bluuebunny/crossref_metadata_2025 huggingface dataset:
lncRNA PAPAS tethered to the rDNA enhancer recruits hypophosphorylated CHD4/NuRD to repress rRNA synthesis at elevated temperatures
Authors: Zhao Zhongliang , Sentürk Nevcin , Song Chenlin , Grummt Ingrid
Published: June 2018

Attenuation of pre-rRNA synthesis in response to elevated temperature is accompanied by increased levels of PAPAS (“promoter and pre-rRNA antisense”), a long noncoding RNA (lncRNA) that is transcribed in an orientation antisense to pre-rRNA. Here we show that PAPAS interacts directly with DNA, forming a DNA–RNA triplex structure that tethers PAPAS to a stretch of purines within the enhancer region, thereby guiding associated CHD4/NuRD (nucleosome remodeling and deacetylation) to the rDNA promoter. Protein–RNA interaction experiments combined with RNA secondary structure mapping revealed that the N-terminal part of CHD4 interacts with an unstructured A-rich region in PAPAS. Deletion or mutation of this sequence abolishes the interaction with CHD4. Stress-dependent up-regulation of PAPAS is accompanied by dephosphorylation of CHD4 at three serine residues, which enhances the interaction of CHD4/NuRD with RNA and reinforces repression of rDNA transcription. The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation.
T-type calcium channels in the orbitofrontal cortex mediate sensory integration as measured using a spontaneous oddity task in rats
Authors: Marks Wendie N. , Parker Madeline E. , Zabder Nadine K. , Greba Quentin , Snutch Terrance P. , Howland John G.
Published: June 2018

The roles of low-voltage-activated (T-type) calcium channels in brain diseases have been studied extensively. Less is known regarding the involvement of T-type channels in cognition and behavior. Sensory integration (SI) is a cognitive process whereby the brain uses unimodal or multimodal sensory features to create a comprehensive representation of the environment. The multisensory object oddity (MSO) task assesses SI using combinations of sensory features of objects, either in the same or different sensory modalities. The regulation of SI involves the orbitofrontal cortex (OFC), an area which shows high levels of T-type calcium channel expression. We tested the effects of blocking T-type calcium channels on the MSO task with the selective T-type antagonist, Z944 (5 mg/kg; i.p. systemic; 100 or 500 µM OFC infusion), in male Long Evans rats. With systemic treatment, Z944 impaired the visual and visual-olfactory versions of the task. Infusion of 100 and 500 µM Z944 produced deficits in the olfactory version of the task. In addition, only vehicle-infused, but not Z944-infused, rats showed significant performance above chance for all task variants. Thus, the present results suggest that T-type calcium channels in OFC are involved in SI of features in an oddity task. Given that unimodal SI was disrupted by OFC infusions of Z944, the deficits in the multimodal task must be interpreted with caution. As SI is disrupted in psychiatric disorders, further investigations elucidating the brain regions implicated in SI regulation by T-type calcium channels may help inform therapeutic development for those suffering from SI impairments.
Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib
Authors: Guan Jikui , Fransson Susanne , Siaw Joachim Tetteh , Treis Diana , Van den Eynden Jimmy , Chand Damini , Umapathy Ganesh , Ruuth Kristina , Svenberg Petter , Wessman Sandra , Shamikh Alia , Jacobsson Hans , Gordon Lena , Stenman Jakob , Svensson Pär-Johan , Hansson Magnus , Larsson Erik , Martinsson Tommy , Palmer Ruth H. , Kogner Per , Hallberg Bengt
Published: June 2018

Tumors with anaplastic lymphoma kinase (ALK) fusion rearrangements, including non-small-cell lung cancer and anaplastic large cell lymphoma, are highly sensitive to ALK tyrosine kinase inhibitors (TKIs), underscoring the notion that such cancers are addicted to ALK activity. Although mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been disappointing. Embryonal tumors in patients with DNA repair defects such as Fanconi anemia (FA) often have a poor prognosis, because of lack of therapeutic options. Here we report a child with underlying FA and ALK mutant high-risk neuroblastoma responding strongly to precision therapy with the ALK TKI ceritinib. Conventional chemotherapy treatment caused severe, life-threatening toxicity. Genomic analysis of the initial biopsy identified germline FANCA mutations as well as a novel ALK-I1171T variant. ALK-I1171T generates a potent gain-of-function mutant, as measured in PC12 cell neurite outgrowth and NIH3T3 transformation. Pharmacological inhibition profiling of ALK-I1171T in response to various ALK TKIs identified an 11-fold improved inhibition of ALK-I1171T with ceritinib when compared with crizotinib. Immunoaffinity-coupled LC-MS/MS phosphoproteomics analysis indicated a decrease in ALK signaling in response to ceritinib. Ceritinib was therefore selected for treatment in this child. Monotherapy with ceritinib was well tolerated and resulted in normalized catecholamine markers and tumor shrinkage. After 7.5 mo treatment, the residual primary tumor shrunk, was surgically removed, and exhibited hallmarks of differentiation together with reduced Ki67 levels. Clinical follow-up after 21 mo treatment revealed complete clinical remission including all metastatic sites. Therefore, ceritinib presents a viable therapeutic option for ALK-positive neuroblastoma.
Rutile- and anatase-type temperature-dependent pre-edge peak intensities inK-edge XANES spectra forAO (A = Mn),A2O3(A = Sc, Cr and Mn) andAO2(A = Ti and V)
Authors: Tobase Tsubasa , Yoshiasa Akira , Hiratoko Tatsuya , Nakatsuka Akihiko
Published: June 2018

