Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Currently, little is known about the evolution of epigenetic regulation in animal stem cells. Here we demonstrate, using the planarian stem cell system to investigate the role of the COMPASS family of MLL3/4 histone methyltransferases that their function as tumor suppressors in mammalian stem cells is conserved over a long evolutionary distance. To investigate the potential conservation of a genome-wide epigenetic regulatory program in animal stem cells, we assess the effects of Mll3/4 loss of function by performing RNA-seq and ChIP-seq on the G2/M planarian stem cell population, part of which contributes to the formation of outgrowths. We find many oncogenes and tumor suppressors among the affected genes that are likely candidates for mediating MLL3/4 tumor suppression function. Our work demonstrates conservation of an important epigenetic regulatory program in animals and highlights the utility of the planarian model system for studying epigenetic regulation

The effects of an active-assisted stretching program on functional performance in elderly persons: A pilot study

This study examined the impact of an eight-week active-assisted (AA) stretching program on functionality, mobility, power, and range of motion (ROM) in elderly residents of a residential retirement community. Seventeen volunteers (4 male, 13 female; 88.8 ± 5.36 years) were randomly assigned to an AA or control group. The AA group performed 10 different AA stretches targeting the major joints of the body twice weekly for eight weeks. Controls attended classes requiring limited physical activity. All participants were assessed using four flexibility and six functional tests, one week before and after the eight-week training period. A fully randomized repeated-measures ANCOVA with pretest scores as a covariate was used to detect differences between groups across time. The AA group demonstrated significant increases in ROM for most of the joints evaluated (p < 0.05) and significant increases in all performance measures (p < 0.05). Controls showed no improvements in functional or ROM measures (α = 0.05). Additionally, the AA group showed significantly better performance outcomes across the training period than controls. We conclude that our eight-week flexibility program effectively reduces age-related losses in ROM and improves functional performance in elderly persons with insufficient physical reserves to perform higher-intensity exercises

Ischemia and Infarction in STEMI Patients With Multivessel Disease : Insights From the CvLPRIT Nuclear Substudy

The CvLPRIT (Complete versus Lesion-only PRimary PCI Trial) trial was undertaken in 7 UK centers (1,2). Patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary stenoses were randomized to primary percutaneous coronary intervention (PPCI) to the infarct-related artery (IRA) only, or complete revascularization. At 12-month follow-up, the rate of the combined primary endpoint (all-cause mortality, recurrent MI, heart failure, ischemia-driven revascularization) was lower after complete revascularization. All surviving patients were asked to undergo myocardial perfusion scintigraphy (MPS) 6 to 8 weeks post-admission. It was expected that this a priori nuclear substudy would provide mechanistic insights into the outcome of the main trial, and help to define the clinical role of MPS in the PPCI era

Public preferences for ecological indicators used in Everglades restoration

The Everglades is one of the largest wetland ecosystems in the world covering almost 18,000 square miles from central Florida southward to Florida Bay. Over the 20th century, efforts to drain the Everglades for agriculture and development severely damaged the ecosystem so that today roughly 50% of the historic flow of water through the Everglades has been diverted elsewhere. In an attempt to restore the Everglades, the U.S. Congress authorized the Comprehensive Everglades Restoration Plan (CERP) in 2000, expected to cost over $16 billion and to take several decades to complete. We used the results from a stated preference choice experiment (SPCE) survey of Florida households to estimate the willingness to pay for several ecological attributes related to CERP performance indicators likely to be impacted by Everglades restoration. We also used a latent class model (LCM) to explore preference heterogeneity among respondents. On average, survey respondents were willing to pay for improvements in all of the attributes included in the survey, namely increased populations of wading birds, American alligators, endangered snail kites, and spotted seatrout, and reduced polluted discharges from Lake Okeechobee to the Caloosahatchee and St. Lucie rivers. Willingness to pay was highest for reduced polluted discharges from Lake Okeechobee.Data Availability: All relevant data are available at https://doi.org/10.17605/OSF.IO/9AG7Z.S1 Table. Comparison between the demographics of the survey sample respondents and the Florida population based on 2010 U.S. Census information. https://doi.org/10.1371/journal.pone.0234051.s001S2 Table. Regression results from conditional logit model with willingness to pay estimates. https://doi.org/10.1371/journal.pone.0234051.s002The Everglades Foundationhttp://www.plosone.orghj2020Mammal Research Institut

