bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of human acetylation stoichiometry defines mechanistic constraints on protein regulation
Authors: Hansen Bogi Karbech , Gupta Rajat , Baldus Linda , Lyon David , Narita Takeo , Lammers Michael , Choudhary Chunaram , Weinert Brian T. 
Published: March 2019

AbstractLysine acetylation is a reversible posttranslational modification that occurs at thousands of sites on human proteins. However, the stoichiometry of acetylation remains poorly characterized, and is important for understanding acetylation-dependent mechanisms of protein regulation. Here we provide accurate, validated measurements of acetylation stoichiometry at 6829 sites on 2535 proteins in human cervical cancer (HeLa) cells. Most acetylation occurs at very low stoichiometry (median 0.02%), whereas high stoichiometry acetylation (>1%) occurs on nuclear proteins involved in gene transcription and on acetyltransferases. Analysis of acetylation copy numbers show that histones harbor the majority of acetylated lysine residues in human cells. Class I deacetylases target a greater proportion of high stoichiometry acetylation compared to SIRT1 and HDAC6. The acetyltransferases CBP and p300 catalyze a majority (65%) of high stoichiometry acetylation. This resource dataset provides valuable information for evaluating the impact of individual acetylation sites on protein function and for building accurate mechanistic models.
The use of technical replication for detection of low-level somatic mutations in next-generation sequencing
Authors: Kim Junho , Kim Dachan , Lim Jae Seok , Maeng Ju Heon , Son Hyeonju , Kang Hoon-Chul , Nam Hojung , Lee Jeong Ho , Kim Sangwoo 
Published: March 2019

AbstractAccurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow, that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing analysis, facilitating remarkable improvement in the detection accuracy for low-VAF somatic mutations (up to ~99% reduction in false positives). The method is validated in independent cancer panel and brain tissue sequencing data. Our study suggests a new paradigm with which to exploit an overwhelming abundance of sequencing data for accurate variant detection.
Spatiotemporal imaging of valence electron motion
Authors: Kübel M. , Dube Z. , Naumov A. Yu. , Villeneuve D. M. , Corkum P. B. , Staudte A. 
Published: March 2019

AbstractElectron motion on the (sub-)femtosecond time scale constitutes the fastest response in many natural phenomena such as light-induced phase transitions and chemical reactions. Whereas static electron densities in single molecules can be imaged in real space using scanning tunnelling and atomic force microscopy, probing real-time electron motion inside molecules requires ultrafast laser pulses. Here, we demonstrate an all-optical approach to imaging an ultrafast valence electron wave packet in real time with a time-resolution of a few femtoseconds. We employ a pump-probe-deflect scheme that allows us to prepare an ultrafast wave packet via strong-field ionization and directly image the resulting charge oscillations in the residual ion. This approach extends and overcomes limitations in laser-induced orbital imaging and may enable the real-time imaging of electron dynamics following photoionization such as charge migration and charge transfer processes.
Anti-quenching NIR-II molecular fluorophores for in vivo high-contrast imaging and pH sensing
Authors: Wang Shangfeng , Fan Yong , Li Dandan , Sun Caixia , Lei Zuhai , Lu Lingfei , Wang Ting , Zhang Fan 
Published: March 2019

AbstractThe contrast and sensitivity of in vivo fluorescence imaging has been revolutionized by molecular fluorophores operating in the second near-infrared window (NIR-II; 1000-1700 nm), but an ongoing challenge is the solvatochromism-caused quenching in aqueous solution for the long-wavelength absorbing fluorophores. Herein, we develop a series of anti-quenching pentamethine cyanine fluorophores that significantly overcome the severe solvatochromism, thus affording stable absorption/emission beyond 1000 nm with up to ~ 44-fold enhanced brightness and superior photostability in aqueous solution. These advantages allow for deep optical penetration (8 mm) as well as high-contrast and highly-stable lymphatic imaging superior to clinical-approved indocyanine green. Additionally, these fluorophores exhibit pH-responsive fluorescence, allowing for noninvasive ratiometric fluorescence imaging and quantification of gastric pH in vivo. The results demonstrate reliable accuracy in tissue as deep as 4 mm, comparable to standard pH electrode method. This work unlocks the potential of anti-quenching pentamethine cyanines for NIR-II biological applications.
Island Ancestors and New World Biogeography: A Case Study from the Scorpions (Buthidae: Centruroidinae)
Authors: Esposito Lauren A. , Prendini Lorenzo 
Published: March 2019

