bluuebunny/crossref_metadata_2025 huggingface dataset:
THE PERSISTENCE OF THE BRAHMIN PRIESTS IN WILKIE COLLINS'STHE MOONSTONE
Authors: Narayan Niketa G.
Published: November 2017

When T. S. Eliotfamously called Wilkie Collins's 1868 novelThe Moonstone“the first, the longest, and the best of modern English detective novels” (The Moonstone1966, v), the implication, presumably, was that the “detectives” are the hero Franklin Blake and other English characters who carry out the detective function, such as the family lawyer, Mr. Bruff. In addition to a detective story, the novel has been read variously as imperialist, anti-imperialist, a narrative invested with economic undertones, and as an exploration of gift theory, among others. In all these iterations, however, the underlying assumption has been that the only real “detectives” in the novel are the English characters; it is they who solve the theft of the diamond and work to police it. The Brahmin priests, whose pursuit of the diamond parallels that of the English, have generally been viewed as peripheral to the main narrative; a marginal acknowledgement of the impact that India, in its various facets, had upon nineteenth-century English society. Vicki Corkran Willey calls the priests, tongue-in-cheek, “‘villains’. . . working in tandem with two other imported troublemakers – [John] Herncastle's stolen diamond and the drug, opium” (226). Timothy L. Carens describes them as practicing “dutiful self-renunciation” (246) in their search for the diamond, implying that passivity is inherent in such dutifulness, and Jenny Bourne Taylor suggests they are important only because of their use of “[c]lairvoyance [which] is projected on to them as a form of romantic fascination, [and] which they then internalize and represent” (193). Critics are in general agreement, then, that the priests are not central to the novel, and their involvement in the solving of the crime is minimal. The present essay will refute this perspective and argue that, in fact, the Brahmin priests are central to the narrative and far more active (and effective) policing agents than the English characters.
THE SENSATIONAL VICTORIAN NURSERY: MRS HENRY WOOD'S PARENTING ADVICE
Authors: Wagner Tamara Silvia
Published: November 2017

Parenting advice has becomea booming industry as well as probably one of the most contested discourses. Its proliferation and continued diversification are often considered a particularly contemporary problem, yet the virulent marketing of “expert” advice on childrearing has its roots as much in the nineteenth-century publishing industry as in the overlapping Victorian cults of domesticity, maternity, and childhood. The nineteenth century saw an explosion of advice literature on the physical, moral, and intellectual education of infants and young children. Childrearing, or parenting, rapidly created a niche market, producing specialised manuals and magazines for mothers, the precursors of the current parenting advice literature. As Victorian novelists tapped into the anxieties that these publications both addressed and further fostered, they laid bare the pressure that the childrearing discourses were exerting on mothers, yet popular authors also quickly realised how their own writing offered a vehicle for specific conceptualisations of motherhood. Harrowing scenes were used to dramatise the effects of different parenting practices; protagonists’ quarrels about such practices served both as characterisation devices and as comments on ideological conflicts between different concepts of childrearing. In the most self-consciously insightful moments, the growing supply of information came itself under criticism. Victorian novelists actively participated in shaping and circulating parenting advice in print. The sensationalised nursery fascinatingly expressed the anxieties surrounding childrearing and showed how versatile the interpellation of mothering instructions in fiction could be.
THE PICTURESQUE, PORTRAITURE, AND THE MANOR HOUSE: THE SOCIAL FUNCTIONS OF ART IN MARY AUGUSTA WARD'SMARCELLA
Authors: Codell Julie
Published: November 2017

The very first line ofMary Augusta Ward's novelMarcellaends with the word “beautiful,” repeated twice, the second time in italics. In this paper I will argue that this symbolizes the central role of aesthetics in the novel in a discourse that engages the social criticism of John Ruskin and William Morris. Some scholars have assessedMarcella(1894) as having a retrograde ending of Marcella marrying a Tory politician and landowner. Judith Wilt's critical study of Ward is entitledBehind Her Times, an indication of the general view of Ward as a political conservative, although Wilt argues that she was also progressive in many ways, and Ward has enjoyed other nuanced, sensitive re-readings and assessments (Argyle; Sutton-Ramspeck). I, too, am arguing that Ward's political and social views in this novel are complex and mixed and that examining the novel's Victorian cultural discourses can illuminate complex socio-political content that draws on late-century art world debates. The very texture ofMarcellabelies an unstable view of class and social problems, as the eponymous protagonist goes through several stages of thinking and trial-and-error solutions, some socialist, to problems of poverty and class disparity.
Material networks: architecture, computers, and corporations
Authors: Martin Reinhold , Bredella Nathalie , Höfler Carolin
Published: November 2017

Reinhold Martin has been writing about industrial corporate architectures and the ways in which they function as technologies of organisation. Looking at the military industrial complex of the postwar period, he connects the discourses of cybernetics, system theory, and architecture. His studies offer a historical and theoretical understanding of architecture as a material complex with its own internal logic that integrates formats of vision, hearing, cognition, and communication into a semi-coordinated ensemble. In his publications on the history and theory of modern and contemporary architecture he deals with structures that characterise the design, the perception, and the communication of architecture, but are often beyond visibility and control. Rather than limit his scope to individual media, he takes up architecture as ‘apparatus of intermediation’.
Of algorithms, buildings and fighter jets: a conversation with Robin Forrest
Authors: Cardoso Llach Daniel , Forrest Robin
Published: November 2017

