bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical soliton molecular complexes in a passively mode-locked fibre laser
Authors: Wang Z. Q. , Nithyanandan K. , Coillet A. , Tchofo-Dinda P. , Grelu Ph.
Published: February 2019

Ultrashort optical pulses propagating in a dissipative nonlinear system can interact and bind stably, forming optical soliton molecules. Soliton molecules in ultrafast lasers are under intense research focus and present striking analogies with their matter molecules counterparts. The recent development of real-time spectral measurements allows probing the internal dynamics of an optical soliton molecule, mapping the dynamics of the pulses’ relative separations and phases that constitute the relevant internal degrees of freedom of the molecule. The soliton-pair molecule, which consists of two strongly bound optical solitons, has been the most studied multi-soliton structure. We here demonstrate that two soliton-pair molecules can bind subsequently to form a stable molecular complex and highlight the important differences between the intra-molecular and inter-molecular bonds. The dynamics of the experimentally observed soliton molecular complexes are discussed with the help of fitting models and numerical simulations, showing the universality of these multi-soliton optical patterns.
High-speed mechano-active multielectrode array for investigating rapid stretch effects on cardiac tissue
Authors: Imboden Matthias , de Coulon Etienne , Poulin Alexandre , Dellenbach Christian , Rosset Samuel , Shea Herbert , Rohr Stephan
Published: February 2019

Systematic investigations of the effects of mechano-electric coupling (MEC) on cellular cardiac electrophysiology lack experimental systems suitable to subject tissues to in-vivo like strain patterns while simultaneously reporting changes in electrical activation. Here, we describe a self-contained motor-less device (mechano-active multielectrode-array, MaMEA) that permits the assessment of impulse conduction along bioengineered strands of cardiac tissue in response to dynamic strain cycles. The device is based on polydimethylsiloxane (PDMS) cell culture substrates patterned with dielectric actuators (DEAs) and compliant gold ion-implanted extracellular electrodes. The DEAs induce uniaxial stretch and compression in defined regions of the PDMS substrate at selectable amplitudes and with rates up to 18 s−1. Conduction along cardiomyocyte strands was found to depend linearly on static strain according to cable theory while, unexpectedly, being completely independent on strain rates. Parallel operation of multiple MaMEAs provides for systematic high-throughput investigations of MEC during spatially patterned mechanical perturbations mimicking in-vivo conditions.
FraC nanopores with adjustable diameter identify the mass of opposite-charge peptides with 44 dalton resolution
Authors: Huang Gang , Voet Arnout , Maglia Giovanni
Published: February 2019

A high throughput single-molecule method for identifying peptides and sequencing proteins based on nanopores could reduce costs and increase speeds of sequencing, allow the fabrication of portable home-diagnostic devices, and permit the characterization of low abundance proteins and heterogeneity in post-translational modifications. Here we engineer the size of Fragaceatoxin C (FraC) biological nanopore to allow the analysis of a wide range of peptide lengths. Ionic blockades through engineered nanopores distinguish a variety of peptides, including two peptides differing only by the substitution of alanine with glutamate. We also find that at pH 3.8 the depth of the peptide current blockades scales with the mass of the peptides irrespectively of the chemical composition of the analyte. Hence, this work shows that FraC nanopores allow direct readout of the mass of single peptide in solution, which is a crucial step towards the developing of a real-time and single-molecule protein sequencing device.
Single gold-bridged nanoprobes for identification of single point DNA mutations
Authors: Ma Xingyi , Song Sojin , Kim Soohyun , Kwon Mi-sun , Lee Hyunsook , Park Wounjhang , Sim Sang Jun
Published: February 2019

Consensus ranking of protein affinity to identify point mutations has not been established. Therefore, analytical techniques that can detect subtle variations without interfering with native biomolecular interactions are required. Here we report a rapid method to identify point mutations by a single nanoparticle sensing system. DNA-directed gold crystallization forms rod-like nanoparticles with bridges based on structural design. The nanoparticles enhance Rayleigh light scattering, achieving high refractive-index sensitivity, and enable the system to monitor even a small number of protein-DNA binding events without interference. Analysis of the binding affinity can compile an atlas to distinguish the potential of various point mutations recognized by MutS protein. We use the atlas to analyze the presence and type of single point mutations in BRCA1 from samples of human breast and ovarian cancer cell lines. The strategy of synthesis-by-design of plasmonic nanoparticles for sensors enables direct identification of subtle biomolecular binding distortions and genetic alterations.
A MST1–FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis
Authors: Kim Yoo Hyung , Choi Jeongwoon , Yang Myung Jin , Hong Seon Pyo , Lee Choong-kun , Kubota Yoshiaki , Lim Dae-Sik , Koh Gou Young
Published: February 2019

Hypoxia is a main driver of sprouting angiogenesis, but how tip endothelial cells are directed to hypoxic regions remains poorly understood. Here, we show that an endothelial MST1–FOXO1 cascade is essential for directional migration of tip cells towards hypoxic regions. In mice, endothelial‐specific deletion of either MST1 or FOXO1 leads to the loss of tip cell polarity and subsequent impairment of sprouting angiogenesis. Mechanistically, MST1 is activated by reactive oxygen species (ROS) produced in mitochondria in response to hypoxia, and activated MST1 promotes the nuclear import of FOXO1, thus augmenting its transcriptional regulation of polarity and migration‐associated genes. Furthermore, endothelial MST1‐FOXO1 cascade is required for revascularization and neovascularization in the oxygen-induced retinopathy model. Together, the results of our study delineate a crucial coupling between extracellular hypoxia and an intracellular ROS‐MST1‐FOXO1 cascade in establishing endothelial tip cell polarity during sprouting angiogenesis.
Dual regulation of Arabidopsis AGO2 by arginine methylation
Authors: Hu Po , Zhao Hongwei , Zhu Pei , Xiao Yongsheng , Miao Weili , Wang Yinsheng , Jin Hailing
Published: February 2019

