bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucosinolate and isothiocyanate intakes are inversely associated with breast cancer risk: a case–control study in China
Authors: Zhang Nai-Qi , Ho Suzanne C. , Mo Xiong-Fei , Lin Fang-Yu , Huang Wu-Qing , Luo Hong , Huang Jing , Zhang Cai-Xia
Published: April 2018

Although previous studies have investigated the association of cruciferous vegetable consumption with breast cancer risk, few studies focused on the association between bioactive components in cruciferous vegetables, glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This study aimed to examine the association between consumption of cruciferous vegetables and breast cancer risk according to GSL and ITC contents in a Chinese population. A total of 1485 cases and 1506 controls were recruited into this case–control study from June 2007 to March 2017. Consumption of cruciferous vegetables was assessed using a validated FFQ. Dietary GSL and ITC were computed by using two food composition databases linking GSL and ITC contents in cruciferous vegetables with responses to the FFQ. The OR and 95 % CI were assessed by unconditional logistic regression after adjusting for the potential confounders. Significant inverse associations were found between consumption of cruciferous vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the highest with the lowest quartile were 0·51 (95 % CI 0·41, 0·63) for cruciferous vegetables, 0·54 (95 % CI 0·44, 0·67) for GSL and 0·62 (95 % CI 0·50, 0·76) for ITC, respectively. These inverse associations were also observed in both premenopausal and postmenopausal women. Subgroup analysis by hormone receptor status found inverse associations between cruciferous vegetables, GSL and ITC and both hormone-receptor-positive or hormone-receptor-negative breast cancer. This study indicated that consumption of cruciferous vegetables, GSL and ITC was inversely associated with breast cancer risk among Chinese women.
Regulation for E-payment Systems: Analytical Approaches Beyond Private Ordering
Authors: Omotubora Adekemi , Basu Subhajit
Published: April 2018

Technology-driven payment instruments and services are facilitating the development of e-commerce; however, security concerns beleaguer their implementation, particularly in developing countries. This article considers the limits of private ordering in the regulation of e-payment systems. It uses Nigeria to exemplify a developing country that is increasingly pushing for the adoption of a regulatory framework for e-payment systems based on private ordering. It argues that, although technical standards and self-regulation by the financial industry are important, law is an essential regulatory mechanism that is largely absent. The article proposes that law be used as a mechanism to set and compel compliance with technical and industry standards, thus building trust, catering to public interest concerns and legitimizing the regulatory process.
A new heligmonellid (Nematoda) species of the genus Stilestrongylus in Euryoryzomys russatus (Rodentia: Sigmodontinae) in the Atlantic Forest, southern Brazil
Authors: Boullosa R.G. , Simões R.O. , Andrade-Silva B.E. , Gentile R. , Maldonado A.
Published: April 2018

A new species of Nippostrongylinae (Nematoda: Heligmonellidae), Stilestrongylus rolandoi n. sp., is described from specimens collected from the small intestine of the rodent Euryoryzomys russatus in the Atlantic Forest (Santo Amaro da Imperatriz, Santa Catarina state, southern Brazil). The genus Stilestrongylus includes 23 species, which parasitize rodents occurring in the Neotropical region. Stilestrongylus aureus (Durette-Desset & Sutton, 1985) from Argentina, S. azarai (Durette-Desset & Sutton, 1985) from Argentina, S. flavescens (Sutton & Durette-Desset, 1991) from Uruguay, S. franciscanus (Digiani & Durette-Desset, 2002) from Argentina, S. gracielae (Digiani & Durette-Desset, 2006) from Argentina, and S. oryzomysi (Sutton & Durette-Desset, 1991) from Argentina are closely related to Stilestrongylus rolandoi n. sp., all having caudal bursa patterns of types 1–4 in one of the lobes. Stilestrongylus rolandoi n. sp. is distinguished from the aforementioned species by its ray 6 being short in relation to rays 4 and 5, which are long and robust, and by having caudal bursa patterns of types 1–4 in both lobes. The new species has 27 ridges in the mid-body in males, and 24 in females, and has one of the highest ratios of spicule length to body length (21−33%) in this genus.
Astrophysical gyrokinetics: turbulence in pressure-anisotropic plasmas at ion scales and beyond
Authors: Kunz M. W. , Abel I. G. , Klein K. G. , Schekochihin A. A.
Published: April 2018