AbstractScorpions are an excellent system for understanding biogeographical patterns. Most major scorpion lineages predate modern landforms, making them suitable for testing hypotheses of vicariance and dispersal. The Caribbean islands are endowed with a rich and largely endemic scorpion fauna, the origins of which have not been previously investigated with modern biogeographical methods. Three sets of hypotheses have been proposed to explain present patterns of diversity in the Caribbean: (1) connections via land bridges, (2) vicariance events, and (3) overwater dispersal from continents and among islands. The present study investigates the biogeographical diversification of the New World buthid scorpion subfamily Centruroidinae Kraus, 1955, a clade of seven genera and more than 110 species; infers the ancestral distributions of these scorpions; and tests the relative roles of vicariance and dispersal in the formation of their present distributions. A fossil-calibrated molecular phylogeny was estimated with a Bayesian criterion to infer the dates of diversification events from which ancestral distributions were reconstructed, and the relative likelihood of models of vicariance vs. dispersal, calculated. Although both the timing of diversification and the ancestral distributions were congruent with the GAARlandia land-bridge hypothesis, there was no significant difference between distance-dependent models with or without the land-bridge.HeteroctenusPocock, 1893, the Caribbean-endemic sister taxon ofCentruroidesMarx, 1890 provides evidence for a Caribbean ancestor, which subsequently colonized Central America and North America, and eventually re-colonized the Greater Antilles. This ‘reverse colonization’ event of a continent from an island demonstrates the importance of islands as a potential source of biodiversity.
Radiated and guided optical waves of a magnetic dipole-nanofiber system
Authors: Atakaramians Shaghik , Dong Feng Q. , Monro Tanya M. , Afshar V. Shahraam 
Published: March 2019

AbstractNanophotonics–photonic structures with subwavelength features–allow accessing high intensity and localized electromagnetic field and hence is an ideal platform for investigating and exploiting strong lightmatter interaction. In particular, such a strong light-matter interaction requires investigating the interaction of a magnetic dipole with the electromagnetic field– a less-explored topic, which has usually been ignored within the framework of electric dipole approximation. Motivated by recent advances in the emerging field of multipolar nanophotonics, here we develop an analytical model that provides a new insight into analyzing a magnetic dipole and a nanofiber. This method enables us to examine the effect of second term in the multipolar expansion of light-matter interaction, magnetic dipole approximation, with individual guided and radiation modes of the nanofiber. This is a critical key in developing nanophotonic integrated devices based on magnetic nature of light for super-imaging, biosensing, and optical computing.
A urinary microRNA panel that is an early predictive biomarker of delayed graft function following kidney transplantation
Authors: Khalid Usman , Newbury Lucy J. , Simpson Kate , Jenkins Robert H. , Bowen Timothy , Bates Lucy , Sheerin Neil S. , Chavez Rafael , Fraser Donald J. 
Published: March 2019

