bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular organization of soluble type III secretion system sorting platform complexes
Authors: Bernal Ivonne , Börnicke Jonathan , Heidemann Johannes , Svergun Dmitri , Tuukkanen Anne , Uetrecht Charlotte , Kolbe Michael
Published: May 2019

Many medically relevant Gram-negative bacteria use the type III secretion system (T3SS) to translocate effector proteins into the host for their invasion and intracellular survival. A multi-protein complex located at the cytosolic interface of the T3SS is proposed to act as a sorting platform by selecting and targeting substrates for secretion through the system. However, the precise stoichiometry and 3D organization of the sorting platform components is unknown. Here we reconstitute soluble complexes of theSalmonellaTyphimurium sorting platform proteins including the ATPase InvC, the regulator OrgB, the protein SpaO and a recently identified subunit SpaOC, which we show to be essential for the solubility of SpaO. We establish domain-domain interactions, determine for the first time the stoichiometry of each subunit within the complexes by native mass spectrometry and gain insight into their organization using small-angle X-ray scattering. Importantly, we find that in solution the assembly of SpaO/SpaOC/OrgB/InvC adopts an extended L-shaped conformation resembling the sorting platform pods seen inin situcryo-electron tomography, proposing that this complex is the core building block that can be conceivably assembled into higher oligomers to form the T3SS sorting platform. The determined molecular arrangements of the soluble complexes of the sorting platform provide important insights into its architecture and assembly.
Altered Nucleoprotein Binding to Influenza Virus RNA Impacts Packaging Efficiency and Replication
Authors: Le Sage Valerie , Kanarek Jack P. , Nturibi Eric , Nanni Adalena V. , Snyder Dan J. , Cooper Vaughn S. , Lakdawala Seema S. , Lee Nara
Published: May 2019

The genome of Influenza A viruses consists of eight negative-sense RNA segments that are bound by viral nucleoprotein (NP). We recently showed that NP binding is not uniform along the segments but exhibits regions of enrichment as well as depletion. Furthermore, genome-wide NP binding profiles are distinct even in strains with high sequence similarity, such as the two H1N1 strains A/WSN/1933 and A/California/07/2009. Here, we performed interstrain segment swapping experiments with segments of either high or low congruency in NP binding, which suggested that a segment with a similar overall NP binding profile preserved replication fitness of the resulting virus. Further sub-segmental swapping experiments demonstrated that NP binding is affected by changes to the underlying nucleotide sequence, as NP peaks can either become lost or appearde novoat mutated regions. Unexpectedly, these local nucleotide changes in one segment not only affect NP bindingin cis, but also impact the genome-wide NP binding profile on other segments in a vRNA sequence-independent manner, suggesting that primary sequence alone is not the sole determinant for NP association to vRNA. Moreover, we observed that sub-segmental mutations that affect NP binding profiles can result in reduced replication fitness, which is caused by defects in vRNA packaging efficiency and an increase in semi-infectious particle production. Taken together, our results indicate that the pattern of NP binding to vRNA is important for efficient virus replication.

Author Summary

Each viral RNA (vRNA) segment is bound by the polymerase complex at the 5′ and 3′ ends, while the remainder of the vRNA is coated non-uniformly and non-randomly by nucleoprotein (NP). To explore the constraints of NP binding to vRNA, we used high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) of mutant H1N1 strains with exchanged vRNA sequences and observed that NP binding can be changed based on vRNA sequence. The most striking observation of our study is that nucleotide changes in one segment can have genome-wide effects on the NP binding profile of other segments. We refer to this phenomenon as the ‘butterfly effect’ of influenza packaging. Our results provide an important context in which to consider future studies regarding influenza packaging and assembly.
Time-Resolved Integrative Optical Imaging of Diffusion during Spreading Depression
Authors: Hrabe J. , Hrabetova S.
Published: May 2019

An improved version of Integrative Optical Imaging method has been developed which substantially increases the time resolution of diffusion measurements. We present a theory for Time-Resolved Integrative Optical Imaging (TR-IOI) that incorporates time-dependent effective diffusion coefficient in homogeneous anisotropic media and time-dependent nonspecific linear clearance. The method was applied to measure the very fast changes in extracellular diffusion that occur during spreading depression in rat hippocampal slices. We were able to achieve time resolution of approximately one second, an improvement of at least ten times compared to the standard methods for extracellular diffusion measurement. We have found that diffusion of a small fluorescent extracellular marker (MW 3000) completely stopped during the maximum DC shift associated with the spreading depression wave, then gradually resumed over several minutes afterward. The effect of spreading depression on extracellular space is much larger than previously estimated by other methods with lower time resolution.
Mechanosensitive junction remodelling promotes robust epithelial morphogenesis
Authors: Staddon Michael F. , Cavanaugh Kate E. , Munro Edwin M. , Gardel Margaret L. , Banerjee Shiladitya
Published: May 2019

