bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal inhibition of osteoclastogenesis by mesenchymal stem cells through the miR-4284/CXCL5 axis in ankylosing spondylitis
Authors: Liu Wenjie , Wang Peng , Xie Zhongyu , Wang Shan , Ma Mengjun , Li Jinteng , Li Ming , Cen Shuizhong , Tang Su’an , Zheng Guan , Ye Guiwen , Wu Xiaohua , Wu Yanfeng , Shen Huiyong 
Published: February 2019

AbstractAnkylosing spondylitis (AS) is a common inflammatory autoimmune disease, characterized by pathological osteogenesis. Mesenchymal stem cells (MSCs), as the main source of osteoblasts, participate in bone remodeling not only through differentiation into osteoblasts but also through indirect regulation of osteoclastogenesis. Our previous study indicated that the stronger osteogenic differentiation of MSCs from AS patients (ASMSCs) involved in pathological osteogenesis. However, whether there is any abnormality in the regulation of osteoclastogenesis by ASMSCs remains unclear. In this study, ASMSCs or MSCs from healthy donors (HDMSCs) were co-cultured with CD14 + monocytes in osteoclast induction medium. Our results demonstrated that ASMSCs exhibited a stronger capacity to inhibit osteoclastogenesis than HDMSCs. To explore underlying mechanisms, cytokine array assays were performed, showing that ASMSCs secreted more CXCL5 than HDMSCs, which was confirmed by enzyme-linked immunosorbent assays. Moreover, inhibition of osteoclastogenesis by ASMSCs was recovered by decreasing CXCL5. Besides, the inhibitory effect of CXCL5 on osteoclastogenesis was confirmed by exogenous addition. Bioinformatics analysis was applied to find the interaction between miR-4284 and CXCL5, which was verified by luciferase reporter assays. Furthermore, we used miR-4284 inhibitors or mimics to prove that the expression of CXCL5 was regulated by miR-4284. Further analysis showed that downregulation of miR-4284 in MSCs resulted in increase of CXCL5, markedly inhibiting osteoclastogenesis, whereas upregulation of miR-4284 in MSCs had the opposite effect. Our findings indicate that ASMSCs exhibit a stronger capacity to inhibit osteoclastogenesis than HDMSCs through the miR-4284/CXCL5 axis, which provide a new perspective on the mechanism of pathologic osteogenesis in AS.
A molecular mechanism for transthyretin amyloidogenesis
Authors: Yee Ai Woon , Aldeghi Matteo , Blakeley Matthew P. , Ostermann Andreas , Mas Philippe J. , Moulin Martine , de Sanctis Daniele , Bowler Matthew W. , Mueller-Dieckmann Christoph , Mitchell Edward P. , Haertlein Michael , de Groot Bert L. , Boeri Erba Elisabetta , Forsyth V. Trevor 
Published: February 2019

AbstractHuman transthyretin (TTR) is implicated in several fatal forms of amyloidosis. Many mutations of TTR have been identified; most of these are pathogenic, but some offer protective effects. The molecular basis underlying the vastly different fibrillation behaviours of these TTR mutants is poorly understood. Here, on the basis of neutron crystallography, native mass spectrometry and modelling studies, we propose a mechanism whereby TTR can form amyloid fibrils via a parallel equilibrium of partially unfolded species that proceeds in favour of the amyloidogenic forms of TTR. It is suggested that unfolding events within the TTR monomer originate at the C-D loop of the protein, and that destabilising mutations in this region enhance the rate of TTR fibrillation. Furthermore, it is proposed that the binding of small molecule drugs to TTR stabilises non-amyloidogenic states of TTR in a manner similar to that occurring for the protective mutants of the protein.
Peptide-oligourea hybrids analogue of GLP-1 with improved action in vivo
Authors: Fremaux Juliette , Venin Claire , Mauran Laura , Zimmer Robert H. , Guichard Gilles , Goudreau Sébastien R. 
Published: February 2019