AbstractPredicting immediate and subsequent graft function is important in clinical decision-making around kidney transplantation, but is difficult using available approaches. Here we have evaluated urinary microRNAs as biomarkers in this context. Profiling of 377 microRNAs in the first urine passed post-transplantation identified 6 microRNAs, confirmed to be upregulated by RT-qPCR in an expanded cohort (miR-9, -10a, -21, -29a, -221, and -429, n = 33, P < 0.05 for each). Receiver operating characteristic analysis showed Area Under the Curve 0.94 for this panel. To establish whether this early signal was sustained, miR-21 was measured daily for 5 days post-transplant, and was consistently elevated in those developing Delayed Graft Function (n = 165 samples from 33 patients, p < 0.05). The biomarker panel was then evaluated in an independent cohort, sampled at varying times in the first week post-transplantation in a separate transplant center. When considered individually, all miRs in the panel showed a trend to increase or a significant increase in those developing delayed Graft Function (miR-9: P = 0.068, mIR-10a: P = 0.397, miR-21: P = 0.003, miR-29a: P = 0.019, miR-221: P = 0.1, and miR-429: P = 0.013, n = 47) with Area Under the Curve 0.75 for the panel. In conclusion, combined measurement of six microRNAs had predictive value for delayed graft function following kidney transplantation.
Wound healing in post-smolt Atlantic salmon (Salmo salar L.)
Authors: Sveen Lene Rydal , Timmerhaus Gerrit , Krasnov Aleksei , Takle Harald , Handeland Sigurd , Ytteborg Elisabeth 
Published: March 2019

AbstractSkin biopsies (5 mm) taken from behind the dorsal fin on Atlantic salmon post-smolts were followed over a 2 month period. The healing process was dominated by hemostasis, acute inflammation, and epidermal repair the first 14 days post wounding (dpw), as shown through imaging, histological evaluation, and transcriptomics. Most of the immune genes showed decreased expression after two weeks, approaching the levels of intact skin, as also reflected in sections where reduced inflammation in the wound bed was observed. Transcriptional events suggest recruitment of lymphocytes to the wound site during the acute phase, with activation of humoral responses from 14 dpw and onward. From the histology, a more adherent mucus was observed that correlated with altered transcription of glycosyltransferases. This may indicate different properties and functions of the mucus during the wound healing process. Wound contraction started between 14 and 36 dpw. The occurrence of these events was concurrent with granulation tissue formation, melanocyte migration and up-regulation of genes involved in extracellular matrix formation. The presented description of the wound healing processes in Atlantic salmon gives insight into comparative ulcerative biology in mammals and fish and provides both novel and updated knowledge that can be applied for improved best operational practices for fish welfare in aquaculture.
Pyroglutamic acidosis as a cause for high anion gap metabolic acidosis: a prospective study
Authors: Raibman Spector Shir , Mayan Haim , Loebstein Ronen , Markovits Noa , Priel Eldar , Massalha Eias , Shafir Yuval , Gueta Itai 
Published: March 2019

Abstract5-oxoprolinemia (pyroglutamic acid, PGA) in the absence of acetaminophen use has been rarely reported as a cause for high anion gap metabolic acidosis. We investigated the prevalence and risk factors for elevated PGA concentrations among hospitalized patients with high anion gap metabolic acidosis: We prospectively enrolled patients with high anion gap metabolic acidosis hospitalized in the department of medicine. For each patient we collected the main diagnosis, concurrent medications and laboratory parameters. Spot urine samples were tested for PGA concentration. Levels ≥63 µmol/mmol creatinine were considered elevated. Overall, forty patients were prospectively followed. Mean age was 66.9 (17.9) years. Four (6.3%) patients had a high urine PGA level and demonstrated also lower blood pH (7.2 vs 7.3, p = 0.05) and lower serum lactate concentration (17.5 mg/dl vs 23.0 mg/dl, p = 0.04). Additionally, the high PGA level group consisted of more patients with septic shock [2/4 (50%) vs 3/36 (8.3%)] with a trend towards significance (p = 0.07). In conclusion, PGA might have a role in patients with septic shock and acidosis. Being a treatable condition, PGA should be taken into consideration particularly when no other cause for high anion gap is identified.
Interface effects in hybrid hBN-graphene nanoribbons
Authors: Leon Carlos , Costa Marcio , Chico Leonor , Latgé Andrea 
Published: March 2019

