bluuebunny/crossref_metadata_2025 huggingface dataset:
The classical NLRP3 inflammasome controls FADD unconventional secretion through microvesicle shedding
Authors: Mouasni Sara , Gonzalez Virginie , Schmitt Alain , Bennana Evangeline , Guillonneau François , Mistou Sylvie , Avouac Jérôme , Ea Hang Korng , Devauchelle Valérie , Gottenberg Jacques-Eric , Chiocchia Gilles , Tourneur Léa
Published: February 2019

Fas-associated death domain (FADD) is a key adaptor molecule involved in numerous physiological processes including cell death, proliferation, innate immunity and inflammation. Therefore, changes in FADD expression have dramatic cellular consequences. In mice and humans, FADD regulation can occur through protein secretion. However, the molecular mechanisms accounting for human FADD secretion were still unknown. Here we report that canonical, non-canonical, but not alternative, NLRP3 inflammasome activation in human monocytes/macrophages induced FADD secretion. NLRP3 inflammasome activation by the bacterial toxin nigericin led to the proinflammatory interleukin-1β (IL-1β) release and to the induction of cell death by pyroptosis. However, we showed that FADD secretion could occur in absence of increased IL-1β release and pyroptosis and, reciprocally, that IL-1β release and pyroptosis could occur in absence of FADD secretion. Especially, FADD, but not IL-1β, secretion following NLRP3 inflammasome activation required extracellular glucose. Thus, FADD secretion was an active process distinct from unspecific release of proteins during pyroptosis. This FADD secretion process required K+ efflux, NLRP3 sensor, ASC adaptor and CASPASE-1 molecule. Moreover, we identified FADD as a leaderless protein unconventionally secreted through microvesicle shedding, but not exosome release. Finally, we established human soluble FADD as a new marker of joint inflammation in gout and rheumatoid arthritis, two rheumatic diseases involving the NLRP3 inflammasome. Whether soluble FADD could be an actor in these diseases remains to be determined. Nevertheless, our results advance our understanding of the mechanisms contributing to the regulation of the FADD protein expression in human cells.
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

Ankylosing 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

Human 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

Peptides 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

Centriole 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: Planar and van der Waals heterostructures for vertical tunnelling single electron transistors
Authors: Kim Gwangwoo , Kim Sung-Soo , Jeon Jonghyuk , Yoon Seong In , Hong Seokmo , Cho Young Jin , Misra Abhishek , Ozdemir Servet , Yin Jun , Ghazaryan Davit , Holwill Matthew , Mishchenko Artem , Andreeva Daria V. , Kim Yong-Jin , Jeong Hu Young , Jang A-Rang , Chung Hyun-Jong , Geim Andre K. , Novoselov Kostya S. , Sohn Byeong-Hyeok , Shin Hyeon Suk
Published: February 2019

The original version of this Article contained an error in the spelling of the author Matthew Holwill, which was incorrectly given as Mathew Holwill. This has now been corrected in both the PDF and HTML versions of the Article.
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

Icefishes (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

Cultivated 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

There 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

Right 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

Quercetin 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

Biofilm 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

Water 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

Soybean (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

It 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

Although 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.
Insights into the antigenic advancement of influenza A(H3N2) viruses, 2011–2018
Authors: Jorquera Patricia A. , Mishin Vasiliy P. , Chesnokov Anton , Nguyen Ha T. , Mann Brian , Garten Rebecca , Barnes John , Hodges Erin , De La Cruz Juan , Xu Xiyan , Katz Jackie , Wentworth David E. , Gubareva Larisa V.
Published: February 2019

Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011–2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo, and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection.
Omega-3 fatty acids modulate cyclophosphamide induced markers of immunosuppression and oxidative stress in pigs
Authors: Lee Sang In , Kang Kyung Soo
Published: February 2019

Immunosuppression directly correlates with economic benefits in livestock. Although omega-3, known as an energy source, is used as a pharmaceutical molecule, it remains unknown whether dietary supplementation with omega-3 can alleviate cyclophosphamide-induced immunosuppression in pigs. Omega-3 treatment increased the number of white blood cell, lymphocytes, and monocytes and decreased tumor necrosis factor (TNF)-α production under CTX challenge. In addition, we confirmed that omega-3 decreased the expression of nuclear factor (NF)-κB, TNF-α, interferon (IFN)-γ, and interleukin (IL)-8 in peripheral blood mononuclear cells. Additionally, omega-3 alleviated the activities of liver injury markers (alanine transaminase [ALT] and aspartate transaminase [AST]) and modulated oxidative stress markers (superoxide dismutase [SOD], malondialdehyde [MDA], and glutathione peroxidase [GPx]) in the blood serum after the CTX challenge. Based on these results, we suggest that omega-3 treatment modulates CTX-induced immunosuppression and oxidative stress in pigs. These results may have important implications in the development of new therapeutic approaches to improve immunosuppression, hepatic injury and dysfunction, and oxidative stress in pigs.
Soil bacterial diversity is positively associated with air temperature in the maritime Antarctic
Authors: Dennis Paul G. , Newsham Kevin K. , Rushton Steven P. , O’Donnell Anthony G. , Hopkins David W.
Published: February 2019