A founding member of the Computer-Aided Design Group at the University of Cambridge, UK, and a student and collaborator of CAD pioneer Steven A. Coons at MIT, Robin Forrest occupies an important place in the history of computational design. Along with important contributions to the mathematics of shape representation, his coining of the term ‘computational geometry’ in 1971 offered a handle on design techniques that started to emerge – somewhat uncomfortably at first – in the interstices of engineering, mathematics, and the fledgling field of computer science. Initially fostered by governmentsponsored research into Computer-Aided Design for aircraft and car manufacturing, the methods he helped develop have since been encoded in countless commercial software systems for 3D modelling and simulation, helping structure the intellectual work – and the professional identity – of architects, engineers, and other practitioners of design.
ON THE MILNOR MONODROMY OF THE IRREDUCIBLE COMPLEX REFLECTION ARRANGEMENTS
Authors: Dimca Alexandru
Published: November 2017

Using recent results by Măcinic, Papadima and Popescu, and a refinement of an older construction of ours, we determine the monodromy action on$H^{1}(F(G),\mathbb{C})$, where$F(G)$denotes the Milnor fiber of a hyperplane arrangement associated to an irreducible complex reflection group$G$.
Ruin probabilities in a Sparre Andersen model with dependency structure based on a threshold window
Authors: Cheung Eric C. K. , Dai Suhang , Ni Weihong
Published: November 2017

We analyse ruin probabilities for an insurance risk process with a more generalised dependence structure compared to the one introduced in Constantinescu et al. (2016). In this paper, we assume that a random threshold window is generated every time after a claim occurs. By comparing the previous inter-claim time with the threshold window, the distributions of the current threshold window and the inter-arrival time are determined. Furthermore, the statuses for the previous and current inter-arrival times give rise to the current claim size distribution as well. Like Constantinescu et al. (2016), we first identify the embedded Markov additive process where all the randomness takes a general form. Inspired by the Erlangisation technique, the key message of this paper is to analyse such risk process using a Markov fluid flow model where the underlying random variables follow phase-type distributions. This would further allow us to approximate the fixed observation windows by Erlang random variables. Then ruin probabilities under the process with Erlang(n) observation windows are proved to be Erlangian approximations for those related to the process with fixed threshold windows at the limit. An exact form of the limit can be obtained whose application will be illustrated further by a numerical example.
A Colonial Media Revolution:The Press in Saint-Domingue, 1789–1793
Authors: Popkin Jeremy D.
Published: November 2017

Like metropolitan France, the Caribbean colony of Saint-Domingue experienced a media revolution during the first four years of the French Revolution. In 1789, there was only one newspaper on the island, the officially licensedAffiches américaines, with two editions, one in the colony's capital, Port-au-Prince, and the other in its commercial center, Cap Français. By the time of the destruction of Cap Français, the colony's major city in June 1793, more than a dozen different newspapers had been founded in the colony, making it the second site in the New World, after Britain's North American colonies, to experience the phenomenon of a revolutionary press. Not only were there more newspapers, but their content and language were radically different from those of theAffiches. Like the newspapers created in France in 1789, those in Saint-Domingue denounced the vestiges of royal power and called on the colony's white citizens to demand the right to govern themselves. By helping to break down traditional authority, the press played an essential if unintentional role in making the revolts against white rule by Saint-Domingue's free people of color and its slave population possible.
Dekontextualisierte Sprache als Vorstufe von konzeptionell schriftlicher Sprache
Authors: Sauerborn Hanna
Published: November 2017

Zusammenfassung. Die Ergebnisse dieser Arbeit zeigen, dass im Laufe des letzten Kindergartenjahres und bis zum Ende der ersten Klasse immer mehr der untersuchten Kinder (N = 26) Texte mit den Merkmalen [+dekontexualisiert] und [+konzept. schriftlich] produzieren. Es wird angenommen, dass Kinder zunächst Texte mit dem Merkmal [+dekont.] und dann [+konzept.schriftlich] äußern.
Significance estimation for large scale metabolomics annotations by spectral matching
Authors: Scheubert Kerstin , Hufsky Franziska , Petras Daniel , Wang Mingxun , Nothias Louis-Félix , Dührkop Kai , Bandeira Nuno , Dorrestein Pieter C. , Böcker Sebastian
Published: November 2017

The annotation of small molecules in untargeted mass spectrometry relies on the matching of fragment spectra to reference library spectra. While various spectrum-spectrum match scores exist, the field lacks statistical methods for estimating the false discovery rates (FDR) of these annotations. We present empirical Bayes and target-decoy based methods to estimate the false discovery rate (FDR) for 70 public metabolomics data sets. We show that the spectral matching settings need to be adjusted for each project. By adjusting the scoring parameters and thresholds, the number of annotations rose, on average, by +139% (ranging from −92 up to +5705%) when compared with a default parameter set available at GNPS. The FDR estimation methods presented will enable a user to assess the scoring criteria for large scale analysis of mass spectrometry based metabolomics data that has been essential in the advancement of proteomics, transcriptomics, and genomics science.
Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy
Authors: Zhu Guizhi , Mei Lei , Vishwasrao Harshad D. , Jacobson Orit , Wang Zhantong , Liu Yijing , Yung Bryant C. , Fu Xiao , Jin Albert , Niu Gang , Wang Qin , Zhang Fuwu , Shroff Hari , Chen Xiaoyuan
Published: November 2017

Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs. CpG and shRNA in iDR-NCs synergistically activate APCs for sustained antigen presentation. Remarkably, iDR-NC/neoantigen nanovaccines elicit 8-fold more frequent neoantigen-specific peripheral CD8+ T cells than CpG, induce T cell memory, and significantly inhibit the progression of neoantigen-specific colorectal tumors. Collectively, iDR-NCs represent potential DNA/RNA/peptide triple-co-delivery nanocarriers and synergistic tumor immunotherapeutic nanovaccines.
GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection
Authors: Yuan Hua , Zhang Jinru , Cai Yujuan , Wu Sheng , Yang Kui , Chan H. C. Stephen , Huang Wei , Jin Wen-Bing , Li Yan , Yin Yue , Igarashi Yasuhiro , Yuan Shuguang , Zhou Jiahai , Tang Gong-Li
Published: November 2017

GyrI-like proteins are widely distributed in prokaryotes and eukaryotes, and recognized as small-molecule binding proteins. Here, we identify a subfamily of these proteins as cyclopropanoid cyclopropyl hydrolases (CCHs) that can catalyze the hydrolysis of the potent DNA-alkylating agents yatakemycin (YTM) and CC-1065. Co-crystallography and molecular dynamics simulation analyses reveal that these CCHs share a conserved aromatic cage for the hydrolytic activity. Subsequent cytotoxic assays confirm that CCHs are able to protect cells against YTM. Therefore, our findings suggest that the evolutionarily conserved GyrI-like proteins confer cellular protection against diverse xenobiotics via not only binding, but also catalysis.
Chromosome segregation occurs by microtubule pushing in oocytes
Authors: Laband Kimberley , Le Borgne Rémi , Edwards Frances , Stefanutti Marine , Canman Julie C. , Verbavatz Jean-Marc , Dumont Julien
Published: November 2017

During cell division, spindle microtubules ensure an equal repartition of chromosomes between the two daughter cells. While the kinetochore-dependent mechanisms that drive mitotic chromosome segregation are well understood, in oocytes of most species atypical spindles assembled in absence of centrosomes entail poorly understood mechanisms of chromosome segregation. In particular, the structure(s) responsible for force generation during meiotic chromosome separation in oocytes is unclear. Using quantitative light microscopy, electron tomography, laser-mediated ablation, and genetic perturbations in the Caenorhabditis elegans oocyte, we studied the mechanism of chromosome segregation in meiosis. We find spindle poles are largely dispensable, and in fact act as brakes for chromosome segregation. Instead, our results suggest that CLS-2-dependent microtubules of the meiotic central spindle, located between the segregating chromosomes and aligned along the axis of segregation, are essential. Our results support a model in which inter-chromosomal microtubules of the central spindle push chromosomes apart during meiotic anaphase in oocytes.
Dynamic tuning of optical absorbers for accelerated solar-thermal energy storage
Authors: Wang Zhongyong , Tong Zhen , Ye Qinxian , Hu Hang , Nie Xiao , Yan Chen , Shang Wen , Song Chengyi , Wu Jianbo , Wang Jun , Bao Hua , Tao Peng , Deng Tao
Published: November 2017

Currently, solar-thermal energy storage within phase-change materials relies on adding high thermal-conductivity fillers to improve the thermal-diffusion-based charging rate, which often leads to limited enhancement of charging speed and sacrificed energy storage capacity. Here we report the exploration of a magnetically enhanced photon-transport-based charging approach, which enables the dynamic tuning of the distribution of optical absorbers dispersed within phase-change materials, to simultaneously achieve fast charging rates, large phase-change enthalpy, and high solar-thermal energy conversion efficiency. Compared with conventional thermal charging, the optical charging strategy improves the charging rate by more than 270% and triples the amount of overall stored thermal energy. This superior performance results from the distinct step-by-step photon-transport charging mechanism and the increased latent heat storage through magnetic manipulation of the dynamic distribution of optical absorbers.
Heterogeneity in the Drosophila gustatory receptor complexes that detect aversive compounds
Authors: Sung Ha Yeon , Jeong Yong Taek , Lim Ji Yeon , Kim Hyeyon , Oh Soo Min , Hwang Sun Wook , Kwon Jae Young , Moon Seok Jun
Published: November 2017

