bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRP2 controls sonic hedgehog-dependent differentiation of cardiac progenitor cells during outflow tract formation
Authors: Christ Annabel , Willnow Thomas E. 
Published: October 2019

ABSTRACTConotruncal malformations are a major cause of congenital heart defects in newborn infants. Recently, genetic screens in humans and mouse models have identified mutations inLRP2as a novel cause of a common arterial trunk, a severe form of outflow tract (OFT) defect. Yet, the underlying mechanism why the morphogen receptor LRP2 is essential for OFT development remained unexplained. Studying LRP2-deficient mouse models, we now show that LRP2 is expressed in the cardiac progenitor niche of the anterior second heart field (SHF) that contributes to elongation of the OFT during separation into aorta and pulmonary trunk. Loss of LRP2 in mutant mice results in depletion of a pool of sonic hedgehog-dependent progenitor cells in the SHF due to premature differentiation into cardiomyocytes as they migrate into the OFT myocardium. Depletion of this cardiac progenitor cell pool results in aberrant shortening of the OFT, the cause of CAT formation in affected mice. Our findings identified the molecular mechanism whereby LRP2 controls maintenance of progenitor cell fate in the anterior SHF essential for OFT separation, and why receptor dysfunction is a novel cause of conotruncal malformation.
Single-cell RNA sequencing of adultDrosophilaovary identifies transcriptional programs governing oogenesis
Authors: Jevitt Allison , Chatterjee Deeptiman , Xie Gengqiang , Wang Xian-Feng , Otwell Taylor , Huang Yi-Chun , Deng Wu-Min 
Published: October 2019

AbstractOogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modelled extensively using theDrosophilaovary. While different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic dataset for the adultDrosophilaovary and connected tissues. This dataset captures the entire transcriptional trajectory of the developing follicle cell population over time. Our findings provide detailed insight into processes such as cell-cycle switching, migration, symmetry breaking, nurse cell engulfment, egg-shell formation, and signaling during corpus luteum formation, marking a newly identified oogenesis-to-ovulation transition. Altogether, these findings provide a broad perspective on oogenesis at a single-cell resolution while revealing new genetic markers and fate-specific transcriptional signatures to facilitate future studies.
Insulator proteins contribute to expression of gene loci repositioned into heterochromatin in the course ofDrosophilaevolution
Authors: Funikov Sergei Yu. , Rezvykh Alexander P. , Kulikova Dina A. , Zelentsova Elena S. , Chuvakova Lyubov N. , Tyukmaeva Venera I. , Arkhipova Irina R. , Evgen’ev Michael B. 
Published: October 2019

AbstractPericentric heterochromatin inDrosophilais generally composed of repetitive DNA forming a transcriptionally repressive environment. Nevertheless, dozens of genes were embedded into pericentric genome regions during evolution ofDrosophilidaelineage and retained functional activity. However, factors that contribute to “immunity” of these gene loci to transcriptional silencing remain unknown. Here, we investigated molecular evolution of the essentialMybandRanbp16genes. These protein-coding genes reside in euchromatic loci of chromosome X inD. melanogasterand related species, while in other studiedDrosophilaspecies, including evolutionary distant ones, they are located in genomic regions highly enriched with the remnants of transposable elements (TEs), suggesting their heterochromatic nature and location. The promoter region ofMybexhibits a conserved structure throughout theDrosophilaphylogeny and carries motifs for binding of chromatin remodeling factors, including insulator BEAF-32, regardless of eu- or heterochromatic surroundings. Importantly, BEAF-32 occupies not only the promoter region ofMybbut is also found in the vicinity of transcriptional start sites (TSS) ofRanbp16gene as well as in a wide range of genes located in the contrasting chromatin types inD. melanogasterandD. virilis,denoting the boundary of the nucleosome-free region available for RNA polymerase II recruitment and the surrounding heterochromatin. We also find that along with BEAF-32, insulators dCTCF and GAF are enriched at the TSS of heterochromatic genes inD. melanogaster. Thus, we propose that insulator proteins contribute to gene expression in the heterochromatic environment and, hence, facilitate the evolutionary repositioning of gene loci into heterochromatin.Author summaryHeterochromatin inDrosophilais generally associated with transcriptional silencing. Nevertheless, hundreds of essential genes have been identified in the pericentric heterochromatin ofDrosophila melanogaster. Interestingly, genes embedded in pericentric heterochromatin ofD. melanogastermay occupy different genomic loci, euchromatic or heterochromatic, due to repositioning in the course of evolution ofDrosophilaspecies. By surveying factors that contribute to the normal functioning of the relocated genes in distantDrosophilaspecies, i.e.D. melanogasterandD. virilis, we identify certain insulator proteins (e.g.BEAF-32) that facilitate the expression of heterochromatic genes in spite of the repressive environment.
Removal of calcifications from distal canals of mandibular molars by a non‐instrumentational cleaning system: A micro‐CT study
Authors: Chen Binwen , Szabo Deb , Shen Ya , Zhang Duo , Li Xianyu , Ma Jingzhi , Haapasalo Markus 
Published: October 2019

