bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective Well-being and Partnership Dynamics: Are Same-Sex Relationships Different?
Authors: Chen Shuai , van Ours Jan C.
Published: November 2018

We analyze Dutch panel data to investigate whether partnership has a causal effect on subjective well-being. As in previous studies, we find that, on average, being in a partnership improves well-being. Well-being gains of marriage are larger than those of cohabitation. The well-being effects of partnership formation and disruption are symmetric. We also find that marriage improves well-being for both younger and older cohorts, whereas cohabitation benefits only the younger cohort. Our main contribution to the literature is on well-being effects of same-sex partnerships. We find that these effects are homogeneous to sexual orientation. Gender differences exist in the well-being effects of same-sex partnerships: females are happier cohabiting, whereas marriage has a stronger well-being effect on males.
A novel intelligent object-oriented three-dimensional simulation system for physics experimentation
Authors: Ghoniem Rania M. , Abas H.A. , Bdair H.A.
Published: November 2018

Despite the fact that there being a large literature on simulation, there is as yet no generic paradigm or architecture to develop a three-dimensional (3-D) simulator which depends on autonomous intelligent objects. This has motivated us to introduce a 3-D simulation system based on intelligent objects for Physics Experimentation. We formulated the system’s components as an object-orientation model. So, the entities in every experiment’s work cell are modeled by characterizing their properties and functions into classes and objects of the system hierarchy. Intelligent objects are realized by developing a knowledge base (KB) that captures a set of rules/algorithms that operate on 3-D objects. Rules fall into two categories: action and property rules. In the simulation layer, the student is allowed, by using the virtual system, to stroll throughout the Physics laboratory in light of a walking model. Student gets to a simulation region to do an experiment through the detection of mathematical collision. From software engineering perspective, the proposed system facilitates the Physics experiment through making the specification of its applicable parts more modular and reusable. Moreover, a major pedagogical objective is achieved by permitting the student tuning parameters, fixing component of a device then visualizing outputs. This provides student well interpretation by viewing how distinct parameters affect the outcomes of the experiment. With the objective of student performance measuring, we utilized an exploratory group relying upon pre- and post-testing. The application results demonstrate that the simulator contributes positively to student performance in regard to practical Physics.
The positive effect of narcissism on depressive symptoms through mental toughness: Narcissism may be a dark trait but it does help with seeing the world less grey
Authors: Papageorgiou Kostas A. , Denovan Andrew , Dagnall Neil
Published: November 2018

Background:

Subclinical Narcissism (SN) is part of the Dark Triad (DT), which includes also Subclinical Psychopathy (SP) and Machiavellianism. SN comprises facets retained from the clinical syndrome, such as grandiosity and dominance. Previous cross-sectional and longitudinal research indicates that SN may increase Mental Toughness (MT) resulting in various positive outcomes, including lower levels of psychopathy.

Method:

The researchers conducted three studies (N = 364, 244 and 144 for Study 1, 2 and 3 respectively) to test if the path model from SN to higher MT predicted lower symptoms of depression (DS). An extension to the model considered Openness to Experience (OE) as a possible mediator. Participants completed self-report measures of SN, MT, OE and DS. In Study 3, participants responded to an additional measure of SN to allow differentiation between grandiose and vulnerable aspects.

Results:

SN exerted a negative indirect effect on DS through MT across studies; and a negative indirect effect on DS through MT and OE in Study 2. In Study 3, Grandiose SN increased MT contributing to lower DS. Vulnerable SN demonstrated the reverse pattern. MT subfactors of Control and Confidence had a mediating effect across studies.

Conclusion:

The current findings support the model that SN to MT predicts positive outcomes in various domains, including lower levels of psychiatric symptoms. Exploring the link between SN with prosocial traits can be particularly helpful when seeking to identify and promote SN’s adaptive tendencies against symptoms of psychopathology.
Exosomes and chronic rhinosinusitis
Authors: Mueller Sarina K.
Published: November 2018

The objective of this manuscripts to review current knowledge regarding exosomes as they relate to the physiology and pathology of the human nose as well as their role as biomarkers of chronic rhinosinusitis with nasal polyps (CRSwNP).

Exosomes are 30–150 nm membrane‐bound vesicles secreted by virtually all cell types. Exosomes contribute to the rapid inter‐epithelial transfer of proteins and mediate innate immunosurveillance and defense mechanisms in the human nasal cavity. Exosomes also protect their cell specific cargo from degradation by nucleases and proteases and mirrorCRS related tissue protein perturbations more effectively than whole mucus. Thus, exosomal isolation and analysis may be used to non‐invasively monitor disease severity, prognosis, and potentially even treatment response.

