bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly
Authors: Liu Yi , Gupta Gagan D. , Barnabas Deepak D. , Agircan Fikret G. , Mehmood Shahid , Wu Di , Coyaud Etienne , Johnson Christopher M. , McLaughlin Stephen H. , Andreeva Antonina , Freund Stefan M. V. , Robinson Carol V. , Cheung Sally W. T. , Raught Brian , Pelletier Laurence , van Breugel Mark 
Published: April 2018

AbstractCentrosomes are required for faithful chromosome segregation during mitosis. They are composed of a centriole pair that recruits and organizes the microtubule-nucleating pericentriolar material. Centriole duplication is tightly controlled in vivo and aberrations in this process are associated with several human diseases, including cancer and microcephaly. Although factors essential for centriole assembly, such as STIL and PLK4, have been identified, the underlying molecular mechanisms that drive this process are incompletely understood. Combining protein proximity mapping with high-resolution structural methods, we identify CEP85 as a centriole duplication factor that directly interacts with STIL through a highly conserved interaction interface involving a previously uncharacterised domain of STIL. Structure-guided mutational analyses in vivo demonstrate that this interaction is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly. Taken together, our results illuminate a molecular mechanism underpinning the spatiotemporal regulation of the early stages of centriole duplication.
Multi-omics profiling of younger Asian breast cancers reveals distinctive molecular signatures
Authors: Kan Zhengyan , Ding Ying , Kim Jinho , Jung Hae Hyun , Chung Woosung , Lal Samir , Cho Soonweng , Fernandez-Banet Julio , Lee Se Kyung , Kim Seok Won , Lee Jeong Eon , Choi Yoon-La , Deng Shibing , Kim Ji-Yeon , Ahn Jin Seok , Sha Ying , Mu Xinmeng Jasmine , Nam Jae-Yong , Im Young-Hyuck , Lee Soohyeon , Park Woong-Yang , Nam Seok Jin , Park Yeon Hee 
Published: April 2018

AbstractBreast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA. We also observe increased mutation prevalence affecting BRCA1, BRCA2, and TP53 in SMC with an enrichment of a mutation signature linked to homologous recombination repair deficiency in TNBC. Finally, virtual microdissection and multivariate analyses reveal that Korean BC status is independently associated with increased TIL and decreased TGF-β signaling expression signatures, suggesting that younger Asian BCs harbor more immune-active microenvironment than western BCs.
Structural basis for energy transduction by respiratory alternative complex III
Authors: Sousa Joana S. , Calisto Filipa , Langer Julian D. , Mills Deryck J. , Refojo Patrícia N. , Teixeira Miguel , Kühlbrandt Werner , Vonck Janet , Pereira Manuela M. 
Published: April 2018

AbstractElectron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c/HiPIP oxidoreductase. In order to understand the catalytic mechanism of this respiratory enzyme, we determined the structure of ACIII from Rhodothermus marinus at 3.9 Å resolution by single-particle cryo-electron microscopy. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron–sulfur clusters and six c-type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. Altogether, this structure provides insights into a mechanism for energy transduction and introduces ACIII as a redox-driven proton pump.
Elevated urinary N-acetyl-β-D-glucosaminidase is associated with high glycoalbumin-to-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease
Authors: Hong Namki , Lee Minyoung , Park Soyoung , Lee Yong-ho , Jin Sang-Man , Kim Jae Hyeon , Lee Byung-Wan 
Published: April 2018

AbstractUrinary N-acetyl-β-D-glucosaminidase (uNAG) predicted the progression of diabetic kidney disease (DKD) prior to development of albuminuria in diabetes patients. We sought whether uNAG level is associated with glycoalbumin-to-hemoglobin A1c ratio (G/A ratio), a marker of postprandial hyperglycemia and glycemic excursion, independent of albuminuria and kidney function. The association between uNAG excretion and G/A ratio was assessed in 204 consecutive subjects with type 1 diabetes (T1D) (mean age 43.9 years; 49.0% men). uNAG excretion level increased along with older age, hyperglycemia, and degree of albuminuria, but was not correlated with body mass index or estimated glomerular filtration rate (eGFR). Elevated uNAG showed robust association with higher G/A ratio (adjusted β = 0.103, P = 0.020) after adjustment for age, sex, body mass index, duration of diabetes, uACR, angiotensin blockers use, fasting plasma glucose, and hemoglobin level. uNAG showed better discriminatory performance for individuals with high G/A ratio than albuminuria (AUC 0.613 vs. 0.518, P = 0.038). Measurement of uNAG improved AUC for high G/A ratio from 0.699 to 0.748 (P = 0.043) when added to conventional risk factors (cutoff 5.24 U/g creatinine; sensitivity 62.5% and specificity 58.0%). In conclusion, Elevated uNAG was found to be associated with high G/A ratio in patients with T1D with early stage DKD, independent of age and albuminuria.
Liquid-Liquid Phase Separation of Patchy Particles Illuminates Diverse Effects of Regulatory Components on Protein Droplet Formation
Authors: Nguemaha Valery , Zhou Huan-Xiang 
Published: April 2018