Terrestrial ecosystems in the maritime Antarctic experienced rapid warming during the latter half of the 20th century. While warming ceased at the turn of the millennium, significant increases in air temperature are expected later this century, with predicted positive effects on soil fungal diversity, plant growth and ecosystem productivity. Here, by sequencing 16S ribosomal RNA genes in 40 soils sampled from along a 1,650 km climatic gradient through the maritime Antarctic, we determine whether rising air temperatures might similarly influence the diversity of soil bacteria. Of 22 environmental factors, mean annual surface air temperature was the strongest and most consistent predictor of soil bacterial diversity. Significant, but weaker, associations between bacterial diversity and soil moisture content, C:N ratio, and Ca, Mg, PO43− and dissolved organic C concentrations were also detected. These findings indicate that further rises in air temperature in the maritime Antarctic may enhance terrestrial ecosystem productivity through positive effects on soil bacterial diversity.
HtrA4 may play a major role in inhibiting endothelial repair in pregnancy complication preeclampsia
Authors: Wang Yao , Lim Rebecca , Nie Guiying
Published: February 2019

Preeclampsia (PE) is a life-threatening complication of human pregnancy with no effective treatment other than premature delivery. It is hallmarked by systemic endothelial injury/dysfunction which is believed to be caused by abnormal levels/types of placenta-derived factors that are circulating in the maternal blood. Emerging evidence suggests that endothelial repair is also dysregulated in PE, as circulating endothelial progenitor cells (EPCs) critical for endothelial regeneration are reduced in number and functionality. However, the underlying mechanisms are poorly understood. HtrA4 is a placenta-specific protease that is secreted into the circulation and significantly elevated in early-onset PE. Here we investigated the impact of HtrA4 on endothelial proliferation and repair. We demonstrated that high levels of HtrA4 halted endothelial cell proliferation and significantly down-regulated a number of genes that are critical for cell cycle progression, including CDKN3, BIRC5, CDK1 and MKI67. Furthermore, HtrA4 significantly inhibited the proliferation of primary EPCs isolated from term human umbilical cord blood and impeded their differentiation into mature endothelial cells. Our data thus suggests that elevated levels of HtrA4 in the early-onset PE circulation may impair endothelial cell repair, not only by halting endothelial cell proliferation, but also by inhibiting the proliferation and differentiation of circulating EPCs.
Tapered arrangement of metallic nanorod chains for magnified plasmonic nanoimaging
Authors: Ohashi Yoshiro , Ranjan Bikas , Saito Yuika , Umakoshi Takayuki , Verma Prabhat
Published: February 2019

Plasmonic nanolens, a 3-dimensional tapered arrangement of metallic nanorod chains, holds a great promise as a new plasmonics-based optical nano-imaging technique. While multiple nanorod chains can transfer the near-field signal originating from a sample to an image at a distance larger than a micro-meter, where each nanorod chain contributes in forming one pixel in the image, the tapered arrangement of the nanorod chains with a certain taper angle allows image magnification. We experimentally demonstrate the feature of image formation and magnification in a nanolens by fabricating a tapered arrangement of two silver nanorod chains, which were separated by a distance smaller than the diffraction limit at one end and larger than the diffraction limit at the other end. We placed two nano-sized optical sources of quantum dots near the first ends of the chains, which served as two subwavelength objects. In the optical measurement, we demonstrated that the unresolved subwavelength optical sources could be imaged at the other ends of the chains and were well resolved in accordance with the magnification feature of a nanolens. This verification is an experimental proof of the image magnification, and an important step toward the realization of plasmonic nanolens.
A nationally representative study on socio-demographic and geographic correlates, and trends in tobacco use in Nepal
Authors: Shrestha Nipun , Mehata Suresh , Pradhan Pranil Man Singh , Joshi Deepak , Mishra Shiva Raj
Published: February 2019