Examining the stability of membrane proteins within SMALPs

Amphipathic co-polymers such as styrene-maleic acid (SMA) have gained popularity over the last few years due to their ability and ease of use in solubilising and purifying membrane proteins in comparison to conventional methods of extraction such as detergents. SMA2000 is widely used for membrane protein studies and is considered as the optimal polymer for this technique. In this study a side-by-side comparison of SMA2000 with the polymer SZ30010 was carried out as both these polymers have similar styrene:maleic acid ratios and average molecular weights. Ability to solubilise, purify and stabilise membrane proteins was tested using three structurally different membrane proteins. Our results show that both polymers can be used to extract membrane proteins at a comparable efficiency to conventional detergent dodecylmaltoside (DDM). SZ30010 was found to give a similar protein yield and, SMALP disc size as SMA2000, and both polymers offered an increased purity and increased thermostability compared to DDM. Further investigation was conducted to investigate SMALP sensitivity to divalent cations. It was found that the sensitivity is polymer specific and not dependent on the protein encapsulated. Neither is it affected by the concentration of SMALPs. Larger divalent cations such as Co2+ and Zn2+ resulted in an increased sensitivity

The relationship between foot arch measurements and walking parameters in children

BACKGROUND: Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children and adults using dynamic measures. METHODS: Data were collected from 638 participants (n = 254 children and n = 384 adults) at the Museum of Science, Boston (MOS) and from 18 4- to 8-year-olds at the Motor Development and Motor Control Laboratories. Digital footprints were used to calculate two arch indices: the Chippaux-Smirak (CSI) and the Keimig Indices (KI). The height of the navicular bone was measured. Gait parameters were captured with a mechanized gait carpet at the MOS and three-dimensional motion analyses and in-ground force plates in the Motor Development and Motor Control Laboratories. RESULTS: Linear regression analyses on data from the MOS confirmed that as age increases, step length increases. With a linear mixed effect regression model, we found that individuals who took longer steps had higher arches as measured by the KI. However, this relationship was no longer significant when only adults were included in the model. A model restricted to children found that amongst this sample, those with higher CSI and higher KI values take longer relative step lengths. Data from the Motor Development and Motor Control Laboratories showed that both CSI and KI added to the prediction; children with lower anterior ground reaction forces had higher CSI and higher KI values. Arch height indices were correlated with navicular height. CONCLUSIONS: These results suggest that more than one measure of the arch may be needed elucidate the relationship between arch height and gait.K12 HD055931 - NICHD NIH HHS; K12HD055931 - NICHD NIH HH

Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1BCR-ABL-JAK2 Complex

This is a pre-copyedited, author-produced version of an article accepted for publication in JNCI: Journal of the National Cancer Institute following peer review. The version of record Chen, M., et al. (2013). "Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1–BCR-ABL–JAK2 Complex." JNCI: Journal of the National Cancer Institute 105(6): 405-423. is available online at: https://doi.org/10.1093/jnci/djt006This work was funded by the Canadian Cancer Society (grant 700289), in part by the Canadian Institutes of Health Research, the Leukemia & Lymphoma Society of Canada, and the Cancer Research Society (XJ), the Canadian Cancer Society Research Institute (AE, XJ, CE), Cancer Research UK Programme grant C11074/A11008 (TLH), the Glasgow Experimental Cancer Medicine Centre, which is funded by Cancer Research UK and by the Chief Scientist’s Office (Scotland), and Cancer Research UK grant C973/A9894 (JP, JS). M. Chen was supported by a fellowship from Lymphoma Foundation Canada, and P. Gallipoli was supported by Medical Research Council grant G1000288. X. Jiang was a Michael Smith Foundation for Health Research Scholar

The genome of the crustacean Parhyale hawaiensis, a model for animal development, regeneration, immunity and lignocellulose digestion

The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion ('wood eating'), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source. DOI: http://dx.doi.org/10.7554/eLife.20062.00

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs