bluuebunny/crossref_metadata_2025_split huggingface dataset:
oxLDL antibody inhibits MCP‐1 release in monocytes/macrophages by regulating Ca2+/K+ channel flow
Authors: Su Jinyu , Zhou Hui , Liu Xianyan , Nilsson Jan , Fredrikson Gunilla Nordin , Zhao Ming 
Published: December 2016

AbstractoxLDL peptide vaccine and its antibody adoptive transferring have shown a significantly preventive or therapeutic effect in atherosclerotic animal model. The molecular mechanism behind this is obscure. Here, we report that oxLDL induces MCP‐1 release in monocytes/macrophages through their TLR‐4 (Toll‐like receptor 4) and ERK MAPK pathway and is calcium/potassium channel‐dependent. Using blocking antibodies against CD36, TLR‐4, SR‐AI and LOX‐1, only TLR‐4 antibody was found to have an inhibitory effect and ERK MAPK‐specific inhibitor (PD98059) was found to have a dramatic inhibitory effect compared to inhibitors of other MAPK group members (p38 and JNK MAPKs) on oxLDL‐induced MCP‐1 release. The release of cytokines and chemokines needs influx of extracellular calcium and imbalance of efflux of potassium. Nifedipine, a voltage‐dependent calcium channel (VDCC) inhibitor, and glyburide, an ATP‐regulated potassium channel (K+ATP) inhibitor, inhibit oxLDL‐induced MCP‐1 release. Potassium efflux and influx counterbalance maintains the negative potential of macrophages to open calcium channels, and our results suggest that oxLDL actually induces the closing of potassium influx channel – inward rectifier channel (Kir) and ensuing the opening of calcium channel. ERK MAPK inhibitor PD98059 inhibits oxLDL‐induced Ca2+/Kir channel alterations. The interfering of oxLDL‐induced MCP‐1 release by its monoclonal antibody is through its FcγRIIB (CD32). Using blocking antibodies against FcγRI (CD64), FcγRIIB (CD32) and FcγRIII (CD16), only CD32 blocking antibody was found to reverse the inhibitory effect of oxLDL antibody on oxLDL‐induced MCP‐1 release. Interestingly, oxLDL antibody specifically inhibits oxLDL‐induced ERK MAPK activation and ensuing Ca2+/Kir channel alterations, and MCP‐1 release. Thus, we found a molecular mechanism of oxLDL antibody on inhibition of oxLDL‐induced ERK MAPK pathway and consequent MCP‐1 release.
Acquired TET2 mutation in one patient with familial platelet disorder with predisposition to AML led to the development of pre‐leukaemic clone resulting in T2‐ALL and AML‐M0
Authors: Manchev Vladimir T. , Bouzid Hind , Antony‐Debré Iléana , Leite Betty , Meurice Guillaume , Droin Nathalie , Prebet Thomas , Costello Régis T. , Vainchenker William , Plo Isabelle , Diop M'boyba , Macintyre Elizabeth , Asnafi Vahid , Favier Rémi , Baccini Véronique , Raslova Hana 
Published: December 2016

AbstractFamilial platelet disorder with predisposition to acute myeloid leukaemia (FPD/AML) is characterized by germline RUNX1 mutations, thrombocytopaenia, platelet dysfunction and a risk of developing acute myeloid and in rare cases lymphoid T leukaemia. Here, we focus on a case of a man with a familial history of RUNX1R174Q mutation who developed at the age of 42 years a T2‐ALL and, 2 years after remission, an AML‐M0. Both AML‐M0 and T2‐ALL blast populations demonstrated a loss of 1p36.32‐23 and 17q11.2 regions as well as other small deletions, clonal rearrangements of both TCRγ and TCRδ and a presence of 18 variants at a frequency of more than 40%. Additional variants were identified only in T2‐ALL or in AML‐M0 evoking the existence of a common original clone, which gave rise to subclonal populations. Next generation sequencing (NGS) performed on peripheral blood‐derived CD34+ cells 5 years prior to T2‐ALL development revealed only the missense TET2P1962T mutation at a frequency of 1%, which increases to more than 40% in fully transformed leukaemic T2‐ALL and AML‐M0 clones. This result suggests that TET2P1962T mutation in association with germline RUNX1R174Q mutation leads to amplification of a haematopoietic clone susceptible to acquire other transforming alterations.
Autophagy: an adaptive physiological countermeasure to cellular senescence and ischaemia/reperfusion‐associated cardiac arrhythmias
Authors: Lekli Istvan , Haines David Donald , Balla Gyorgy , Tosaki Arpad 
Published: December 2016