Tobacco control still poses an immense challenge for the government of Nepal. Updated knowledge on the current pattern of tobacco use and its associated factors will be helpful for policy makers to curb the tobacco epidemic. This study fills this gap by, (i) exploring demographic, socio-economic and geographic correlates of current tobacco use using a nationally representative sample of 15–49-year adults from Nepal Demographic Health survey 2016, and (ii) examining the prevalence and trends of both smoking and non-smoking forms of tobacco use in a nationally representative sample of 15–49-year adults drawn from three consecutive Demographic Health Surveys (DHS) between 2006 and 2016.Among males, the prevalence of smokeless tobacco use was higher than that of smoking (40.1% and 27.4% respectively), whereas among females smoking was more common than smokeless tobacco use (prevalence of 5.5% and 3.8% respectively). Both smoking and smokeless tobacco use were associated with older age and lower level of education. Among males, those living in urban areas were more likely to consume any form of tobacco. Residents of terai/plains were more likely to use smokeless tobacco. The concentration curves on cumulative proportion of tobacco use ranked by wealth quintiles showed tobacco use to be highest among the lowest socio-economic groups in both males and females in all three survey years. We found a decreasing trend of tobacco smoking and an increasing trend of smokeless tobacco use over the 10-year period. However, the consumption of both forms of tobacco increased in young males during the same period. Proper monitoring of adherence to directives of the anti-tobacco law should be ensured to curb the increasing burden of tobacco use among young males, and a similar effort is needed to sustain the decline in tobacco uses among other population groups in Nepal.
Asthma, Rhinoconjunctivitis, Eczema, and the Association with Perinatal Anthropometric Factors in Vietnamese Children
Authors: Toizumi Michiko , Hashizume Masahiro , Nguyen Hien Anh T. , Yasunami Michio , Kitamura Noriko , Iwasaki Chihiro , Takegata Mizuki , Moriuchi Hiroyuki , Dang Duc Anh , Ariyoshi Koya , Yoshida Lay-Myint
Published: February 2019

Few studies have investigated possible causative and protective factors associated with allergic diseases in resource-limited countries, Southeast Asia. We estimated the current prevalence of asthma, rhinoconjunctivitis, and eczema among 6-year-old children, and identified anthropometric factors associated with asthma, rhinoconjunctivitis and eczema, in South-Central Vietnam. A birth cohort study recruited 1,999 children born at a provincial hospital in Nha Trang, Vietnam between May 2009 and May 2010. A 6-year follow-up survey was conducted where clinical, familial, and environmental information was collected by interviewing caregivers using a standardized form based on the International Study of Asthma and Allergies in Childhood, Phase Three Core and Environmental Questionnaire for 6–7-year-old children. The odds ratios of asthma, rhinoconjunctivitis, and eczema for anthropometric factors were estimated using logistic regression analysis. In total, 1202 children participated in the follow-up survey. The proportions of children who had current asthma, rhinoconjunctivitis, and eczema were 5.1% (95% confidence interval [CI] 3.9–6.5%), 11.5% (9.7–13.4%), and 6.7% (5.3–8.2%), respectively. Low birthweight (adjusted odds ratio 5.12, 95% CI 1.92–13.64) was independently associated with increased risk of eczema. Further studies are necessary to understand the involved mechanism.
Ultralong Ca2B2O5·H2O nanowires: water-bath pretreated eco-friendly hydrothermal synthesis, optical and rare earth-doped photoluminescence properties
Authors: Zhu Wancheng , Zhang Zhaoqiang , Xu Lin , Zhai Kuilu , Sun Panpan
Published: February 2019

A facile water-bath pretreated hydrothermal route is developed for ultralong Ca2B2O5·H2O nanowires (length: <230 μm) as a promising photoluminescent host candidate.
Temperature dependence of the ultrafast vibrational echo spectroscopy of OD modes in liquid water from first principles simulations
Authors: Ojha Deepak , Chandra Amalendu
Published: February 2019

The temperature dependence of the vibrational spectral diffusion of OD modes in liquid water is investigated through calculations of vibrational echo spectral observables from first principles molecular dynamics.
A magnetic self-contained thermochromic system with convenient temperature range
Authors: Billeci Floriana , Gunaratne H. Q. Nimal , D'Anna Francesca , Morgan Grace G. , Seddon Kenneth R. , Plechkova Natalia V.
Published: February 2019

A sugar-based ionic liquid ligand coordinated to cobalt(ii) exhibits magnetic switching and marked thermochromism in spectator ionic liquid solution/polymer films over a convenient temperature range (20–60 °C), resulting in a potential energy storage system.
Pyrazolopyrimidinones, a novel class of copper-dependent bactericidal antibiotics against multi-drug resistant S. aureus
Authors: Crawford Cameron L , Dalecki Alex G , Narmore Whitney T , Hoff Jessica , Hargett Audra A , Renfrow Matthew B , Zhang Man , Kalubowilage Madumali , Bossmann Stefan H , Queern Stacy L , Lapi Suzanne E , Hunter Robert N , Bao Donghui , Augelli-Szafran Corinne E , Kutsch Olaf , Wolschendorf Frank
Published: February 2019