AbstractPeptides have gained so much attention in the last decade that they are now part of the main strategies, with small molecules and biologics, for developing new medicines. Despite substantial progress, the successful development of peptides as drugs still requires a number of limitations to be addressed, including short in vivo half-lives and poor membrane permeability. Here, we describe the use of oligourea foldamers as tool to improve the pharmaceutical properties of GLP-1, a 31 amino acid peptide hormone involved in metabolism and glycemic control. Our strategy consists in replacing four consecutive amino acids of GLP-1 by three consecutive ureido residues by capitalizing on the structural resemblance of oligourea and α-peptide helices. The efficacy of the approach is demonstrated with three GLP-1-oligourea hybrids showing prolonged activity in vivo. Our findings should enable the use of oligoureas in other peptides to improve their pharmaceutical properties and may provide new therapeutic applications.
The Cep57-pericentrin module organizes PCM expansion and centriole engagement
Authors: Watanabe Koki , Takao Daisuke , Ito Kei K , Takahashi Mikiko , Kitagawa Daiju 
Published: February 2019

AbstractCentriole duplication occurs once per cell cycle to ensure robust formation of bipolar spindles and chromosome segregation. Each newly-formed daughter centriole remains connected to its mother centriole until late mitosis. The disengagement of the centriole pair is required for centriole duplication. However, the mechanisms underlying centriole engagement remain poorly understood. Here, we show that Cep57 is required for pericentriolar material (PCM) organization that regulates centriole engagement. Depletion of Cep57 causes PCM disorganization and precocious centriole disengagement during mitosis. The disengaged daughter centrioles acquire ectopic microtubule-organizing-center activity, which results in chromosome mis-segregation. Similar defects are observed in mosaic variegated aneuploidy syndrome patient cells with cep57 mutations. We also find that Cep57 binds to the well-conserved PACT domain of pericentrin. Microcephaly osteodysplastic primordial dwarfism disease pericentrin mutations impair the Cep57-pericentrin interaction and lead to PCM disorganization. Together, our work demonstrates that Cep57 provides a critical interface between the centriole core and PCM.
Author Correction: Recent increases in tropical cyclone intensification rates
Authors: Bhatia Kieran T. , Vecchi Gabriel A. , Knutson Thomas R. , Murakami Hiroyuki , Kossin James , Dixon Keith W. , Whitlock Carolyn E. 
Published: February 2019

The original version of this Article contained an error in the second sentence of the first paragraph of the ‘Quantile mapping’ section of the Methods, which incorrectly read ‘We primarily focus on results produced using an additive version of QDM26 by making use of R programming language code contained in the CRAN MBC package version 0.10–438.’ The correct version states ‘QDM29’ in place of ‘QDM26’. Also, the third sentence of the first paragraph of the ‘Quantile mapping’ section of the Methods originally incorrectly read ‘As reported in Appendix A of Cannon et al.26 the additive version of QDM is functionally very similar to the equidistant CDF matching algorithm of Li et al.39.’ The correct version states ‘Cannon et al.29’ in place of ‘Cannon et al.26’. This has been corrected in both the PDF and HTML versions of the Article.
Antarctic blackfin icefish genome reveals adaptations to extreme environments
Authors: Kim Bo-Mi , Amores Angel , Kang Seunghyun , Ahn Do-Hwan , Kim Jin-Hyoung , Kim Il-Chan , Lee Jun Hyuck , Lee Sung Gu , Lee Hyoungseok , Lee Jungeun , Kim Han-Woo , Desvignes Thomas , Batzel Peter , Sydes Jason , Titus Tom , Wilson Catherine A. , Catchen Julian M. , Warren Wesley C. , Schartl Manfred , Detrich H. William , Postlethwait John H. , Park Hyun 
Published: February 2019

