bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation in the constitutive defensive metabolome and its inducibility are geographically structured and largely determined by demographic processes in maritime pine
Authors: López‐Goldar Xosé , Villari Caterina , Bonello Pierluigi , Borg‐Karlson Anna Karin , Grivet Delphine , Sampedro Luis , Zas Rafael 
Published: March 2019

Abstract

Interspecific phenotypic variation in plant secondary metabolites (PSM) is often explained by biotic and abiotic factors. However, patterns of variation within species do not clearly fit the theoretical predictions. Exploring how genetics, environment and demographic processes shape such variation among and within populations is crucial for understanding evolution of PSM, particularly in long‐lived plants such as forest trees.

Here, we quantified genetic variation in PSM among and within populations, and explored drivers of local adaptation by studying the role of climate as a source of population differentiation in PSM of maritime pine. Constitutive profile and concentrations of 63 PSM and their herbivory‐associated inducibility were determined in the bark of 130 clonally replicated genotypes with known familial structure from 10 populations covering the distribution range of the species. We compared neutral and quantitative population genetic differentiation of PSM (FST and QST). Also, we accounted for population genetic structure and kinship among individuals when exploring climate–trait relationships.

We found large population differentiation and additive genetic variation in constitutive PSM. Many PSM were inducible, although very low genetic variation was observed with respect to their inducibility. QST–FST comparisons suggest that differentiation of most diterpenes, monoterpenes, and phenolics can be explained by neutral demographic processes. Spatially heterogeneous selection across populations leading to local adaptation was only found for total constitutive sesquiterpenes and a few individual PSM. After accounting for population genetic structure, only the constitutive concentration of two sesquiterpenes showing signs of diversifying selection was predicted by climate, with decreasing concentrations along a growth‐prone climatic gradient.

Synthesis. Evolutionary patterns of plant secondary metabolites depended on their chemical nature, with neutral differentiation governing most plant secondary metabolites. Evidence of local adaptation was only found for total constitutive sesquiterpenes and a few individual plant secondary metabolites. The low genetic variation in the inducibility of plant secondary metabolites suggests a conserved model of defensive induction in this species. Since population differentiation linked to past demographic history could lead to false positives of adaptive differentiation signals, accounting for the genetic relatedness among populations is required to infer the environmental determinants of intraspecific genetic variation in putatively adaptive traits such as plant defences.
The Network of Law Reviews: Citation Cartels, Scientific Communities, and Journal Rankings
Authors: Perez Oren , Bar‐Ilan Judit , Cohen Reuven , Schreiber Nir 
Published: March 2019

AbstractResearch evaluation is increasingly influenced by quantitative data. We focus on the influential Web of Science Journal Citation Reports (JCR) ranking of law journals and critically assess its methodology. In particular, we consider the existence and impact of a tacit citation cartel between US law reviews. A study of 45 US student‐edited (SE) and 45 peer‐reviewed (PR) journals included in the category of Law in the JCR revealed that PR and SE journals are more inclined to cite members of their own class and that this phenomenon is more pronounced in SE generalist journals, reflecting tacit cartelistic behavior generated by deeply entrenched institutional practices. Because US SE journals produce more citations than PR journals, the fact that their citations are directed almost exclusively to SE journals elevates their scores and distorts the journals' ranking and can consequently undermine the flow and creation of ideas. We discuss policy measures that can counter the adverse effects of this situation.
Lessons learnt from anonymized review of cases of peripartum hysterectomy by international experts: A qualitative pilot study
Authors: Jónasdóttir Eva , Aabakke Anna J. M. , Colmorn Lotte B. , Jakobsson Maija , Äyräs Outi , Baghestan Elham , Svanvik Teresia , van den Akker Thomas , Bloemenkamp Kitty , van Roosmalen Jos , Krebs Lone , Knight Marian , Langhoff‐Roos Jens ,   on behalf of the Nordic Obstetric Surveillance System and the International Network of Obstetric Survey Systems
Published: March 2019

