bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between lipoproteins, thrombosis, and atrial fibrillation
Authors: Ding Wern Yew , Protty Majd B , Davies Ian G , Lip Gregory Y H 
Published: January 2021

AbstractThe prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow’s triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis.
Long-Term Efficacy and Safety of Ozanimod in Moderately to Severely Active Ulcerative Colitis: Results From the Open-Label Extension of the Randomized, Phase 2 TOUCHSTONE Study
Authors: Sandborn William J , Feagan Brian G , Hanauer Stephen , Vermeire Severine , Ghosh Subrata , Liu Wenzhong J , Petersen AnnKatrin , Charles Lorna , Huang Vivian , Usiskin Keith , Wolf Douglas C , D’Haens Geert 
Published: January 2021

Abstract

Background and Aims
This analysis examined the long-term safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitis [UC] with ≥ 4 years of follow-up in the phase 2 TOUCHSTONE open-label extension [OLE].

Methods
Patients receiving placebo or ozanimod HCl 0.5 mg or 1 mg during the double-blind period could enter the OLE [ozanimod HCl 1 mg daily]. Partial Mayo score [pMS] clinical response and remission were assessed through OLE week 200 and summarized descriptively using observed cases [OC] and non-responder imputation [NRI]. Endoscopy was required at OLE week 56 and the end of treatment. Parameters associated with endoscopy were summarized at weeks 56 and 104 [OC], and week 56 [NRI]. C-reactive protein and faecal calprotectin were assessed. Adverse events were monitored throughout the study.

Results
Of 197 patients receiving double-blind treatment, 170 entered the OLE. Discontinuation rates were 28% at year 1 and 15–18% annually through year 4. Partial Mayo measures indicated clinical response and remission rates at OLE week 200 of 93.3% and 82.7%, respectively, using OC and 41% and 37% with the more conservative NRI analysis. At weeks 56 and 104, respectively, histological remission rates were 46.3% and 38.5%, and endoscopic improvement rates were 46.4% and 46.5% [OC]. No new safety signals were identified during ≥ 4 years of follow-up.

Conclusions
There was a high rate of continued study participation and long-term benefit with ozanimod HCl 1 mg daily based on clinical, histological and biomarker measures in patients with moderately to severely active UC in the TOUCHSTONE OLE. [NCT02531126]
Prognostic value of inflammatory biomarkers and GRACE score for cardiac death and acute kidney injury after acute coronary syndromes
Authors: Rossi Valentina A , Denegri Andrea , Candreva Alessandro , Klingenberg Roland , Obeid Slayman , Räber Lorenz , Gencer Baris , Mach François , Nanchen David , Rodondi Nicolas , Heg Dik , Windecker Stephan , Buhmann Joachim , Ruschitzka Frank , Lüscher Thomas F , Matter Christian M 
Published: January 2021

Abstract

Aims
The aim of this study was to analyse the role of inflammation and established clinical scores in predicting acute kidney injury (AKI) after acute coronary syndromes (ACS).

Methods and results
In a prospective multicentre cohort including 2034 patients with ACS undergoing percutaneous coronary intervention, high-sensitivity C-reactive protein (hsCRP), neutrophil count, neutrophil-to-lymphocyte ratio (NL-ratio), and creatinine were measured at the index procedure. AKI (n = 39, defined according to RIFLE criteria) and major cardiovascular and cerebrovascular events were adjudicated after 1 year. Associations between inflammation, AKI, and cardiac death (CD) were assessed by C-statistics and Cox proportional hazard models with log-rank test to compare survival. Patients with ACS with elevated neutrophil count &gt;7.8 × 109/L, NL-ratio &gt;5, combined neutrophil-count/creatinine, or NL-ratio/creatinine at baseline showed a higher incidence of AKI (all P &lt; 0.05) and CD (all P &lt; 0.001). The risk of AKI, CD, and their combination was increased in patients with higher neutrophil count/creatinine (heart rate (HR) = 3.7, 95% cardiac index (CI) 1.9–7.1; HR = 2.7, 95% CI 1.6–4.6; HR = 3.2, 95% CI 2.1–4.9); NL-ratio/creatinine (HR = 2.1, 95% CI 1.6–4.1; HR = 2.2, 95% CI 1.3–3.8; HR = 2.3, 95% CI 1.5–3.5); and hsCRP (HR = 1.8, 95% CI 0.9–3.5; HR = 2.2, 95% CI 1.3–3.6; HR = 1.9, 95% CI 1.2–2.8) after adjustment for age, diabetes, hypertension, previous heart failure, kidney function, haemodynamic instability at admission, statin, and renin–angiotensin–aldosterone antagonists use. Subjects with higher GRACE score 1.0/NL-ratio had higher rate of AKI, CD, and both (HR = 1.4, 95% CI 0.5–4.2; HR = 2.7, 95% CI 1.3–5.9; HR = 2.1, 95% CI 1–4.3).

