bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel upregulation of amyloid-β precursor protein (APP) by microRNA-346 via targeting of APP mRNA 5′-untranslated region: Implications in Alzheimer’s disease
Authors: Long Justin M. , Maloney Bryan , Rogers Jack T. , Lahiri Debomoy K. 
Published: November 2018

AbstractIn addition to the devastating symptoms of dementia, Alzheimer’s disease (AD) is characterized by accumulation of the processing products of the amyloid-β (Aβ) peptide precursor protein (APP). APP’s non-pathogenic functions include regulating intracellular iron (Fe) homeostasis. MicroRNAs are small (~ 20 nucleotides) RNA species that instill specificity to the RNA-induced silencing complex (RISC). In most cases, RISC inhibits mRNA translation through the 3′-untranslated region (UTR) sequence. By contrast, we report a novel activity of miR-346: specifically, that it targets the APP mRNA 5′-UTR to upregulate APP translation and Aβ production. This upregulation is reduced but not eliminated by knockdown of argonaute 2. The target site for miR-346 overlaps with active sites for an iron-responsive element (IRE) and an interleukin-1 (IL-1) acute box element. IREs interact with iron response protein1 (IRP1), an iron-dependent translational repressor. In primary human brain cultures, miR-346 activity required chelation of Fe. In addition, miR-346 levels are altered in late-Braak stage AD. Thus, miR-346 plays a role in upregulation of APP in the CNS and participates in maintaining APP regulation of Fe, which is disrupted in late stages of AD. Further work will be necessary to integrate other metals, and IL-1 into the Fe-miR-346 activity network. We, thus, propose a “FeAR” (Fe, APP, RNA) nexus in the APP 5′-UTR that includes an overlapping miR-346-binding site and the APP IRE. When a “healthy FeAR” exists, activities of miR-346 and IRP/Fe interact to maintain APP homeostasis. Disruption of an element that targets the FeAR nexus would lead to pathogenic disruption of APP translation and protein production.
A pilot study of the clinical evidence for the methodology for prevention of oral mucositis during cancer chemotherapy by measuring salivary excretion of 5-fluorouracil
Authors: Kumagai Akiko , Iijima Shin , Nomiya Takayuki , Furuya Izuru , Ohashi Yu , Tsunoda Koichi , Onodera Kei , Tsunoda Naoko , Komatsu Yuko , Hirano Taifu 
Published: November 2018

AbstractObjective to re-examine measures to prevent oral mucositis caused by drugs in head and neck cancer patients during cancer treatment by measuring salivary excretion of 5-fluorouracil. Saliva, blood, and urine were simultaneously collected from oral cancer patients and breast cancer patient at the point in time of before, during, and after the administration of 5-FU, then the 5-FU levels of the samples were quantitatively analysed using LC-MS/MS. In all patients, the 5-FU levels in saliva and serum peaked at 30 min to 3 h after the start of 5-FU treatment, and high levels were maintained throughout the administration of the drug. With regard to urinary 5-FU levels, they remained high from 3 to 120 h after the start of 5-FU treatment. After the completion of 5-FU treatment, even though it not appeared in the patients’ serum and urine promptly, 5-FU was detected in saliva at 12 h after the completion of 5-FU treatment in one oral cancer patient and at 48 h after the completion of 5-FU treatment in the breast cancer patient. It was suggested that the level of hydration after the completion of chemotherapy may be involved in the differences in 5-FU excretion.
Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne
Authors: Petridis Christos , Navarini Alexander A. , Dand Nick , Saklatvala Jake , Baudry David , Duckworth Michael , Allen Michael H. , Curtis Charles J. , Lee Sang Hyuck , Burden A. David , Layton Alison , Bataille Veronique , Pink Andrew E. ,   The Acne Genetic Study Group, Alexandroff Anton , Anstey Alex , Azad Jaskiran , Aziz Omar , Burrows Nigel , Butt Aamir , Cartwright Peter , Chapman Anna , Clayton Timothy H. , Cliff Sandeep , Cutler Tim , Daly Brigid , Darvay Amrit , DeGiovanni Claudia , Downs Anthony , Dwyer Colm , English John , Ferguson Adam , Fleming Colin , Fraser-Andrews Elizabeth , Goodfield Mark , Grattan Clive E. , Hempel Hartmut , Hood Sue , Hughes Bronwyn , Ladoyanni Evmorfia , Lyon Calum , Mahmud Ali , Malik Moshin , Mallon Eleanor , Meggitt Simon , Messenger Andrew , Moosa Yaaseen , Munn Stephanie , Ormerod Anthony , Rallan Deepak , Ross Janet , Salvary Ingrid , Wachsmuth Rachel , Wahie Shyamal , Walton Shernaz , Walsh Sarah , Williamson Diane , Willis Carolyn , Carlavan Isabelle , Voegel Johannes J. , Spector Timothy D. , Trembath Richard C. , McGrath John A. , Smith Catherine H. , Barker Jonathan N. , Simpson Michael A. 
Published: November 2018