AbstractSevere obstetric complications are not extensively studied and individual cases are used too little and inappropriately in quality improvement activities, due to limited numbers and prioritization of quantitative research. Nordic and European experts performed a qualitative pilot study using anonymized cases of peripartum hysterectomy. It was feasible to anonymize narratives and we learned lessons in the form of themes for improved clinical care and future research. Therefore, we plan a Nordic anonymized review of the care of women who have undergone peripartum hysterectomy based on narratives. The qualitative outcomes of clinically relevant themes for quality improvement and research will add value to the quantitative analyses from the Nordic medical birth registries. In the longer term, we believe that qualitative audits should be an essential part of the process of continuing improvement in maternity care.
Effects of woody species encroachment and fire on vegetation and the soil seed bank in dry grasslands of Transylvania
Authors: Görzen Eugen , Borisova Karina , Fenesi Annamária , Ruprecht Eszter , Donath Tobias W. 
Published: March 2019

AbstractQuestions(a) In which ways do woody species encroachment and fire affect vegetation and seed bank composition, structure and diversity in Transylvanian dry grassland; (b) do native and non‐native woody species differ with respect to their impact on grassland community composition and structure; (c) is burning useful to control woody species encroachment; and (d) can soil seed banks contribute to the restoration of grasslands in Transylvania?LocationTransylvania, Romania.MethodsWe collected data on vegetation and seed bank composition in 4 m2plots in 16 shrub‐encroached grasslands and adjacent open grassland. Data were analyzed with regard to the impact of woody species encroachment (native vs non‐native) and fire on grassland vegetation and the seed bank usingNMDSandLMEmodels combined withANOVAand Tukey contrast tests.ResultsEncroachment was accompanied by a decrease in plant species diversity and altered microclimatic conditions. There was a lack of sufficient evidence for a difference in effect size between native and non‐native woody species on tested vegetation or seed bank parameters. While the effects of fire on vegetation were weak compared to encroachment, burning failed to reduce the cover of woody species sustainably. Grassland vegetation and the seed bank differed significantly in species composition and diversity, indicating a limited potential for restoration from the seed bank alone.ConclusionsTo halt secondary succession in Transylvanian grassland sustainably, we suggest the establishment of a post‐fire management regime including the cutting of woody species and/or re‐introduction of grazing and mowing. Grassland restoration from the seed bank may be supported by the introduction of species from surrounding intact grassland.
Why do women fast during breast cancer chemotherapy? A qualitative study of the patient experience
Authors: Mas Sébastien , Le Bonniec Alice , Cousson‐Gélie Florence 
Published: March 2019

BackgroundWhy do patients practice fasting? The effects of fasting before treatment with chemotherapy for cancer in humans are currently unknown. However, there is an apparent enthusiasm for fasting among cancer patients. This qualitative study provides data on the motivations to fast and the experience of fasting among a population of women with breast cancer.MethodSixteen semi‐structured interviews were conducted, and two researchers independently performed a thematic analysis. To ensure the internal validity of the study, patients had the possibility to rate their agreement with the study results through a satisfaction questionnaire.ResultsSix main themes were identified in this study: main reasons to fast, alternative authorities to the oncologist, adapting the fast to social and lifestyle constraints, fasting effects felt during chemotherapy, barriers and facilitators of fasting during chemotherapy, and seeking for a more integrative medicine. Patients’ primary motivation to fast was to lower the negative side effects of chemotherapy. Fasting was also reported as a coping strategy to give them a greater sense of control over their treatment and to reduce their anxiety.Clinical implicationsResults from the study suggest that, if discouraged from fasting, patients may turn to complementary health care practitioners for support. Medical professionals may thus not know of patients’ fasting practice. Health psychologists could play a key role fostering the dialogue between different health professionals and the patient. They could also help to meet patients’ needs during cancer treatment to reduce treatment anxiety.
Statement of contribution

What is already known on this subject?

Fasting diet in cancer treatment has become an important topic since Raffaghello et al. published their study on mice in 2008. While the (positive) effects of fasting in humans remain to be proven, there has been a significant enthusiasm for this practice among patients in the last few years. However, patients’ motivations to fast remain unclear to the scientific community and clinicians.

What does this study add?

This study is the first to investigate patients’ motivations to fast and patients’ experience of fasting in a cancer population.

Patients’ primary motivation to fast was to lower the side effects of chemotherapy.

Fasting acts as an active coping strategy that helps to reduce anxiety.

