bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular determinants of plaque size as an indicator of dengue virus attenuation
Authors: Goh Kenneth Choon Meng , Tang Choon Kit , Norton Diana Catherine , Gan Esther Shuyi , Tan Hwee Cheng , Sun Bo , Syenina Ayesa , Yousuf Amjad , Ong Xin Mei , Kamaraj Uma Sangumathi , Cheung Yin Bun , Gubler Duane J , Davidson Andrew , St John Ashley Lauren , Sessions October Michael , Ooi Eng Eong 
Published: May 2016

AbstractThe development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines.
Direct determination of three-phase contact line properties on nearly molecular scale
Authors: Winkler P. M. , McGraw R. L. , Bauer P. S. , Rentenberger C. , Wagner P. E. 
Published: May 2016

AbstractWetting phenomena in multi-phase systems govern the shape of the contact line which separates the different phases. For liquids in contact with solid surfaces wetting is typically described in terms of contact angle. While in macroscopic systems the contact angle can be determined experimentally, on the molecular scale contact angles are hardly accessible. Here we report the first direct experimental determination of contact angles as well as contact line curvature on a scale of the order of 1nm. For water nucleating heterogeneously on Ag nanoparticles we find contact angles around 15 degrees compared to 90 degrees for the corresponding macroscopically measured equilibrium angle. The obtained microscopic contact angles can be attributed to negative line tension in the order of −10−10 J/m that becomes increasingly dominant with increasing curvature of the contact line. These results enable a consistent theoretical description of heterogeneous nucleation and provide firm insight to the wetting of nanosized objects.
KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification
Authors: Tetreault Marie-Pier , Weinblatt Daniel , Shaverdashvili Khvaramze , Yang Yizeng , Katz Jonathan P. 
Published: May 2016

AbstractEpithelial differentiation and stratification are essential for normal homeostasis, and disruption of these processes leads to both injury and cancer. The zinc-finger transciption factor KLF4 is a key driver of epithelial differentiation, yet the mechanisms and targets by which KLF4 controls differentiation are not well understood. Here, we define WNT5A, a non-canonical Wnt ligand implicated in epithelial differentiation, repair, and cancer, as a direct transcriptional target that is activated by KLF4 in squamous epithelial cells. Further, we demonstrate functionally that WNT5A mediates KLF4 control of epithelial differentiation and stratification, as treatment of keratinocytes with WNT5A rescues defective epithelial stratification resulting from KLF4 loss. Finally, we show that the small GTPase CDC42 is regulated by KLF4 in a WNT5A dependent manner. As such, we delineate a novel pathway for epithelial differentiation and stratification and define potential therapeutic targets for epithelial diseases.
Differential contributions of subregions of medial temporal lobe to memory system in amnestic mild cognitive impairment: insights from fMRI study
Authors: Chen Jiu , Duan Xujun , Shu Hao , Wang Zan , Long Zhiliang , Liu Duan , Liao Wenxiang , Shi Yongmei , Chen Huafu , Zhang Zhijun 
Published: May 2016

AbstractAltered function of the medial temporal lobe (MTL) is a valuable indicator of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. This study is to delineate the functional circuitry of multiple subdivisions of parahippocampal gyrus and hippocampus (HIP) and to examine how this knowledge contributes to a more principled understanding of the contributions of its subregions to memory in aMCI. The functional connectivity (FC) analysis was performed in 85 aMCI and 129 healthy controls. The aMCI demonstrated the distinct disruptive patterns of the MTL subregional connectivity with the whole-brain. The right entorhinal cortex (ERC) and perirhinal cortex (PRC) showed increased connectivity with the left inferior and middle occipital gyrus, respectively, which potentially indicated a compensatory mechanism. Furthermore, the right altered MTL subregional FC was associated with episodic memory performance in aMCI. These results provide novel insights into the heterogeneous nature of its large-scale connectivity in MTL subregions in memory system underlying the memory deficits in aMCI. It further suggests that altered FC of MTL subregions is associated with the impairment of the differential encoding stages of memories and the functional changes in the specific right HIP-ERC-PRC-temporal circuitry may contribute to the impairment of episodic memory in aMCI.
Feasibility demonstration of a massively parallelizable optical near-field sensor for sub-wavelength defect detection and imaging
Authors: Mostafavi Mahkamehossadat , Diaz Rodolfo E. 
Published: May 2016

