bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in alpha-7 nicotinic acetylcholine receptor and macrophage polarization state participate in the regulation of cervical remodeling in pregnant rats†
Authors: Yang Jinying , Lai Yumian , Chen Juanhua , Lin Baohua , Zhou Bei , Han Xinjia 
Published: July 2019

AbstractTo test the hypothesis that changes in alpha-7 nicotinic acetylcholine receptor (α7nAChR) expression on macrophages and macrophage polarization participate in cervical remodeling during normal pregnancy, pregnant rats from gestational days (GDs) 14, 16, 18, 20, and 22 were used in the present study. The expression of α7nAChR on macrophages and the numbers of M1 and M2 macrophages were detected by double immunofluorescence staining. The levels of α7nAChR and collagens were detected by western blotting. M1 markers (inducible nitric oxide synthase and inflammatory cytokines) and M2 markers (arginase 1, anti-inflammatory cytokines) were detected to evaluate the macrophage polarization state by immunohistochemistry staining, western blotting, and the enzyme-linked immunosorbent assay. Matrix metalloproteinase 9 (MMP-9) expression was determined by immunohistochemistry staining and western blotting. We found that the α7nAChR expression on macrophages significantly decreased on GD22 compared to GDs 14, 16, 18, and 20. There was an increased number of M1 macrophages and decreased number of M2 macrophages in late pregnancy. The expression of M1 macrophage biomarkers was much higher on GDs 20 and 22 than on GDs 14, 16, and 18, but expression of M2 biomarkers decreased on GDs 20 and 22 compared to GDs 14, 16, and 18. MMP-9 expression was higher on GD22 than on GDs 14, 16, 18, and 20, and collagen expression significantly decreased on GDs 18, 20, and 22 compared to GD14. Our results indicated that the decreased expression of α7nAChR and increased number of M1 macrophages are associated with cervical remodeling.
Evidence-Based, High-Intensity Exercise and Physical Activity for Compressing Morbidity in Older Adults: A Narrative Review
Authors: Winett Richard A , Ogletree Aaron M 
Published: July 2019

Abstract
Recent research in exercise science has important applications for middle-aged and older adults and points to how the programming of individual and multicomponent interventions including theory-based health behavior change strategies may be improved to compress morbidity by delaying or reducing the disabling process. High-intensity interval training and sprint interval training until recently were seen as only applicable to athletes. But recent lab-based research has adapted these interventions for even older adults and demonstrated their safety with beneficial outcomes on cardiometabolic risk factors comparable to or surpassing the usual lower- to moderate-intensity endurance training, and their potential translatability by showing the efficacy of much lower duration and frequency of training, even by systematic stair climbing. Moreover, people report positive affect while engaged in such training. For a century, resistance training was conceived as weightlifting with heavy weights required. Recent research has shown that using a higher degree of effort with lighter to moderate resistance in simple, time efficient protocols result in gains in strength and muscle mass similar to heavy resistance, as well as improvement of cardiometabolic risk factors, strength, body composition, and cognitive, affective, and functional abilities. More effort-based resistance training with moderate resistance may make resistance training more appealing and accessible to older adults. A key potential translational finding is that with correct technique and a high degree of effort, training with inexpensive, portable elastic bands, useable virtually anywhere, can provide appreciable benefits. More emphasis should be placed on long-term, translational interventions, resources, and programs that integrate interval and resistance trainings. This work may improve public health programs for middle-aged and older adults and reflects an emerging evidence base.
Soft and hard X-ray dips in the light curves of γ Cassiopeiae
Authors: Smith M A , Lopes de Oliveira R 
Published: July 2019