We present a theoretical framework for describing electromagnetic kinetic turbulence in a multi-species, magnetized, pressure-anisotropic plasma. The turbulent fluctuations are assumed to be small compared to the mean field, to be spatially anisotropic with respect to it and to have frequencies small compared to the ion cyclotron frequency. At scales above the ion-Larmor radius, the theory reduces to the pressure-anisotropic generalization of kinetic reduced magnetohydrodynamics (KRMHD) formulated by Kunz et al. (J. Plasma Phys., vol. 81, 2015, 325810501). At scales at and below the ion-Larmor radius, three main objectives are achieved. First, we analyse the linear response of the pressure-anisotropic gyrokinetic system, and show it to be a generalization of previously explored limits. The effects of pressure anisotropy on the stability and collisionless damping of Alfvénic and compressive fluctuations are highlighted, with attention paid to the spectral location and width of the frequency jump that occurs as Alfvén waves transition into kinetic Alfvén waves. Secondly, we derive and discuss a very general gyrokinetic free-energy conservation law, which captures both the KRMHD free-energy conservation at long wavelengths and dual cascades of kinetic Alfvén waves and ion entropy at sub-ion-Larmor scales. We show that non-Maxwellian features in the distribution function change the amount of phase mixing and the efficiency of magnetic stresses, and thus influence the partitioning of free energy amongst the cascade channels. Thirdly, a simple model is used to show that pressure anisotropy, even within the bounds imposed on it by firehose and mirror instabilities, can cause order-of-magnitude variations in the ion-to-electron heating ratio due to the dissipation of Alfvénic turbulence. Our theory provides a foundation for determining how pressure anisotropy affects turbulent fluctuation spectra, the differential heating of particle species and the ratio of parallel and perpendicular phase mixing in space and astrophysical plasmas.
Nanoencapsulation of benznidazole in calcium carbonate increases its selectivity to Trypanosoma cruzi
Authors: Tessarolo Louise Donadello , de Menezes Ramon Róseo Paula Pessoa Bezerra , Mello Clarissa Perdigão , Lima Dânya Bandeira , Magalhães Emanuel Paula , Bezerra Eveline Matias , Sales Francisco Adilson Matos , Barroso Neto Ito Liberato , Oliveira Maria de Fátima , dos Santos Ricardo Pires , Albuquerque Eudenilson L. , Freire Valder Nogueira , Martins Alice Maria
Published: April 2018

Chagas disease is a public health problem, affecting about 7 million people worldwide. Benznidazole (BZN) is the main treatment option, but it has limited effectiveness and can cause severe adverse effects. Drug delivery through nanoparticles has attracted the interest of the scientific community aiming to improve therapeutic options. The aim of this study was to evaluate the cytotoxicity of benznidazole-loaded calcium carbonate nanoparticles (BZN@CaCO3) on Trypanosoma cruzi strain Y. It was observed that BZN@CaCO3 was able to reduce the viability of epimastigote, trypomastigote and amastigote forms of T. cruzi with greater potency when compared with BZN. The amount of BZN necessary to obtain the same effect was up to 25 times smaller when loaded with CaCO3 nanoparticles. Also, it was observed that BZN@CaCO3 enhanced the selectivity index. Furthermore, the cell-death mechanism induced by both BZN and BZN@CaCO3 was evaluated, indicating that both substances caused necrosis and changed mitochondrial membrane potential.
The reduced genome of Candidatus Kinetoplastibacterium sorsogonicusi, the endosymbiont of Kentomonas sorsogonicus (Trypanosomatidae): loss of the haem-synthesis pathway
Authors: Silva Flávia M. , Kostygov Alexei Y. , Spodareva Viktoria V. , Butenko Anzhelika , Tossou Regis , Lukeš Julius , Yurchenko Vyacheslav , Alves João M. P.
Published: April 2018

Trypanosomatids of the genera Angomonas and Strigomonas (subfamily Strigomonadinae) have long been known to contain intracellular beta-proteobacteria, which provide them with many important nutrients such as haem, essential amino acids and vitamins. Recently, Kentomonas sorsogonicus, a divergent member of Strigomonadinae, has been described. Herein, we characterize the genome of its endosymbiont, Candidatus Kinetoplastibacterium sorsogonicusi. This genome is completely syntenic with those of other known Ca. Kinetoplastibacterium spp., but more reduced in size (~742 kb, compared with 810–833 kb, respectively). Gene losses are not concentrated in any hot-spots but are instead distributed throughout the genome. The most conspicuous loss is that of the haem-synthesis pathway. For long, removing haemin from the culture medium has been a standard procedure in cultivating trypanosomatids isolated from insects; continued growth was considered as an evidence of endosymbiont presence. However, we demonstrate that, despite bearing the endosymbiont, K. sorsogonicus cannot grow in culture without haem. Thus, the traditional test cannot be taken as a reliable criterion for the absence or presence of endosymbionts in trypanosomatid flagellates. It remains unclear why the ability to synthesize such an essential compound was lost in Ca. K. sorsogonicusi, whereas all other known bacterial endosymbionts of trypanosomatids retain them.
CYP51 as drug targets for fungi and protozoan parasites: past, present and future
Authors: Lepesheva Galina I. , Friggeri Laura , Waterman Michael R.
Published: April 2018

The efficiency of treatment of human infections with the unicellular eukaryotic pathogens such as fungi and protozoa remains deeply unsatisfactory. For example, the mortality rates from nosocomial fungemia in critically ill, immunosuppressed or post-cancer patients often exceed 50%. A set of six systemic clinical azoles [sterol 14α-demethylase (CYP51) inhibitors] represents the first-line antifungal treatment. All these drugs were discovered empirically, by monitoring their effects on fungal cell growth, though it had been proven that they kill fungal cells by blocking the biosynthesis of ergosterol in fungi at the stage of 14α-demethylation of the sterol nucleus. This review briefs the history of antifungal azoles, outlines the situation with the current clinical azole-based drugs, describes the attempts of their repurposing for treatment of human infections with the protozoan parasites that, similar to fungi, also produce endogenous sterols, and discusses the most recently acquired knowledge on the CYP51 structure/function and inhibition. It is our belief that this information should be helpful in shifting from the traditional phenotypic screening to the actual target-driven drug discovery paradigm, which will rationalize and substantially accelerate the development of new, more efficient and pathogen-oriented CYP51 inhibitors.
Azealia Banks: ‘Chasing Time’, erotics, and body politics
Authors: Hansen Kai Arne , Hawkins Stan
Published: April 2018