Pre-edge peaks in 3dtransition-metal element (Sc, Ti, V, Cr and Mn)K-edge XANES (X-ray absorption near-edge structure) spectra inAO2(A = Ti and V),A2O3(A = Sc, Cr and Mn) andAO (A = Mn) are measured at various temperatures. Quantitative comparisons for the XANES spectra were investigated by using absorption intensity invariant point normalization. The energy position of the difference peak (D peak) is obtained from the difference between the low- and high-temperature XANES spectra. There are two kinds of temperature dependence for pre-edge peak intensity: rutile- and anatase-type. The true temperature dependence of a transition to each orbital is obtained from the difference spectrum. In both anatase and rutile, the pre-edge peak positions of A2 and A3 are clearly different from the D1- and D2-peak positions. The A1 peak-top energies in both phases of VO2differ from the D1 peak-top energies. The D-peak energy position determined by the difference spectrum should represent one of the true energies for the transition to an independent orbital. The peak-top positions for pre-edge peaks in XANES do not always represent the true energy for independent transitions to orbitals because several orbital transitions overlap with similar energies. This work suggests that deformation vibration (bending mode) is effective in determining the temperature dependence for the D-peak intensity.
Betaine (trimethylammonioacetate) binary compound with sodium iodide
Authors: Nazarenko Alexander Y.
Published: June 2018

In the title compound,catena-poly[[[bis[2-(trimethylazaniumyl)acetato-κO]sodium]-di-μ-aqua-[diaquasodium]-di-μ-aqua] diiodide], {[Na2(C5H11NO2)2(H2O)6]I2}n, both Na+ions have distorted octahedral environments (coordination number 6). The coordination polyhedra of the sodium ions are connected by common edges forming an infinite chain of ions along [100]. The chains and betaine zwitterions are assembled into infinitive layersviahydrogen bonds. These layers are connectedviaelectrostatic attraction between iodide ions and positive trimethylazanium groups in the crystal.
Effects of MHD mixed convection with non-uniform heat source/sink and cross-diffusion over exponentially stretching sheet
Authors: Patil Prabhugouda Mallanagouda , Kumbarwadi Nafisabanu , A. Shashikant
Published: June 2018

Purpose

The purpose of this paper is to investigate the magnetohydrodynamics mixed convection flow over an exponentially stretching surface in the presence of non-uniform heat source/sink and cross-diffusion. Adequate non-similar transformations are used to transform governing mixed convection boundary layer equations to dimensionless form.

Design/methodology/approach

These dimensionless partial differential equations are solved by using implicit finite difference scheme in conjunction with Quasi-linearization technique.

Findings

The effects of admissible parameters such as Eckert number (Ec), the ratio of buoyancy forces parameter (N), non-uniform heat source/sink, Soret and Dufour numbers on flow, temperature and concentration distributions are discussed and analysed through graphs. In addition, the results for skin friction coefficient, Sherwood number and Nusselt number are presented and discussed graphically.

Originality/value

In literature, no research work has been found in similar to this research paper.
Social capital, knowledge sharing and innovation of small- and medium-sized enterprises in a tourism cluster
Authors: Kim Namhyun , Shim Changsup
Published: June 2018

Purpose

This study aims to identify the structural relationship among social capital, knowledge sharing, innovation and performance of small- and medium-sized enterprises (SMEs) in a tourism cluster.

Design/methodology/approach

A total of 199 valid questionnaires are collected from SMEs in the Bomun tourism cluster in South Korea. A structural equation modeling approach is used to test the research hypotheses.

Findings

The findings suggest that social capital constructs, including network density of structural capital, relational capital and cognitive capital, all positively influence knowledge sharing among SMEs in the cluster. This implies that creating social capital is critical to enhancing the competitiveness of SMEs. This study confirms that knowledge sharing positively affects SME performance through innovation.

Research limitations/implications

This study suggests that social capital, consisting of structural, cognitive and relational capital, facilitates increased knowledge sharing and innovation in a tourism cluster, which in turn enhances SME business performance.

Practical/implications

This study suggests that tourism cluster policies should focus on how to create a friendly operational climate to build social capital and support SME innovation.

Originality/value

This study contributes to the literature on social capital and innovation as well as the discourse on tourism clusters by addressing knowledge sharing among SMEs in a tourism cluster. It also expands the knowledge sharing and innovation literature by focusing on inter-organizational social networking among SMEs.
Size of training firms – the role of firms, luck, and ability in young workers’ careers
Authors: Müller Steffen , Neubaeumer Renate
Published: June 2018

Purpose

The purpose of this paper is to analyze how long-run unemployment of former apprentices depends on the size of their training firm and their ability.