Recent studies of exosomes in CRS suggest they can be used to study the immunopathology of chronic sinonasal inflammation. Furthermore, their relative accessibility suggests that exosomal proteomescan be used as non‐invasive, serial, and quantitative biosignatures for rhinosinusitis that can be sampled in clinic in order to predict disease severity, prognosis, and treatment response. Exosomal research has also led to important revelations regarding their physiologic function as they seem to play an important role in innate immunosurveillance and defense. However, exosomal research is still nascent and cost‐effectiveness as well as feasibility of implementation in the routine workup for CRS have to be further explored.
Transition of a Hyperpycnal Flow Into a Saline Turbidity Current Due to Differential Diffusivities
Authors: Zhao Liang , Ouillon Raphael , Vowinckel Bernhard , Meiburg Eckart , Kneller Benjamin , He Zhiguo
Published: November 2018

We provide a new perspective on the transition of hyperpycnal flows into saline turbidity currents, which permits longer runout lengths than might be otherwise expected. This mechanism relies on the differential turbulent diffusion of salt and sediment, and in contrast to ambient saltwater entrainment it enables the salinification of the freshwater current without diluting the sediment concentration field by a corresponding amount. The freshness‐to‐sediment ratio is introduced in order to quantify the transition process. The results of high‐resolution simulations provide estimates for the transition distance of hyperpycnal model flows into saline turbidity currents.
Numerical Simulation of the Atmospheric Signature of Artificial and Natural Seismic Events
Authors: Martire Léo , Brissaud Quentin , Lai Voon Hui , Garcia Raphaël F. , Martin Roland , Krishnamoorthy Siddharth , Komjathy Attila , Cadu Alexandre , Cutts James A. , Jackson Jennifer M. , Mimoun David , Pauken Michael T. , Sournac Anthony
Published: November 2018

The mechanical coupling between solid planets and their atmospheres enables seismically induced acoustic waves to propagate in the atmosphere. We numerically simulate this coupled system for two application cases: active seismic experiments (ASEs) and passive seismic experiments. A recent ASE (Krishnamoorthy et al., 2018, https://doi.org/10.1002/2018GL077481) observed the infrasonic signals produced by a seismic hammer. To measure the sensitivity of observations to seismic parameters, we attempt to reproduce the results from this experiment at short range by considering a realistic unconsolidated subsurface and an idealized rock‐solid subsurface. At long range, we investigate the influence of the source by using two focal mechanisms. We found surface waves generate an infrasonic plane head wave in the ASE case of the rock‐solid material. For the passive seismic experiments, the amplitude of atmospheric infrasound generated by seismic surface waves is investigated in detail. Despite some limitations, the simulations suggest that balloon measurement of seismically induced infrasound might help to constrain ground properties.
Interannual to Multidecadal Forcing of Mesoscale Eddy Kinetic Energy in the Subtropical Southern Indian Ocean
Authors: Delman Andrew S. , Lee Tong , Qiu Bo
Published: November 2018

A region of elevated mesoscale eddy activity spans the subtropical southern Indian Ocean (SSIO) between Madagascar and Australia. The interannual and decadal changes in eddy activity in the SSIO eddy band, as represented by the variability of eddy kinetic energy (EKE), have implications for the large‐scale circulation, mixed‐layer budgets, and biological activity. An analysis of nearly two and a half decades of sea level anomaly (SLA) data from merged satellite altimetry shows that, in the southeast Indian Ocean east of 90°E, the variations of EKE and SLA are positively correlated on interannual and decadal time scales. Moreover, EKE exhibits a multidecadal increasing linear trend that corresponds to an increasing trend of SLA in the region. The EKE‐SLA covariability in the southeast Indian Ocean does not appear to be associated with a preference for anticyclonic over cyclonic eddy activity; rather, it can be attributed to the common remote forcing from the tropical Pacific associated with the El Niño–Southern Oscillation and the Pacific Decadal Oscillation. In the west central SSIO, wind stress curl just south of the eddy band forces potential vorticity anomalies that affect conditions for instability in the west central SSIO; potential density and potential vorticity gradient anomalies also suggest a remote forcing mechanism originating in the region southwest of Australia. The interannual to multidecadal variability of EKE in the SSIO and its relationship with large‐scale SLA has implications for mixed‐layer dynamics and biogeochemistry and provides a basis for assessment of model simulations of eddy activity in the region.
Variation in the Current Shear Front and Its Potential Effect on Sediment Transport Over the Inner Shelf of the East China Sea in Winter
Authors: Liu S. D. , Qiao L. L. , Li G. X. , Shi J. H. , Huang L. L. , Yao Z. G. , Gao F. , Wang Z. , Min J. X.
Published: November 2018

The current shear fronts (CSFs) in the East China Sea have been observed during winter in previous studies. In this research, we systematically study characteristics and variation mechanism of the CSFs and its potential effects on the transport of water and suspended sediment and on the inner shelf mud area (ISMA), using the methods of observation data analysis and numerical simulation. The spatial structures, shear intensities, and sea‐land locations of the CSFs are obviously affected by wind, temperature and salinity. The CSFs curve seaward due to the nonuniformity of topography, and the tide causes its periodic and sea‐land shift. The landward U component near the CSFs indicate little cross‐CSF transport (i.e., the barrier effect). The CSFs are important hydrodynamic factors that affect the formation of the ISMA. The periodic shift of the CSFs in the longitudinal direction and its variations in spatial structure are the main mechanisms affecting the spatial distribution and thickness of the ISMA. However, the barrier effect of the CSFs can be interrupted, and both the strong wind in the northeast direction and baroclinic conditions are beneficial for cross‐CSF transport. Furthermore, cross‐CSF transports occur in the upper layers under northwest wind condition, in areas with nonuniformity of topography and during the spring tide period. Three cross‐shelf channels are identified in areas where the CSFs curve seaward resulting from nonuniformity of topography.
Cooling and Freshening of the West Spitsbergen Current by Shelf‐Origin Cold Core Lenses
Authors: Koenig Zoé , Meyer Amelie , Provost Christine , Sennéchael Nathalie , Sundfjord Arild , Beguery Laurent , Athanase Marylou , Gascard Jean‐Claude
Published: November 2018

