Identification of differentially methylated CpG Sites in fibroblasts from Keloid Scars

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission

Alpha-decay branching ratios of near-threshold states in 19Ne and the astrophysical rate of 15O(alpha,gamma)19Ne

The 15O(alpha,gamma)19Ne reaction is one of two routes for breakout from the hot CNO cycles into the rp process in accreting neutron stars. Its astrophysical rate depends critically on the decay properties of excited states in 19Ne lying just above the 15O + alpha threshold. We have measured the alpha-decay branching ratios for these states using the p(21Ne,t)19Ne reaction at 43 MeV/u. Combining our measurements with previous determinations of the radiative widths of these states, we conclude that no significant breakout from the hot CNO cycle into the rp process in novae is possible via 15O(alpha,gamma)19Ne, assuming current models accurately represent their temperature and density conditions

Elastic electron deuteron scattering with consistent meson exchange and relativistic contributions of leading order

The influence of relativistic contributions to elastic electron deuteron scattering is studied systematically at low and intermediate momentum transfers ($Q^2\leq 30$ fm$^{-2}$). In a $(p/M)$-expansion, all leading order relativistic $\pi$-exchange contributions consistent with the Bonn OBEPQ models are included. In addition, static heavy meson exchange currents including boost terms and lowest order $\rho\pi\gamma$-currents are considered. Sizeable effects from the various relativistic two-body contributions, mainly from $\pi$-exchange, have been found in form factors, structure functions and the tensor polarization $T_{20}$. Furthermore, static properties, viz. magnetic dipole and charge quadrupole moments and the mean square charge radius are evaluated.Comment: 15 pages Latex including 5 figures, final version accepted for publication in Phys.Rev.C Details of changes: (i) The notation of the curves in Figs. 1 and 2 have been clarified with respect to left and right panels. (ii) In Figs. 3 and 4 an experimental point for T_20 has been added and a corresponding reference [48] (iii) At the end of the text we have added a paragraph concerning the quality of the Bonn OBEPQ potential

Investigating the topology of interacting networks - Theory and application to coupled climate subnetworks

Network theory provides various tools for investigating the structural or functional topology of many complex systems found in nature, technology and society. Nevertheless, it has recently been realised that a considerable number of systems of interest should be treated, more appropriately, as interacting networks or networks of networks. Here we introduce a novel graph-theoretical framework for studying the interaction structure between subnetworks embedded within a complex network of networks. This framework allows us to quantify the structural role of single vertices or whole subnetworks with respect to the interaction of a pair of subnetworks on local, mesoscopic and global topological scales. Climate networks have recently been shown to be a powerful tool for the analysis of climatological data. Applying the general framework for studying interacting networks, we introduce coupled climate subnetworks to represent and investigate the topology of statistical relationships between the fields of distinct climatological variables. Using coupled climate subnetworks to investigate the terrestrial atmosphere's three-dimensional geopotential height field uncovers known as well as interesting novel features of the atmosphere's vertical stratification and general circulation. Specifically, the new measure "cross-betweenness" identifies regions which are particularly important for mediating vertical wind field interactions. The promising results obtained by following the coupled climate subnetwork approach present a first step towards an improved understanding of the Earth system and its complex interacting components from a network perspective

Light microscopic observations of the ruminal papillae of cattle on diets with divergent forage to cereal ratios

High levels of supplementation with cereal increases production rates in cattle but can increase incidence of disease, ranging from mild indigestion to acute ruminal acidosis and death. Therefore, there is motivation to determine biological markers which can be used to identify whether animals have been, or are being fed, sufficient or excessive cereals. This study aimed to describe light microscopic findings from animals being fed diverse dietary cereal proportions and to test the performance of a novel rumen epithelial scoring system. Rumen wall tissue samples were obtained from the abattoir from 195 cattle from 11 Scottish farms and processed for histological examination. Light microscopic examination was used to characterise ruminal epithelial response to dietary challenge. Secondary objectives included describing the distribution of immune-related cells in bovine ruminal epithelium and assessing the use of a modified Elastin Martius Scarlet Blue stain (EMSB) for histological examination of the rumen epithelium. Cells staining positive for cluster of differentiation 3 were distributed mainly in the lower layers of the stratum basale and were found in higher densities in animals offered lower cereal proportion diets. Cells staining positive for major histocompatibility complex class 2 (MHCII) were most common in perivascular locations and in the junction between the lower stratum basale and the propria-submucosa. The density of MHCII positive staining cells was higher in animals on lower cereal diets. The level of supplementation with cereal was also associated with the thickness of the stratum corneum (SCT) and stratum granulosum (SGT), the integrity of the stratum corneum and sloughing of cornified cells. There were no advantages in using EMSB stain over haematoxylin and eosin (H and E) in this scoring system. We concluded that a scoring system that included only SCT, SGT and a measure of the loss of appearance of intercellular space allowed differentiation of groups of animals according to the level of cereal supplementation

