bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromoselective access to Z- or E- allylated amines and heterocycles by a photocatalytic allylation reaction
Authors: Martínez-Gualda Ana María , Cano Rafael , Marzo Leyre , Pérez-Ruiz Raúl , Luis-Barrera Javier , Mas-Ballesté Rubén , Fraile Alberto , de la Peña O’Shea Víctor A. , Alemán José 
Published: June 2019

AbstractThe most useful strategies for the alkylation of allylic systems are related to the Tsuji–Trost reaction or the use of different Lewis acids. Herein we report a photocatalytic approach for the allylation reaction of a variety of nucleophiles, such as heteroarenes, amines and alcohols. This method is compatible with a large variety of pyrroles and indoles, containing different substituents such as electron-withdrawing and electron-donating groups, unprotected nitrogen atoms and bromo derivatives. Moreover, this methodology enables the chromoselective synthesis of Z- or E-allylated compounds. While the use of UV-light irradiation has allowed the synthesis of the previously inaccessible Z-allylated products, E-isomers are prepared simply by changing both the light source to the visible region, and the catalytic system. Based on mechanistic and photochemical proofs, laser flash photolysis studies and DFT calculations, a rational mechanism is presented.
Impact hotspots of reduced nutrient discharge shift across the globe with population and dietary changes
Authors: Wang Xu , Daigger Glen , de Vries Wim , Kroeze Carolien , Yang Min , Ren Nan-Qi , Liu Junxin , Butler David 
Published: June 2019

AbstractReducing nutrient discharge from wastewater is essential to mitigating aquatic eutrophication; however, energy- and chemicals-intensive nutrient removal processes, accompanied with the emissions of airborne contaminants, can create other, unexpected, environmental consequences. Implementing mitigation strategies requires a complete understanding of the effects of nutrient control practices, given spatial and temporal variations. Here we simulate the environmental impacts of reducing nutrient discharge from domestic wastewater in 173 countries during 1990–2050. We find that improvements in wastewater infrastructure achieve a large-scale decline in nutrient input to surface waters, but this is causing detrimental effects on the atmosphere and the broader environment. Population size and dietary protein intake have the most significant effects over all the impacts arising from reduction of wastewater nutrients. Wastewater-related impact hotspots are also shifting from Asia to Africa, suggesting a need for interventions in such countries, mostly with growing populations, rising dietary intake, rapid urbanisation, and inadequate sanitation.
XX sex chromosome complement promotes atherosclerosis in mice
Authors: AlSiraj Yasir , Chen Xuqi , Thatcher Sean E. , Temel Ryan E. , Cai Lei , Blalock Eric , Katz Wendy , Ali Heba M. , Petriello Michael , Deng Pan , Morris Andrew J. , Wang Xuping , Lusis Aldons J. , Arnold Arthur P. , Reue Karen , Thompson Katherine , Tso Patrick , Cassis Lisa A. 
Published: June 2019

AbstractMen and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating a primary effect of sex chromosomes. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly are greater in XX male and female mice with higher intestinal lipids. Together, our results show that an XX sex chromosome complement promotes the bioavailability of dietary fat to accelerate atherosclerosis.
The hydrolase LpqI primes mycobacterial peptidoglycan recycling
Authors: Moynihan Patrick J. , Cadby Ian T. , Veerapen Natacha , Jankute Monika , Crosatti Marialuisa , Mukamolova Galina V. , Lovering Andrew L. , Besra Gurdyal S. 
Published: June 2019

