Expanded Disability Status Scale (EDSS) is commonly used as a disability status rating scale in PwMS. Nevertheless, the EDSS is largely comprised of neurological tests and may not best reflect functional performance. A functional battery such as The Adult Myopathy Assessment Tool (AMAT) may better reflect functional performance. The AMAT was designed to assess both functional strength and endurance in clinical settings. However, the AMAT has not been validated for the assessment of PwMS. Objective: The purpose of the study was to determine the comparative association of the AMAT and EDSS with measures of strength, fatigability, and functional performance. Methods: Twenty-nine people (mean age 48.6 ±11.2), with a history of MS (EDSS \u3c 7.0) were recruited. Participants completed functional testing (5 times sit to stand and gait speed) and an assessment of disability and functional status using the EDSS and AMAT, respectively. Muscle performance was assessed via a 60 s maximal volitional isometric contraction (MVIC) of the knee extensors using an isokinetic dynamometer, and expressed as fatigability (exhaustion time to 60% of MVIC), peak torque, and peak torque scaled to body weight. Results:The participants exhibited moderate levels of disability (EDSS, 3.6 ±1.4) and function (AMAT total score, 36.1 ±7.6; AMAT function subscale, 18.2 ±3.3). Peak force was 70.1 kg ±22.0 kg, exhaustion time was 38.4 s ±17.4 s, gait speed was 1.3 m/s ±0.3 m/s, and five time sit to stand was 11.4 s ±4.1 s. The AMAT function subscale was associated with scaled peak torque (r=0.426, p=.021), gait speed (r=0.825, p=0.00), and 5 time sit to stand (r=-0.632, p Conclusions: The AMAT was more strongly associated with scaled peak torque and functional measures in comparison to the EDSS. This may reflect the observation that relative strength is a better predictor of functional abilities than unadjusted strength measures. Whereas, the stronger association of the EDSS with fatigability may be explained by the pyramidal systems measures within the tool and the well-known association of MS-related fatigue with disability. Based on the results of the study, we suggest clinicians administer the AMAT in addition to the EDSS, to gain insight into functional impairments and assist with formulating a comprehensive plan of care

Giving VCU A Choice... VCUHS ChoiceCare

Virginia Commonwealth University has the opportunity to promote the quality health care services being rendered by the VCU Health System and the VCU School of Dentistry to its staff and faculty. Our project proposes that the VCUHS ChoiceCARE Health Plan be made available as an option to the entire University community. The VCUHS ChoiceCARE Health Plan is currently being offered to all employees of the Virginia Commonwealth University Health System. This is an exceptional health care plan that encourages employees to utilize the services ofthe MCV Physicians/Hospitals and VCU Dentists/Oral Dentistry practitioners. Through financial incentives of lower or no copays required and competitive monthly premiums, employees will benefit from this alternative. The VCU Health System and the VCU School of Dentistry will benefit from an improved insured patient base and from maintaining a healthy workforce. As the third largest employer in the Richmond metropolitan area, VCU employees and their families are an obvious market for the health care services. This project is another step in helping University programs become less financially dependent on governmental funding

The effects of whole‐body vibration amplitude on glucose metabolism, inflammation, and skeletal muscle oxygenation

Whole‐body vibration (WBV) is an exercise mimetic that elicits beneficial metabolic effects. This study aims to investigate the effects of WBV amplitude on metabolic, inflammatory, and muscle oxygenation responses. Forty women and men were assigned to a high (HI; n = 20, Age: 31 ± 6 y) or a low‐amplitude group (LO; n = 20, Age: 33 ± 6 y). Participants engaged in 10 cycles of WBV [1 cycle =1 min of vibration followed by 30 s of rest], while gastrocnemius muscle oxygen consumption (mVO(2)) was assessed using near‐infrared spectroscopy (NIRS). Blood samples were collected PRE, POST, 1H, 3Hs, and 24H post‐WBV and analyzed for insulin, glucose, and IL‐6. In the LO group, Homeostatic Model Assessment for Insulin Resistant (HOMA‐IR) at 3 h (0.7 ± 0.2) was significantly lower compared to PRE (1.1 ± 0.2; p = 0.018), POST (1.3 ± 0.3; p = 0.045), 1H (1.3 ± 0.3; p = 0.010), and 24H (1.4 ± 0.2; p < 0.001). In addition, at 24H, HOMA‐IR was significantly lower in the LO when compared to the HI group (LO: 1.4 ± 0.2 vs. HI: 2.2 ± 0.4; p = 0.030). mVO(2) was higher (p = 0.003) in the LO (0.93 ± 0.29 ml/min/100 ml) when compared to the HI group (0.63 ± 0.28 ml/min/100 ml). IL‐6 at 3H (LO: 13.2 ± 2.7 vs. HI: 19.6 ± 4.0 pg·ml(−1); p = 0.045) and 24H (LO: 4.2 ± 1.1 vs. HI: 12.5 ± 3.1 pg·ml(−1); p = 0.016) was greater in the HI compared to the LO group. These findings indicate that low‐amplitude WBV provides greater metabolic benefits compared to high‐amplitude WBV

Cx43 Overexpression in Osteocytes Prevents Osteocyte Apoptosis and Preserves Cortical Bone Quality in Aging Mice