AbstractRecently many cellular functions have been associated with membraneless organelles, or protein droplets, formed by liquid-liquid phase separation (LLPS). Proteins in these droplets often contain RNA-binding domains, but the effects of RNA on LLPS have been controversial. To gain better understanding on the roles of RNA and other macromolecular regulators, here we used Gibbs-ensemble simulations to determine phase diagrams of two-component patchy particles, as models for mixtures of proteins with regulatory components. Protein-like particles have four patches, with attraction strength εPP; regulatory particles experience mutual steric repulsion but have two attractive patches toward proteins, with the strength εPR tunable. At low εPR, the regulator, due to steric repulsion, preferentially partitions in the dispersed phase, thereby displacing the protein into the droplet phase and promoting LLPS. At moderate εPR, the regulator starts to partition and displace the protein in the droplet phase, but only to weaken bonding networks and thereby suppress LLPS. At εPR > εPP, the enhanced bonding ability of the regulator initially promotes LLPS, but at higher amounts, the resulting displacement of the protein suppresses LLPS. These results illustrate how RNA can have disparate effects on LLPS, thus able to perform diverse functions in different organelles.
TMS Over the Cerebellum Interferes with Short-term Memory of Visual Sequences
Authors: Ferrari C. , Cattaneo Z. , Oldrati V. , Casiraghi L. , Castelli F. , D’Angelo E. , Vecchi T. 
Published: April 2018

AbstractGrowing evidence suggests that the cerebellum is not only involved in motor functions, but it significantly contributes to sensory and cognitive processing as well. In particular, it has been hypothesized that the cerebellum identifies recurrent serial events and recognizes their violations. Here we used transcranial magnetic stimulation (TMS) to shed light on the role of the cerebellum in short-term memory of visual sequences. In two experiments, we found that TMS over the right cerebellar hemisphere impaired participants’ ability to recognize the correct order of appearance of geometrical stimuli varying in shape and/or size. In turn, cerebellar TMS did not affect recognition of highly familiar short sequences of letters or numbers. Overall, our data suggest that the cerebellum is involved in memorizing the order in which (concatenated) stimuli appear, this process being important for sequence learning.
Properties of the ternary complex formed by yeast eIF4E, p20 and mRNA
Authors: Arndt Nick , Ross-Kaschitza Daniela , Kojukhov Artyom , Komar Anton A. , Altmann Michael 
Published: April 2018

AbstractYeast p20 is a small, acidic protein that binds eIF4E, the cap-binding protein. It has been proposed to affect mRNA translation and degradation, however p20′s function as an eIF4E-binding protein (4E-BP) and its physiological significance has not been clearly established. In this paper we present data demonstrating that p20 is capable of binding directly to mRNA due to electrostatic interaction of a stretch of arginine and histidine residues in the protein with negatively charged phosphates in the mRNA backbone. This interaction contributes to formation of a ternary eIF4E/p20/capped mRNA complex that is more stable than complexes composed of capped mRNA bound to eIF4E in the absence of p20. eIF4E/p20 complex was found to have a more pronounced stimulatory effect on capped mRNA translation than purified eIF4E alone. Addition of peptides containing the eIF4E-binding domains present in p20 (motif  YTIDELF), in eIF4G (motif  YGPTFLL) or Eap1 (motif  YSMNELY) completely inhibited eIF4E-dependent capped mRNA translation (in vitro), but had a greatly reduced inhibitory effect when eIF4E/p20 complex was present. We propose that the eIF4E/p20/mRNA complex serves as a stable depository of mRNAs existing in a dynamic equilibrium with other complexes such as eIF4E/eIF4G (required for translation) and eIF4E/Eap1 (required for mRNA degradation).
High‐frequency InAlN/GaN HFET with fmax over 400 GHz
Authors: Fu Xing‐Chang , Lv Yuanjie , Zhang Li‐Jiang , Zhang Tong , Li Xian‐Jie , Song Xubo , Zhang Zhirong , Fang Yulong , Feng Zhihong 
Published: April 2018

