bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression
Authors: Sng Ming Keat , Chan Jeremy Soon Kiat , Teo Ziqiang , Phua Terri , Tan Eddie Han Pin , Wee Jonathan Wei Kiat , Koh Nikki Jun Ning , Tan Chek Kun , Chen Jia Peng , Pal Mintu , Tong Benny Meng Kiat , Tnay Ya Lin , Ng Xuan Rui , Zhu Pengcheng , Chiba Shunsuke , Wang Xiaomeng , Wahli Walter , Tan Nguan Soon 
Published: April 2018

AbstractConnective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre-Pparb/d−/−) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 (Lrg1), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of Lrg1 by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre-Pparb/d−/− mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.
Dop1 enhances conspecific olfactory attraction by inhibiting miR-9a maturation in locusts
Authors: Guo Xiaojiao , Ma Zongyuan , Du Baozhen , Li Ting , Li Wudi , Xu Lingling , He Jing , Kang Le 
Published: April 2018

AbstractDopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the mechanism by which Dop1 modulates this process remains unknown to date. Here, we identify differentially expressed small RNAs associated with locust olfactory attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis and qPCR validation reveal that Dop1 activation and inhibition downregulates and upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in solitarious locusts increases their attraction to gregarious volatiles, whereas miR-9a overexpression in gregarious locusts reduces olfactory attraction. Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression through inducing the dissociation of La protein from pre-miR-9a and resulting in miR-9a maturation inhibition. Our results reveal a Dop1–miR-9a–AC2 circuit that modulates locust olfactory attraction underlying aggregation. This study suggests that miRNAs act as key messengers in the GPCR signaling.
High-capacity optical long data memory based on enhanced Young’s modulus in nanoplasmonic hybrid glass composites
Authors: Zhang Qiming , Xia Zhilin , Cheng Yi-Bing , Gu Min 
Published: April 2018

AbstractEmerging as an inevitable outcome of the big data era, long data are the massive amount of data that captures changes in the real world over a long period of time. In this context, recording and reading the data of a few terabytes in a single storage device repeatedly with a century-long unchanged baseline is in high demand. Here, we demonstrate the concept of optical long data memory with nanoplasmonic hybrid glass composites. Through the sintering-free incorporation of nanorods into the earth abundant hybrid glass composite, Young’s modulus is enhanced by one to two orders of magnitude. This discovery, enabling reshaping control of plasmonic nanoparticles of multiple-length allows for continuous multi-level recording and reading with a capacity over 10 terabytes with no appreciable change of the baseline over 600 years, which opens new opportunities for long data memory that affects the past and future.
Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance
Authors: Meyer Melissa A. , Baer John M. , Knolhoff Brett L. , Nywening Timothy M. , Panni Roheena Z. , Su Xinming , Weilbaecher Katherine N. , Hawkins William G. , Ma Cynthia , Fields Ryan C. , Linehan David C. , Challen Grant A. , Faccio Roberta , Aft Rebecca L. , DeNardo David G. 
Published: April 2018

AbstractTumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid cells can impair tumor immunity. As myeloid cells and conventional dendritic cells (cDCs) are derived from the same progenitors, we postulated that myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes human CD141+DCs and mouse CD103+DCs, supports anti-tumor immunity by stimulating CD8+T-cell responses. Here, to understand how cDC1 development changes during tumor progression, we investigated cDC bone marrow progenitors. We found localized breast and pancreatic cancers induce systemic decreases in cDC1s and their progenitors. Mechanistically, tumor-produced granulocyte-stimulating factor downregulates interferon regulatory factor-8 in cDC progenitors, and thus results in reduced cDC1 development. Tumor-induced reductions in cDC1 development impair anti-tumor CD8+T-cell responses and correlate with poor patient outcomes. These data suggest immune surveillance can be impaired by tumor-induced alterations in cDC development.
Design of high-strength refractory complex solid-solution alloys
Authors: Singh Prashant , Sharma Aayush , Smirnov A. V. , Diallo Mouhamad S. , Ray Pratik K. , Balasubramanian Ganesh , Johnson Duane D. 
Published: April 2018