AbstractGrowth and division by most bacteria requires remodelling and cleavage of their cell wall. A byproduct of this process is the generation of free peptidoglycan (PG) fragments known as muropeptides, which are recycled in many model organisms. Bacteria and hosts can harness the unique nature of muropeptides as a signal for cell wall damage and infection, respectively. Despite this critical role for muropeptides, it has long been thought that pathogenic mycobacteria such as Mycobacterium tuberculosis do not recycle their PG. Herein we show that M. tuberculosis and Mycobacterium bovis BCG are able to recycle components of their PG. We demonstrate that the core mycobacterial gene lpqI, encodes an authentic NagZ β-N-acetylglucosaminidase and that it is essential for PG-derived amino sugar recycling via an unusual pathway. Together these data provide a critical first step in understanding how mycobacteria recycle their peptidoglycan.
Domain-interface dynamics of CFTR revealed by stabilizing nanobodies
Authors: Sigoillot Maud , Overtus Marie , Grodecka Magdalena , Scholl Daniel , Garcia-Pino Abel , Laeremans Toon , He Lihua , Pardon Els , Hildebrandt Ellen , Urbatsch Ina , Steyaert Jan , Riordan John R. , Govaerts Cedric 
Published: June 2019

AbstractThe leading cause of cystic fibrosis (CF) is the deletion of phenylalanine 508 (F508del) in the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR). The mutation affects the thermodynamic stability of the domain and the integrity of the interface between NBD1 and the transmembrane domain leading to its clearance by the quality control system. Here, we develop nanobodies targeting NBD1 of human CFTR and demonstrate their ability to stabilize both isolated NBD1 and full-length protein. Crystal structures of NBD1-nanobody complexes provide an atomic description of the epitopes and reveal the molecular basis for stabilization. Furthermore, our data uncover a conformation of CFTR, involving detachment of NBD1 from the transmembrane domain, which contrast with the compact assembly observed in cryo-EM structures. This unexpected interface rearrangement is likely to have major relevance for CF pathogenesis but also for the normal function of CFTR and other ABC proteins.
Long non-coding and coding RNA profiling using strand-specific RNA-seq in human hypertrophic cardiomyopathy
Authors: Liu Xuanyu , Ma Yi , Yin Kunlun , Li Wenke , Chen Wen , Zhang Yujing , Zhu Changsheng , Li Tianjiao , Han Bianmei , Liu Xuewen , Wang Shuiyun , Zhou Zhou 
Published: June 2019

AbstractHypertrophic cardiomyopathy (HCM) represents one of the most common heritable heart diseases. However, the signalling pathways and regulatory networks underlying the pathogenesis of HCM remain largely unknown. Here, we present a strand-specific RNA-seq dataset for both coding and lncRNA profiling in myocardial tissues from 28 HCM patients and 9 healthy donors. This dataset constitutes a valuable resource for the community to examine the dysregulated coding and lncRNA genes in HCM versus normal conditions.
Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development
Authors: Kwon Jeongwoo , Jo Yu-Jin , Namgoong Suk , Kim Nam-Hyung 
Published: June 2019

AbstractHeterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) plays an important role in RNA processing via in m6A modification of pre-mRNA or pre-miRNA. However, the functional role of and relationship between m6A and hnRNPA2/B1 in early embryonic development are unclear. Here, we found that hnRNPA2/B1 is crucial for early embryonic development by virtue of regulating specific gene transcripts. HnRNPA2/B1 was localized to the nucleus and cytoplasm during subsequent embryonic development, starting at fertilization. Knockdown of hnRNPA2/B1 delayed embryonic development after the 4-cell stage and blocked further development. RNA-Seq analysis revealed changes in the global expression patterns of genes involved in transcription, translation, cell cycle, embryonic stem cell differentiation, and RNA methylation in hnRNPA2/B1 KD blastocysts. The levels of the inner cell mass markers OCT4 and SOX2 were decreased in hnRNPA2/B1 KD blastocysts, whereas that of the differentiation marker GATA4 was decreased. N6-Adenosine methyltransferase METTL3 knock-down caused embryonic developmental defects similar to those in hnRNPA2/B1 KD embryos. Moreover, METTL3 KD blastocysts showed increased mis-localization of hnRNPA2/B1 and decreased m6A RNA methylation. Taken together, our results suggest that hnRNPA2/B1 is essential for early embryogenesis through the regulation of transcription-related factors and determination of cell fate transition. Moreover, hnRNPA2/B1 is regulated by METTL3-dependent m6A RNA methylation.
Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
Authors: Shyu Peter , Ng Benjamin S. H. , Ho Nurulain , Chaw Ruijie , Seah Yi Ling , Marvalim Charlie , Thibault Guillaume 
Published: June 2019