Conclusions
Inflammation markers may predict AKI after correction for renal function at the index procedure. hsCRP performed better than the NL-ratio. However, the integration of inflammation markers to traditional risk factors or scores does not add prognostic information.

Trial registration
ClinicalTrials.gov, NCT01000701.
Firm-specific responses to energy policies in Dutch horticulture
Authors: Los Evert , Gardebroek Cornelis , Huirne Ruud 
Published: January 2021

AbstractReducing the usage of fossil fuels is a central issue in ongoing policy debates. This in particular holds for Dutch horticulture, given its energy-intensive production. We analyse differences in energy usage and price responsiveness of horticultural firms by estimating energy demand functions using a Bayesian random coefficient model. Beyond, the effects of a proposed energy tax are assessed. Allowing for firm-specific energy price coefficients gives a better model fit compared to conventional models with fixed slope parameters. This confirms that firms respond differently to energy prices, which is taken into account in simulating the effects of more restrictive energy policies. The results show that larger-sized firms use less gas per square meter yet also point at a considerable spread in additional energy expenses between firms.
Precision Medicine and cardiac channelopathies: when dreams meet reality
Authors: Gnecchi Massimiliano , Sala Luca , Schwartz Peter J 
Published: January 2021

Abstract
Precision Medicine (PM) is an innovative approach that, by relying on large populations’ datasets, patients’ genetics and characteristics, and advanced technologies, aims at improving risk stratification and at identifying patient-specific management through targeted diagnostic and therapeutic strategies. Cardiac channelopathies are being progressively involved in the evolution brought by PM and some of them are benefiting from these novel approaches, especially the long QT syndrome. Here, we have explored the main layers that should be considered when developing a PM approach for cardiac channelopathies, with a focus on modern in vitro strategies based on patient-specific human-induced pluripotent stem cells and on in silico models. PM is where scientists and clinicians must meet and integrate their expertise to improve medical care in an innovative way but without losing common sense. We have indeed tried to provide the cardiologist’s point of view by comparing state-of-the-art techniques and approaches, including revolutionary discoveries, to current practice. This point matters because the new approaches may, or may not, exceed the efficacy and safety of established therapies. Thus, our own eagerness to implement the most recent translational strategies for cardiac channelopathies must be tempered by an objective assessment to verify whether the PM approaches are indeed making a difference for the patients. We believe that PM may shape the diagnosis and treatment of cardiac channelopathies for years to come. Nonetheless, its potential superiority over standard therapies should be constantly monitored and assessed before translating intellectually rewarding new discoveries into clinical practice.
Democratization of fungal highway columns as a tool to investigate bacteria associated with soil fungi
Authors: Junier Pilar , Cailleau Guillaume , Palmieri Ilona , Vallotton Celine , Trautschold Olivia C , Junier Thomas , Paul Christophe , Bregnard Danae , Palmieri Fabio , Estoppey Aislinn , Buffi Matteo , Lohberger Andrea , Robinson Aaron , Kelliher Julia M , Davenport Karen , House Geoffrey L , Morales Demosthenes , Gallegos-Graves La Verne , Dichosa Armand E K , Lupini Simone , Nguyen Hang N , Young Jamey D , Rodrigues Debora F , Parra-Vasquez A Nicholas G , Bindschedler Saskia , Chain Patrick S G 
Published: January 2021