The West Spitsbergen Current (WSC) cools and freshens as it flows northward along the western Svalbard shelf. The cooling takes place at the ocean surface through interaction with the atmosphere and also in subsurface. We present observations with high horizontal resolution (around 2 km) from a SeaExplorer glider deployed in July 2017 for 14 days in the WSC offshore Kongsfjorden around 79°N. They document small lenses (less than 10‐km diameter) of cold (less than 3.8 °C) and fresh (less than 35.2 g/kg) waters in the core of the WSC, coming from the shelf and contributing to its cooling and freshening. Data show that water from the shelf cascades to the bottom of the slope and then detaches on the offshore side of the WSC core where it is baroclinically unstable. The presence of these lenses from the shelf can be related to the wind regime. Strong southerly winds cause upwelling of the warm Atlantic Water onto the shelf in winter. Weak and/or northerly winds allow modified Atlantic Water formed by mixing with cold waters on the shelf to cascade down the slope, leading to lenses of colder and fresher water protruding into the WSC. If lenses are common in the WSC, they could be contributing significantly to its cooling and freshening especially in summer when the influence of the atmosphere on the cooling of the WSC is less important.
Toward a Methodology for Estimating Coastal Extreme Sea Levels From Satellite Altimetry
Authors: Lobeto H. , Menendez M. , Losada I. J.
Published: November 2018

This work represents the first attempt to study the behavior of sea level extreme events nearshore using satellite altimetry data. A novel approach based on the application of a nonstationary extreme model to nontidal residual monthly maxima from remote data is presented. With the aim of countering the lack of accuracy, an extreme scale factor to correct satellite data is defined. The extreme scale factor depends on local morphology and its definition makes use of the information provided by 14 tide gauges along the North American East Coast. The methodology is validated using eight additional tide gauge records along the study region. Low differences on values associated to high return periods using satellite and tide gauge data input are found for all the validated locations. Besides, a regional study of the climate variability of extreme sea levels from satellite is also presented. The found climate patterns strongly agree with the historical climate variations from in situ data. Results show a great potential of this approach, especially at those locations where in situ information is not available.
Multiband Simulations of Multistream Polarimetric Microwave Radiances Over Aspherical Hydrometeors
Authors: Zhang Kun , Gasiewski Albin J.
Published: November 2018

A numerical precision assessment and simulation results of the Unified Microwave Radiative Transfer (UMRT) model incorporating aspherical frozen hydrometeors based on the NASA Goddard Space Flight Center (NASA/GSFC) OpenSSP database are presented. It is shown that UMRT maintains unconditional numerical stability and computational efficiency for absorbing and scattering clouds. UMRT requires symmetry of the transition matrix for the discretized planar‐stratified radiative transfer equation to realize numerically stable and accurate matrix operations as required by the discrete ordinate eigenanalysis method. UMRT has heretofore been restricted to spherical polydispersive hydrometeors. In this study, the necessary block‐diagonal structure of the full Stokes matrix for randomly oriented OpenSSP aspherical hydrometeors is shown to be maintained, albeit with small asymmetric deviations, which introduce small asymmetric components into the transition matrix that are negligible for most remote sensing applications. An upper bound of the brightness temperature error calculated by neglecting the asymmetric components of the transition matrix under even extreme atmospheric conditions is shown to be small. Hence, the OpenSSP hydrometeor database can be reliably used within the UMRT model. Block‐diagonal Stokes matrix elements along with other single‐scattering hydrometeor parameters were subsequently used in radiative simulations of multistream dual‐polarization radiances for a simulated hurricane event to demonstrate the inherent numerical stability and utility of the enhanced UMRT model. An intercomparison of computed upwelling radiances for a multiphase distribution of aspherical OpenSSP hydrometeors versus a mass‐equivalent Mie hydrometeor polydispersion for key sensing frequencies from 10 to 874 GHz shows the considerable impact of complex (vs. simple spherical) hydrometeors on predicted microwave radiances.
A Study of Enhanced Heterogeneous Ice Nucleation in Simulated Deep Convective Clouds Observed During DC3
Authors: Takeishi Azusa , Storelvmo Trude
Published: November 2018

The impacts of enhanced heterogeneous ice nucleation (HET) on the properties of deep convective clouds (DCCs) have been investigated in cloud‐resolving simulations with the WRF‐CHEM model. The study focuses on a case observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. For the simulated DCCs, which had cold cloud‐base temperatures, an inverse relationship exists between ice crystal mass produced through HET and anvil ice crystal number concentrations. This seems to be due to the indirect competition between HET and subsequent homogeneous freezing (HOM) for liquid droplets. Furthermore, our simulations suggest that HET enhancements at warmer temperatures are more efficient in depleting liquid droplets below and hence have larger impacts on anvil properties than HET enhancements at colder temperatures do. This temperature dependence indicates that similar increases in the number of ice nucleating particles (INPs) may potentially have different impacts on DCCs, depending on the INP type and at which temperatures they can nucleate ice crystals. We also found that the reduced anvil ice number concentrations due to the enhanced HET may lead to optically thinner anvil clouds. The reduction in cloud optical depth comes from a decrease in ice crystal mass concentrations, and in some runs also from an increase in ice crystal sizes. These results suggest potentially large impacts of INPs on the properties of DCCs, especially if precipitation is predominantly produced through ice processes in the DCCs. The results underscore the importance of fully understanding the temperature‐dependent ability of aerosol particles to nucleate ice crystals.
Community-Based Mental Health Intervention Skills: Task Shifting in Low- and Middle-Income Settings
Authors: Deimling Johns Lauren , Power Jessica , MacLachlan Malcolm
Published: November 2018

