bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing cross-national invariance of the Community Assessment of Psychic Experiences (CAPE)
Authors: Pignon Baptiste , Peyre Hugo , Ferchiou Aziz , van Os Jim , Rutten Bart P. F. , Murray Robin M. , Morgan Craig , Leboyer Marion , Schürhoff Franck , Szöke Andrei ,   EU-GEI WP2 Group Author
Published: December 2018

Background

The Community Assessment of Psychic Experiences (CAPE) is a 42-item self-report questionnaire that has been developed and validated to measure the dimensions of psychosis in the general population. The CAPE has a three-factor structure with dimensions of positive, negative and depression. Assessing the cross-national equivalence of a questionnaire is an essential prerequisite before pooling data from different countries. In this study, our aim was to investigate the measurement invariance of the CAPE across different countries.

Methods

Data were drawn from the European Union Gene-Environment Interaction (EU-GEI) study. Participants (incident cases of psychotic disorder, controls and siblings of cases) were recruited in Brazil, France, Italy, the Netherlands, Spain and UK. To analyse the measurement invariance across these samples, we tested configural invariance (i.e. identical structures of the factors), metric invariance (i.e. equivalence of the factor loadings) and scalar invariance (i.e. equivalence of the thresholds) of the three CAPE dimensions using multigroup categorical confirmatory factor analysis methods.

Results

The configural invariance model fits well, providing evidence for identical factorial structure across countries. In comparison with the configural model invariance, the fit indices were very similar in the metric and scalar invariance models, indicating that factor loadings and thresholds did not differ across the six countries.

Conclusion

We found that, across six countries, the CAPE showed equivalent factorial structure, factor loadings and thresholds. Thus, differences observed in scores between individuals from different countries should be considered as reflecting different levels of psychosis.
Establishing long-term research relationships with older people: exploring care practices in longitudinal studies
Authors: Attuyer Katia , Gilroy Rose , Croucher Karen
Published: December 2018

Drawing on a recently completed longitudinal research project with 96 participants aged 55+, the paper provides insight into the challenges of carrying out ethical practices when engaged in longer-term research relationships with older people. It builds on a body of work that purposely records in detail the ethical dilemmas researchers face, the options available to them and the rationale guiding their reaction. The Co-Motion research, led by the University of York, examined the impact of major later-life transitions on mobility and wellbeing, and was therefore focused on times of change that were, for some participants, accompanied by suffering. Over three years, the project used a range of methods to explore with each individual the dynamic nature of lived experience: change, continuity, endurance, transition and causality. The paper addresses the negotiation of informed consent over the life of long-term research relationships; the ‘care work’ involved; contested understandings of vulnerability; and the need for ongoing ethical reflection. The paper concludes by calling for greater reflexivity and suggests a more participant-focused approach to ethics in the field, demanding both greater self-awareness from researchers and allowing the participants to have greater voice in the research processes.
Health of migrant care-givers across Europe: what is the role of origin and welfare state context?
Authors: Kaschowitz Judith
Published: December 2018

Across Europe a rising number of migrants are reaching higher ages. As old age is related to care dependency, care-giving within migrant families is becoming more important. To date, little research has focused on health outcomes for migrant care-givers. Theories and empirical evidence suggest differences in the relationship of care-giving and health between migrants and non-migrants due to differences in support, income, norms and values. Furthermore, across Europe the degree of formal care supply and the obligation to provide informal care vary considerably and presumably lead to different health outcomes of care-giving in different countries. Based on data from the Survey of Health, Ageing and Retirement in Europe (Waves 1, 2, 4, 5 and 6) and the English Longitudinal Study of Ageing (Waves 2–6), this paper studies the relationship between informal care-giving inside the household and health for migrant and non-migrant care-givers across Europe and analyses changes in health. In most countries migrant care-givers are in worse self-perceived and mental health compared to non-migrant care-givers. When controlling for important influences no differences in the relationship between health and care-giving for migrants and non-migrants can be found. Moreover, care-giving deteriorates mental health irrespective of origin. The country models showed that for non-migrants care-giving is most detrimental in Southern welfare states whereas for migrants care-giving is also burdening in Nordic welfare states.
Deviating from IDSA treatment guidelines for non-purulent skin infections increases the risk of treatment failure in emergency department patients
Authors: Haran J. P. , Wilsterman E. , Zeoli T. , Goulding M. , McLendon E. , Clark M. A.
Published: December 2018