Animals must detect aversive compounds to survive. Bitter taste neurons express heterogeneous combinations of bitter receptors that diversify their response profiles, but this remains poorly understood. Here we describe groups of taste neurons in Drosophila that detect the same bitter compounds using unique combinations of gustatory receptors (GRs). These distinct complexes also confer responsiveness to non-overlapping sets of additional compounds. While either GR32a/GR59c/GR66a or GR22e/GR32a/GR66a heteromultimers are sufficient for lobeline, berberine, and denatonium detection, only GR22e/GR32a/GR66a responds to strychnine. Thus, despite minimal sequence-similarity, Gr22e and Gr59c show considerable but incomplete functional overlap. Since the gain- or loss-of-function of Gr22e or Gr59c alters bitter taste response profiles, we conclude a taste neuron’s specific combination of Grs determines its response profile. We suspect the heterogeneity of Gr expression in Drosophila taste neurons diversifies bitter compound detection, improving animal fitness under changing environmental conditions that present a variety of aversive compounds.
Antimicrobial peptides in frog poisons constitute a molecular toxin delivery system against predators
Authors: Raaymakers Constantijn , Verbrugghe Elin , Hernot Sophie , Hellebuyck Tom , Betti Cecilia , Peleman Cindy , Claeys Myriam , Bert Wim , Caveliers Vicky , Ballet Steven , Martel An , Pasmans Frank , Roelants Kim
Published: November 2017

Animals using toxic peptides and proteins for predation or defense typically depend on specialized morphological structures, like fangs, spines, or a stinger, for effective intoxication. Here we show that amphibian poisons instead incorporate their own molecular system for toxin delivery to attacking predators. Skin-secreted peptides, generally considered part of the amphibian immune system, permeabilize oral epithelial tissue and enable fast access of cosecreted toxins to the predator’s bloodstream and organs. This absorption-enhancing system exists in at least three distantly related frog lineages and is likely to be a widespread adaptation, determining the outcome of predator–prey encounters in hundreds of species.
Dogs and humans respond to emotionally competent stimuli by producing different facial actions
Authors: Caeiro Cátia , Guo Kun , Mills Daniel
Published: November 2017

The commonality of facial expressions of emotion has been studied in different species since Darwin, with most of the research focusing on closely related primate species. However, it is unclear to what extent there exists common facial expression in species more phylogenetically distant, but sharing a need for common interspecific emotional understanding. Here we used the objective, anatomically-based tools, FACS and DogFACS (Facial Action Coding Systems), to quantify and compare human and domestic dog facial expressions in response to emotionally-competent stimuli associated with different categories of emotional arousal. We sought to answer two questions: Firstly, do dogs display specific discriminatory facial movements in response to different categories of emotional stimuli? Secondly, do dogs display similar facial movements to humans when reacting in emotionally comparable contexts? We found that dogs displayed distinctive facial actions depending on the category of stimuli. However, dogs produced different facial movements to humans in comparable states of emotional arousal. These results refute the commonality of emotional expression across mammals, since dogs do not display human-like facial expressions. Given the unique interspecific relationship between dogs and humans, two highly social but evolutionarily distant species sharing a common environment, these findings give new insight into the origin of emotion expression.
IVIG activates FcγRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress inflammation after ICH in mice
Authors: Akyol Gokce Yilmaz , Manaenko Anatol , Akyol Onat , Solaroglu Ihsan , Ho Wing Mann , Ding Yan , Flores Jerry , Zhang John H. , Tang Jiping
Published: November 2017

Following intracerebral hemorrhage (ICH), the activation of mast cell contributes to brain inflammation and brain injury. The mast cell activation is negatively regulated by an inhibitory IgG-receptor. It’s signals are mediated by SHIP (Src homology 2-containing inositol 5′ phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3, leading to the inhibition of calcium mobilization and to the attenuation of mast cell activation. Intravenous immunoglobulin (IVIG) is a FDA-approved drug containing IgG. We hypothesized that IVIG will attenuate the ICH-induced mast cell activation via FcγRIIB/SHIP1 pathway, resulting in a decrease of brain inflammation, protection of the blood-brain-barrier, and improvement of neurological functions after ICH. To prove this hypothesis we employed the ICH collagenase mouse model. We demonstrated that while ICH induced mast cell activation/degranulation, IVIG attenuated post-ICH mast cell activation. Mast cell deactivation resulted in reduced inflammation, consequently attenuating brain edema and improving of neurological functions after ICH. Furthermore using siRNA-inducedin vivoknockdown approach we demonstrated that beneficial effects of IVIG were mediated, at least partly, via SHIP1/PIP3 pathway. We conclude that IVIG treatment represents a promising therapeutic approach potentially able to decrease mortality and morbidity after ICH in experimental models.
Determining phase coherence time of stored light in warm atomic vapor
Authors: Jeong Taek , Park Jumi , Moon Han Seb
Published: November 2017

In quantum memory based on an atomic medium, we may have a question about whether all information on the stored light is preserved. In particular, the phase coherence between the stored and retrieval light pulses is very interesting, because it can indicate the relationship between the coherence time and storage time of the light. In this paper, we investigate the phase coherence time of light stored in a warm atomic vapor, by examining the beat-note interference between the retrieval light pulse and a reference light beam optically delayed using an optical fiber. The beat-note interference fringes are measured for different reference-light optical delays. The observed retrieval-light phase indicates that the phase of the input probe light is preserved in the medium. However, we further confirm that the retrieval-light phase coherence depends on the phase coherence of the coupling light used for retrieval in the storage process.
Targeting SxIP-EB1 interaction: An integrated approach to the discovery of small molecule modulators of dynamic binding sites
Authors: Almeida T. B. , Carnell A. J. , Barsukov I. L. , Berry N. G.
Published: November 2017

