bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-frequency random DNA insertions upon co-delivery of CRISPR-Cas9 ribonucleoprotein and selectable marker plasmid in rice
Authors: Banakar Raviraj , Eggenberger Alan L. , Lee Keunsub , Wright David A. , Murugan Karthik , Zarecor Scott , Lawrence-Dill Carolyn J. , Sashital Dipali G. , Wang Kan 
Published: December 2019

AbstractAn important advantage of delivering CRISPR reagents into cells as a ribonucleoprotein (RNP) complex is the ability to edit genes without reagents being integrated into the genome. Transient presence of RNP molecules in cells can reduce undesirable off-target effects. One method for RNP delivery into plant cells is the use of a biolistic gun. To facilitate selection of transformed cells during RNP delivery, a plasmid carrying a selectable marker gene can be co-delivered with the RNP to enrich for transformed/edited cells. In this work, we compare targeted mutagenesis in rice using three different delivery platforms: biolistic RNP/DNA co-delivery; biolistic DNA delivery; and Agrobacterium-mediated delivery. All three platforms were successful in generating desired mutations at the target sites. However, we observed a high frequency (over 14%) of random plasmid or chromosomal DNA fragment insertion at the target sites in transgenic events generated from both biolistic delivery platforms. In contrast, integration of random DNA fragments was not observed in transgenic events generated from the Agrobacterium-mediated method. These data reveal important insights that must be considered when selecting the method for genome-editing reagent delivery in plants, and emphasize the importance of employing appropriate molecular screening methods to detect unintended alterations following genome engineering.
Significant effect of HIV/HAART on oral microbiota using multivariate analysis
Authors: Griffen Ann L. , Thompson Zachary A. , Beall Clifford J. , Lilly Elizabeth A. , Granada Carolina , Treas Kelly D. , DuBois Kenneth R. , Hashmi Shahr B. , Mukherjee Chiranjit , Gilliland Aubrey E. , Vazquez Jose A. , Hagensee Michael E. , Leys Eugene J. , Fidel Paul L. 
Published: December 2019

AbstractPersons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.
Evidence for a dominantly reducing Archaean ambient mantle from two redox proxies, and low oxygen fugacity of deeply subducted oceanic crust
Authors: Aulbach Sonja , Woodland Alan B. , Stern Richard A. , Vasilyev Prokopiy , Heaman Larry M. , Viljoen K. S. 
Published: December 2019

AbstractOxygen fugacity (ƒO2) is an intensive variable implicated in a range of processes that have shaped the Earth system, but there is controversy on the timing and rate of oxidation of the uppermost convecting mantle to its present ƒO2 around the fayalite-magnetite-quartz oxygen buffer. Here, we report Fe3+/ΣFe and ƒO2 for ancient eclogite xenoliths with oceanic crustal protoliths that sampled the coeval ambient convecting mantle. Using new and published data, we demonstrate that in these eclogites, two redox proxies, V/Sc and Fe3+/ΣFe, behave sympathetically, despite different responses of their protoliths to differentiation and post-formation degassing, seawater alteration, devolatilisation and partial melting, testifying to an unexpected robustness of Fe3+/ΣFe. Therefore, these processes, while causing significant scatter, did not completely obliterate the underlying convecting mantle signal. Considering only unmetasomatised samples with non-cumulate and little-differentiated protoliths, V/Sc and Fe3+/ΣFe in two Archaean eclogite suites are significantly lower than those of modern mid-ocean ridge basalts (MORB), while a third suite has ratios similar to modern MORB, indicating redox heterogeneity. Another major finding is the predominantly low though variable estimated ƒO2 of eclogite at mantle depths, which does not permit stabilisation of CO2-dominated fluids or pure carbonatite melts. Conversely, low-ƒO2 eclogite may have caused efficient reduction of CO2 in fluids and melts generated in other portions of ancient subducting slabs, consistent with eclogitic diamond formation ages, the disproportionate frequency of eclogitic diamonds relative to the subordinate abundance of eclogite in the mantle lithosphere and the general absence of carbonate in mantle eclogite. This indicates carbon recycling at least to depths of diamond stability and may have represented a significant pathway for carbon ingassing through time.
Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry)
Authors: Lopez-Tarruella Sara , Escudero M. J. , Pollan Marina , Martín Miguel , Jara Carlos , Bermejo Begoña , Guerrero-Zotano Angel , García-Saenz José , Santaballa Ana , Alba Emilio , Andrés Raquel , Martínez Purificación , Calvo Lourdes , Fernández Antonio , Batista Norberto , Llombart-Cussac Antonio , Antón Antonio , Lahuerta Ainhara , de la Haba Juan , López-Vega José Manuel , Carrasco E. 
Published: December 2019