Argonaute (AGO) proteins are core components of RNA interference (RNAi) but the mechanisms of their regulation, especially at the post-translational level, remain unclear. Among the ten AGOs in Arabidopsis, only AGO2 is induced by bacterial infection and is known to positively regulate immunity. Here we show that the N-terminal domain of AGO2 is enriched with arginine-glycine RG/GR repeats, which are methylated by protein arginine methyltransferase5 (PRMT5). Arginine methylation has dual functions in AGO2 regulation. Methylated arginine residues can promote AGO2 protein degradation and are also bound by Tudor-domain proteins (TSNs), which can degrade AGO2-associated small RNAs (sRNAs). PRMT5 is down-regulated during infection and the prmt5 mutant is more resistant to bacteria. We speculate that reduced PRMT5 expression during infection may lead to reduced arginine methylation of AGO2, resulting in accumulation of both AGO2 and, via reduced interaction with TSNs, accumulation of AGO2-associated sRNAs, to promote plant immunity. These results reveal that both the arginine methylation writer (PRMT5) and readers (TSNs) can regulate AGO2-mediated RNAi.
Arbitrary order exceptional point induced by photonic spin–orbit interaction in coupled resonators
Authors: Wang Shubo , Hou Bo , Lu Weixin , Chen Yuntian , Zhang Z. Q. , Chan C. T.
Published: February 2019

Many novel properties of non-Hermitian systems are found at or near the exceptional points—branch points of complex energy surfaces at which eigenvalues and eigenvectors coalesce. In particular, higher-order exceptional points can result in optical structures that are ultrasensitive to external perturbations. Here we show that an arbitrary order exceptional point can be achieved in a simple system consisting of identical resonators placed near a waveguide. Unidirectional coupling between any two chiral dipolar states of the resonators mediated by the waveguide mode leads to the exceptional point, which is protected by the transverse spin–momentum locking of the guided wave and is independent of the positions of the resonators. Various analytic response functions of the resonators at the exceptional points are experimentally manifested in the microwave regime. The enhancement of sensitivity to external perturbations near the exceptional point is also numerically and analytically demonstrated.
Author Correction: Caution in inferring viral strategies from abundance correlations in marine metagenomes
Authors: Alrasheed Hend , Jin Rong , Weitz Joshua S.
Published: February 2019

The original version of the Article contained a spelling error in the word ‘piggyback’. This error has been corrected in both the PDF and HTML versions of the Article.
A potential peptide derived from cytokine receptors can bind proinflammatory cytokines as a therapeutic strategy for anti-inflammation
Authors: Jiang Shinn-Jong , Tsai Pei-I , Peng Shih-Yi , Chang Chun-Chun , Chung Yi , Tsao Hao-Hsiang , Huang Hsin-Ting , Chen San-Yuan , Hsu Hao-Jen
Published: February 2019

Chronic inflammation is a pivotal event in the pathogenesis of cardiovascular diseases, including atherosclerosis, restenosis, and coronary artery disease. The efficacy of current treatment or preventive strategies for such inflammation is still inadequate. Thus, new anti-inflammatory strategies are needed. In this study, based on molecular docking and structural analysis, a potential peptide KCF18 with amphiphilic properties (positively charged and hydrophobic residues) derived from the receptors of proinflammatory cytokines was designed to inhibit cytokine-induced inflammatory response. Simulations suggested that KCF18 could bind to cytokines simultaneously, and electrostatic interactions were dominant. Surface plasmon resonance detection showed that KCF18 bound to both tumor necrosis factor-α (TNF-α) and interleukin-6, which is consistent with MM/PBSA binding free energy calculations. The cell experiments showed that KCF18 significantly reduced the binding of proinflammatory cytokines to their cognate receptors, suppressed TNF-α mRNA expression and monocyte binding and transmigration, and alleviated the infiltration of white blood cells in a peritonitis mouse model. The designed peptide KCF18 could remarkably diminish the risk of vascular inflammation by decreasing plasma cytokines release and by directly acting on the vascular endothelium. This study demonstrated that a combination of structure-based in silico design calculations, together with experimental measurements can be used to develop potential anti-inflammatory agents.
Efficient system for upstream mRNA trans-splicing to generate covalent, head-to-tail, protein multimers
Authors: Mitsuhashi Hiroaki , Homma Sachiko , Beermann Mary Lou , Ishimaru Satoshi , Takeda Hayato , Yu Bryant K. , Liu Kevin , Duraiswamy Swetha , Boyce Frederick M. , Miller Jeffrey Boone
Published: February 2019