ABSTRACTBacteria–fungi interactions (BFIs) are essential in ecosystem functioning. These interactions are modulated not only by local nutritional conditions but also by the physicochemical constraints and 3D structure of the environmental niche. In soils, the unsaturated and complex nature of the substrate restricts the dispersal and activity of bacteria. Under unsaturated conditions, some bacteria engage with filamentous fungi in an interaction (fungal highways) in which they use fungal hyphae to disperse. Based on a previous experimental device to enrich pairs of organisms engaging in this interaction in soils, we present here the design and validation of a modified version of this sampling system constructed using additive printing. The 3D printed devices were tested using a novel application in which a target fungus, the common coprophilous fungus Coprinopsis cinerea, was used as bait to recruit and identify bacterial partners using its mycelium for dispersal. Bacteria of the genera Pseudomonas, Sphingobacterium and Stenotrophomonas were highly enriched in association with C. cinerea. Developing and producing these new easy-to-use tools to investigate how bacteria overcome dispersal limitations in cooperation with fungi is important to unravel the mechanisms by which BFIs affect processes at an ecosystem scale in soils and other unsaturated environments.
Comparative study of sodium bicarbonate- and magnesium hydroxide-based gastric antacids for the effectiveness of Salmonella delivered Brucella antigens against wild type challenge in BALB/c mice
Authors: Hewawaduge Chamith , Senevirathne Amal , Yang Myeon-Sik , Jeong Tae-Won , Kim Bumseok , Lee John Hwa 
Published: January 2021

ABSTRACT
We compared the effects of two antacid formulations based on sodium bicarbonate and magnesium hydroxide on a Salmonella-delivered oral Brucella live attenuated vaccine. We conducted a series of in vitro and in vivo experiments to investigate the pH buffering capacity, buffering longevity and the effects of these formulations on the survival of Salmonella under neutralized pH conditions and its impact on immune responses. Magnesium hydroxide had a greater, stable and prolonged buffering capacity than sodium bicarbonate and was safer when administered orally. Oral administration of sodium bicarbonate resulted in discomfort as reflected by mouse behavior and mild muscle tremors, whereas mice treated with magnesium hydroxide and PBS were completely normal. Gastric survival studies using BALB/c mice revealed that a higher number of Salmonella reached the intestine when the magnesium hydroxide-based antacid buffer was administrated. Co-administration with attenuated Salmonella secreting Brucella antigens, SodC and Omp19 along with individual antacid formulations, significantly enhanced the antigen-specific protective immune responses against virulent Brucella challenge. Together, our results indicated that the pre vaccinated oral administration of bicarbonate-citric acid or magnesium hydroxide-based neutralizing buffers significantly counteract stomach acidity by maintaining the viability of an oral enteric vaccine formulation.
Ethanol Disrupts Hormone-Induced Calcium Signaling in Liver
Authors: Gaspers Lawrence D , Thomas Andrew P , Hoek Jan B , Bartlett Paula J 
Published: January 2021