Ultra‐thin InAlN/GaN heterostructure field‐effect transistors (HFETs) having high maximum oscillation frequency (fmax) are fabricated by scaling lateral dimensions. A 3 nm GaN cap layer is adopted to reduce the electron density and suppress the short‐channel effects. Non‐alloyed regrown n+‐GaN ohmic contacts with total ohmic resistance (Rtot) of 0.13 Ω.mm is also introduced into the device, in which the virtual source‐to‐drain distance is 600 nm. T‐shaped gate with 40 nm length is formed in the centre of the source‐to‐drain region by self‐aligned e‐beam lithography. The peak extrinsic transconductance (gm) reaches 956 mS/mm. Most of all, a high fmax of 405 GHz is obtained, which is the highest value among the reported InAlN/GaN HFETs. These obtained results mean that the InAlN/GaN HFETs having reliability should be still suitable for G‐band (140–220 GHz) power‐amplifier application with further optimisation.
VLTI/MIDI atlas of disks around low- and intermediate-mass young stellar objects
Authors: Varga J. , Ábrahám P. , Chen L. , Ratzka Th. , Gabányi K. É. , Kóspál Á. , Matter A. , van Boekel R. , Henning Th. , Jaffe W. , Juhász A. , Lopez B. , Menu J. , Moór A. , Mosoni L. , Sipos N. 
Published: April 2018

Context. Protoplanetary disks show large diversity regarding their morphology and dust composition. With mid-infrared interferometry the thermal emission of disks can be spatially resolved, and the distribution and properties of the dust within can be studied.
Aims. Our aim is to perform a statistical analysis on a large sample of 82 disks around low- and intermediate-mass young stars, based on mid-infrared interferometric observations. We intend to study the distribution of disk sizes, variability, and the silicate dust mineralogy.
Methods. Archival mid-infrared interferometric data from the MIDI instrument on the Very Large Telescope Interferometer are homogeneously reduced and calibrated. Geometric disk models are used to fit the observations to get spatial information about the disks. An automatic spectral decomposition pipeline is applied to analyze the shape of the silicate feature.
Results. We present the resulting data products in the form of an atlas, containing N band correlated and total spectra, visibilities, and differential phases. The majority of our data can be well fitted with a continuous disk model, except for a few objects, where a gapped model gives a better match. From the mid-infrared size–luminosity relation we find that disks around T Tauri stars are generally colder and more extended with respect to the stellar luminosity than disks around Herbig Ae stars. We find that in the innermost part of the disks (r ≲ 1 au) the silicate feature is generally weaker than in the outer parts, suggesting that in the inner parts the dust is substantially more processed. We analyze stellar multiplicity and find that in two systems (AB Aur and HD 72106) data suggest a new companion or asymmetric inner disk structure. We make predictions for the observability of our objects with the upcoming Multi-AperTure mid-Infrared SpectroScopic Experiment (MATISSE) instrument, supporting the practical preparations of future MATISSE observations of T Tauri stars.
GaiaData Release 2
Authors: Soubiran C. , Jasniewicz G. , Chemin L. , Zurbach C. , Brouillet N. , Panuzzo P. , Sartoretti P. , Katz D. , Le Campion J.-F. , Marchal O. , Hestroffer D. , Thévenin F. , Crifo F. , Udry S. , Cropper M. , Seabroke G. , Viala Y. , Benson K. , Blomme R. , Jean-Antoine A. , Huckle H. , Smith M. , Baker S. G. , Damerdji Y. , Dolding C. , Frémat Y. , Gosset E. , Guerrier A. , Guy L. P. , Haigron R. , Janßen K. , Plum G. , Fabre C. , Lasne Y. , Pailler F. , Panem C. , Riclet F. , Royer F. , Tauran G. , Zwitter T. , Gueguen A. , Turon C. 
Published: April 2018