The Infectious Disease Society of America (IDSA) publishes guidelines regularly for the management of skin and soft tissue infections; however, the extent to which practice patterns follow these guidelines and if this can affect treatment failure rates is unknown. We observed the treatment failure rates from a multicentre retrospective ambulatory cohort of adult emergency department patients treated for a non-purulent skin infection. We used multivariable logistic regression to examine the role of IDSA classification and whether adherence to IDSA guidelines reduced treatment failure. A total of 759 ambulatory patients were included in the cohort with 17.4% failing treatment. Among all patients, 56.0% had received treatments matched to the IDSA guidelines with 29.1% over-treated, and 14.9% under-treated based on the guidelines. After adjustment for age, gender, infection location and medical comorbidities, patients with a moderate infection type had three times increased risk of treatment failure (adjusted risk ratio (aRR) 2.98; 95% confidence interval (CI) 1.15–7.74) and two times increased risk with a severe infection type (aRR 2.27; 95% CI 1.25–4.13) compared with mild infection types. Patients who were under-treated based on IDSA guidelines were over two times more likely to fail treatment (aRR 2.65; 95% CI 1.16–6.05) while over-treatment was not associated with treatment failure. Patients ⩾70 years of age had a 56% increased risk of treatment failure (aRR 1.56; 95% CI 1.04–2.33) compared with those <70 years. Following the IDSA guidelines for non-purulent SSTIs may reduce the treatment failure rates; however, older adults still carry an increased risk of treatment failure.
Double-orifice mitral valve repair
Authors: Gonzalez Teresa , Vera Francisco , Ruiz Enrique
Published: December 2018

We present the case of a 6-year-old patient with double-orifice mitral valve and severe regurgitation, which was successfully repaired. We demonstrate that mitral valve repair may be attempted even in complex anatomy such as the double-orifice mitral valve, where it can offer excellent results.
Die Zufriedenheit mit der Austrittsplanung und die Informiertheit von Angehörigen beeinflussen die Bereitschaft, Pflege zu übernehmen
Authors: Weiler Katharina , Wittwer Yvonne , Händler Schuster Daniela , Mahrer-Imhof Romy
Published: December 2018

Zusammenfassung. Hintergrund: Angehörige stellen für ältere Menschen, die nach einer Hospitalisation entlassen werden, eine große Ressource dar. Aus Studien ist bisher sehr wenig über die Pflegebereitschaft von Angehörigen bekannt. Ziel: Die Studie untersuchte, ob es bei Angehörigen einen Zusammenhang zwischen der Bereitschaft zur Pflege und der Zufriedenheit mit dem Austrittsmanagement sowie Gruppenunterschiede zwischen gut informierten und weniger gut informierten Angehörigen gibt. Methode: Mittels einer retrospektiven Querschnittstudie wurden neben den demografischen Daten die Bereitschaft zur Pflege, die Zufriedenheit und Informiertheit von Angehörigen erhoben. Analysen wurden zum Zusammenhang zwischen der Bereitschaft und der Zufriedenheit sowie zu Gruppenunterschieden zwischen informierten und weniger informierten Angehörigen, in Bezug auf ihre Bereitschaft, Pflege zu übernehmen, gemacht. Ergebnisse: 111 Angehörige, mehrheitlich erwachsene Nachkommen (55,9 %) und Partner (32,4 %), nahmen an der Studie teil. Es konnte eine schwache Korrelation zwischen der Zufriedenheit mit der Austrittsplanung von Angehörigen und deren Bereitschaft, Pflege zu übernehmen, nachgewiesen werden (rs = −0,113, p = 0,267). Die Gruppenunterschiede zwischen gut informierten und weniger gut informierten Angehörigen waren signifikant (t(102) = 2,301, p = 0,023). Schlussfolgerung: Angehörige, die sich als besser informiert zeigten, fühlten sich auch eher in der Lage, Pflege zu übernehmen. Deshalb ist es notwendig, Angehörige vermehrt in die Austrittsplanung einzubeziehen und besser zu informieren. Experimentelle Studien sind notwendig, um herauszufinden, ob die Pflegebereitschaft, mithilfe einer guten Austrittsplanung und gezielter Informationsabgabe, erhöht werden kann.
Nitrogen and Isotope Flows Through the Costa Rica Dome Upwelling Ecosystem: The Crucial Mesozooplankton Role in Export Flux
Authors: Stukel Michael R. , Décima Moira , Landry Michael R. , Selph Karen E.
Published: December 2018

The Costa Rica Dome (CRD) is an open‐ocean upwelling ecosystem, with high biomasses of picophytoplankton (especiallySynechococcus), mesozooplankton, and higher trophic levels. To elucidate the food web pathways supporting the trophic structure and carbon export in this unique ecosystem, we used Markov Chain Monte Carlo techniques to assimilate data from four independent realizations of δ15N and planktonic rate measurements from the CRD into steady state, multicompartment ecosystem box models (linear inverse models). Model results present well‐constrained snapshots of ecosystem nitrogen and stable isotope fluxes. New production is supported by upwelled nitrate, not nitrogen fixation. Protistivory (rather than herbivory) was the most important feeding mode for mesozooplankton, which rely heavily on microzooplankton prey. Mesozooplankton play a central role in vertical nitrogen export, primarily through active transport of nitrogen consumed in the surface layer and excreted at depth, which comprised an average 36–46% of total export. Detritus or aggregate feeding is also an important mode of resource acquisition by mesozooplankton and regeneration of nutrients within the euphotic zone. As a consequence, the ratio of passively sinking particle export to phytoplankton production is very low in the CRD. Comparisons to similar models constrained with data from the nearby equatorial Pacific demonstrate that the dominant role of vertical migrators to the biological pump is a unique feature of the CRD. However, both regions show efficient nitrogen transfer from mesozooplankton to higher trophic levels (as expected for regions with large fish, cetacean, and seabird populations) despite the dominance of protists as major grazers of phytoplankton.
Mutual Allocation of the Artificial Airglow Patches and Large‐Scale Irregularities in the HF‐Pumped Ionosphere
Authors: Grach S. M. , Nasyrov I. A. , Kogogin D. A. , Shindin A. V. , Sergeev E. N. , Razi Mousavi S. A.
Published: December 2018

The paper reports first simultaneous observations of artificial emission of 630‐nm oxygen red line, along with perturbations of slant total electron content (STEC). They were induced by the high‐frequency (HF) ionospheric heating produced by the SURA facility situated near Nijniy Novgorod, Russia. The HF heating affects differently the optical emission and STEC. While the patches of the artificial airglow are close to the area of the reduced STEC, the STEC increases at the periphery of the patches. Thus, the artificial airglow occurs mostly inside the large plasma cavities.
Causes of East Asian Temperature Multidecadal Variability Since 850 CE
Authors: Wang Jianglin , Yang Bao , Osborn Timothy J. , Ljungqvist Fredrik Charpentier , Zhang Huan , Luterbacher Jürg
Published: December 2018

The drivers of multidecadal‐ to centennial‐scale variability in East Asian temperature, apparent in temperature reconstructions, are poorly understood. Here we apply a multivariate regression analysis to distinguish the influences of large‐scale modes of internal variability (Atlantic Multidecadal Oscillation and Pacific Multidecadal Oscillation) and external natural (orbital, solar, and volcanic) and anthropogenic (greenhouse gas concentrations, aerosols, and land use changes) forcings on East Asian warm‐season temperature over the period 850–1999 CE (Common Era). We find that ~80% of the temperature change on time scales longer than 30 years can be explained including all drivers over the full‐length period. The Pacific Multidecadal Oscillation was the most important driver of multidecadal temperature variability during the Medieval Climate Anomaly (here 950–1250), while solar contribution was important during the Little Ice Age (here 1350–1850). Since 1850, two thirds of temperature change can be explained with anthropogenic forcing, whereas one third was related mainly to the Atlantic Multidecadal Oscillation and volcanic forcing.
Mars Science Laboratory Observations of the 2018/Mars Year 34 Global Dust Storm
Authors: Guzewich Scott D. , Lemmon M. , Smith C. L. , Martínez G. , de Vicente‐Retortillo Á. , Newman C. E. , Baker M. , Campbell C. , Cooper B. , Gómez‐Elvira J. , Harri A.‐M. , Hassler D. , Martin‐Torres F. J. , McConnochie T. , Moores J. E. , Kahanpää H. , Khayat A. , Richardson M. I. , Smith M. D. , Sullivan R. , de la Torre Juarez M. , Vasavada A. R. , Viúdez‐Moreiras D. , Zeitlin C. , Zorzano Mier Maria‐Paz
Published: December 2018

Mars Science Laboratory Curiosity rover observations of the 2018/Mars year 34 global/planet‐encircling dust storm represent the first in situ measurements of a global dust storm with dedicated meteorological sensors since the Viking Landers. The Mars Science Laboratory team planned and executed a science campaign lasting approximately 100 Martian sols to study the storm involving an enhanced cadence of environmental monitoring using the rover's meteorological sensors, cameras, and spectrometers. Mast Camera 880‐nm optical depth reached 8.5, and Rover Environmental Monitoring Station measurements indicated a 97% reduction in incident total ultraviolet solar radiation at the surface, 30K reduction in diurnal range of air temperature, and an increase in the semidiurnal pressure tide amplitude to 40 Pa. No active dust‐lifting sites were detected within Gale Crater, and global and local atmospheric dynamics were drastically altered during the storm. This work presents an overview of the mission's storm observations and initial results.
Seismic Attenuation of the Eastern Himalayan and Indo‐Burman Plate Boundary Systems, Northeast India
Authors: Sharma Shubham , Mitra Supriyo
Published: December 2018

We use local earthquake coda waveform to characterize the seismic attenuation across northeast India. We measure temporal decay of coda amplitude to estimate coda quality factor (Qc) at frequencies 1 to 14 Hz and abstract Q0 and its frequency dependence (η). Single‐trace measurements reveal similar average Qc between 1 and 3 Hz and significant variation at higher frequencies. We combine single‐trace Qc measurements into a backprojection algorithm to compute 2‐D Qc tomography maps. The Qc maps reveal strong correlation with tectonic settings. At low frequencies (1–5 Hz) we observe relatively lower Qc in the Sikkim and Eastern Himalaya, southern Tibetan Plateau, and Bengal Basin, while the intraplate region and Indo‐Burman subduction zone have higher Qc. At higher frequencies (>5 Hz) we observe pronounced low Qc beneath Sikkim Himalaya, relatively lower Qc in the intraplate region and relatively higher Qc in the Bengal Basin and Indo‐Burman subduction zone. We compare our Q0 map with Vs tomography to characterize the crust. The lateral variation in the structure of the Himalayan thrust sheets between Sikkim and Eastern Himalaya is highlighted by low and intermediate Q0, respectively. The southern Tibetan Plateau, known to have low Vs due to elevated crustal temperatures, is characterized by low Q0, indicating associated scattering and anelastic effects. The intraplate continental crust and the cold elastic subducting oceanic lithosphere have intermediate‐to‐high Vs and are marked by high Q0. The Bengal Basin, with thick low Vs sedimentary layers overlying a rift‐faulted high Vs transitional crust, has low‐to‐intermediate Q0 due to depth averaging of attenuation characteristics.
The Viscosities of Partially Molten Materials Undergoing Diffusion Creep
Authors: Rudge John F.
Published: December 2018