We present a plasmid-based system in which upstream trans-splicing efficiently generates mRNAs that encode head-to-tail protein multimers. In this system, trans-splicing occurs between one of two downstream splice donors in the sequence encoding a C-terminal V5 epitope tag and an upstream splice acceptor in the 5′ region of the pCS2(+) host plasmid. Using deletion and fusion constructs of the DUX4 protein as an example, we found that this system produced trans-spliced mRNAs in which coding regions from independent transcripts were fused in phase such that covalent head-to-tail protein multimers were translated. For a cDNA of ~450 bp, about half of the expressed proteins were multimeric, with the efficiency of trans-splicing and extent of multimer expression decreasing as cDNA length increased. This system generated covalent heterodimeric proteins upon co-transfections of plasmids encoding separate proteins and did not require a long complementary binding domain to position mRNAs for trans-splicing. This plasmid-based trans-splicing system is adaptable to multiple gene delivery systems, and it presents new opportunities for investigating molecular mechanisms of trans-splicing, generating covalent protein multimers with novel functions within cells, and producing mRNAs encoding large proteins from split precursors.
Network Analysis of the Multidimensional Symptom Experience of Oncology
Authors: Papachristou Nikolaos , Barnaghi Payam , Cooper Bruce , Kober Kord M. , Maguire Roma , Paul Steven M. , Hammer Marilyn , Wright Fay , Armes Jo , Furlong Eileen P. , McCann Lisa , Conley Yvette P. , Patiraki Elisabeth , Katsaragakis Stylianos , Levine Jon D. , Miaskowski Christine
Published: February 2019

Oncology patients undergoing cancer treatment experience an average of fifteen unrelieved symptoms that are highly variable in both their severity and distress. Recent advances in Network Analysis (NA) provide a novel approach to gain insights into the complex nature of co-occurring symptoms and symptom clusters and identify core symptoms. We present findings from the first study that used NA to examine the relationships among 38 common symptoms in a large sample of oncology patients undergoing chemotherapy. Using two different models of Pairwise Markov Random Fields (PMRF), we examined the nature and structure of interactions for three different dimensions of patients’ symptom experience (i.e., occurrence, severity, distress). Findings from this study provide the first direct evidence that the connections between and among symptoms differ depending on the symptom dimension used to create the network. Based on an evaluation of the centrality indices, nausea appears to be a structurally important node in all three networks. Our findings can be used to guide the development of symptom management interventions based on the identification of core symptoms and symptom clusters within a network.
AEO7 Surfactant as an Eco-Friendly Corrosion Inhibitor for Carbon Steel in HCl solution
Authors: Sliem Mostafa H. , Afifi Mohammed , Bahgat Radwan A. , Fayyad Eman M. , Shibl Mohamed F. , Heakal Fakiha El-Taib , Abdullah Aboubakr M.
Published: February 2019

The impact of AEO7 surfactant on the corrosion inhibition of carbon steel (C-steel) in 0.5 M HCl solution at temperatures between 20 °C and 50 °C was elucidated using weight loss and different electrochemical techniques. The kinetics and thermodynamic parameters of the corrosion and inhibition processes were reported. The corrosion inhibition efficiency (IE%) improved as the concentration of AEO7 increased. In addition, a synergistic effect was observed when a concentration of 1 × 10−3 mol L−1or higher of potassium iodide (KI) was added to 40 µmol L−1of the AEO7 inhibitor where the corrosionIE% increased from 87.4% to 99.2%. Also, it was found that the adsorption of AEO7 surfactant on C-steel surface followed the Freundlich isotherm. Furthermore, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization measurements indicated that AEO7 was physically adsorbed on the steel surface. The surface topography was examined using an optical profilometer, an atomic force microscope (AFM), and a scanning electron-microscope (SEM) coupled with an energy dispersion X-ray (EDX) unit. Quantum chemical calculations based on the density functional theory were performed to understand the relationship between the corrosionIE% and the molecular structure of the AEO7 molecule.
Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel
Authors: Reichhart Nadine , Schöberl Simon , Keckeis Susanne , Alfaar Ahmad S. , Roubeix Christophe , Cordes Magdalena , Crespo-Garcia Sergio , Haeckel Akvile , Kociok Norbert , Föckler Renate , Fels Gabriele , Mataruga Anja , Rauh Robert , Milenkovic Vladimir M. , Zühlke Kerstin , Klussmann Enno , Schellenberger Eyk , Strauß Olaf
Published: February 2019

Changes in cell function occur by specific patterns of intracellular Ca2+, activating Ca2+-sensitive proteins. The anoctamin (TMEM16) protein family has Ca2+-dependent ion channel activity, which provides transmembrane ion transport, and/or Ca2+-dependent phosphatidyl-scramblase activity. Using amino acid sequence analysis combined with measurements of ion channel function, we clarified the so far unknown Ano4 function as Ca2+-dependent, non-selective monovalent cation channel; heterologous Ano4 expression in HEK293 cells elicits Ca2+ activated conductance with weak selectivity of K+ > Na+ > Li+. Endogenously expressed Ca2+-dependent cation channels in the retinal pigment epithelium were identified as Ano4 by KO mouse-derived primary RPE cells and siRNA against Ano4. Exchanging a negatively charged amino acid in the putative pore region (AA702–855) into a positive one (E775K) turns Ano4-elicited currents into Cl− currents evidencing its importance for ion selectivity. The molecular identification of Ano4 as a Ca2+-activated cation channel advances the understanding of its role in Ca2+ signaling.
Dynamic Networks that Drive the Process of Irreversible Step-Growth Polymerization
Authors: Schamboeck Verena , Iedema Piet D. , Kryven Ivan
Published: February 2019

