bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic Analysis of IPEC‐J2 Cells in Response to Coinfection by Porcine Transmissible Gastroenteritis Virus and Enterotoxigenic Escherichia coli K88
Authors: Xia Lu , Dai Lei , Zhu Liqi , Hu Weiwei , Yang Qian
Published: November 2017

Scope

Piglet diarrhea causes large economic losses to the swine industry. Epidemiological investigations show that piglet diarrhea is often caused by mixed infections, but the mechanisms by which multiple microorganisms cause disease are unclear.

Experimental design

Because transmissible gastroenteritis virus (TGEV) and enterotoxigenic Escherichia coli K88 (ETEC K88) are important contributors to piglet diarrhea, coinfection experiments are conducted using porcine intestinal columnar epithelial cells (IPEC‐J2) as a model system. In order to evaluate piglet diarrhea caused TGEV and ETEC K88, the authors examin the effects of coinfection in IPEC‐J2 cells. In TGEV pre‐infected IPEC‐J2 cells, ETEC K88 adhesion is enhanced over uninfected cells. ETEC K88 is also found to inhibit the proliferation of TGEV. Additionally, cytokine levels (IL‐1β, IL‐6, IL‐8, and TNF‐α) in coinfected cells are lower than cells infected by TGEV alone, and higher than cells infected by ETEC K88 alone. LCMS/MS coupled to isobaric tags for relative and absolute quantification (iTRAQ) is used to profile expressed proteins in IPEC‐J2 cells infected by TGEV alone, ETEC K88 alone, and by both agents together.

Results

77, 89, and 136 differentially expressed proteins are identified in TGEV infected, ETEC K88 infected, and coinfected cells, respectively.

Conclusion and clinical relevance

Based on these data, the authors suspect that integrin α5 might enable TGEV to promote ETEC K88 adhesion. This study is the first to analyze piglet diarrhea caused by TGEV‐ETEC K88 coinfection using high‐throughput quantitative proteomics. The results advance the understanding of coinfection and its role in causing piglet diarrhea.
Computational design of membrane proteins using RosettaMembrane
Authors: Duran Amanda M. , Meiler Jens
Published: November 2017

Computational membrane protein design is challenging due to the small number of high‐resolution structures available to elucidate the physical basis of membrane protein structure, multiple functionally important conformational states, and a limited number of high‐throughput biophysical assays to monitor function. However, structural determination of membrane proteins has made tremendous progress in the past years. Concurrently the field of soluble computational design has made impressive inroads. These developments allow us to tackle the formidable challenge of designing functional membrane proteins. Herein, Rosetta is benchmarked for membrane protein design. We evaluate strategies to cope with the often reduced quality of experimental membrane protein structures. Further, we test the usage of symmetry in design protocols, which is particularly important as many membrane proteins exist as homo‐oligomers. We compare a soluble scoring function with a scoring function optimized for membrane proteins, RosettaMembrane. Both scoring functions recovered around half of the native sequence when completely redesigning membrane proteins. However, RosettaMembrane recovered the most native‐like amino acid property composition. While leucine was overrepresented in the inner and outer‐hydrophobic regions of RosettaMembrane designs, it resulted in a native‐like surface hydrophobicity indicating that it is currently the best option for designing membrane proteins with Rosetta.
%MinMax: A versatile tool for calculating and comparing synonymous codon usage and its impact on protein folding
Authors: Rodriguez Anabel , Wright Gabriel , Emrich Scott , Clark Patricia L.
Published: November 2017

Most amino acids can be encoded by more than one synonymous codon, but these are rarely used with equal frequency. In many coding sequences the usage patterns of rare versus common synonymous codons is nonrandom and under selection. Moreover, synonymous substitutions that alter these patterns can have a substantial impact on the folding efficiency of the encoded protein. This has ignited broad interest in exploring synonymous codon usage patterns. For many protein chemists, biophysicists and structural biologists, the primary motivation for codon analysis is identifying and preserving usage patterns most likely to impact high‐yield production of functional proteins. Here we describe the core functions and new features of %MinMax, a codon usage calculator freely available as a web‐based portal and downloadable script (http://www.codons.org). %MinMax evaluates the relative usage frequencies of the synonymous codons used to encode a protein sequence of interest and compares these results to a rigorous null model. Crucially, for analyzing codon usage in common host organisms %MinMax requires only the coding sequence as input; with a user‐input codon frequency table, %MinMax can be used to evaluate synonymous codon usage patterns for any coding sequence from any fully sequenced genome. %MinMax makes no assumptions regarding the impact of transfer ribonucleic acid concentrations or other molecular‐level interactions on translation rates, yet its output is sufficient to predict the effects of synonymous codon substitutions on cotranslational folding mechanisms. A simple calculation included within %MinMax can be used to harmonize codon usage frequencies for heterologous gene expression.
Coupling of surface air and sea surface temperatures in the CERA‐20C reanalysis
Authors: Feng Xiangbo , Haines Keith , de Boisséson Eric
Published: November 2017

ECMWF has recently produced its first ocean‐atmosphere coupled twentieth century reanalysis CERA‐20C, with ten ensemble members. CERA‐20C is based on a coupled climate model with data assimilation implemented individually for the atmosphere and ocean components. This article focuses on the relationships between 2 m air temperature (T2m) and sea surface temperature (SST) in this new coupled climate reanalysis from the perspective of ensemble statistics. The results show where the atmosphere or the ocean are driving the ensemble variability of temperature at the air–sea interface on varying time‐scales.