Morphogenesis of epithelial tissues requires tight spatiotemporal coordination of cell shape changes. In vivo, many tissue-scale shape changes are driven by pulsatile contractions of intercellular junctions, which are rectified to produce irreversible deformations. The functional role of this pulsatory ratchet and its mechanistic basis remain unknown. Here we combine theory and biophysical experiments to show that mechanosensitive tension remodelling of epithelial cell junctions promotes robust epithelial shape changes via ratcheting. Using optogenetic control of actomyosin contractility, we find that epithelial junctions show elastic behaviour under low contractile stress, returning to their original lengths after contraction, but undergo irreversible deformation under higher magnitudes of contractile stress. Existing vertex-based models for the epithelium are unable to capture these results, with cell junctions displaying purely elastic or fluid-like behaviours, depending on the choice of model parameters. To describe the experimental results, we propose a modified vertex model with two essential ingredients for junction mechanics: thresholded tension remodelling and continuous strain relaxation. First, a critical strain threshold for tension remodelling triggers irreversible junction length changes for sufficiently strong contractions, making the system robust to small fluctuations in contractile activity. Second, continuous strain relaxation allows for mechanical memory removal, enabling frequency-dependent modulation of cell shape changes via mechanical ratcheting. Taken together, the combination of mechanosensitive tension remodelling and junctional strain relaxation provides a robust mechanism for large-scale morphogenesis.
Comprehensive model for X-ray-induced damage in protein crystallography
Authors: Close David M. , Bernhard William A.
Published: May 2019

Acquisition of X-ray crystallographic data is always accompanied by structural degradation owing to the absorption of energy. The application of high-fluency X-ray sources to large biomolecules has increased the importance of finding ways to curtail the onset of X-ray-induced damage. A significant effort has been under way with the aim of identifying strategies for protecting protein structure. A comprehensive model is presented that has the potential to explain, both qualitatively and quantitatively, the structural changes induced in crystalline protein at ∼100 K. The first step is to consider the qualitative question: what are the radiation-induced intermediates and expected end products? The aim of this paper is to assist in optimizing these strategies through a fundamental understanding of radiation physics and chemistry, with additional insight provided by theoretical calculations performed on the many schemes presented.
Crystal structure of (N,N′-ethylenebis{3-[2-(3-nitrophenyl)hydrazin-1-ylidene]-4-oxopentan-2-iminato})copper(II)–3-[2-(3-nitrophenyl)hydrazin-1-ylidene]pentane-2,4-dione (1/1)
Authors: Marten Jan , Seichter Wilhelm , Weber Edwin
Published: May 2019

In the title 1:1 co-crystal, [Cu(C24H24N8O6)]·C11H11N3O4, each of the crystal components forms undulating layers which stack alternately along the b-axis direction. Molecules of the CuII complex are connected via C—H...O hydrogen bonds involving the nitro and keto oxygen atoms, thus forming supramolecular networks. Molecules of the arylhydrazone component are linked by C—H...O interactions into zigzag strands showing no interstrand association.
Determinants of hotel guests’ satisfaction from the perspective of online hotel reviewers
Authors: Alrawadieh Zaid , Law Rob
Published: May 2019

Purpose

With the proliferation of Web 2.0 and the travel-related user-generated content platforms, researchers can obtain abundant unsolicited data to examine guests’ perceptions, preferences and behaviors. Drawing on online reviews, this study aims to identify the key factors that determine guest satisfaction in lodging businesses.

Design/methodology/approach

A total of 400 English-language reviews posted about the best-rated hotels in Istanbul, Turkey, according to TripAdvisor’s ranking system, were selected and content-analyzed. A hybrid approach of inductive and deductive content analysis was adopted in this study.

Findings

The findings suggested that the quality and size of rooms, along with the service quality from staff, mainly determine guest satisfaction. The findings also reveal that relatively young European male travelers who stay in couple and with family are more likely to share their accommodation experiences in cyberspace.

Originality/value

The study adds to the literature on the determinants of guest satisfaction by examining online reviews. Unlike research using conventional research methods, the present study contributes to the existing literature of guest satisfaction in the hotel industry by harnessing the power of the word of mouse.
A multi-level analysis of mixed gender couple’s food decisions in a tourism context
Authors: Coskun Guliz , Jodice Laura W. , Moore DeWayne
Published: May 2019

Purpose

Through application of multi-level structural equation modeling as the data analysis technique, the purpose of this paper is to analyze the group-level impacts on a couple’s food choices during travel at a coastal destination.

Design/methodology/approach

Researchers obtained 380 individual questionnaires from 190 mixed gender couples (who eat oysters) in Charleston and Beaufort County, South Carolina, USA. Data were collected from both members of the couple during their vacation. Due to missing data and normality issues 5 couples and 30 individuals were eliminated. The remaining data were analyzed with SPSS 21 and EQS 6.2 with advanced confirmatory factor analysis and multi-level (ML) regression techniques.