Design/methodology/approach

The authors use a large administrative data set that follows graduated apprentices during their working life. They show that training in large and medium-sized firms is associated with considerably less unemployment. This, however, may simply be the result of sorting processes, i.e. larger training firms with higher wage levels attract and choose the most able young workers. Therefore, the authors use a proxy for ability to estimate and control for the impact of ability on long-run unemployment. They assume that rank-order tournaments for the most attractive training positions take place and take into account an institutional peculiarity of the German training system, the empirically observable regional immobility of apprentices. Accordingly, they use a region-specific ranking based on training plants’ size or median wages, respectively, to proxy for apprentices’ ability.

Findings

The negative association between training plant size and long-run unemployment is muted but still statistically well determined even after controlling for the rank of an individual’s training firm in the local plant size distribution or the local wage distribution, respectively. Thus, the rank itself is a predictor for long-run unemployment of apprentices. The fact that the position in the local size distribution matters conditional on plant size shows that there is a local competition for training places.

Practical implications

Lacking mobility may increases aggregate unemployment, as mobility reduces the risk of unemployment.

Social implications

The results imply that supporting regional mobility of young workers, e.g., by informing them better about existing mobility subsidies and dormitories for apprentices and by creating additional mobility incentives is warranted.

Originality/value

This is the first study to investigate long-run unemployment of former apprentices. Furthermore, the authors develop new variables to proxy for ability.
Parental leave length, social norms, and female labor market re-entry frictions
Authors: Bartoš Vojtech , Pertold-Gebicka Barbara
Published: June 2018

Purpose

The purpose of this paper is to identify the role of employers in creating employment gaps among women returning to the labor market after parental leaves of different durations.

Design/methodology/approach

The authors use a controlled correspondence field experiment that orthogonally manipulates parental leave length and the quality of fictitious female job candidates. The experiment is complemented with a survey among human resource managers.

Findings

High-quality candidates receive more interview invitations when applying after a short parental leave, while low-quality (LQ) candidates receive more interview invitations when applying after a typical three years long parental leave. Survey results suggest that the difference in invitations between short and typical leave treatments is driven by a social norm that mothers should stay home with children younger than three. Productivity gains from employing a LQ job applicant with a shorter career break might not be high enough to outweigh the adverse social norm effect.

Social implications

The presented results point toward the strong effect of prevailing social norms on job search prospects of women returning to the labor market after parental leave.

Originality/value

A correspondence experiment has not been used before to study the relationship between time spent on leave and the labor market prospects of mothers. It also extends research on social norms to the domain of hiring decisions.
Reconstructing my identity
Authors: Campbell Elaine
Published: June 2018

Purpose

The purpose of this paper is to offer an insight into mental health illness in academia, and its impact on academic identity.

Design/methodology/approach

The study adopts an evocative autoethnographic approach, utilising diary entries collected during the author’s three-month absence from her university due to depression and anxiety. A contemporary methodology, autoethnography seeks to use personal experience to provide a deeper understanding of culture. In this personal story, the author explores her decline in mental health and subsequent re-construction of her academic identity in order to enhance understanding of the organisational culture of higher education.

Findings

This paper illustrates how, rather than being an achievement, academic identity is an ongoing process of construction. Although mental health illness can contribute to a sense of loss of self, identity can be re-constructed during and after recovery. Autoethnographic explorations of depression and anxiety in higher education provide a deeper understanding of an often stigmatized issue, but researchers should be alive to the political and ethical pitfalls associated with deeply reflexive research.

Originality/value

There is little autoethnographic research on mental health illness in a university setting. This paper offers unique insights into the lived experience of depression and anxiety in the context of academic life, through the lens of academic identity.
The effect of treatments on the allergenicity of ß-lactoglobulin in Moroccan population
Authors: Azdad Ouarda , Mejrhit Najlae , Aarab Lotfi
Published: June 2018

Purpose

This study aims to evaluate the effect of heating and pepsin hydrolysis on the allergenicity of purified cow’s milk ß-lactoglobulin using individual sera from Moroccan population.

Design/methodology/approach

A cross-sectional study was carried out in Hospitals of Fez-Meknes region, to evaluate specific IgE to raw cow milk, as well as to heated and pepsin-hydrolyzed β-lactoglobulin.

Findings

Results showed that 6.6 per cent of studied patients presented high values of serial IgE. The effect of treatments on the allergenicity of ß-lactoglobulin showed that heating at 90°C and pepsin hydrolysis, for 1 h each, showed an important decrease in the recognition of human IgE with a maximum of reduction of 81 and 91 per cent, respectively.