AbstractAcne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.
Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor
Authors: Infield Daniel T. , Matulef Kimberly , Galpin Jason D. , Lam Kin , Tajkhorshid Emad , Ahern Christopher A. , Valiyaveetil Francis I. 
Published: November 2018

AbstractMembrane proteins are universal signal decoders. The helical transmembrane segments of these proteins play central roles in sensory transduction, yet the mechanistic contributions of secondary structure remain unresolved. To investigate the role of main-chain hydrogen bonding on transmembrane function, we encoded amide-to-ester substitutions at sites throughout the S4 voltage-sensing segment ofShakerpotassium channels, a region that undergoes rapid, voltage-driven movement during channel gating. Functional measurements of ester-harboring channels highlight a transitional region between α-helical and 310segments where hydrogen bond removal is particularly disruptive to voltage-gating. Simulations of an active voltage sensor reveal that this region features a dynamic hydrogen bonding pattern and that its helical structure is reliant upon amide support. Overall, the data highlight the specialized role of main-chain chemistry in the mechanism of voltage-sensing; other catalytic transmembrane segments may enlist similar strategies in signal transduction mechanisms.
Efficient labeling and imaging of protein-coding genes in living cells using CRISPR-Tag
Authors: Chen Baohui , Zou Wei , Xu Haiyue , Liang Ying , Huang Bo 
Published: November 2018

AbstractThe lack of efficient tools to image non-repetitive genes in living cells has limited our ability to explore the functional impact of the spatiotemporal dynamics of such genes. Here, we addressed this issue by developing a CRISPR-Tag system using one to four highly active sgRNAs to specifically label protein-coding genes with a high signal-to-noise ratio for visualization by wide-field fluorescence microscopy. Our approach involves assembling a CRISPR-Tag within the intron region of a fluorescent protein and then integrating this cassette to N- or C-terminus of a specific gene, which enables simultaneous real-time imaging of protein and DNA of human protein-coding genes, such as HIST2H2BE, LMNA and HSPA8 in living cells. This CRISPR-Tag system, with a minimal size of ~250 bp DNA tag, represents an easily and broadly applicable technique to study the spatiotemporal organization of genomic elements in living cells.
Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment
Authors: Saggu Gurpanna , Okubo Koshu , Chen Yunfeng , Vattepu Ravi , Tsuboi Naotake , Rosetti Florencia , Cullere Xavier , Washburn Nathaniel , Tahir Suhail , Rosado Aaron M. , Holland Steven M. , Anthony Robert M. , Sen Mehmet , Zhu Cheng , Mayadas Tanya N. 
Published: November 2018