Many research fields, reaching from social networks and epidemiology to biology and physics, have experienced great advance from recent developments in random graphs and network theory. In this paper we propose a generic model of step-growth polymerisation as a promising application of the percolation on a directed random graph. This polymerisation process is used to manufacture a broad range of polymeric materials, including: polyesters, polyurethanes, polyamides, and many others. We link features of step-growth polymerisation to the properties of the directed configuration model. In this way, we obtain new analytical expressions describing the polymeric microstructure and compare them to data from experiments and computer simulations. The molecular weight distribution is related to the sizes of connected components, gelation to the emergence of the giant component, and the molecular gyration radii to the Wiener index of these components. A model on this level of generality is instrumental in accelerating the design of new materials and optimizing their properties, as well as it provides a vital link between network science and experimentally observable physics of polymers.
Mitochondrial Haplogroup and the Risk of Acute Kidney Injury Following Cardiac Bypass Surgery
Authors: Kanagasundaram Nigel S. , Baudouin Simon V. , Rowling Sarah , Prabhu Mahesh , Dark John H. , Goodship Timothy H. J. , Chinnery Patrick F. , Hudson Gavin
Published: February 2019

Although mitochondrial dysfunction plays a key role in the pathophysiology of acute kidney injury (AKI), the influence of mitochondrial genetic variability in this process remains unclear. We explored the association between the risk of post-cardiac bypass AKI and mitochondrial haplotype – inherited mitochondrial genomic variations of potentially functional significance. Our single-centre study recruited consecutive patients prior to surgery. Exclusions included stage 5 CKD, non-Caucasian race and subsequent off-pump surgery. Haplogroup analysis allowed characterisation of the study population using the common mutations and by phylogenetic supergroup (WXI and HV). Chi-square tests for association allowed the identification of potential predictors of AKI for use in logistic regression analysis. AKI occurred in 12.8% of the study population (n = 881; male 69.6%, non-diabetic 78.5%, median (interquartile range) age 68.0 (61.0–75.0) years). The haplogroup profile comprised H (42.7%), J (12.1%), T (10.9%), U (14.4%) and K (7.6%). Although the regression model was statistically significant (χ2 = 95.483, p < 0.0005), neither the phylogenetic supergroups nor any individual haplogroup was a significant contributor. We found no significant association between common European haplogroups and the risk of post-cardiac bypass AKI. However, given the major role of mitochondrial dysfunction in AKI, there is a need to replicate our findings in other cohorts and with other aetiologies of AKI.
Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity
Authors: Lee Ba-Wool , Ha Thi Kim Quy , Pham Ha Thanh Tung , Hoang Quynh Hoa , Tran Van On , Oh Won Keun
Published: February 2019

As part of an ongoing study of new insulin mimetic agents from medicinal plants, the 70% EtOH extract of Symplocos cochinchinensis was found to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. The intensive targeted isolation of this active extract resulted in ten new hydroxyoleoside-type compounds conjugated with a phenolic acid and monoterpene (1–6 and 8–11), as well as four known compounds (7 and 12–14). The chemical structures of the new compounds were determined based on spectroscopic data analysis (1H and 13C NMR, HSQC, HMBC, NOESY and MS). The absolute configurations of the isolated compounds were determined by electronic circular dichroism (ECD) analysis of derivatives obtained after a series of reactions, such as those with dirhodium (ІІ) tetrakis (trifluoroacetate) and dimolybdenum (ІІ) tetraacetate. In vitro, compounds 3, 7 and 8 moderately increased the 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) uptake level in differentiated 3T3-L1 adipocytes. For further studies, we evaluated their effects on the expression of glucose transporter-4 (GLUT4), its translocation, protein tyrosine phosphatase 1B (PTP1B) inhibition and expression of phosphorylated Akt. Our results strongly suggest that the traditional uses of this plant can be described as active constituents by hydroxyoleoside-type compounds.
A New Stress Test for Knee Joint Cartilage
Authors: Paranjape Chinmay S. , Cutcliffe Hattie C. , Grambow Steven C. , Utturkar Gangadhar M. , Collins Amber T. , Garrett William E. , Spritzer Charles E. , DeFrate Louis E.
Published: February 2019

Cartilage metabolism—both the synthesis and breakdown of cartilage constituents and architecture—is influenced by its mechanical loading. Therefore, physical activity is often recommended to maintain cartilage health and to treat or slow the progression of osteoarthritis, a debilitating joint disease causing cartilage degeneration. However, the appropriate exercise frequency, intensity, and duration cannot be prescribed because directin vivoevaluation of cartilage following exercise has not yet been performed. To address this gap in knowledge, we developed a cartilage stress test to measure thein vivostrain response of healthy human subjects’ tibial cartilage to walking exercise. We varied both walk duration and speed in a dose-dependent manner to quantify how these variables affect cartilage strain. We found a nonlinear relationship between walk duration andin vivocompressive strain, with compressive strain initially increasing with increasing duration, then leveling off with longer durations. This work provides innovative measurements of cartilage creep behavior (which has been well-documentedin vitrobut notin vivo) during walking. This study showed that compressive strain increased with increasing walking speed for the speeds tested in this study (0.9–2.0 m/s). Furthermore, our data provide novel measurements of thein vivostrain response of tibial cartilage to various doses of walking as a mechanical stimulus, with maximal strains of 5.0% observed after 60 minutes of walking. These data describe physiological benchmarks for healthy articular cartilage behavior during walking and provide a much-needed baseline for studies investigating the effect of exercise on cartilage health.
Comparing the effects of intravenous and subcutaneous Erythropoietin on blood indices in hemodialysis patients
Authors: Ghasemi Faramarz , Abdi Alireza , Salari Nader , Tohidi Mohammad Reza , Faraji Aazam
Published: February 2019