Originality/value

This reduction of immunoreactivity of human IgE to treated ß-lactoglobulin suggested that this Moroccan population recognized mostly conformational epitopes.
Lactobacillus plantarum AR501 Alleviates the Oxidative Stress of D‐Galactose‐Induced Aging Mice Liver by Upregulation of Nrf2‐Mediated Antioxidant Enzyme Expression
Authors: Lin Xiangna , Xia Yongjun , Wang Guangqiang , Xiong Zhiqiang , Zhang Hui , Lai Fengxi , Ai Lianzhong
Published: June 2018

Lactic acid bacteria (LAB) have been used as ingredients of functional foods to promote health and prevent diseases because of their beneficial effects. This study aimed to investigate the antioxidative effects of LAB on the hepatotoxicity in D‐galactose‐induced aging mice. LAB were isolated from the traditional Chinese fermented foods and screened by the tolerance of hydrogen peroxide (H2O2). Male ICR (Institute of Cancer Research) mice were subcutaneously injected with D‐galactose for 5 weeks and then gastric gavage with LAB for 6 weeks. The results showed that Lactobacillus plantarum AR113 and AR501, and Pediococcu pentosaceus AR243 could tolerate up to 1.5 mM H2O2 in vitro, and they could live through simulated gastrointestinal tract (GIT) to colonizing the GIT of host. In vivo, oral administration of L. plantarum AR113 and AR501 improved the antioxidant status of D‐galactose‐induced oxidative stress mice such as alleviated liver damages and reduced abnormal activities of superoxide dismutase, glutathione peroxidase, and catalase to normal levels. In addition, L. plantarum AR501 markedly elevated the gene expression of nuclear factor erythroid‐2‐related factor 2 and upregulated the expressions of several antioxidant genes such as glutathione reductase, glutathione S‐transferase, glutamate‐cysteine ligase catalytic subunit, glutamate‐cysteine ligase modifier subunit, and NAD(P)H quinone oxidoreductase 1 in the liver of an aging mice. Therefore, L. plantarum AR501 could be a good candidate for producing antiaging functional foods.
Interferon epsilon in the reproductive tract of healthy and genital herpes simplex virus‐infected pregnant women: Results of a pilot study
Authors: Nickodem Colette , Criscitiello Michael F. , Bazer Fuller , Abiodun‐Ojo Olayinka , Taylor Brandie D.
Published: June 2018

Problem

Recently characterized interferon epsilon (IFNe) protects against sexually transmitted infections, including genital herpes simplex virus (HSV), in animal models. There are no reports of IFNe in genital tract secretions of pregnant women, and data on IFNe in non‐pregnant women are limited. This pilot study is the first to measure concentrations of IFNe in vaginal and cervical secretions during pregnancy and compare values between healthy and genital HSV‐infected women.

Method of Study

Vaginal or cervical specimens from 30 pregnant women were obtained from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) repository. Cervical samples were collected during the first trimester and vaginal samples across pregnancy. Enzyme‐linked immunosorbent assay determined concentrations of IFNe (pg/mL). Data for IFNe were log‐transformed and compared by maternal demographics, clinical variables, and HSV status using t tests and linear regression. Repeated measures analysis explored trends across pregnancy.

Results

Among the entire cohort, first trimester concentrations of IFNe in vaginal or cervical secretions decreased as body mass index increased (β = −0.14, P = .0466). Concentrations of vaginal IFNe increased across pregnancy in HSV‐infected and healthy women (P = .009). Average vaginal IFNe across pregnancy was lower in women with HSV compared to healthy women (P = .0009).

Conclusion

Interferon epsilon increased across pregnancy, but was less abundant in women with HSV. This pilot investigation cannot make any definitive conclusions. However, animal models suggest that IFNe may protect against STIs. Thus, larger studies are required to validate expression of IFNe in the reproductive tract of pregnant women with and without genital infections.
Platinum sensitivity of ovarian cancer cells does not influence their ability to induce M2‐type macrophage polarization
Authors: Mlynska Agata , Povilaityte Egle , Zemleckaite Inga , Zilionyte Karolina , Strioga Marius , Krasko Jan , Dobrovolskiene Neringa , Peng Mei‐Wen , Intaite Birute , Pasukoniene Vita
Published: June 2018

Problem

Development of platinum resistance in ovarian cancer is mediated by both cancer cells and tumor microenvironment. Activation of epithelial‐mesenchymal transition program in cancer cells may lead to enrichment for resistant clones. These processes can be affected by tumor‐associated macrophages, a highly plastic population of cells that participate in tumor progression and response to treatment by shaping the microenvironment. We aimed to study how platinum resistance influences the crosstalk between macrophages and ovarian cancer cells.

Method of study

Using cisplatin‐sensitive ovarian cancer cell line A2780, we developed and characterized cisplatin‐resistant A2780Cis and cisplatin and doxorubicin co‐resistant A2780Dox cell lines. Next, we set up an indirect coculture system with THP‐1 cell line‐derived M0‐type‐, M1‐type‐ and M2‐type‐like polarized macrophages. We monitored the expression of genes associated with cellular stemness, multidrug resistance, and epithelial‐mesenchymal transition in cancer cells, and expression profile of M1/M2 markers in macrophages.

Results

Development of drug resistance in ovarian cancer cell lines was accompanied by increased migration, clonogenicity, and upregulated expression of transcription factors, associated with cellular stemness and epithelial‐mesenchymal transition. Upon coculture, we noted that the most relevant changes in gene expression profile occurred in A2780 cells. Moreover, M0‐ and M1‐type macrophages, but not M2‐type macrophages, showed significant transcriptional alterations.