AbstractVascular-deposited IgG immune complexes promote neutrophil recruitment, but how this process is regulated is still unclear. Here we show that the CD18 integrin Mac-1, in its bent state, interacts with the IgG receptor FcγRIIA incisto reduce the affinity of FcγRIIA for IgG and inhibit FcγRIIA-mediated neutrophil recruitment under flow. The Mac-1 rs1143679 lupus-risk variant reverses Mac-1 inhibition of FcγRIIA, as does a Mac-1 ligand and a mutation in Mac-1’s ligand binding αI-domain. Sialylated complex glycans on FcγRIIA interact with the αI-domain via divalent cations, and this interaction is required for FcγRIIA inhibition by Mac-1. Human neutrophils deficient in CD18 integrins exhibit augmented FcγRIIA-dependent recruitment to IgG-coated endothelium. In mice, CD18 integrins on neutrophils dampen IgG-mediated neutrophil accumulation in the kidney. In summary,cisinteraction between sialylated FcγRIIA and the αI-domain of Mac-1 alters the threshold for IgG-mediated neutrophil recruitment. A disruption of this interaction may increase neutrophil influx in autoimmune diseases.
Charge transfer drives anomalous phase transition in ceria
Authors: Zhu He , Yang Chao , Li Qiang , Ren Yang , Neuefeind Joerg C. , Gu Lin , Liu Huibiao , Fan Longlong , Chen Jun , Deng Jinxia , Wang Na , Hong Jiawang , Xing Xianran 
Published: November 2018

AbstractCeria has conventionally been thought to have a cubic fluorite structure with stable geometric and electronic properties over a wide temperature range. Here we report a reversible tetragonal (P42/nmc) to cubic (Fm-3m) phase transition in nanosized ceria, which triggers negative thermal expansion in the temperature range of −25 °C–75 °C. Local structure investigations using neutron pair distribution function and Raman scatterings reveal that the tetragonal phase involves a continuous displacement of O2− anions along the fourfold axis, while the first-principles calculations clearly show oxygen vacancies play a pivotal role in stabilizing the tetragonal ceria. Further experiments provide evidence of a charge transfer between oxygen vacancies and 4f orbitals in ceria, which is inferred to be the mechanism behind this anomalous phase transition.
Antibiotic sensitivity reveals that wall teichoic acids mediate DNA binding during competence in Bacillus subtilis
Authors: Mirouze Nicolas , Ferret Cécile , Cornilleau Charlène , Carballido-López Rut 
Published: November 2018

AbstractDespite decades of investigation of genetic transformation in the model Gram-positive bacterium Bacillus subtilis, the factors responsible for exogenous DNA binding at the surface of competent cells remain to be identified. Here, we report that wall teichoic acids (WTAs), cell wall-anchored anionic glycopolymers associated to numerous critical functions in Gram-positive bacteria, are involved in this initial step of transformation. Using a combination of cell wall-targeting antibiotics and fluorescence microscopy, we show that competence-specific WTAs are produced and specifically localized in the competent cells to mediate DNA binding at the proximity of the transformation apparatus. Furthermore, we propose that TuaH, a putative glycosyl transferase induced during competence, modifies competence-induced WTAs in order to promote (directly or indirectly) DNA binding. On the basis of our results and previous knowledge in the field, we propose a model for DNA binding and transport during genetic transformation in B. subtilis.
Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate
Authors: Knorr Sebastian , Sinn Malte , Galetskiy Dmitry , Williams Rhys M. , Wang Changhao , Müller Nicolai , Mayans Olga , Schleheck David , Hartig Jörg S. 
Published: November 2018

AbstractLysine degradation has remained elusive in many organisms including Escherichia coli. Here we report catabolism of lysine to succinate in E. coli involving glutarate and L-2-hydroxyglutarate as intermediates. We show that CsiD acts as an α-ketoglutarate-dependent dioxygenase catalysing hydroxylation of glutarate to L-2-hydroxyglutarate. CsiD is found widespread in bacteria. We present crystal structures of CsiD in complex with glutarate, succinate, and the inhibitor N-oxalyl-glycine, demonstrating strong discrimination between the structurally related ligands. We show that L-2-hydroxyglutarate is converted to α-ketoglutarate by LhgO acting as a membrane-bound, ubiquinone-linked dehydrogenase. Lysine enters the pathway via 5-aminovalerate by the promiscuous enzymes GabT and GabD. We demonstrate that repression of the pathway by CsiR is relieved upon glutarate binding. In conclusion, lysine degradation provides an important link in central metabolism. Our results imply the gut microbiome as a potential source of glutarate and L-2-hydroxyglutarate associated with human diseases such as cancer and organic acidurias.
Engineering Saccharomyces cerevisiae for co-utilization of d-galacturonic acid and d-glucose from citrus peel waste
Authors: Protzko Ryan J. , Latimer Luke N. , Martinho Ze , de Reus Elise , Seibert Tanja , Benz J. Philipp , Dueber John E. 
Published: November 2018