Aims.The Radial Velocity Spectrometer (RVS) on board the ESA satellite missionGaiahas no calibration device. Therefore, the radial velocity zero point needs to be calibrated with stars that are proved to be stable at a level of 300 m s−1during theGaiaobservations.Methods.We compiled a dataset of ~71 000 radial velocity measurements from five high-resolution spectrographs. A catalogue of 4813 stars was built by combining these individual measurements. The zero point was established using asteroids.Results.The resulting catalogue has seven observations per star on average on a typical time baseline of 6 yr, with a median standard deviation of 15 m s−1. A subset of the most stable stars fulfilling the RVS requirements was used to establish the radial velocity zero point provided inGaiaData Release 2. The stars that were not used for calibration are used to validate the RVS data.
Endoscopic ultrasound elastography of small solid pancreatic lesions: a multicenter study
Authors: Ignee Andre , Jenssen Christian , Arcidiacono Paolo G. , Hocke Michael , Möller Kathleen , Saftoiu Adrian , Will Uwe , Fusaroli Pietro , Iglesias-Garcia Julio , Ponnudurai Ryan , Petrone Maria C. , Braden Barbara , Burmester Eike , Dong Yi , Atkinson Nathan S. , Dietrich Christoph F. 
Published: April 2018

Abstract
Background The prevalence of malignancy in patients with small solid pancreatic lesions is low; however, early diagnosis is crucial for successful treatment of these cases. Therefore, a method to reliably distinguish between benign and malignant small solid pancreatic lesions would be highly desirable. We investigated the role of endoscopic ultrasound (EUS) elastography in this setting.
Methods Patients with solid pancreatic lesions ≤ 15 mm in size and a definite diagnosis were included. Lesion stiffness relative to the surrounding pancreatic parenchyma, as qualitatively assessed and documented at the time of EUS elastography, was retrospectively compared with the final diagnosis obtained by fine-needle aspiration/biopsy or surgical resection.
Results 218 patients were analyzed. The average size of the lesions was 11 ± 3 mm; 23 % were ductal adenocarcinoma, 52 % neuroendocrine tumors, 8 % metastases, and 17 % other entities; 66 % of the lesions were benign. On elastography, 50 % of lesions were stiffer than the surrounding pancreatic parenchyma (stiff lesions) and 50 % were less stiff or of similar stiffness (soft lesions). High stiffness of the lesion had a sensitivity of 84 % (95 % confidence interval 73 % – 91 %), specificity of 67 % (58 % – 74 %), positive predictive value (PPV) of 56 % (50 % – 62 %), and negative predictive value (NPV) of 89 % (83 % – 93 %) for the diagnosis of malignancy. For the diagnosis of pancreatic ductal adenocarcinoma, the sensitivity, specificity, PPV, and NPV were 96 % (87 % – 100 %), 64 % (56 % – 71 %), 45 % (40 % – 50 %), and 98 % (93 % – 100 %), respectively.
Conclusions In patients with small solid pancreatic lesions, EUS elastography can rule out malignancy with a high level of certainty if the lesion appears soft. A stiff lesion can be either benign or malignant.
Systematic review and meta-analysis of the effectiveness of radiofrequency ablation in low grade dysplastic Barrett’s esophagus
Authors: Pandey Gargi , Mulla Mubashir , Lewis Wyn , Foliaki Antonio , Chan David 
Published: April 2018

Abstract
Background Barrett’s esophagus (BE) is a premalignant condition characterized by replacement of the esophageal lining with metastatic columnar epithelium, and its management when complicated by low grade dysplasia (LGD) is controversial. This systematic review and meta-analysis aimed to determine the efficacy of radiofrequency ablation (RFA) in patients with LGD.
Methods MEDLINE, EMBASE, and Web of Science were searched for studies including patients with BE-associated LGD receiving RFA (January 1990 to May 2017). The outcome measures were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D), rates of progression to high grade dysplasia (HGD) or cancer, and recurrence.
Results Eight studies including 619 patients with LGD (RFA = 404, surveillance = 215) were analyzed. After a median follow-up of 26 months (range 12 – 44 months), the overall pooled rates of CE-IM and CE-D after RFA were 88.17 % (95 % confidence interval [CI] 88.13 % – 88.20 %; P < 0.001) and 96.69 % (95 %CI 96.67 % – 96.71 %; P < 0.001), respectively. When compared with surveillance, RFA resulted in significantly lower rates of progression to HGD or cancer (odds ratio [OR] 0.07, 95 %CI 0.02 – 0.22). The pooled recurrence rates of IM and dysplasia were 5.6 % (95 %CI 5.57 – 5.63; P < 0.001) and 9.66 % (95 %CI 9.61 – 9.71; P < 0.001), respectively.
Conclusions RFA safely eradicates IM and dysplasia and reduces the rates of progression from LGD to HGD or cancer in the short term.
Three New Cytotoxic Monoterpenoid Bisindole Alkaloids from Tabernaemontana bufalina
Authors: Zhou Si-Yuan , Zhou Ting-Lan , Qiu Guofu , Huan Xiajuan , Miao Ze-Hong , Yang Sheng-Ping , Cao Shugeng , Fan Fengkai , Cai You-Sheng 
Published: April 2018