Unsupported patients may turn to complementary health care practitioners.
A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome
Authors: Martini Alberto , Wang Joanna , Brown Nicholas M. , Cumarasamy Shivaram , Sfakianos John P. , Rastinehad Ardeshir R. , Haines Kenneth G. , Wiklund Nils Peter , Nair Sujit S. , Tewari Ashutosh K. 
Published: March 2019

ObjectiveTo investigate the genomic features of tertiary pattern 5 (TP5) on radical prostatectomy specimens in an effort to explain the poor clinical outcomes associated with this disease subtype.Patients and methodsData from 159 men with Gleason Grade Group (GGG) 3 or 4 were considered. All patients had Decipher diagnostic testing with transcript profiles and single‐channel array normalisation (SCAN)‐normalised expression of coding genes.The relationship between Decipher and TP5 was investigated by linear and binary logistic regressions. A differential transcriptomic analysis between patients with and without TP5 was performed. The prognostic role of these genes on progression‐free survival (PFS) and overall survival (OS) was evaluated using The Cancer Genome Atlas.ResultsIn all, 52/159 (33%) patients had GGG 3–4 with TP5 disease. TP5 was associated with a higher Decipher score (β 0.07, 95% confidence interval [CI] 0.02–0.13; P = 0.04) and higher likelihood of falling within the intermediate‐ or high‐risk categories (odds ratio 3.34, 95% CI 1.34–8.35; P = 0.01). Analysis of microarray data revealed an 18‐gene signature that was differentially expressed in patients with TP5; 13 genes were over‐ and five under‐expressed in the TP5 cohort.The overexpression of cyclin dependent kinase inhibitor 2B (CDKN2B), polo‐like kinase 1 (PLK1), or cell division cycle 20 (CDC20) was associated with worse PFS. The group harbouring overexpression of at least one gene had a 5‐year PFS rate of 50% vs 74% in the group without overexpression (P < 0.001).ConclusionsOur studies have elucidated unique genomic features of TP5, whilst confirming previous clinical findings that patients harbouring TP5 tend to have worse prognosis. This is the first RNA‐based study to investigate the molecular diversity of TP5 and the first correlating CDKN2B to poorer prognosis in patients with prostate cancer.
Late Quaternary glacial history of Khentey Mountains, Central Mongolia
Authors: Khandsuren Purevmaa , Seong Yeong Bae , Oh Jeong Sik , Rhee Hyun Hee , Sandag Khadbaatar , Yu Byung Yong 
Published: March 2019

Mongolian glaciers have been the subject of relatively little research, resulting in less geochronological constraint than other parts of Central Asia. The Khentey Mountains (latitude 47–51°N, longitude 105–112°E) are a typical landlocked mountain range exhibiting clear geomorphic evidence of late Quaternary glaciation. Yet, compared to western parts of Mongolia such as the Mongolian Altay, Gobi Altay, Khangay, and Khovsgol, glacial history of the Khentey Mountains is poorly understood. To address this, and permit comparison of the Khentey glacier–climate record with other alpine regions in Mongolia, we performed geomorphological mapping and cosmogenic10Be surface‐exposure dating in two glaciated regions of the Khentey Mountains: Yestii and Khagiin Khar. Specifically, we measured10Be in 34 samples collected from five moraine sequences, which, together with morphostratigraphy, correspond to four main glacial stages: (i) The My1terminal moraine sequence for Yestii (21.0±4.9 ka) and the Mk1moraine for Khagiin Khar (19.6±2.6 ka), both of which represent the Last Glacial Maximum; (ii) the Lateglacial Mk2moraine, dated to 16.0±3.5 ka; (iii) the Mk3moraine, dated to either 17.6±7.0 ka (Lateglacial) or 12.1±1.1 ka (Younger Dryas); and (iv) the currently undated Mk4moraine (~2200 m a.s.l.), to which we assign a Holocene age. Our results suggest that the timing of maximum glacier extent in Mongolia was regionally variable. In the Khentey Mountains, maximum glaciation occurred during Marine Isotope Stage (MIS) 2, whereas the maximum occurred duringMIS3 in Khangay and Khovsgol and duringMIS4 in the Altay. TheMIS2 glacial maximum in the Khentey Mountains coincided with the global sea level minimum during the Last Glacial Maximum, and was followed by at least three glacial re‐advances during the Lateglacial to possibly the Holocene.
Hypoxia modulates protein phosphatase 2A through HIF‐1α dependent and independent mechanisms in human aortic smooth muscle cells and ventricular cardiomyocytes
Authors: Elgenaidi Ismail Suliman , Spiers James Paul 
Published: March 2019