During the 2010s a new generation of queer hip hop artists emerged, providing an opportunity to engage with a set of politics defined by art, fashion, lyrics and music. A leading proponent of this movement was Azealia Banks, the controversial rapper, artist and actress from New York. This study instigates a critical investigation of her performance strategies in the track and video, ‘Chasing Time’ (2014), offering up various perspectives that probe into queer agency. It is suggested that techniques of sonic styling necessitate a consideration of subjectivity alongside genre and style. Employing audiovisual methods of analysis, we reflect on the relationship between gendered subjectivity and modalities of queerness as a means for demonstrating how aesthetics are staged and aligned to advanced techniques of production. It is argued that the phenomenon of eroticised agency, through hyperembodied display, is central to understanding body politics. This article opens a space for problematising issues of black female subjectivity in a genre that is traditionally relegated to the male domain.
BOOTSTRAP-ASSISTED UNIT ROOT TESTING WITH PIECEWISE LOCALLY STATIONARY ERRORS
Authors: Rho Yeonwoo , Shao Xiaofeng
Published: April 2018

In unit root testing, a piecewise locally stationary process is adopted to accommodate nonstationary errors that can have both smooth and abrupt changes in second- or higher-order properties. Under this framework, the limiting null distributions of the conventional unit root test statistics are derived and shown to contain a number of unknown parameters. To circumvent the difficulty of direct consistent estimation, we propose to use the dependent wild bootstrap to approximate the nonpivotal limiting null distributions and provide a rigorous theoretical justification for bootstrap consistency. The proposed method is compared through finite sample simulations with the recolored wild bootstrap procedure, which was developed for errors that follow a heteroscedastic linear process. Furthermore, a combination of autoregressive sieve recoloring with the dependent wild bootstrap is shown to perform well. The validity of the dependent wild bootstrap in a nonstationary setting is demonstrated for the first time, showing the possibility of extensions to other inference problems associated with locally stationary processes.
Preparation of Bi4Te3 highly oriented nanopillars array film with enhanced electrical properties
Authors: Wu Jing , Jian Jikang , Wang Shufang , Guo Shuang , Lei Renbo , Liu Haitao
Published: April 2018

The Bi4Te3 films with well-ordered orientation and microstructure were successfully prepared on SiO2 substrate by a vacuum thermal evaporation deposition technique for the first time. We discussed the effects of evaporation temperature and substrate temperature on the phase and its well-ordered growth of Bi4Te3 films. The formation of Bi4Te3 phase is owing to the differences of the saturated vapor pressure. The thermoelectric transport properties of the Bi4Te3 films were investigated and the (00l)-oriented nanopillars array film has a better electrical transport performance, whose value of PF is 0.032 mWm−1 K−2 at 339 K, approaching twice that of the non-oriented ordinary film. The enhanced electrical properties of Bi4Te3 films could be achieved via the high-crystallinity well-controlled (00l)-oriented nanopillars array.
A Tutte Polynomial for Maps
Authors: GOODALL ANDREW , KRAJEWSKI THOMAS , REGTS GUUS , VENA LLUÍS
Published: April 2018

We follow the example of Tutte in his construction of the dichromate of a graph (i.e. the Tutte polynomial) as a unification of the chromatic polynomial and the flow polynomial in order to construct a new polynomial invariant of maps (graphs embedded in orientable surfaces). We call this the surface Tutte polynomial. The surface Tutte polynomial of a map contains the Las Vergnas polynomial, the Bollobás–Riordan polynomial and the Krushkal polynomial as specializations. By construction, the surface Tutte polynomial includes among its evaluations the number of local tensions and local flows taking values in any given finite group. Other evaluations include the number of quasi-forests.
Aurangzeb in Mewar through the stories of Sultan Singh
Authors: HARLAN LINDSEY
Published: April 2018

Examining narratives about Sultan Singh, Udaipur's most prominent sagasji (divine, heroic guardian), this essay analyzes the narrative frame of contention between Sultan Singh's father, the Maharana (“Great King”) Raj Singh and the emperor Aurangzeb. It argues that the frame inevitably glorifies the Maharana and contrasts him with emperor, invariably represented as a worthy opponent, as it contextuales variant lore about the life and tragic death of the Maharana's heir apparent. In some accounts, Sultan Singh's demise is blamed on a plot devised by the emperor. This lore exalts both father and son while also demonstrating a pervasive anxiety about the danger inherent in power.
Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival
Authors: Shiota Megumi , Naya Masayuki , Yamamoto Takehiro , Hishiki Takako , Tani Takeharu , Takahashi Hiroyuki , Kubo Akiko , Koike Daisuke , Itoh Mai , Ohmura Mitsuyo , Kabe Yasuaki , Sugiura Yuki , Hiraoka Nobuyoshi , Morikawa Takayuki , Takubo Keiyo , Suina Kentaro , Nagashima Hideaki , Sampetrean Oltea , Nagano Osamu , Saya Hideyuki , Yamazoe Shogo , Watanabe Hiroyuki , Suematsu Makoto
Published: April 2018

Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.
Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii
Authors: Bielska Ewa , Sisquella Marta Arch , Aldeieg Maha , Birch Charlotte , O’Donoghue Eloise J. , May Robin C.
Published: April 2018