AbstractTo detect and resolve sub-wavelength features at optical frequencies, beyond the diffraction limit, requires sensors that interact with the electromagnetic near-field of those features. Most instruments operating in this modality scan a single detector element across the surface under inspection because the scattered signals from a multiplicity of such elements would end up interfering with each other. However, an alternative massively parallelized configuration, capable of interrogating multiple adjacent areas of the surface at the same time, was proposed in 2002. Full physics simulations of the photonic antenna detector element that enables this instrument, show that using conventional red laser light (in the 600 nm range) the detector magnifies the signal from an 8 nm particle by up to 1.5 orders of magnitude. The antenna is a shaped slot element in a 60 nm silver film. The ability of this detector element to resolve λ/78 objects is confirmed experimentally at radio frequencies by fabricating an artificial material structure that mimics the optical permittivity of silver scaled to 2 GHz and “cutting” into it the slot antenna. The experimental set-up is also used to demonstrate the imaging of a patterned surface in which the critical dimensions of the pattern are λ/22 in size.
Jurassic zircons from the Southwest Indian Ridge
Authors: Cheng Hao , Zhou Huaiyang , Yang Qunhui , Zhang Lingmin , Ji Fuwu , Dick Henry 
Published: May 2016

AbstractThe existence of ancient rocks in present mid-ocean ridges have long been observed but received less attention. Here we report the discovery of zircons with both reasonably young ages of about 5 Ma and abnormally old ages of approximate 180 Ma from two evolved gabbroic rocks that were dredged from the Southwest Indian Ridge (SWIR) in the Gallieni fracture zone. U–Pb and Lu–Hf isotope analyses of zircons were made using ion probe and conventional laser abrasion directly in petrographic thin sections. Young zircons and their host oxide gabbro have positive Hf isotope compositions (εHf = +15.7–+12.4), suggesting a highly depleted mantle beneath the SWIR. The spread εHf values (from−2.3 to−4.5) of abnormally old zircons, together with the unradiogenic Nd-Hf isotope of the host quartz diorite, appears to suggest an ancient juvenile magmatism along the rifting margin of the southern Gondwana prior to the opening of the Indian Ocean. A convincing explanation for the origin of the unusually old zircons is yet to surface, however, an update of the theory of plate tectonics would be expected with continuing discovery of ancient rocks in the mid-oceanic ridges and abyssal ocean basins.
Disentangling the initiation from the response in joint attention: an eye-tracking study in toddlers with autism spectrum disorders
Authors: Billeci L , Narzisi A , Campatelli G , Crifaci G , Calderoni S , Gagliano A , Calzone C , Colombi C , Pioggia G , Muratori F ,   ALERT group, Raso Rossella , Ruta Liliana , Rossi Ilaria , Ballarani Agnese , Fulceri Francesca , Darini Alessandra , Maroscia Emilia , Lattarulo Caterina , Tortorella Gaetano , Siracusano Rosamaria , Comminiello Valentina 
Published: May 2016

AbstractJoint attention (JA), whose deficit is an early risk marker for autism spectrum disorder (ASD), has two dimensions: (1) responding to JA and (2) initiating JA. Eye-tracking technology has largely been used to investigate responding JA, but rarely to study initiating JA especially in young children with ASD. The aim of this study was to describe the differences in the visual patterns of toddlers with ASD and those with typical development (TD) during both responding JA and initiating JA tasks. Eye-tracking technology was used to monitor the gaze of 17 children with ASD and 15 age-matched children with TD during the presentation of short video sequences involving one responding JA and two initiating JA tasks (initiating JA-1 and initiating JA-2). Gaze accuracy, transitions and fixations were analyzed. No differences were found in the responding JA task between children with ASD and those with TD, whereas, in the initiating JA tasks, different patterns of fixation and transitions were shown between the groups. These results suggest that children with ASD and those with TD show different visual patterns when they are expected to initiate joint attention but not when they respond to joint attention. We hypothesized that differences in transitions and fixations are linked to ASD impairments in visual disengagement from face, in global scanning of the scene and in the ability to anticipate object’s action.
The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples
Authors: Schiavone S , Neri M , Mhillaj E , Morgese M G , Cantatore S , Bove M , Riezzo I , Tucci P , Pomara C , Turillazzi E , Cuomo V , Trabace L 
Published: May 2016

AbstractRecent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2’-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention.
Nuclear localizations of phosphatidylinositol 5-phosphate 4-kinases α and β are dynamic and independently regulated during starvation-induced stress
Authors: Droubi Alaa , Bulley Simon J. , Clarke Jonathan H. , Irvine Robin F. 
Published: May 2016

