bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanisms underlying nuchal hump formation in dolphin cichlid, Cyrtocara moorii
Authors: Lecaudey Laurène Alicia , Sturmbauer Christian , Singh Pooja , Ahi Ehsan Pashay
Published: December 2019

East African cichlid fishes represent a model to tackle adaptive changes and their connection to rapid speciation and ecological distinction. In comparison to bony craniofacial tissues, adaptive morphogenesis of soft tissues has been rarely addressed, particularly at the molecular level. The nuchal hump in cichlids fishes is one such soft-tissue and exaggerated trait that is hypothesized to play an innovative role in the adaptive radiation of cichlids fishes. It has also evolved in parallel across lakes in East Africa and Central America. Using gene expression profiling, we identified and validated a set of genes involved in nuchal hump formation in the Lake Malawi dolphin cichlid,Cyrtocara moorii. In particular, we found genes differentially expressed in the nuchal hump, which are involved in controlling cell proliferation (btg3,fosl1aandpdgfrb), cell growth (dlk1), craniofacial morphogenesis (dlx5a,mycnandtcf12), as well as regulators of growth-related signals (dpt,pappaandsocs2). This is the first study to identify the set of genes associated with nuchal hump formation in cichlids. Given that the hump is a trait that evolved repeatedly in several African and American cichlid lineages, it would be interesting to see if the molecular pathways and genes triggering hump formation follow a common genetic track or if the trait evolved in parallel, with distinct mechanisms, in other cichlid adaptive radiations and even in other teleost fishes.
In silico definition of new ligninolytic peroxidase sub-classes in fungi and putative relation to fungal life style
Authors: Mathé Catherine , Fawal Nizar , Roux Christophe , Dunand Christophe
Published: December 2019

Ligninolytic peroxidases are microbial enzymes involved in depolymerisation of lignin, a plant cell wall polymer found in land plants. Among fungi, only Dikarya were found to degrade lignin. The increase of available fungal genomes allows performing an expert annotation of lignin-degrading peroxidase encoding sequences with a particular focus on Class II peroxidases (CII Prx). In addition to the previously described LiP, MnP and VP classes, based on sequence similarity, six new sub-classes have been defined: three found in plant pathogen ascomycetes and three in basidiomycetes. The presence of CII Prxs could be related to fungal life style. Typically, necrotrophic or hemibiotrophic fungi, either ascomycetes or basidiomycetes, possess CII Prxs while symbiotic, endophytic or biotrophic fungi do not. CII Prxs from ascomycetes are rarely subjected to duplications unlike those from basidiomycetes, which can form large recent duplicated families. Even if these CII Prxs classes form two well distinct clusters with divergent gene structures (intron numbers and positions), they share the same key catalytic residues suggesting that they evolved independently from similar ancestral sequences with few or no introns. The lack of CII Prxs encoding sequences in early diverging fungi, together with the absence of duplicated class I peroxidase (CcP) in fungi containing CII Prxs, suggests the potential emergence of an ancestral CII Prx sequence from the duplicated CcP after the separation between ascomycetes and basidiomycetes. As some ascomycetes and basidiomycetes did not possess CII Prx, late gene loss could have occurred.
Amyloidophilic Molecule Interactions on the Surface of Insulin Fibrils: Cooperative Binding and Fluorescence Quenching
Authors: Ziaunys Mantas , Mikalauskaite Kamile , Smirnovas Vytautas
Published: December 2019

Protein aggregation into insoluble fibrillar aggregates is linked to several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease. Commonly used methods to study aggregation inhibition or fibril destabilization by potential drugs include spectroscopic measurements of amyloidophilic dye molecule fluorescence or absorbance changes. In this work we show the cross-interactions of five different dye molecules on the surface of insulin amyloid fibrils, resulting in cooperative binding and fluorescence quenching.
Water channel pore size determines exclusion properties but not solute selectivity
Authors: Kitchen Philip , Salman Mootaz M. , Pickel Simone U. , Jennings Jordan , Törnroth-Horsefield Susanna , Conner Matthew T. , Bill Roslyn M. , Conner Alex C.
Published: December 2019

Aquaporins (AQPs) are a ubiquitous family of transmembrane water channel proteins. A subgroup of AQP water channels also facilitates transmembrane diffusion of small, polar solutes. A constriction within the pore, the aromatic/arginine (ar/R) selectivity filter, is thought to control solute permeability: previous studies on single representative water channel proteins suggest narrow channels conduct water, whilst wider channels permit passage of solutes. To assess this model of selectivity, we used mutagenesis, permeability measurements and in silico comparisons of water-specific as well as glycerol-permeable human AQPs. Our studies show that single amino acid substitutions in the selectivity filters of AQP1, AQP4 and AQP3 differentially affect glycerol and urea permeability in an AQP-specific manner. Comparison between in silico-calculated channel cross-sectional areas and in vitro permeability measurements suggests that selectivity filter cross-sectional area predicts urea but not glycerol permeability. Our data show that substrate discrimination in water channels depends on a complex interplay between the solute, pore size, and polarity, and that using single water channel proteins as representative models has led to an underestimation of this complexity.
Characterization and engineering of broadly reactive monoclonal antibody against hepatitis B virus X protein that blocks its interaction with DDB1
Authors: Tao Shuai , Pan Shaokun , Gu Chenjian , Wei Lili , Kang Ning , Xie Youhua , Liu Jing
Published: December 2019