AbstractIcefishes (suborder Notothenioidei; family Channichthyidae) are the only vertebrates that lack functional haemoglobin genes and red blood cells. Here, we report a high-quality genome assembly and linkage map for the Antarctic blackfin icefish Chaenocephalus aceratus, highlighting evolved genomic features for its unique physiology. Phylogenomic analysis revealed that Antarctic fish of the teleost suborder Notothenioidei, including icefishes, diverged from the stickleback lineage about 77 million years ago and subsequently evolved cold-adapted phenotypes as the Southern Ocean cooled to sub-zero temperatures. Our results show that genes involved in protection from ice damage, including genes encoding antifreeze glycoprotein and zona pellucida proteins, are highly expanded in the icefish genome. Furthermore, genes that encode enzymes that help to control cellular redox state, including members of the sod3 and nqo1 gene families, are expanded, probably as evolutionary adaptations to the relatively high concentration of oxygen dissolved in cold Antarctic waters. In contrast, some crucial regulators of circadian homeostasis (cry and per genes) are absent from the icefish genome, suggesting compromised control of biological rhythms in the polar light environment. The availability of the icefish genome sequence will accelerate our understanding of adaptation to extreme Antarctic environments.
Origin and evolution of the octoploid strawberry genome
Authors: Edger Patrick P. , Poorten Thomas J. , VanBuren Robert , Hardigan Michael A. , Colle Marivi , McKain Michael R. , Smith Ronald D. , Teresi Scott J. , Nelson Andrew D. L. , Wai Ching Man , Alger Elizabeth I. , Bird Kevin A. , Yocca Alan E. , Pumplin Nathan , Ou Shujun , Ben-Zvi Gil , Brodt Avital , Baruch Kobi , Swale Thomas , Shiue Lily , Acharya Charlotte B. , Cole Glenn S. , Mower Jeffrey P. , Childs Kevin L. , Jiang Ning , Lyons Eric , Freeling Michael , Puzey Joshua R. , Knapp Steven J. 
Published: February 2019

AbstractCultivated strawberry emerged from the hybridization of two wild octoploid species, both descendants from the merger of four diploid progenitor species into a single nucleus more than 1 million years ago. Here we report a near-complete chromosome-scale assembly for cultivated octoploid strawberry (Fragaria × ananassa) and uncovered the origin and evolutionary processes that shaped this complex allopolyploid. We identified the extant relatives of each diploid progenitor species and provide support for the North American origin of octoploid strawberry. We examined the dynamics among the four subgenomes in octoploid strawberry and uncovered the presence of a single dominant subgenome with significantly greater gene content, gene expression abundance, and biased exchanges between homoeologous chromosomes, as compared with the other subgenomes. Pathway analysis showed that certain metabolomic and disease-resistance traits are largely controlled by the dominant subgenome. These findings and the reference genome should serve as a powerful platform for future evolutionary studies and enable molecular breeding in strawberry.
Thioredoxin Reductase as a Novel and Efficient Plasma Biomarker for the Detection of Non-Small Cell Lung Cancer: a Large-scale, Multicenter study
Authors: Ye Suofu , Chen Xiaofeng , Yao Yi , Li Yueqin , Sun Ruoxuan , Zeng Huihui , Shu Yongqian , Yin Hanwei 
Published: February 2019

AbstractThere is an increased demand for efficient biomarkers for the diagnosis of non-small cell lung cancer (NSCLC). This study aimed to evaluate plasma levels of TrxR activity in a large population to confirm its validity and efficacy in NSCLC diagnosis. Blood samples were obtained from 1922 participants (638 cases of NSCLC, 555 cases of benign lung diseases (BLDs) and 729 sex- and age-matched healthy controls). The plasma levels of TrxR activity in patients with NSCLC (15.66 ± 11.44 U/ml) were significantly higher (P < 0.01) than in patients with BLDs (6.27 ± 3.78 U/ml) or healthy controls (2.05 ± 1.86 U/ml). The critical value of plasma TrxR activity levels for diagnosis of NSCLC was set at 10.18 U/ml, with a sensitivity of 71.6% and a specificity of 91.9%. The combination of NSE, CEA, CA19-9, Cyfra21-1, and TrxR was more effective for NSCLC diagnosis (sensitivity and specificity in the training set: 85.6%, 90.2%; validation set: 86.2%, 92.4%) than was each biomarker individually (P < 0.001). TrxR can also efficiently distinguish the metastatic status of the tumor, and it can further differentiate between various histological differentiations. Together, plasma TrxR activity was identified as a convenient, non-invasive, and efficient biomarker for the diagnosis of NSCLCs, particularly for discriminating between metastatic and non-metastatic tumors, or for histologic differentiation.
Presaccadic attention improves or impairs performance by enhancing sensitivity to higher spatial frequencies
Authors: Li Hsin-Hung , Pan Jasmine , Carrasco Marisa 
Published: February 2019