AbstractPectin-rich biomasses, such as citrus peel and sugar beet pulp, hold promise as inexpensive feedstocks for microbial fermentations as enzymatic hydrolysis of their component polysaccharides can be accomplished inexpensively to yield high concentrations of fermentable sugars and d-galacturonic acid (d-galUA). In this study, we tackle a number of challenges associated with engineering a microbial strain to convert pectin-rich hydrolysates into commodity and specialty chemicals. First, we engineer d-galUA utilization into yeast, Saccharomyces cerevisiae. Second, we identify that the mechanism of d-galUA uptake into yeast is mediated by hexose transporters and that consumption of d-galUA is inhibited by d-glucose. Third, we enable co-utilization of d-galUA and d-glucose by identifying and expressing a heterologous transporter, GatA, from Aspergillus niger. Last, we demonstrate the use of this transporter for production of the platform chemical, meso-galactaric acid, directly from industrial Navel orange peel waste.
The impact of immune response on endochondral bone regeneration
Authors: Longoni A. , Knežević L. , Schepers K. , Weinans H. , Rosenberg A. J. W. P. , Gawlitta D. 
Published: November 2018

AbstractTissue engineered cartilage substitutes, which induce the process of endochondral ossification, represent a regenerative strategy for bone defect healing. Such constructs typically consist of multipotent mesenchymal stromal cells (MSCs) forming a cartilage template in vitro, which can be implanted to stimulate bone formation in vivo. The use of MSCs of allogeneic origin could potentially improve the clinical utility of the tissue engineered cartilage constructs in three ways. First, ready-to-use construct availability can speed up the treatment process. Second, MSCs derived and expanded from a single donor could be applied to treat several patients and thus the costs of the medical interventions would decrease. Finally, it would allow more control over the quality of the MSC chondrogenic differentiation. However, even though the envisaged clinical use of allogeneic cell sources for bone regeneration is advantageous, their immunogenicity poses a significant obstacle to their clinical application. The aim of this review is to increase the awareness of the role played by immune cells during endochondral ossification, and in particular during regenerative strategies when the immune response is altered by the presence of implanted biomaterials and/or cells. More specifically, we focus on how this balance between immune response and bone regeneration is affected by the implantation of a cartilaginous tissue engineered construct of allogeneic origin.
PynPoint: a modular pipeline architecture for processing and analysis of high-contrast imaging data
Authors: Stolker T. , Bonse M. J. , Quanz S. P. , Amara A. , Cugno G. , Bohn A. J. , Boehle A. 
Published: November 2018

Context. The direct detection and characterization of planetary and substellar companions at small angular separations is a rapidly advancing field. Dedicated high-contrast imaging instruments deliver unprecedented sensitivity, enabling detailed insights into the atmospheres of young low-mass companions. In addition, improvements in data reduction and point spread function (PSF)-subtraction algorithms are equally relevant for maximizing the scientific yield, both from new and archival data sets.
Aims. We aim at developing a generic and modular data-reduction pipeline for processing and analysis of high-contrast imaging data obtained with pupil-stabilized observations. The package should be scalable and robust for future implementations and particularly suitable for the 3–5 μm wavelength range where typically thousands of frames have to be processed and an accurate subtraction of the thermal background emission is critical.
Methods. PynPoint is written in Python 2.7 and applies various image-processing techniques, as well as statistical tools for analyzing the data, building on open-source Python packages. The current version of PynPoint has evolved from an earlier version that was developed as a PSF-subtraction tool based on principal component analysis (PCA).
Results. The architecture of PynPoint has been redesigned with the core functionalities decoupled from the pipeline modules. Modules have been implemented for dedicated processing and analysis steps, including background subtraction, frame registration, PSF subtraction, photometric and astrometric measurements, and estimation of detection limits. The pipeline package enables end-to-end data reduction of pupil-stabilized data and supports classical dithering and coronagraphic data sets. As an example, we processed archival VLT/NACO L′ and M′ data of β Pic b and reassessed the brightness and position of the planet with a Markov chain Monte Carlo analysis; we also provide a derivation of the photometric error budget.
Inter-Individual Variability in The Joint Negative Work During Running
Authors: Hashizume Satoru , Hobara Hiroaki , Kobayashi Yoshiyuki , Tada Mitsunori , Mochimaru Masaaki 
Published: November 2018