There is a global need to provide human resources for health in low- and middle-income countries. To increase access to care, task shifting has been implemented in community-based rehabilitation (CBR) programs where skills and responsibilities are transferred to local people with shorter and more focused training. Through realist review and synthesis, this research aimed to consolidate the literature when considering (a) what skills CBR workers are reportedly using and/or being trained in relating to mental health, (b) how different settings affect how these task shifting programs work, and (c) the evidence of effectiveness when community health workers come from within the community itself. A total of 11 databases (PubMed, ABI/Inform Global, CINAHL, Cochrane, Emerald, Google Scholar, PsycINFO, SAGE, Science Direct, Scopus, and Web of Science) were systematically searched for specific terms relating to mental health, CBR, and low- and middle-income country. A total of 27 publications were identified as fitting the criteria (4 qualitative, 20 quantitative including 10 randomized controlled trials, and 3 noninvestigatory editorials). Core skills have been identified along with themes that affect how programs work in particular contexts. The use of task shifting in this area may be a potentially viable option for increasing access to mental health care. This resulted in the development of a theory to explain the outcomes being observed. When Task-shifting mental health intervention skills collaboration, harnessing resources available within the community, and the provision of ongoing supervision interact to influence awareness gains, social bonding, the building of trust, and the development of skills and understanding within the community itself. This effects intervention buy-in, overall effectiveness and sustainability, mental health symptoms and local empowerment. These findings can be considered when developing training programs for CBR mental health workers, as well as policy and intervention program design.
PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury
Authors: Wang Ying , Tang Chengyuan , Cai Juan , Chen Guochun , Zhang Dongshan , Zhang Zhuohua , Dong Zheng
Published: November 2018

Cisplatin is a widely used chemotherapeutic drug with notorious toxicity in the kidneys, which involves mitochondrial dysfunction and damage in renal tubular cells. Mitophagy is a form of selective autophagy that removes damaged or dysfunctional mitochondria to maintain cellular homeostasis. In this study, we have used mouse and cell models to examine the role and regulation of mitophagy in cisplatin nephrotoxicity. Cisplatin treatment was associated with the activation of autophagy and mitophagy. Rapamycin, a pharmacological inhibitor of mTOR, stimulated autophagy and mitophagy, and alleviated the development of cisplatin nephrotoxicity. PINK1 and Parkin were increased in kidney tissues during cisplatin treatment of mice. In PINK1 or Parkin gene knockout mouse models, both basal and cisplatin-induced mitophagy in kidneys were defective. Compared with wild-type littermates, PINK1 and Parkin knockout mice showed more severe renal functional loss, tissue damage, and apoptosis during cisplatin treatment. The results suggest that PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity and has a protective role against kidney injury.
The SGK3-triggered ubiquitin–proteasome degradation of podocalyxin (PC) and ezrin in podocytes was associated with the stability of the PC/ezrin complex
Authors: Yuan Ya-Pei , Zhao Hong , Peng Li-Qin , Li Zi-Fang , Liu Song , Yuan Cheng-Yan , Mwamunyi Mercy-Julian , Pearce David , Yao Li-Jun
Published: November 2018

Podocyte damage is commonly accompanied by destabilization of the podocalyxin (PC)/ezrin complex. Serum- and glucocorticoid-inducible kinase 3 (SGK3) plays a role in the maintenance of podocyte function, but the details of this role are poorly understood. Herein we demonstrated that SGK3 and its downstream target protein neural precursor cell expressed developmentally downregulated protein 4 subtype 2 (Nedd4-2) triggered PC and ezrin interaction. In adriamycin (ADR)-induced nephritic mice, and after puromycin aminonucleoside (PAN)-induced podocyte damage in vitro, PC and ezrin protein expression levels decreased significantly, while Nedd4-2 activity increased. Moreover, PAN treatment increased PC and ezrin ubiquitination and decreased PC/ezrin interaction in cultured mouse podocytes. The downregulation of SGK3 activity in mouse podocytes resulted in decreased PC and ezrin protein expression and increased the ubiquitin–proteasome degradation of PC and ezrin. Furthermore, upregulation of SGK3 activity mostly reversed the PAN-induced decrease in PC and ezrin protein expression. Overexpression of Nedd4-2 led to decreased ezrin protein expression via the upregulation of ezrin ubiquitination. In contrast, Nedd4-2 knockdown resulted in increased ezrin protein expression but decreased ezrin ubiquitination. In PC-transfected human embryonic kidney (HEK293T) cells, SGK3 activity downregulation and Nedd4-2 overexpression resulted in decreased PC/ezrin interaction. These results suggested that SGK3 triggers the ubiquitin–proteasome degradation of PC and ezrin, while the SGK3/Nedd4-2 signaling pathway regulates ezrin, but not PC, ubiquitination. Thus SGK3 helps to regulate podocyte function by maintaining the stability of the PC/ezrin complex.
Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation
Authors: Cui Chun-Ping , Zhang Yuan , Wang Chanjuan , Yuan Fang , Li Hongchang , Yao Yuying , Chen Yuhan , Li Chunnan , Wei Wenyi , Liu Cui Hua , He Fuchu , Liu Yan , Zhang Lingqiang
Published: November 2018