ABSTRACT
The available six archival XMM–Newton observations of the anomalous X-ray emitter γ Cas (B0.5 IVe) have been surveyed for the presence of soft X-ray ‘dips’ in X-ray light curves. In addition to discovering such events in the soft band (≤2 keV), we show that sometimes they are accompanied by minor, nearly simultaneous dips in the hard X-ray band. Herein, we investigate how these occurrences can be understood in the ‘magnetic star–disc interaction’ hypothesis proposed in the literature to explain the hard, variable X-ray emission of this Be star. In this scenario, the soft X-ray dips are interpreted as transits by comparatively dense, soft X-ray-absorbing blobs that move across the lines of sight to the surface of the Be star. We find that these blobs have similar properties as the ‘cloudlets’ responsible for migrating subfeatures in UV and optical spectral lines and therefore may be part of a common distribution of co-rotating occulters. The frequencies, amplitudes, and longevities of these dips vary widely. Additionally, the most recent spectra from 2014 July suggest that the ‘warm’ (kT ≈ 0.6–4 keV) plasma sources responsible for some of the soft flux are much more widely spread over the Be star’s surface than the hot plasma sites that dominate the flux at all X-ray energies. We finally call attention to a sudden drop in all X-ray energies of the 2014 light curve of γ Cas and a similar sudden drop in a light curve of the ‘analog’ HD 110432. We speculate that these could be related to appearances of particularly strong soft X-ray dips several hours earlier.
Absolute properties of RU Cnc revisited: an active RS CVn-type eclipsing binary with red giant branch and main-sequence components
Authors: Çokluk K A , Koçak D , İçli T , Karaköse S , Üstündağ S , Yakut K 
Published: July 2019

ABSTRACT
We present observations and analysis of an RS CVn-type double-lined eclipsing binary system, RU Cnc. The system has been observed for over a century. High-quality long-cadence observations, newly obtained from the Kepler K2 C5 and C18 campaigns, and two radial velocity curves were combined and analysed simultaneously, assuming a multispot model. The masses, radii and luminosities of the component stars have been precisely obtained as $M_\textrm{c} = 1.386\pm 0.044\, \mathrm{M}_{\odot }$, $M_\textrm{h} = 1.437 \pm 0.046\, \mathrm{M}_{\odot }$, $R_\textrm{h} = 2.39\pm 0.07\, \mathrm{R}_{\odot }$, $R_\textrm{c} = 5.02 \pm 0.08\, \mathrm{R}_{\odot }$, $L_\textrm{h} = 11.4\pm 1.2\, \mathrm{L}_{\odot }$ and$L_\textrm{c} = 12.0 \pm 1.0\, \mathrm{L}_{\odot }$, with a separation of $a = 27.914 \pm 0.016\, \mathrm{R}_{\odot }$. The distance of the system is determined to be $380\pm 57\,$ pc, which is consistent with the Gaia Data Release 2 result. Long-term detailed period variation analysis of the system indicates a period decrease of 7.9 × 10−7 d yr–1. The results suggest that the cooler component is on the red giant branch (RGB) and the hotter component is still on the main sequence.
Discovery of Novel Sequences in 1,000 Swedish Genomes
Authors: Eisfeldt Jesper , Mårtensson Gustaf , Ameur Adam , Nilsson Daniel , Lindstrand Anna 
Published: July 2019

AbstractNovel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin.
Updating the use of the Madrid Sonographic Enthesis Index (MASEI): a systematic review of the literature
Authors: Macía-Villa Cristina , De Miguel Eugenio 
Published: July 2019

Abstract

Objective
To perform a systematic review of the literature to evaluate the use of the enthesis ultrasound Madrid Sonographic Entesis Index (MASEI) from its publication.

Methods
A systematic search of MEDLINE, EMBASE, and Cochrane Central Register databases was performed. The search strategy was constructed to identify publications containing terms related to enthesis and ultrasound. The only applied filter was studies conducted in humans. One reviewer systematically screened the search. A second reviewer verified the selection. The data extraction was focused on study characteristics, including population and components of the OMERACT filter.