AbstractThe debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach’s outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990–2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study’s criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.
Clinical and neuroimaging disparity between Chinese and German patients with cerebral small vessel disease: a comparative study
Authors: Shu Junlong , Neugebauer Hermann , Li Fan , Lulé Dorothée , Müller Hans-Peter , Zhang Jing , Ludolph Albert C. , Huang Yining , Kassubek Jan , Zhang Wei 
Published: December 2019

AbstractEthnic disparity of cerebral small vessel disease (CSVD) has been reported previously but understanding of its clinical-anatomical is sparse. Two cohorts of CSVD patients from Peking University First Hospital, China and University Hospital of Ulm, Germany were retrospectively collected between 2013 and 2017. Visual rating scales and semiautomatic computer-assisted quantitative analysis were used to describe the neuroimaging features of CSVD, including lacunes, enlarged perivascular spaces, white matter changes and microbleeds. After exclusion of confounding neurological disorders, 165 out of 220 Chinese and 86 out of 98 German patients’ data were analyzed. Mean age of patients was 64.0 ± 11.9 years in China and 73.9 ± 10.3 years in Germany. Cognitive deficits were more prominent in the German group, mainly in the cognitive domains of language and delayed recall. Neuroimaging comparison showed that lacunes were more common and white matter lesion load was more severe in German than Chinese patients. Spatial distribution analysis suggested that Chinese patients showed more deep and infratentorial lesions (microbleeds and lacunes), while lesions in German patients were more frequently located in the lobes or subcortical white matter. In conclusion, different age of onset and anatomical distribution of lesions exist between Chinese and German CSVD patients in the observed population.
Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy
Authors: Mugahid D. A. , Sengul T. G. , You X. , Wang Y. , Steil L. , Bergmann N. , Radke M. H. , Ofenbauer A. , Gesell-Salazar M. , Balogh A. , Kempa S. , Tursun B. , Robbins C. T. , Völker U. , Chen W. , Nelson L. , Gotthardt M. 
Published: December 2019

AbstractMuscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment.
Chronic heavy alcohol consumption influences the association between genetic variants of GCK or INSR and the development of diabetes in men: A 12-year follow-up study
Authors: Jang Han Byul , Go Min Jin , Park Sang Ick , Lee Hye-Ja , Cho Seong Beom 
Published: December 2019

AbstractChronic heavy alcohol consumption is a risk factor for diabetes, which is characterized by impaired β-cell function and insulin resistance. We aimed to determine whether the longitudinal associations between genetic variants of glucokinase (GCK) and insulin receptor (INSR) and the risk of developing diabetes were influenced by chronic heavy alcohol consumption. Data were obtained from the Korean Genome and Epidemiology Study. To identify candidate variants, 1,520 subjects (726 non-drinkers and 794 heavy drinkers) were included in the baseline cross-sectional study. After excluding patients with diabetes at baseline and those with insufficient data on diabetes incidence, prospective analyses were conducted in 773 subjects (353 non-drinkers and 420 heavy drinkers). In the baseline cross-sectional study, one SNP (rs758989) in GCK and four SNPs (rs7245757, rs1035942, rs1035940, and rs2042901) in INSR were selected as candidate SNPs that interact with alcohol to affect prediabetes and diabetes. We identified that these GCK and INSR polymorphisms are affected by chronic heavy alcohol consumption and have an effect on the incidence of diabetes. The incidence of diabetes was increased in chronic heavy alcohol drinkers carrying the C allele of GCK compared with never-drinkers with the C allele (HR, 2.15; 95% CI 1.30–3.57), and was increased in chronic heavy alcohol drinkers who were not carrying the INSR haplotype (−/−) compared with never-drinkers carrying the AACT haplotype (HR, 1.98; 95% CI 1.24–3.18). Moreover, we observed that the aggravating effects on the late insulin secretion (I/G120 and I/G AUC 60–120) in individuals who were chronic heavy drinkers with C allele of GCK. In the INSR haplotype, chronic heavy drinkers not carrying AACT were associated with lower disposition index. These results potentially suggest that chronic heavy alcohol consumption induce β-cell dysfunction partially mediated by decreased GCK expression or decline of insulin sensitivity via inhibition of INSR, thereby contributing to the development of diabetes.
Promoted diffusion mechanism of Fe2.7wt.%Si-Fe10wt.%Si couples under magnetic field by atomic-scale observations
Authors: Fan L. J. , Zhong Y. B. , Xu Y. L. , Zheng T. X. , Shen Z. , Ren Z. M. 
Published: December 2019