Hepatitis B virus (HBV) X protein (HBx) plays diverse roles in both viral life cycle and HBV-related carcinogenesis. Its interaction with DNA damage-binding protein 1 (DDB1) was shown to be essential for engendering cellular conditions favorable for optimal viral transcription and replication. Previously, we described a mouse monoclonal antibody against HBx (anti-HBx 2A7) recognizing HBx encoded by representative strains from 7 of 8 known HBV genotypes. In this work, we further characterized 2A7 in order to explore its potential usefulness in HBx-targeting applications. We demonstrated that 2A7 recognizes a linear epitope mapped to L89PKVLHKR96 on HBx, a segment that is highly conserved across genotypes and coincidentally overlaps with the DDB1-interacting segment. HBx-DDB1 binding could be inhibited by 2A7 in vitro, suggesting therapeutic potential. Nucleic acid and amino acid sequences of 2A7 were then obtained, which allowed construction of recombinant antibody and single chain variable fragments (scFv). 2A7-derived recombinant antibody and scFv recapitulate 2A7’s HBx-binding capacity and epitope specificity. We also reported preliminary results using cell-penetrating peptide for delivering 2A7 antibody across cell membrane to target intracellular HBx. Anti-HBx 2A7 and 2A7-derived scFv characterized here may give rise to novel HBx-targeting diagnostics and therapeutics for HBV- and HBx-related pathologies.
Levosimendan and systemic vascular resistance in cardiac surgery patients: a systematic review and meta-analysis
Authors: Terbeck Sandra , Heinisch Paul Philipp , Lenz Armando , Friess Jan-Oliver , Guensch Dominik , Carrel Thierry , Eberle Balthasar , Erdoes Gabor
Published: December 2019

Levosimendan is a potent non-adrenergic inodilator agent. The net effect of hemodynamic changes may result in a hyperdynamic state with low systemic vascular resistance. We conducted a systematic review and meta-analysis assessing hemodynamics in cardiac surgery patients treated with levosimendan. English-language literature was searched systematically from 2006 until October 2018, including randomized controlled trials and case-matched or retrospective studies providing at least two sequentially measured hemodynamic variables in adult patients who underwent cardiac surgery with cardiopulmonary bypass and were treated with levosimendan in comparison to alternative drugs or devices. Cardiac index significantly increased in the levosimendan group by 0.74 (0.24 to 1.23) [standardized mean difference (95% CI); p = 0.003] from baseline to postoperative day (POD) 1, and by 0.75 (0.25 to 1.25; p = 0.003) from baseline to POD 7, when corrected for the standardized mean difference at baseline by a multivariate mixed effects meta-analysis model. With this correction for baseline differences, other hemodynamic variables including systemic vascular resistance did not significantly differ until POD 1 [−0.17 (−0.64 to 0.30), p = 0.48] and POD 7 [−0.13 (−0.61 to 0.34), p = 0.58] between the levosimendan and the comparator group. Levosimendan increases cardiac index in patients undergoing cardiac surgery. Although levosimendan has inodilator properties, this meta-analysis finds no clinical evidence that levosimendan produces vasopressor-resistant vasoplegic syndrome.
Adipose-derived Mesenchymal Stromal Cells Modulate Lipid Metabolism and Lipid Droplet Biogenesis via AKT/mTOR –PPARγ Signalling in Macrophages
Authors: Souza-Moreira Luciana , Soares Vinicius Cardoso , Dias Suelen da Silva Gomes , Bozza Patricia T.
Published: December 2019

Mesenchymal stromal cells (MSCs) are a potential therapy for many chronic inflammatory diseases due to their regenerative, immunologic and anti-inflammatory properties. The two-way dialogue between MSCs and macrophages is crucial to tissue regeneration and repair. Previous research demonstrated that murine adipose-derived MSC conditioned medium (ASCcm) reprograms macrophages to an M2-like phenotype which protects from experimental colitis and sepsis. Here, our focus was to determine the molecular mechanism of lipid droplet biogenesis in macrophages re-educated using ASCcm. Adipose-derived MSC conditioned medium promotes phosphorylation of AKT/mTOR pathway proteins in macrophages. Furthermore, increased expression of PPARγ, lipid droplet biogenesis and PGE2 synthesis were observed in M2-like phenotype macrophages (high expression of arginase 1 and elevated IL-10). Treatment with mTOR inhibitor rapamycin or PPARγ inhibitor GW9662 suppressed lipid droplets and PGE2 secretion. However, these inhibitors had no effect on arginase-1 expression. Rapamycin, but not GW9662, inhibit IL-10 secretion. In conclusion, we demonstrate major effects of ASCcm to reprogram macrophage immunometabolism through mTOR and PPARγ dependent and independent pathways.
Chaos theory discloses triggers and drivers of plankton dynamics in stable environment
Authors: Telesh Irena V. , Schubert Hendrik , Joehnk Klaus D. , Heerkloss Reinhard , Schumann Rhena , Feike Martin , Schoor Arne , Skarlato Sergei O.
Published: December 2019