AbstractWe analyze the electronic properties of a hybrid graphene-BN nanoribbon system, using a Hubbard model Hamiltonian within a mean field approximation. Due to the different electronegativities of the boron and nitrogen atoms, an electric field is induced across the zigzag graphene strip, breaking the spin degeneracy of the electronic band structure. Optimal tight-binding parameters are found from first-principles calculations. Edge potentials are proposed as corrections for the on-site energies, modeling the BN-graphene nanoribbon interfaces. We show that half-metallic responses in the hybrid systems may be driven with the help of an external electric field. We also study the role of defects across the graphene nanoribbon and at the h-BN/graphene interface regions. Modulations on the spin-dependent gaps may be achieved depending on the nature and position of the defect, constituting a way towards spin-gap engineering by means of spatial doping.
Ancestral mitochondrial N lineage from the Neolithic ‘green’ Sahara
Authors: Vai Stefania , Sarno Stefania , Lari Martina , Luiselli Donata , Manzi Giorgio , Gallinaro Marina , Mataich Safaa , Hübner Alexander , Modi Alessandra , Pilli Elena , Tafuri Mary Anne , Caramelli David , di Lernia Savino 
Published: March 2019

AbstractBecause Africa’s climate hampers DNA preservation, knowledge of its genetic variability is mainly restricted to modern samples, even though population genetics dynamics and back-migrations from Eurasia may have modified haplotype frequencies, masking ancient genetic scenarios. Thanks to improved methodologies, ancient genetic data for the African continent are now increasingly available, starting to fill in the gap. Here we present newly obtained mitochondrial genomes from two ~7000-year-old individuals from Takarkori rockshelter, Libya, representing the earliest and first genetic data for the Sahara region. These individuals carry a novel mutation motif linked to the haplogroup N root. Our result demonstrates the presence of an ancestral lineage of the N haplogroup in the Holocene “Green Sahara”, associated to a Middle Pastoral (Neolithic) context.
Thresholds for identifying pathological intracranial pressure in paediatric traumatic brain injury
Authors: Kayhanian Saeed , Young Adam M. H. , Ewen Ross L. , Piper Rory J. , Guilfoyle Mathew R. , Donnelly Joseph , Fernandes Helen M. , Garnett Matthew , Smielewski Peter , Czosnyka Marek , Agrawal Shruti , Hutchinson Peter J. 
Published: March 2019

AbstractIntracranial pressure (ICP) monitoring forms an integral part of the management of severe traumatic brain injury (TBI) in children. The prediction of elevated ICP from imaging is important when deciding on whether to implement invasive ICP monitoring for a patient. However, the radiological markers of pathologically elevated ICP have not been specifically validated in paediatric studies. Here in, we describe an objective, non-invasive, quantitative method of stratifying which patients are likely to require invasive monitoring. A retrospective review of patients admitted to Cambridge University Hospital’s Paediatric Intensive Care Unit between January 2009 and December 2016 with a TBI requiring invasive neurosurgical monitoring was performed. Radiological biomarkers of TBI (basal cistern volume, ventricular volume, volume of extra-axial haematomas) from CT scans were measured and correlated with epochs of continuous high frequency variables of pressure monitoring around the time of imaging. 38 patients were identified. Basal cistern volume was found to correlate significantly with opening ICP (r = −0.53, p < 0.001). The optimal threshold of basal cistern volume for predicting high ICP ($$\ge $$

≥

20 mmHg) was a relative volume of 0.0055 (sensitivity 79%, specificity 80%). Ventricular volume and extra-axial haematoma volume did not correlate significantly with opening ICP. Our results show that the features of pathologically elevated ICP in children may differ considerably from those validated in adults. The development of quantitative parameters can help to predict which patients would most benefit from invasive neurosurgical monitoring and we present a novel radiological threshold for this.
Suppression of glioblastoma by a drug cocktail reprogramming tumor cells into neuronal like cells
Authors: Gao Longfei , Huang Shichao , Zhang Hong , Hua Wei , Xin Shunmei , Cheng Lin , Guan Wuqiang , Yu Yongchun , Mao Ying , Pei Gang 
Published: March 2019