The chicken B-cell line DT40 has two isoforms of phosphatidylinositol 5-phosphate 4-kinase (PI5P4K), α and β, which are likely to exist as a mixture of obligate homo- and hetero-dimers. Previous work has led us to speculate that an important role of the β isoform may be to target the more active PI5P4Kα isoform to the nucleus. In the present study we expand upon that work by genomically tagging the PI5P4Ks with fluorochromes in the presence or absence of stable or acute depletions of PI5P4Kβ. Consistent with our original hypothesis we find that PI5P4Kα is predominantly (possible entirely) cytoplasmic when PI5P4Kβ is stably deleted from cells. In contrast, when PI5P4Kβ is inducibly removed within 1 h PI5P4Kα retains its wild-type distribution of approximately 50:50 between cytoplasm and nucleus even through a number of cell divisions. This leads us to speculate that PI5P4Kα is chromatin-associated. We also find that when cells are in the exponential phase of growth PI5P4Kβ is primarily cytoplasmic but translocates to the nucleus upon growth into the stationary phase or upon serum starvation. Once again this is not accompanied by a change in PI5P4Kα localization and we show, using an in vitro model, that this is possible because the dimerization between the two isoforms is dynamic. Given this shift in PI5P4Kβ upon nutrient deprivation we explore the phenotype of PI5P4K B-null cells exposed to this stress and find that they can sustain a greater degree of nutrient deprivation than their wild-type counterparts possibly as a result of up-regulation of autophagy.
Serum Levels of IL-17, IL-6, TNF-α and Disease Activity in Patients with Rheumatoid Arthritis
Authors: Beyazal M. , Devrimsel G. , Cüre M. , Türkyılmaz A. , Çapkın E. , Karkucak M. 
Published: May 2016

Abstract
Objective: The aim of this study was to evaluate serum levels of interleukin (IL)-17, IL-6, and tumor necrosis factor alpha (TNF-α) in RA patients and to assess the correlation of these cytokines with clinical and laboratory parameters.
Materials and Methods: 48 patients with RA and 35 healthy volunteers were enrolled in the study. Disease activity was determined by disease activity score (DAS28) in patients with RA. Patients with RA were categorized as mild (DAS28≤3.2), moderate (3.2<DAS28≤5.1), and severe (5.1<DAS28) according to DAS28. The serum levels of IL-17, IL-6 and TNF-α cytokines were measured by enzyme-linked immuno sorbent assay.
Results: The mean serum IL-17 and TNF-α levels did not differ between RA patients and controls (P>0.05). Serum IL-6 levels were significantly elevated in RA patients compared with controls (P<0.001). The increasing trend in mean serum IL-6 levels across group with mild, moderate, and severe disease activity was significant (P<0.001, respectively). In RA patients, serum IL-6 concentrations were significantly correlated with ESR, CRP, DAS28, and VAS (r=0.371, P=0.009; r=0.519, P<0.001; r=0.536, P<0.001; r=0.539, P<0.001, respectively). Also, Serum IL-17 concentrations demonstrated significant correlations with ESR, CRP, but not DAS28 (r=0.349, P=0.015; r=0.299, P=0.039; r=0.274, P=0.060, respectively). Serum TNF-α showed no significant correlation with disease activity indices.
Conclusions: This study showed that patients with RA had significantly increased cytokine level for IL-6, but not IL-17 and TNF-α and high level of serum IL-6 cytokine was associated with disease activity. However, further follow-up studies involving large samples are required to clarify precise role of these cytokines in disease development and progress.
“Marginalization” in third world feminism: its problematics and theoretical reconfiguration
Authors: Mansoor Asma 
Published: May 2016

AbstractWith the imposition of certain notions of agency and marginalization prescribed by first world feminist discourses, global feminism has cumulatively remained mired within a binaristic closure. This closure is based on the idea of an agentive Western feminist center and a passive third world feminism at the margin. This article endeavours to go beyond this closure to initiate debates regarding the operational praxis of a third world woman’s marginal placement as articulated in third world feminist discourses. It problematizes the idea of “disempowerment” that stems from a patriarchal model depicting man as the nucleus and a woman as a peripheral and centripetal entity, drawn within the mise en abyme of self-consolidating representations. Therefore, the argument presented here revisits the notion of the marginalization of third world women by subjecting the theoretical approaches regarding female marginalization and agency—as articulated by Spivak, Irigaray and Kristeva, et al.—to a deconstructive mode of analysis to explore the theoretical reconfiguration of a third world woman’s marginal placement. This article reconsiders the margin as discursively “limitrophic” so that the binaries between the margin/center, agency/disempowerment and third world feminism/first world feminism are re-scrutinized. The margin, thus, becomes an agentive plane for a third world woman as she uses it to direct her gaze away from any discursive center. In this way, a third world woman undermines the West-centric centripetal force despite being englobed within what Kristeva calls “supranational sociocultural ensembles” and sees her “self” as independent of any fixed center so that she redefines herself as an autonomous thinking woman able to dismantle the notion of a congealed subalternity. This article is published as part of a thematic collection on gender studies.
Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity
Authors: Matsui Teppei , Murakami Tomonari , Ohki Kenichi 
Published: May 2016