AbstractNickel-based superalloys and near-equiatomic high-entropy alloys containing molybdenum are known for higher temperature strength and corrosion resistance. Yet, complex solid-solution alloys offer a huge design space to tune for optimal properties at slightly reduced entropy. For refractory Mo-W-Ta-Ti-Zr, we showcase KKR electronic structure methods via the coherent-potential approximation to identify alloys over five-dimensional design space with improved mechanical properties and necessary global (formation enthalpy) and local (short-range order) stability. Deformation is modeled with classical molecular dynamic simulations, validated from our first-principle data. We predict complex solid-solution alloys of improved stability with greatly enhanced modulus of elasticity (3× at 300 K) over near-equiatomic cases, as validated experimentally, and with higher moduli above 500 K over commercial alloys (2.3× at 2000 K). We also show that optimal complex solid-solution alloys are not described well by classical potentials due to critical electronic effects.
Cardiac arrhythmia and neuroexcitability gene variants in resected brain tissue from patients with sudden unexpected death in epilepsy (SUDEP)
Authors: Friedman Daniel , Kannan Kasthuri , Faustin Arline , Shroff Seema , Thomas Cheddhi , Heguy Adriana , Serrano Jonathan , Snuderl Matija , Devinsky Orrin 
Published: April 2018

AbstractSudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in young adults. The exact mechanisms are unknown but death often follows a generalized tonic–clonic seizure. Proposed mechanisms include seizure-related respiratory, cardiac, autonomic, and arousal dysfunction. Genetic drivers underlying SUDEP risk are largely unknown. To identify potential SUDEP risk genes, we compared whole-exome sequences (WES) derived from formalin-fixed paraffin embedded surgical brain specimens of eight epilepsy patients who died from SUDEP with seven living controls matched for age at surgery, sex, year of surgery and lobe of resection. We compared identified variants from both groups filtering known polymorphisms from publicly available data as well as scanned for epilepsy and candidate SUDEP genes. In the SUDEP cohort, we identified mutually exclusive variants in genes involved in µ-opiod signaling, gamma-aminobutyric acid (GABA) and glutamate-mediated synaptic signaling, including ARRB2, ITPR1, GABRR2, SSTR5, GRIK1, CTNAP2, GRM8, GNAI2 and GRIK5. In SUDEP patients we also identified variants in genes associated with cardiac arrhythmia, including KCNMB1, KCNIP1, DPP6, JUP, F2, and TUBA3D, which were not present in living epilepsy controls. Our data shows that genomic analysis of brain tissue resected for seizure control can identify potential genetic biomarkers of SUDEP risk.
Rhythmic abilities and musical training in Parkinson’s disease: do they help?
Authors: Cochen De Cock V. , Dotov D. G. , Ihalainen P. , Bégel V. , Galtier F. , Lebrun C. , Picot M. C. , Driss V. , Landragin N. , Geny C. , Bardy B. , Dalla Bella S. 
Published: April 2018

AbstractRhythmic auditory cues can immediately improve gait in Parkinson’s disease. However, this effect varies considerably across patients. The factors associated with this individual variability are not known to date. Patients’ rhythmic abilities and musicality (e.g., perceptual and singing abilities, emotional response to music, and musical training) may foster a positive response to rhythmic cues. To examine this hypothesis, we measured gait at baseline and with rhythmic cues in 39 non-demented patients with Parkinson’s disease and 39 matched healthy controls. Cognition, rhythmic abilities and general musicality were assessed. A response to cueing was qualified as positive when the stimulation led to a clinically meaningful increase in gait speed. We observed that patients with positive response to cueing (n = 17) were more musically trained, aligned more often their steps to the rhythmic cues while walking, and showed better music perception as well as poorer cognitive flexibility than patients with non-positive response (n = 22). Gait performance with rhythmic cues worsened in six patients. We concluded that rhythmic and musical skills, which can be modulated by musical training, may increase beneficial effects of rhythmic auditory cueing in Parkinson’s disease. Screening patients in terms of musical/rhythmic abilities and musical training may allow teasing apart patients who are likely to benefit from cueing from those who may worsen their performance due to the stimulation.
Response of Aquatic Bacterial Communities to Hydraulic Fracturing in Northwestern Pennsylvania: A Five-Year Study
Authors: Ulrich Nikea , Kirchner Veronica , Drucker Rebecca , Wright Justin R. , McLimans Christopher J. , Hazen Terry C. , Campa Maria F. , Grant Christopher J. , Lamendella Regina 
Published: April 2018