Fecundity and spawning of the Atlantic horseshoe crab, Limulus polyphemus, in Pleasant Bay, Cape Cod, Massachusetts, USA

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Marine Ecology 27 (2006): 54-65, doi:10.1111/j.1439-0485.2005.00053.x.This study provided the first comprehensive analysis of Atlantic horseshoe crab (Limulus polyphemus) fecundity. Limulus appear to be determinate spawners, maturing all their eggs for the breeding season before spawning begins. On average, larger females held a larger number of eggs (63,500) than smaller females (14,500). By the end of the breeding season there was an average of 11,600 mature eggs female-1 left undeposited, regardless of female size. Larger females laid a higher percentage of the eggs they contained. Thus they not only contain more eggs, but are more effective at laying them as well. Size of spawning females ranged from about 185-300 mm prosomal width, with by far the highest concentration in the mid-size ranges. Although on an individual basis large females carry and lay the greatest number of eggs, mid-size crabs as a group contributed more to the horseshoe crab population in Pleasant Bay because they were more plentiful (net fecundity was highest for mid-size crabs). These results have implications for the management of this important species, which is harvested for bait, scientific, and biomedical uses. Incorporation of these results into models and other management tools can help predict growth rates, effects of size-selective harvest, reproductive value, and stable stage distribution of populations.This project was partially funded by MIT Sea Grant 8247-5