End binding protein 1 (EB1) is a key element in the complex network of protein-protein interactions at microtubule (MT) growing ends, which has a fundamental role in MT polymerisation. EB1 is an important protein target as it is involved in regulating MT dynamic behaviour, and has been associated with several disease states, such as cancer and neuronal diseases. Diverse EB1 binding partners are recognised through a conserved four amino acid motif, (serine-X-isoleucine-proline) which exists within an intrinsically disordered region. Here we report the use of a multidisciplinary computational and experimental approach for the discovery of the first small molecule scaffold which targets the EB1 recruiting domain. This approach includes virtual screening (structure- and ligand-based design) and multiparameter compound selection. Subsequent studies on the selected compounds enabled the elucidation of the NMR structures of the C-terminal domain of EB1 in the free form and complexed with a small molecule. These structures show that the binding site is not preformed in solution, and ligand binding is fundamental for the binding site formation. This work is a successful demonstration of the combination of modelling and experimental methods to enable the discovery of compounds which bind to these challenging systems.
Predicting the Origin of Ventricular Arrhythmia Using Acoustic Cardiography
Authors: Lin Chin-Yu , Chang Shih-Lin , Lin Yenn-Jiang , Lo Li-Wei , Hu Yu-Feng , Chao Tze-Fan , Chung Fa-Po , Tuan Ta-Chuan , Liao Jo-Nan , Chang Yao-Ting , Te Abigail Louise D. , Yamada Shinya , Cheng Hao-Min , Sung Shih-Hsien , Kuo Ling , Li Hsing-Yuan , Chang Ting-Yung , Minh Hoang Quang , Salim Simon , Huang Ting-Chung , Chen Shih-Ann
Published: November 2017

This study aimed to examine the relationship between measurements related to heart sounds and the origin of ventricular arrhythmia. We retrospectively evaluated 45 patients undergoing catheter ablation with contemporaneous digital acoustic cardiography of the first heart sound (S1) and the second heart sound (S2). The patients with baseline wide QRS morphology (>120 ms or aberrant conduction), heart failure, valvular heart disease, chronic pulmonary disease, and obesity were excluded. Ventricular arrhythmias from the left ventricle had an increased S1 complexity score and S1 duration in comparison to adjacent sinus beats. On the other hand, ventricular arrhythmia from right ventricle had decreased S1 complexity score and S1 duration in comparison to adjacent sinus beats. The difference of S1 (ΔS1) parameters between premature ventricular complex and sinus beat was significantly smaller in right ventricular arrhythmia group compared with and left ventricular arrhythmia group. For predicting the origin of ventricular arrhythmia, the ΔS1 duration provide better predictive accuracy (sensitivity: 100%, specificity: 100%, cutoff value: −1.28 ms) in comparison to ΔS1 complexity score (sensitivity 71.4%, specificity 75.0%, cutoff value: −0.13). The change of S1 complexity and duration determined from acoustic cardiography could accurately predict the ventricular arrhythmia origin.
The antigenic variability of HCV in viral HLA-Ag binding is related to the activation of the host immune response
Authors: Muñoz de Rueda P. , Jiménez-Ruiz S. M. , Quiles R. , Pavón-Castillero E. J. , Muñoz-Gámez J. A. , Casado J. , Gila A. , Ruiz-Extremera A. , Salmerón J.
Published: November 2017

Our previous data show that hepatitis C virus (HCV) genotype 1 patients expressing the HLA-DQB1 * 0301 allele have a combined response probability of 69%, while the remaining 31% do not respond, probably because the HCV immunodominant epitope (IE) against the DQB1 * 0301 allele is mutated. HCV IE (region sequenced in NS3 is a region encoding aa 1253–1272) from 37 patients (21 Sustained Virological Response, SVR; 16 non-SVR) HLA-DQB1 * 0301+, were analysed by pyrosequencing.In vitrocultures were also determined by CD4+ proliferation, using non-mutated IE (wild-type synthetic peptide) and synthetic mutated peptide. The pyrosequencing study revealed 34 different haplotypes. The SVR patients had fewer haplotypes (P = 0.07), mutations/haplotypes (P = 0.01) and polymorphic sites (P = 0.02) than non-SVR. Three polymorphic sites were associated with the non-SVR patients: haplotype 7 (L5P); haplotype 11 (L7P); and haplotype 15, (L15S) (P = 0.02). Thein vitrostudy (n = 7) showed that in 4/7 patients (Group 1) the CD4+ proliferation obtained with wild-type synthetic peptide was higher than that obtained with the negative control and with the synthetic mutated peptide (P = 0.039). However, in the remaining 3/7 patients (Group 2) this pattern was not observed (P = 0.7). Our findings suggest that HLA-DQB1 * 0301+ patients with high antigenic variability in HCV IE (NS31253-1272) have a lower SVR rate, due to reduced CD4+ proliferation as a result of incorrect viral HLA-Ag binding.
PLA2-like proteins myotoxic mechanism: a dynamic model description
Authors: Borges Rafael J. , Lemke Ney , Fontes Marcos R. M.
Published: November 2017