Sox2 is a key transcriptional factor for maintaining pluripotency of stem cells. Sox2 deficiency causes neurodegeneration and impairs neurogenesis. Although the transcriptional regulation of Sox2 has been extensively studied, the mechanisms that control Sox2 protein turnover are yet to be clarified. Here we show that the RING-finger ubiquitin ligase complex CUL4ADET1-COP1 and the deubiquitylase OTUD7B govern Sox2 protein stability during neural progenitor cells (NPCs) differentiation. Sox2 expression declines concordantly with OTUD7B and reciprocally with CUL4A and COP1 levels upon NPCs differentiation. COP1, as the substrate receptor, interacts directly with and ubiquitylates Sox2, while OTUD7B removes polyUb conjugates from Sox2 and increases its stability. COP1 knockdown stabilizes Sox2 and prevents differentiation, while OTUD7B knockdown destabilizes Sox2 and induces differentiation. Thus, CUL4ADET1-COP1 and OTUD7B exert opposite roles in regulating Sox2 protein stability at the post-translational level, which represents a critical regulatory mechanism involved in the maintenance and differentiation of NPCs.
Overcoming EGFRG724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors
Authors: Fassunke Jana , Müller Fabienne , Keul Marina , Michels Sebastian , Dammert Marcel A. , Schmitt Anna , Plenker Dennis , Lategahn Jonas , Heydt Carina , Brägelmann Johannes , Tumbrink Hannah L. , Alber Yannic , Klein Sebastian , Heimsoeth Alena , Dahmen Ilona , Fischer Rieke N. , Scheffler Matthias , Ihle Michaela A. , Priesner Vanessa , Scheel Andreas H. , Wagener Svenja , Kron Anna , Frank Konrad , Garbert Katia , Persigehl Thorsten , Püsken Michael , Haneder Stefan , Schaaf Bernhard , Rodermann Ernst , Engel-Riedel Walburga , Felip Enriqueta , Smit Egbert F. , Merkelbach-Bruse Sabine , Reinhardt H. Christian , Kast Stefan M. , Wolf Jürgen , Rauh Daniel , Büttner Reinhard , Sos Martin L.
Published: November 2018

The emergence of acquired resistance against targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. In a subgroup of these patients we identified an association between selection of EGFRT790M-negative but EGFRG724S-positive subclones and osimertinib resistance. We demonstrate that EGFRG724S limits the activity of third-generation EGFR inhibitors both in vitro and in vivo. Structural analyses and computational modeling indicate that EGFRG724S mutations may induce a conformation of the glycine-rich loop, which is incompatible with the binding of third-generation TKIs. Systematic inhibitor screening and in-depth kinetic profiling validate these findings and show that second-generation EGFR inhibitors retain kinase affinity and overcome EGFRG724S-mediated resistance. In the case of afatinib this profile translates into a robust reduction of colony formation and tumor growth of EGFRG724S-driven cells. Our data provide a mechanistic basis for the osimertinib-induced selection of EGFRG724S-mutant clones and a rationale to treat these patients with clinically approved second-generation EGFR inhibitors.
Basal freeze-on generates complex ice-sheet stratigraphy
Authors: Leysinger Vieli G. J.-M. C. , Martín C. , Hindmarsh R. C. A. , Lüthi M. P.
Published: November 2018

Large, plume-like internal ice-layer-structures have been observed in radar images from both Antarctica and Greenland, rising from the ice-sheet base to up to half of the ice thickness. Their origins are not yet understood. Here, we simulate their genesis by basal freeze-on using numerical ice-flow modelling and analyse the transient evolution of the emerging ice-plume and the surrounding ice-layer structure as a function of both freeze-on rate and ice flux. We find good agreement between radar observations, modelled ice-plume geometry and internal layer structure, and further show that plume height relates primarily to ice-flux and only secondarily to freeze-on. An in-depth analysis, performed for Northern Greenland of observed spatial plume distribution related to ice flow, basal topography and water availability supports our findings regarding ice flux and suggests freeze-on is controlled by ascending subglacial water flow. Our results imply that widespread basal freeze-on strongly affects ice stratigraphy and consequently ice-core interpretations.
Molecular structure of promoter-bound yeast TFIID
Authors: Kolesnikova Olga , Ben-Shem Adam , Luo Jie , Ranish Jeff , Schultz Patrick , Papai Gabor
Published: November 2018

Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBP-associate factors (Tafs) providing regulatory and chromatin binding functions. Here we present the cryo-electron microscopy structure of promoter-bound yeast TFIID at a resolution better than 5 Å, except for a flexible domain. We position the crystal structures of several subunits and, in combination with cross-linking studies, describe the quaternary organization of TFIID. The compact tri lobed architecture is stabilized by a topologically closed Taf5-Taf6 tetramer. We confirm the unique subunit stoichiometry prevailing in TFIID and uncover a hexameric arrangement of Tafs containing a histone fold domain in the Twin lobe.
Gene inversion potentiates bacterial evolvability and virulence
Authors: Merrikh Christopher N. , Merrikh Houra
Published: November 2018