Despite the enticing discoveries of chaos in nature, triggers and drivers of this phenomenon remain a classical enigma which needs irrefutable empirical evidence. Here we analyze results of the yearlong replicated mesocosm experiment with multi-species plankton community that allowed revealing signs of chaos at different trophic levels in strictly controlled abiotic environment. In mesocosms without external stressors, we observed the “paradox of chaos” when biotic interactions (internal drivers) were acting as generators of internal abiotic triggers of complex plankton dynamics. Chaos was registered as episodes that vanished unpredictably or were substituted by complex behaviour of other candidates when longer time series were considered. Remarkably, episodes of chaos were detected even in the most abiotically stable conditions. We developed the Integral Chaos Indicator to validate the results of the Lyapunov exponent analysis. These findings are essential for modelling and forecasting behaviour of a variety of natural and other global systems.
Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice
Authors: Gouveia Kelly , Hurst Jane L.
Published: December 2019

Handling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling stress that results in strong aversion to the handler, while mice familiarised with being picked up in a tunnel or cupped on the open hand show low stress and anxiety, and actively seek interaction with their handlers. Here we investigate the duration and frequency of handling required for effective familiarisation with these non-aversive handling methods, and test whether this is sufficient to prevent aversion and anxiety when animals then experience immobilisation and a mild procedure (subcutaneous injection). Very brief handling (2 s) was sufficient to familiarise mice with tunnel handling, even when experienced only during cage cleaning. Brief but more frequent handling was needed for familiarisation with cup handling, while pick up by tail induced strong aversion even when handling was brief and infrequent. Experience of repeated immobilisation and subcutaneous injection did not reverse the positive effects of tunnel handling. Our findings demonstrate that replacing tail with tunnel handling during routine cage cleaning and procedures provides a major refinement with little if any cost for familiarisation.
Epigenetic reprogramming underlies efficacy of DNA demethylation therapy in osteosarcomas
Authors: Asano Naofumi , Takeshima Hideyuki , Yamashita Satoshi , Takamatsu Hironori , Hattori Naoko , Kubo Takashi , Yoshida Akihiko , Kobayashi Eisuke , Nakayama Robert , Matsumoto Morio , Nakamura Masaya , Ichikawa Hitoshi , Kawai Akira , Kondo Tadashi , Ushijima Toshikazu
Published: December 2019

Osteosarcoma (OS) patients with metastasis or recurrent tumors still suffer from poor prognosis. Studies have indicated the efficacy of DNA demethylation therapy for OS, but the underlying mechanism is still unclear. Here, we aimed to clarify the mechanism of how epigenetic therapy has therapeutic efficacy in OS. Treatment of four OS cell lines with a DNA demethylating agent, 5-aza-2′-deoxycytidine (5-aza-dC) treatment, markedly suppressed their growth, and in vivo efficacy was further confirmed using two OS xenografts. Genome-wide DNA methylation analysis showed that 10 of 28 primary OS had large numbers of methylated CpG islands while the remaining 18 OS did not, clustering together with normal tissue samples and Ewing sarcoma samples. Among the genes aberrantly methylated in primary OS, genes involved in skeletal system morphogenesis were present. Searching for methylation-silenced genes by expression microarray screening of two OS cell lines after 5-aza-dC treatment revealed that multiple tumor-suppressor and osteo/chondrogenesis-related genes were re-activated by 5-aza-dC treatment of OS cells. Simultaneous activation of multiple genes related to osteogenesis and cell proliferation, namely epigenetic reprogramming, was considered to underlie the efficacy of DNA demethylation therapy in OS.
Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis
Authors: Hong Jung Yong , Yoon Dok Hyun , Yoon Sang Eun , Kim Seok Jin , Lee Ho Sup , Eom Hyeon-Seok , Lee Hye Won , Shin Dong-Yeop , Koh Youngil , Yoon Sung-Soo , Jo Jae-Cheol , Kim Jin Seok , Kim Soo-Jeong , Cho Su-Hee , Lee Won-Sik , Won Jong-Ho , Kim Won Seog , Suh Cheolwon
Published: December 2019

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29–80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0–33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6–24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7–1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4–9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.
Phenylethylamides derived from bacterial secondary metabolites specifically inhibit an insect serotonin receptor
Authors: Hasan Ariful , Yeom Hyun-Suk , Ryu Jaewook , Bode Helge B. , Kim Yonggyun
Published: December 2019

Serotonin (5-hydroxytryptamine: 5-HT) is a biogenic monoamine that mediates immune responses and modulates nerve signal in insects. Se-5HTR, a specific receptor of serotonin, has been identified in the beet armyworm, Spodoptera exigua. It is classified into subtype 7 among known 5HTRs. Se-5HTR was expressed in all developmental stages of S. exigua. It was expressed in all tested tissues of larval stage. Its expression was up-regulated in hemocytes and fat body in response to immune challenge. RNA interference (RNAi) of Se-5HTR exhibited significant immunosuppression by preventing cellular immune responses such as phagocytosis and nodulation. Treatment with an inhibitor (SB-269970) specific to 5HTR subtype 7 resulted in significant immunosuppression. Furthermore, knockout mutant of Se-5HTR by CRISPR-Cas9 led to significant reduction of phagocytotic activity of S. exigua hemocytes. Such immunosuppression was also induced by bacterial secondary metabolites derived from Xenorhabdus and Photorhabdus. To determine specific bacterial metabolites inhibiting Se-5HTR, this study screened 37 bacterial secondary metabolites with respect to cellular immune responses associated with Se-5HTR and selected 10 potent inhibitors. These 10 selected compounds competitively inhibited cellular immune responses against 5-HT and shared phenylethylamide (PEA) chemical skeleton. Subsequently, 46 PEA derivatives were screened and resulting potent chemicals were used to design a compound to be highly inhibitory against Se-5HTR. The designed compound was chemically synthesized. It showed high immunosuppressive activities along with specific and competitive inhibition activity for Se-5HTR. This study reports the first 5HT receptor from S. exigua and provides its specific inhibitor designed from bacterial metabolites and their derivatives.
Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein
Authors: Ikemura Kenji , Hiramatsu Shun-ichi , Shinogi Yuri , Nakatani Yusuke , Tawara Isao , Iwamoto Takuya , Katayama Naoyuki , Okuda Masahiro
Published: December 2019