Findings

The study results indicated that while women have a more negative attitude than men toward oysters, their intention to eat oysters during vacation is not different from their partner. By detecting the interdependency of responses of individuals within a couple, this study revealed that a ML approach is a more powerful way to understand the decision-making process of couples. Additionally the difference in the results of single- and ML models showed that the latter approach lowers the chance of Type 2 error and provides more accurate results.

Originality/value

In tourism decision-making literature, the focus has been mostly on the individual despite the collectivistic nature of tourism activity. The current study is the first to analyze a couple’s decision-making process at the group level. Furthermore by collecting data from both members of the group during their vacation, this study has distinguished itself from previous studies.
Foreign direct investments and round tripping between Cyprus and Russia
Authors: Repousis Spyridon , Lois Petros , Kougioumtsidis Pavlos
Published: May 2019

Purpose

This paper aims to look at the linkage of foreign direct investments (FDIs) and round-tripping in the Cyprus–Russia corridor.

Design/methodology/approach

The paper is divided into two chapters. The first chapter looks at the relationship between FDIs and round-tripping in Cyprus and Russia. The second chapter discusses and combines statistical data from different sources about illiciting financial flows from Russia and the linkage of FDIs and round-tripping with Cyprus.

Findings

Evidence suggests that, despite the obviously numerous and varied legislative provisions and initiatives, the movement of vast amounts of capital to or through the Cypriot financial system is a phenomenon, which has absolutely not been removed. The illegal outflow of money seems to grow rapidly over the years instead of decreasing. What actually happens is that after a dramatic decline in the years 2013-2015, the FDIs of the Russians to and from Cyprus in 2016 returned to pre-crisis levels of 2013, and so far, it seems the inflows–outflows system returned to “normal” levels. Cyprus ranks first in inward FDI and outward FDI with almost 35 per cent of total flows from Russia. An element that demonstrates the presence of round-tripping, is the sharp and rapid parallel increase of inward FDI and outward FDI, and that the category of total deposits in Cyprus by nonresidents, including special-purpose entity, recorded significant fluctuations caused by not only the large size of deposits but also the short time remaining in the banking sector. Russia ranked second among the countries with the largest average illegal capital outflows in the years 2004-2013. Movement of capital to exploit the particularly beneficial Cyprus tax system is still a tax backdoor for Europe and worldwide (hence the neologisms like Cyp-Rus), especially after the “de-offshorization” law in Russia in practice since January 1, 2015.

Originality/value

Evidence presented in this paper is important for national and supernational supervisory anti-money laundering bodies and compliance authorities to understand bad practices in financial transactions between Russia and Cyprus.
CEO ability and regulatory review risk
Authors: Hesarzadeh Reza , Bazrafshan Ameneh
Published: May 2019

Purpose

Chief executive officer (CEO) ability may have an effect on various corporate reporting decisions, and consequently, the CEO ability is subject to scrutiny by regulatory reviewers. However, theoretical literature provides mixed evidence on how the CEO ability affects the regulatory review risk. Thus, this study aims to empirically examine the effect of CEO ability on regulatory review risk.

Design/methodology/approach

To measure CEO ability, this study uses the CEO ability-score developed by Demerjian et al. (2012). Further, to measure regulatory review risk, the study uses the probability of receiving a comment letter from the Securities and Exchange Organization of Iran.

Findings

This study finds that the relationship between CEO ability and regulatory review risk is generally negative and statistically significant but not economically significant, i.e. the relationship is very small. In this regard, the study shows that the relationship is negative and also statistically and economically significant for firms with low levels of agency conflicts and high levels of corporate governance quality; and is positive and also statistically and economically significant for firms with high levels of agency conflicts and low levels of corporate governance quality. In addition, while the study finds no evidence that the regulatory reviewers’ workload compression influences the general relationship between CEO ability and regulatory review risk, it documents that low (high) regulatory reviewers’ workload compression weakens (strengthens) both the relationships stated above.

Originality/value

Collectively, the results suggest that the agency conflicts/corporate governance quality and regulatory reviewers’ workload compression are important factors in the analysis of the relationship between the CEO ability and regulatory review risk. The results offer insights into the opposing theoretical viewpoints about the relationship between CEO ability and regulatory review risk. Thus, the results will be of interest to boards of directors and other stakeholders involved in the regulatory review process.
Relative reference prices and M&A misvaluations
Authors: Li Zhenlong , Guo Jie , Andrikopoulos Panagiotis
Published: May 2019

Purpose

The purpose of this paper is to examine the misvaluation hypothesis using a relative reference point (RRP) in mergers and acquisitions (M&A) market.

Design/methodology/approach

The paper studies 1,878 M&A deals in the US market announced between January 1985 and December 2014.