Conclusion

Our results provide the evidence for bidirectional interplay between cancer cells and macrophages. Independent of platinum resistance status, ovarian cancer cells polarize macrophages toward M2‐like type, whereas macrophages induce epithelial‐mesenchymal transition and stemness‐related gene expression profile in cisplatin‐sensitive, but not cisplatin‐resistant cancer cells.
Nasal cytology: Methodology with application to clinical practice and research
Authors: Heffler E. , Landi M. , Caruso C. , Fichera S. , Gani F. , Guida G. , Liuzzo M. T. , Pistorio M. P. , Pizzimenti S. , Riccio A. M. , Seccia V. , Ferrando M. , Malvezzi L. , Passalacqua G. , Gelardi M.
Published: June 2018

Nasal cytology is an easy, cheap, non‐invasive and point‐of‐care method to assess nasal inflammation and disease‐specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non‐allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time‐course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non‐allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic‐mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non‐invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.
Cultural Antecedents to Community: An Evaluation of Community Experience in the United States, Thailand, and Vietnam
Authors: Muir Jonathan A. , Braudt David B. , Swindle Jeffrey , Flaherty Jeremy , Brown Ralph B.
Published: June 2018

To what extent does community experience differ between low–context and high–context societies? Prior literature theorizes that community experience consists of two separate, yet highly related concepts: community attachment, an individual's general rootedness to a place, and community satisfaction, how well an individual's community meets their societal needs. We test this conceptualization of community experience across communities in the United States and two Southeast Asian nations: Thailand and Vietnam. We argue that Southeast Asian nations constitute “high–context” societies with relatively high social integration and solidarity while the United States is more individualized and less socially integrated and thus constitutes a “low–context” society. Our results provide empirical evidence that individuals’ experience of community varies between low– and high–context societies. These results demonstrate that cultural context continues to matter in regards to the lived experience of community and researchers need to remain vigilant in accounting for such differences as they seek to examine the concept of community more broadly.
Alterations in desmosomal adhesion at protein and ultrastructure levels during the sequential progressive grades of human oral tumorigenesis
Authors: Sawant Sharada , Dongre Harsh , Ahire Chetan , Sharma Shilpi , Jamghare Sayli , Kansara Yashvi , Rane Pallavi , Kanojia Deepak , Patil Asawari , Chaukar Devendra , Gupta Sudeep , D'Cruz Anil , Vaidya Milind , Dongre Prabhakar
Published: June 2018

With the aim of developing early diagnostic/prognostic markers for oral cancer, desmosomal adhesion in sequentially progressive grades of tissues from oral normal/disorders (normal, hyperplastic, dysplastic, non‐metastatic/metastatic tumours, and metastatic nodes) was investigated at protein and ultrastructural levels using immunohistochemistry and transmission electron microscopy, respectively. The expression of desmosomal proteins was higher in hyperplastic tissues than in normal tissues but was significantly decreased in subsequent progressive stages of the disease. Altered expression of desmosomal proteins was significantly correlated with local recurrence and disease‐free survival. Ultrastructural analysis in the corresponding tissues revealed cytoplasmic clustering of desmosomes in hyperplasia; in more advanced disease stages, a significantly lower number of desmosomes and widened intercellular spaces were observed. Altered protein expression resulting in structural changes was confirmed by knocking down desmoplakin expression in non‐transformed cells, which failed to form normal desmosome structures and induced a cell‐transformation phenotype. Our data suggest that alterations in desmosomal assembly initiate at an early hyperplastic grade and, with more advanced disease stages, the severity of the alterations gradually becomes higher. Alterations in desmosomal adhesion can be useful for early detection of high‐risk premalignant lesions, as well as for identification of invasive characteristics of primary non‐metastatic tumours. Early detection will help to control further progression of disease by timely intervention.
A crystal structure of coil 1B of vimentin in the filamentous form provides a model of a high‐order assembly of a vimentin filament
Authors: Pang Allan H. , Obiero Josiah M. , Kulczyk Arkadiusz W. , Sviripa Vitaliy M. , Tsodikov Oleg V.
Published: June 2018

Vimentin is an intermediate filament (IF) protein that is expressed in leukocytes, fibroblasts and endothelial cells of blood vessels. Vimentin filaments contribute to structural stability of the cell membrane, organelle positioning and protein transport. Vimentin self‐assembles into a dimer that subsequently forms high‐order structures, including tetramers and octamers. The details of IF assembly at crystallographic resolutions are limited to the tetrameric form. We describe a crystal structure of a fragment of a vimentin rod domain (coil 1B) with a dimer of tetramers in the asymmetric unit. Coil 1B in the crystal is in an infinitely high‐order filamentous assembly state, in which the tetramers are packed against each other laterally in an antiparallel fashion across the crystal lattice. In one of the directions of lateral packing, the tetramers pack against each other strictly head‐to‐tail, and in the orthogonal direction the tetramers pack in a staggered manner. This organization of the tetramers of coil 1B in the crystal lattice, together with previously reported biochemical and structural data, yield a model of high‐order vimentin filament assembly.