The Pacific Northwest outbreak of cryptococcosis, caused by a near-clonal lineage of the fungal pathogen Cryptococcus gattii, represents the most significant cluster of life-threatening fungal infections in otherwise healthy human hosts currently known. The outbreak lineage has a remarkable ability to grow rapidly within human white blood cells, using a unique ‘division of labour’ mechanism within the pathogen population, where some cells adopt a dormant behaviour to support the growth of neighbouring cells. Here we demonstrate that pathogenic ‘division of labour’ can be triggered over large cellular distances and is mediated through the release of extracellular vesicles by the fungus. Isolated vesicles released by virulent strains are taken up by infected host macrophages and trafficked to the phagosome, where they trigger the rapid intracellular growth of non-outbreak fungal cells that would otherwise be eliminated by the host. Thus, long distance pathogen-to-pathogen communication via extracellular vesicles represents a novel mechanism to control complex virulence phenotypes in Cryptococcus gattii and, potentially, other infectious species.
The molecular basis of JAK/STAT inhibition by SOCS1
Authors: Liau Nicholas P. D. , Laktyushin Artem , Lucet Isabelle S. , Murphy James M. , Yao Shenggen , Whitlock Eden , Callaghan Kimberley , Nicola Nicos A. , Kershaw Nadia J. , Babon Jeffrey J.
Published: April 2018

The SOCS family of proteins are negative-feedback inhibitors of signalling induced by cytokines that act via the JAK/STAT pathway. SOCS proteins can act as ubiquitin ligases by recruiting Cullin5 to ubiquitinate signalling components; however, SOCS1, the most potent member of the family, can also inhibit JAK directly. Here we determine the structural basis of both these modes of inhibition. Due to alterations within the SOCS box domain, SOCS1 has a compromised ability to recruit Cullin5; however, it is a direct, potent and selective inhibitor of JAK catalytic activity. The kinase inhibitory region of SOCS1 targets the substrate binding groove of JAK with high specificity and thereby blocks any subsequent phosphorylation. SOCS1 is a potent inhibitor of the interferon gamma (IFNγ) pathway, however, it does not bind the IFNγ receptor, making its mode-of-action distinct from SOCS3. These findings reveal the mechanism used by SOCS1 to inhibit signalling by inflammatory cytokines.
Domain imaging across the magneto-structural phase transitions in Fe1+yTe
Authors: Warmuth Jonas , Bremholm Martin , Hofmann Philip , Wiebe Jens , Wiesendanger Roland
Published: April 2018

The investigation of the magnetic phase transitions in the parent compounds of Fe-based superconductors is regarded essential for an understanding of the pairing mechanism in the related superconducting compounds. Even though the chemical and electronic properties of these materials are often strongly inhomogeneous on a nanometer length scale, studies of the magnetic phase transitions using spatially resolved experimental techniques are still scarce. Here, we present a real space spin-resolved scanning tunneling microscopy investigation of the surface of Fe1+yTe single crystals with different excess Fe content, y, which are continuously driven through the magnetic phase transition. For Fe1.08Te, the transition into the low-temperature monoclinic phase is accompanied by the appearance of a chevron-patterned structural ordering due to the four 90° rotational domains of the monoclinic lattice. Each of the structural domains contains locally commensurate nanoscale diagonal double stripe antiferromagnetic spin order domains with π-phase slips accross domain boundaries. In the low-temperature phase of Fe1.12Te, on the other hand, the chevron pattern gets rather narrow and less well-defined, and an additional 90° rotated component of the spin-order with local plaquette order emerges. The simultaneous imaging of spin and structural order we show here gives valuable insights into the nature of the magneto-structural domains of Fe1+yTe near the tricritical point, which presumably add to the understanding of the mechanism of superconductivity in the related Fe1+yTe
x
Se1−x material.
Author Correction: Radioligand binding analysis of α 2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding
Authors: Phan Jenny-Ann , Landau Anne M. , Jakobsen Steen , Wong Dean F. , Gjedde Albert
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Antimicrobial activity of Ti-ZrN/Ag coatings for use in biomaterial applications
Authors: Slate Anthony J. , Wickens David J. , El Mohtadi Mohamed , Dempsey-Hibbert Nina , West Glen , Banks Craig E. , Whitehead Kathryn A.
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Entrainment of theta, not alpha, oscillations is predictive of the brightness enhancement of a flickering stimulus
Authors: Bertrand Jennifer K. , Wispinski Nathan J. , Mathewson Kyle E. , Chapman Craig S.
Published: April 2018

Frequency-dependent brightness enhancement, where a flickering light can appear twice as bright as an equiluminant constant light, has been reported to exist within the alpha (8–12 Hz) band. Could oscillatory neural activity be driving this perceptual effect? Here, in two experiments, human subjects reported which of two flickering stimuli were brighter. Strikingly, 4 Hz stimuli were reported as brighter more than 80% of the time when compared to all other tested frequencies, even though all stimuli were equiluminant and of equal temporal length. Electroencephalography recordings showed that inter-trial phase coherence (ITC) of theta (4 Hz) was: (1) Significantly greater than alpha, contralateral to the flickering stimulus; (2) Enhanced by the presence of a second ipsilateral 4 Hz flickering stimulus; and (3) Uniquely lateralized, unlike the alpha band. Importantly, on trials with two identical stimuli (i.e. 4 Hz vs 4 Hz), the brightness discrimination judgment could be predicted by the hemispheric balance in the amount of 4 Hz ITC. We speculate that the theta rhythm plays a distinct information transfer role, where its ability to share information between hemispheres via entrainment promotes a better processing of visual information to inform a discrimination decision.
Clinicopathological and prognostic significance of high circulating lymphocyte ratio in patients receiving neoadjuvant chemotherapy for advanced gastric cancer
Authors: Li Yang , Wei Yao , He Qi , Wang Xulin , Fan Chaogang , Li Guoli
Published: April 2018