Findings

The paper finds that bidders prefer stock payments when the RRP increases. The RRP is positively related to the offer premium and the target announcement returns. Although the RRP is negatively related to the bidder announcement returns, it is positively related to the long-run performance of bidders who time the market with overvalued stocks. The results are consistent with the predictions of the misvaluation hypothesis and reference point (RP) theory.

Originality/value

The authors construct a dynamic valuation framework to explain the misvaluation hypothesis by linking M&As’ misvaluation with RP theory. This paper provides direct evidence that the reference-dependence bias is prevalent for more experienced investors in major corporate investment decisions and offers fresh insights into the method of payment hypothesis.
Recovery of ecosystem functions after experimental disturbance in 73 grasslands differing in land‐use intensity, plant species richness and community composition
Authors: Schäfer Deborah , Klaus Valentin H. , Kleinebecker Till , Boeddinghaus Runa S. , Hinderling Judith , Kandeler Ellen , Marhan Sven , Nowak Sascha , Sonnemann Ilja , Wurst Susanne , Fischer Markus , Hölzel Norbert , Hamer Ute , Prati Daniel
Published: May 2019

Drivers of ecosystem stability have been a major topic in ecology for decades. Most studies have focused on the influence of species richness on ecosystem stability and found positive diversity‐stability relationships. However, land use and abiotic factors shape species richness and functional composition of plant communities and may override species richness‐stability relations in managed grasslands.

We analysed the relative importance of land‐use intensity (LUI), resident plant species richness and functional composition for recovery of plant communities (plant species richness, plant cover, above‐ and below‐ground biomass) and release of soil nutrients after a severe mechanical disturbance. Experimental sward disturbance was applied to 73 grassland sites along a LUI gradient in three German regions. We considered relative (ln(disturbance/control)) and absolute (disturbance − control) treatment effects. Using structural equation modelling, we disentangled direct effects of LUI and resident species richness on recovery and indirect effects via changes in functional richness.

Community‐weighted‐mean traits rarely mattered for recovery or nutrient release, while functional richness especially increased relative recovery of plant communities but also relative release of NO3‐N and NH4‐N. These effects were enhanced by increasing resident plant species richness and decreasing LUI. Next to these indirect influences of LUI and resident plant species richness via functional community composition, grasslands of high compared with grasslands of low resident plant species richness generally showed decreased recovery of plant communities. In grasslands of high LUI, absolute recovery of some aspects of plant communities was decreased. We did not find consistent differences between the relative importance of the different drivers of recovery after the first and the second season. Overall, resident species richness seemed most important for relative recovery and less important for absolute recovery, where direct effects of LUI were more common.

Synthesis. The stability of ecosystems in managed grasslands depends on more than species richness. Thus, drivers that directly affect species richness and functional community composition have to be considered when studying the stability of real‐world ecosystems. More specifically, in managed grasslands high resident species richness but also high land‐use intensity (LUI) decreased the stability of ecosystem functions, which was partially buffered by increases in functional richness.
Shame on Who? The Effects of Corporate Irresponsibility and Social Performance on Organizational Reputation
Authors: Nardella Giulio , Brammer Stephen , Surdu Irina
Published: May 2019

This study examines the relationship between corporate irresponsibility, corporate social performance and changes in organizational reputation. By combining attribution theory with expectancy violations theory, we provide the first systematic analysis of how organizational reputations are influenced by attributions of corporate irresponsibility in the context of social expectations. Drawing on a comprehensive and unique corporate irresponsibility dataset, this study reveals that firms previously believed to be most socially responsible are penalized by evaluators when corporate culpability is verified by a court of law. Conversely, firms perceived as least socially responsible were more likely to suffer reputation penalties when accused of irresponsibility, without their culpability established through litigation. Overall, the results of our study suggest that organizational reputations are mostly stable in light of irresponsibility, in that evaluators only penalize certain firms, in certain circumstances. Specifically, reputation penalties occur when highly responsible firms are perceived as hypocritical and least responsible firms were not found culpable by a court of law. Upon reflection on these findings, our study reveals that the mechanisms of social sanction previously assumed to regulate irresponsibility are weaker than currently understood. The theoretical and policy implications of this study are discussed, along with directions for future research on social evaluations.
Recombinant Urbanization: Agrarian–urban Landed Property and Uneven Development in India
Authors: Balakrishnan Sai
Published: May 2019

This article develops the concept of recombinant urbanization to show how agrarian landed property and land‐based caste/class relations shape the production of post‐liberalization urban real estate markets in India. I focus on two interrelated but differentiated agrarian property regimes in western Maharashtra to argue that real estate development is building on prior uneven agrarian land markets, which were themselves sociotechnically produced by colonial and postcolonial development politics. Through an examination of the organizational form of sugar cooperatives, which mediated agrarian capitalism in an earlier era, I track how these primary agricultural cooperatives are now being reorganized into real estate companies, sometimes with former sugarcane growers as company shareholders. The same caste‐based political and social capital that made sugar cooperatives possible in a capitalist agrarian society is now being leveraged by agrarian elites to ease their own and their constituents’ entry into an urbanizing economy. The concept of recombinant urbanization opens new methodological entryways to analyze the entangled agrarian and urban question in predominantly agrarian and late liberalizing societies.
Lower Serum Albumin Level Is Associated With an Increased Risk for Loss of Residual Kidney Function in Patients Receiving Peritoneal Dialysis
Authors: Yamada Shunsuke , Kawai Yasuhiro , Tsuneyoshi Shoji , Tsujikawa Hiroaki , Arase Hokuto , Yoshida Hisako , Tsuruya Kazuhiko , Nakano Toshiaki , Kitazono Takanari
Published: May 2019