AbstractHorizontal drilling and hydraulic fracturing extraction procedures have become increasingly present in Pennsylvania where the Marcellus Shale play is largely located. The potential for long-term environmental impacts to nearby headwater stream ecosystems and aquatic bacterial assemblages is still incompletely understood. Here, we perform high-throughput sequencing of the 16 S rRNA gene to characterize the bacterial community structure of water, sediment, and other environmental samples (n = 189) from 31 headwater stream sites exhibiting different histories of fracking activity in northwestern Pennsylvania over five years (2012–2016). Stream pH was identified as a main driver of bacterial changes within the streams and fracking activity acted as an environmental selector for certain members at lower taxonomic levels within stream sediment. Methanotrophic and methanogenic bacteria (i.e. Methylocystaceae, Beijerinckiaceae, and Methanobacterium) were significantly enriched in sites exhibiting Marcellus shale activity (MSA+) compared to MSA− streams. This study highlighted potential sentinel taxa associated with nascent Marcellus shale activity and some of these taxa remained as stable biomarkers across this five-year study. Identifying the presence and functionality of specific microbial consortia within fracking-impacted streams will provide a clearer understanding of the natural microbial community’s response to fracking and inform in situ remediation strategies.
A transmission electron microscope study of Néel skyrmion magnetic textures in multilayer thin film systems with large interfacial chiral interaction
Authors: McVitie S. , Hughes S. , Fallon K. , McFadzean S. , McGrouther D. , Krajnak M. , Legrand W. , Maccariello D. , Collin S. , Garcia K. , Reyren N. , Cros V. , Fert A. , Zeissler K. , Marrows C. H. 
Published: April 2018

AbstractSkyrmions in ultrathin ferromagnetic metal (FM)/heavy metal (HM) multilayer systems produced by conventional sputtering methods have recently generated huge interest due to their applications in the field of spintronics. The sandwich structure with two correctly-chosen heavy metal layers provides an additive interfacial exchange interaction which promotes domain wall or skyrmion spin textures that are Néel in character and with a fixed chirality. Lorentz transmission electron microscopy (TEM) is a high resolution method ideally suited to quantitatively image such chiral magnetic configurations. When allied with physical and chemical TEM analysis of both planar and cross-sectional samples, key length scales such as grain size and the chiral variation of the magnetisation variation have been identified and measured. We present data showing the importance of the grain size (mostly < 10 nm) measured from direct imaging and its potential role in describing observed behaviour of isolated skyrmions (diameter < 100 nm). In the latter the region in which the magnetization rotates is measured to be around 30 nm. Such quantitative information on the multiscale magnetisation variations in the system is key to understanding and exploiting the behaviour of skyrmions for future applications in information storage and logic devices.
Bordetella pseudohinzii targets cilia and impairs tracheal cilia-driven transport in naturally acquired infection in mice
Authors: Perniss Alexander , Schmidt Nadine , Gurtner Corinne , Dietert Kristina , Schwengers Oliver , Weigel Markus , Hempe Julia , Ewers Christa , Pfeil Uwe , Gärtner Ulrich , Gruber Achim D. , Hain Torsten , Kummer Wolfgang 
Published: April 2018

