bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Behavioral, Experiential, and Conceptual Dimensions of	the Self
Authors: Weger Ulrich , Meyer Andreas , Wagemann Johannes
Published: September 2016

Abstract. The self has become a prominent field of research in psychology but despite its eminent first-person character, it is typically studied from a third-person perspective. Such a third-person approach is well suited to enquire into the behavioral expression of the sense of selfhood but it does not capture the core experience – the so-called qualia nature – of the self. In the current article we illuminate the challenges that a predominant third-person approach poses to an understanding of the self. We outline two levels of analysis that can complement and enrich a third-person, behavior-focused view, namely the level of experience and the level of conceptual insight. Both these additional levels are accessible via a first-person mode of enquiry and can reveal a degree of richness about the self that reaches beyond a third-person approach. We here provide a methodological justification for such a qualitative mode of enquiry, as well as a synopsis of findings from our own first-person research which involved introspective reports of the authors’ experiences during meditation on geometrical shapes, words, and short phrases.
Animals as Social Objects
Authors: Sevillano Verónica , Fiske Susan T.
Published: September 2016

Abstract. Nonhuman animals are typically excluded from the scope of social psychology. This article presents animals as social objects – targets of human social responses – overviewing the similarities and differences with human targets. The focus here is on perceiving animal species as social groups. Reflecting the two fundamental dimensions of humans’ social cognition – perceived warmth (benign or ill intent) and competence (high or low ability), proposed within the Stereotype Content Model ( Fiske, Cuddy, Glick, & Xu, 2002 ) – animal stereotypes are identified, together with associated prejudices and behavioral tendencies. In line with human intergroup threats, both realistic and symbolic threats associated with animals are reviewed. As a whole, animals appear to be social perception targets within the human sphere of influence and a valid topic for research.
Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways
Authors: Chen Xiaosong , Yan Liu , Guo Zhihui , Chen Zhaohong , Chen Ying , Li Ming , Huang Chushan , Zhang Xiaoping , Chen Liangwan
Published: September 2016

Autologous fat grafting is an effective reconstructive surgery technique; however, its success is limited by inconsistent graft retention and an environment characterized by high oxidative stress and inflammation. Adipose-derived stem cells (ADSCs) increase the survival of fat grafts, although the underlying mechanisms remain unclear. Here, TLR4−/− and Nrf2−/− mice were used to explore the effects of oxidative stress and inflammation on the viability and function of ADSCs in vitro and in vivo. Enrichment of fat grafts with ADSCs inhibited inflammatory cytokine production, enhanced growth factor levels, increased fat graft survival, downregulated NADPH oxidase (NOX)1 and 4 expression, increased vascularization and reduced ROS production in a manner dependent on toll-like receptor (TLR)-4 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Immunohistochemical analysis showed that exposure to hypoxia enhanced ADSC growth and promoted the differentiation of ADSCs into vascular endothelial cells. Hypoxia-induced inflammatory cytokine, growth factor and NOX1/4 upregulation, as well as increased ROS production and apoptosis in ADSCs were dependent on TLR4 and Nrf2, which also modulated the effect of ADSCs on promoting endothelial progenitor cell migration and angiogenesis. Western blot analyses showed that the effects of hypoxia on ADSCs were regulated by crosstalk between Nrf2 antioxidant responses and NF-κB- and TLR4-mediated inflammatory responses. Taken together, our results indicate that ADSCs can increase the survival of fat transplants through the modulation of inflammatory and oxidative responses via Nrf2 and TLR4, suggesting potential strategies to improve the use of ADSCs for cell therapy.
Broad activation of latent HIV-1 in vivo
Authors: Barton Kirston , Hiener Bonnie , Winckelmann Anni , Rasmussen Thomas Aagaard , Shao Wei , Byth Karen , Lanfear Robert , Solomon Ajantha , McMahon James , Harrington Sean , Buzon Maria , Lichterfeld Mathias , Denton Paul W. , Olesen Rikke , Østergaard Lars , Tolstrup Martin , Lewin Sharon R. , Søgaard Ole Schmeltz , Palmer Sarah
Published: September 2016

The ‘shock and kill’ approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4+ T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diverse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1.
Characterization of a putative NsrR homologue in Streptomyces venezuelae reveals a new member of the Rrf2 superfamily
Authors: Munnoch John T. , Martinez Ma Teresa Pellicer , Svistunenko Dimitri A. , Crack Jason C. , Le Brun Nick E. , Hutchings Matthew I.
Published: September 2016