In CERA‐20C, the T2m–SST ensemble relationships are changing on diurnal, seasonal and longer time‐scales and also within regions. The T2m ensemble spread is much larger than the SST ensemble spread at high frequencies (3 h), normally with low correlations due to different time‐scales of oceanic and atmospheric dynamics, showing the atmospherically driven variability of T2m. On monthly time‐scales, the T2m spread is mostly slightly lower than the SST spread, with high correlations and strong coupling, reflecting the SST‐forced variability. T2m–SST coupling is strongest where atmospheric and oceanic boundary layers are shallow, e.g. in the summer hemisphere, and weakest where the atmospheric boundary layer becomes deep, e.g. in the ITCZ region. As the twentieth century progresses, ensemble spreads decline, while T2m–SST coupling becomes stronger as both atmosphere and oceans are better constrained to observations. In the Tropics, strong ENSO‐related variability is found in T2m–SST coupling as atmospheric convection centres move interannually to break the SST‐dominated relationships.
Tissue Uptake Mechanisms Involved in the Clearance of Non‐Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice
Authors: Daminelli Elaine N. , Fotakis Panagiotis , Mesquita Carlos H. , Maranhão Raul C. , Zannis Vassilis I.
Published: November 2017

Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A‐I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with 3H‐cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p < 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA‐I KO than in WT. In apoA‐I transgenic mice, LDE clearance was lower than in apoA‐I KO and than in apoA‐I KO infusion with human HDL. Infusion of human HDL into the apoA‐I KO mice resulted in higher LDE clearance than in the apoA‐I transgenic mice (p < 0.05). In apoA‐I KO and apoA‐I KO infused human HDL, the liver uptake was greater than in WT animals and apoA‐I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A‐I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA‐I also influences those processes.
QCA in Empirical Marketing Research: An Experiment Featuring Dorah Explorah, Investigating Celebrity Endorsement's Effect on Product Selection
Authors: De Villiers Rouxelle
Published: November 2017

This study explains how to disentangle the relationships between outcomes and the configurations of marketing brand tactics and consumer attributes for a particular marketing phenomenon. We demonstrate that qualitative comparative analysis (QCA) can be implemented in marketing contexts, and that it can explain marketing phenomena to the standards of rigour, generality and complexity demanded by scientific research. Fuzzy set QCA (fsQCA) need not be feared; it can be a very useful case-based method for marketing theorists. The “thought experiment” featuring the hypothetical Dorah Explorah brand demonstrates fsQCA's value and its similitude with real markets, and confirms that a single attribute, marketing tactic or condition can affect the examined outcome differently when it is part of a different configuration, although it may not be necessary or sufficient for the outcome by itself. We extend the literature on marketing theory creation by drawing on social psychology and management disciplines (for methodology) and Heider's (1958) balance theory to propose a specific hypothesis. We then test this hypothesis via an experimental manipulation. We present the theoretical background supporting the study's hypothesis and make a strong plea for marketing scholars to develop theories using truly useful, highly predictive asymmetrical logic. We hope that this paper will act as a tutorial for marketing researchers, novices and experts, making the application of fsQCA as a methodology and as a set of techniques easier and more transparent. We explicitly highlight the configurationally important aspects of qualitative research in empirical marketing studies and comparative scientific enquiry.
How do Economic Circumstances Determine Preferences? Evidence from Long-run Panel Data
Authors: O’Grady Tom
Published: November 2017

Preferences for redistribution and social spending are correlated with income and unemployment risk, but it is unclear how these relationships come about. I build a theory emphasizing that only large changes in economic circumstances provide the information and motivation needed for people to change their preferences. Stable long-run preferences are shaped mainly by early socialization, which includes economic and ideological influences from the family, and early labor market experiences. Enduring shocks, low intergenerational mobility and the tendency of left-wing parents to be poorer generate correlations between circumstances and preferences. Because preferences are stable, greater inequality may not increase aggregate support for redistribution. Support is found for the theory with panel data from Switzerland, using a range of empirical tests.
EDUCATING THE NATION: IV. SUBJECT CHOICE
Authors: Mandler Peter
Published: November 2017