This study was designed to investigate the prognostic value of circulating blood cell counts and subsets for patients with advanced gastric cancer (AGC) treated with neoadjuvant chemotherapy (NAC) and the factors determining pathological complete response (pCR). In 112 patients with AGC, we retrospectively examined the ratios of lymphocyte, monocyte, and neutrophil during and after NAC before surgery, and the percentages of CD3+, CD3+ CD4+, CD3+ CD8+ and CD4+/CD8+ lymphocytes as well. We also investigated their associations with the pCR rate and overall survival (OS). The ratios of lymphocyte taken before and after NAC were significantly greater in forty-four pCR cases than that in sixty-eight non-pCR cases. During NAC, the proportion of lymphocyte and the percentages of CD3+, CD3+ CD4+, and CD3+ CD8+ lymphocytes were dramatically increased in pCR group. The lymphocyte ratio showed an independent association with pCR by multivariate analysis and maintained at a relatively high level in pCR cases. By mean of 31.53% lymphocyte ratio before-NAC and 41.68% after-NAC, cases with high lymphocyte ratio showed significantly better outcome in OS. High circulating lymphocyte ratios, both before and after NAC, are positively associated with pCR and improved OS in advanced gastric cancer, which may be considered as a new prognostic biomarker.
Association between radiological parameters and clinical and molecular characteristics in human somatotropinomas
Authors: Alhambra-Expósito María R. , Ibáñez-Costa Alejandro , Moreno-Moreno Paloma , Rivero-Cortés Esther , Vázquez-Borrego Mari C. , Blanco-Acevedo Cristóbal , Toledano-Delgado Álvaro , Lombardo-Galera María S. , Vallejo-Casas Juan A. , Gahete Manuel D. , Castaño Justo P. , Gálvez María A. , Luque Raúl M.
Published: April 2018

Acromegaly is a rare but severe disease, originated in 95% of cases by a growth hormone-secreting adenoma (somatotropinoma) in the pituitary. Magnetic resonance imaging (MRI) is a non-invasive technique used for the diagnosis and prognosis of pituitary tumours. The aim of this study was to determine whether the use of T2-weighted signal intensity at MRI could help to improve the characterisation of somatotropinomas, by analysing its relationship with clinical/molecular features. An observational study was implemented in a cohort of 22 patients (mean age = 42.1 ± 17.2 years; 59% women; 95% size>10 mm). Suprasellar-extended somatotropinomas presented larger diameters vs. non-extended tumours. T2-imaging revealed that 59% of tumours were hyperintense and 41% isointense adenomas, wherein hyperintense were more invasive (according to Knosp-score) than isointense adenomas. A higher proportion of hyperintense somatotropinomas presented extrasellar-growth, suprasellar-growth and invasion of the cavernous sinus compared to isointense adenomas. Interestingly, somatostatin receptor-3 and dopamine receptor-5 (DRD5) expression levels were associated with extrasellar and/or suprasellar extension. Additionally, DRD5 was also higher in hyperintense adenomas and its expression was directly correlated with Knosp-score and with tumour diameter. Hence, T2-weighted MRI on somatotropinomas represents a potential tool to refine their diagnosis and prognosis, and could support the election of preoperative treatment, when required.
Perineuronal Net Protein Neurocan Inhibits NCAM/EphA3 Repellent Signaling in GABAergic Interneurons
Authors: Sullivan Chelsea S. , Gotthard Ingo , Wyatt Elliott V. , Bongu Srihita , Mohan Vishwa , Weinberg Richard J. , Maness Patricia F.
Published: April 2018

Perineuronal nets (PNNs) are implicated in closure of critical periods of synaptic plasticity in the brain, but the molecular mechanisms by which PNNs regulate synapse development are obscure. A receptor complex of NCAM and EphA3 mediates postnatal remodeling of inhibitory perisomatic synapses of GABAergic interneurons onto pyramidal cells in the mouse frontal cortex necessary for excitatory/inhibitory balance. Here it is shown that enzymatic removal of PNN glycosaminoglycan chains decreased the density of GABAergic perisomatic synapses in mouse organotypic cortical slice cultures. Neurocan, a key component of PNNs, was expressed in postnatal frontal cortex in apposition to perisomatic synapses of parvalbumin-positive interneurons. Polysialylated NCAM (PSA-NCAM), which is required for ephrin-dependent synapse remodeling, bound less efficiently to neurocan than mature, non-PSA-NCAM. Neurocan bound the non-polysialylated form of NCAM at the EphA3 binding site within the immunoglobulin-2 domain. Neurocan inhibited NCAM/EphA3 association, membrane clustering of NCAM/EphA3 in cortical interneuron axons, EphA3 kinase activation, and ephrin-A5-induced growth cone collapse. These studies delineate a novel mechanism wherein neurocan inhibits NCAM/EphA3 signaling and axonal repulsion, which may terminate postnatal remodeling of interneuron axons to stabilize perisomatic synapses in vivo.
Identification of QTL controlling domestication-related traits in cowpea (Vigna unguiculata L. Walp)
Authors: Lo Sassoum , Muñoz-Amatriaín María , Boukar Ousmane , Herniter Ira , Cisse Ndiaga , Guo Yi-Ning , Roberts Philip A. , Xu Shizhong , Fatokun Christian , Close Timothy J.
Published: April 2018