Significance
Resting-state functional connectivity (FC) is a commonly used method in neuroimaging to noninvasively study network organization of brains in humans and other animals. FC is reproducible across different institutions and sensitive enough to detect network changes due to psychiatric disorders. FC is thus a core tool for projects such as the Human Connectome Project. However, because hemodynamic signals are an indirect measure of neuronal activity, actual spatiotemporal neuronal activity underlying FC is still unknown. This study used simultaneous wide-field optical imaging of neuronal calcium signals and hemodynamic signals in transgenic mice to understand the spatiotemporal neuronal dynamics underlying FC. Transient spatial patterns of neuronal coactivations embedded within waves of activity propagating across neocortex were found to be particularly important for FC.
Clouds at Barbados are representative of clouds across the trade wind regions in observations and climate models
Authors: Medeiros Brian , Nuijens Louise 
Published: May 2016

SignificanceThis paper shows that clouds near Barbados exhibit similar properties to those over much of the tropical oceans. This finding allows observations taken at Barbados to be generalized to the broader tropics. The same approach is applied to climate models to show that errors in simulated clouds near Barbados are similar to errors across the tropical oceans. The errors are related to the representation of the vertical structure of clouds and the boundary layer and the underlying turbulent and convective mixing that create the clouds. Because trade wind clouds are a key contribution to the spread in climate model estimates of climate sensitivity, improvements in these clouds could reduce uncertainty in climate projections.
Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril
Authors: Schmidt Andreas , Annamalai Karthikeyan , Schmidt Matthias , Grigorieff Nikolaus , Fändrich Marcus 
Published: May 2016

Significance
Previous studies suggested that the interactions within amyloid fibrils correspond to those seen in peptide microcrystals consisting of steric zippers. Using electron cryomicroscopy, we can now provide further evidence for this hypothesis in a fibril structure that consists of peptide dimers forming steric zippers. These zippers are arranged in a periodic fibrillar lattice, similar to the periodic structure of a crystal. The fibril structure can be rationalized as a hierarchical assembly that is based on simple chemical principles. Identifying the chemical principles that drive fibril formation may deepen our understanding of human diseases linked to these fibrils and of functional amyloids underlying vital biological functions. Furthermore, it may enable novel biotechnological applications and the design of new fibril-based nanomaterials.
KdgF, the missing link in the microbial metabolism of uronate sugars from pectin and alginate
Authors: Hobbs Joanne K. , Lee Seunghyae M. , Robb Melissa , Hof Fraser , Barr Christopher , Abe Kento T. , Hehemann Jan-Hendrik , McLean Richard , Abbott D. Wade , Boraston Alisdair B. 
Published: May 2016

Significance
Pectin and alginate are polysaccharides found in the cell walls of plants and brown algae, respectively. These polysaccharides largely consist of chains of uronates, which can be metabolized by bacteria through a pathway of enzymatic steps to the key metabolite 2-keto-3-deoxygluconate (KDG). Understanding the metabolism of these sugars is important because pectin degradation is used by many plant-pathogenic bacteria during infection, and both pectin and alginate represent abundant sources of carbohydrate for the production of biofuels. Here we demonstrate that KdgF, a protein of previously unknown function, catalyzes the linearization of unsaturated uronates from both pectin and alginate. Furthermore, we show that KdgF contributes to efficient production of KDG and a bacterium’s ability to grow on uronates.
Elevated CO2maintains grassland net carbon uptake under a future heat and drought extreme
Authors: Roy Jacques , Picon-Cochard Catherine , Augusti Angela , Benot Marie-Lise , Thiery Lionel , Darsonville Olivier , Landais Damien , Piel Clément , Defossez Marc , Devidal Sébastien , Escape Christophe , Ravel Olivier , Fromin Nathalie , Volaire Florence , Milcu Alexandru , Bahn Michael , Soussana Jean-François 
Published: May 2016

SignificanceEcosystems are responding to climate change and increasing atmospheric CO2concentrations. Interactions between these factors have rarely been assessed experimentally during and after extreme climate events despite their predicted increase in intensity and frequency and their negative impact on primary productivity and soil carbon stocks. Here, we document how a grassland exposed to a forecasted 2050s climate shows a remarkable recovery of ecosystem carbon uptake after a severe drought and heat wave, this recovery being amplified under elevated CO2. Over the growing season, elevated CO2entirely compensated for the negative impact of extreme heat and drought on net carbon uptake. This study highlights the importance of incorporating all interacting factors in the predictions of climate change impacts.