AbstractDiffusion behavior of newly designed Fe2.7wt.%Si-Fe10wt.%Si couples at 1100 °C for up to 12 h has been investigated under the 0, 0.8 and 3 T magnetic fields. Diffusion thickness of solid solution layer and weight percent of Si on Fe2.7wt.%Si side increase significantly under a magnetic field. Application of a magnetic field promotes the diffusion of solid solution layer through the possible diffusion of vacancies mainly due to the appearance of defects, which has been demonstrated by the increased dislocation density and broadening of the typical XRD peaks. Replacement of Si sits by Fe atoms in the crystal structure leads to the appearance of Fe diffraction peaks, which has been confirmed by the increased interplanar spacings under a magnetic field. The magnetic field benefits the depinning of dislocations and leads to higher dislocation density because of the magnetoplastic effect which has been confirmed by the significantly reduced thickness of Fe2.7wt.%Si. Nano-sized Fe3Si particles precipitate in the matrix with an orientation relationship on Fe10wt.%Si side as {220}Fe3Si || {220}matrix & < 1–10 >Fe3Si || < 1–10 >matrix. Fe3Si particles pin dislocation moving and lead to higher dislocation density.
A generic workflow for Single Locus Sequence Typing (SLST) design and subspecies characterization of microbiota
Authors: Ederveen Thomas H. A. , Smits Jos P. H. , Hajo Karima , van Schalkwijk Saskia , Kouwenhoven Tessa A. , Lukovac Sabina , Wels Michiel , van den Bogaard Ellen H. , Schalkwijk Joost , Boekhorst Jos , Zeeuwen Patrick L. J. M. , van Hijum Sacha A. F. T. 
Published: December 2019

AbstractWe present TaxPhlAn, a new method and bioinformatics pipeline for design and analysis of single-locus sequence typing (SLST) markers to type and profile bacteria beyond the species-level in a complex microbial community background. TaxPhlAn can be applied to any group of phylogenetically-related bacteria, provided reference genomes are available. As TaxPhlAn requires the SLST targets identified to fit the phylogenetic pattern as determined through comprehensive evolutionary reconstruction of input genomes, TaxPhlAn allows for the identification and phylogenetic inference of new biodiversity. Here, we present a clinically relevant case study of high-resolution Staphylococcus profiling on skin of atopic dermatitis (AD) patients. We demonstrate that SLST enables profiling of cutaneous Staphylococcus members at (sub)species level and provides higher resolution than current 16S-based techniques. With the higher discriminative ability provided by our approach, we further show that the presence of Staphylococcus capitis on the skin together with Staphylococcus aureus associates with AD disease.
3D bioprinting via an in situ crosslinking technique towards engineering cartilage tissue
Authors: Galarraga Jonathan H. , Kwon Mi Y. , Burdick Jason A. 
Published: December 2019

Abstract3D bioprinting is a promising approach for the repair of cartilage tissue after damage due to injury or disease; however, the design of 3D printed scaffolds has been limited by the availability of bioinks with requisite printability, cytocompatibility, and bioactivity. To address this, we developed an approach termed in situ crosslinking that permits the printing of non-viscous, photocrosslinkable bioinks via the direct-curing of the bioink with light through a photopermeable capillary prior to deposition. Using a norbornene-modified hyaluronic acid (NorHA) macromer as a representative bioink and our understanding of thiol-ene curing kinetics with visible light, we varied the printing parameters (e.g., capillary length, flow rate, light intensity) to identify printing conditions that were optimal for the ink. The printing process was cytocompatible, with high cell viability and homogenous distribution of mesenchymal stromal cells (MSCs) observed throughout printed constructs. Over 56 days of culture in chondrogenic media, printed constructs increased in compressive moduli, biochemical content (i.e., sulfated glycosaminoglycans, collagen), and histological staining of matrix associated with cartilage tissue. This generalizable printing approach may be used towards the repair of focal defects in articular cartilage or broadly towards widespread biomedical applications across a range of photocrosslinkable bioinks that can now be printed.
Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth and Tooth Eruption in Growing Mice
Authors: Isawa Motoki , Karakawa Akiko , Sakai Nobuhiro , Nishina Saki , Kuritani Miku , Chatani Masahiro , Negishi-Koga Takako , Sato Masashi , Inoue Mitsuko , Shimada Yukie , Takami Masamichi 
Published: December 2019