Abstract
Receptor-coupled phospholipase C (PLC) is an important target for the actions of ethanol. In the ex vivo perfused rat liver, concentrations of ethanol &gt;100 mM were required to induce a rise in cytosolic calcium (Ca2+) suggesting that these responses may only occur after binge ethanol consumption. Conversely, pharmacologically achievable concentrations of ethanol (≤30 mM) decreased the frequency and magnitude of hormone-stimulated cytosolic and nuclear Ca2+ oscillations and the parallel translocation of protein kinase C-β to the membrane. Ethanol also inhibited gap junction communication resulting in the loss of coordinated and spatially organized intercellular Ca2+ waves in hepatic lobules. Increasing the hormone concentration overcame the effects of ethanol on the frequency of Ca2+ oscillations and amplitude of the individual Ca2+ transients; however, the Ca2+ responses in the intact liver remained disorganized at the intercellular level, suggesting that gap junctions were still inhibited. Pretreating hepatocytes with an alcohol dehydrogenase inhibitor suppressed the effects of ethanol on hormone-induced Ca2+ increases, whereas inhibiting aldehyde dehydrogenase potentiated the inhibitory actions of ethanol, suggesting that acetaldehyde is the underlying mediator. Acute ethanol intoxication inhibited the rate of rise and the magnitude of hormone-stimulated production of inositol 1,4,5-trisphosphate (IP3), but had no effect on the size of Ca2+ spikes induced by photolysis of caged IP3. These findings suggest that ethanol inhibits PLC activity, but does not affect IP3 receptor function. We propose that by suppressing hormone-stimulated PLC activity, ethanol interferes with the dynamic modulation of [IP3] that is required to generate large, amplitude Ca2+ oscillations.
MutSα mismatch repair protein stability is governed by subunit interaction, acetylation, and ubiquitination
Authors: Arlow Tim , Kim Junwon , Haye-Bertolozzi Joanna E. , Martínez Cristina Balbás , Fay Caitlin , Zorensky Emma , Rose Mark D. , Gammie Alison E. 
Published: January 2021

Abstract
In eukaryotes, DNA mismatch recognition is accomplished by the highly conserved MutSα (Msh2/Msh6) and MutSβ (Msh2/Msh3) complexes. Previously, in the yeast Saccharomyces cerevisiae, we determined that deleting MSH6 caused wild-type Msh2 levels to drop by ∼50%. In this work, we determined that Msh6 steady-state levels are coupled to increasing or decreasing levels of Msh2. Although Msh6 and Msh2 are reciprocally regulated, Msh3 and Msh2 are not. Msh2 missense variants that are able to interact with Msh6 were destabilized when Msh6 was deleted; in contrast, variants that fail to dimerize were not further destabilized in cells lacking Msh6. In the absence of Msh6, Msh2 is turned over at a faster rate and degradation is mediated by the ubiquitin-proteasome pathway. Mutagenesis of certain conserved lysines near the dimer interface restored the levels of Msh2 in the absence of Msh6, further supporting a dimer stabilization mechanism. We identified two alternative forms of regulation both with the potential to act via lysine residues, including acetylation by Gcn5 and ubiquitination by the Not4 ligase. In the absence of Gcn5, Msh2 levels were significantly decreased; in contrast, deleting Not4 stabilized Msh2 and Msh2 missense variants with partial function. The stabilizing effect on Msh2 by either the presence of Msh6 or the absence of Not4 are dependent on Gcn5. Taken together, the results suggest that the wild-type MutSα mismatch repair protein stability is governed by subunit interaction, acetylation, and ubiquitination.
A possible case of negative segregation distortion in the SD system of Drosophila melanogaster.
Authors: Hiraizumi Y 
Published: January 2021

Abstract
Models proposed to explain segregation distortion in Drosophila melanogaster are based partly upon the observation that, in the Sd heterozygous Rspi/Rsps male, the chromosome carrying the sensitive Rsps allele is distorted, but the chromosome carrying the insensitive Rspi allele is not. The results of the present study suggest that this may not always be the case. Under a certain genotypic condition, the chromosome carrying the Rsps allele can be transmitted to the progeny in frequencies of more than 0.5 (about 0.6), or correspondingly, the chromosome carrying the Rspi allele may be distorted with respect to the one with the Rsps allele. Thus, the relative sensitivity and insensitivity of the two Rsp alleles in a male are not absolute, but relative; and they may be reversed depending upon the residual genotype. If this is true, a major modification of the current models or a proposal of an entirely new model may become necessary to explain the mechanism of segregation distortion satisfactorily.
A generalized approach for estimating effective population size from temporal changes in allele frequency.
Authors: Waples R S 
Published: January 2021