Background and PurposeAlthough protein phosphatases regulate multiple cellular functions, their modulation under hypoxia remains unclear. We investigated expression of the protein phosphatase system under normoxic/hypoxic conditions and the mechanism by which hypoxia alters protein phosphatase 2A (PP2A) activity.Experimental ApproachHuman cardiovascular cells were cultured in cell type specific media under normoxic or hypoxic conditions (1% O2). Effects on mRNA expression, phosphatase activity, post‐translational modification, and involvement of hypoxia inducible factor 1α (HIF‐1α) were assessed using RT‐PCR, immunoblotting, an activity assay, and siRNA silencing.Key ResultsAll components of the protein phosphatase system studied were expressed in each cell line. Hypoxia attenuated mRNA expression of the transcripts in a cell line‐ and time‐dependent manner. In human aortic smooth muscle cells (HASMC) and AC16 cells, hypoxia decreased PP2Ac activity and mRNA expression without altering PP2Ac abundance. Hypoxia increased demethylated PP2Ac (DPP2Ac) and phosphatase methylesterase 1 (PME‐1) abundance but decreased leucine carboxyl methyltransferase 1 (LCMT‐1) abundance. HIF‐1α siRNA prevented the hypoxia‐mediated decrease in phosphatase activity and expression of the catalytic subunit of protein phosphatase 2A (PPP2CA), independently of altering pPP2Ac, DPP2Ac, LCMT‐1, or PME‐1 abundance.Conclusion and ImplicationsCardiovascular cells express multiple components of the PP2A system. In HASMC and AC16 cells, hypoxia inhibits PP2A activity through HIF‐1α‐dependent and ‐independent mechanisms, with the latter being consistent with altered PP2A holoenzyme assembly. This indicates a complex inhibitory effect of hypoxia on the PP2A system, and highlights PP2A as a therapeutic target for diseases associated with dysregulated protein phosphorylation.
Cyclic nucleotide signalling compartmentation by PDEs in cultured vascular smooth muscle cells
Authors: Zhang Liang , Bouadjel Kaouter , Manoury Boris , Vandecasteele Grégoire , Fischmeister Rodolphe , Leblais Véronique 
Published: March 2019

Background and PurposeUp‐regulation of phosphodiesterases (PDEs) is associated with several vascular diseases, and better understanding of the roles of each PDE isoform in controlling subcellular pools of cyclic nucleotides in vascular cells is needed. We investigated the respective role of PDE1, PDE5, and PDE9 in controlling intracellular cAMP and/or cGMP concentrations ([cAMP]i, [cGMP]i) in cultured rat aortic smooth muscle cells (RASMCs).Experimental ApproachWe used selective inhibitors of PDE1 (PF‐04471141), PDE5 (sildenafil), and PDE9 (PF‐04447943) to measure cAMP‐ and cGMP‐PDE activities with a radioenzymatic assay, in RASMC extracts. Real‐time [cAMP]i and [cGMP]i were recorded by Förster resonance energy transfer‐imaging in single living cells, and cell proliferation was assessed in FBS‐stimulated cells.Key ResultsPDE1, PDE5, and PDE9 represented the major cGMP‐hydrolyzing activity in RASMCs. Basal PDE1 exerted a functional role in degrading in situ the cGMP produced in response to activation of particulate GC by C‐type natriuretic peptide. In high intracellular Ca2+ concentrations, PDE1 also regulated the NO/soluble GC‐dependent cGMP response, as well as the β‐adrenoceptor‐mediated cAMP response. PDE5 exerted a major role in degrading cGMP produced by NO and the natriuretic peptides. PDE9 only regulated the NO‐induced [cGMP]i increase. All three PDEs contributed differently to regulate cell proliferation under basal conditions and upon cGMP‐elevating stimuli.Conclusions and ImplicationsOur data emphasize the distinct roles of PDE1, PDE5, and PDE9 in local regulation of [cAMP]i and [cGMP]i, in vascular smooth muscle cells, strengthening the concept of PDEs as key actors in the subcellular compartmentation of cyclic nucleotides.
Identification of the Raf kinase inhibitor TAK‐632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3
Authors: Chen Xiaofei , Zhuang Chunlin , Ren Yibin , Zhang Hao , Qin Xia , Hu Longmiao , Fu Jing , Miao Zhenyuan , Chai Yifeng , Liu Zheng‐gang , Zhang Haibing , Cai Zhenyu , Wang Hong‐yang 
Published: March 2019