Methotrexate (MTX) is an antifolate agent used for the treatment of various malignancies and is eliminated by breast cancer resistance protein (BCRP). Because febuxostat (FBX) is known to inhibit BCRP activity, FBX might exacerbate MTX-related adverse effects. In this study, we examined the drug-drug interaction between FBX and MTX in BCRP-expressing membrane vesicles. Moreover, we retrospectively investigated the impact of FBX on MTX-related adverse effects in 38 patients (144 cycles) receiving high-dose MTX therapy (HDMTX). The Food and Drug Administration Adverse Event Reporting System (FAERS) database and human hepatocellular carcinoma cell line HepG2 cells were used to evaluate the effects of FBX on MTX-induced hepatotoxicity. In the membrane vesicle study, FBX significantly inhibited BCRP-mediated transport of MTX. Concomitant FBX significantly increased the incidence of hepatotoxicity, but not of nephrotoxicity and hematological toxicity in patients receiving HDMTX. FAERS database analyses revealed that the reporting odds ratio of FBX for MTX-induced hepatotoxicity was 4.16 (95% CI: 2.89–5.98). Co-incubated FBX significantly decreased the cell viability and increased cytotoxicity in MTX-treated HepG2 cells. These findings suggest that concomitant FBX enhances MTX-induced hepatotoxicity by inhibiting hepatic BCRP. These findings provide important information for the safe management of HDMTX therapy in clinical settings.
Nervous system-wide profiling of presynaptic mRNAs reveals regulators of associative memory
Authors: Arey Rachel N. , Kaletsky Rachel , Murphy Coleen T.
Published: December 2019

Presynaptic protein synthesis is important in the adult central nervous system; however, the nervous system-wide set of mRNAs localized to presynaptic areas has yet to be identified in any organism. Here we differentially labeled somatic and synaptic compartments in adult C. elegans with fluorescent proteins, and isolated synaptic and somatic regions from the same population of animals. We used this technique to determine the nervous system-wide presynaptic transcriptome by deep sequencing. Analysis of the synaptic transcriptome reveals that synaptic transcripts are predicted to have specialized functions in neurons. Differential expression analysis identified 542 genes enriched in synaptic regions relative to somatic regions, with synaptic functions conserved in higher organisms. We find that mRNAs for pumilio RNA-binding proteins are abundant in synaptic regions, which we confirmed through high-sensitivity in situ hybridization. Presynaptic PUMILIOs regulate associative memory. Our approach enables the identification of new mechanisms that regulate synaptic function and behavior.
Using transfer learning from prior reference knowledge to improve the clustering of single-cell RNA-Seq data
Authors: Mieth Bettina , Hockley James R. F. , Görnitz Nico , Vidovic Marina M.-C. , Müller Klaus-Robert , Gutteridge Alex , Ziemek Daniel
Published: December 2019

In many research areas scientists are interested in clustering objects within small datasets while making use of prior knowledge from large reference datasets. We propose a method to apply the machine learning concept of transfer learning to unsupervised clustering problems and show its effectiveness in the field of single-cell RNA sequencing (scRNA-Seq). The goal of scRNA-Seq experiments is often the definition and cataloguing of cell types from the transcriptional output of individual cells. To improve the clustering of small disease- or tissue-specific datasets, for which the identification of rare cell types is often problematic, we propose a transfer learning method to utilize large and well-annotated reference datasets, such as those produced by the Human Cell Atlas. Our approach modifies the dataset of interest while incorporating key information from the larger reference dataset via Non-negative Matrix Factorization (NMF). The modified dataset is subsequently provided to a clustering algorithm. We empirically evaluate the benefits of our approach on simulated scRNA-Seq data as well as on publicly available datasets. Finally, we present results for the analysis of a recently published small dataset and find improved clustering when transferring knowledge from a large reference dataset. Implementations of the method are available athttps://github.com/nicococo/scRNA.
Modeling Electrical Percolation to optimize the Electromechanical Properties of CNT/Polymer Composites in Highly Stretchable Fiber Strain Sensors
Authors: Jung Sungmin , Choi Hyung Woo , Mocanu Felix Cosmin , Shin Dong-Wook , Chowdhury Mohamed Foysol , Han Soo Deok , Suh Yo-Han , Cho Yuljae , Lee Hanleem , Fan Xiangbing , Bang Sang Yun , Zhan Shijie , Yang Jiajie , Hou Bo , Chun Young Tea , Lee Sanghyo , Occhipinti Luigi Giuseppe , Kim Jong Min
Published: December 2019