Most bacterial genes are encoded on the leading strand, co-orienting the movement of the replication machinery with RNA polymerases. This bias reduces the frequency of detrimental head-on collisions between the two machineries. The negative outcomes of these collisions should lead to selection against head-on alleles, maximizing genome co-orientation. Our findings challenge this model. Using the GC skew calculation, we reveal the evolutionary inversion record of all chromosomally encoded genes in multiple divergent bacterial pathogens. Against expectations, we find that a large number of co-oriented genes have inverted to the head-on orientation, presumably increasing the frequency of head-on replication-transcription conflicts. Furthermore, we find that head-on genes, (including key antibiotic resistance and virulence genes) have higher rates of non-synonymous mutations and are more frequently under positive selection (dN/dS > 1). Based on these results, we propose that spontaneous gene inversions can increase the evolvability and pathogenic capacity of bacteria through head-on replication-transcription collisions.
Epithelial cells release adenosine to promote local TNF production in response to polarity disruption
Authors: Poernbacher Ingrid , Vincent Jean-Paul
Published: November 2018

Disruption of epithelial integrity contributes to chronic inflammatory disorders through persistent activation of stress signalling. Here we uncover a mechanism whereby disruption of apico-basal polarity promotes stress signalling. We show that depletion of Scribbled (Scrib), a baso-lateral determinant, causes epithelial cells to release adenosine through equilibrative channels into the extracellular space. Autocrine activation of the adenosine receptor leads to transcriptional upregulation of TNF, which in turn boosts the activity of JNK signalling. Thus, disruption of cell polarity feeds into a well-established stress pathway through the intermediary of an adenosine signalling branch. Although this regulatory input could help ensuring an effective response to acute polarity stress, we suggest that it becomes deleterious in situations of low-grade chronic disruption by provoking a private inflammatory-like TNF-driven response within the polarity-deficient epithelium.
Modern slavery and the race to fish
Authors: Tickler David , Meeuwig Jessica J. , Bryant Katharine , David Fiona , Forrest John A. H. , Gordon Elise , Larsen Jacqueline Joudo , Oh Beverly , Pauly Daniel , Sumaila Ussif R. , Zeller Dirk
Published: November 2018

Marine fisheries are in crisis, requiring twice the fishing effort of the 1950s to catch the same quantity of fish, and with many fleets operating beyond economic or ecological sustainability. A possible consequence of diminishing returns in this race to fish is serious labour abuses, including modern slavery, which exploit vulnerable workers to reduce costs. Here, we use the Global Slavery Index (GSI), a national-level indicator, as a proxy for modern slavery and labour abuses in fisheries. GSI estimates and fisheries governance are correlated at the national level among the major fishing countries. Furthermore, countries having documented labour abuses at sea share key features, including higher levels of subsidised distant-water fishing and poor catch reporting. Further research into modern slavery in the fisheries sector is needed to better understand how the issue relates to overfishing and fisheries policy, as well as measures to reduce risk in these labour markets.
Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer
Authors: Niemeijer A. N. , Leung D. , Huisman M. C. , Bahce I. , Hoekstra O. S. , van Dongen G. A. M. S. , Boellaard R. , Du S. , Hayes W. , Smith R. , Windhorst A. D. , Hendrikse N. H. , Poot A. , Vugts D. J. , Thunnissen E. , Morin P. , Lipovsek D. , Donnelly D. J. , Bonacorsi S. J. , Velasquez L. M. , de Gruijl T. D. , Smit E. F. , de Langen A. J.
Published: November 2018

PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.
PRKAA1/AMPKα1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis
Authors: Yang Qiuhua , Xu Jiean , Ma Qian , Liu Zhiping , Sudhahar Varadarajan , Cao Yapeng , Wang Lina , Zeng Xianqiu , Zhou Yaqi , Zhang Min , Xu Yiming , Wang Yong , Weintraub Neal L. , Zhang Chunxiang , Fukai Tohru , Wu Chaodong , Huang Lei , Han Zhen , Wang Tao , Fulton David J. , Hong Mei , Huo Yuqing
Published: November 2018

Increased aerobic glycolysis in endothelial cells of atheroprone areas of blood vessels has been hypothesized to drive increased inflammation and lesion burden but direct links remain to be established. Here we show that endothelial cells exposed to disturbed flow in vivo and in vitro exhibit increased levels of protein kinase AMP-activated (PRKA)/AMP-activated protein kinases (AMPKs). Selective deletion of endothelial Prkaa1, coding for protein kinase AMP-activated catalytic subunit alpha1, reduces glycolysis, compromises endothelial cell proliferation, and accelerates the formation of atherosclerotic lesions in hyperlipidemic mice. Rescue of the impaired glycolysis in Prkaa1-deficient endothelial cells through Slc2a1 overexpression enhances endothelial cell viability and integrity of the endothelial cell barrier, and reverses susceptibility to atherosclerosis. In human endothelial cells, PRKAA1 is upregulated by disturbed flow, and silencing PRKAA1 reduces glycolysis and endothelial viability. Collectively, these results suggest that increased glycolysis in the endothelium of atheroprone arteries is a protective mechanism.
Magnetically driven orbital-selective insulator–metal transition in double perovskite oxides
Authors: Chen Hanghui
Published: November 2018