Phospholipase A2-like (PLA2-like) proteins contribute to the development of muscle necrosis in Viperidae snake bites and are not efficiently neutralized by current antivenom treatments. The toxic mechanisms of PLA2-like proteins are devoid of catalytic activity and not yet fully understood, although structural and functional experiments suggest a dimeric assembly and that the C-terminal residues are essential to myotoxicity. Herein, we characterized the functional mechanism of bothropic PLA2-like structures related to global and local measurements using the available models in the Protein Data Bank and normal mode molecular dynamics (NM-MD). Those measurements include: (i) new geometric descriptions between their monomers, based on Euler angles; (ii) characterizations of canonical and non-canonical conformations of the C-terminal residues; (iii) accessibility of the hydrophobic channel; (iv) inspection of ligands; and (v) distance of clustered residues to toxin interface of interaction. Thus, we described the allosteric activation of PLA2-like proteins and hypothesized that the natural movement between monomers, calculated from NM-MD, is related to their membrane disruption mechanism, which is important for future studies of the inhibition process. These methods and strategies can be applied to other proteins to help understand their mechanisms of action.
Improvement on lipid production by Scenedesmus obliquus triggered by low dose exposure to nanoparticles
Authors: He Meilin , Yan Yongquan , Pei Feng , Wu Mingzhu , Gebreluel Temesgen , Zou Shanmei , Wang Changhai
Published: November 2017

Carbon nanotubes (CNTs), α-Fe2O3 nanoparticles (nano Fe2O3) and MgO nanoparticles (nano MgO) were evaluated for the effects on algae growth and lipid production. Nano Fe2O3 promoted cell growth in the range of 0–20 mg·L−1. CNTs, nano Fe2O3 and nano MgO inhibited cell growth of Scenedesmus obliquus at 10, 40 and 0.8 mg·L−1 respectively. Neutral lipid and total lipid content increased with the increasing concentration of all tested nanoparticles. The maximum lipid productivity of cultures exposed to CNTs, nano Fe2O3 and nano MgO was observed at 5 mg·L−1, 5 mg·L−1 and 40 mg·L−1, with the improvement by 8.9%, 39.6% and 18.5%. High dose exposure to nanoparticles limited increase in lipid productivity, possibly due to the repression on cell growth caused by nanoparticles-catalyzed reactive oxygen species (ROS) generation, finally leading to reduction in biomass and lipid production. Reduced accumulation of fatty acids of C18:3n3, C18:3n6 and C20:2 was observed in cells exposed to nanoparticles.
Haemodynamic Recovery Properties of the Torsioned Testicular Artery Lumen
Authors: Goktas Selda , Yalcin Ozlem , Ermek Erhan , Piskin Senol , Capraz Can T. , Cakmak Yusuf O. , Pekkan Kerem
Published: November 2017

Testicular artery torsion (twisting) is one such severe vascular condition that leads spermatic cord injury. In this study, we investigate the recovery response of a torsioned ram testicular artery in an isolated organ-culture flow loop with clinically relevant twisting modes (90°, 180°, 270° and 360° angles). Quantitative optical coherence tomography technique was employed to track changes in the lumen diameter, wall thickness and the three-dimensional shape of the vessel in the physiological pressure range (10–50 mmHg). As a control, pressure-flow characteristics of the untwisted arteries were studied when subjected to augmented blood flow conditions with physiological flow rates up to 36 ml/min. Both twist and C-shaped buckling modes were observed. Acute increase in pressure levels opened the narrowed lumen of the twisted arteries noninvasively at all twist angles (at ∼22 mmHg and ∼35 mmHg for 360°-twisted vessels during static and dynamic flow experiments, respectively). The association between the twist-opening flow rate and the vessel diameter was greatly influenced by the initial twist angle. The biomechanical characteristics of the normal (untwisted) and torsioned testicular arteries supported the utilization of blood flow augmentation as an effective therapeutic approach to modulate the vessel lumen and recover organ reperfusion.
Bone regeneration is associated with the concentration of tumour necrosis factor-α induced by sericin released from a silk mat
Authors: Jo You-Young , Kweon HaeYong , Kim Dae-Won , Baek Kyunghwa , Kim Min-Keun , Kim Seong-Gon , Chae Weon-Sik , Choi Je-Yong , Rotaru Horatiu
Published: November 2017

To understand the osteogenic effect of the middle layer of the silk cocoon, sericin was examined for its cellular effects associated with tumor necrosis factor-α (TNF-α) signaling in this study. The fragmented sericin proteins in the silk mat were evaluated for the TNF-α expression level in murine macrophages. The concentration of protein released from silk mats was higher in the outermost and the innermost layers than in the middle layers, and the protein released from the silk mat was identified as sericin. The level of TNF-α in murine macrophages was dependent on the applied concentration of sericin, and the expression of genes associated with osteogenesis in osteoblast-like cells was dependent on the applied concentration of TNF-α. In animal experiments, silk mats from the middle layers led to a higher regenerated bone volume than silk mats from the innermost layer or the outermost layer. If TNF-α protein was incorporated into the silk mats from the middle layers, bone regeneration was suppressed compared with unloaded silk mats from the middle layers. Accordingly, silk mats from the silk cocoon can be considered to be a fragmented sericin-secreting carrier, and the level of sericin secretion is associated with TNF-α induction and bone regeneration.
Rapid Purification of Human Bispecific Antibodies via Selective Modulation of Protein A Binding
Authors: Zwolak Adam , Leettola Catherine N. , Tam Susan H. , Goulet Dennis R. , Derebe Mehabaw G. , Pardinas Jose R. , Zheng Songmao , Decker Rose , Emmell Eva , Chiu Mark L.
Published: November 2017