This address tracks the choices made by students at English schools (O-Level, GCSE and A-Level) and at British universities (undergraduate degree) of what subjects to study over the whole of the period since the Second World War. There are marked long-term trends towards a greater diversity in subjects studied, especially at A-Level and degree level, and this tended to reduce over time the dominance of science, to the advantage of a range of subjects including social studies, traditional humanities and latterly creative arts. These trends reflect (most of all) the growing size and diversity of the student body staying on to further study, but also the broadening of the labour market which this more diverse body of students is entering, and social and cultural changes favouring creativity and self-expression in education. The address closes with a reflection on the possible significance of a very recent halting and even a reversal of these trends in subject choice, to the apparent benefit of the sciences.
THE MAKING OF CHRONICLES AND THE MAKING OF ENGLAND: THE ANGLO-SAXON CHRONICLES AFTER ALFREDProthero Lecture
Authors: Stafford Pauline
Published: November 2017

Betweenc. 900 and the mid-twelfth century, a series of Old English vernacular chronicles were produced, growing out of the text produced at the court of King Alfred. These chronicles are collectively known as ‘the Anglo-Saxon Chronicle’. They have long been accorded fundamental status in the English national story. No others have shaped our view of the origins of England between the fifth and eleventh centuries to the same extent. They provide between them the only continuous narrative of this period. They are the story that has made England. This paper deals with the relationship between that story, these texts and England: how they have been read and edited – made – in the context of the English national story since the sixteenth century; but also their relationship to, the part they may have played in, the original making of the English kingdom. The focus is on developments during the tenth and eleventh centuries, when a political unit more or less equivalent to the England we now know emerged. It is argued that these texts were the ideological possession and expression of the southern English elite, especially of bishops and archbishops, at this critical period of kingdom-making. Special attention is given to their possible role in the incorporation of Northumbria into that kingdom. These chronicles were made by scribes a millennium ago, and to some extent have been reworked by modern editors from the sixteenth century on. They are daunting in their complexity. The differences between them are as important as the common ground they share. Understanding the making of these foundational texts has its own light to shed on the making of England.
Ethique: Quelques questions face à la démence
Authors: Hurst Samia
Published: November 2017

Zusammenfassung. In der klinischen Praxis werden im Zusammenhang mit Demenz werden einige ethische Fragen schwieriger und werden öfters gestellt. Ohne auf die Vollständigkeit zu zielen – und um dem Praktiker zu helfen – befassen wir uns hier mit einigen von ihnen hier kurz.
Strong laser field control of fragment spatial distributions from a photodissociation reaction
Authors: Corrales María E. , de Nalda Rebeca , Bañares Luis
Published: November 2017

The notion that strong laser light can intervene and modify the dynamical processes of matter has been demonstrated and exploited both in gas and condensed phases. The central objective of laser control schemes has been the modification of branching ratios in chemical processes, under the philosophy that conveniently tailored light can steer the dynamics of a chemical mechanism towards desired targets. Less explored is the role that strong laser control can play on chemical stereodynamics, i.e. the angular distribution of the products of a chemical reaction in space. This work demonstrates for the case of methyl iodide that when a molecular bond breaking process takes place in the presence of an intense infrared laser field, its stereodynamics is profoundly affected, and that the intensity of this laser field can be used as an external knob to control it.
Structural basis for high-affinity actin binding revealed by a β-III-spectrin SCA5 missense mutation
Authors: Avery Adam W. , Fealey Michael E. , Wang Fengbin , Orlova Albina , Thompson Andrew R. , Thomas David D. , Hays Thomas S. , Egelman Edward H.
Published: November 2017

Spinocerebellar ataxia type 5 (SCA5) is a neurodegenerative disease caused by mutations in the cytoskeletal protein β-III-spectrin. Previously, a SCA5 mutation resulting in a leucine-to-proline substitution (L253P) in the actin-binding domain (ABD) was shown to cause a 1000-fold increase in actin-binding affinity. However, the structural basis for this increase is unknown. Here, we report a 6.9 Å cryo-EM structure of F-actin complexed with the L253P ABD. This structure, along with co-sedimentation and pulsed-EPR measurements, demonstrates that high-affinity binding caused by the CH2-localized mutation is due to opening of the two CH domains. This enables CH1 to bind actin aided by an unstructured N-terminal region that becomes α-helical upon binding. This helix is required for association with actin as truncation eliminates binding. Collectively, these results shed light on the mechanism by which β-III-spectrin, and likely similar actin-binding proteins, interact with actin, and how this mechanism can be perturbed to cause disease.
Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer
Authors: Valdés-Mora Fátima , Gould Cathryn M. , Colino-Sanguino Yolanda , Qu Wenjia , Song Jenny Z. , Taylor Kylie M. , Buske Fabian A. , Statham Aaron L. , Nair Shalima S. , Armstrong Nicola J. , Kench James G. , Lee Kenneth M. L. , Horvath Lisa G. , Qiu Minru , Ilinykh Alexei , Yeo-Teh Nicole S. , Gallego-Ortega David , Stirzaker Clare , Clark Susan J.
Published: November 2017

Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers. H2A.Zac nucleosome occupancy is rapidly remodeled to flank the AR sites to initiate the formation of nucleosome-free regions and the production of AR-enhancer RNAs upon androgen treatment. Remarkably higher levels of global H2A.Zac correlate with poorer prognosis. Altogether these data demonstrate the novel contribution of H2A.Zac in activation of newly formed enhancers in prostate cancer.
Competition between crystal and fibril formation in molecular mutations of amyloidogenic peptides
Authors: Reynolds Nicholas P. , Adamcik Jozef , Berryman Joshua T. , Handschin Stephan , Zanjani Ali Asghar Hakami , Li Wen , Liu Kun , Zhang Afang , Mezzenga Raffaele
Published: November 2017

Amyloidogenic model peptides are invaluable for investigating assembly mechanisms in disease related amyloids and in protein folding. During aggregation, such peptides can undergo bifurcation leading to fibrils or crystals, however the mechanisms of fibril-to-crystal conversion are unclear. We navigate herein the energy landscape of amyloidogenic peptides by studying a homologous series of hexapeptides found in animal, human and disease related proteins. We observe fibril-to-crystal conversion occurring within single aggregates via untwisting of twisted ribbon fibrils possessing saddle-like curvature and cross-sectional aspect ratios approaching unity. Changing sequence, pH or concentration shifts the growth towards larger aspect ratio species assembling into stable helical ribbons possessing mean-curvature. By comparing atomistic calculations of desolvation energies for association of peptides we parameterise a kinetic model, providing a physical explanation of fibril-to-crystal interconversion. These results shed light on the self-assembly of amyloidogenic peptides, suggesting amyloid crystals, not fibrils, represent the ground state of the protein folding energy landscape.
The effect of artificial selection on phenotypic plasticity in maize
Authors: Gage Joseph L. , Jarquin Diego , Romay Cinta , Lorenz Aaron , Buckler Edward S. , Kaeppler Shawn , Alkhalifah Naser , Bohn Martin , Campbell Darwin A. , Edwards Jode , Ertl David , Flint-Garcia Sherry , Gardiner Jack , Good Byron , Hirsch Candice N. , Holland Jim , Hooker David C. , Knoll Joseph , Kolkman Judith , Kruger Greg , Lauter Nick , Lawrence-Dill Carolyn J. , Lee Elizabeth , Lynch Jonathan , Murray Seth C. , Nelson Rebecca , Petzoldt Jane , Rocheford Torbert , Schnable James , Schnable Patrick S. , Scully Brian , Smith Margaret , Springer Nathan M. , Srinivasan Srikant , Walton Renee , Weldekidan Teclemariam , Wisser Randall J. , Xu Wenwei , Yu Jianming , de Leon Natalia
Published: November 2017

Remarkable productivity has been achieved in crop species through artificial selection and adaptation to modern agronomic practices. Whether intensive selection has changed the ability of improved cultivars to maintain high productivity across variable environments is unknown. Understanding the genetic control of phenotypic plasticity and genotype by environment (G × E) interaction will enhance crop performance predictions across diverse environments. Here we use data generated from the Genomes to Fields (G2F) Maize G × E project to assess the effect of selection on G × E variation and characterize polymorphisms associated with plasticity. Genomic regions putatively selected during modern temperate maize breeding explain less variability for yield G × E than unselected regions, indicating that improvement by breeding may have reduced G × E of modern temperate cultivars. Trends in genomic position of variants associated with stability reveal fewer genic associations and enrichment of variants 0–5000 base pairs upstream of genes, hypothetically due to control of plasticity by short-range regulatory elements.
The effect of genetic variation on promoter usage and enhancer activity
Authors: Garieri Marco , Delaneau Olivier , Santoni Federico , Fish Richard J. , Mull David , Carninci Piero , Dermitzakis Emmanouil T. , Antonarakis Stylianos E. , Fort Alexandre
Published: November 2017

The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Here, we use natural genetic variation and CAGE transcriptomes from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals, to map 5376 and 110 regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs), respectively. We characterize five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, we find puQTL effects either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters. Our analyses identify differential promoter usage and modulation of enhancer activity as molecular mechanisms underlying eQTLs related to regulatory elements.
Multi-scale investigation of uranium attenuation by arsenic at an abandoned uranium mine, South Terras
Authors: Corkhill Claire L. , Crean Daniel E. , Bailey Daniel J. , Makepeace Carmen , Stennett Martin C. , Tappero Ryan , Grolimund Daniel , Hyatt Neil C.
Published: November 2017