Results
Sixty-eight of the 1581 identified studies had used MASEI, including 41 (60%) abstracts and 27 (40%) articles. Of the 27 articles, MASEI was mainly used for spondyloarthritis and related diseases in 12 (44%) articles, followed by both psoriatic arthritis and rheumatoid arthritis in five (19%) articles; however, it was also used in diseases such as Behçet disease, FM, familiar Mediterranean fever, SS, crystal arthropathies and systemic sclerosis. The feasibility of MASEI was reported in three (11%) articles, and the reliability in 12 (44%) with good to excellent values. No article evaluated the responsiveness to treatment. The construct validity of MASEI was assessed using biomarkers in seven (26%) articles, clinical examination in 13 (48%) and imaging procedures (only X-rays) in two (7%). The discriminative validity was assessed in 16 (59%) articles, not only in SpAs.

Conclusion
MASEI is a feasible, reliable and valid ultrasound score for the study of enthesis in spondyloarthritis, psoriatic arthritis and other diseases.
Effects of ractopamine hydrochloride supplementation on feeding behavior, growth performance, and carcass characteristics of finishing steers1,2
Authors: Trotta Ronald J , Maddock Carlin Kasey R , Swanson Kendall C 
Published: July 2019

Abstract
Ractopamine hydrochloride (RAC) is a β-adrenergic agonist that functions as a repartitioning agent to improve muscling in feedlot cattle. Many studies have investigated the effects of RAC on growth performance and carcass characteristics; however, there is minimal information about the influence of RAC on feeding behavior. Sixty-nine steers (body weight [BW] = 364 ± 3.9 kg) predominately of Angus and Simmental breeding were subjected to a 126-d (n = 46) or 154-d (n = 23) feeding period and randomly assigned to one of two treatment groups: supplementation to provide 0 (CON; n = 34) or 267 ± 4.9 mg/d of RAC (n = 35). Ractopamine was provided as Optaflexx 45 at 0.024% of the diet (dry matter [DM] basis; Elanco Animal Health, Greenfield, IN). Dietary treatments were fed the final 42 d in the feed yard (treatment period). Feeding behavior and growth performance were measured using radio frequency identification tags and the Insentec feeding system. Following the final day of treatment, steers were slaughtered and carcass measurements were recorded. Data were analyzed using MIXED models in SAS. There were no differences in BW, average daily gain (ADG), DM intake (DMI), gain:feed ratio (G:F), or feeding behavior during the pretreatment period (P &gt; 0.44). Ractopamine supplementation increased G:F during the treatment period (P = 0.02) and during the total period (P = 0.03) and tended to increase ADG during the treatment and total period (P ≤ 0.08). DMI was not affected during the treatment or total period (P &gt; 0.67). Eating time per visit, per meal, and per day were decreased (P &lt; 0.02) in steers supplemented with RAC during the treatment period. DMI per minute was increased (P = 0.02) in steers supplemented with RAC. Hot carcass weight, dressing percentage, and 12th rib fat were not influenced by RAC supplementation. Ractopamine supplementation decreased marbling (P = 0.008) and kidney, pelvic, and heart percentage (P = 0.04) and increased longissimus muscle area (P = 0.01). These data demonstrate that RAC supplementation for 42 d improves feed efficiency, increases the rate of DMI without altering DMI, and increases muscling in finishing cattle.
Factors associated with the institutionalization of a physical activity program in Australian elementary schools
Authors: Bourke Matthew , Hilland Toni A , Craike Melinda 
Published: July 2019