Members of the Rrf2 superfamily of transcription factors are widespread in bacteria but their functions are largely unexplored. The few that have been characterized in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulfur (Fe-S) cluster status of the cell (IscR). In this study we combined ChIP- and dRNA-seq with in vitro biochemistry to characterize a putative NsrR homologue in Streptomyces venezuelae. ChIP-seq analysis revealed that rather than regulating the nitrosative stress response like Streptomyces coelicolor NsrR, Sven6563 binds to a conserved motif at a different, much larger set of genes with a diverse range of functions, including a number of regulators, genes required for glutamine synthesis, NADH/NAD(P)H metabolism, as well as general DNA/RNA and amino acid/protein turn over. Our biochemical experiments further show that Sven6563 has a [2Fe-2S] cluster and that the switch between oxidized and reduced cluster controls its DNA binding activity in vitro. To our knowledge, both the sensing domain and the putative target genes are novel for an Rrf2 protein, suggesting Sven6563 represents a new member of the Rrf2 superfamily. Given the redox sensitivity of its Fe-S cluster we have tentatively named the protein RsrR for Redox sensitive response Regulator.
Rapid conversions and avoided deforestation: examining four decades of industrial plantation expansion in Borneo
Authors: Gaveau David L. A. , Sheil Douglas , Husnayaen  , Salim Mohammad A. , Arjasakusuma Sanjiwana , Ancrenaz Marc , Pacheco Pablo , Meijaard Erik
Published: September 2016

New plantations can either cause deforestation by replacing natural forests or avoid this by using previously cleared areas. The extent of these two situations is contested in tropical biodiversity hotspots where objective data are limited. Here, we explore delays between deforestation and the establishment of industrial tree plantations on Borneo using satellite imagery. Between 1973 and 2015 an estimated 18.7 Mha of Borneo’s old-growth forest were cleared (14.4 Mha and 4.2 Mha in Indonesian and Malaysian Borneo). Industrial plantations expanded by 9.1 Mha (7.8 Mha oil-palm; 1.3 Mha pulpwood). Approximately 7.0 Mha of the total plantation area in 2015 (9.2 Mha) were old-growth forest in 1973, of which 4.5–4.8 Mha (24–26% of Borneo-wide deforestation) were planted within five years of forest clearance (3.7–3.9 Mha oil-palm; 0.8–0.9 Mha pulpwood). This rapid within-five-year conversion has been greater in Malaysia than in Indonesia (57–60% versus 15–16%). In Indonesia, a higher proportion of oil-palm plantations was developed on already cleared degraded lands (a legacy of recurrent forest fires). However, rapid conversion of Indonesian forests to industrial plantations has increased steeply since 2005. We conclude that plantation industries have been the principle driver of deforestation in Malaysian Borneo over the last four decades. In contrast, their role in deforestation in Indonesian Borneo was less marked, but has been growing recently. We note caveats in interpreting these results and highlight the need for greater accountability in plantation development.
Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines
Authors: Pfeiffer Thomas , Avignone Elena , Nägerl U. Valentin
Published: September 2016

Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain.
Ultra-portable, wireless smartphone spectrometer for rapid, non-destructive testing of fruit ripeness
Authors: Das Anshuman J. , Wahi Akshat , Kothari Ishan , Raskar Ramesh
Published: September 2016

We demonstrate a smartphone based spectrometer design that is standalone and supported on a wireless platform. The device is inherently low-cost and the power consumption is minimal making it portable to carry out a range of studies in the field. All essential components of the device like the light source, spectrometer, filters, microcontroller and wireless circuits have been assembled in a housing of dimensions 88 mm × 37 mm × 22 mm and the entire device weighs 48 g. The resolution of the spectrometer is 15 nm, delivering accurate and repeatable measurements. The device has a dedicated app interface on the smartphone to communicate, receive, plot and analyze spectral data. The performance of the smartphone spectrometer is comparable to existing bench-top spectrometers in terms of stability and wavelength resolution. Validations of the device were carried out by demonstrating non-destructive ripeness testing in fruit samples. Ultra-Violet (UV) fluorescence from Chlorophyll present in the skin was measured across various apple varieties during the ripening process and correlated with destructive firmness tests. A satisfactory agreement was observed between ripeness and fluorescence signals. This demonstration is a step towards possible consumer, bio-sensing and diagnostic applications that can be carried out in a rapid manner.
Ultra-high electrochemical catalytic activity of MXenes
Authors: Pan Hui
Published: September 2016