AbstractPulpal calcifications can present problems in endodontic treatment. This micro‐CT study examined the removal of calcifications by a multisonic cleaning system in uninstrumented mandibular molar distal canals. The teeth were accessed and distal canals located and their patency ensured. Micro‐CT images were obtained, and 15 teeth with distal canal calcifications were selected. The volume of distal canals and calcifications were calculated from the micro‐CT images before and after cleaning with the GentleWave system. Calcifications were observed in all thirds of the canals. Attached and free calcification were detected. Root canal volumes were slightly increased after GentleWave treatment, whereas the calcifications were completely or partially removed in all canals. Mean reduction percentage of calcification was 86.4 ± 3.9%, in individual canals from 60% to 100%. Calcifications in the distal canals of mandibular molars could be partially or completely removed by the multisonic cleaning system without instrumentation.
Economywide effects of climate‐smart agriculture in Ethiopia
Authors: Komarek Adam M. , Thurlow James , Koo Jawoo , De Pinto Alessandro 
Published: October 2019

AbstractClimate‐smart agriculture (CSA) is an approach for transforming and reorienting agricultural systems to support food security under climate change. Few studies, however, quantify at the national scale CSA's economic effects or compare CSA to input‐intensive technologies, like fertilizer or irrigation. Such quantification may help with priority setting among competing agricultural investment options. Our study uses an integrated biophysical and economic modeling approach to quantify and contrast the economywide effects of CSA (integrated soil fertility management in our study) and input‐intensive technologies in Ethiopia's cereal systems. We simulate impacts for 20‐year sequences of variable weather, with and without climate change. Results indicate that adopting CSA on 25% of Ethiopia's maize and wheat land increases annual gross domestic product (GDP) by an average 0.18% (US$49.8 million) and reduces the national poverty rate by 0.15 percentage points (112,100 people). CSA is more effective than doubling fertilizer use on the same area, which increases GDP by US$33.0 million and assists 75,300 people out of poverty. CSA and fertilizer have some substitutability, but CSA and irrigation appear complementary. Although not a panacea for food security concerns, greater adoption of CSA in Ethiopia could deliver economic gains but would need substantial tailoring to farmer‐specific contexts.
New insights into the sensitization to nonspecific lipid transfer proteins from pollen and food: New role of allergen Ole e 7
Authors: Oeo‐Santos Carmen , Navas Ana , Benedé Sara , Ruíz‐León Berta , Díaz‐Perales Araceli , Vogel Lothar , Moreno‐Aguilar Carmen , Jurado Aurora , Villalba Mayte , Barderas Rodrigo 
Published: October 2019

AbstractBackgroundOle e 7 is a nonspecific lipid transfer protein (nsLTP) from olive pollen, one of the main allergenic pollens worldwide. This allergenic nsLTP is responsible for severe symptoms in regions with high olive pollen exposure, where many Ole e 7‐sensitized patients exhibit a co‐sensitization to the peach nsLTP, Pru p 3. However, there is no evidence of cross‐reactivity, which explains this observed co‐sensitization. Therefore, the purpose of this study was to explore the relationship between Ole e 7 and Pru p 3.MethodsA total of 48 patients sensitized to Ole e 7 and/or Pru p 3 were included in the study. Specific IgE serum levels were measured by ImmunoCAP 250 and ELISA. Inhibition assays were performed to determine the existence of cross‐reactivity between both nsLTPs. Allergic response was analyzed ex vivo (basophil activation test) and in vitro (RBL‐2H3 mast cell model).ResultsCommon IgG and IgE epitopes were identified between both allergens. IgE‐binding inhibition was detected in Ole e 7–monosensitized patients using rPru p 3 as inhibitor, reaching inhibition values of 25 and 100%. Ex vivo and in vitro assays revealed a response against rPru p 3 in four (31%) Ole e 7–monosensitized patients.ConclusionsOur results suggest that Ole e 7 could play a new role as primary sensitizer in regions with high olive pollen exposure, leading to the peach nsLTP sensitization. This co‐sensitization process would occur because of the cross‐reactivity between Ole e 7 and Pru p 3 observed in some allergic patients.
Temporal changes of noninvasive electrocardiographic risk factors for sudden cardiac death in post‐myocardial infarction patients with preserved ejection fraction: Insights from the PRESERVE‐EF study
Authors: Xenogiannis Iosif , Gatzoulis Konstantinos A. , Flevari Panagiota , Ikonomidis Ignatios , Iliodromitis Efstathios , Trachanas Konstantinos , Vlachos Konstantinos , Arsenos Petros , Tsiachris Dimitrios , Tousoulis Dimitrios , Brilakis Emmanouil S. , Alexopoulos Dimitrios 
Published: October 2019