Abstract
The health benefits of classroom-based physical activity programs may only be sustained if programs are continually implemented over time. Despite the importance of instituting physical activity programs to ensure their continued implementation, little is known about factors associated with institutionalization of programs at a school level. The purpose of this study is to examine how school context, principal characteristics, and program attributes are associated with the institutionalization of Bluearth Foundation’s Active Schools program in Australian elementary schools. Current principals from schools who participated in the Active Schools program between 2015 and 2017 reported the level of institutionalization of the program, school context, principal characteristics, and perceived attributes of the program. Univariate associations were calculated using Pearson’s correlation coefficient, independent sample t-tests and one-way ANOVA. Linear regression using backward deletion was used to calculate significant or marginally significant (p < .1) multivariate associations. Thirty of the 211 eligible principals participated in the study. School capacity (r = .617, p < .001); perceived student behavioral (r = .577, p < .001), health (r = .499, p < .001), and enjoyment benefits (r = .529, p < .001), relative advantage (r = .417, p = .022), observability (r = .385, p = .036), and having the program delivered by a Bluearth coach at the time of the study (η 2 = .426, p < .001) all had a significant positive univariate association with institutionalization. School capacity (β = 1.802, p = .001), observability (β = 0.902, p = .061), and having the program delivered by a Bluearth coach at the time of the study (β = 2.580, p = .003) remained significant in the final multivariate model. Results suggest that schools that have someone who can provide support implementing a program are more likely to institute the program into policies and practices. It is also important that school administrators have the tools to evaluate the benefits of physical activity programs and to perceive them as being beneficial for their students. However, schools may struggle to institutionalize physical activity programs after formal program delivery has concluded.
Long-lasting Analgesia via Targetedin vivoEpigenetic Repression of Nav1.7
Authors: Moreno Ana M. , Catroli Glaucilene F. , Alemán Fernando , Pla Andrew , Woller Sarah A. , Hu Michael , Yaksh Tony , Mali Prashant 
Published: July 2019

ABSTRACTCurrent treatments for chronic pain rely largely on opioids despite their unwanted side effects and risk of addiction. Genetic studies have identified in humans key targets pivotal to nociceptive processing, with the voltage-gated sodium channel, NaV1.7 (SCN9A), being perhaps the most promising candidate for analgesic drug development. Specifically, a hereditary loss-of-function mutation in NaV1.7 leads to insensitivity to pain without other neurodevelopmental alterations. However, the high sequence similarity between NaVsubtypes has frustrated efforts to develop selective inhibitors. Here, we investigated targeted epigenetic repression of NaV1.7 via genome engineering approaches based on clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 and zinc finger proteins as a potential treatment for chronic pain. Towards this end, we first optimized the efficiency of NaV1.7 repressionin vitroin Neuro2A cells, and then by the lumbar intrathecal route delivered both genome-engineering platforms via adeno-associated viruses (AAVs) to assess their effects in three mouse models of pain: carrageenan-induced inflammatory pain, paclitaxel-induced neuropathic pain and BzATP-induced pain. Our results demonstrate: one, effective repression of NaV1.7 in lumbar dorsal root ganglia; two, reduced thermal hyperalgesia in the inflammatory state; three, decreased tactile allodynia in the neuropathic state; and four, no changes in normal motor function. We anticipate this genomically scarless and non-addictivepainamelioration approach enablingLong-lastingAnalgesia viaTargetedin vivoEpigeneticRepression of Nav1.7, a methodology we dubpain LATER, will have significant therapeutic potential, such as for preemptive administration in anticipation of a pain stimulus (pre-operatively), or during an established chronic pain state.One sentence summaryIn situepigenome engineering approach for genomically scarless, durable, and non-addictive management of pain.
LncRNA Mrhl orchestrates differentiation programs in mouse embryonic stem cells through chromatin mediated regulation
Authors: Pal Debosree , Neha C V , Bhaduri Utsa , Zenia  , Chidambaram Subbulakshmi , Rao M.R.S 
Published: July 2019

AbstractLong non-coding RNAs (lncRNAs) have been well-established to act as regulators and mediators of development and cell fate specification programs. LncRNA Mrhl (meiotic recombination hotspot locus) has been shown to act in a negative feedback loop with WNT signaling to regulate male germ cell meiotic commitment. In our current study, we have addressed the role of Mrhl in development and differentiation using mouse embryonic stem cells (mESCs) as our model system of study. We found Mrhl to be a nuclear-localized, chromatin-bound lncRNA with moderately stable expression in mESCs. Transcriptome analyses and loss-of-function phenotype studies revealed dysregulation of developmental processes and lineage-specific genes along with aberrance in specification of early lineages during differentiation of mESCs. Genome-wide chromatin occupancy studies suggest regulation of chromatin architecture at key target loci through triplex formation. Our studies thus reveal a role for lncRNA Mrhl in regulating differentiation programs in mESCs in the context of appropriate cues through chromatin-mediated responses.
Exon definition facilitates reliable control of alternative splicing in the RON proto-oncogene
Authors: Enculescu M. , Braun S. , Setty S. T. , Zarnack K. , König J. , Legewie S. 
Published: July 2019