AbstractOxidative stress placed on tissues that involved in pathogenesis of a disease activates compensatory metabolic changes, such as DNA damage repair that in turn causes intracellular accumulation of detritus and ‘proteotoxic stress’, leading to emergence of ‘senescent’ cellular phenotypes, which express high levels of inflammatory mediators, resulting in degradation of tissue function. Proteotoxic stress resulting from hyperactive inflammation following reperfusion of ischaemic tissue causes accumulation of proteinaceous debris in cells of the heart in ways that cause potentially fatal arrhythmias, in particular ventricular fibrillation (VF). An adaptive response to VF is occurrence of autophagy, an intracellular bulk degradation of damaged macromolecules and organelles that may restore cellular and tissue homoeostasis, improving chances for recovery. Nevertheless, depending on the type and intensity of stressors and inflammatory responses, autophagy may become pathological, resulting in excessive cell death. The present review examines the multilayered defences that cells have evolved to reduce proteotoxic stress by degradation of potentially toxic material beginning with endoplasmic reticulum‐associated degradation, and the unfolded protein response, which are mechanisms for removal from the endoplasmic reticulum of misfolded proteins, and then progressing through the stages of autophagy, including descriptions of autophagosomes and related vesicular structures which process material for degradation and autophagy‐associated proteins including Beclin‐1 and regulatory complexes. The physiological roles of each mode of proteotoxic defence will be examined along with consideration of how emerging understanding of autophagy, along with a newly discovered regulatory cell type called telocytes, may be used to augment existing strategies for the prevention and management of cardiovascular disease.
Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe)
Authors: Lee JungIn , Lee Wonhwa , Kim Mi‐Ae , Hwang Jae Sam , Na MinKyun , Bae Jong‐Sup 
Published: December 2016

AbstractProtaetia brevitarsis seulensis (Kolbe) has been temporarily registered as a food material by the Ministry of Food and Drug Safety of Korea (MFDS). The current study aimed to discover small antithrombotic molecules from this edible insect. Five indole alkaloids, 5‐hydroxyindolin‐2‐one (1), (1R,3S)‐1‐methyl‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylic acid (2), (1S,3S)‐1‐methyl‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylic acid (3), (3S)‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylic acid (4) and L‐tryptophan (5), were isolated from the insect. Among them, compounds 1 and 2 prolonged aPTT and PT and impaired thrombin and FXa generation on HUVEC surface. Moreover, these compounds inhibited platelet aggregation. Antithrombotic effects of compounds 1 and 2 were further confirmed in pre‐clinical models of pulmonary embolism and arterial thrombosis. Collectively, these results demonstrated that compounds 1 and 2 could be effective antithrombotic agents and serve as new scaffolds for the development of antithrombotic drug.
Self‐administered medications in the postpartum wards: A study on satisfaction and perceptions
Authors: Schérer Hugo , Bernier Emmy , Rivard Julie , Yu Lavina , Duchesne‐Côté Guillaume , Lebel Denis , Bussières Jean‐François , Ferreira Ema 
Published: December 2016