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections poses a therapeutic challenge as even last resort drugs become increasingly ineffective. As the demand for antibiotics with novel modes of action is growing, new approaches are needed to probe a greater spectrum of antimicrobial activities for their potential efficacy against drug-resistant pathogens. The use of copper (Cu) by the innate immune system to mount an antimicrobial response against bacterial invaders has created an opportunity to explore a role for Cu in antimicrobial therapy. Here we describe pyrazolopyrimidinones (PZP) as novel copper-dependent inhibitors (CDI) of S. aureus. 5-Benzyl-3-(4-chlorophenyl)-2-methyl-4H,7H-pyrazolo[1,5-a]pyrimidin-7-one (PZP-915) showed potent bactericidal properties at sub-micromolar concentrations and activity against clinical MRSA isolates and biofilms cultures. This cupricidal activity is founded on the molecule’s ability to coordinate Cu and induce accumulation of Cu ions inside S. aureus cells. We demonstrate that exposure to 915 + Cu led to an almost instantaneous collapse of the membrane potential which was accompanied by a complete depletion of cellular ATP, loss of cell-associated K+, a substantial gain of cell associated Na+, and an inability to control the influx of protons in slightly acidic medium, while the integrity of the cell membrane remained intact. These findings highlight PZP-915 as a novel membrane-directed metalloantibiotic against S. aureus that is likely to target a multiplicity of membrane associated protein functions rather than imposing physical damage to the membrane structure.
Enantioselective Cu-catalyzed 1,4-additions of organozinc and Grignard reagents to enones: exceptional performance of the hydrido-phosphite-ligand BIFOP-H
Authors: Brüllingen Eric , Neudörfl Jörg-Martin , Goldfuss Bernd
Published: February 2019

Enantioselective CuI-catalyzed 1,4-additions and DFT computations concerning the enantioselective mechanism.
Random D1–A1–D1–A2 terpolymers based on diketopyrrolopyrrole and benzothiadiazolequinoxaline (BTQx) derivatives for high-performance polymer solar cells
Authors: Keshtov M. L. , Kuklin S. A. , Konstantinov I. O. , Ostapov I. E. , Makhaeva E. E. , Nikolaev A. Yu. , Xie Zh. , Zou Y. , Sharma Ganesh D.
Published: February 2019

The overall power conversion efficiency of the polymer solar cell based on P13 (DPP/BTQx ratio is 1/1) showed the highest value of 9.20% with a Voc of 0.86 V, Jsc of 15.74 mA cm−2, and FF of 0.68.
Phase-change nanoclusters embedded in a memristor for simulating synaptic learning
Authors: Wan Qin , Zeng Fei , Yin Jun , Sun Yiming , Hu Yuandong , Liu Jialu , Wang Yingcong , Li Guoqi , Guo Dong , Pan Feng
Published: February 2019

A type of memristor with structure of Pd/Nb : AlNO/Pd is designed to mimic synaptical plasticity and kinetics.
Comparison of performance and biofouling resistance of thin-film composite forward osmosis membranes with substrate/active layer modified by graphene oxide
Authors: Li Yuan , Yang Yu , Li Chen , Hou Li-an
Published: February 2019

The substrate modified by GO could greatly improve water flux, whereas the GO-functionalized active layer is favorable for biofouling mitigation.
Phospholipase D encapsulated into metal-surfactant nanocapsules for enhancing biocatalysis in a two-phase system
Authors: Li Hui , Pang Yang , Wang Xin , Cao Xun , He Xun , Chen Kequan , Li Ganlu , Ouyang Pingkai , Tan Weiming
Published: February 2019

PLD@MSNC transforms a two-phase system into an emulsion phase, and enhances transphosphatidylation.
A versatile liquid-jet/sessile droplet system for operando studies of reactions in liquid dispersions and solutions by X-ray absorption spectroscopy
Authors: Chang S.-Y. , Kathyola T. A. , Willneff E. A. , Willis Colin John , Wilson P. , Dowding P. J. , Cibin G. , Kroner A. B. , Shotton E. J. , Schroeder S. L. M.
Published: February 2019