Cheap and abundant electrocatalysts for hydrogen evolution reactions (HER) have been widely pursued for their practical application in hydrogen-energy technologies. In this work, I present systematical study of the hydrogen evolution reactions on MXenes (Mo2X and W2X, X = C and N) based on density-functional-theory calculations. I find that their HER performances strongly depend on the composition, hydrogen adsorption configurations, and surface functionalization. I show that W2C monolayer has the best HER activity with near-zero overpotential at high hydrogen density among all of considered pure MXenes, and hydrogenation can efficiently enhance its catalytic performance in a wide range of hydrogen density further, while oxidization makes its activity reduced significantly. I further show that near-zero overpotential for HER on Mo2X monolayers can be achieved by oxygen functionalization. My calculations predict that surface treatment, such as hydrogenation and oxidization, is critical to enhance the catalytic performance of MXenes. I expect that MXenes with HER activity comparable to Pt in a wide range of hydrogen density can be realized by tuning composition and functionalizing, and promotes their applications into hydrogen-energy technologies.
Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration
Authors: Kim Hye-Jung , Ahn Seong Joon , Woo Se Joon , Hong Hye Kyoung , Suh Eui Jin , Ahn Jeeyun , Park Ji Hyun , Ryoo Na-Kyung , Lee Ji Eun , Kim Ki Woong , Park Kyu Hyung , Lee Cheolju
Published: September 2016

Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.
The effects of dissipation on topological mechanical systems
Authors: Xiong Ye , Wang Tianxiang , Tong Peiqing
Published: September 2016

We theoretically study the effects of isotropic dissipation in a topological mechanical system which is an analogue of Chern insulator in mechanical vibrational lattice. The global gauge invariance is still conserved in this system albeit it is destroyed by the dissipation in the quantum counterpart. The chiral edge states in this system are therefore robust against strong dissipation. The dissipation also causes a dispersion of damping for the eigenstates. It will modify the equation of motion of a wave packet by an extra effective force. After taking into account the Berry curvature in the wave vector space, the trace of a free wave packet in the real space should be curved, feinting to break the Newton’s first law.
Suppressing the Fluorescence Blinking of Single Quantum Dots Encased in N-type Semiconductor Nanoparticles
Authors: Li Bin , Zhang Guofeng , Wang Zao , Li Zhijie , Chen Ruiyun , Qin Chengbing , Gao Yan , Xiao Liantuan , Jia Suotang
Published: September 2016

N-type semiconductor indium tin oxide (ITO) nanoparticles are used to effectively suppress the fluorescence blinking of single near-infrared-emitting CdSeTe/ZnS core/shell quantum dots (QDs), where the ITO could block the electron transfer from excited QDs to trap states and facilitate more rapid regeneration of neutral QDs by back electron transfer. The average blinking rate of QDs is significantly reduced by more than an order of magnitude and the largest proportion of on-state is 98%, while the lifetime is not considerably reduced. Furthermore, an external electron transfer model is proposed to analyze the possible effect of radiative, nonradiative, and electron transfer pathways on fluorescence blinking. Theoretical analysis based on the model combined with measured results gives a quantitative insight into the blinking mechanism.
Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia
Authors: McCarthy Cathal , Kenny Louise C.
Published: September 2016

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.
Mass production of highly-porous graphene for high-performance supercapacitors
Authors: Amiri Ahmad , Shanbedi Mehdi , Ahmadi Goodarz , Eshghi Hossein , Kazi S. N. , Chew B. T. , Savari Maryam , Zubir Mohd Nashrul Mohd
Published: September 2016

This study reports on a facile and economical method for the scalable synthesis of few-layered graphene sheets by the microwave-assisted functionalization. Herein, single-layered and few-layered graphene sheets were produced by dispersion and exfoliation of functionalized graphite in ethylene glycol. Thermal treatment was used to prepare pure graphene without functional groups, and the pure graphene was labeled as thermally-treated graphene (T-GR). The morphological and statistical studies about the distribution of the number of layers showed that more than 90% of the flakes of T-GR had less than two layers and about 84% of T-GR were single-layered. The microwave-assisted exfoliation approach presents us with a possibility for a mass production of graphene at low cost and great potentials in energy storage applications of graphene-based materials. Owing to unique surface chemistry, the T-GR demonstrates an excellent energy storage performance, and the electrochemical capacitance is much higher than that of the other carbon-based nanostructures. The nanoscopic porous morphology of the T-GR-based electrodes made a significant contribution in increasing the BET surface as well as the specific capacitance of graphene. T-GR, with a capacitance of 354.1 Fg−1 at 5 mVs−1 and 264 Fg−1 at 100 mVs−1, exhibits excellent performance as a supercapacitor.
Therapeutic TNF Inhibitors can Differentially Stabilize Trimeric TNF by Inhibiting Monomer Exchange
Authors: van Schie Karin A. , Ooijevaar-de Heer Pleuni , Dijk Lisanne , Kruithof Simone , Wolbink Gertjan , Rispens Theo
Published: September 2016