AbstractBackgroundSeveral noninvasive risk factors (NIRFs) have been proposed for sudden cardiac death risk stratification in post‐myocardial infarction (post‐MI) patients with preserved ejection fraction (EF). However, it remains unclear if these factors change over time.MethodsWe evaluated seven electrocardiographic NIRFs as they were described in the PRESERVE‐EF trial in 80 post‐MI patients with EF ≥ 40%, at least 40 days after revascularization and 1 year later.ResultsMean patient age was 56 ± 10 years, and 88% were men. Mean EF was 50 ± 5%. The prevalence of (a) positive late potentials (27.5% vs. 28.8%, p = .860), (b) >30 premature ventricular complexes/hour (8.8% vs. 11.3%, p = .598), (c) nonsustained ventricular tachycardia (8.8% vs. 5%, p = .349), (d) standard deviation of normal RR intervals <75 ms (3.8% vs. 3.8%, p = 1.000), (e) QTc derived from 24‐hr electrocardiography >440 ms (men) or >450 ms (women) (17.5% vs. 17.5%, p = 1.000), (f) deceleration capacity ≤4.5 ms and heart rate turbulence onset ≥0% and slope ≤2.5 ms (2.5% vs. 3.8%. p = 1.000), and (g) ambulatory T‐wave alternans ≥65 μV in two Holter channels (6.3% vs. 6.3%, p = 1.000) were similar between the two measurements. However, five patients (6.3%) without any NIRFs during the first assessment had at least one positive NIRF at the second assessment and six patients (7.5%) with at least one NIRF at baseline had no positive NIRFs at 1 year.ConclusionsWhile the prevalence of the examined electrocardiographic NIRFs between the two examinations was similar on a population basis, some patients without NIRFs at baseline developed NIRFs at 1 year and vice versa, highlighting the need for risk factor reassessment during follow‐up.
Inter‐sonographer reproducibility of carotid ultrasound plaque detection using Mannheim consensus in subclinical atherosclerosis
Authors: Nyman Emma , Vanoli Davide , Näslund Ulf , Grönlund Christer 
Published: October 2019

SummaryAimsTo determine the inter‐sonographer reproducibility of carotid ultrasound plaque detection using Mannheim consensus in a subclinical population and evaluate associations related to the reproducibility.Methods and resultsBilateral ultrasound screening for carotid plaques defined by Mannheim consensus was performed on 106 subclinical participants. Two different sonographers scanned the same participant, and reproducibility of plaque detection was measured by Cohens kappa. Associations with reproducibility were evaluated by comparing wall, and plaque characteristics between subjects with plaques identified in one and both scans. In general, the inter‐sonographer reproducibility of plaque detection was substantial with a kappa value of 0·70 (95% CI 0·60–0·80). Plaques detected in only one scan had significantly lower plaque area and plaque thickness (6·82 mm2 and 1·45 mm) as compared to plaques detected in both scans (11·65 mm2 and 1·96 mm, P<0·001).ConclusionMinor carotid plaques contribute to decreased reproducibility as compared to large plaques when screening for subclinical atherosclerosis using Mannheim consensus. Using an alternative plaque definition based on plaque thickness >1.5 mm and plaque area >10 mm2 could increase the reproducibility of plaque detection in subclinical atherosclerosis.
Mechanisms of NMDA receptor inhibition by diarylamidine compounds
Authors: Dron Mikhail Y. , Zhigulin Arseniy S. , Barygin Oleg I. 
Published: October 2019