Erythropoietin is used routinely in hemodialysis patients to increase hemoglobin levels in patients with ESRD and anemia. Considering the importance of anemia in hemodialysis patients and its complications, in this study, the effect of erythropoietin administration on blood parameters by comparing the methods of subcutaneous and intravenous administrations was investigated. The research was done as a retrospective descriptive-analytic study. The subjects were 300 hemodialysis patients receiving erythropoietin in two groups (intravenous and subcutaneous) from hospitals affiliated to Kurdistan and Kermanshah University of Medical Sciences. Data were extracted from the patients’ records and entered into a researcher-made checklist during 6 months and analyzed using SPSS version 20 and descriptive and inferential statistics. The results showed that there was a significant difference between the mean rank of hematocrit in subcutaneous and intravenous injections (P-value = 0.002) and it was higher in the subcutaneous injection group. Also, independent t-test showed that there was a significant difference between the mean of hemoglobin concentration among subcutaneous and intravenous injections (P-value = 0.001) and it was higher in the subcutaneous injection group. However, there was no significant difference between the mean of ferritin in both groups (P-value = 0.084). According to the results, the injection of erythropoietin in the subcutaneous method was more effective than intravenous. It is recommended to use this approach to improve blood indices in hemodialysis patients.
Pressure build-up and stress variations within the Earth’s crust in the light of analogue models
Authors: Moulas Evangelos , Sokoutis Dimitrios , Willingshofer Ernst
Published: February 2019

Strength contrasts and spatial variations in rheology are likely to produce significant stress differences in the Εarth’s crust. The buildup and the relaxation of stresses have important consequences for the state of stress of the brittle crust, its deformational behaviour and seismicity. We performed scaled analogue experiments of a classic wedge-type geometry wherein we introduced a weak, fluid-filled body representing a low-stress heterogeneity. The experiments were coupled to direct pressure measurements that revealed significant pressure differences from their surrounding stressed matrix. The magnitude of the pressure variations is similar to the magnitude of the differential stress of the strongest lithology in the system. When rocks with negligible differential stresses are considered, their pressure can be more than twice larger than the surrounding lithostatic stress. The values of the pressure variations are consistent with the stresses that are estimated in analytical studies. This behaviour is not restricted to a particular scale or rheology, but it requires materials that are able to support different levels of stress upon deformation. For non-creeping rheological behaviours, the stress and pressure variations are maintained even after deformation ceases, implying that these stress variations can be preserved in nature over geological timescales.
Assessing Molecular Epidemiology of Carbapenem-resistant Klebsiella pneumoniae (CR-KP) with MLST and MALDI-TOF in Central China
Authors: Meng Xiujuan , Yang Jun , Duan Juping , Liu Sidi , Huang Xun , Wen Ximao , Huang Xin , Fu Chenchao , Li Jie , Dou Qingya , Liu Yao , Wang Jia , Yan Qun , Zou Mingxiang , Liu Wenen , Peng Zhong , Chen Liang , Li Chunhui , Wu Anhua
Published: February 2019

Carbapenem-resistant K. pneumoniae (CR-KP) posts significant public health challenge worldwide. The aim of this study is to assess clinical characteristics and molecular epidemiology of CR-KP infections with Multilocus sequence typing (MLST) and Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF) in Central China. A total of 71 CR-KP isolates were recovered in a teaching hospital from October 2014 to December 2015. Among all CR-KP isolates, 73.2% (52) produced K. pneumoniae carbapenemases-2 (KPC-2). Eighteen ST types were identified by MLST, among these ST types, forty-seven isolates belonged to ST11 type, which was the predominant outbreak strain in China, and most ST11 isolates produced KPC-2. Eleven mass spectrometry (MS) types were identified by MALDI-TOF MS analysis, 53.5% isolates were MS4 and MS6, which matched with ST11 in MLST analysis. CR-KP infection was associated with increased medical cost and longer hospitalization. Therefore, we found that KPC-2-producing ST11 (MS4 and MS6) CR-KP isolates were the predominant clone identified by MLST and MALDI-TOF, and CR-KP infection was associated with increased hospital costs and longer hospitalization.
Shrub establishment favoured and grass dominance reduced in acid heath grassland systems cleared of invasive Rhododendron ponticum
Authors: Jones Gruffydd Lloyd , Tomlinson Max , Owen Rhys , Scullion John , Winters Ana , Jenkins Tom , Ratcliffe John , Gwynn-Jones Dylan
Published: February 2019