Database

Structural data are available in the PDB under the accession number 5WHF.
Cancer: the dark side of wound healing
Authors: Sundaram Gopinath M. , Quah Shan , Sampath Prabha
Published: June 2018

Complex multicellular organisms have evolved sophisticated mechanisms to rapidly resolve epithelial injuries. Epithelial integrity is critical to maintaining internal homeostasis. An epithelial breach represents the potential for pathogen ingress and fluid loss, both of which may have severe consequences if not limited. The mammalian wound healing response involves a finely tuned, self‐limiting series of cellular and molecular events orchestrated by the transient activation of specific signalling pathways. Accurate regulation of these events is essential; failure to initiate key steps at the right time delays healing and leads to chronic wounds, while aberrant initiation of wound healing processes may produce cell behaviours that promote cancer progression. In this review, we discuss how wound healing pathways co‐opted in cancer lose their stringent regulation and become compromised in their reversibility. We hypothesize on how the commandeering of wound healing ‘master regulators’ is involved in this process, and also highlight the implications of these findings in the treatment of both chronic wounds and cancer.
High cycle fatigue analysis in the presence of autofrettage compressive residual stress
Authors: Okorokov V. , MacKenzie D. , Gorash Y. , Morgantini M. , van Rijswick R. , Comlekci T.
Published: June 2018

An experimental and numerical investigation of the effect of residual compressive stress on the high cycle fatigue life of notched low carbon steel test specimens is presented. Experimentally determined cyclic stress strain curves for S355 low carbon steel are utilized in a finite element analysis plasticity modelling framework incorporating a new cyclic plasticity material model representative of cyclic hardening and softening, cyclic mean stress relaxation, and ratcheting behaviors. Fatigue test results are presented for standard tensile fatigue test specimens and novel double notch specimens. Double notch specimens are tested with and without compressive residual stress prior‐induced through tensile overload. It is shown that cyclic plasticity phenomena have a significant influence on the induced residual stress distribution and also on material behavior when fatigue tested in the high cycle regime. It is observed that higher initial compressive residual stresses magnitude does not necessarily lead to a longer fatigue life. Finite element analysis using the new cyclic plasticity material model shows this behavior is due to combined residual stress redistribution under fatigue test cyclic loading and cyclic hardening effects. A fatigue life methodology based on the stress‐life approach augmented by a critical distance method is proposed and shown to give good agreement with experimental results for test specimens with no induced residual stress. The results obtained for specimens with induced residual stress are more conservative, but the degree of conservatism is significantly lower than that in the conventional stress life approach. The proposed methodology is therefore suitable for analysis and design assessment of components with pre‐service induced compressive residual stress, such as autofrettaged pressure components.
Corporate Governance and Financial Peer Effects
Authors: Fairhurst Douglas (DJ) , Nam Yoonsoo
Published: June 2018

Growing evidence suggests that managers select financial policies partially by mimicking policies of peer firms. We find that these peer effects in capital structure choice are unique to firms operating under weak external corporate governance. Cross‐sectional tests suggest that this finding is best explained by a quiet life hypothesis in which managers may be able to avoid the effort required to optimize financial policies and the scrutiny of market participants. Leverage ratios of mimicking firms display less sensitivity to a profitability shock. Finally, mimicking correlates to higher financing costs and lower future profitability, especially if it results in high leverage.
The effect of cheats on siderophore diversity in Pseudomonas aeruginosa
Authors: Stilwell Peter , Lowe Chris , Buckling Angus
Published: June 2018

Cooperation can be maintained if cooperative behaviours are preferentially directed towards other cooperative individuals. Tag‐based cooperation (greenbeards) – where cooperation benefits individuals with the same tag as the actor – is one way to achieve this. Tag‐based cooperation can be exploited by individuals who maintain the specific tag but do not cooperate, and selection to escape this exploitation can result in the evolution of tag diversity. We tested key predictions crucial for the evolution of cheat‐mediated tag diversity using the production of iron‐scavenging pyoverdine by the opportunistic pathogen, Pseduomonas aeruginosa as a model system. Using two strains that produce different pyoverdine types and their respective cheats, we show that cheats outcompete their homologous pyoverdine producer, but are outcompeted by the heterologous producer in well‐mixed environments. As a consequence, co‐inoculating two types of pyoverdine producer and one type of pyoverdine cheat resulted in the pyoverdine type whose cheat was not present having a large fitness advantage. Theory suggests that in such interactions, cheats can maintain tag diversity in spatially structured environments, but that tag‐based cooperation will be lost in well‐mixed populations, regardless of tag diversity. We saw that when all pyoverdine producers and cheats were co‐inoculated in well‐mixed environments, both types of pyoverdine producers were outcompeted, whereas spatial structure (agar plates and compost microcosms), rather than maintaining diversity, resulted in the domination of one pyoverdine producer. These results suggest cheats may play a more limited role in the evolution of pyoverdine diversity than predicted.
PARATETHYAN PETROLEUM SOURCE ROCKS: AN OVERVIEW
Authors: Sachsenhofer R. F. , Popov S.V. , Coric S. , Mayer J. , Misch D. , Morton M.T. , Pupp M. , Rauball J. , Tari G.
Published: June 2018

The Paratethys area extends from Central Europe to the borders of the Caspian Sea in Central Asia and hosts a significant number of petroleum provinces, many of which have been charged by Eocene to Miocene source rocks of supra‐regional significance. These include highly oil‐prone Middle Eocene marls and limestones in the Eastern Paratethys (Kuma Formation and equivalents) which are several tens of metres thick. Estimates of the source potential index (SPI) indicate that the Kuma Formation in the northern Caucasus and the Rioni Basin (Georgia) may generate 1 to 2 tons of hydrocarbons per square metre (tHC/m2). This implies that the Kuma Formation may also be an important and additional source rock in the eastern Black Sea.