A simulation model of electrical percolation through a three-dimensional network of curved CNTs is developed in order to analyze the electromechanical properties of a highly stretchable fiber strain sensor made of a CNT/polymer composite. Rigid-body movement of the curved CNTs within the polymer matrix is described analytically. Random arrangements of CNTs within the composite are generated by a Monte-Carlo simulation method and a union-find algorithm is utilized to investigate the network percolation. Consequently, the strain-induced resistance change curves are obtained in a wide strain range of the composite. In order to compare our model with experimental results, two CNT/polymer composite fibers were fabricated and tested as strain sensors. Their effective CNT volume fractions are estimated by comparing the experimental data with our simulation model. The results confirm that the proposed simulation model reproduces well the experimental data and is useful for predicting and optimizing the electromechanical characteristics of highly stretchable fiber strain sensors based on CNT/polymer composites.
Duplication and parallel evolution of the pancreatic ribonuclease gene (RNASE1) in folivorous non-colobine primates, the howler monkeys (Alouatta spp.)
Authors: Janiak Mareike C. , Burrell Andrew S. , Orkin Joseph D. , Disotell Todd R.
Published: December 2019

In foregut-fermenting mammals (e.g., colobine monkeys, artiodactyl ruminants) the enzymes pancreatic ribonuclease (RNASE1) and lysozyme C (LYZ), originally involved in immune defense, have evolved new digestive functions. Howler monkeys are folivorous non-colobine primates that lack the multi-chambered stomachs of colobines and instead digest leaves using fermentation in the caeco-colic region. We present data on the RNASE1 and LYZ genes of four species of howler monkey (Alouatta spp.). We find that howler monkey LYZ is conserved and does not share the substitutions found in colobine and cow sequences, whereas RNASE1 was duplicated in the common ancestor of A. palliata, A. seniculus, A. sara, and A. pigra. While the parent gene (RNASE1) is conserved, the daughter gene (RNASE1B) has multiple amino acid substitutions that are parallel to those found in RNASE1B genes of colobines. The duplicated RNase in Alouatta has biochemical changes similar to those in colobines, suggesting a novel, possibly digestive function. These findings suggest that pancreatic ribonuclease has, in parallel, evolved a new role for digesting the products of microbial fermentation in both foregut- and hindgut-fermenting folivorous primates. This may be a vital digestive enzyme adaptation allowing howler monkeys to survive on leaves during periods of low fruit availability.
Transcriptomic changes during TGF-β-mediated differentiation of airway fibroblasts to myofibroblasts
Authors: Walker Erin Joanne , Heydet Deborah , Veldre Timothy , Ghildyal Reena
Published: December 2019

Asthma is the most common chronic lung disease in children and young adults worldwide. Airway remodelling (including increased fibroblasts and myofibroblasts in airway walls due to chronic inflammation) differentiates asthmatic from non-asthmatic airways. The increase in airway fibroblasts and myofibroblasts occurs via epithelial to mesenchymal transition (EMT) where epithelial cells lose their tight junctions and are transdifferentiated to mesenchymal cells, with further increases in myofibroblasts occurring via fibroblast-myofibroblast transition (FMT). Transforming growth factor (TGF)-β is the central EMT- and FMT-inducing cytokine. In this study, we have used next generation sequencing to delineate the changes in the transcriptome induced by TGF-β treatment of WI-38 airway fibroblasts in both the short term and after differentiation into myofibroblasts, to gain an understanding of the contribution of TGF-β induced transdifferentiation to the asthmatic phenotype. The data obtained from RNAseq analysis was confirmed by quantitative PCR (qPCR) and protein expression investigated by western blotting. As expected, we found that genes coding for intermediates in the TGF-β signalling pathways (SMADs) were differentially expressed after TGF-β treatment, SMAD2 being upregulated and SMAD3 being downregulated as expected. Further, genes involved in cytoskeletal pathways (FN1, LAMA, ITGB1) were upregulated in myofibroblasts compared to fibroblasts. Importantly, genes that were previously shown to be changed in asthmatic lungs (ADAMTS1, DSP, TIMPs, MMPs) were similarly differentially expressed in myofibroblasts, strongly suggesting that TGF-β mediated differentiation of fibroblasts to myofibroblasts may underlie important changes in the asthmatic airway. We also identified new intermediates of signalling pathways (PKB, PTEN) that are changed in myofibroblasts compared to fibroblasts. We have found a significant number of genes that are altered after TGF-β induced transdifferentiation of WI-38 fibroblasts into myofibroblasts, many of which were expected or predicted. We also identified novel genes and pathways that were affected after TGF-β treatment, suggesting additional pathways are activated during the transition between fibroblasts and myofibroblasts and may contribute to the asthma phenotype.
Age-related changes of individual macular retinal layers among Asians
Authors: Chua Jacqueline , Tham Yih Chung , Tan Bingyao , Devarajan Kavya , Schwarzhans Florian , Gan Alfred , Wong Damon , Cheung Carol Y. , Majithia Shivani , Thakur Sahil , Fischer Georg , Vass Clemens , Cheng Ching-Yu , Schmetterer Leopold
Published: December 2019