Interaction-driven metal–insulator transitions or Mott transitions are widely observed in condensed matter systems. In multi-orbital systems, many-body physics is richer in which an orbital-selective metal–insulator transition is an intriguing and unique phenomenon. Here we use first-principles calculations to show that a magnetic transition (from paramagnetic to long-range magnetically ordered) can simultaneously induce an orbital-selective insulator–metal transition in rock-salt ordered double perovskite oxidesA2BB′O6, whereBis a non-magnetic ion (Y3+and Sc3+) andB′ a magnetic ion with ad3electronic configuration (Ru5+and Os5+). The orbital-selectivity originates from geometrical frustration of a face-centered-cubic lattice on which the magnetic ionsB′ reside. Including realistic structural distortions and spin-orbit interaction do not affect the transition. The predicted orbital-selective transition naturally explains the anomaly observed in the electric resistivity of Sr2YRuO6. Implications of other available experimental data are also discussed. This work shows that by exploiting geometrical frustration on non-bipartite lattices, new electronic/magnetic/orbital-coupled phase transitions can occur in correlated materials that are in the vicinity of metal–insulator phase boundary.
Bio-inspired Z-scheme g-C3N4/Ag2CrO4 for efficient visible-light photocatalytic hydrogen generation
Authors: Che Yuping , Lu Bingxin , Qi Qi , Chang Huaiqiu , Zhai Jin , Wang Kefeng , Liu Zhaoyue
Published: November 2018

Due to low charge separation efficiency and poor stability, it is usually difficult for single-component photocatalysts such as graphitic carbon nitride (g-C3N4) and silver chromate (Ag2CrO4) to fulfill photocatalytic hydrogen production efficiently. Z-scheme charge transport mechanism that mimics the photosynthesis in nature is an effective way to solve the above problems. Inspired by photosynthesis, we report Ag2CrO4 nanoparticles-decorated g-C3N4 nanosheet as an efficient photocatalyst for hydrogen evolution reaction (HER) with methanol as sacrificial agent. The formation of Z-scheme g-C3N4/Ag2CrO4 nanosheets photocatalysts could inhibit the recombination of photogenerated electron-hole pairs, promote the generation of hydrogen by photosplitting of water. The experiment results indicate that g-C3N4/Ag2CrO4 nanocomposites present enhanced photocatalytic activity and stability in the H2 evolution of water splitting. And the nanocomposites g-C3N4/Ag2CrO4(23.1%) show the 14 times HER efficiency compared to that of bare g-C3N4.
Dynamic recognition and linkage specificity in K63 di-ubiquitin and TAB2 NZF domain complex
Authors: Moritsugu Kei , Nishi Hafumi , Inariyama Keiichi , Kobayashi Masanori , Kidera Akinori
Published: November 2018

Poly-ubiquitin (poly-Ub) is involved in various cellular processes through the linkage-specific recognition of Ub-binding domains (UBD). In this study, using molecular dynamics (MD) simulation together with an enhanced sampling method, we demonstrated that K63-linked di-Ub recognizes the NZF domain of TAB2, a zinc finger UBD, in an ensemble of highly dynamic structures that form from the weak interactions between UBD and the flexible linker connecting the two Ubs. However, the K63 di-Ub/TAB2 NZF complex showed a much more compact and stable ensemble than the non-native complexes, linear di-Ub/TAB2 NZF and K33 di-Ub/TAB2 NZF, that were modeled from linear di-Ub/HOIL-1L NZF and K33 di-Ub/TRABID NZF1, respectively. We further demonstrated the importance of the length and position of the Ub-Ub linker in the results of MD simulations of K63 di-Ub/TAB2 NZF by changing the Ub linkage from the native K63 to four different non-native linkages, linear, K6, K11, and K48, while maintaining inter-molecular contacts in the native complex. No systems with non-native linkage maintained the native binding configuration. These simulation results provide an atomistic picture of the linkage specific recognition of poly-Ubs leading to the biological functions such as cellular colocalization of various component proteins in the signal transduction pathways.
Conserved Noncoding Sequences Boost ADR1 and SP1 Regulated Human Swiprosin-1 Promoter Activity
Authors: Thylur Ramesh P. , Ahn Sung Yong , Jung Eunhea , Jun Chang-Duk , Hyun Young-Min
Published: November 2018

Swiprosin-1 is expressed in various types of cells or tissues of different species. To investigate the mechanisms underlying Swiprosin-1 expression pattern, we analyzed the promoter activity of 2-kilobase genomic sequences located at 5′ flanking region of the Swiprosin-1 gene. The −2000/+41 bp of 5′ flanking untranslated promoter region of Swiprosin-1 gene was constitutively transactivated without significant effect of PMA, A23187, or PMA/A23187 stimulation in Jurkat T cells. Further, we identified 5′ deletant of proximal promoter region (−100/+41 to −70/+41) plays a pivotal role in activating the Swiprosin-1 gene in Jurkat T cells. Our studies also verified that ADR1 and Sp1 transcription factors were located between −70 and -100 locus of 5′ flanking proximal promoter region, which is critical for the Swiprosin-1 promoter activity. ADR1 and Sp1 were shown to bind the regions of −82, −79, −76, −73 and −70 and; −79, −78 and −77, respectively, within the proximal promoter region of Swiprosin-1. Finally conserved noncoding sequences (CNS) -1, -2 and -3 were located between the exon 1 and exon 2 of Swiprosin-1 gene and synergistically transactivated the Swiprosin-1 promoter. In summary, Swiprosin-1 was constitutively expressed in Jurkat T cells by the coordinate action of ADR1 and SP1 transcription factors at the transcriptional level and CNS further boost the proximal region of Swiprosin-1 promoter activity. Our findings provide novel insights that the transcriptional regulation of Swiprosin-1 by targeting ADR1 and Sp1 binding sites may be helpful in exploring novel therapeutic strategies for advanced immune or other disorders.
Evidences for a shared history for spectacled salamanders, haplotypes and climate
Authors: Iannella Mattia , D’Alessandro Paola , Biondi Maurizio
Published: November 2018