Oligocene and Lower Miocene pelitic rocks (Maikop Group and equivalents) are considered to be the most important source rocks in the Paratethys. Vertical variations in source potential record different stages of basin isolation that reached a maximum during the Early Oligocene (NP23) Solenovian Event. However major variations exist between different sub‐basins in the Central and the Eastern Paratethys. In the Central Paratethys, the highest quality source rocks occur in the Carpathian Basin where the Menilite Formation, several hundreds of metres thick, can generate up to 10 tHC/m2. Locally the Menilite Formation is about 1500 m thick and continues into the Lower Miocene. In these settings, the Menilite Formation can generate approximately 70 tHC/m2. In the Alpine Foreland Basin (Schöneck and Eggerding Formations) and the Pannonian Basin (Tard Clay Formation), oil‐prone source rocks are restricted to the Lower Oligocene. In the Eastern Paratethys, the best source rock intervals of the Maikop Group are typically associated with the Early Oligocene Solenovian Event. By contrast, with the exception of the Kura Basin in Azerbaijan, the potential of Upper Oligocene and Lower Miocene rocks is often limited. In total, the Maikop Group may generate up to 2 tHC/m2 in the North Caucasus area and 4 tHC/m2 in the Rioni Basin.

A particular source rock facies is found in the Western Black Sea where diatomaceous rocks with good oil potential accumulated in the Kaliakra Canyon during Early Miocene time. This facies may generate up to 8 tHC/m2, but is probably limited to shelf‐break canyons.

Middle and Upper Miocene rocks are the main source for oil and thermogenic gas in the Pannonian Basin System, and also contributed to thermogenic hydrocarbons in the Moesian Platform and the South Caspian Basin. In addition, Upper Oligocene and Miocene rocks are the source for microbial gas in several basins including the Alpine and Carpathian foredeeps.
Sputtering of Si by Ar: A binary collision approach based on quantum-mechanical cross sections
Authors: Palov Alexander P. , Balint-Kurti Gabriel G. , Voronina Ekaterina N. , Rakhimova Tatyana V.
Published: June 2018

A new binary collision approach for the calculation of the sputtering yield of Si under nonreactive ionic bombardment by Ar+ is presented for the energy range from threshold to 200 eV. Unlike conventional Monte Carlo approaches that use a classical calculation of the scattering angle from a known potential, their approach employs quantum-mechanical methods to compute the scattering angle. Comparison of the energy and angular dependence of sputtering yields computed using their new quantum-based method with experimental data and with transport of ions in matter (TRIM) and molecular dynamics (MD) calculations supports the accuracy and usefulness of their approach. It is shown that their new approach leads to results of an accuracy intermediate between that of the TRIM and MD methods. The authors expect the new approach to be useful in plasma processing applications.
Multifunctional structural design of graphene thermoelectrics by Bayesian optimization
Authors: Yamawaki Masaki , Ohnishi Masato , Ju Shenghong , Shiomi Junichiro
Published: June 2018

Efficient multifunctional materials informatics enables the design of optimal graphene thermoelectrics.
Anthropogenic changes to the Holocene nitrogen cycle in Ireland
Authors: Guiry Eric , Beglane Fiona , Szpak Paul , Schulting Rick , McCormick Finbar , Richards Michael P.
Published: June 2018

Chemical signatures from Bronze Age animal bones show that prehistoric humans had a major impact on the nitrogen cycle in Ireland.
Stacking symmetry governed second harmonic generation in graphene trilayers
Authors: Shan Yuwei , Li Yingguo , Huang Di , Tong Qingjun , Yao Wang , Liu Wei-Tao , Wu Shiwei
Published: June 2018

A novel optical second harmonic generation arises from the stacking order of three centrosymmetric graphene monolayer sheets.
ZNF341 controls STAT3 expression and thereby immunocompetence
Authors: Frey-Jakobs Stefanie , Hartberger Julia M. , Fliegauf Manfred , Bossen Claudia , Wehmeyer Magdalena L. , Neubauer Johanna C. , Bulashevska Alla , Proietti Michele , Fröbel Philipp , Nöltner Christina , Yang Linlin , Rojas-Restrepo Jessica , Langer Niko , Winzer Sandra , Engelhardt Karin R. , Glocker Cristina , Pfeifer Dietmar , Klein Adi , Schäffer Alejandro A. , Lagovsky Irina , Lachover-Roth Idit , Béziat Vivien , Puel Anne , Casanova Jean-Laurent , Fleckenstein Bernhard , Weidinger Stephan , Kilic Sara S. , Garty Ben-Zion , Etzioni Amos , Grimbacher Bodo
Published: June 2018