Preserving residual kidney function (RKF) is important in the management of patients on peritoneal dialysis. However, few studies have examined the association between serum albumin level and the risk of RKF loss. We prospectively recruited 104 patients who began peritoneal dialysis treatment at our hospital between 2006 and 2016. The primary outcome was complete RKF loss, defined as urine volume < 100 mL/day. Serum albumin level at baseline was the main exposure. During a median observation period of 24 months, 33 patients developed RKF loss. A Cox proportional hazards model showed that hypoalbuminemia was associated with an increased risk of RKF, even after adjustments for potential confounding factors. Multivariable‐adjusted linear regression analysis also showed that hypoalbuminemia was associated with greater rates of decline in 24‐h urine volume and in renal Kt/V urea. Our findings suggest that hypoalbuminemia is associated with an increased risk of RKF loss in patients with peritoneal dialysis.
Precipitation Extremes and Flood Frequency in a Changing Climate in Southeastern Virginia
Authors: Sridhar Venkataramana , Modi Parthkumar , Billah Mirza M. , Valayamkunnath Prasanth , Goodall Jonathan L.
Published: May 2019

Despite the advances in climate change modeling, extreme events pose a challenge to develop approaches that are relevant for urban stormwater infrastructure designs and best management practices. The study first investigates the statistical methods applied to the land‐based daily precipitation series acquired from the Global Historical Climatology Network‐Daily (GHCN‐D). Additional analysis was carried out on the simulated Multivariate Adaptive Constructed Analogs (MACA)‐based downscaled daily extreme precipitation of 15 General Circulation Models and Weather Research and Forecasting‐based hourly extreme precipitation of North American Regional Reanalysis to discern the return period of 24‐hr and 48‐hr events. We infer that the GHCN‐D and MACA‐based precipitation reveals increasing trends in annual and seasonal extreme daily precipitation. Both BCC‐CSM1‐1‐m and GFDL‐ESM2M models revealed that the magnitude and frequency of extreme precipitation events are projected to increase between 2016 and 2099. We conclude that the future scenarios show an increase in magnitudes of extreme precipitation up to three times across southeastern Virginia resulting in increased discharge rates at selected gauge locations. The depth‐duration‐frequency curve predicted an increase of 2–3 times in 24‐ and 48‐h precipitation intensity, higher peaks, and indicated an increase of up to 50% in flood magnitude in future scenarios.
Diabetes news
Authors: Kurian Martin J. , Rentzepis Peter J. , Carracher Ann M. , Close Kelly L.
Published: May 2019

Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Rentzepis, Carracher, and Close review the latest developments relevant to researchers and clinicians.
A genomic approach to inferring kinship reveals limited intergenerational dispersal in the yellow fever mosquito
Authors: Jasper Moshe , Schmidt Thomas L. , Ahmad Nazni W. , Sinkins Steven P. , Hoffmann Ary A.
Published: May 2019

Understanding past dispersal and breeding events can provide insight into ecology and evolution and can help inform strategies for conservation and the control of pest species. However, parent–offspring dispersal can be difficult to investigate in rare species and in small pest species such as mosquitoes. Here, we develop a methodology for estimating parent–offspring dispersal from the spatial distribution of close kin, using pairwise kinship estimates derived from genome‐wide single nucleotide polymorphisms (SNPs). SNPs were scored in 162 Aedes aegypti (yellow fever mosquito) collected from eight close‐set, high‐rise apartment buildings in an area of Malaysia with high dengue incidence. We used the SNPs to reconstruct kinship groups across three orders of kinship. We transformed the geographical distances between all kin pairs within each kinship category into axial standard deviations of these distances, then decomposed these into components representing past dispersal events. From these components, we isolated the axial standard deviation of parent–offspring dispersal and estimated neighbourhood area (91 m), median parent–offspring dispersal distance (38 m) and oviposition dispersal radius within a gonotrophic cycle (25 m). We also analysed genetic structure using distance‐based redundancy analysis and linear regression, finding isolation by distance both within and between buildings and estimating neighbourhood size at 268 individuals. These findings indicate the scale required to suppress local outbreaks of arboviral disease and to target releases of modified mosquitoes for mosquito and disease control. Our methodology is readily implementable for studies of other species, including pests and species of conservation significance. [Correction added on 09 October 2020, after first online publication: 129 m corrected to 91 m; 75 m to 38 m; 36 m to 25 m.]
CBLL1 is highly expressed in non‐small cell lung cancer and promotes cell proliferation and invasion
Authors: Hui Linping , Zhang Siyang , Wudu Muli , Ren Hongjiu , Xu Yitong , Zhang Qingfu , Qiu Xueshan
Published: May 2019