AbstractPhospholipid homeostasis in biological membranes is essential to maintain functions of organelles such as the endoplasmic reticulum. Phospholipid perturbation has been associated to cellular stress responses. However, in most cases, the implication of membrane lipid changes to homeostatic cellular response has not been clearly defined. Previously, we reported that Saccharomyces cerevisiae adapts to lipid bilayer stress by upregulating several protein quality control pathways such as the endoplasmic reticulum-associated degradation (ERAD) pathway and the unfolded protein response (UPR). Surprisingly, we observed certain ER-resident transmembrane proteins, which form part of the UPR programme, to be destabilised under lipid bilayer stress. Among these, the protein translocon subunit Sbh1 was prematurely degraded by membrane stiffening at the ER. Moreover, our findings suggest that the Doa10 complex recognises free Sbh1 that becomes increasingly accessible during lipid bilayer stress, perhaps due to the change in ER membrane properties. Premature removal of key ER-resident transmembrane proteins might be an underlying cause of chronic ER stress as a result of lipid bilayer stress.
Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors
Authors: Kiuchi Yoshiaki , Yanagi Masahide , Itakura Katsumasa , Takahashi Ikuno , Hida Ayumi , Ohishi Waka , Furukawa Kyoji 
Published: June 2019

AbstractWe examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.
Shallow landslide disposition in burnt European beech (Fagus sylvatica L.) forests
Authors: Gehring Eric , Conedera Marco , Maringer Janet , Giadrossich Filippo , Guastini Enrico , Schwarz Massimiliano 
Published: June 2019

AbstractTree roots contribute significantly to soil strength on hillslopes. In the case of wildfires, this effect may abruptly vanish and be lacking for a considerable period of time depending on the resistance and resilience of the forest. Despite its importance, quantitative data on the impact and dynamics of wildfires on slope stabilization is still lacking. We use the study case of the Fagus sylvatica L. to quantify the medium-term evolution of root reinforcement and its effect on slope stability in fire-injured forests. In the study, we upscale root reinforcement using field data for the calibration of the Root Bundle Model and detailed information on forest structure in 244 plots, and calculate the spatio-temporal dynamics of forest protective capacity using a three-dimensional probabilistic slope stability model (slideforNET) for different site types. In unburnt and low-burn forests, the protective capacity was found to remain constant over time. Forests hit by moderate burns continue to provide adequate protection for shallow (depth < 0.5 m) and cohesive soils only, whereas in the case of high severity fires, the protective capacity vanishes for 15 years and an increased shallow landslide probability remains for at least 40 years. These conditions call for appropriate sylvicultural post-fire measures.
C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice
Authors: Ackermann Tobias , Hartleben Götz , Müller Christine , Mastrobuoni Guido , Groth Marco , Sterken Britt A. , Zaini Mohamad A. , Youssef Sameh A. , Zuidhof Hidde R. , Krauss Sara R. , Kortman Gertrud , de Haan Gerald , de Bruin Alain , Wang Zhao-Qi , Platzer Matthias , Kempa Stefan , Calkhoven Cornelis F. 
Published: June 2019

AbstractThe transcription factors LAP1, LAP2 and LIP are derived from theCebpb-mRNA through the use of alternative start codons. High LIP expression has been associated with human cancer and increased cancer incidence in mice. However, how LIP contributes to cellular transformation is poorly understood. Here we present that LIP induces aerobic glycolysis and mitochondrial respiration reminiscent of cancer metabolism. We show that LIP-induced metabolic programming is dependent on the RNA-binding protein LIN28B, a translational regulator of glycolytic and mitochondrial enzymes with known oncogenic function. LIP activates LIN28B through repression of thelet-7microRNA family that targets theLin28b-mRNA. Transgenic mice overexpressing LIP have reduced levels oflet-7and increased LIN28B expression, which is associated with metabolic reprogramming as shown in primary bone marrow cells, and with hyperplasia in the skin. This study establishes LIP as an inducer of cancer-type metabolic reprogramming and as a regulator of thelet-7/LIN28B regulatory circuit.
Accurately cleavable goat β-lactoglobulin signal peptide efficiently guided translation of a recombinant human plasminogen activator in transgenic rabbit mammary gland
Authors: Lu Rui , Zhang Ting , Song Shaozheng , Zhou Minya , Jiang Lei , He Zhengyi , Yuan Yuguo , Yuan Tingting , Lu Yaoyao , Yan Kunning , Cheng Yong 
Published: June 2019