We characterized the age-related changes of the intra-retinal layers measured with spectral-domain optical coherence tomography (SD-OCT; Cirrus high-definition OCT [Carl Zeiss Meditec]. The Singapore Epidemiology of Eye Diseases is a population-based, cross-sectional study of Chinese, Malays and Indians living in Singapore. Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) were used for intra-retinal layer segmentation and mean thickness of 10 intra-retinal layers rescaled with magnification correction using axial length value. Linear regression models were performed to investigate the association of retinal layers with risk factors. After excluding participants with history of diabetes or ocular diseases, high-quality macular SD-OCT images were available for 2,047 participants (44–89 years old). Most of the retinal layers decreased with age except for foveal retinal nerve fiber layer (RNFL) and the inner/outer segments of photoreceptors where they increased with age. Men generally had thicker retinal layers than women. Chinese have the thickest RNFL and retinal pigment epithelium amongst the ethnic groups. Axial length and refractive error remained correlated with retinal layers in spite of magnification correction. Our data show pronounced age-related changes in retinal morphology. Age, gender, ethnicity and axial length need be considered when establishing OCT imaging biomarkers for ocular or systemic disease.
Versatile electrochemical approaches towards the fabrication of molecular electronic devices
Authors: Sachan Pradeep , Mondal Prakash Chandra
Published: December 2019

We highlight state-of-the-art electrochemical approaches for diazonium electroreduction on various electrodes that may be suitable for flexible molecular electronic junctions.
A strategy for boosting the thermoelectric performance of famatinite Cu3SbS4
Authors: Tanishita Taiki , Suekuni Koichiro , Nishiate Hirotaka , Lee Chul-Ho , Ohtaki Michitaka
Published: December 2019

Co-substitution of Ge and P for Sb in Cu3SbS4famatinite boosted dimensionless thermoelectric figure of merit.
Synthesis of a CeO2/Co3O4 catalyst with a remarkable performance for the soot oxidation reaction
Authors: Medina J. C. , Rodil S. E. , Zanella Rodolfo
Published: December 2019

A highly active catalyst based on CeO2/Co3O4 for soot oxidation at low temperatures with complete selectivity toward CO2.
Photocatalyzed preferential oxidation of CO under simulated sunlight using Au–transition metal oxide–sepiolite catalysts
Authors: Rodríguez Aguado Elena , Cecilia Juan Antonio , Infantes-Molina Antonia , Talon Aldo , Storaro Loretta , Moretti Elisa , Rodríguez-Castellón Enrique
Published: December 2019

A series of Au–transition metal oxides supported on sepiolite was tested in the preferential oxidation of CO in an excess of H2 under simulated solar light irradiation and in the absence of light, at 30 °C and atmospheric pressure.
Synthesis and structures of mono- and di-nuclear aluminium and zinc complexes bearing α-diimine and related ligands, and their use in the ring opening polymerization of cyclic esters
Authors: Xiao Lin , Zhao Yanxia , Qiao Sijie , Sun Ziyue , Santoro Orlando , Redshaw Carl
Published: December 2019

Multi-metallic complexes (of Al, Zn) derived from imine-based ligands effectively operate as catalysts for the ring opening polymerization (ROP) of ε-caprolactone (ε-CL), δ-valerolactone (δ-VL) and co-polymerization thereof.
Effect of anion dimensionality on optical properties: the ∞[B7O10(OH)2] layer in CsB7O10(OH)2vs. the ∞[B7O12] framework in CsBaB7O12
Authors: Miao Zhaohong , Yang Yun , Wei Zhonglei , Yang Zhihua , Pan Shilie
Published: December 2019

CsB7O10(OH)2 with new FBB features a 2D anionic structure whose band gap is about 6.6 eV and CsBaB7O12 features a 3D anionic structure whose band gap is 5.6 eV. And their simulated birefringence are about 0.08 and 0.05 at 1064 nm, respectively.
Switchable on–off spin-crossover properties of iron(ii) compounds by trimming intermolecular hydrogen bonds
Authors: Li Na , Xue Jin-Peng , Liu Jing-Lin , Wang Yao-Yao , Yao Zi-Shuo , Tao Jun
Published: December 2019

Spin crossover on–off switching is realized by reversible single crystal-to-single crystal transformations,1·3MeOH⇌1⇌1·2HO.
Molecular imprinted polymers for the controlled uptake of sinapic acid from aqueous media
Authors: Fathi Til Roya , Alizadeh-Khaledabad Mohammad , Mohammadi Reza , Pirsa Sajad , Wilson Lee D.
Published: December 2019

Molecularly imprinted polymers (MIPs) were synthesized via a precipitation polymerization method using 4-vinylpyridine as a functional monomer and ethylene glycol dimethacrylate as a cross-linker for selective separation of sinapic acid from water.
Acrylamide in French fries prepared at primary school canteens
Authors: Mesias Marta , Delgado-Andrade Cristina , Holgado Francisca , Morales Francisco J.
Published: December 2019

Children are one of the most exposed groups to dietary acrylamide with ‘potato fried products’ that account for up to half the total exposure to this contaminant.
Intelligent optofluidic analysis for ultrafast single bacterium profiling of cellulose production and morphology
Authors: Yu Jiaqing , Sun Guoyun , Lin Nicholas Weikang , Vadanan Sundaravadanam Vishnu , Lim Sierin , Chen Chia-Hung
Published: December 2019

A continuous-flow intelligent optofluidic device using a convolutional neural network (CNN) computational method was developed to enable high-throughput single-bacterium profiling of bacteria cellulose (BC) with a throughput of ∼35 bacteria per second.
DFT investigation on the mechanisms of Csp3–H functionalization of glycine derivatives induced by radical cation salt
Authors: Zhou Da-Gang , Wang Peng
Published: December 2019