AbstractObjectiveThe objective of this study was to describe women's satisfaction and perceptions on the postpartum self‐administered medication (SAM) program at our institution and on pain relief. Also, we aimed at describing maternal and breastfed infants' adverse events with the use of the postpartum SAM program.MethodThis prospective 1‐group mixed methods survey conducted in a mother‐and‐child tertiary center included women enrolled in the postpartum SAM program who had a live newborn, understood French or English, and were at least 18 years old. Newborns included cohabited with their mother during their hospitalization and had received breast milk at least once. Data were collected through direct interviews using a questionnaire and through medical charts.ResultsWe included 314 mothers and 263 breastfed newborns in the study. Ninety‐seven percent of all users appreciated the SAM. The self‐reported median overall improvement of pain was 80% (interquartile range, 70%‐90%). However, 18% of users who delivered vaginally and 32% who delivered through caesarean would have preferred traditional drug dispensing by the nurse (P = .009). Drugs used in the SAM program were generally well tolerated. There were no worrisome adverse drug events reported in newborns' medical charts.ConclusionResults show a 97% rate of satisfaction of the SAM program and a high self‐reported pain improvement in a cohort of 314 women using our SAM program. The results suggest that the SAM program should remain a standard practice in our institution. Some recommendations will be drawn to better tailor the SAM program to the needs expressed by the users.
Biofilms for Monitoring Presence of Microsporidia in Environmental Water
Authors: Moss Joseph A. , Snyder Richard A. 
Published: December 2016

AbstractThe development of molecular methodologies for targeting pathogens such as the Microsporidia has greatly improved our monitoring capabilities and initiatives. This study analyzed samples collected from five locations in Pensacola, Florida, USA for the presence of Microsporidian pathogens. To circumvent various impediments associated with water collection and filtration, we utilized biofilms as sentinels for detection of Microsporidia. We implemented membrane‐dissolution and sample purification in a single confined step followed by real‐time PCR to confirm pathogen presence. The results of this study demonstrate that microsporidia are present in environmental water sites in the Florida panhandle and that biofilms may serve as another alternative mode to circumvent filtration methods for their detection.
Drug Therapy for Gender Transitions and Health Screenings in Transgender Older Adults
Authors: Mahan Rebecca J. , Bailey Trista Askins , Bibb Teryn J. , Fenney Megan , Williams Tara 
Published: December 2016

AbstractTransgender medicine is a relatively new field in health care, with only a small amount of evidence‐based literature available for reference. This is especially true for the older adult population, for whom most information must be extrapolated from younger adults. Be it a newly transitioned older adult or a transgendered individual who has been undergoing hormonal therapy for many years, it is important that healthcare professionals be aware of the significant effects that transgender pharmacotherapy can have on older adults. Healthcare providers must also recommend appropriate preventative screenings to transgendered persons.
WRKY transcription factors in plant responses to stresses
Authors: Jiang Jingjing , Ma Shenghui , Ye Nenghui , Jiang Ming , Cao Jiashu , Zhang Jianhua 
Published: December 2016

AbstractThe WRKY gene family is among the largest families of transcription factors (TFs) in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress. Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mechanisms. However, very little summarization has been done to review their research progress. Not just important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senescence, development, and secondary metabolites synthesis. WRKY proteins can bind to W‐box (TGACC (A/T)) in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses.
Two‐Year Follow‐up Outcomes in Emotionally Focused Couple Therapy: An Investigation of Relationship Satisfaction and Attachment Trajectories
Authors: Wiebe Stephanie A. , Johnson Susan M. , Lafontaine Marie‐France , Burgess Moser Melissa , Dalgleish Tracy L. , Tasca Giorgio A. 
Published: December 2016

Emotionally Focused Couple Therapy (EFT; The practice of emotionally focused couple therapy: Creating connection. New York, NY: Brunner‐Routledge) is an evidence‐based couple therapy that aims to create lasting change for couples (Clinical Psychology: Science and Practice, 6(1), 67–79). Although studies have demonstrated strong results in follow‐up (Journal of Marital and Family Therapy, 28(4), 391–398), less is known about relationship functioning across time after therapy has ended. We modelled change in relationship satisfaction and attachment from pre‐therapy through 24 months follow‐up in 32 couples. HLM results confirmed a significant growth pattern demonstrating increases in relationship satisfaction and secure base behaviour and decreases in relationship specific attachment anxiety over the course of therapy and across follow‐up at a decelerated rate. These findings support the theoretical assumption that EFT helps couples engaged in therapy create lasting relationship satisfaction and attachment change.
Bi‐objective Modeling Approach for Repairing Multiple Feature Infrastructure Systems
Authors: Sousa Nuno , Alçada‐Almeida Luís , Coutinho‐Rodrigues João 
Published: December 2016