Young, skeletally mature mice lacking Cx43 in osteocytes exhibit increased osteocyte apoptosis and decreased bone strength, resembling the phenotype of old mice. Further, the expression of Cx43 in bone decreases with age, suggesting a contribution of reduced Cx43 levels to the age-related changes in the skeleton. We report herein that Cx43 overexpression in osteocytes achieved by using the DMP1-8kb promoter (Cx43OT mice) attenuates the skeletal cortical but not trabecular bone phenotype of aged, 14-month-old mice. The percentage of Cx43-expressing osteocytes was higher in Cx43OT mice, whereas the percentage of Cx43-positive osteoblasts remained similar to wild-type (WT) littermate control mice. The percentage of apoptotic osteocytes and osteoblasts was increased in aged WT mice compared with skeletally mature, 6-month-old WT mice, and the percentage of apoptotic osteocytes, but not osteoblasts, was decreased in age-matched Cx43OT mice. Aged WT mice exhibited decreased bone formation and increased bone resorption as quantified by histomorphometric analysis and circulating markers compared with skeletally mature mice. Further, aged WT mice exhibited the expected decrease in bone biomechanical structural and material properties compared with young mice. Cx43 overexpression prevented the increase in osteoclasts and decrease in bone formation on the endocortical surfaces and the changes in circulating markers in the aged mice. Moreover, the ability of bone to resist damage was preserved in aged Cx43OT mice both at the structural and material level. All together, these findings suggest that increased Cx43 expression in osteocytes ameliorates age-induced cortical bone changes by preserving osteocyte viability and maintaining bone formation, leading to improved bone strength. © 2018 American Society for Bone and Mineral Research

Treatment of Fibromyalgia with Formula Acupuncture: Investigation of Needle Placement, Needle Stimulation, and Treatment Frequency

Objectives: The objective of this study was to investigate whether typical acupuncture methods such as needle placement, needle stimulation, and treatment frequency were important factors in fibromyalgia symptom improvement. Design/settings/subjects: A single-site, single-blind, randomized trial of 114 participants diagnosed with fibromyalgia for at least 1 year was performed. Intervention: Participants were randomized to one of four treatment groups: (1) T/S needles placed in traditional sites with manual needle stimulation (n = 29): (2) T/0 traditional needle location without stimulation (n = 30); (3) N/S needles inserted in nontraditional locations that were not thought to be acupuncture sites, with stimulation (n = 28); and (4) N/0 nontraditional needle location without stimulation (n = 2 7). All groups received treatment once weekly, followed by twice weekly, and finally three times weekly, for a total of 18 treatments. Each increase in frequency was separated by a 2-week washout period. Outcome measures: Pain was assessed by a numerical rating scale, fatigue by the Multi-dimensional Fatigue Inventory, and physical function by the Short Form–36. Results: Overall pain improvement was noted with 25%–35% of subjects having a clinically significant decrease in pain; however this was not dependent upon "correct" needle stimulation (t = 1.03; p = 0.307) or location (t = 0.76; p = 0.450). An overall dose effect of treatment was observed, with three sessions weekly providing more analgesia than sessions once weekly (t = 2.10; p = 0.039). Among treatment responders, improvements in pain, fatigue, and physical function were highly codependent (all p ≤ 0.002). Conclusions: Although needle insertion led to analgesia and improvement in other somatic symptoms, correct needle location and stimulation were not crucial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63411/1/acm.2005.11.663.pd

Dengue Reporter Virus Particles for Measuring Neutralizing Antibodies against Each of the Four Dengue Serotypes

The lack of reliable, high-throughput tools for characterizing anti-dengue virus (DENV) antibodies in large numbers of serum samples has been an obstacle in understanding the impact of neutralizing antibodies on disease progression and vaccine efficacy. A reporter system using pseudoinfectious DENV reporter virus particles (RVPs) was previously developed by others to facilitate the genetic manipulation and biological characterization of DENV virions. In the current study, we demonstrate the diagnostic utility of DENV RVPs for measuring neutralizing antibodies in human serum samples against all four DENV serotypes, with attention to the suitability of DENV RVPs for large-scale, long-term studies. DENV RVPs used against human sera yielded serotype-specific responses and reproducible neutralization titers that were in statistical agreement with Plaque Reduction Neutralization Test (PRNT) results. DENV RVPs were also used to measure neutralization titers against the four DENV serotypes in a panel of human sera from a clinical study of dengue patients. The high-throughput capability, stability, rapidity, and reproducibility of assays using DENV RVPs offer advantages for detecting immune responses that can be applied to large-scale clinical studies of DENV infection and vaccination

Migration, Dispersal, and Gene Flow of Harvested Aquatic Species in the Canadian Arctic

Migration occurs when key aspects of the life cycle such as growth, reproduction, or maintenance cannot all be completed in one location. The Arctic habitats are variable and Arctic species are often migratory. The predictable nature of migrations in both space and time allow Arctic people to harvest fishes and marine mammals. We describe migratory/dispersal behavior in four types of taxa from the Canadian Arctic: anadromous and freshwater fishes, marine fishes, marine invertebrates, and marine mammals. Patterns of migration are remarkably different between these groups, in particular between distances migrated, seasonal timing of migrations, and the degree of reproductive isolation. Migratory anadromous and freshwater fishes become adapted to specific locations resulting in complex life histories and intra- and inter-population variation. Marine mammals not only migrate longer distances but also appear to have distinct demographic populations over large scales. Marine fishes tend to be panmictic, probably due to the absence of barriers that would restrict gene flow. Migratory patterns also reflect feeding or rearing areas and/or winter refugia. Migratory patterns of harvested aquatic organisms in the Canadian north are extremely variable and have shaped the north in terms of harvest, communities, and culture