Detailed mineralogical analysis of soils from the UK’s historical uranium mine, South Terras, was performed to elucidate the mechanisms of uranium degradation and migration in the 86 years since abandonment. Soils were sampled from the surface (0–2 cm) and near-surface (25 cm) in two distinct areas of ore processing activities. Bulk soil analysis revealed the presence of high concentrations of uranium (<1690 p.p.m.), arsenic (1830 p.p.m.) and beryllium (~250 p.p.m.), suggesting pedogenic weathering of the country rock and ore extraction processes to be the mechanisms of uranium ore degradation. Micro-focus XRF analysis indicated the association of uranium with arsenic, phosphate and copper; µ-XRD data confirmed the presence of the uranyl-arsenate minerals metazeunerite (Cu(UO2)2(AsO4)2·8H2O) and metatorbernite (Cu(UO2)2(PO4)2·8H2O) to be ubiquitous. Our data are consistent with the solid solution of these two uranyl-mica minerals, not previously observed at uranium-contaminated sites. Crystallites of uranyl-mica minerals were observed to coat particles of jarosite and muscovite, suggesting that the mobility of uranium from degraded ores is attenuated by co-precipitation with arsenic and phosphate, which was not previously considered at this site.
Topological networks for quantum communication between distant qubits
Authors: Lang Nicolai , Büchler Hans Peter
Published: November 2017

Efficient communication between qubits relies on robust networks, which allow for fast and coherent transfer of quantum information. It seems natural to harvest the remarkable properties of systems characterized by topological invariants to perform this task. Here, we show that a linear network of coupled bosonic degrees of freedom, characterized by topological bands, can be employed for the efficient exchange of quantum information over large distances. Important features of our setup are that it is robust against quenched disorder, all relevant operations can be performed by global variations of parameters, and the time required for communication between distant qubits approaches linear scaling with their distance. We demonstrate that our concept can be extended to an ensemble of qubits embedded in a two-dimensional network to allow for communication between all of them.
Salt stress-induced FERROCHELATASE 1 improves resistance to salt stress by limiting sodium accumulation in Arabidopsis thaliana
Authors: Zhao Wen Ting , Feng Sheng Jun , Li Hua , Faust Franziska , Kleine Tatjana , Li Long Na , Yang Zhi Min
Published: November 2017

Ferrochelatase-1 as a terminal enzyme of heme biosynthesis regulates many essential metabolic and physiological processes. Whether FC1 is involved in plant response to salt stress has not been described. This study shows that Arabidopsis overexpressing AtFC1 displays resistance to high salinity, whereas a T-DNA insertion knock-down mutant fc1 was more sensitive to salt stress than wild-type plants. AtFC1 conferred plant salt resistance by reducing Na+ concentration, enhancing K+ accumulation and preventing lysis of the cell membrane. Such observations were associated with the upregulation of SOS1, which encodes a plasma membrane Na+/H+ antiporter. AtFC1 overexpression led to a reduced expression of several well known salt stress-responsive genes such as NHX1 and AVP1, suggesting that AtFC1-regulated low concentration of Na+ in plants might not be through the mechanism for Na+ sequestration. To investigate the mechanism leading to the role of AtFC1 in mediating salt stress response in plants, a transcriptome of fc1 mutant plants under salt stress was profiled. Our data show that mutation of AtFC1 led to 490 specific genes up-regulated and 380 specific genes down-regulated in fc1 mutants under salt stress. Some of the genes are involved in salt-induced oxidative stress response, monovalent cation-proton (Na+/H+) exchange, and Na+ detoxification.
Epigenetic Transitions and Knotted Solitons in Stretched Chromatin
Authors: Michieletto D. , Orlandini E. , Marenduzzo D.
Published: November 2017

The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamic mechanism leading to the establishment and maintenance of tissue-specific, epigenetic pattern is still poorly understood. In this work we propose, and investigate in silico, a possible experimental strategy to illuminate the interplay between 3D chromatin structure and epigenetic dynamics. We consider a set-up where a reconstituted chromatin fibre is stretched at its two ends (e.g., by laser tweezers), while epigenetic enzymes (writers) and chromatin-binding proteins (readers) are flooded into the system. We show that, by tuning the stretching force and the binding affinity of the readers for chromatin, the fibre undergoes a sharp transition between a stretched, epigenetically disordered, state and a crumpled, epigenetically coherent, one. We further investigate the case in which a knot is tied along the chromatin fibre, and find that the knotted segment enhances local epigenetic order, giving rise to “epigenetic solitons” which travel and diffuse along chromatin. Our results point to an intriguing coupling between 3D chromatin topology and epigenetic dynamics, which may be investigated via single molecule experiments.
Topographic effect on the phenology of Ficus pedunculosa var. mearnsii (Mearns fig) in its northern boundary distribution, Taiwan
Authors: Kuo Chu-Chia , Bain Anthony , Chiu Yu-Ting , Ho Yi-Chiao , Chen Wen-Hsuan , Chou Lien-Siang , Tzeng Hsy-Yu
Published: November 2017