The mechanism of Csp3–H functionalization between ethyl 2-(p-tolylamino)acetate and phenylethylene initiated by tris(4-bromophenyl)aminium hexachloroantimonate was elaborated based on DFT calculations.
Constructing consistent pore microstructures of bacterial cellulose-derived cathode and anode materials for high energy density sodium-ion capacitors
Authors: Zhang Tianyun , Wang Fujuan , Yang Liang , Li Hongxia , Chen Jiangtao , Yang Bingjun , Lang Junwei , Yan Xingbin
Published: December 2019

Bacterial cellulose-derived cathode and anode with similar carbon microstructure are well match in kinetic for high energy density sodium-ion capacitor.
Sr-Doped NiO3 nanorods synthesized by a simple sonochemical method as excellent materials for voltammetric determination of quercetin
Authors: Vinothkumar Venkatachalam , Sangili Arumugam , Chen Shen-Ming , Veerakumar Pitchaimani , Lin King-Chuen
Published: December 2019

A fabricated Sr-doped NiO3 nanorod-modified GCE was developed for electrochemical sensing of quercetin.
Radial aggregation of proteins prevails over axial aggregation on membrane tubes
Authors: Liu Xuejuan , Tian Falin , Yue Tongtao , Zhang Xianren , Zhong Chongli
Published: December 2019

Our simulations show that radial aggregation of proteins prevails over axial aggregation on membrane tubes.
Two-dimensional semiconducting Lu2CT2(T = F, OH) MXene with low work function and high carrier mobility
Authors: Bai Xiaojing , Zha Xian-Hu , Qiao Yingjie , Qiu Nianxiang , Zhang Yiming , Luo Kan , He Jian , Li Qiuwu , Huang Qing , Francisco Joseph S. , Lin Cheng-Te , Du Shiyu
Published: December 2019

Potential structures for Lu-Based MXenes.
L. pneumophilaCMP-5,7-di-N-acetyllegionaminic acid synthetase (LpCLS)-involved chemoenzymatic synthesis of sialosides and analogues
Authors: McArthur John B. , Santra Abhishek , Li Wanqing , Kooner Anoopjit S. , Liu Ziqi , Yu Hai , Chen Xi
Published: December 2019

A bacterial CMP-5,7-di-N-acetyllegionaminic acid synthetase was characterized and used in one-pot multienzyme systems for efficient synthesis of Leg5,7Ac2-glycosides and analogs.
A high-performance polycyanurate network derived from 4,4′-biscyanato-2,2′-trifluoromethylbiphenyl
Authors: Liu Jingfeng , Meng Qingjie , Li Liying , Lu Gewu , Yuan Hang , Cui Lei , Liu Xia , Mu Hongliang , Ji Jingjing , Zhou Defeng , Wang Zhen , Yan Jingling
Published: December 2019

Polycyanurates with excellent thermal, mechanical, and dielectric properties were derived from 4,4′-biscyanato-2,2′-trifluoromethylbiphenyl, and their properties were systematically compared with those of polycyanurates derived from bisphenol A dicyanate.
From Douglas fir to renewable H2-enriched syngas via ex situ catalytic pyrolysis over metal nanoparticles–nanocellulose derived carbon catalysts
Authors: Zhang Yayun , Duan Dengle , Lei Hanwu , Wang Chenxi , Qian Moriko , Villota Elmar , Mateo Wendy
Published: December 2019

A carbon catalyst, which was derived from nanocellulose (NC) and doped with uniform sized and well dispersed metal nanoparticles, showed optimal performance for the generation of H2-enriched (67.4 vol%) syngas from the catalytic pyrolysis of biomass.
A luminescent lyotropic liquid crystal with UV irradiation induced photochromism
Authors: Li Qingrun , Qiu Juan , Liu Hongguo , Chen Xiao
Published: December 2019

A lyotropic liquid crystal of photochromism by UV irradiation was fabricated through doping a unique europium complex with a protic ionic liquid as a solvent.
Bimetallic metal–organic framework-derived MoFe-PC microspheres for electrocatalytic ammonia synthesis under ambient conditions
Authors: Chen Silong , Jang Haeseong , Wang Jia , Qin Qing , Liu Xien , Cho Jaephil
Published: December 2019

MoFe-PC exhibits a high yield rate and faradaic efficiency for NH3 electrosynthesis in acidic electrolytes due to the multicomponent active sites and inherent porous structure.
Promoting the hydrogen evolution reaction through oxygen vacancies and phase transformation engineering on layered double hydroxide nanosheets
Authors: Liu Shujie , Zhu Jie , Sun Mao , Ma Zhixue , Hu Kan , Nakajima Tomohiko , Liu Xianhu , Schmuki Patrik , Wang Lei
Published: December 2019

Effective HER activity on layered double hydroxide nanosheets through a plasma etching strategy.
Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis
Authors: Mao Jinzhu , Wang Hua , Xie Ying , Fu Yangxue , Li Yuce , Liu Pei , Du Hongyao , Zhu Jinjin , Dong Liyun , Hussain Mubashir , Li Yan , Zhang Lianbin , Zhu Jintao , Tao Juan
Published: December 2019

Rapamycin-loaded dissolving microneedles (RAPA DMNs) are fabricated by using polyvinylpyrrolidone (PVP) as the matrix and exhibit the good anti-angiogenic effect.
Synthesis of bismuth sulfide nanobelts for high performance broadband photodetectors
Authors: Xu Jinzhuo , Li Henan , Fang Shaofan , Jiang Ke , Yao Huizhen , Fang Feier , Chen Fuming , Wang Ye , Shi Yumeng
Published: December 2019