Cowpea (Vigna unguiculata L. Walp) is a warm-season legume with a genetically diverse gene-pool composed of wild and cultivated forms. Cowpea domestication involved considerable phenotypic changes from the wild progenitor, including reduction of pod shattering, increased organ size, and changes in flowering time. Little is known about the genetic basis underlying these changes. In this study, 215 recombinant inbred lines derived from a cross between a cultivated and a wild cowpea accession were used to evaluate nine domestication-related traits (pod shattering, peduncle length, flower color, days to flowering, 100-seed weight, pod length, leaf length, leaf width and seed number per pod). A high-density genetic map containing 17,739 single nucleotide polymorphisms was constructed and used to identify 16 quantitative trait loci (QTL) for these nine traits. Based on annotations of the cowpea reference genome, genes within these regions are reported. Four regions with clusters of QTL were identified, including one on chromosome 8 related to increased organ size. This study provides new knowledge of the genomic regions controlling domestication-related traits in cowpea as well as candidate genes underlying those QTL. This information can help to exploit wild relatives in cowpea breeding programs.
Publisher Correction: Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R receptors
Authors: Chepurny Oleg G. , Bonaccorso Ron L. , Leech Colin A. , Wöllert Torsten , Langford George M. , Schwede Frank , Roth Christian L. , Doyle Robert P. , Holz George G.
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Gunn-Hilsum Effect in Mechanically Strained Silicon Nanowires: Tunable Negative Differential Resistance
Authors: Shiri Daryoush , Verma Amit , Nekovei Reza , Isacsson Andreas , Selvakumar C. R. , Anantram M. P.
Published: April 2018

Gunn (or Gunn-Hilsum) Effect and its associated negative differential resistivity (NDR) emanates from transfer of electrons between two different energy subbands. This effect was observed in semiconductors like GaAs which has a direct bandgap of very low effective mass and an indirect subband of high effective mass which lies ~300 meV above the former. In contrast to GaAs, bulk silicon has a very high energy spacing (~1 eV) which renders the initiation of transfer-induced NDR unobservable. Using Density Functional Theory (DFT), semi-empirical 10 orbital (sp3d5s*) Tight Binding and Ensemble Monte Carlo (EMC) methods we show for the first time that (a) Gunn Effect can be induced in silicon nanowires (SiNW) with diameters of 3.1 nm under +3% strain and an electric field of 5000 V/cm, (b) the onset of NDR in the I-V characteristics is reversibly adjustable by strain and (c) strain modulates the resistivity by a factor 2.3 for SiNWs of normal I-V characteristics i.e. those without NDR. These observations are promising for applications of SiNWs in electromechanical sensors and adjustable microwave oscillators. It is noteworthy that the observed NDC is different in principle from Esaki-Diode and Resonant Tunneling Diodes (RTD) in which NDR originates from tunneling effect.
Gelatinous plankton is important in the diet of European eel (Anguilla anguilla) larvae in the Sargasso Sea
Authors: Ayala Daniel J. , Munk Peter , Lundgreen Regitze B. C. , Traving Sachia J. , Jaspers Cornelia , Jørgensen Tue S. , Hansen Lars H. , Riemann Lasse
Published: April 2018

Limited insight into eel larvae feeding and diet prevents a holistic overview of the life-cycle of catadromous eels and an understanding of the ecological position of their early stages in marine waters. The present study evaluated the diet of larval European eel, Anguilla anguilla - a critically endangered species. Next-generation 18S rRNA gene sequencing data of Sargasso Sea eel larvae gut contents and marine snow aggregates was compared with a reference plankton database to assess the trophic relations of eel larvae. Gut contents of A. anguilla larvae were not well explained by the eukaryotic composition of marine snow aggregates; gut contents being dominated by gene sequences of Hydrozoa taxa (phylum Cnidaria), while snow aggregates were dominated by Crustacea taxa. Pronounced differences between gut contents and marine snow aggregates were also seen in the prokaryotic 16S rRNA gene composition. The findings, in concert with significant abundances of Hydrozoa in the study area, suggest that Hydrozoa plankton are important in the diet of A. anguilla larvae, and that consideration of these organisms would further our understanding of A. anguilla feeding strategies in the oligotrophic Sargasso Sea, which may be important for potential future rearing of A. anguilla larvae in captivity.
Y-box protein-associated acidic protein (YBAP1/C1QBP) affects the localization and cytoplasmic functions of YB-1
Authors: Matsumoto Ken , Kose Shingo , Kuwahara Iku , Yoshimura Mami , Imamoto Naoko , Yoshida Minoru
Published: April 2018