AbstractA bi‐objective decision aid model for planning long‐term maintenance of infrastructure systems is presented, oriented to interventions on their constituent elements, with two upgrade levels possible for each element (partial/full repairs). The model aims at maximizing benefits and minimizing costs, and its novelty is taking into consideration, and combining, the system/element structure, volume discounts, and socioeconomic factors. The model is tested with field data from 229 sidewalks (systems) and compared to two simpler repair policies, of allowing only partial or full repairs. Results show that the efficiency gains are greater in the lower mid‐range budget region. The proposed modeling approach is an innovative tool to optimize cost/benefits for the various repair options and analyze the respective trade‐offs.
Insulation and wiring specificity of BceR‐like response regulators and their target promoters in Bacillus subtilis
Authors: Fang Chong , Nagy‐Staroń Anna , Grafe Martin , Heermann Ralf , Jung Kirsten , Gebhard Susanne , Mascher Thorsten 
Published: December 2016

SummaryBceRS and PsdRS are paralogous two‐component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up‐regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross‐regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high‐affinity, low‐specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low‐affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.
Euglossine bees mediate only limited long‐distance gene flow in a tropical vine
Authors: Opedal Øystein H. , Falahati‐Anbaran Mohsen , Albertsen Elena , Armbruster W. Scott , Pérez‐Barrales Rocío , Stenøien Hans K. , Pélabon Christophe 
Published: December 2016

SummaryEuglossine bees (Apidae: Euglossini) have long been hypothesized to act as long‐distance pollinators of many low‐density tropical plants. We tested this hypothesis by the analysis of gene flow and genetic structure within and among populations of the euglossine bee‐pollinated vineDalechampia scandens.Using microsatellite markers, we assessed historical gene flow by the quantification of regional‐scale genetic structure and isolation by distance among 18 populations, and contemporary gene flow by the estimation of recent migration rates among populations. To assess bee‐mediated pollen dispersal on a smaller scale, we conducted paternity analyses within a focal population, and quantified within‐population spatial genetic structure in four populations.Gene flow was limited to certain nearby populations within continuous forest blocks, whereas drift appeared to dominate on larger scales. Limited long‐distance gene flow was supported by within‐population patterns; gene flow was biased towards nearby plants, and significant small‐scale spatial genetic structure was detected within populations.These findings suggest that, although female euglossine bees might be effective at moving pollen within populations, and perhaps within forest blocks, their contribution to gene flow on the regional scale seems too limited to counteract genetic drift in patchily distributed tropical plants. Among‐population gene flow might have been reduced following habitat fragmentation.
Regulation of gene expression by manipulating transcriptional repressor activity using a novel CoSRI technology
Authors: Xu Yue , Li Song Feng , Parish Roger W. 
Published: December 2016

SummaryTargeted gene manipulation is a central strategy for studying gene function and identifying related biological processes. However, a methodology for manipulating the regulatory motifs of transcription factors is lacking as these factors commonly possess multiple motifs (e.g. repression and activation motifs) which collaborate with each other to regulate multiple biological processes. We describe a novel approach designated conserved sequence‐guided repressor inhibition (CoSRI) that can specifically reduce or abolish the repressive activities of transcription factors in vivo. The technology was evaluated using the chimeric MYB80‐EAR transcription factor and subsequently the endogenous WUS transcription factor. The technology was employed to develop a reversible male sterility system applicable to hybrid seed production. In order to determine the capacity of the technology to regulate the activity of endogenous transcription factors, the WUS repressor was chosen. The WUS repression motif could be inhibited in vivo and the transformed plants exhibited the wus‐1 phenotype. Consequently, the technology can be used to manipulate the activities of transcriptional repressor motifs regulating beneficial traits in crop plants and other eukaryotic organisms.
Nintedanib in Japanese patients with idiopathic pulmonary fibrosis: A subgroup analysis of the INPULSIS® randomized trials
Authors: Azuma Arata , Taniguchi Hiroyuki , Inoue Yoshikazu , Kondoh Yasuhiro , Ogura Takashi , Homma Sakae , Fujimoto Tsuyoshi , Sakamoto Wataru , Sugiyama Yukihiko , Nukiwa Toshihiro 
Published: December 2016