Background

Studies have shown that E3 ubiquitin ligase CBLL1 plays multiple roles in development and tumorigenesis. CBLL1 is over‐expressed in colon cancer and associated with cancer cell proliferation. While, the overexpression of CBLL1 inhibited the estrogenic dependent cell proliferation and migration in ER alpha dependent breast cancer cell MCF‐7.

Methods

We used an immunohistochemical method to detect CBLL1 expression in human NSCLC and corresponding normal lung tissues and analyzed its relationship with clinicopathological parameters. Moreover, we investigated the role of CBLL1 in NSCLC cell behavior by inhibiting its expression in A549 and H1299 cells.

Results

In this study, we found that CBLL1 was frequently upregulated in non‐small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. We found that the high expression of CBLL1 was associated with the tumor size in NSCLC tissues. It has been recently reported that CBLL1 promotes cell proliferation and invasion in A549 and H460 cells. Our results confirmed that CBLL1 promoted the proliferation by promoting G1/S cell cycle transition in NSCLCs cells. Moreover, CBLL1 knockdown inhibited cell invasion via increased E‐cadherin protein expression, and decreased expression of MMP2 and MMP9 in NSCLC cell lines. The protein expression of E‐cadherin was increased after CBLL1 depletion while the E‐cadherin mRNA was not affected after knockdown of the endogenous CBLL1.

Conclusion

These results provide important insights for using CBLL1 as an oncogenic marker gene in the development and progression of non‐small cell lung cancer.
Maori Self‐Determination: Towards Differentiated Liberal Citizenship
Authors: O'Sullivan Dominic
Published: May 2019

During the 1980s and 1990s biculturalism was the ascendant political philosophy for managing the relationship between the New Zealand Crown and the indigenous Maori population. Biculturalism understood Maori politics as a partnership between Maori and the state, grounded in the Treaty of Waitangi, the agreement signed in 1840 from which British government was established. Biculturalism was presented as morally superior to multiculturalism which was understood as setting aside Maori Treaty rights and rights of prior occupancy in favour of less substantive rights available to Maori as one of many ethnic minorities. However, a deeper reading of multicultural political theory provides an instructive critique of biculturalism's inherent limits from the perspective of the Maori right to self‐determination. It shows why biculturalism's influence waned. It also shows why Matike Mai o Aotearoa, a blueprint for constitutional transformation commissioned by tribal leaders is unlikely to succeed as a contemporary attempt to reassert biculturalism's influence. Multicultural theory is not a panacea for the right to self‐determination, but it does not restrict the development of a broader Maori‐centred differentiated liberal citizenship in the ways that biculturalism precludes.
Cytokine patterns in critically ill patients undergoing percutaneous tracheostomy
Authors: Trahtemberg U , Bazak N , Sviri S , Beil M , Paschke S , van Heerden PV
Published: May 2019

The inflammatory response to acute injury among humans has proved difficult to study due to the significant heterogeneity encountered in actual patients. We set out to characterize the immune response to a model injury with reduced heterogeneity, a tracheostomy, among stable critical care patients, using a broad cytokine panel and clinical data. Twenty-three critical care patients undergoing percutaneous bedside tracheostomies were recruited in a medical intensive care unit. Blood samples were collected at five intervals during 24-h peri-procedure. Patients were followed-up for 28 days for clinical outcomes. There were no statistically significant changes in any of the cytokines between the five time-points when studied as a whole cohort. Longitudinal analysis of the cytokine patterns at the individual patient level with a clustering algorithm showed that, notwithstanding the significant heterogeneity observed, the patients’ cytokine responses can be classified into three broad patterns that show increasing, decreasing or no major changes from the baseline. This analytical approach also showed statistically significant associations between cytokines, with those most likely to be associated being interleukin (IL)-6, granulocyte colony-stimulating factor (GCSF) and ferritin, as well as a strong tri-way correlation between GCSF, monocyte chemoattractant protein 1 (MCP1) and macrophage inflammatory protein-1β (MIP1β). In conclusion, in this standard human model of soft tissue injury, by applying longitudinal analysis at the individual level, we have been able to identify the cytokine patterns underlying the seemingly random, heterogeneous patient responses. We have also identified consistent cytokine interactions suggesting that IL-6, GCSF, MCP1 and MIP1β are the cytokines most probably driving the immune response to this injury.
The immune system and psychiatric disease: a basic science perspective
Authors: Bennett F C , Molofsky A V
Published: May 2019