Methods to rapidly generate high quality bispecific antibodies (BsAb) having normal half-lives are critical for therapeutic programs. Here, we identify 3 mutations (T307P, L309Q, and Q311R or “TLQ”) in the Fc region of human IgG1 which disrupt interaction with protein A while enhancing interaction with FcRn. The mutations are shown to incrementally alter the pH at which a mAb elutes from protein A affinity resin. A BsAb comprised of a TLQ mutant and a wild-type IgG1 can be efficiently separated from contaminating parental mAbs by differential protein A elution starting from either a) purified parental mAbs, b) in-supernatant crossed parental mAbs, or c) co-transfected mAbs. We show that the Q311R mutation confers enhanced FcRn interactionin vitro, and Abs harboring either the Q311R or TLQ mutations have serum half-lives as long as wild-type human IgG1. The mutant Abs have normal thermal stability and Fcγ receptor interactions. Together, the results lead to a method for high-throughput generation of BsAbs suitable forin vivostudies.
Structural Basis for DNA Recognition of a Single-stranded DNA-binding Protein from Enterobacter Phage Enc34
Authors: Cernooka Elina , Rumnieks Janis , Tars Kaspars , Kazaks Andris
Published: November 2017

Modern DNA sequencing capabilities have led to the discovery of a large number of new bacteriophage genomes, which are a rich source of novel proteins with an unidentified biological role. The genome of Enterobacter cancerogenus bacteriophage Enc34 contains several proteins of unknown function that are nevertheless conserved among distantly related phages. Here, we report the crystal structure of a conserved Enc34 replication protein ORF6 which contains a domain of unknown function DUF2815. Despite the low (~15%) sequence identity, the Enc34 ORF6 structurally resembles the gene 2.5 protein from bacteriophage T7, and likewise is a single-stranded DNA (ssDNA)-binding protein (SSB) that consists of a variation of the oligosaccharide/oligonucleotide-binding (OB)-fold and an unstructured C-terminal segment. We further report the crystal structure of a C-terminally truncated ORF6 in complex with an ssDNA oligonucleotide that reveals a DNA-binding mode involving two aromatic stacks and multiple electrostatic interactions, with implications for a common ssDNA recognition mechanism for all T7-type SSBs.
Facilitation of information processing in the primary somatosensory area in the ball rotation task
Authors: Wasaka Toshiaki , Kida Tetsuo , Kakigi Ryusuke
Published: November 2017

Somatosensory input to the brain is known to be modulated during voluntary movement. It has been demonstrated that the response in the primary somatosensory cortex (SI) is generally gated during simple movement of the corresponding body part. This study investigated sensorimotor integration in the SI during manual movement using a motor task combining movement complexity and object manipulation. While the amplitude of M20 and M30 generated in the SI showed a significant reduction during manual movement, the subsequent component (M38) was significantly higher in the motor task than in the stationary condition. Especially, that in the ball rotation task showed a significant enhancement compared with those in the ball grasping and stone and paper tasks. Although sensorimotor integration in the SI generally has an inhibitory effect on information processing, here we found facilitation. Since the ball rotation task seems to be increasing the demand for somatosensory information to control the complex movements and operate two balls in the palm, it may have resulted in an enhancement of M38 generated in the SI.
A dual-channel endoscope for quantitative imaging, monitoring, and triggering of doxorubicin release from liposomes in living mice
Authors: Kress Jeremy , Rohrbach Daniel J. , Carter Kevin A. , Luo Dandan , Poon Chien , Aygun-Sunar Semra , Shao Shuai , Lele Shashikant , Lovell Jonathan F. , Sunar Ulas
Published: November 2017

Doxorubicin (Dox) is approved for use in liposomal form for the treatment of ovarian cancer. We previously developed a long-circulating Dox formulation in liposomes containing small amounts of porphyrin-phospholipid, which enables on-demand drug release with near-infrared irradiation. In this study, we present and evaluate a dual-modal, dual-channel light endoscope that allows quantitative reflectance and fluorescence imaging for monitoring of local Dox concentrations in target areas. The endoscope consists of two flexible imaging fibers; one to transmit diagnostic and therapeutic light to the target, and the other to detect fluorescent and reflected light. Thus, the endoscope serves for imaging, for light delivery to trigger drug release, and for monitoring drug concentration kinetics during drug release. We characterized the performance of this endoscope in tissue phantoms and in an in vivo model of ovarian cancer. This study demonstrates the feasibility of non-invasive, quantitative mapping of Dox distribution in vivo via endoscopic imaging.
Global Sequestration Potential of Increased Organic Carbon in Cropland Soils
Authors: Zomer Robert J. , Bossio Deborah A. , Sommer Rolf , Verchot Louis V.
Published: November 2017