ABSTRACTBackground and objectiveIdiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo in patients with IPF in two replicate trials (INPULSIS®). We examined the efficacy and safety of nintedanib in Japanese patients.MethodsWe conducted pre‐specified subgroup analyses of the annual rate of decline in FVC, time to first acute exacerbation (AE), change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and safety using pooled data from the INPULSIS® trials for Japanese patients.ResultsIn the overall population, 76 of 638 and 50 of 423 patients in the nintedanib and placebo groups, respectively, were Japanese. Results in Japanese patients were consistent with those in the overall population. In Japanese patients, the adjusted annual rate of decline in FVC was −135.9 mL/year in the nintedanib group and −267.7 mL/year in the placebo group (difference (95% CI): 131.9 (50.7, 213.1) mL/year); the hazard ratio for the time to first AE was 0.25 (0.06, 1.02); and the adjusted mean change from baseline in SGRQ total score at week 52 was 5.81 in the nintedanib group and 9.68 in the placebo group (difference: −3.87 (−8.51, 0.76)). Diarrhoea and liver‐related adverse events were the most common events in the nintedanib group, but were reversible following dose reduction, drug interruption or symptomatic therapy.ConclusionThe present results indicate that the efficacy and safety of nintedanib in Japanese patients are comparable with those in the overall population.
Differential Fractionation of Rare Earth Elements in Oxidized and Reduced Granitic Rocks: Implication for Heavy Rare Earth Enriched Ion Adsorption Mineralization
Authors: Watanabe Yasushi , Kon Yoshiaki , Echigo Takuya , Kamei Atsushi 
Published: December 2016

AbstractIon adsorption rare earth element (REE) deposits in southern China are the exclusive source of heavy REEs (HREEs) in the world, and this HREE‐enriched character of the deposits is inherited from the REE compositions of the underlying granitic rocks. Such HREE‐enriched rocks form from heavy fractionation of reduced granitic magmas. We explore why reduced granitic magmas are enriched in HREEs during the fractionation, based on the REE geochemistry of granitic rocks and abundance of REEs in their constituent minerals in the southwestern Japan arc of Cretaceous to Paleogene age.The compilation of the whole rock geochemistry and REE compositions of the granitic rocks of the Sanin (oxidized), Sanyo (reduced) and Ryoke (reduced) belts in the southwestern Japan arc indicates that: (i) light REEs (LREEs) decease with fractionation of the granitoids in the Sanin belt but this trend is not clear in the granitoids in the Sanyo belt and LREEs rather increase in the Ryoke granitoids; (ii) Eu decreases with fractionation in all the belts; and (iii) HREEs slightly, but steadily decrease in the Sanin belt but enrich significantly in the Sanyo and Ryoke belts with fractionation.Analytical results of REE concentrations by scanning electron microscope with energy dispersive X‐ray spectroscope and laser ablation‐inductively coupled plasma mass spectrometer in the constituent minerals in a granodiorite sample from the Sanin belt show a moderate concentration of REEs in hornblende (577 ppm) in addition to high concentrations in allanite (~20 %), britholite (~30 %), primary titanite (8922 ppm), apatite (4062 ppm), and zircon (1693 ppm). Because primary titanite and allanite are commonly present in the oxidized granitoids but not in the reduced ones, the REE depletion in the fractionated, oxidized granites is attributed to the crystallization of these minerals. In contrast, scarcity of these minerals in the reduced granitoids enriches REEs, in particular HREEs in the fractionated magmas, which finally precipitate REEs in the granites and pegmatites. Both positive, but different correlation ratios between the Nb and Dy concentrations in the granitoids of the Sanin and Sanyo‐Ryoke belts suggest that columbite–pyrochlore‐group and fergusonite‐group minerals are the major HREE host in the oxidized and reduced granites, respectively.