AbstractPentamidine, diminazene and 4′,6‐diamidino‐2‐phenylindole (DAPI) are antiprotozoal diarylamidine compounds. In the present work, we have studied their action on native N‐methyl‐D‐aspartate (NMDA) receptors in rat hippocampal pyramidal neurons. All three compounds inhibited NMDA receptors at −80 mV holding voltage with IC50 of 0.41 ± 0.08, 13 ± 3 and 3.1 ± 0.6 μM, respectively. The inhibition by pentamidine was strongly voltage‐dependent, while that of DAPI was practically voltage‐independent. Inhibition by diminazene had both voltage‐dependent and voltage‐independent components. Diminazene and DAPI demonstrated tail currents and overshoots suggesting “foot‐in‐the‐door” mechanism of action. In contrast, pentamidine was partially trapped in the closed NMDA receptor channels. Such difference in the mechanism of action can be explained by the difference in the 3D structure of compounds. In the pentamidine molecule, two benzamidine groups are connected with a flexible linker, which allows the molecule to fold up and fit in the cavity of a closed NMDA receptor channel. Diminazene and DAPI, in contrast, have an extended form and could not be trapped.
Prevention of parvovirus B19‐induced repetitive acute kidney failure by subcutaneous immunoglobulins
Authors: Bailly Elodie , Stefic Karl , Gatault Philippe , Miquelestorena‐Standley Elodie , Machet Marie‐Christine , Barbet Christelle , Barin Francis , Halimi Jean‐Michel 
Published: October 2019

AbstractHuman parvovirus B19 has been associated with various cases of kidney injuries with different glomerular phenotypes. In immunocompromised individuals, insufficient production of neutralizing antibodies can lead to chronic PVB19 carriage and manifestations. However, PVB19 DNA has been detected in bone marrow and peripheral blood for months or years in seemingly immunocompetent individuals, despite the presence of neutralizing antibodies. We report here PVB19‐induced recurrent anuric acute kidney failures in a 57‐year‐old man over a 7‐year period with persistent PVB19 infection and then PVB19‐associated cryoglobulinemia. Acute renal failures were preceded by influenza‐like syndrome associated with arthralgia, skin rash, and low‐grade fever. Serum, bone marrow, renal, and digestive PVB19 replication was found in the different episodes. Endocapillary proliferative glomerulonephritis evolved into membranoproliferative glomerulonephritis. Complete renal recovery occurred after each bout. Off‐label subcutaneous immunoglobulin therapy resulted in disappearance of blood and bone marrow PVB19 viral load and stopped the glomerulonephritis recurrence. Subcutaneous immunoglobulin therapy withdrawal resulted in renal relapse with cryoglobulin‐associated manifestations.
Frontal fibrosing alopecia in Asians: a retrospective clinical study
Authors: Suchonwanit Poonkiat , Pakornphadungsit Kallapan , Leerunyakul Kanchana , Khunkhet Saranya , Sriphojanart Tueboon , Rojhirunsakool Salinee 
Published: October 2019

AbstractBackgroundFrontal fibrosing alopecia (FFA) is a distinctive form of primary lymphocytic cicatricial alopecia and predominantly occurs in postmenopausal women. The condition is increasing in prevalence worldwide. However, there is a paucity of information regarding FFA in Asians because of a lack of published literature. We aimed to describe the demographics, clinical and trichoscopic features, and treatment outcomes of FFA in Asian patients.MethodsWe conducted a retrospective clinical study including patients diagnosed with FFA. Data regarding demographics, clinical and trichoscopic findings, and treatment outcomes were collected. The data were analyzed using descriptive statistics.ResultsFifty‐six Thai patients with FFA met the inclusion criteria. There were 54 females (96.4%) and two males (3.6%), and the average age of disease onset was 51.3 ± 6.3 years. All patients presented with frontotemporal hairline recession, and 49 patients (87.5%) experienced eyebrow loss. Trichoscopy in 35 patients revealed follicular dropout, perifollicular erythema, and lonely hair in 35 (100%), 29 (82.8%) and 26 patients (74.2%), respectively. Disease stabilization was superiorly observed in patients treated with a combination of topical corticosteroids and hydroxychloroquine or finasteride (79.3% and 73.3%, respectively).ConclusionOur study presents the largest series of FFA in Asians and reports mixed clinical patterns between Caucasian and African patients. Combination therapy of topical corticosteroids and hydroxychloroquine or the use of topical corticosteroids and finasteride may halt the progression of FFA in Asians.
Origins of global mountain plant biodiversity: Testing the ‘mountain‐geobiodiversity hypothesis’
Authors: Muellner‐Riehl Alexandra N. , Schnitzler Jan , Kissling W. Daniel , Mosbrugger Volker , Rijsdijk Kenneth F. , Seijmonsbergen Arie C. , Versteegh Hannes , Favre Adrien 
Published: October 2019