AbstractThree new bisindole alkaloids, 3′-(2-oxopropyl)-19,20-dihydrotabernamine (1), 3′-(2-oxopropyl)-ervahanine B (2), 19,20-dihydrovobparicine (3), and 20 known compounds were isolated from the aerial parts of Tabernaemontana bufalina. The structures of these alkaloids were elucidated using spectroscopic methods. The absolute configurations of 1–3 were determined by the circular dichroic exciton chirality method. Compounds 1–23 were screened for their cytotoxicity against two human cancer cell lines, A-549 and MCF-7. Ten compounds (1–3, 10, 14, 16, 17, 19, 22, and 23) exhibited inhibitory effects against the two human cancer cells with IC50 values of 1.19 ~ 6.13 µM.
Enhanced Solubility and Permeability of Salicis cortex Extract by Formulating as a Microemulsion
Authors: Piazzini Vieri , Bigagli Elisabetta , Luceri Cristina , Bilia Anna Rita , Bergonzi Maria Camilla 
Published: April 2018

AbstractA microemulsion system was developed and investigated as a novel oral formulation to increase the solubility and absorption of Salicis cortex extract. This extract possesses many pharmacological activities, in particular, it is beneficial for back pain and osteoarthritic and rheumatic complaints. In this work, after qualitative and quantitative characterization of the extract and the validation of an HPLC/diode array detector analytical method, solubility studies were performed to choose the best components for microemulsion formulation. The optimized microemulsion consisted of 2.5 g of triacetin, as the oil phase, 2.5 g of Tween 20 as the surfactant, 2.5 g of labrasol as the cosurfactant, and 5 g of water. The microemulsion was visually checked, characterized by light scattering techniques and morphological observations. The developed formulation appeared transparent, the droplet size was around 40 nm, and the ζ-potential result was negative. The maximum loading content of Salicis cortex extract resulted in 40 mg/mL. Furthermore, storage stability studies and an in vitro digestion assay were performed. The advantages offered by microemulsion were evaluated in vitro using artificial membranes and cells, i.e., parallel artificial membrane permeability assay and a Caco-2 model. Both studies proved that the microemulsion was successful in enhancing the permeation of extract compounds, so it could be useful to ameliorate the bioefficacy of Salicis cortex.
Peripartum Morbidity after Cesarean Delivery for Arrest of Dilation at 4 to 5 cm Compared with 6 to 10 cm
Authors: Sperling Jeffrey , Has Phinnara , Lovgren Todd , Connealy Brendan , Rouse Dwight , Dahlke Joshua 
Published: April 2018

Objective Given that recent consensus guidelines established to decrease cesarean delivery (CD) rates use 6 cm to define the onset of the active phase of labor, our objective was to evaluate maternal and neonatal outcomes after CD for the indication of arrest of dilation at 4 to 5 cm compared with ≥ 6 cm.
Study Design We performed a secondary analysis using data from the Maternal Fetal-Medicine Units Network Cesarean Registry. We included nulliparous women with term, singleton, vertex gestations who underwent primary CD for arrest of dilation. We compared those who reached a maximum cervical dilation of 4 to 5 cm with those of ≥6 cm. Our primary outcome was composite maternal morbidity that included chorioamnionitis, endometritis, transfusion, wound complication, operative injury, intensive care unit admission, or death.
Results Of the 73,257 women in the dataset, 5,681 met the inclusion criteria. After adjusting for confounders, there was no difference in composite maternal (adjusted odds ratio [aOR]: 1.19; 95% confidence interval [CI]: 0.94–1.52) or neonatal morbidity (aOR: 0.94; 95% CI: 0.79–1.10) between the groups.
Conclusion In this historical cohort, maternal and neonatal outcomes after CD for arrest of dilation ≥ 6 cm were comparable to those performed at 4 to 5 cm and support recent labor management guidelines.