AbstractSeveral species of the Gram-negative genus Bordetella are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. Very recently, a novel atypical species, Bordetella pseudohinzii, was isolated from laboratory mice. These mice presented no obvious clinical symptoms but elevated numbers of neutrophils in bronchoalveolar lavage fluid and inflammatory signs in histopathology. We noted that this species can occur at high prevalence in a mouse facility despite regular pathogen testing according to the FELASA-recommendations. Affected C57BL/6 J mice had, in addition to the reported pulmonary alterations, tracheal inflammation with reduced numbers of ciliated cells, slower ciliary beat frequency, and largely (>50%) compromised cilia-driven particle transport speed on the mucosal surface, a primary innate defence mechanism. In an in vitro-model, Bordetella pseudohinzii attached to respiratory kinocilia, impaired ciliary function within 4 h and caused epithelial damage within 24 h. Regular testing for this ciliotropic Bordetella species and excluding it from colonies that provide mice for lung research shall be recommended. On the other hand, controlled colonization and infection with Bordetella pseudohinzii may serve as an experimental model to investigate mechanisms of mucociliary clearance and microbial strategies to escape from this primary innate defence response.
The tremendous potential of deep-sea mud as a source of rare-earth elements
Authors: Takaya Yutaro , Yasukawa Kazutaka , Kawasaki Takehiro , Fujinaga Koichiro , Ohta Junichiro , Usui Yoichi , Nakamura Kentaro , Kimura Jun-Ichi , Chang Qing , Hamada Morihisa , Dodbiba Gjergj , Nozaki Tatsuo , Iijima Koichi , Morisawa Tomohiro , Kuwahara Takuma , Ishida Yasuyuki , Ichimura Takao , Kitazume Masaki , Fujita Toyohisa , Kato Yasuhiro 
Published: April 2018

AbstractPotential risks of supply shortages for critical metals including rare-earth elements and yttrium (REY) have spurred great interest in commercial mining of deep-sea mineral resources. Deep-sea mud containing over 5,000 ppm total REY content was discovered in the western North Pacific Ocean near Minamitorishima Island, Japan, in 2013. This REY-rich mud has great potential as a rare-earth metal resource because of the enormous amount available and its advantageous mineralogical features. Here, we estimated the resource amount in REY-rich mud with Geographical Information System software and established a mineral processing procedure to greatly enhance its economic value. The resource amount was estimated to be 1.2 Mt of rare-earth oxide for the most promising area (105 km2 × 0–10 mbsf), which accounts for 62, 47, 32, and 56 years of annual global demand for Y, Eu, Tb, and Dy, respectively. Moreover, using a hydrocyclone separator enabled us to recover selectively biogenic calcium phosphate grains, which have high REY content (up to 22,000 ppm) and constitute the coarser domain in the grain-size distribution. The enormous resource amount and the effectiveness of the mineral processing are strong indicators that this new REY resource could be exploited in the near future.
Targeting the polyadenylation factor EhCFIm25 with RNA aptamers controls survival in Entamoeba histolytica
Authors: Ospina-Villa Juan David , Dufour Alexandre , Weber Christian , Ramirez-Moreno Esther , Zamorano-Carrillo Absalom , Guillen Nancy , Lopez-Camarillo César , Marchat Laurence A. 
Published: April 2018

AbstractMessenger RNA 3′-end polyadenylation is an important regulator of gene expression in eukaryotic cells. In our search for new ways of treating parasitic infectious diseases, we looked at whether or not alterations in polyadenylation might control the survival of Entamoeba histolytica (the agent of amoebiasis in humans). We used molecular biology and computational tools to characterize the mRNA cleavage factor EhCFIm25, which is essential for polyadenylation in E. histolytica. By using a strategy based on the systematic evolution of ligands by exponential enrichment, we identified single-stranded RNA aptamers that target EhCFIm25. The results of RNA-protein binding assays showed that EhCFIm25 binds to the GUUG motif in vitro, which differs from the UGUA motif bound by the homologous human protein. Accordingly, docking experiments and molecular dynamic simulations confirmed that interaction with GUUG stabilizes EhCFIm25. Incubating E. histolytica trophozoites with selected aptamers inhibited parasite proliferation and rapidly led to cell death. Overall, our data indicate that targeting EhCFIm25 is an effective way of limiting the growth of E. histolytica in vitro. The present study is the first to have highlighted the potential value of RNA aptamers for controlling this human pathogen.
Fine Needle-Diathermy Regresses Pathological Corneal (Lymph)Angiogenesis and Promotes High-Risk Corneal Transplant Survival
Authors: Le Viet Nhat Hung , Schneider Ann-Charlott , Scholz Rebecca , Bock Felix , Cursiefen Claus 
Published: April 2018