We fabricated a superior broadband photodetector based on single crystal Bi2S3nanobelts with a high sensitivity to UV-near infrared light.
Microbiology of Cystic Fibrosis Airway Disease
Authors: Blanchard Ana C. , Waters Valerie J.
Published: December 2019

Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and species of the Burkholderia cepacia complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.
High-Content Immunophenotyping and Hierarchical Clustering Reveal Sources of Heterogeneity and New Surface Markers of Human Blood Monocyte Subsets
Authors: Hoffmann Jedrzej , Fišer Karel , Liebetrau Christoph , Staubach Nora , Kost David , Voss Sandra , Heiden Annkathrin zur , Dörr Oliver , Lipps Christoph , Nef Holger M. , Möllmann Helge , Hamm Christian W. , Keller Till , Troidl Christian
Published: December 2019

Objective Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving.

Rationale In this study, we sought to investigate the immunophenome of circulating human monocyte subsets.

Methods Multiplexed, high-throughput flow cytometry screening arrays and computational data analysis were used to analyze the expression and hierarchical relationships of 242 specific surface markers on circulating classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes in healthy adults.

Results Using generalized linear models and hierarchical cluster analysis, we selected and clustered epitopes that most reliably differentiate between monocyte subsets. We validated existing transcriptional profiling data and revealed potential new surface markers that uniquely define the classical (e.g., BLTR1, CD35, CD38, CD49e, CD89, CD96), intermediate (e.g., CD39, CD275, CD305, CDw328), and nonclassical (e.g., CD29, CD132) subsets. In addition, our analysis revealed phenotypic cell clusters, identified by dendritic markers CMRF-44 and CMRF-56, independent of the traditional monocyte classification.

Conclusion These results reveal an advancement of the clinically applicable multiplexed screening arrays that may facilitate monocyte subset characterization and cytometry-based biomarker selection in various inflammatory disorders.
Organ Transplantation for Cystic Fibrosis
Authors: Morrell Matthew R. , Kiel Sarah C. , Pilewski Joseph M.
Published: December 2019

Cystic fibrosis (CF) remains the most common indication for lung transplantation in children and the third most common in adults and has the highest median survival posttransplant for all pretransplant diagnoses. Criteria for transplant in patients with CF vary widely among transplant centers and early referral to multiple centers may be needed to maximize opportunities for lung transplantation. Comorbidities unique to CF such as resistant and atypical pathogens like Burkholderia and Mycobacterium abscessus, and cirrhosis require special consideration for lung transplantation but should not be considered as absolute contraindications. For those patients who are listed for lung transplantation, mechanical support with extracorporeal membrane oxygenation and mechanical ventilation can be efficacious as bridges to lung transplantation in experienced centers with adequate resources. Liver and pancreas transplantations are also acceptable options for end-organ disease related to CF and can provide improvements in both quantity and quality of life.
Adult Care in Cystic Fibrosis
Authors: Elborn J. Stuart
Published: December 2019

Cystic fibrosis (CF) is now more common in adults than children in countries with well-developed health care systems. The number of adults continues to increase and will further increase if the new cystic fibrosis transmembrane conductance regulator (CFTR) modulators are disease modifying. Most of the complex morbidity and almost all the mortality of CF occur in adults and will increasingly follow this pattern even with new effective modulator therapies. Maintaining good quality of life including social functioning and maximizing survival for adults are the key priorities. This requires a highly knowledgeable and adaptable multidisciplinary team, which, though focused on maintaining lung health, requires an increasing range of other disciplines and specialties to maximize well-being. Changes in health care systems will require current models of care to adapt to provide care for the large number of adult patients. With increasing survival and age, many are likely to have both CF morbidities and additional diseases of aging. New models are needed for health care delivery for this expanding population with complex medical conditions.
Aspirin Therapy for Primary Prevention: The Case for Continuing Prescribing to Patients at High Cardiovascular Risk—A Review
Authors: De Caterina Raffaele , Aimo Alberto , Ridker Paul M.
Published: December 2019

Current evidence supports the use of low-dose aspirin for secondary cardiovascular prevention. By contrast, the benefit-to-risk ratio of aspirin use in primary prevention is debated: three contemporary randomized control trials have been conflicting, and meta-analyses have concluded for an unclear clinical benefit, based on the consideration that the reduction in thromboembolic events is counterbalanced by increased bleeding. The primary prevention setting is, however, a heterogeneous mix of subjects at highly variable cardiovascular risk. One possible explanation for the uncertainty of data interpretation is the progressive reduction in risk of major adverse cardiovascular events (MACEs) in primary prevention that has accompanied global education programs, leading patients to smoke less, exercise more, and increasingly take lipid-lowering therapies. Based on a meta-regression of the benefits and harm of aspirin therapy in primary prevention as a function of the 10-year risk of MACE, we favor a nuanced approach still, however, based on the evaluation of cardiovascular risk, acknowledging differences between patients and emphasizing an individualized assessment of both benefits and harm. After optimal control of cardiovascular risk factors, and when patients are less than 70 years of age, clinicians should assess the risk of MACE and base decision on such stratification, considering the risk of bleeding and patient preferences. Clinicians would then advise the use of aspirin in primary prevention patients at the highest risk of MACE who do not have a prohibitive risk of bleeding, and in the majority of cases after initiation of properly titrated statin therapy.