results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

Funding Information: MP, KK, and ES contributed equally and are co-first authors. JHS, JASp, and JFS contributed equally and are co-senior authors. The authors thank Berk Degirmenci, Christele Feliix, Shangyi Jin, Candace A Palmerlee, Andrea Peirce, Lisa G Rider, Esra Sari, Robert Tseng, and Leslie Wang for their invaluable contributions to the GRA Vax Survey. MP, KK, ES, SES, and JWL contributed to data collection, data quality control, and data analysis and interpretation. AAA, DA-R, SA, RPB, FB, IB, YPEC, RC, AD-G, ED, KLD, TAG, CLH, RH, BFH, EH, LK, AK, AHJK, DFLL, CL, EFM, BM, SM, MN, ADS, JASi, NS, MFU-G, JW, KJY, and EAZ-T, critically revised the manuscript and provided intellectual content. TTM, CH, MJL, ML, GF, and LT contributed to planning and data collection, reviewed the manuscript, and provided important intellectual content. SB, WC, RG, PMM, PCR, PS, ZSW, and JY contributed to the acquisition, analysis, and interpretation of the data. JASp, JFS, and JSH directed the work, designed the data collection methods, and contributed to the analysis and interpretation of the data. MP, KK, ES, SES, JWL, SB, WC, RG, PMM, PCR, PS, ZSW, JY, JASp, JFS, and JSH drafted and revised the manuscript critically for important intellectual content and gave final approval of the version to be published. SES, JWL, KK, JFS, and JASp had full access to the data and verify the credibility of the underlying data. All authors have read, revised, and approved this manuscript and take final responsibility for the decision to submit for publication. MP reports clinical trials participation with AbbVie and grants from Rheumatology Research Foundation, outside the submitted work. ES is a board member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. JWL has received research grant funding from Pfizer unrelated to this work. SES reports research funding related to clinical trials from AstraZeneca (MANDARA), outside of the submitted work and is supported by the Vasculitis Clinical Research Consortium and Vasculitis Foundation outside of the submitted work. DA-R is a scientific advisor for GlaxoSmithKilne unrelated to this work. RC reports speaker fees from Janssen, Roche, Sanofi, and AbbVie, outside of the submitted work. AD-G reports grants from the Center for Disease Control and Prevention, Rheumatology Research Foundation, and Mayo Clinic, outside the submitted work. KLD is an unpaid volunteer president of the Autoinflammatory Alliance and reports grants from Novartis, Sobi, National Institutes of Health (NIH), and Horizon Bio, all received by the non-profit organisation outside of the submitted work. CLH received funding under a sponsored research agreement unrelated to the data in the paper from Vifor Pharmaceuticals. RH reports grants from AbbVie, Amgen, Boehringer Ingleheim, Johnson and Johnson, Lilly, Novartis, Pfizer, and Union Chimique Belge, all paid to Spondylitis Association of America, consultant fees from GlaxoSmithKline and Novartis, outside the submitted work. RH also owns stocks (<20 shares and representing <4% of personal investments) in AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Merck, Novartis, Pfizer, Teva, and Union Chimique Belge. AHJK reports personal fees from Exagen Diagnostics, Alexion Pharmaceuticals, and Aurinia Pharmaceuticals, grants from National Institutes of Health, Rheumatology Research Foundation, and Helmsley Charitable Trust, grants and personal fees from GlaxoSmithKline, outside the submitted work. EFM reports personal fees from Boehringer Ingelheim, and that Liga Portuguesa Contra as Doenças Reumaticas has received grants from AbbVie, Novartis, Lilly Portugal, Amgen Biofarmacêutica, Grünenthal, Merck Sharp & Dohme, Medac and from A Menarini Portugal–Farmacêutica; grants and non-financial support from Pfizer and Grünenthal, outside the submitted work. JASi has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, United BioMed, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health, and the American College of Rheumatology. JASi owns stock options in TPT Global Tech, Vaxart pharmaceuticals, and Charlotte's Web Holdings and previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JASi is on the speaker's bureau of Simply Speaking and is a member of the executive of Outcomes Measures in Rheumatology, an organisation that develops outcome measures in rheumatology and receives funding from eight companies . JASi also serves on the FDA Arthritis Advisory Committee and is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JASi is also the editor and the Director of the University of Alabama at Birmingham Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. MFU-G has received research support from Pfizer and Janssen, unrelated to this work. SB reports non-branded consulting fees from Novartis, AbbVie, Pfizer, and Horizon Pharma, outside the submitted work, and is a Pfizer employee as of September, 2021. RG reports personal fees from AbbVie New Zealand, Cornerstones, Janssen New Zealand, and Novartis, and personal fees and non-financial support Pfizer Australia (all <AU$10,000) outside the submitted work. PMM reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and Union Chimique Belge; and grants and personal fees from Orphazyme, outside the submitted work. PCR reports personal fees from AbbVie, Gilead, Lilly, and Roche; grants and personal fees from Novartis, Union Chimique Belge, Janssen, and Pfizer; and non-financial support from Bristol Myers Squibb, outside the submitted work. PS reports honoraria from bring the social media editor for the American College of Rheumatology journals, outside the submitted work. ZSW reports grants from NIH, Bristol Myers Squibb, and Principia/Sanofi; and personal fees from Viela Bio and MedPace, outside the submitted work. JY reports personal fees from Pfizer and Eli Lilly, and grants and personal fees from AstraZeneca, outside the submitted work. CH reports personal fees from AstraZeneca and Aurinia Pharmaceuticals, outside the submitted work. MJL reports grants from American College of Rheumatology, during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gilead, Johnson and Johnson, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi, and Union Chimique Belge, outside the submitted work. JSH reports grants from Childhood Arthritis and Rheumatology Research Alliance and Rheumatology Research Alliance, and personal fees from Novartis, Pfizer, and Biogen, outside the submitted work. JASp reports grants from National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rheumatology Research Foundation, and R Bruce and Joan M Mickey Research Scholar Fund; and consulting fees for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer, unrelated to this work. JFS received research grant funding from the National Institutes of Health unrelated to this work (NIAMS R01 AR077103, and NIAID R01 AI154533). All other authors report no competing interests. This study was funded by the American College of Rheumatology (ACR). The ACR was not involved in any aspect of study design, collection, analysis, or interpretation of data, writing of the report, or the decision to submit the paper for publication. The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the ACR, the European Alliance of Associations for Rheumatology, the UK National Health Service, the National Institute for Health Research, or the UK Department of Health, or any other organisation. Researchers interested in performing additional analyses from survey data are invited to submit proposals through the COVID-19 Global Rheumatology Alliance at rheumcovid.org . For approved projects, we will provide summary tables and data analyses as requested. We do not currently have institutional review board approval to make the raw data available to other researchers.publishersversionpublishe

Accounting for International War: The State of the Discipline

In studies of war it is important to observe that the processes leading to so frequent an event as conflict are not necessarily those that lead to so infrequent an event as war. Also, many models fail to recognize that a phenomenon irregularly distributed in time and space, such as war, cannot be explained on the basis of relatively invariant phenomena. Much research on periodicity in the occurrence of war has yielded little result, suggesting that the direction should now be to focus on such variables as diffusion and contagion. Structural variables, such as bipolarity, show contradictory results with some clear inter-century differences. Bipolarity, some results suggest, might have different effects on different social entities. A considerable number of studies analysing dyadic variables show a clear connection between equal capabilities among contending nations and escalation of conflict into war. Finally, research into national attributes often points to strength and geographical location as important variables. In general, the article concludes, there is room for modest optimism, as research into the question of war is no longer moving in non-cumulative circles. Systematic research is producing results and there is even a discernible tendency of convergence, in spite of a great diversity in theoretical orientations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69148/2/10.1177_002234338101800101.pd