Rhododendron ponticum L. is a damaging invasive alien species in Britain, favouring the moist, temperate climate, and the acidic soils of upland areas. It outshades other species and is thought to create a soil environment of low pH that may be higher in phytotoxic phenolic compounds. We investigated native vegetation restoration and R. ponticum regeneration post-clearance using heathland sites within Snowdonia National Park, Wales; one site had existing R. ponticum stands and three were restoring post-clearance. Each site also had an adjacent, uninvaded control for comparison. We assessed whether native vegetation restoration was influenced post-invasion by soil chemical properties, including pH and phytotoxic compounds, using Lactuca sativa L. (lettuce) bioassays supported by liquid chromatography-mass spectroscopy (LC-MSn). Cleared sites had higher shrub and bare ground cover, and lower grass and herbaceous species cover relative to adjacent uninvaded control sites; regenerating R. ponticum was also observed on all cleared sites. No phenolic compounds associated with R. ponticum were identified in any soil water leachates, and soil leachates from cleared sites had no inhibitory effect in L. sativa germination assays. We therefore conclude that reportedly phytotoxic compounds do not influence restoration post R. ponticum clearance. Soil pH however was lower beneath R. ponticum and on cleared sites, relative to adjacent uninvaded sites. The lower soil pH post-clearance may have favoured shrub species, which are typically tolerant of acidic soils. The higher shrub cover on cleared sites may have greater ecological value than unaffected grass dominated sites, particularly given the recent decline in such valuable heathland habitats. The presence of regenerating R. ponticum on all cleared sites however highlights the critical importance of monitoring and re-treating sites post initial clearance.
Cell-Penetrating Protein/Corrole Nanoparticles
Authors: Soll Matan , Goswami Tridib K. , Chen Qiu-Cheng , Saltsman Irena , Teo Ruijie D. , Shahgholi Mona , Lim Punnajit , Di Bilio Angel J. , Cohen Sarah , Termini John , Gray Harry B. , Gross Zeev
Published: February 2019

Recent work has highlighted the potential of metallocorroles as versatile platforms for the development of drugs and imaging agents, since the bioavailability, physicochemical properties and therapeutic activity can be dramatically altered by metal ion substitution and/or functional group replacement. Significant advances in cancer treatment and imaging have been reported based on work with a water-soluble bis-sulfonated gallium corrole in both cellular and rodent-based models. We now show that cytotoxicities increase in the order Ga < Fe < Al < Mn < Sb < Au for bis-sulfonated corroles; and, importantly, that they correlate with metallocorrole affinities for very low density lipoprotein (VLDL), the main carrier of lipophilic drugs. As chemotherapeutic potential is predicted to be enhanced by increased lipophilicity, we have developed a novel method for the preparation of cell-penetrating lipophilic metallocorrole/serum-protein nanoparticles (NPs). Cryo-TEM revealed an average core metallocorrole particle size of 32 nm, with protein tendrils extending from the core (conjugate size is ~100 nm). Optical imaging of DU-145 prostate cancer cells treated with corrole NPs (≤100 nM) revealed fast cellular uptake, very slow release, and distribution into the endoplasmic reticulum (ER) and lysosomes. The physical properties of corrole NPs prepared in combination with transferrin and albumin were alike, but the former were internalized to a greater extent by the transferrin-receptor-rich DU-145 cells. Our method of preparation of corrole/protein NPs may be generalizable to many bioactive hydrophobic molecules to enhance their bioavailability and target affinity.
Crystal structure and substrate interactions of an unusual fungal non-CBM carrying GH26 endo-β-mannanase from Yunnania penicillata
Authors: von Freiesleben Pernille , Moroz Olga V. , Blagova Elena , Wiemann Mathias , Spodsberg Nikolaj , Agger Jane W. , Davies Gideon J. , Wilson Keith S. , Stålbrand Henrik , Meyer Anne S. , Krogh Kristian B. R. M.
Published: February 2019

Endo-β(1 → 4)-mannanases (endomannanases) catalyse degradation of β-mannans, an abundant class of plant polysaccharides. This study investigates structural features and substrate binding of YpenMan26A, a non-CBM carrying endomannanase from Yunnania penicillata. Structural and sequence comparisons to other fungal family GH26 endomannanases showed high sequence similarities and conserved binding residues, indicating that fungal GH26 endomannanases accommodate galactopyranosyl units in the −3 and −2 subsites. Two striking amino acid differences in the active site were found when the YpenMan26A structure was compared to a homology model of Wsp.Man26A from Westerdykella sp. and the sequences of nine other fungal GH26 endomannanases. Two YpenMan26A mutants, W110H and D37T, inspired by differences observed in Wsp.Man26A, produced a shift in how mannopentaose bound across the active site cleft and a decreased affinity for galactose in the −2 subsite, respectively, compared to YpenMan26A. YpenMan26A was moreover found to have a flexible surface loop in the position where PansMan26A from Podospora anserina has an α-helix (α9) which interacts with its family 35 CBM. Sequence alignment inferred that the core structure of fungal GH26 endomannanases differ depending on the natural presence of this type of CBM. These new findings have implications for selecting and optimising these enzymes for galactomannandegradation.
Rapid confocal imaging of vesicle-to-sponge phase droplet transition in dilute dispersions of the C10E3 surfactant
Authors: Schroder André Pierre , Crassous Jérôme Joseph , Marques Carlos Manuel , Olsson Ulf
Published: February 2019