Abstract
Poor expression is the key factor hampering the large-scale application of transgenic animal mammary gland bioreactors. A very different approach would be to evaluate the secretion of recombinant proteins into milk in response to a cleavable signal peptide of highly secreted lactoproteins.
We previously reported rabbits harboring mammary gland-specific expression vector containing a fusion cDNA (goat β-lactoglobulin (BLG) signal peptide and recombinant human plasminogen activator (rhPA) coding sequences) expressed rhPA in the milk, but we did not realize the signal peptide contributed to the high rhPA concentration and did not mention it at that time. And the molecular structure and biological characteristics still remain unknown. So, rhPA in the milk was purified and characterized in the present study.
rhPA was purified from the milk, and the purity of the recovered product was 98% with no loss of biological activity. Analysis of the N-terminal sequence, C-terminal sequence, and the molecular mass of purified rhPA revealed that they matched the theoretical design requirements. The active systemic anaphylaxis (ASA) reactions of the purified rhPA were negative. Taken together, these results indicated that the goat BLG signal peptide can efficiently mediate rhPA secretion into milk and was accurately cleaved off from rhPA by endogenous rabbit signal peptidase.
We have reinforced the importance of a rhPA coding region fused to a cleavable heterologous signal peptide from highly secreted goat BLG to improve recombinant protein expression. It is anticipated that these findings will be widely applied to high-yield production of medically important recombinant proteins.
Diagnostic value of RASSF1A methylation for breast cancer: a meta-analysis
Authors: Li Mingyi , Wang Chunpeng , Yu Binbin , Zhang Xueyuan , Shi Fang , Liu Xin 
Published: June 2019

Abstract
Background: Numerous studies reported that RAS-association domain family 1 isoform A (RASSF1A) methylation might act as diagnostic biomarker for breast cancer (BC), this meta-analysis aimed to evaluate the value of RASSF1A methylation for diagnosing BC.
Methods: Such databases as PubMed, Cochrane Library and Web of Science databases were searched for literatures until May 2019. A meta-analysis was performed utilizing STATA and Revman softwares. Furthermore, subgroup analysis was adopted to determine likely sources of heterogeneity.
Results: Totally 19 literatures with 1849 patients and 1542 controls were included in the present study. Sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic curve (AUC) of RASSF1A methylation for diagnosing BC were 0.49, 0.95, 19.0 and 0.83, respectively. The sensitivity (0.54 vs 0.43), DOR (30.0 vs 10.0) and AUC (0.84 vs 0.81) of RASSF1A methylation in Caucasian were higher than other ethnicities. The sensitivity (0.64 vs 0.57), DOR (21.0 vs 14.0) and AUC (0.89 vs 0.86) of methylation-specific PCR (MSP) were superior to other methods (q-MSP, OS-MSP and MethyLight). The sensitivity, DOR and AUC of serum RASSF1A methylation vs RASSF1A methylation in other samples (tissue or plasma) were 0.55 vs 0.40, 22.0 vs 14.0 and 0.86 vs 0.74, respectively.
Conclusions: RASSF1A methylation might be a potential diagnostic biomarker for BC. Considering its low sensitivity and high specificity, it should combine with others to upgrade the sensitivity. Besides, under such conditions, MSP detection, serum RASSF1A methylation and Caucasian are shown to be more effective and suitable for diagnosing BC.
Formation and morphology of anomalous solar circular polarization
Authors: Carlin E. S. 
Published: June 2019