X-ray absorption spectroscopy for operando studies of liquid dispersions and solutions.
Analysis of the role of a writing-to-learn assignment in student understanding of organic acid–base concepts
Authors: Schmidt-McCormack Jennifer A. , Judge Jessyca A. , Spahr Kellie , Yang Ellen , Pugh Raymond , Karlin Ashley , Sattar Atia , Thompson Barry C. , Gere Anne Ruggles , Shultz Ginger V.
Published: February 2019

Acid–base chemistry is a foundational topic that is taught in courses across the chemistry curriculum. Students often have difficulty distinguishing between the different theories of acid–base chemistry—Brønsted–Lowry and Lewis acid–base chemistry—and applying these two definitions correctly in unfamiliar scenarios. To help students learn these definitions and be able to apply them, an acid–base Writing-to-Learn assignment was developed and evaluated. The Writing-to-Learn assignment involved a three-step process where students constructed an initial draft in response to a writing prompt, participated in peer review, and made revisions based on peer review feedback, before submitting a final draft. This process is informed by sociocultural theory applied to writing, which states that student learning of concepts increases through engagement with their peers’ work and receiving peer feedback on their own writing. To test the efficacy of the acid–base writing assignment, an external assessment, comprised of conceptual questions related to acid–base chemistry and students’ confidence when responding to them, was administered in two groups; a treatment group who completed the Writing-to-Learn assignment, and a comparison group who completed a separate assignment. Additionally, students who completed the Writing-to-Learn assignment were interviewed about their experiences. Regression analysis revealed that students in the treatment group had a greater increase in their conceptual understanding and confidence as compared to the students in the comparison group. The results demonstrate the students could successfully write about the Brønsted–Lowry and Lewis acid–base models separately, but were less successful with connecting these two concepts together in their writing. These results demonstrate the efficacy of Writing-to-Learn as an approach for promoting conceptual learning of acid–base chemistry.
Thermoinduced structural-transformation and thermochromic luminescence in organic manganese chloride crystals
Authors: Sun Meng-En , Li Yao , Dong Xi-Yan , Zang Shuang-Quan
Published: February 2019

The [Mn2Cl9]5− mode in the binuclear red emissive (C4NOH10)5Mn2Cl9·C2H5OH is cleaved into [MnCl4]2− in the green emissive (C4NOH10)2MnCl4.
Efficient cell surface labelling of live zebrafish embryos: wash-free fluorescence imaging for cellular dynamics tracking and nanotoxicity evaluation
Authors: Jia Hao-Ran , Zhu Ya-Xuan , Xu Ke-Fei , Pan Guang-Yu , Liu Xiaoyang , Qiao Ying , Wu Fu-Gen
Published: February 2019

We developed a red-fluorescent stain capable of achieving wash-free plasma membrane imagingin vitroandin vivo.
Crisscrossing coordination networks: ligand doping to control the chemomechanical properties of stimuli-responsive metallogels
Authors: Kim Junghwan , Lee Dongwhan
Published: February 2019

Intentional structural mismatch was exploited to control the chemomechanical properties of gelating coordination networks built with crisscrossing ligands.
Vanadium(V) oxide clusters synthesized by sublimation from bulk under fully inert conditions
Authors: Lasserus Maximilian , Schnedlitz Martin , Messner Roman , Lackner Florian , Ernst Wolfgang E. , Hauser Andreas W.
Published: February 2019

While laser ablation in combination with electron impact mass spectroscopy yield numerous fragments and reaction products, helium-mediated mass analysis reveals the sublimation from bulk in units of (V2O5)2.
Curvature dynamics and long-range effects on fluid–fluid interfaces with colloids
Authors: Tiribocchi A. , Bonaccorso F. , Lauricella M. , Melchionna S. , Montessori A. , Succi S.
Published: February 2019

The fluid–fluid interface curvature can provide new insights into local inhomogeneities of a binary fluid mixture containing colloidal particles.
Structure–property relationship of metal–organic frameworks for alcohol-based adsorption-driven heat pumps via high-throughput computational screening
Authors: Li Wei , Xia Xiaoxiao , Cao Meng , Li Song
Published: February 2019

Adsorption-driven heat pumps (AHPs) based on metal–organic frameworks (MOFs) have been garnering rapidly growing research interests due to their outstanding adsorption performance.
In situsynthesized low-PtCo@porous carbon catalyst for highly efficient hydrogen evolution
Authors: Qin Yudao , Han Xiaoyu , Gadipelli Srinivas , Guo Jian , Wu Shijie , Kang Liqun , Callison June , Guo Zhengxiao
Published: February 2019

Synthesis of a highly efficient HER catalyst with low Pt that exceeds the efficiency of the commercial 20 wt% Pt/C.