The lamellar-to-sponge phase transition of fluorescently labelled large unilamellar vesicles (LUVs) of the non-ionic surfactant triethylene glycol mono n-decyl ether (C10E3) was investigated in situ by confocal laser scanning microscopy (CLSM). Stable dispersions of micrometer-sized C10E3 LUVs were prepared at 20 °C and quickly heated at different temperatures close to the lamellar-to-sponge phase transition temperature. Phase transition of the strongly fluctuating individual vesicles into micrometre-sized sponge phase droplets was observed to occur via manyfold multilamellar morphologies with increasing membrane confinement through inter- and intra- lamellar fusion. The very low bending rigidity and lateral tension of the C10E3 bilayer were supported by quantitative image analysis of a stable fluctuating membrane using both flicker noise spectroscopy and spatial autocorrelation function.
Hypoallergenic and anti-inflammatory feeds in children with complicated severe acute malnutrition: an open randomised controlled 3-arm intervention trial in Malawi
Authors: Bartels Rosalie H. , Chimwezi Emmanuel , Watson Victoria , Pei Leilei , Potani Isabel , Allubha Benjamin , Chidzalo Kate , Wang Duolao , Dube Queen , Mallewa Macpherson , Allen Angela , Bandsma Robert H. J. , Voskuijl Wieger P. , Allen Stephen J.
Published: February 2019

Intestinal pathology in children with complicated severe acute malnutrition (SAM) persists despite standard management. Given the similarity with intestinal pathology in non-IgE mediated gastrointestinal food allergy and Crohn’s disease, we tested whether therapeutic feeds effective in treating these conditions may benefit children with complicated SAM. After initial clinical stabilisation, 95 children aged 6–23 months admitted at Queen Elizabeth Central Hospital, Blantyre, Malawi between January 1st and December 31st, 2016 were allocated randomly to either standard feeds, an elemental feed or a polymeric feed for 14 days. Change in faecal calprotectin as a marker of intestinal inflammation and the primary outcome was similar in each arm: elemental vs. standard 4.1 μg/mg stool/day (95% CI, −29.9, 38.15; P = 0.81) and polymeric vs. standard 10 (−23.96, 43.91; P = 0.56). Biomarkers of intestinal and systemic inflammation and mucosal integrity were highly abnormal in most children at baseline and abnormal values persisted in all three arms. The enteropathy in complicated SAM did not respond to either standard feeds or alternative therapeutic feeds administered for up to 14 days. A better understanding of the pathogenesis of the gut pathology in complicated SAM is an urgent priority to inform the development of improved therapeutic interventions.
Impact of origin-destination information in epidemic spreading
Authors: Gómez Sergio , Fernández Alberto , Meloni Sandro , Arenas Alex
Published: February 2019

The networked structure of contacts shapes the spreading of epidemic processes. Recent advances on network theory have improved our understanding of the epidemic processes at large scale. The relevance of several considerations still needs to be evaluated in the study of epidemic spreading. One of them is that of accounting for the influence of origin and destination patterns in the flow of the carriers of an epidemic. Here we compute origin-destination patterns compatible with empirical data of coarse grained flows in the air transportation network. We study the incidence of epidemic processes in a metapopulation approach considering different alternatives to the flows prior knowledge. The data-driven scenario where the estimation of origin and destination flows is considered turns out to be relevant to assess the impact of the epidemics at a microscopic level (in our scenario, which populations are infected). However, this information is irrelevant to assess its macroscopic incidence (fraction of infected populations). These results are of interest to implement even better computational platforms to forecast epidemic incidence.
Sources and selection of snow-specific microbial communities in a Greenlandic sea ice snow cover
Authors: Maccario Lorrie , Carpenter Shelly D. , Deming Jody W. , Vogel Timothy M. , Larose Catherine
Published: February 2019

Sea ice and its snow cover are critical for global processes including climate regulation and biogeochemical cycles. Despite an increase in studies focused on snow microorganisms, the ecology of snow inhabitants remains unclear. In this study, we investigated sources and selection of a snowpack-specific microbial community by comparing metagenomes from samples collected in a Greenlandic fjord within a vertical profile including atmosphere, snowpack with four distinct layers of snow, sea ice brine and seawater. Microbial communities in all snow layers derived from mixed sources, both marine and terrestrial, and were more similar to atmospheric communities than to sea ice or seawater communities. The surface snow metagenomes were characterized by the occurrence of genes involved in photochemical stress resistance, primary production and metabolism of diverse carbon sources. The basal saline snow layer that was in direct contact with the sea ice surface harbored a higher abundance of cells than the overlying snow layers, with a predominance of Alteromonadales and a higher relative abundance of marine representatives. However, the overall taxonomic structure of the saline layer was more similar to that of other snow layers and the atmosphere than to underlying sea ice and seawater. The expulsion of relatively nutrient-rich sea ice brine into basal snow might have stimulated the growth of copiotrophic psychro- and halotolerant snow members. Our study indicates that the size, composition and function of snowpack microbial communities over sea ice were influenced primarily by atmospheric deposition and inflow of sea ice brine and that they form a snow-specific assemblage reflecting the particular environmental conditions of the snowpack habitat.
Delayed treatment of α5 GABAA receptor inverse agonist improves functional recovery by enhancing neurogenesis after cerebral ischemia-reperfusion injury in rat MCAO model
Authors: He Wei-Ming , Ying-Fu Li , Wang He , Peng Yu-Ping
Published: February 2019