The Y-box proteins are multifunctional nucleic acid-binding proteins involved in various aspects of gene regulation. The founding member of the Y-box protein family, YB-1, functions as a transcription factor as well as a principal component of messenger ribonucleoprotein particles (mRNPs) in somatic cells. The nuclear level of YB-1 is well correlated with poor prognosis in many human cancers. Previously, we showed that a Y-box protein–associated acidic protein, YBAP1, which is identical to complement component 1, q subcomponent-binding protein (C1QBP, also called gC1qR, hyaluronan-binding protein 1 [HABP1] or ASF/SF2-associated protein p32), relieves translational repression by YB-1. Here we show that the nuclear localization of YB-1 harboring a point mutation in the cold shock domain was inhibited when co-expressed with YBAP1, whereas cytoplasmic accumulation of the wild-type YB-1 was not affected. We showed that YBAP1 inhibited the interaction between YB-1 and transportin 1. In the cytoplasm, YBAP1 affected the accumulation of YB-1 to processing bodies (P-bodies) and partially abrogated the mRNA stabilization by YB-1. Our results, indicating that YBAP1/C1QBP regulates the nucleo-cytoplasmic distribution of YB-1 and its cytoplasmic functions, are consistent with a model that YBAP1/C1QBP acts as an mRNP remodeling factor.
BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia
Authors: Miao Liu , Yin Rui-Xing , Pan Shang-Ling , Yang Shuo , Yang De-Zhai , Lin Wei-Xiong
Published: April 2018

Little is known about the association of the BCL3-PVRL2-TOMM40 SNPs and dyslipidemia. This study was to detect 12 BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia in the Chinese Maonan population. Genotyping was performed in 1130 normal and 832 dyslipidemia participants. Generalized multifactor dimensionality reduction was used to screen the best interaction combination among SNPs and environmental exposures. Allele and genotype frequencies of the detected SNPs were different between the two groups (P < 0.05–0.001). Association of the 12 SNPs and serum lipid levels was observed (P < 0.004–0.001). Multiple-locus linkage disequilibrium was not statistically independent in the population (D’ = 0.01–0.98). The dominant model of rs8100239 and rs157580 SNPs, several haplotypes and G × G interaction haplotypes contributed to a protection, whereas the dominant model of rs10402271, rs3810143, rs519113, rs6859 SNPs, another haplotypes and G × G interaction haplotypes revealed an increased morbidity function (P < 0.05–0.001). There were significant three-locus model involving SNP-SNP, SNP-environment, haplotype-haplotype interactions (P < 0.05–0.001). The subjects carrying several genotypes and haplotypes decreased dyslipidemia risk, whereas the subjects carrying other genotypes and haplotypes increased dyslipidemia risk. The BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia were observed in the Chinese Maonan population.
Evolutionary convergence and divergence in archaeal chromosomal proteins and Chromo-like domains from bacteria and eukaryotes
Authors: Kaur Gurmeet , Iyer Lakshminarayan M. , Subramanian Srikrishna , Aravind L.
Published: April 2018

SH3-fold-β-barrel domains of the chromo-like superfamily recognize epigenetic marks in eukaryotic proteins. Their provenance has been placed either in archaea, based on apparent structural similarity to chromatin-compacting Sul7d and Cren7 proteins, or in bacteria based on the presence of sequence homologs. Using sequence and structural evidence we establish that the archaeal Cren7/Sul7 proteins emerged from a zinc ribbon (ZnR) ancestor. Further, we show that the ancestral eukaryotic chromo-like domains evolved from bacterial versions, likely acquired from early endosymbioses, which already possessed an aromatic cage for recognition of modified amino-groups. These bacterial versions are part of a radiation of secreted SH3-fold domains, which spawned both chromo-like domains and classical SH3 domains in the context of peptide-recognition in the peptidoglycan or the extracellular matrix. This establishes that Cren7/Sul7 converged to a “SH3”-like state from a ZnR precursor via the loss of metal-chelation and acquisition of stronger hydrophobic interactions; it is unlikely to have participated in the evolution of the chromo-like domains. We show that archaea possess several Cren7/Sul7-related proteins with intact Zn-chelating ligands, which we predict to play previously unstudied roles in chromosome segregation during cell-division comparable to the PRC barrel and CdvA domain proteins.
Impact of Three Different Mutations in Ehrlichia chaffeensis in Altering the Global Gene Expression Patterns
Authors: Kondethimmanahalli Chandramouli , Ganta Roman
Published: April 2018

The rickettsial pathogenEhrlichia chaffeensiscauses a tick-borne disease, human monocytic ehrlichiosis. Mutations within certain genomic locations of the pathogen aid in understanding the pathogenesis and in developing attenuated vaccines. Our previous studies demonstrated that mutations in different genomic sites inE.chaffeensiscaused variable impacts on their growth and attenuation in vertebrate and tick hosts. Here, we assessed the effect of three mutations on transcriptional changes using RNA deep-sequencing technology. RNA sequencing aided in detecting 66–80% of the transcripts of wildtype and mutantE.chaffeensis. Mutation in an antiporter gene (ECH_0379) causing attenuated growth in vertebrate hosts resulted in the down regulation of many transcribed genes. Similarly, a mutation downstream to the ECH_0490 coding sequence resulted in minimal impact on the pathogen’sin vivogrowth, but caused major changes in its transcriptome. This mutation caused enhanced expression of several host stress response genes. Even though the ECH_0660 gene mutation caused the pathogen’s rapid clearance in vertebrate hosts and aids in generating a protective response, there was minimal impact on the transcriptome. The transcriptomic data offer novel insights about the impact of mutations on global gene expression and how they may contribute to the pathogen’s resistance and/or clearance from the host.
Improvement of cerebellar ataxic gait by injecting Cbln1 into the cerebellum of cbln1-null mice
Authors: Takeuchi Eri , Ito-Ishida Aya , Yuzaki Michisuke , Yanagihara Dai
Published: April 2018