ABSTRACTAlternative splicing is a key step in eukaryotic gene expression that allows the production of multiple protein isoforms from the same gene. Even though splicing is perturbed in many diseases, we currently lack insights into regulatory mechanisms promoting its precision and efficiency. We analyse high-throughput mutagenesis data obtained for an alternatively spliced exon in the proto-oncogene RON and determine the functional units that control this splicing event. Using mathematical modeling of distinct splicing mechanisms, we show that alternative splicing is based in RON on a so-called ‘exon definition’ mechanism. Here, the recognition of the adjacent exons by the spliceosome is required for removal of an intron. We use our model to analyze the differences between the exon and intron definition scenarios and find that exon definition is crucial to prevent the accumulation of deleterious, partially spliced retention products during alternative splicing regulation. Furthermore, it modularizes splicing control, as multiple regulatory inputs are integrated into a common net input, irrespective of the location and nature of the corresponding cis-regulatory elements in the pre-mRNA. Our analysis suggests that exon definition promotes robust and reliable splicing outcomes in RON splicing.SIGNIFICANCEDuring mRNA maturation, pieces of the pre-mRNA (introns) are removed during splicing, and remaining parts (exons) are joined together. In alternative splicing, certain exons are either included or excluded, resulting in different splice products. Inclusion of RON alternative exon 11 leads to a functional receptor tyrosine kinase, while skipping results in a constitutively active receptor that promotes epithelial-to-mesenchymal transition and contributes to tumour invasiveness. Intron retention results in to deleterious isoforms that cannot be translated properly. Using kinetic modeling, we investigate the combinatorial regulation of this important splicing decision, and find that the experimental data supports a so-called exon definition mechanism. We show that this mechanism enhances the precision of alternative splicing regulation and prevents the retention of introns in the mature mRNA.
Position-theta-phase model of hippocampal place cell activity applied to quantification of running speed modulation of firing rate
Authors: McClain Kathryn , Tingley David , Heeger David , Buzsáki György 
Published: July 2019

AbstractSpiking activity of place cells in the hippocampus encodes the animal’s position as it moves through an environment. Within a cell’s place field, both the firing rate and the phase of spiking in the local theta oscillation contain spatial information. We propose a position-theta-phase (PTP) model that captures the simultaneous expression of the firing-rate code and theta-phase code in place cell spiking. This model parametrically characterizes place fields to compare across cells, time and condition, generates realistic place cell simulation data, and conceptualizes a framework for principled hypothesis testing to identify additional features of place cell activity. We use the PTP model to assess the effect of running speed in place cell data recorded from rats running on linear tracks. For the majority of place fields we do not find evidence for speed modulation of the firing rate. For a small subset of place fields, we find firing rates significantly increase or decrease with speed. We use the PTP model to compare candidate mechanisms of speed modulation in significantly modulated fields, and determine that speed acts as a gain control on the magnitude of firing rate. Our model provides a tool that connects rigorous analysis with a computational framework for understanding place cell activity.SignificanceThe hippocampus is heavily studied in the context of spatial navigation, and the format of spatial information in hippocampus is multifaceted and complex. Furthermore, the hippocampus is also thought to contain information about other important aspects of behavior such as running speed, though there is not agreement on the nature and magnitude of their effect. To understand how all of these variables are simultaneously represented and used to guide behavior, a theoretical framework is needed that can be directly applied to the data we record. We present a model that captures well-established spatial-encoding features of hippocampal activity and provides the opportunity to identify and incorporate novel features for our collective understanding.