Mearns fig grows at the edge of coastal vegetation on uplifted coral reefs, its population and mutualistic-pollinators are susceptible to the influence of extreme weather. To determine the phenology of Mearns fig and the effects of various weather events under small-scale topographic differences, phenology was conducted for 3 years and 7 months. Results showed that Mearns figs had multiple leaf and fig productions year-round. Topographic effects caused population in Frog Rock Trail and Jialeshuei, which are less than 10 km away from each other, to exhibit different phenological patterns after experiencing severe weather events. Northeast monsoons led the Jialeshuei population to show low amounts of leaves and figs in winter and the phenological production was also susceptible to disturbances by typhoons in summer. Fig reproduction in such environment was disadvantageous to maintain pollinators. Besides, topographic complex in microhabitat of Frog Rock Trail protected some individuals from these same events thus safeguard population’s survival. The phenology of Mearns fig would respond to the weather events sensitively, which serve as references for estimating the mutualism system, and as indicators of climate change.
Risk Factors and Molecular Features of Sequence Type (ST) 131 Extended-spectrum β-Lactamase-producing Escherichia coli in Community-onset Bacteremia
Authors: Kim Hyunsoo , Kim Young Ah , Park Yoon Soo , Choi Min Hyuk , Lee Gyeong In , Lee Kyungwon
Published: November 2017

Due to the spread of a single CTX-M-type extended-spectrum β-lactamase (ESBL) clone of sequence type (ST) 131, community-onset bacteremia caused by ESBL-producing Escherichia coli has increased dramatically. We evaluated the risk factors and molecular features of ESBL-producing E. coli ST131 clones isolated from Korean patients with community-onset bacteremia. We collected a total of 124 ESBL-producing E. coli isolates from blood in patients with community-onset bacteremia over a 2 year-period. Among 124 patients, the number of community-associated bacteremia cases was 57 (46%). ST131 strains accounted for 49.1% (28/57) of community-associated bacteremia cases and 44.8% (30/67) of healthcare-associated community-onset bacteremia cases. Among 58 ST131 strains, nine isolates were shown to harbor O16-H41, and 61.1% (30/49) of O25 had H30Rx. In a multivariate analysis, independent risk factors for acquisition of ST131 isolates over non-ST131 isolates were underlying diabetes mellitus and absence of prior chemotherapy history. The most common ESBL genotype was CTX-M-15 (46.0%), followed by CTX-M-14 (37.1%). A considerable proportion of community-onset ESBL-producing E. coli bacteremia was observed. ST131 clones appear to be associated with the spread of community-associated bacteremia exhibiting high antimicrobial resistance and highly virulent H30Rx traits, which could become a major public health concern in Korea.
Giant Slip Induced Anomalous Dewetting of an Ultrathin Film on a Viscous Sublayer
Authors: Xu Lin , Bandyopadhyay Dipankar , Reddy Puchalapalli Dinesh Sankar , Sharma Ashutosh , Joo Sang Woo
Published: November 2017

A ‘giant’ slip dynamics was engineered to a highly confined interface of a dewetting polymethylmethacrylate (PMMA) ultrathin film by introducing a lubricating viscous polystyrene (PS) sublayer. The crossover of regimes from no-slip to giant-slip was engendered by tuning the viscosity and thickness of the sublayer. A long-range hole-rim interaction with increase in slippage on the PMMA-PS interface transformed the circular holes on the PMMA surface into the noncircular faceted ones. The extent of the slippage and the transition of the length scales from slip-dominated to no-slip regime were evaluated using a general linear stability analysis. The proposed formulation provided an analytical tool to evaluate the slippage effective at the soft and deformable liquid-liquid interfaces.
Microscopy as a statistical, Rényi-Ulam, half-lie game: a new heuristic search strategy to accelerate imaging
Authors: Drumm Daniel W. , Greentree Andrew D.
Published: November 2017

Finding a fluorescent target in a biological environment is a common and pressing microscopy problem. This task is formally analogous to the canonical search problem. In ideal (noise-free, truthful) search problems, the well-known binary search is optimal. The case of half-lies, where one of two responses to a search query may be deceptive, introduces a richer, Rényi-Ulam problem and is particularly relevant to practical microscopy. We analyse microscopy in the contexts of Rényi-Ulam games and half-lies, developing a new family of heuristics. We show the cost of insisting on verification by positive result in search algorithms; for the zero-half-lie case bisectioning with verification incurs a 50% penalty in the average number of queries required. The optimal partitioning of search spaces directly following verification in the presence of random half-lies is determined. Trisectioning with verification is shown to be the most efficient heuristic of the family in a majority of cases.
Constitutive expression of NF-κB inducing kinase in regulatory T cells impairs suppressive function and promotes instability and pro-inflammatory cytokine production
Authors: Polesso Fanny , Sarker Minhazur , Anderson Arian , Parker David C. , Murray Susan E.
Published: November 2017