Background and PurposeNecroptosis is a form of programmed, caspase‐independent, cell death, mediated by receptor‐interacting protein kinases, RIPK1 and RIPK3, and the mixed lineage kinase domain‐like (MLKL). Necroptosis contributes to the pathophysiology of various inflammatory, infectious, and degenerative diseases. Thus, identification of low MW inhibitors for necroptosis has broad therapeutic relevance. Here, we identified that the pan‐Raf inhibitor TAK‐632 was also an inhibitor of necroptosis. We have further generated a more selective, highly potent analogue of TAK‐632 by targeting RIPK1 and RIPK3.Experimental ApproachCell viability was measured by MTT, propidium staining, or CellTiter‐Glo luminescent assays. Effects of TAK‐632 on necroptosis signalling pathways were investigated by western blotting, immunoprecipitation, and in vitro kinase assays. Downstream targets of TAK‐632 were identified by a drug affinity responsive target stability assay and a pull‐down assay with biotinylated TAK‐632. A mouse model of TNF‐α‐induced systemic inflammatory response syndrome (SIRS) was further used to explore the role of TAK‐632 in protecting against necroptosis‐associated inflammation in vivo.Key ResultsTAK‐632 protected against necroptosis in human and mouse cells but did not protect cells from apoptosis. TAK‐632 directly bound with RIPK1 and RIPK3 to inhibit kinase activities of both enzymes. In vivo, TAK‐632 alleviated TNF‐induced SIRS. Furthermore, we performed a structure–activity relationship analysis of TAK‐632 analogues and generated SZM594, a highly potent inhibitor of RIPK1/3.Conclusions and ImplicationsTAK‐632 is an inhibitor of necroptosis and represents a new lead compound in the development of highly potent inhibitors of RIPK1 and RIPK3.
Classroom Popularity Hierarchy Predicts Prosocial and Aggressive Popularity Norms Across the School Year
Authors: Laninga‐Wijnen Lydia , Harakeh Zeena , Garandeau Claire F. , Dijkstra Jan K. , Veenstra René , Vollebergh Wilma A. M. 
Published: March 2019

This study examined the coevolution of prosocial and aggressive popularity norms with popularity hierarchy (asymmetries in students’ popularity). Cross‐lagged‐panel analyses were conducted on 2,843 secondary school students (Nclassrooms = 120; Mage = 13.18; 51.3% girls). Popularity hierarchy predicted relative change in popularity norms over time, but not vice versa. Specifically, classrooms with few highly popular and many unpopular students increased in aggressive popularity norms at the beginning of the school year and decreased in prosocial popularity norms at the end of the year. Also, strong within‐classroom asymmetries in popularity predicted relatively higher aggressive popularity norms. These findings may indicate that hierarchical contexts elicit competition for popularity, with high aggression and low prosocial behavior being seen as valuable tools to achieve popularity.
Luther's Heidelberg Disputation and identity formation
Authors: Bräutigam Michael 
Published: March 2019

AbstractLuther's famous Ninety‐five Theses overshadowed his twenty‐eight theses of the Heidelberg Disputation. This is regrettable insofar as Luther broke in Heidelberg with the traditional scholastic method and introduced for the first time publicly his influential theology of the cross. Luther's existential emphasis in this Disputation is particularly significant, because he answers here the big questions for us: Who am I really in the sight of God? What is my true identity in Christ? Luther radically exposes our self‐centeredness and calls us to look at the world, God, and ourselves through “suffering and the cross,” as only in this way will we be able to perceive clearly and “say what a thing is.” He encourages us to become theologians of the cross who have given up on themselves and discovered that “everything is already done.” Luther's passionate plea to put the cross of Christ at the center of our lives is a welcome reminder for us today, even five hundred years later, as we seek to find out who we are, who God is, and what God is accomplishing in and through us. Rescuing Luther's Heidelberg Disputation from oblivion is vital for the health of both church and academia today.