Patients and rodents with cerebellar damage display ataxic gaits characterized by impaired coordination of limb movements. Here, gait ataxia in mice with a null mutation of the gene for the cerebellin 1 precursor protein (cbln1-null mice) was investigated by kinematic analysis of hindlimb movements during locomotion. The Cbln1 protein is predominately produced and secreted from cerebellar granule cells. The cerebellum of cbln1-null mice is characterized by an 80% reduction in the number of parallel fiber-Purkinje cell synapses compared with wild-type mice. Our analyses identified prominent differences in the temporal parameters of locomotion between cbln1-null and wild-type mice. The cbln1-null mice displayed abnormal hindlimb movements that were characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles and knees. When recombinant Cbln1 protein was injected into the cerebellum of cbln1-null mice, the step cycle and stance phase durations increased toward those of wild-type mice, and the angular excursions of the knee during a cycle period showed a much closer agreement with those of wild-type mice. These findings suggest that dysfunction of the parallel fiber-Purkinje cell synapses might underlie the impairment of hindlimb movements during locomotion in cbln1-null mice.
Crystallization behavior of the Li2S–P2S5 glass electrolyte in the LiNi1/3Mn1/3Co1/3O2 positive electrode layer
Authors: Tsukasaki Hirofumi , Mori Yota , Otoyama Misae , Yubuchi So , Asano Takamasa , Tanaka Yoshinori , Ohno Takahisa , Mori Shigeo , Hayashi Akitoshi , Tatsumisago Masahiro
Published: April 2018

Sulfide-based all-solid-state lithium batteries are a next-generation power source composed of the inorganic solid electrolytes which are incombustible and have high ionic conductivity. Positive electrode composites comprising LiNi1/3Mn1/3Co1/3O2 (NMC) and 75Li2S·25P2S5 (LPS) glass electrolytes exhibit excellent charge–discharge cycle performance and are promising candidates for realizing all-solid-state batteries. The thermal stabilities of NMC–LPS composites have been investigated by transmission electron microscopy (TEM), which indicated that an exothermal reaction could be attributed to the crystallization of the LPS glass. To further understand the origin of the exothermic reaction, in this study, the precipitated crystalline phase of LPS glass in the NMC–LPS composite was examined. In situ TEM observations revealed that the β-Li3PS4 precipitated at approximately 200 °C, and then Li4P2S6 and Li2S precipitated at approximately 400 °C. Because the Li4P2S6 and Li2S crystalline phases do not precipitate in the single LPS glass, the interfacial contact between LPS and NMC has a significant influence on both the LPS crystallization behavior and the exothermal reaction in the NMC–LPS composites.
Moonlight controls lunar-phase-dependency and regular oscillation of clock gene expressions in a lunar-synchronized spawner fish, Goldlined spinefoot
Authors: Takeuchi Yuki , Kabutomori Ryo , Yamauchi Chihiro , Miyagi Hitomi , Takemura Akihiro , Okano Keiko , Okano Toshiyuki
Published: April 2018

Goldlined spinefoot, Siganus guttatus, inhabits tropical and subtropical waters and synchronizes its spawning around the first quarter moon likely using an hourglass-like lunar timer. In previous studies, we have found that clock genes (Cryptochrome3 and Period1) could play the role of state variable in the diencephalon when determining the lunar phase for spawning. Here, we identified three Cry, two Per, two Clock, and two Bmal genes in S. guttatus and investigated their expression patterns in the diencephalon and pituitary gland. We further evaluated the effect on their expression patterns by daily interruptions of moonlight stimuli for 1 lunar cycle beginning at the new moon. It significantly modified the expression patterns in many of the examined clock(-related) genes including Cry3 in the diencephalon and/or pituitary gland. Acute interruptions of moonlight around the waxing gibbous moon upregulated nocturnal expressions of Cry1b and Cry2 in the diencephalon and pituitary gland, respectively, but did not affect expression levels of the other clock genes. These results highlighted the importance of repetitive moonlight illumination for stable or lunar-phase-specific daily expression of clock genes in the next lunar cycle that may be important for the lunar-phase-synchronized spawning on the next first quarter moon.
The impact of genome variation and diet on the metabolic phenotype and microbiome composition of Drosophila melanogaster
Authors: Jehrke Lisa , Stewart Fiona A. , Droste Andrea , Beller Mathias
Published: April 2018

The metabolic phenotype of an organism depends on a complex regulatory network, which integrates the plethora of intrinsic and external information and prioritizes the flow of nutrients accordingly. Given the rise of metabolic disorders including obesity, a detailed understanding of this regulatory network is in urgent need. Yet, our level of understanding is far from completeness and complicated by the discovery of additional layers in metabolic regulation, such as the impact of the microbial community present in the gut on the hosts’ energy storage levels. Here, we investigate the interplay between genome variation, diet and the gut microbiome in the shaping of a metabolic phenotype. For this purpose, we reared a set of fully sequenced wild type Drosophila melanogaster flies under basal and nutritionally challenged conditions and performed metabolic and microbiome profiling experiments. Our results introduce the fly as a model system to investigate the impact of genome variation on the metabolic response to diet alterations and reveal candidate single nucleotide polymorphisms associated with different metabolic traits, as well as metabolite-metabolite and metabolite-microbe correlations. Intriguingly, the dietary changes affected the microbiome composition less than anticipated. These results challenge the current view of a rapidly changing microbiome in response to environmental fluctuations.