CD4+Foxp3+ regulatory T cells (Tregs) are indispensable negative regulators of immune responses. To understand Treg biology in health and disease, it is critical to elucidate factors that affect Treg homeostasis and suppressive function. Tregs express several costimulatory TNF receptor family members that activate non-canonical NF-κB via accumulation of NF-κB inducing kinase (NIK). We previously showed that constitutive NIK expression in all T cells causes fatal multi-organ autoimmunity associated with hyperactive conventional T cell responses and poor Treg-mediated suppression. Here, we show that constitutive NIK expression that is restricted to Tregs via a Cre-inducible transgene causes an autoimmune syndrome. We found that constitutive NIK expression decreased expression of numerous Treg signature genes and microRNAs involved in Treg homeostasis and suppressive phenotype. NIK transgenic Tregs competed poorly with WT Tregs in vivo and produced pro-inflammatory cytokines upon stimulation. Lineage tracing experiments revealed accumulation of ex-Foxp3+ T cells in mice expressing NIK constitutively in Tregs, and these former Tregs produced copious IFNγ and IL-2. Our data indicate that under inflammatory conditions in which NIK is activated, Tregs may lose suppressive function and may actively contribute to inflammation.
Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
Authors: Pingel Jessica , Nielsen Mikkel Schou , Lauridsen Torsten , Rix Kristian , Bech Martin , Alkjaer Tine , Andersen Ida Torp , Nielsen Jens Bo , Feidenhansl R.
Published: November 2017

Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.
Chemodrug delivery using integrin-targeted PLGA-Chitosan nanoparticle for lung cancer therapy
Authors: Babu Anish , Amreddy Narsireddy , Muralidharan Ranganayaki , Pathuri Gopal , Gali Hariprasad , Chen Allshine , Zhao Yan D. , Munshi Anupama , Ramesh Rajagopal
Published: November 2017

In this study, we report the efficacy of RGD (arginine-glycine-aspartic acid) peptide-modified polylactic acid-co-glycolic acid (PLGA)-Chitosan nanoparticle (CSNP) for integrin αvβ3 receptor targeted paclitaxel (PTX) delivery in lung cancer cells and its impact on normal cells. RGD peptide-modified chitosan was synthesized and then coated onto PTX-PLGA nanoparticles prepared by emulsion-solvent evaporation. PTX-PLGA-CSNP-RGD displayed favorable physicochemical properties for a targeted drug delivery system. The PTX-PLGA-CSNP-RGD system showed increased uptake via integrin receptor mediated endocytosis, triggered enhanced apoptosis, and induced G2/M cell cycle arrest and more overall cytotoxicity than its non-targeted counterpart in cancer cells. PTX-PLGA-CSNP-RGD showed less toxicity in lung fibroblasts than in cancer cells, may be attributed to low drug sensitivity, nevertheless the study invited close attention to their transient overexpression of integrin αvβ3 and cautioned against corresponding uptake of toxic drugs, if any at all. Whereas, normal human bronchial epithelial (NHBE) cells with poor integrin αvβ3 expression showed negligible toxicity to PTX-PLGA-CSNP-RGD, at equivalent drug concentrations used in cancer cells. Further, the nanoparticle demonstrated its capacity in targeted delivery of Cisplatin (CDDP), a drug having physicochemical properties different to PTX. Taken together, our study demonstrates that PLGA-CSNP-RGD is a promising nanoplatform for integrin targeted chemotherapeutic delivery to lung cancer.
Multiple Behavior Phenotypes of the Fragile-X Syndrome Mouse Model Respond to Chronic Inhibition of Phosphodiesterase-4D (PDE4D)
Authors: Gurney Mark E. , Cogram Patricia , Deacon Robert M , Rex Christopher , Tranfaglia Michael
Published: November 2017

Fragile-X syndrome (FXS) patients display intellectual disability and autism spectrum disorder due to silencing of the X-linked, fragile-X mental retardation-1 (FMR1) gene. Dysregulation of cAMP metabolism is a consistent finding in patients and in the mouse and fly FXS models. We therefore explored if BPN14770, a prototypic phosphodiesterase-4D negative allosteric modulator (PDE4D-NAM) in early human clinical trials, might provide therapeutic benefit in the mouse FXS model. Daily treatment of adult male fmr1 C57Bl6 knock-out mice with BPN14770 for 14 days reduced hyperarousal, improved social interaction, and improved natural behaviors such as nesting and marble burying as well as dendritic spine morphology. There was no decrement in behavioral scores in control C57Bl6 treated with BPN14770. The behavioral benefit of BPN14770 persisted two weeks after washout of the drug. Thus, BPN14770 may be useful for the treatment of fragile-X syndrome and other disorders with decreased cAMP signaling.
Optical mapping of the dominant frequency of brain signal oscillations in motor systems
Authors: Lu Feng-Mei , Wang Yi-Feng , Zhang Juan , Chen Hua-Fu , Yuan Zhen
Published: November 2017