Partially molten materials resist shearing and compaction. This resistance is described by a fourth‐rank effective viscosity tensor. When the tensor is isotropic, two scalars determine the resistance: an effective shear and an effective bulk viscosity. Here calculations are presented of the effective viscosity tensor during diffusion creep for a 2‐D tiling of hexagonal unit cells and a 3‐D tessellation of tetrakaidecahedrons (truncated octahedrons). The geometry of the melt is determined by assuming textural equilibrium. The viscosity tensor for the 2‐D tiling is isotropic but that for the 3‐D tessellation is anisotropic. Two parameters control the effect of melt on the viscosity tensor: the porosity and the dihedral angle. Calculations for both Nabarro‐Herring (volume diffusion) and Coble (surface diffusion) creep are presented. For Nabarro‐Herring creep the bulk viscosity becomes singular as the porosity vanishes. This singularity is logarithmic, a weaker singularity than typically assumed in geodynamic models. The presence of a small amount of melt (0.1% porosity) causes the effective shear viscosity to approximately halve. For Coble creep, previous modeling work has argued that a very small amount of melt may lead to a substantial, factor of 5, drop in the shear viscosity. Here a much smaller, factor of 1.4, drop is obtained for tetrakaidecahedrons. Owing to a Cauchy relation symmetry, the Coble creep bulk viscosity is a constant multiple of the shear viscosity when melt is present.
Small‐Scale Metal/Silicate Equilibration During Core Formation: The Influence of Stretching Enhanced Diffusion on Mixing
Authors: Lherm V. , Deguen R.
Published: December 2018

Geochemical data provide key information on the timing of accretion and on the prevailing physical conditions during core/mantle differentiation. However, their interpretation depends critically on the efficiency of metal/silicate chemical equilibration, which is poorly constrained. Fluid dynamics experiments suggest that, before its fragmentation, a volume of liquid metal falling into a magma ocean undergoes a change of topology from a compact volume of metal toward a collection of sheets and ligaments. We investigate here to what extent the vigorous stretching of the metal phase by the turbulent flow can increase the equilibration efficiency through what is known as stretching enhanced diffusion. We obtain scaling laws giving the equilibration times of sheets and ligaments as functions of a Péclet number based on the stretching rate. At large Péclet, stretching drastically decreases the equilibration time, which in this limit depends only weakly on the diffusivity. We also perform 2‐D numerical simulations of the evolution of a volume of metal falling into a magma ocean, from which we identify several equilibration regimes depending on the values of the Péclet (Pe), Reynolds (Re), and Bond (Bo) numbers. At large Pe, Re, and Bo, the metal phase is vigorously stretched and convoluted in what we call a stirring regime. The equilibration time is found to be independent of viscosity and surface tension and depends weakly on diffusivity. Equilibration is controlled by an efficient thermochemical stretching enhanced diffusion mechanism developing from the mean flow and entraining the surrounding silicate phase.
An Analysis of Gravitational Gradients in Rotated Frames and Their Relation to Oriented Mass Sources
Authors: Panet Isabelle
Published: December 2018

Many mass sources within the Earth and its fluid envelopes show elongated geometries, aligning with the orientations of plate boundaries and plate motions, coastlines, rivers, and drainage basins for instance. To enhance their identification and separation in global or regional gravity observations and models, a dedicated method based on gravitational gradients analysis is presented here. This approach provides a detailed description of the geographic pattern of the gravity variations, which are accurately mapped thanks to the regular spatial coverage of high‐accuracy satellite data and arise from lateral density changes within the planet. First, gravity gradients are defined at different spatial scales in spherical frames, which are rotated along the radial axis according to the orientation of the source. The sensitivity of these gradients to the mass distribution inside a spherical Earth is described and analytical expressions relating the source to the observable are introduced. Then, the gravity gradients responses at different spatial scales to flat, elementary mass sources located at the surface and at increasing depth are studied. Specifically, the paper investigates how a source width and orientation can be determined, for localized and oscillatory mass anomalies with different width‐to‐length aspect ratios. This theoretical case study aims at providing a basis for the analysis of more complex mass structures, when applying the presented method to static or time‐varying satellite gravity field models. It may help deciphering the nature of the gravity sources by the detection of meaningful geometries and orientations in the gravity field.
Wintertime Fjord‐Shelf Interaction and Ice Sheet Melting in Southeast Greenland
Authors: Fraser Neil J. , Inall Mark E. , Magaldi Marcello G. , Haine Thomas W. N. , Jones Sam C.
Published: December 2018