AbstractGlioblastoma (GBM) is the most common and aggressive malignant tumor in adult brain. Even with the current standard therapy including surgical resection followed by postoperative radiotherapy and chemotherapy with temozolomide (Temo), GBM patients still have a poor median survival. Reprogramming of tumor cells into non-malignant cells might be a promising therapeutic strategy for malignant tumors, including GBM. Based on previous studies using small molecules to reprogram astrocytes into neuronal cells, here we further identified a FTT cocktail of three commonly used drugs (Fasudil, Tranilast, and Temo) to reprogram patient-derived GBM cells, either cultured in serum containing or serum-free medium, into neuronal like cells. FTT-treated GBM cells displayed a neuronal like morphology, expressed neuronal genes, exhibited neuronal electrophysiological properties, and showed attenuated malignancy. More importantly, FTT cocktail more significantly suppressed tumor growth and prolonged survival in GBM patient derived xenograft than Temo alone. Our study provided preclinical evidence that the neuronal reprogramming drug cocktail might be a promising strategy to improve the existing treatment for GBM.
Widely targeted metabolome and transcriptome landscapes of Allium fistulosum–A. cepa chromosome addition lines revealed a flavonoid hot spot on chromosome 5A
Authors: Abdelrahman Mostafa , Hirata Sho , Sawada Yuji , Hirai Masami Yokota , Sato Shusei , Hirakawa Hideki , Mine Yoko , Tanaka Keisuke , Shigyo Masayoshi 
Published: March 2019

AbstractHere, we report a comprehensive analysis of the widely targeted metabolome and transcriptome profiles of Allium fistulosum L. (FF) with the single extra chromosome of shallot [A. cepa L. Aggregatum group (AA)] to clarify the novel gene functions in flavonoid biosynthesis. An exhaustive metabolome analysis was performed using the selected reaction monitoring mode of liquid chromatography–tandem quadrupole mass spectrometry, revealing a specific accumulation of quercetin, anthocyanin and flavone glucosides in AA and FF5A. The addition of chromosome 5A from the shallot to A. fistulosum induced flavonoid accumulation in the recipient species, which was associated with the upregulation of several genes including the dihydroflavonol 4-reductase, chalcone synthase, flavanone 3-hydroxylase, UDP-glucose flavonoid-3-O-glucosyltransferase, anthocyanin 5-aromatic acyltransferase-like, pleiotropic drug resistance-like ATP binding cassette transporter, and MYB14 transcriptional factor. Additionally, an open access Allium Transcript Database (Allium TDB, http://alliumtdb.kazusa.or.jp) was generated by using RNA-Seq data from different genetic stocks including the A. fistulosum–A. cepa monosomic addition lines. The functional genomic approach presented here provides an innovative means of targeting the gene responsible for flavonoid biosynthesis in A. cepa. The understanding of flavonoid compounds and biosynthesis-related genes would facilitate the development of noble Allium varieties with unique chemical constituents and, subsequently, improved plant stress tolerance and human health benefits.
Optimal cardiac strategy based on the history of myocardial infarction in type 2 diabetic patients with coronary artery disease
Authors: Tsujimoto Tetsuro , Kajio Hiroshi 
Published: March 2019

AbstractThe aim of this study was to evaluate the association between the cardiac treatment strategy and cardiac event risk in type 2 diabetic patients with coronary artery disease (CAD) based on the history of myocardial infarction. Using Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial data, a Cox proportional hazard model was used for calculating hazard ratios (HRs) for major cardiac events in patients receiving early revascularization or intensive medical therapy. Patients without (n = 1,557) and with myocardial infarction (n = 736) were separately analyzed. In patients without myocardial infarction, risk of major cardiac events was similar for percutaneous coronary intervention and intensive medical therapy groups, whereas it was significantly lower in the coronary artery bypass grafting group than in the intensive medical therapy group (HR: 0.48, 95% confidence interval [95%CI]: 0.30–0.76, P = 0.002). Conversely, in patients with myocardial infarction, risk of major cardiac events was significantly higher in the early revascularization group than in the intensive medical therapy group (HR: 1.47, 95%CI: 1.03–2.11, P = 0.03). In type 2 diabetic patients with CAD, benefits of early revascularization were observed only in those without previous myocardial infarction. For patients with previous myocardial infarction, intensive medical therapy exerted superior benefits.