AbstractThe inter-individual variability of running technique is an important factor affecting the negative work of lower extremity joints that leads to muscle damage. Our study examines the relationships between the negative work of the lower extremity joints and the associated mechanical parameters that account for inter-individual variability in the negative work. Twenty-four young male adults were asked to run on a runway at a speed of 3.0 m·s−1. Multiple linear regression analysis was conducted to examine the relationships between the negative work and the associated mechanical parameters for each lower extremity joint. With regards to the results, 76.3% of inter-individual variability in the negative work of the hip joint was accounted for by inter-individual variabilities in the corresponding moment (25.4%) and duration (50.9%). For the knee joint, the inter-individual variabilities in the moment (40.6%), angular velocity (24.5%), and duration (23.8%) accounted for 88.9% of inter-individual variability in the negative work. The inter-individual variability in the moment of the ankle joint alone accounted for 89.3% of the inter-individual variability in the corresponding negative work. These results suggest that runners can change the negative work by adapting their running techniques to influence the relevant mechanical parameter values; however, major parameters corresponding to the change in the negative work are not the same among the lower extremity joints.
Advanced Adrenocortical Carcinoma – What to do when First-Line Therapy Fails?
Authors: Megerle Felix , Kroiss Matthias , Hahner Stefanie , Fassnacht Martin 
Published: November 2018

AbstractAdrenocortical carcinoma is a rare endocrine malignant disease with a generally unfavorable but heterogeneous prognosis. Although even in advanced stages a subset of patients experiences long-term disease stabilisation, effective systemic treatment options are limited. Mitotane is the only approved drug and the combination of etoposide, doxorubicin and cisplatin (plus mitotane) is currently considered as treatment standard for advanced adrenocortical carcinoma based on the results of a large randomized phase III trial. However, progression-free survival is often limited and further treatment options are frequently needed. Here we summarize the current knowledge about second and third-line therapeutic modalities (local and systemic) in advanced disease. Following the recent ESE-ENSAT guidelines local therapies play an important role for these patients. Regarding systemic therapies the best data are available for gemcitabine+capecitabine or streptozotocin (both with or without mitotane). Furthermore, we introduce our own approach to patients with advanced adrenocortical carcinoma based on our experience as a large multidisciplinary clinic dedicated to the care of patients with this orphan disease.
The Role of US Contrast Agents in US-Guided Biopsy of Focal Liver Lesions: A Pictorial Review
Authors: Lorentzen Torben , Nolsoe Christian 
Published: November 2018

AbstractUS-guided percutaneous biopsy of focal liver lesions (FLL) is a classic interventional procedure performed by almost all radiology units. Typically, an incidental focal finding on US or a focal indeterminate lesion diagnosed on CT, MRI or PET/CT is referred for US-guided biopsy for final diagnosis. The introduction of microbubble US contrast agents has overcome some of the limitations of standard US in diagnosing FLLs by displaying the microvasculature together with the US morphology, which has increased both the sensitivity and the specificity. The combination of CEUS and intervention is facilitated by newer US equipment providing split-screen mode, which displays the CEUS mode alongside the standard US mode simultaneously on a single monitor. The puncture line is displayed in both modes as well as on the monitor. The interventional device (i. e., biopsy needle) is typically best visualized in the standard US mode, while the characteristic tissue pattern in an FLL is typically best visualized in CEUS mode. There are 3 main categories in which CEUS has an impact on US-guided biopsy of FLLs: • CEUS improves the visualization of FLLs • CEUS improves the quality of the biopsy specimen from an FLL • CEUS reduces the need for US-guided biopsy of an FLL In the two first categories, CEUS is utilized simultaneously with US-guided biopsy to ensure correct needle targeting. In the last category, US-guided biopsy of the FLL becomes superfluous as a result of the CEUS examination.