A realistic numerical model was constructed to simulate the oceanic conditions and circulation in a large southeast Greenland fjord (Kangerdlugssuaq) and the adjacent shelf sea region during winter 2007–2008. The major outlet glaciers in this region recently destabilized, contributing to sea level rise and ocean freshening, with increased oceanic heating a probable trigger. It is not apparent a priori whether the fjord dynamics will be influenced by rotational effects, as the fjord width is comparable to the internal Rossby radius. The modeled currents, however, describe a highly three‐dimensional system, where rotational effects are of order‐one importance. Along‐shelf wind events drive a rapid baroclinic exchange, mediated by coastally trapped waves, which propagate from the shelf to the glacier terminus along the right‐hand boundary of the fjord. The terminus was regularly exposed to around 0.5 TW of heating over the winter season. Wave energy dissipation provoked vertical mixing, generating a buoyancy flux which strengthened overturning. The coastally trapped waves also acted to strengthen the cyclonic mean flow via Stokes' drift. Although the outgoing wave was less energetic and located at the opposite sidewall, the fjord did exhibit a resonant response, suggesting that fjords of this scale can also exhibit two‐dimensional dynamics. Long periods of moderate wind stress greatly enhanced the cross‐shelf delivery of heat toward the fjord, in comparison to stronger events over short intervals. This suggests that the timescale over which the shelf wind field varies is a key parameter in dictating wintertime heat delivery from the ocean to the ice sheet.
The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
Authors: Shen Cheng-Ying , Chang Ya-Chu , Chen Li-Han , Lin Wen-Chun , Lee Yung-Hua , Yeh Shu-Tsen , Chen Hsin-Kuang , Fang Wentao , Hsu Chung-Ping , Lee Jang-Ming , Lu Tzu-Pin , Hsiao Pei-Wen , Lai Liang-Chuan , Tsai Mong-Hsun , Chuang Eric Y.
Published: December 2018

Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.
Taxonomic and functional heterogeneity of the gill microbiome in a symbiotic coastal mangrove lucinid species
Authors: Lim Shen Jean , Davis Brenton G , Gill Danielle E , Walton Jillian , Nachman Erika , Engel Annette Summers , Anderson Laurie C , Campbell Barbara J
Published: December 2018

Lucinidae clams harbor gammaproteobacterial thioautotrophic gill endosymbionts that are environmentally acquired. Thioautotrophic lucinid symbionts are related to metabolically similar symbionts associated with diverse marine host taxa and fall into three distinct phylogenetic clades. Most studies on the lucinid–bacteria chemosymbiosis have been done with seagrass-dwelling hosts, whose symbionts belong to the largest phylogenetic clade. In this study, we examined the taxonomy and functional repertoire of bacterial endosymbionts at an unprecedented resolution from Phacoides pectinatus retrieved from mangrove-lined coastal sediments, which are underrepresented in chemosymbiosis studies. The P. pectinatus thioautotrophic endosymbiont expressed metabolic gene variants for thioautotrophy, respiration, and nitrogen assimilation distinct from previously characterized lucinid thioautotrophic symbionts and other marine symbionts. At least two other bacterial species with different metabolisms were also consistently identified in the P. pectinatus gill microbiome, including a Kistimonas-like species and a Spirochaeta-like species. Bacterial transcripts involved in adhesion, growth, and virulence and mixotrophy were highly expressed, as were host-related hemoglobin and lysozyme transcripts indicative of sulfide/oxygen/CO2 transport and bactericidal activity. This study suggests the potential roles of P. pectinatus and its gill microbiome species in mangrove sediment biogeochemistry and offers insights into host and microbe metabolisms in the habitat.
Loss of the candidate tumor suppressor ZEB1 (TCF8, ZFHX1A) in Sézary syndrome
Authors: Caprini Elisabetta , Bresin Antonella , Cristofoletti Cristina , Helmer Citterich Mauro , Tocco Valeria , Scala Enrico , Monopoli Alessandro , Benucci Roberto , Narducci Maria Grazia , Russo Giandomenico
Published: December 2018

Cutaneous T-cell lymphoma is a group of incurable extranodal non-Hodgkin lymphomas that develop from the skin-homing CD4+ T cell. Mycosis fungoides and Sézary syndrome are the most common histological subtypes. Although next-generation sequencing data provided significant advances in the comprehension of the genetic basis of this lymphoma, there is not uniform consensus on the identity and prevalence of putative driver genes for this heterogeneous group of tumors. Additional studies may increase the knowledge about the complex genetic etiology characterizing this lymphoma. We used SNP6 arrays and GISTIC algorithm to prioritize a list of focal somatic copy-number alterations in a dataset of multiple sequential samples from 21 Sézary syndrome patients. Our results confirmed a prevalence of significant focal deletions over amplifications: single well-known tumor suppressors, such as TP53, PTEN, and RB1, are targeted by these aberrations. In our cohort, ZEB1 (TCF8, ZFHX1A) spans a deletion having the highest level of significance. In a larger group of 43 patients, we found that ZEB1 is affected by deletions and somatic inactivating mutations in 46.5% of cases; also, we found potentially relevant ZEB1 germline variants. The survival analysis shows a worse clinical course for patients with ZEB1 biallelic inactivation. Multiple abnormal expression signatures were found associated with ZEB1 depletion in Sézary patients we verified that ZEB1 exerts a role in oxidative response of Sézary cells. Our data confirm the importance of deletions in the pathogenesis of cutaneous T-cell lymphoma. The characterization of ZEB1 abnormalities in Sézary syndrome fulfils the criteria of a canonical tumor suppressor gene. Although additional confirmations are needed, our findings suggest, for the first time, that ZEB1 germline variants might contribute to the risk of developing this disease. Also, we provide evidence that ZEB1 activity in Sézary cells, influencing the reactive oxygen species production, affects cell viability and apoptosis.
Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition
Authors: Pareek Gautam , Pallanck Leo J.
Published: December 2018