Development of effective therapeutics and treatment strategy to promote recovery after cerebral ischemia-reperfusion injury necessitates further understandings of the complex pathophysiology of ischemic stroke. Given that α5-GABAAR inhibition has been shown to be involved in functional recovery after stroke, the present study was designed to evaluate the effects of treatment timing of α5 GABAAR inhibition on post-middle cerebral artery occlusion (MCAO) functional recovery. To this end, we examined the effects of L655,708 (α5 GABAAR inverse agonist) treatment at 3 or 7 days post-ischemia on apoptosis and neurogenesis in the peri-infarct region, brain infarction size, as well as modified neurological severity score (mNSS) and rotarod test time in rats. Consistent with previous reports, we found that when the treatment of L655,708 was initiated at post-MCAO day 3, it did not alter the functional recovery in rats. However, when the treatment of L655,708 was initiated at post-MCAO day 7, it demonstrated beneficial effects on functional recovery in rats. Interestingly, this phenomenon was not associated with altered brain infarction size nor with changes in brain cell apoptosis. However, we found that delayed treatment of L655,708 at post-MCAO day 7 significantly increased neurogenesis in peri-infarct zone in rats. These results suggested that removing α5 GABAAR-mediated tonic inhibition after cerebral ischemia-reperfusion injury may be an effective therapeutic strategy for promoting functional recovery from stroke.
Multiple neuropeptides produced by sex-specific neurons control activity of the male accessory glands and gonoducts in the silkworm Bombyx mori
Authors: Čižmár Daniel , Roller Ladislav , Pillerová Miriam , Sláma Karel , Žitňan Dušan
Published: February 2019

The male accessory glands (AG) and gonoducts of moths develop during metamorphosis and are essential for successful fertilization of females. We found that these reproductive organs are innervated by a sex-specific cluster of peptidergic neurons in the posterior 9th neuromere of the terminal abdominal ganglion (TAG). This cluster of ~20 neurons differentiate during metamorphosis to innervate the accessory glands and sperm ducts. Using immunohistochemistry and in situ hybridization (ISH) we showed that these neurons express four neuropeptide precursors encoding calcitonin-like diuretic hormone (CT-DH), allatotropin (AT) and AT-like peptides (ATLI-III), allatostatin C (AST-C), and myoinhibitory peptides (MIPs). We used contraction bioassay in vitro to determine roles of these neuropeptides in the gonoduct and accessory gland activity. Spontaneous contractions of the seminal vesicle and AG were stimulated in a dose depended manner by CT-DH and AT, whereas AST-C and MIP elicited dose dependent inhibition. Using quantitative RT-PCR we confirmed expression of receptors for these neuropeptides in organs innervated by the male specific cluster of neurons. Our results suggest a role of these neuropeptides in regulation of seminal fluid movements during copulation.
Safety of temporary ileostomy via specimen extraction site in rectal cancer patients who underwent laparoscopic low anterior resection
Authors: Lee Kil-yong , Park Ji Won , Lee Ki-young , Cho Sangsik , Kwon Yoon-Hye , Kim Min Jung , Ryoo Seung-Bum , Jeong Seung-Yong , Park Kyu Joo
Published: February 2019

If anastomotic site leakage is expected after laparoscopic low anterior resection (LAR), de-functioning ileostomy is required. However, there is controversy about the consequence of stoma formation via the specimen extraction site (SES). Therefore, we aimed to investigate stoma-related complication according to stoma formation via the SES. We enrolled rectal cancer patients who underwent laparoscopic LAR with temporary ileostomy between January 2013 and December 2017. Patients were divided into two groups: stoma through the SES (SES) and stoma through a new site (NS). The difference in the incidence of stoma-related complications was analysed. In total, 198 patients underwent laparoscopic LAR (SES = 141 patients, NS = 57 patients). The SES group had a shorter operation time (204.7 ± 74.4 min vs 229.5 ± 90.5 min, p = 0.049) and was associated with fewer cases of wound infection (0% vs 7%, p = 0.006) than the NS group. There was no statistically significant difference between the SES group and NS group in all-stoma complications (22.7% vs 12.3%, p = 0.095). The incidence of parastomal hernia also was not significantly different (11.3% vs 5.3%, p = 0.286). Stoma via the SES is feasible after laparoscopic LAR with temporary ileostomy, although stoma-related complication rate was higher, without a significant difference. It can shorten the operation time and reduce wound infection rate.
In-situ preparation of plant samples in ESEM for energy dispersive x-ray microanalysis and repetitive observation in SEM and ESEM
Authors: Tihlaříková Eva , Neděla Vilém , Đorđević Biljana
Published: February 2019

The Extended Low Temperature Method (ELTM) for the in-situ preparation of plant samples in an environmental scanning electron microscope enables carrying out repetitive topographical and material analysis at a higher resolution in the vacuum conditions of a scanning electron microscope or in the low gas pressure conditions of an environmental scanning electron microscope. The method does not require any chemical intervention and is thus suitable for imaging delicate structures rarely observable with common treatment methods. The method enables both sample stabilization as close to their native state as possible, as well as the transfer of the same sample from a low vacuum to an atmospheric condition for sample storage or later study. It is impossible for wet samples in the environmental scanning electron microscope. Our studies illustrate the high applicability of the ELTM for different types of plant tissue, from imaging of plant waxes at higher resolution, the morphological study of highly susceptible early somatic embryos to the elemental microanalysis of root cells. The method established here provides a very fast, universal and inexpensive solution for plant sample treatment usable in a commercial environmental scanning electron microscope equipped with a cooling Peltier stage.