The role of soil organic carbon in global carbon cycles is receiving increasing attention both as a potentially large and uncertain source of CO2 emissions in response to predicted global temperature rises, and as a natural sink for carbon able to reduce atmospheric CO2. There is general agreement that the technical potential for sequestration of carbon in soil is significant, and some consensus on the magnitude of that potential. Croplands worldwide could sequester between 0.90 and 1.85 Pg C/yr, i.e. 26–53% of the target of the “4p1000 Initiative: Soils for Food Security and Climate”. The importance of intensively cultivated regions such as North America, Europe, India and intensively cultivated areas in Africa, such as Ethiopia, is highlighted. Soil carbon sequestration and the conservation of existing soil carbon stocks, given its multiple benefits including improved food production, is an important mitigation pathway to achieve the less than 2 °C global target of the Paris Climate Agreement.
Obesity-promoting and anti-thermogenic effects of neutrophil gelatinase-associated lipocalin in mice
Authors: Ishii Akira , Katsuura Goro , Imamaki Hirotaka , Kimura Hiroyuki , Mori Keita P. , Kuwabara Takashige , Kasahara Masato , Yokoi Hideki , Ohinata Kousaku , Kawanishi Tomoko , Tsuchida Junichi , Nakamoto Yuji , Nakao Kazuwa , Yanagita Motoko , Mukoyama Masashi , Mori Kiyoshi
Published: November 2017

Neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2 or LCN2) is an iron carrier protein whose circulating level is increased by kidney injury, bacterial infection and obesity, but its metabolic consequence remains elusive. To study physiological role of LCN2 in energy homeostasis, we challenged female Lcn2 knockout (KO) and wild-type (WT) mice with high fat diet (HFD) or cold exposure. Under normal diet, physical constitutions of Lcn2 KO and WT mice were indistinguishable. During HFD treatment, Lcn2 KO mice exhibited larger brown adipose tissues (BAT), consumed more oxygen, ate more food and gained less body weights as compared to WT mice. When exposed to 4 °C, KO mice showed higher body temperature and more intense 18F-fluorodeoxyglucose uptake in BAT, which were cancelled by β3 adrenergic receptor blocker or iron-loaded (but not iron-free) LCN2 administration. These findings suggest that circulating LCN2 possesses obesity-promoting and anti-thermogenic effects through inhibition of BAT activity in an iron-dependent manner.
Prep1 prevents premature adipogenesis of mesenchymal progenitors
Authors: Maroni Giorgia , Tkachuk Vsevolod A. , Egorov Alexander , Morelli Marco J. , Luongo Raffaele , Levantini Elena , Blasi Francesco , Magli Maria Cristina , Penkov Dmitry
Published: November 2017

Transcriptional regulators are crucial in adipocyte differentiation. We now show that the homeodomain-containing transcription factor Prep1 is a repressor of adipogenic differentiation since its down-regulation (DR) in both ex vivo bone marrow-derived mesenchymal stromal cells (MSC) and in vitro 3T3-L1 preadipocytes significantly increases their adipogenic differentiation ability. Prep1 acts at a stage preceding the activation of the differentiation machinery because its DR makes cells more prone to adipogenic differentiation even in the absence of the adipogenic inducers. Prep1 DR expands the DNA binding landscape of C/EBPβ (CCAAT enhancer binding protein β) without affecting its expression or activation. The data indicate that Prep1 normally acts by restricting DNA binding of transcription factors to adipogenic enhancers, in particular C/EBPβ.
Fine Tuning the Energy Barrier of Molecular Nanomagnets via Lattice Solvent Molecules
Authors: Liu Cai-Ming , Zhang De-Qing , Zhu Dao-Ben
Published: November 2017

Solvents play important roles in our lives, they are also of interest in molecular materials, especially for molecular magnets. The solvatomagnetic effect is generally used for trigger and/or regulation of magnetic properties in molecule-based systems, however, molecular nanomagnets showing solvatomagnetic effects are very difficult to obtain. Here we report four 3d-4f heterometallic cluster complexes containing ROH lattice solvent molecules, [Cu3Tb2(H3L)2(OAc)2(hfac)4]∙2ROH {H6L = 1,3-Bis[tris(hydroxymethyl)methylamino]propane, hfac− = hexafluoroacetylacetonate; R = CH3, 1; R = C2H5, 2; R = C3H7, 3; R = H, 4}. Single-molecule magnet (SMM) properties of these four complexes were observed to be dependent on the ROH lattice solvent molecule. There is an interesting magneto-structural correlation: the larger the R group, the higher the energy barrier. For the first time, the solvatomagnetic effect is used for the continuous fine adjustment of the energy barrier of 0D molecular nanomagnets. Additionally, [Cu3Dy2(H3L)2(OAc)2(hfac)4]∙2MeOH (5), an analogue of [Cu3Tb2(H3L)2(OAc)2(hfac)4]∙2MeOH (1), is also reported for comparison.
Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer
Authors: Conteduca V. , Scarpi E. , Caroli P. , Salvi S. , Lolli C. , Burgio S. L. , Menna C. , Schepisi G. , Testoni S. , Gurioli G. , Paganelli G. , Casadio V. , Matteucci F. , De Giorgi U.
Published: November 2017

The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.