AbstractRight before we move our eyes, visual performance and neural responses for the saccade target are enhanced. This effect, presaccadic attention, is considered to prioritize the saccade target and to enhance behavioral performance for the saccade target. Recent evidence has shown that presaccadic attention modulates the processing of feature information. Hitherto, it remains unknown whether presaccadic modulations on feature information are flexible, to improve performance for the task at hand, or automatic, so that they alter the featural representation similarly regardless of the task. Using a masking procedure, here we report that presaccadic attention can either improve or impair performance depending on the spatial frequency content of the visual input. These counterintuitive modulations were significant at a time window right before saccade onset. Furthermore, merely deploying covert attention within the same temporal interval without preparing a saccade did not affect performance. This study reveals that presaccadic attention not only prioritizes the saccade target, but also automatically modifies its featural representation.
Quercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes
Authors: Jiang Hao , Yamashita Yoko , Nakamura Asuka , Croft Kevin , Ashida Hitoshi 
Published: February 2019

AbstractQuercetin and its metabolite isorhamnetin elicit various beneficial effects on human health. However, their bioavailability is low. In this study, we investigated whether low concentrations in the physiological range could promote glucose uptake in L6 myotubes, as well as the underlying molecular mechanisms. We found that 0.1 nM and 1 nM quercetin or 1 nM isorhamnetin significantly increased glucose uptake via translocation of glucose transporter type 4 (GLUT4) to the plasma membrane of L6 myotubes. Quercetin principally activated the CaMKKβ/AMPK signalling pathway at these concentrations, but also activated IRS1/PI3K/Akt signalling at 10 nM. In contrast, 1 nM and 10 nM isorhamnetin principally activated the JAK/STAT pathway. Treatment with siAMPKα and siJAK2 abolished quercetin- and isorhamnetin-induced GLUT4 translocation, respectively. However, treatment with siJAK3 did not affect isorhamnetin-induced GLUT4 translocation, indicating that isorhamnetin induced GLUT4 translocation mainly through JAK2, but not JAK3, signalling. Thus, quercetin preferably activated the AMPK pathway and, accordingly, stimulated IRS1/PI3K/Akt signalling, while isorhamnetin activated the JAK2/STAT pathway. Furthermore, after oral administration of quercetin glycoside at 10 and 100 mg/kg body weight significantly induced GLUT4 translocation to the plasma membrane of skeletal muscles in mice. In the same animals, plasma concentrations of quercetin aglycone form were 4.95 and 6.80 nM, respectively. In conclusion, at low-concentration ranges, quercetin and isorhamnetin promote glucose uptake by increasing GLUT4 translocation via different signalling pathways in skeletal muscle cells; thus, these compounds may possess beneficial functions for maintaining glucose homeostasis by preventing hyperglycaemia at physiological concentrations.
Hypochlorous-Acid-Generating Electrochemical Scaffold for Treatment of Wound Biofilms
Authors: Kiamco Mia Mae , Zmuda Hannah M. , Mohamed Abdelrhman , Call Douglas R. , Raval Yash S. , Patel Robin , Beyenal Haluk 
Published: February 2019

AbstractBiofilm formation causes prolonged wound infections due to the dense biofilm structure, differential gene regulation to combat stress, and production of extracellular polymeric substances. Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa are three difficult-to-treat biofilm-forming bacteria frequently found in wound infections. This work describes a novel wound dressing in the form of an electrochemical scaffold (e-scaffold) that generates controlled, low concentrations of hypochlorous acid (HOCl) suitable for killing biofilm communities without substantially damaging host tissue. Production of HOCl near the e-scaffold surface was verified by measuring its concentration using needle-type microelectrodes. E-scaffolds producing 17, 10 and 7 mM HOCl completely eradicated S. aureus, A. baumannii, and P. aeruginosa biofilms after 3 hours, 2 hours, and 1 hour, respectively. Cytotoxicity and histopathological assessment showed no discernible harm to host tissues when e-scaffolds were applied to explant biofilms. The described strategy may provide a novel antibiotic-free strategy for treating persistent biofilm-associated infections, such as wound infections.
Water table management and fertilizer application impacts on CO2, N2O and CH4 fluxes in a corn agro-ecosystem
Authors: Crézé Cynthia M. , Madramootoo Chandra A. 
Published: February 2019