The mitochondrial Unfolded Protein Response (UPRmt) pathway confers protection from misfolded and aggregated proteins by activating factors that promote protein folding and degradation. Our recent work on Lon protease, a member of the mitochondrial ATPase Associated with diverse cellular Activities (AAA+) family of mitochondrial resident proteases, suggests that mitochondrial translational inhibition may also be a feature of the UPRmt pathway.
Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination
Authors: Codo Ana Campos , Saraiva Amanda Correia , dos Santos Leonardo Lima , Visconde Marina Francisco , Gales Ana Cristina , Zamboni Dario Simões , Medeiros Alexandra Ivo
Published: December 2018

Klebsiella pneumoniae is a Gram-negative bacterium responsible for severe cases of nosocomial pneumonia. During the infectious process, both neutrophils and monocytes migrate to the site of infection, where they carry out their effector functions and can be affected by different patterns of cell death. Our data show that clinical strains of K. pneumoniae have dissimilar mechanisms for surviving within macrophages; these mechanisms include modulation of microbicidal mediators and cell death. The A28006 strain induced high IL-1β production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1β production by macrophages. Pyroptotic cell death induced by the A28006 strain leads to a significant increase in bacterial sensitivity to hydrogen peroxide, and efferocytosis of the pyroptotic cells results in efficient bacterial clearance both in vitro and in vivo. In addition, the A54970 strain was able to inhibit inflammasome activation and pyroptotic cell death by inducing IL-10 production. Here, for the first time, we present a K. pneumoniae strain able to inhibit inflammasome activation, leading to bacterial survival and dissemination in the host. The understanding of possible escape mechanisms is essential in the search for alternative treatments against multidrug-resistant bacteria.
Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC
Authors: Shen Chaoqin , Yan Tingting , Wang Zhenhua , Su Heng-chuan , Zhu Xiaoqiang , Tian Xianglong , Fang Jing-Yuan , Chen Haoyan , Hong Jie
Published: December 2018

Genome-wide association studies (GWAS) have identified several loci harboring variants that affected the risk of colorectal cancer; however, the specific mechanisms by which germline variation influenced the tumorigenesis of colorectal cancer (CRC) remains unrevealed. We found the T>C variant of rs1317082, locating at the exon 1 of lncRNA RP11-362K14.5 (CCSlnc362), was predicted to be a protective locus for cancer. However, the specific role of CCSlnc362 and the interaction between CCSlnc362 and rs1317082 variation in colorectal cancer and its mechanisms remain unclear. Here we explored the expression and function of CCSlnc362 in CRC cells and tissues. We found lncRNA CCSlnc362 expression was significantly increased in CRC samples. Follow-up functional experiments elucidated that downregulation of CCSlnc362 inhibited cell proliferation, arrested cell cycle, and promoted apoptosis in CRC cells. The T>C variant of rs1317082 at CCSlnc362 exon 1 created a binding site for miR-4658 to reduce the expression of CCSlnc362 and thus decreased the susceptibility to CRC. Our findings have provided supporting evidence for the protective role of rs1317082 variation and the potential oncogenic role of lncRNA CCSlnc362 in CRC. The data shed new light on the relationship between germline variation, miRNAs, and lncRNAs and opened a new avenue for targeted therapy in CRC.
Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons
Authors: He Zhigang , Song Jian , Hua Jie , Yang Muqing , Ma Yuanyuan , Yu Tianyu , Feng Junlan , Liu Bin , Wang Xiaodong , Li Yue , Li Jiyu
Published: December 2018

Mast cells (MCs) are potent tissue-resident immune cells that are distributed in the intraepithelial space of the intestine and have been implicated in regulating immune homeostasis and coordinating epithelial responses in inflamed mucosa of inflammatory bowel disease (IBD). IL-33 functions as an endogenous danger signal or alarmin in inflamed intestine segments. MCs highly express the IL-33 receptor ST2. However, the mechanisms underlying the immune regulation of MC-dependent IL-33/ST2 signaling at the barrier surface of the intestine remain largely unknown. We confirmed that MCs are required for the effective resolution of tissue damage using an experimental colitis model that allows for conditional ablation of MCs. After elucidating the IL-33 signaling involved in MC activity in the context of intestinal inflammation, we found that the function of restricted IL-33/ST2 signaling by MCs was consistent with an MC deficiency in response to the breakdown of the epithelial barrier. We observed that a tissue environment with a spectrum of protective cytokines was orchestrated by MC-dependent IL-33/ST2 signaling. Given the significant downregulation of IL-22 and IL-13 due to the loss of MC-dependent IL-33/ST2 signaling and their protective functions in inflammation settings, induction of IL-22 and IL-13 may be responsible for an immune network favorable to mucosal repair. Collectively, our data showed an important feedback loop in which cytokine cues from damaged epithelia activate MCs to regulate tissue environments essential for MC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.
Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis
Authors: Varela-Eirín Marta , Varela-Vázquez Adrián , Guitián-Caamaño Amanda , Paíno Carlos Luis , Mato Virginia , Largo Raquel , Aasen Trond , Tabernero Arantxa , Fonseca Eduardo , Kandouz Mustapha , Caeiro José Ramón , Blanco Alfonso , Mayán María D.
Published: December 2018