The so-called glacial refugia, formed during the Pleistocene climatic oscillations, played a major role in shaping the distribution of European species, triggering migrations or isolating populations. Many of these events were recently investigated by genetic data, mainly for the European Last Glacial stage, in the Iberic, Italian and Greek-Balkan peninsulas. The amphibian genus Salamandrina, the most ancient living salamandrid lineage, was widespread in Europe until the climatic oscillations of Miocene probably forced it to shelter in the only suitable territory at that time, the Apennines. Nowadays this genus is endemic of peninsular Italy with two parapatric species, S. perspicillata and S. terdigitata, sharing an area of secondary contact formed after the Last Glacial Maximum. Climate is generally identified as the key factor for the interpretation of genetic data. In this research, we directly measure climate influences on the two Salamandrina known species through Ensemble Modelling techniques and post-modelling GIS analyses, integrating updated genetic data in this process. Our results confirm the hypotheses of southwards (and subsequent northwards) shifts, identify glacial refugia and corridors used for the post-glacial re-colonization. Finally, we map a contact zone deserving more sampling effort to disentangle the introgression and hybridization observed.
Catalase, superoxide dismutase and ascorbate-glutathione cycle enzymes confer drought tolerance of Amaranthus tricolor
Authors: Sarker Umakanta , Oba Shinya
Published: November 2018

The study was performed to explore physiological, non-enzymatic and enzymatic detoxification pathways of reactive oxygen species (ROS) in tolerance ofAmaranthus tricolorunder drought stress. The tolerant genotype VA13 exhibited lower reduction in growth, photosynthetic pigments, relative water content (RWC) and negligible increment in electrolyte leakage (EL), lower increment in proline, guaiacol peroxidase (GPOX) activity compared to sensitive genotype VA15. This genotype also had higher catalase (CAT), superoxide dismutase (SOD), remarkable and dramatic increment in ascorbate-glutathione content, ascorbate-glutathione redox and ascorbate-glutathione cycle enzymes activity compared to sensitive genotype VA15. The negligible increment of ascorbate-glutathione content, ascorbate-glutathione redox and ascorbate-glutathione cycle enzymes activities and dramatic increment in malondialdehyde (MDA), hydrogen peroxide (H2O2) and EL were observed in the sensitive genotype VA15. SOD contributed superoxide radical dismutation and CAT contributed H2O2detoxification in both sensitive and tolerant varieties, however, these had a great contribution in the tolerant variety. Conversely, proline and GPOX accumulation were higher in the sensitive variety compared to the tolerant variety. Increase in ascorbate-glutathione cycle enzymes activities, CAT, ascorbate-glutathione content, SOD, and ascorbate-glutathione redox clearly evident that CAT, ascorbate-glutathione cycle and SOD played a significant activity in ROS detoxification of tolerantA. tricolorvariety.
Emergence of ozone recovery evidenced by reduction in the occurrence of Antarctic ozone loss saturation
Authors: Kuttippurath J. , Kumar P. , Nair P. J. , Pandey P. C.
Published: November 2018

Industrial emissions of ozone depleting substances (ODSs) during the second half of the twentieth century have led to one of the most visible human impacts on the Earth: the Antarctic ozone hole. The ozone loss intensified in the 1980s and reached the level of saturation (i.e., complete loss of ozone) due to the high levels of ODSs in the atmosphere. Significant changes in the southern hemispheric climate have been observed in the past decades due to this unprecedented ozone loss. Although the most recent studies suggest healing in the Antarctic ozone hole, the status of ozone in the loss saturation layer (~13–21 km) has not been discussed in detail. Here, a comprehensive analysis of vertical, spatial and temporal evolution of ozone loss saturation (ozone mixing ratio ≤ 0.1 ppmv) in the Antarctic vortex using high resolution measurements for the 1979–2017 period reveals that the loss saturation began in 1987 and continued to occur in all winters thereafter, except in the major warming winters of 1988 and 2002. However, our analysis shows a clear reduction in the frequency of occurrence of ozone loss saturation over the period 2001–2017 consistently throughout various datasets (e.g., ozonesonde and satellite measurements of ozone profiles and total columns), thereby revealing the emergence of an important milestone in ozone recovery.
Characterization of manganese oxide amendments for in situ remediation of mercury-contaminated sediments
Authors: Leven Alexander , Vlassopoulos Dimitri , Kanematsu Masakazu , Goin Jessica , O'Day Peggy A.
Published: November 2018

Mn(iv)-oxide amendment experiments with mercury-contaminated sediments demonstrate mineral redox buffering by mixed-valent (Mn, Fe)(iii, ii) oxides to limit mercury methylation.
Role of microstructures in the compression response of three-dimensional foam-formed wood fiber networks
Authors: Alimadadi Majid , Lindström Stefan B. , Kulachenko Artem
Published: November 2018

Experimental and numerical study of the large deformation compressional behavior of 3D wood fiber networks.
A high-throughput serum Raman spectroscopy platform and methodology for colorectal cancer diagnostics
Authors: Jenkins Cerys A. , Jenkins Rhys A. , Pryse Meleri M. , Welsby Kathryn A. , Jitsumura Maki , Thornton Catherine A. , Dunstan Peter R. , Harris Dean A.
Published: November 2018

Translating Raman spectroscopy for colorectal cancer diagnosis with a focus on high-throughput design, inter-user variability and sample handling considerations.