AbstractWater table management with controlled drainage and subsurface-irrigation (SI) has been identified as a Beneficial Management Practice (BMP) to reduce nitrate leaching in drainage water. It has also been shown to increase crop yields during dry periods of the growing season, by providing water to the crop root zone, via upward flux or capillary rise. However, by retaining nitrates in anoxic conditions within the soil profile, SI could potentially increase greenhouse gas (GHG) fluxes, particularly N2O through denitrification. This process may be further exacerbated by high precipitation and mineral N-fertilizer applications very early in the growing season. In order to investigate the effects of water table management (WTM) with nitrogen fertilization on GHG fluxes from corn (Zea mays) agro-ecosystems, we conducted a research study on a commercial farm in south-western Quebec, Canada. Water table management treatments were: free drainage (FD) and controlled drainage with subsurface-irrigation. GHG samples were taken using field-deployed, vented non-steady state gas chambers to quantify soil CO2, N2O and CH4 fluxes weekly. Our results indicate that fertilizer application timing coinciding with intense (≥24 mm) precipitation events and high temperatures (>25 °C) triggered pulses of N2O fluxes, accounting for up to 60% of cumulative N2O fluxes. Our results also suggest that splitting bulk fertilizer applications may be an effective mitigation strategy, reducing N2O fluxes by 50% in our study. In both seasons, pulse GHG fluxes mostly occurred in the early vegetative stages of the corn, prior to activation of the subsurface-irrigation. Our results suggest that proper timing of WTM mindful of seasonal climatic conditions has the potential to reduce GHG emissions.
Genetic map construction and QTL analysis of leaf-related traits in soybean under monoculture and relay intercropping
Authors: Liu Dai-Ling , Chen Si-Wei , Liu Xin-Chun , Yang Feng , Liu Wei-Guo , She Yue-Hui , Du Jun-Bo , Liu Chun-Yan , Yang Wen-Yu , Wu Xiao-Ling 
Published: February 2019

AbstractSoybean (Glycine max L.) is an important food and oil crop widely planted by intercropping in southwest China. The shade caused by intercropping changes plant growth traits, such as soybean leaf and dry mass, thereby reducing yields. To improve the yield and elucidate the genetic mechanism of the leaf-related traits in intercropped soybeans, we measured the F6:7–8 recombinant inbred lines (RILs) derived from the cross of ‘Nandou 12’ and ‘Jiuyuehuang’ for six leaf-related traits under monoculture and relay intercropping in 2015 and 2016. We found 6366 single-nucleotide polymorphisms (SNPs) markers that covered the whole genome of soybean distributed in 20 linkage groups, which spanned 2818.67 cM with an average interval of 0.44 cM between adjacent markers. Nineteen quantitative trait loci (QTLs) were detected in two environments in 2 years. Three candidate genes associated to leaf-related traits were found according to gene expression and GO enrichment analyses. These results revealed the susceptibility of leaf phenotype to shading and helped elucidate the mechanisms that control leaf-related traits.
Increased neuronal signatures of targeted memory reactivation during slow-wave up states
Authors: Göldi Maurice , van Poppel Eva Anna Maria , Rasch Björn , Schreiner Thomas 
Published: February 2019

AbstractIt is assumed that slow oscillatory up-states represent crucial time windows for memory reactivation and consolidation during sleep. We tested this assumption by utilizing closed-loop targeted memory reactivation: Participants were re-exposed to prior learned foreign vocabulary during up- and down-states of slow oscillations. While presenting memory cues during slow oscillatory up-states improved recall performance, down-state cueing did not result in a clear behavioral benefit. Still, no robust behavioral benefit of up- as compared to down-state cueing was observable. At the electrophysiological level however, successful memory reactivation during up-states was associated with a characteristic power increase in the theta and sleep spindle band. No oscillatory changes were observable for down-state cues. Our findings provide experimental support for the assumption that slow oscillatory up-states may represent privileged time windows for memory reactivation, while the interplay of slow oscillations, theta and sleep spindle activity promotes successful memory consolidation during sleep.
A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis
Authors: Claus Heike , Hubert Kerstin , Becher Dörte , Otto Andreas , Pawlik Marie-Christin , Lappann Ines , Strobel Lea , Vogel Ulrich , Johswich Kay 
Published: February 2019

AbstractAlthough usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.