Homozygous nonsense mutations in
ZNF341
impair its ability to activate
STAT3
transcription and thereby cause immunodeficiency.
A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity
Authors: Béziat Vivien , Li Juan , Lin Jian-Xin , Ma Cindy S. , Li Peng , Bousfiha Aziz , Pellier Isabelle , Zoghi Samaneh , Baris Safa , Keles Sevgi , Gray Paul , Du Ning , Wang Yi , Zerbib Yoann , Lévy Romain , Leclercq Thibaut , About Frédégonde , Lim Ai Ing , Rao Geetha , Payne Kathryn , Pelham Simon J. , Avery Danielle T. , Deenick Elissa K. , Pillay Bethany , Chou Janet , Guery Romain , Belkadi Aziz , Guérin Antoine , Migaud Mélanie , Rattina Vimel , Ailal Fatima , Benhsaien Ibtihal , Bouaziz Matthieu , Habib Tanwir , Chaussabel Damien , Marr Nico , El-Benna Jamel , Grimbacher Bodo , Wargon Orli , Bustamante Jacinta , Boisson Bertrand , Müller-Fleckenstein Ingrid , Fleckenstein Bernhard , Chandesris Marie-Olivia , Titeux Matthias , Fraitag Sylvie , Alyanakian Marie-Alexandra , Leruez-Ville Marianne , Picard Capucine , Meyts Isabelle , Di Santo James P. , Hovnanian Alain , Somer Ayper , Ozen Ahmet , Rezaei Nima , Chatila Talal A. , Abel Laurent , Leonard Warren J. , Tangye Stuart G. , Puel Anne , Casanova Jean-Laurent
Published: June 2018

ZNF341 is a newly characterized transcription factor controlling baseline and inducible transcription of the human
STAT3
gene.
Probiotic strains detect and suppress cholera in mice
Authors: Mao Ning , Cubillos-Ruiz Andres , Cameron D. Ewen , Collins James J.
Published: June 2018

A probiotic intervention with
Lactococcus lactis
strains provides colonization resistance and in vivo detection of cholera in mice.
Statins enhance efficacy of venetoclax in blood cancers
Authors: Lee J. Scott , Roberts Andrew , Juarez Dennis , Vo Thanh-Trang T. , Bhatt Shruti , Herzog Lee-or , Mallya Sharmila , Bellin Richard J. , Agarwal Suresh K. , Salem Ahmed Hamed , Xu Tu , Jia Jia , Li Lingxiao , Hanna John R. , Davids Matthew S. , Fleischman Angela G. , O’Brien Susan , Lam Lloyd T. , Leverson Joel D. , Letai Anthony , Schatz Jonathan H. , Fruman David A.
Published: June 2018

Statins cooperate with proapoptotic drugs to enhance tumor killing in blood cancers.
CapC, a Novel Autotransporter and Virulence Factor of Campylobacter jejuni
Authors: Mehat Jai W. , Park Simon F. , van Vliet Arnoud H. M. , La Ragione Roberto M.
Published: June 2018

Campylobacter jejuni
is a major causative agent of human gastroenteritis, making this zoonotic pathogen of significant importance to human and veterinary public health worldwide. The mechanisms by which
C. jejuni
interacts with intestinal epithelial cells and causes disease are still poorly understood due, in part, to the heterogeneity of
C. jejuni
infection biology. Given the importance of
C. jejuni
to public health, the need to characterize novel and existing virulence mechanisms is apparent. The significance of our research is in demonstrating the role of CapC, a novel virulence factor in
C. jejuni
that contributes to adhesion and invasion of the intestinal epithelium, thereby in part, addressing the dearth of knowledge concerning the factors involved in
Campylobacter
pathogenesis and the variation observed in the severity of human infection.
Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43
Authors: Dubé Mathieu , Le Coupanec Alain , Wong Alan H. M. , Rini James M. , Desforges Marc , Talbot Pierre J.
Published: June 2018

Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.
Cataract surgery refractive outcomes: representative standards in a National Health Service setting
Authors: Brogan Kerr , Diaper Charles J M , Rotchford Alan P
Published: June 2018

Background/aims

To report refractive outcomes from an National Health Service (NHS) cataract surgery service and assess if results meet suggested benchmark standard.

Methods

Details of all patients undergoing cataract surgery in the Southern General and New Victoria hospitals in Glasgow, UK, between November 2006 and December 2016 were prospectively entered into an electronic database. Patients were reviewed 4 weeks postoperatively in the eye clinic and underwent refraction at their local optometrist prior to this appointment. Surgically uncomplicated cases with in the bag’ non-toric intraocular lens implantation were included. Patients with previous laser refractive procedures or failing to achieve 6/12 acuity or better postoperatively were excluded. Proximity to targeted postoperative refraction was documented.

Results

Over this 10-year period, 11 083 eyes underwent cataract surgery. Of these, 8943 eyes of 6936 patients (80.69%) met the inclusion criteria and had both target and postoperative outcome refraction recorded. The mean difference between the targeted and outcome refraction was −0.07 D (SD 0.67). The mean absolute error was 0.50 D. Postoperative refraction was within 1 D of target refraction for 7938 eyes (88.76%) and within 0.50 D for 5577 eyes (62.36%).

Conclusion

Refractive outcomes following routine cataract surgery reported here are well within the targets recommended by the Royal College of Ophthalmologists and European guidelines, but suggest that higher cataract refractive outcome benchmark standards may not yet be a realistic expectation for all NHS units with current biometry practice.