Mental illness exerts a major burden on human health, yet evidence-based treatments are rudimentary due to a limited understanding of the underlying pathologies. Clinical studies point to roles for the immune system in psychiatric diseases, while basic science has revealed that the brain has an active and multi-cellular resident immune system that interacts with peripheral immunity and impacts behavior. In this perspective, we highlight evidence of immune involvement in human psychiatric disease and review data from animal models that link immune signaling to neuronal function and behavior. We propose a conceptual framework for linking advances in basic neuroimmunology to their potential relevance for psychiatric diseases, based on the subtypes of immune responses defined in peripheral tissues. Our goal is to identify novel areas of focus for future basic and translational studies that may reveal the potential of the immune system for diagnosing and treating mental illnesses
Visual Analysis of Missing Values in Longitudinal Cohort Study Data
Authors: Alemzadeh S. , Niemann U. , Ittermann T. , Völzke H. , Schneider D. , Spiliopoulou M. , Bühler K. , Preim B.
Published: May 2019

Attrition or dropout is the most severe missingness problem in longitudinal cohort study data where some participants do not show up for follow‐up examinations. Dropouts result in biased data and cause the reduction of 1ata set size. Moreover, they limit the power of statistical analysis and the validity of study findings. Visualization can play a strong role in analysing and displaying the missingness patterns. In this work, we present VIVID, a framework for the visual analysis of missing values in cohort study data. VIVID is inspired by discussions with epidemiologists and adds visual components to their current statistics‐based approaches. VIVID provides functions for exploration, imputation and validity check of imputations. The main focus of this paper is multiple imputation to fix the missing data.
Indeterminate thyroid nodules (TIR3A/TIR3B) according to the new Italian reporting system for thyroid cytology: A cytomorphological study
Authors: Rullo Emma , Minelli Giada , Bosco Daniela , Nardi Francesco , Grani Giorgio , Durante Cosimo , Ascoli Valeria
Published: May 2019

Objective

The Italian reporting system for thyroid cytology classifies indeterminate lesions as TIR3A (low risk) or TIR3B (high risk) and is meant to provide practical guidance rather than a detailed consideration of morphological features. We aimed to assess which cytological features have the most diagnostic value and whether they are effective in classifying nodules as either TIR3A or TIR3B and in predicting histological outcomes.

Methods

Thyroid fine‐needle aspirates from 111 indeterminate nodules were reviewed blinded to clinical information, TIR3A/TIR3B classification, and histology in order to assess which cytological features (pooled into artefacts, smear background, architectural and nuclear atypia, and oncocytes) differentiate TIR3A from TIR3B, and benign from malignant histological outcomes.

Results

Of the cytological features examined, those specific for TIR3B included high cellularity, nuclear atypia, oncocyte predominance and transgressing vessels. Features specific for TIR3A included artefacts, low cellularity and oncocyte sparseness. Other features, such as microfollicules/trabeculae, were non‐specific. Due to the different distributions of these features, three TIR3B subgroups were identifiable: follicular lesions with oncocytic changes, pure follicular lesions, and follicular lesions with nuclear atypia, whereas no subgroups were identifiable in TIR3A. Nuclear atypia was a significant indicator of malignancy, whereas oncocyte predominance was not a reliable predictor of malignancy. High cellularity and microfollicules/trabeculae were not indicative of any histological outcome.

Conclusions

The majority of the assessed features were good predictors of histological outcomes. The TIR3A category included undefined nodules due to the absence of characterising features, whereas the TIR3B category included nodules with a greater number of distinguishing features.
Development of predictive responses in theory of mind brain regions
Authors: Richardson Hilary , Saxe Rebecca
Published: May 2019

When we watch movies, we consider the characters’ mental states in order to understand and predict the narrative. Recent work in functional magnetic resonance imaging (fMRI) uses movie‐viewing paradigms to measure functional responses in brain regions recruited for such mental state reasoning (the theory of mind [“ToM”] network). Here, two groups of young children (n = 30 3–4 years old, n = 26 6–7 years old) viewed a short animated movie twice while undergoing fMRI. As children get older, ToM brain regions were recruited earlier in time during the second presentation of the movie. This “narrative anticipation” effect is specific: there was no such effect in a control network of brain regions that responds just as robustly to the movie (the “Pain Matrix”). These results complement prior studies in adults that suggest that ToM brain regions play a role not just in inferring, but in actively predicting, other people's thoughts and feelings, and provide novel evidence that as children get older, their ToM brain regions increasingly make such predictions.
Mapping differential responses to cognitive training using machine learning
Authors: Rennie Joseph P. , Zhang Mengya , Hawkins Erin , Bathelt Joe , Astle Duncan E.
Published: May 2019