Abstract
The temporal method for estimating effective population size (Ne) from the standardized variance in allele frequency change (F) is presented in a generalized form. Whereas previous treatments of this method have adopted rather limiting assumptions, the present analysis shows that the temporal method is generally applicable to a wide variety of organisms. Use of a revised model of gene sampling permits a more generalized interpretation of Ne than that used by some other authors studying this method. It is shown that two sampling plans (individuals for genetic analysis taken before or after reproduction) whose differences have been stressed by previous authors can be treated in a uniform way. Computer simulations using a wide variety of initial conditions show that different formulas for computing F have much less effect on Ne than do sample size (S), number of generations between samples (t), or the number of loci studied (L). Simulation results also indicate that (1) bias of F is small unless alleles with very low frequency are used; (2) precision is typically increased by about the same amount with a doubling of S, t, or L; (3) confidence intervals for Ne computed using a chi 2 approximation are accurate and unbiased under most conditions; (4) the temporal method is best suited for use with organisms having high juvenile mortality and, perhaps, a limited effective population size.
DNA repair and the evolution of transformation in Bacillus subtilis. II. Role of inducible repair.
Authors: Wojciechowski M F , Hoelzer M A , Michod R E 
Published: January 2021

Abstract
In Bacillus subtilis, DNA repair and recombination are intimately associated with competence, the physiological state in which the bacterium can bind, take up and recombine exogenous DNA. Previously, we have shown that the homologous DNA transformation rate (ratio of transformants to total cells) increases with increasing UV dosage if cells are transformed after exposure to UV radiation (UV-DNA), whereas the transformation rate decreases if cells are transformed before exposure to UV (DNA-UV). In this report, by using different DNA repair-deficient mutants, we show that the greater increase in transformation rate in UV-DNA experiments than in DNA-UV experiments does not depend upon excision repair or inducible SOS-like repair, although certain quantitative aspects of the response do depend upon these repair systems. We also show that there is no increase in the transformation rate in a UV-DNA experiment when repair and recombination proficient cells are transformed with nonhomologous plasmid DNA, although the results in a DNA-UV experiment are essentially unchanged by using plasmid DNA. We have used din operon fusions as a sensitive means of assaying for the expression of genes under the control of the SOS-like regulon in both competent and noncompetent cell subpopulations as a consequence of competence development and our subsequent experimental treatments. Results indicate that the SOS-like system is induced in both competent and noncompetent subpopulations in our treatments and so should not be a major factor in the differential response in transformation rate observed in UV-DNA and DNA-UV treatments. These results provide further support to the hypothesis that the evolutionary function of competence is to bring DNA into the cell for use as template in the repair of DNA damage.
Pheromones and pheromone receptors are the primary determinants of mating specificity in the yeast Saccharomyces cerevisiae.
Authors: Bender A , Sprague G F 
Published: January 2021

Abstract
Saccharomyces cerevisiae has two haploid cell types, a and alpha, each of which produces a unique set of proteins that participate in the mating process. We sought to determine the minimum set of proteins that must be expressed to allow mating and to confer specificity. We show that the capacity to synthesize alpha-factor pheromone and a-factor receptor is sufficient to allow mating by mat alpha 1 mutants, mutants that normally do not express any alpha- or a-specific products. Likewise, the capacity to synthesize a-factor receptor and alpha-factor pheromone is sufficient to allow a ste2 ste6 mutants, which do not produce the normal a cell pheromone and receptor, to mate with wild-type a cells. Thus, the a-factor receptor and alpha-factor pheromone constitute the minimum set of alpha-specific proteins that must be produced to allow mating as an alpha cell. Further evidence that the pheromones and pheromone receptors are important determinants of mating specificity comes from studies with mat alpha 2 mutants, cells that simultaneously express both pheromones and both receptors. We created a series of strains that express different combinations of pheromones and receptors in a mat alpha 2 background. These constructions reveal that mat alpha 2 mutants can be made to mate as either a cells or as alpha cells by causing them to express only the pheromone and receptor set appropriate for a particular cell type. Moreover, these studies show that the inability of mat alpha 2 mutants to respond to either pheromone is a consequence of two phenomena: adaptation to an autocrine response to the pheromones they secrete and interference with response to alpha factor by the a-factor receptor.