AbstractPathological corneal hem- and lymphangiogenesis are prime risk factors for corneal graft rejection. Fine needle-diathermy (FND) is an option to regress corneal blood vessels; however, whether this treatment besides clinically visible blood vessels also affects invisible lymphatic vessels is so far unknown. Here we test the hypothesis that FND destroys not only blood but also lymphatic vessels, thereby promotes corneal high-risk graft survival. The effect of FND was studied in vivo using BALB/c mice and the model of suture-induced corneal neovascularization. Mice were divided into three groups: FND, ANTI (anti-inflammatory therapy) and NON (control). Five, 7, 10 and 20 days after cauterization, corneas were harvested and stained with LYVE-1, CD31 to quantify (lymph)angiogenesis. The long-term survival of allografts was compared between the three groups. FND caused significant regression of both blood and lymphatic vessels compared to the control group at all time points (p < 0.05) with the most obvious effect at day 7 (p < 0.01). Graft survival was significantly prolonged when transplants were placed into the FND pretreated group (p < 0.0001). The effect of the anti-inflammatory therapy alone was less effective compared to FND (p < 0.05). This novel lymphangioregressive effect of FND can be used clinically to precondition high-risk recipients to promote graft survival.
GC–MS-based urinary organic acid profiling reveals multiple dysregulated metabolic pathways following experimental acute alcohol consumption
Authors: Irwin Cindy , Mienie Lodewyk J. , Wevers Ron A. , Mason Shayne , Westerhuis Johan A. , van Reenen Mari , Reinecke Carolus J. 
Published: April 2018

AbstractMetabolomics studies of diseases associated with chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways. Moreover, the holistic approach of such studies gives insights into the pathophysiological risk factors associated with chronic alcohol-induced disability, morbidity and mortality. Here, we report on a GC–MS-based organic acid profiling study on acute alcohol consumption. Our investigation — involving 12 healthy, moderate-drinking young men — simulated a single binge drinking event, and indicated its metabolic consequences. We generated time-dependent data that predicted the metabolic pathophysiology of the alcohol intervention. Multivariate statistical modelling was applied to the longitudinal data of 120 biologically relevant organic acids, of which 13 provided statistical evidence of the alcohol effect. The known alcohol-induced increased NADH:NAD+ ratio in the cytosol of hepatocytes contributed to the global dysregulation of several metabolic reactions of glycolysis, ketogenesis, the Krebs cycle and gluconeogenesis. The significant presence of 2-hydroxyisobutyric acid supports the emerging paradigm that this compound is an important endogenous metabolite. Its metabolic origin remains elusive, but recent evidence indicated 2-hydroxyisobutyrylation as a novel regulatory modifier of histones. Metabolomics has thus opened an avenue for further research on the reprogramming of metabolic pathways and epigenetic networks in relation to the severe effects of alcohol consumption.
Study of mucin turnover in the small intestine by in vivo labeling
Authors: Schneider Hannah , Pelaseyed Thaher , Svensson Frida , Johansson Malin E. V. 
Published: April 2018

AbstractMucins are highly glycosylated proteins which protect the epithelium. In the small intestine, the goblet cell-secreted Muc2 mucin constitutes the main component of the loose mucus layer that traps luminal material. The transmembrane mucin Muc17 forms part of the carbohydrate-rich glycocalyx covering intestinal epithelial cells. Our study aimed at investigating the turnover of these mucins in the small intestine by using in vivo labeling of O-glycans with N-azidoacetylgalactosamine. Mice were injected intraperitoneally and sacrificed every hour up to 12 hours and at 24 hours. Samples were fixed with preservation of the mucus layer and stained for Muc2 and Muc17. Turnover of Muc2 was slower in goblet cells of the crypts compared to goblet cells along the villi. Muc17 showed stable expression over time at the plasma membrane on villi tips, in crypts and at crypt openings. In conclusion, we have identified different subtypes of goblet cells based on their rate of mucin biosynthesis and secretion. In order to protect the intestinal epithelium from chemical and bacterial hazards, fast and frequent renewal of the secreted mucus layer in the villi area is combined with massive secretion of stored Muc2 from goblet cells in the upper crypt.