AbstractAimOur objective is to analyse global‐scale patterns of mountain biodiversity and the driving forces leading to the observed patterns. More specifically, we test the ‘mountain geobiodiversity hypothesis’ (MGH) which is based on the assumption that it is not mountain‐uplift alone which drives the evolution of mountain biodiversity, but rather the combination of geodiversity evolution and Neogene and Pleistocene climate changes. We address the following questions: (a) Do areas of high geodiversity and high biodiversity in mountains overlap, that is can mountain geodiversity predict mountain biodiversity? (b) What is the role of Pleistocene climate change in shaping mountain biodiversity? (c) Did diversification rate shifts occur predominantly with the onset of more pronounced climate fluctuations in the late Neogene and Pleistocene fostering a ‘species pump’ effect, as predicted by the MGH?LocationGlobal.TaxonVascular plants.MethodsWe used generalized linear models to test to what extent vascular plant species diversity in mountains is explained by net primary productivity (NPP), geodiversity and Pleistocene climate fluctuations (i.e. changes in temperature between the Last Glacial Maximum [LGM] and today). In addition, we compiled dates of diversification rate shifts from mountain systems and investigated whether these shifts occurred predominantly before or after the global major climatic fluctuations of the late Neogene and Pleistocene.ResultsBoth NPP and elevation range show a positive relationship, whereas Pleistocene climatic fluctuations show a negative impact on plant species diversity. The availability of climatic niche space during the LGM differs markedly among mountain systems. Shifts to higher diversification rates or starts of radiations showed the highest concentration from the late Miocene towards the Pleistocene, supporting the MGH. The most commonly inferred drivers of diversification were key innovations, geological processes (uplift) and climate.Main conclusionsOur analyses point towards an important role of historical factors on mountain plant species richness. Mountain systems characterized by small elevational ranges and strong modifications of temperature profiles appear to harbour fewer radiations, and fewer species. In contrast, mountain systems with the largest elevational ranges and stronger overlap between today´s and LGM temperature profiles are also those where most plant radiations and highest species numbers were identified.
Chemical imaging of evolving amyloid plaque pathology and associated Aβ peptide aggregation in a transgenic mouse model of Alzheimer’s disease
Authors: Michno Wojciech , Wehrli Patrick , Meier Silvio R. , Sehlin Dag , Syvänen Stina , Zetterberg Henrik , Blennow Kaj , Hanrieder Jörg 
Published: October 2019

AbstractOne of the major hallmarks of Alzheimer’s disease (AD) pathology is the formation of extracellular amyloid β (Aβ) plaques. While Aβ has been suggested to be critical in inducing and, potentially, driving the disease, the molecular basis of AD pathogenesis is still under debate. Extracellular Aβ plaque pathology manifests itself upon aggregation of distinct Aβ peptides, resulting in morphologically different plaque morphotypes, including mainly diffuse and cored senile plaques. As plaque pathology precipitates long before any clinical symptoms occur, targeting the Aβ aggregation processes provides a promising target for early interventions. However, the chain of events of when, where and what Aβ species aggregate and form plaques remains unclear. The aim of this study was to investigate the potential of matrix‐assisted laser desorption/ionization imaging mass spectrometry as a tool to study the evolving pathology in transgenic mouse models for AD. To that end, we used an emerging, chemical imaging modality – matrix‐assisted laser desorption/ionization imaging mass spectrometry – that allows for delineating Aβ aggregation with specificity at the single plaque level. We identified that plaque formation occurs first in cortical regions and that these younger plaques contain higher levels of 42 amino acid‐long Aβ (Aβ1–42). Plaque maturation was found to be characterized by a relative increase in deposition of Aβ1–40, which was associated with the appearance of a cored morphology for those plaques. Finally, other C‐terminally truncated Aβ species (Aβ1–38 and Aβ1–39) exhibited a similar aggregation pattern as Aβ1–40, suggesting that these species have similar aggregation characteristics. These results suggest that initial plaque formation is seeded by Aβ1–42; a process that is followed by plaque maturation upon deposition of Aβ1–40 as well as deposition of other C‐terminally modified Aβ species.
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