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. In OA, chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favouring disease progression. Similar to other wound-healing disorders, chondrocytes from OA patients show a chronic increase in the gap junction channel protein connexin43 (Cx43), which regulates signal transduction through the exchange of elements or recruitment/release of signalling factors. Although immature or stem-like cells are present in cartilage from OA patients, their origin and role in disease progression are unknown. In this study, we found that Cx43 acts as a positive regulator of chondrocyte-mesenchymal transition. Overactive Cx43 largely maintains the immature phenotype by increasing nuclear translocation of Twist-1 and tissue remodelling and proinflammatory agents, such as MMPs and IL-1β, which in turn cause cellular senescence through upregulation of p53, p16INK4a and NF-κB, contributing to the senescence-associated secretory phenotype (SASP). Downregulation of either Cx43 by CRISPR/Cas9 or Cx43-mediated gap junctional intercellular communication (GJIC) by carbenoxolone treatment triggered rediferentiation of osteoarthritic chondrocytes into a more differentiated state, associated with decreased synthesis of MMPs and proinflammatory factors, and reduced senescence. We have identified causal Cx43-sensitive circuit in chondrocytes that regulates dedifferentiation, redifferentiation and senescence. We propose that chondrocytes undergo chondrocyte-mesenchymal transition where increased Cx43-mediated GJIC during OA facilitates Twist-1 nuclear translocation as a novel mechanism involved in OA progression. These findings support the use of Cx43 as an appropriate therapeutic target to halt OA progression and to promote cartilage regeneration.
Long non-coding RNA C5orf66-AS1 promotes cell proliferation in cervical cancer by targeting miR-637/RING1 axis
Authors: Rui Xiaohui , Xu Yun , Jiang Xiping , Ye Wenfeng , Huang Yaqing , Jiang Jingting
Published: December 2018

Long non-coding RNA (lncRNA) plays an important role in the development of human malignant tumours. Recently, an increasing number of lncRNAs have been identified and investigated in a variety of tumours. However, the expression pattern and biological function of lncRNAs in cervical cancer still remain largely unexplored. Differentially expressed lncRNAs in cervical cancer and para-carcinoma tissues were identified by screening using The Cancer Genome Atlas (TCGA), and candidate lncRNAs were verified by quantitative real-time PCR. We found that lncRNAC5orf66-AS1 was significantly upregulated in cervical cancer tissues and cells. Over-expression of C5orf66-AS1 promoted the proliferation of cervical cancer cells, while downregulation of C5orf66-AS1 promoted the apoptosis of cervical cancer cells. C5orf66-AS1 was identified as the sponge of miR-637 by RNA immunoprecipitation (RIP) and luciferase reporter assays. Exogenous miR-637 and RING1 interventions could reverse the proliferation ability mediated by C5orf66-AS1 in cervical cancer cells. In vivo experiments also confirmed that downregulation of C5orf66-AS1 inhibited the tumour growth. LncRNA C5orf66-AS1, as a competitive endogenous RNA (ceRNA), regulated the effect of RING1 on the proliferation, apoptosis and cell cycle of cervical cancer cells through adsorbing miR-637. Taken together, our findings provided a new theoretical and experimental basis for investigating the pathogenesis and exploring effective therapeutic targets for cervical cancer.
Nutritional stress reprograms dedifferention in glioblastoma multiforme driven by PTEN/Wnt/Hedgehog axis: a stochastic model of cancer stem cells
Authors: Mondal Susmita , Bhattacharya Kaushik , Mandal Chitra
Published: December 2018

The emergence and maintenance of cancer stem-like cells (CSCs) are usually governed by tumor niche. Tumor niche always provides metabolic challenges to cancer cells and CSCs mostly because of tissue hypoxia. However, the role of micro-environmental nutritional stress (NS) in dedifferentiation of cancer cells is poorly defined. Here, we developed a stochastic model of CSCs by gradual nutritional deprivation in glioblastoma multiforme (GBM) cells used as a model system. Nutritional deprivation induced enhanced expression of glioblastoma stem-like cells (GSCs)-specific biomarkers with higher invasive and angiogenic properties. This NS-induced cells showed higher xenobiotic efflux ability, and hence exhibit resistance to multiple anticancer drugs. In the molecular level, such NS activated Wnt and Hedgehog (Hh) signaling pathways by stabilizing β-catenin and Gli1, respectively, through modulation of GSK3β/AKT axis. GBM-specific PTEN (phosphatase and tensin homolog) mutation contributed to better phenoconversion toward GSCs. Knocking down of PTEN coupled with NS induction enhanced neurosphere formation, GSC-specific biomarker expressions, and activation of Wnt/Hh signaling. Thus, such an in-depth understanding of dedifferentiation of GBM cells to GSCs under NS suggested that targeting Wnt/Hh signaling possibly be a better therapeutic approach.
Challenges hindering memristive neuromorphic hardware from going mainstream
Authors: Adam Gina C. , Khiat Ali , Prodromakis Themis
Published: December 2018