We used two simple unsupervised machine learning techniques to identify differential trajectories of change in children who undergo intensive working memory (WM) training. We used self‐organizing maps (SOMs)—a type of simple artificial neural network—to represent multivariate cognitive training data, and then tested whether the way tasks are represented changed as a result of training. The patterns of change we observed in the SOM weight matrices implied that the processes drawn upon to perform WM tasks changed following training. This was then combined with K‐means clustering to identify distinct groups of children who respond to the training in different ways. Firstly, the K‐means clustering was applied to an independent large sample (N = 616, Mage = 9.16 years, range = 5.16–17.91 years) to identify subgroups. We then allocated children who had been through cognitive training (N = 179, Mage = 9.00 years, range = 7.08–11.50 years) to these same four subgroups, both before and after their training. In doing so, we were able to map their improvement trajectories. Scores on a separate measure of fluid intelligence were predictive of a child's improvement trajectory. This paper provides an alternative approach to analysing cognitive training data that go beyond considering changes in individual tasks. This proof‐of‐principle demonstrates a potentially powerful way of distinguishing task‐specific from domain‐general changes following training and of establishing different profiles of response to training.
Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study
Authors: Lee Jeong Hoon , Ahn Ji Yong , Choi Kee Don , Jung Hwoon‐Yong , Kim Jung Mogg , Baik Gwang Ho , Kim Byung‐Wook , Park Jun Chul , Jung Hye‐Kyung , Cho Soo Jeong , Shin Cheol Min , Choi Yoon Jin , Lee Si Hyung , Kim Ji Hyun , Lee Wan Sik , Sung Jae Kyu , Chung Jun‐Won , Cheung Dae Young , Lee Hyuk , Min Yang Won , Kim Jae J. , Kim Seung Young ,   Korean College of Helicobacter,   Upper Gastrointestinal Research
Published: May 2019

Introduction

The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.

Materials and Methods

Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at −80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.

Results

The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.

Conclusion

The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.
Association between knowledge, risk behaviours, and testing for sexually transmitted infections among men who have sex with men: findings from a large online survey in the United Kingdom
Authors: Wayal S , Reid D , Weatherburn P , Blomquist P , Fabiane S , Hughes G , Mercer CH
Published: May 2019

Objectives

In the UK, men who have sex with men (MSM) bear a disproportionate sexually transmitted infection (STI) burden. We investigated MSM's STI knowledge; whether their STI testing behaviour met national guidelines (annually if sexually active; 3‐monthly if engaging in STI risk behaviours); and the relationship between STI testing in the last 3 months, STI knowledge and STI risk behaviours by HIV status.

Methods

Sexually active (in the last year) men aged > 15 years who were UK residents and were recruited from gay‐orientated online dating platforms completed an anonymous online survey about STI knowledge, STI risk behaviours, and STI testing (March–May 2017). This included 11 true statements about STIs. Respondents scored 1 for each statement they ‘knew’, with those scoring < 6 overall treated as having ‘poor’ STI knowledge. Descriptive and multivariable analyses were conducted, separately by HIV status, to test our hypothesis and calculate adjusted odds ratios (AORs) with 95% confidence intervals (CIs).

Results

Compared to HIV‐positive men (n = 489), the proportion of HIV‐negative/unknown‐status men (n = 3157) with ‘poor’ STI knowledge was significantly higher (46.4% versus 22.9% for HIV‐positive men) and the proportion with STI testing in the last 12 months was lower (71.6% versus 87.2%, respectively). In the last 3 months, 56.9% of HIV‐negative/unknown‐status and 74.1% of HIV‐positive men reported STI risk behaviours, of whom 45.8% and 55.1%, respectively, had been tested for STIs during this time. Among HIV‐negative/unknown‐status men, those reporting STI risk behaviours were more likely (AOR 1.52; 95% CI 1.26–1.84) and those with poor STI knowledge less likely (AOR 0.73; 95% CI 0.61–0.89) to have been tested during the last 3 months. However, neither factor was independently associated with 3‐monthly testing among HIV‐positive men.

Conclusions

Improving STI knowledge, especially among HIV‐negative/unknown‐status men, and promoting frequent STI testing among men engaging in STI risk behaviours are vital to address the poor sexual health of MSM.
Identifying financially illiterate groups: An international comparison
Authors: De Beckker Kenneth , De Witte Kristof , Van Campenhout Geert
Published: May 2019

Targeted policy interventions are more effective than one‐size‐fits‐all initiatives. This paper proposes the use of k‐means cluster analysis to identify vulnerable groups with respect to financial literacy. Using a rich sample of 12 countries, we distinguish 4 groups with varying financial literacy levels, and examine their socio‐economic characteristics. The results suggest that individuals in the most vulnerable financially illiterate groups are on average, single, less‐educated and unemployed with low incomes. This contrasts with those in the strongest group: individuals with the highest financial knowledge, financial behaviour and financial attitudes scores are on average highly educated males who live together with a partner. They earn a high income and hold several financial products. Integrating these insights into national strategies which promote financial literacy will not only lead to more effective but also to more efficient policy initiatives by focusing on the particular weaknesses of certain subgroups and using the appropriate transmission channels.