Context. The morphology of spectral line polarization is the most valuable observable to investigate the magnetic and dynamic solar atmosphere. However, in order to develop solar diagnosis, it is fundamental to understand the different kinds of anomalous solar signals that are routinely found in linear and circular polarization (LP,CP).
Aims. We aim to explain and characterize the morphology of solar CP signals considering nonlocal thermodynamical equilibrium (NLTE) effects.
Methods. An analytical two-layer model of the polarized radiative transfer equation is developed and used to solve the NLTE problem with atomic polarization in a semi-parametric way. The potential of the model for reproducing anomalous CP is shown with detailed calculations and examples. A new approach based on the zeroes of polarization signals is developed to explain their morphology.
Results. We have obtained a comprehensive model that insightfully describes the formation of solar polarization with certain precision without sacrificing key physical ingredients or resorting to complex atmospheric models. The essential physical behavior of dichroism and atomic orientation has been described, introducing the concepts of dichroic inversion, neutral and reinforcing medium, critical intensity spectrum, and critical source function. We show that the zero-crossings of the CP spectrum are useful to classify its morphology and understand its formation. This led to identification and explanation of the morphology of the seven most characteristic CP signals that a single (depth-resolved) scattering layer can produce. We find that a minimal number of two magnetic layers along the line of sight is required to fully explain anomalous solar CP signals and that the morphology and polarity of Stokes V depends on magnetic, radiative, and atomic “polarities”. Some implications of these results are presented through a preliminary modeling of anomalous CP signals in the Fe I 1564.8 nm and Na I D lines.
Mütterliches Malignom in der Schwangerschaft als Ursache eines wiederholten Testversagens im nicht-invasiven Pränataltest
Authors: Karge Anne , Graupner Oliver , Abel Kathrin , Kuschel Bettina 
Published: June 2019

ZusammenfassungDer nicht-invasive Pränataltest (NIPT) ist ein Screening-Test für fetale Chromosomenstörungen. Aktuelle Studien zeigen eine inzidentelle Detektion mütterlicher Malignome im Rahmen der NIPT-Diagnostik, wobei als NIPT-„Anomalie“ das simultane Vorliegen multipler Aneuploidien beschrieben wird. In diesem Fall konnte aufgrund eines wiederholten Testversagens („no call“) im NIPT die Diagnose einer maternalen Tumorerkrankung gestellt werden.
Grammaticalization of semi-modals of necessity in Asian Englishes
Authors: Loureiro-Porto Lucía 
Published: June 2019

AbstractThe decline of central modalmustand the increase in frequency of the semi-modalshave (got) to, need (to), andwant tois one of the most conspicuous grammatical changes that inner-circle varieties of English underwent in the second half of the 20th century. Such a replacement correlates with the increasing grammaticalization of the semi-modals in terms of semantic and quantitative developments. The current paper explores the differential grammaticalization of these items in four Asian varieties of English – those spoken in India, Hong Kong, Singapore, and the Philippines – with the aim of building a grammaticalization index that will allow us to measure the extent to which the replacement of modalmustwith the semi-modals is completed in each of the varieties as compared to British English. After analyzing data from the private dialogue sections of the corresponding ICE corpora, Hong Kong English is shown to be the variety in which the replacement is closest to British English, followed by the Philippines, Singapore and India.
Extracellular vesicles in type 2 diabetes mellitus: key roles in pathogenesis, complications, and therapy
Authors: Xiao Yongwei , Zheng Lei , Zou Xiaofeng , Wang Jigang , Zhong Jianing , Zhong Tianyu 
Published: June 2019

ABSTRACTType 2 diabetes mellitus (T2DM), a chronic disease, is widely prevalent all over the world. In recent years, the roles of some extracellular vesicles (EVs) in T2DM have attracted much attention. EVs are bilayer membrane vesicles secreted from most cells and can participate in regulating various physiological and pathological processes in vivo by being transported between cells. Recently, it was discovered that some abnormal EVs can contribute to the occurrence of T2DM by inducing insulin resistance and can also participate in the complications of T2DM. In addition, some stem/progenitor cells‐derived EVs have a potential application in the therapy of T2DM. This review introduces basic concepts of EVs and summarizes the roles of EVs in the pathogenesis, complications, and therapy of T2DM.