AbstractThe anti-bone resorptive drugs denosumab, an anti-human-RANKL antibody, and zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, have recently been applied for treatment of pediatric patients with bone diseases, though details regarding their effects in growing children have yet to be fully elucidated. In the present study, we administered these anti-resorptive drugs to mice from the age of 1 week and continued once-weekly injections for a total of 7 times. Mice that received the anti-RANKL antibody displayed normal growth and tooth eruption, though osteopetrotic bone volume gain in long and alveolar bones was noted, while there were nearly no osteoclasts and a normal of number osteoblasts observed. In contrast, ZOL significantly delayed body growth, tooth root formation, and tooth eruption, with increased osteoclast and decreased osteoblast numbers. These findings suggest regulation of tooth eruption via osteoblast differentiation by some types of anti-resorptive drugs.
Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans
Authors: Nyimanu Duuamene , Kay Richard G. , Sulentic Petra , Kuc Rhoda E. , Ambery Philip , Jermutus Lutz , Reimann Frank , Gribble Fiona M. , Cheriyan Joseph , Maguire Janet J. , Davenport Anthony P. 
Published: December 2019

Abstract[Pyr1]apelin-13 is the predominant apelin peptide isoform in the human cardiovascular system and plasma. To date, few studies have investigated [Pyr1]apelin-13 metabolism in vivo in rats with no studies examining its stability in humans. We therefore aimed to develop an LC-MS/MS method for detection and quantification of intact [Pyr1]apelin-13 and have used this method to identify the metabolites generated in vivo in humans. [Pyr1]apelin-13 (135 nmol/min) was infused into six healthy human volunteers for 120 minutes and blood collected at time 0 and 120 minutes after infusion. Plasma was extracted in the presence of guanidine hydrochloride and analysed by LC-MS/MS. Here we report a highly sensitive, robust and reproducible method for quantification of intact [Pyr1]apelin-13 and its metabolites in human plasma. Using this method, we showed that the circulating concentration of intact peptide was 58.3 ± 10.5 ng/ml after 120 minutes infusion. We demonstrated for the first time that in humans, [Pyr1]apelin-13 was cleaved from both termini but the C-terminal was more susceptible to cleavage. Consequently, of the metabolites identified, [Pyr1]apelin-13(1–12), [Pyr1]apelin-13(1–10) and [Pyr1]apelin-13(1–6) were the most abundant. These data suggest that apelin peptides designed for use as cardiovascular therapeutics, should include modifications that minimise C-terminal cleavage.
Quantitation of the ROS production in plasma and radiation treatments of biotargets
Authors: Ji Wan-Ook , Lee Min-Ho , Kim Gon-Ho , Kim Eun-Hee 
Published: December 2019

AbstractMedical treatment utilizing non-thermal plasma is based on the production of reactive oxygen species (ROS) and their interactions with biomatters. On the basis of empirical data from practices, plasma treatment has been planned with regard to the setup of a plasma generator’s parameters, including gas combination, gas-flow rate, and applied voltage. In this study, we quantitated plasma treatment in terms of the plasma dose on the target matter, which can be contrasted with the radiation dose to targets under radiation exposure. We measured the OH radical production in cell culture medium and intracellular ROS production from plasma treatment in comparison with those from X-ray exposure. The clonogenic cell deaths from plasma and X-ray exposures were also compared. In plasma treatment, the clonogenic cell death was better predicted by intracellular ROS production rather than by medium OH production.
Quantifying the spatial risk of Avian Influenza introduction into British poultry by wild birds
Authors: Hill Andrew , Gillings Simon , Berriman Alexander , Brouwer Adam , Breed Andrew C. , Snow Lucy , Ashton Adam , Byrne Charles , Irvine Richard M. 
Published: December 2019

AbstractThe transmission of pathogens across the interface between wildlife and livestock presents a challenge to the development of effective surveillance and control measures. Wild birds, especially waterbirds such as the Anseriformes and Charadriiformes are considered to be the natural hosts of Avian Influenza (AI), and are presumed to pose one of the most likely vectors for incursion of AI into European poultry flocks. We have developed a generic quantitative risk map, derived from the classical epidemiological risk equation, to describe the relative, spatial risk of disease incursion into poultry flocks via wild birds. We then assessed the risk for AI incursion into British flocks. The risk map suggests that the majority of AI incursion risk is highly clustered within certain areas of Britain, including in the east, the south west and the coastal north-west of England. The clustering of high risk areas concentrates total risk in a relatively small land area; the top 33% of cells contribute over 80% of total incursion risk. This suggests that targeted risk-based sampling in a relatively small geographical area could be a much more effective and cost-efficient approach than representative sampling. The generic nature of the risk map method, allows rapid updating and application to other diseases transmissible between wild birds and poultry.