Memristive devices have elicited intense research in the past decade thanks to their inherent low voltage operation, multi-bit storage and cost-effective manufacturability. Nonetheless, several outstanding performance and manufacturability challenges have prevented the widespread industry adoption of redox-based memristive matrices. Here, we discuss these challenges in terms of key metrics and propose a roadmap towards realizing competitive memristive-based neuromorphic processing systems.
Magic number colloidal clusters as minimum free energy structures
Authors: Wang Junwei , Mbah Chrameh Fru , Przybilla Thomas , Apeleo Zubiri Benjamin , Spiecker Erdmann , Engel Michael , Vogel Nicolas
Published: December 2018

Clusters in systems as diverse as metal atoms, virus proteins, noble gases, and nucleons have properties that depend sensitively on the number of constituent particles. Certain numbers are termed ‘magic’ because they grant the system with closed shells and exceptional stability. To this point, magic number clusters have been exclusively found with attractive interactions as present between atoms. Here we show that magic number clusters exist in a confined soft matter system with negligible interactions. Colloidal particles in an emulsion droplet spontaneously organize into a series of clusters with precisely defined shell structures. Crucially, free energy calculations demonstrate that colloidal clusters with magic numbers possess higher thermodynamic stability than those off magic numbers. A complex kinetic pathway is responsible for the efficiency of this system in finding its minimum free energy configuration. Targeting similar magic number states is a strategy towards unique configurations in finite self-organizing systems across the scales.
CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages
Authors: Percin Gulce Itir , Eitler Jiri , Kranz Andrea , Fu Jun , Pollard Jeffrey W. , Naumann Ronald , Waskow Claudia
Published: December 2018

Regulatory mechanisms controlling the pool size of spleen dendritic cells (DC) remain incompletely understood. DCs are continuously replenished from hematopoietic stem cells, and FLT3-mediated signals cell-intrinsically regulate homeostatic expansion of spleen DCs. Here we show that combining FLT3 and CSF1R-deficiencies results in specific and complete abrogation of spleen DCs in vivo. Spatiotemporally controlled CSF1R depletion reveals a cell-extrinsic and non-hematopoietic mechanism for DC pool size regulation. Lack of CSF1R-mediated signals impedes the differentiation of spleen macrophages of embryonic origin, and the resulted macrophage depletion during development or in adult mice results in loss of DCs. Moreover, embryo-derived macrophages are important for the physiologic regeneration of DC after activation-induced depletion in situ. In summary, we show that the differentiation of DC and their regeneration relies on ontogenetically distinct spleen macrophages, thereby providing a novel regulatory principle that may also be important for the differentiation of other hematopoietic cell types.
Migration alters oscillatory dynamics and promotes survival in connected bacterial populations
Authors: Gokhale Shreyas , Conwill Arolyn , Ranjan Tanvi , Gore Jeff
Published: December 2018

Migration influences population dynamics on networks, thereby playing a vital role in scenarios ranging from species extinction to epidemic propagation. While low migration rates prevent local populations from becoming extinct, high migration rates enhance the risk of global extinction by synchronizing the dynamics of connected populations. Here, we investigate this trade-off using two mutualistic strains ofE. colithat exhibit population oscillations when co-cultured. In experiments, as well as in simulations using a mechanistic model, we observe that high migration rates lead to synchronization whereas intermediate migration rates perturb the oscillations and change their period. Further, our simulations predict, and experiments show, that connected populations subjected to more challenging antibiotic concentrations have the highest probability of survival at intermediate migration rates. Finally, we identify altered population dynamics, rather than recolonization, as the primary cause of extended survival.
Membrane water for probing neuronal membrane potentials and ionic fluxes at the single cell level
Authors: Didier M. E. P. , Tarun O. B. , Jourdain P. , Magistretti P. , Roke S.
Published: December 2018

Neurons communicate through electrochemical signaling within a complex network. These signals are composed of changes in membrane potentials and are traditionally measured with the aid of (toxic) fluorescent labels or invasive electrical probes. Here, we demonstrate an improvement in label-free second harmonic neuroimaging sensitivity by ~3 orders of magnitude using a wide-field medium repetition rate illumination. We perform a side-by-side patch-clamp and second harmonic imaging comparison to demonstrate the theoretically predicted linear correlation between whole neuron membrane potential changes and the square root of the second harmonic intensity. We assign the ion induced changes to the second harmonic intensity to changes in the orientation of membrane interfacial water, which is used to image spatiotemporal changes in the membrane potential and K+ ion flux. We observe a non-uniform spatial distribution and temporal activity of ion channels in mouse brain neurons.