Recent neuroimaging studies revealed that the dominant frequency of neural oscillations is brain-region-specific and can vary with frequency-specific reorganization of brain networks during cognition. In this study, we examined the dominant frequency in low-frequency neural oscillations represented by oxygenated hemoglobin measurements after the hemodynamic response function (HRF) deconvolution. Twenty-nine healthy college subjects were recruited to perform a serial finger tapping task at the frequency of 0.2 Hz. Functional near-infrared spectroscopy (fNIRS) was applied to record the hemodynamic signals over the primary motor cortex, supplementary motor area (SMA), premotor cortex, and prefrontal area. We then explored the low frequency steady-state brain response (lfSSBR), which was evoked in the motor systems at the fundamental frequency (0.2 Hz) and its harmonics (0.4, 0.6, and 0.8 Hz). In particular, after HRF deconvolution, the lfSSBR at the frequency of 0.4 Hz in the SMA was identified as the dominant frequency. Interestingly, the domain frequency exhibited the correlation with behavior data such as reaction time, indicating that the physiological implication of lfSSBR is related to the brain anatomy, stimulus frequency and cognition. More importantly, the HRF deconvolution showed its capability for recovering signals probably reflecting neural-level events and revealing the physiological meaning of lfSSBR.
Urinary sulphatoxymelatonin as a biomarker of serotonin status in biogenic amine-deficient patients
Authors: Batllori Marta , Molero-Luis Marta , Arrabal Luisa , Heras Javier de las , Fernandez-Ramos Joaquín-Alejandro , Gutiérrez-Solana Luis González , Ibáñez-Micó Salvador , Domingo Rosario , Campistol Jaume , Ormazabal Aida , Sedel Frederic , Opladen Thomas , Zouvelou Basiliki , Pons Roser , Garcia-Cazorla Angels , Lopez-Laso Eduardo , Artuch Rafael
Published: November 2017

Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency. Further 11 patients were studied after receiving serotoninergic treatment (serotonin precursors, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors): 5 with aromatic L-amino acid decarboxylase deficiency; 1 with sepiapterin reductase deficiency; 3 with dihydropteridine reductase deficiency; and 2 with 6-pyruvoyltetrahydropterin synthase deficiency. Among the patients without therapy, 6 presented low urinary sulphatoxymelatonin values, while most of the patients with guanosine triphosphate cyclohydrolase-I deficiency showed normal values. 5 of 11 patients under treatment presented low urine sulphatoxymelatonin values. Thus, decreased excretion of sulphatoxymelatonin is frequently observed in cases with severe genetic disorders affecting serotonin biosynthesis. In conclusion, sulphatoxymelatonin can be a good biomarker to estimate serotonin status in the brain, especially for treatment monitoring purposes.
ToxId: an efficient algorithm to solve occlusions when tracking multiple animals
Authors: Rodriguez Alvaro , Zhang Hanqing , Klaminder Jonatan , Brodin Tomas , Andersson Magnus
Published: November 2017

Video analysis of animal behaviour is widely used in fields such as ecology, ecotoxicology, and evolutionary research. However, when tracking multiple animals, occlusion and crossing are problematic, especially when the identity of each individual needs to be preserved. We present a new algorithm, ToxId, which preserves the identity of multiple animals by linking trajectory segments using their intensity histogram and Hu-moments. We verify the performance and accuracy of our algorithm using video sequences with different animals and experimental conditions. The results show that our algorithm achieves state-of-the-art accuracy using an efficient approach without the need of learning processes, complex feature maps or knowledge of the animal shape. ToxId is also computationally efficient, has low memory requirements, and operates without accessing future or past frames.
Development of multivariable models to predict change in Body Mass Index within a clinical trial population of psychotic individuals
Authors: Harrison Rebecca N. S. , Gaughran Fiona , Murray Robin M. , Lee Sang Hyuck , Cano Jose Paya , Dempster David , Curtis Charles J. , Dima Danai , Patel Hamel , de Jong Simone , Breen Gerome
Published: November 2017

Many antipsychotics promote weight gain, which can lead to non-compliance and relapse of psychosis. By developing models that accurately identify individuals at greater risk of weight gain, clinicians can make informed treatment decisions and target intervention measures. We examined clinical, genetic and expression data for 284 individuals with psychosis derived from a previously published randomised controlled trial (IMPACT). These data were used to develop regression and classification models predicting change in Body Mass Index (BMI) over one year. Clinical predictors included demographics, anthropometrics, cardiac and blood measures, diet and exercise, physical and mental health, medication and BMI outcome measures. We included genetic polygenic risk scores (PRS) for schizophrenia, bipolar disorder, BMI, waist-hip-ratio, insulin resistance and height, as well as gene co-expression modules generated by Weighted Gene Co-expression Network Analysis (WGCNA). The best performing predictive models for BMI and BMI gain after one year used clinical data only, which suggests expression and genetic data do not improve prediction in this cohort.