Tumor necrosis factor (TNF) is a homotrimeric cytokine that is a key mediator of inflammation. It is unstable at physiological concentrations and slowly converts into an inactive form. Here, we investigated the mechanism of this process by using a Förster resonance energy transfer (FRET) assay that allowed monitoring of monomeric subunit exchange in time. We observed continuous exchange of monomeric subunits even at concentrations of TNF high enough to maintain its bioactivity. The kinetics of this process closely corresponds with the appearance of monomeric subunits and disappearance of trimeric TNF in time at ng/ml concentrations as monitored by high-performance size-exclusion chromatography (HP-SEC). Furthermore, of the five therapeutic TNF inhibitors that are currently used in the clinic, three (adalimumab, infliximab, etanercept) were found to completely inhibit the monomer exchange reaction and stabilize TNF trimers, whereas golimumab and certolizumab could not prevent monomer exchange, but did slow down the exchange process. These differences were not correlated with the affinities of the TNF inhibitors, measured with both surface plasmon resonance (SPR) and in fluid phase using fluorescence-assisted HP-SEC. The stabilizing effect of these TNF inhibitors might result in prolonged residual TNF bioactivity under conditions of incomplete blocking, as observed in vitro for adalimumab.
Micro RNA-98 interferes with expression interleukin-10 in peripheral B cells of patients with lung cancer
Authors: Li Yun , Rong Jian , Qin Jie , He Jin-yuan , Chen Hui-guo , Huang Shao-hong
Published: September 2016

Interleukin (IL)-10-producing B cells (B10 cells) plays an important role in the tumor tolerance. High frequency of peripheral B10 cell was reported in patients with lung cancer recently. Micro RNA (miR) regulates some gene expression. This study test a hypothesis that miR-98 suppresses the expression of IL-10 in B cells of subjects with lung cancer. The results showed that the levels of miR-98 were significantly less in peripheral B cells of patients with lung cancer than that in healthy subjects. IL-10 mRNA levels in peripheral B cells were significantly higher in lung cancer patients as compared with healthy controls. A negative correlation was identified between miR-98 and IL-10 in peripheral B cells. Serum IL-13 was higher in lung cancer patients than that in healthy controls. The levels of IL-13 were also negatively correlated with IL-10 in B cells. Exposure B10 cells to IL-13 in the culture or over expression of miR-98 reduced the expression of IL-10 in B cells. Administration with miR-98-laden liposomes inhibited the lung cancer growth in a mouse model. In conclusion, up regulation of miR-98 inhibits the expression of IL-10 in B cells, which may contribute to inhibit the lung cancer tolerance in the body.
Induction of colitis in mice with food allergen-specific immune response
Authors: Li Lin-Jing , Zeng Lu , Li Xiao-Xi , Mo Li-Hua , Geng Xiao-Rui , Zheng Peng-Yuan , Liu Zhi-Gang , Feng Bai-Sui , Yang Ping-Chang
Published: September 2016

The pathogenesis of intestinal chronic inflammation is unclear. Food allergy plays an important role in the induction of intestinal inflammation. This study aims to test a hypothesis that food allergy initiates colitis. In this study, BALB/c mice were sensitized to a common food allergen, ovalbumin (OVA) with cholera toxin (CT) as an adjuvant. The colon epithelial barrier function was assessed with Ussing chamber technique. Expression of T cell immunoglobulin mucin domain molecule-4 (TIM4) in dendritic cells was evaluated by flow cytometry, RT-PCR and Western blotting. The results showed that allergen-related colitis was induced in mice as shown by heavy infiltration of inflammatory cells in the colon mucosa, loss of body weight of mice, increases in myeloperoxidase, tumor necrosis factor-α, interleukin-4, OVA-specific IgE in the colon tissue. The colon epithelial barrier function was markedly compromised in colitis group mice, which was mimicked by exposure the colon mucosa to CT in Ussing chamber. High frequency of TIM4+ dendritic cells was detected in the colon mucosa of colitis mice. Exposure of dendritic cells to CT markedly increased the expression of TIM4. We conclude that IBD-like inflammation can be induced in the mouse colon by the food allergen-related immune response.
Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells
Authors: Behnan Jinan , Stangeland Biljana , Langella Tiziana , Finocchiaro Gaetano , Murrell Wayne , Brinchmann Jan E.
Published: September 2016

Glioma stem cells (GSCs) are thought to be the source of tumor growth and therapy resistance. To understand the biology of GSCs, and target these tumors therapeutically, we need robust strategies for in vitro expansion of primary GSCs. To date, tumor core biopsies have been the main established source of GSCs. Since these samples are used for diagnostic purposes, the available tissue for cell culture and therapeutic targeting can be limited. In addition, a core biopsy is usually taken from one part of the tumor, thus would be unlikely to represent intra-tumor heterogeneity. To overcome these problems, tissue fragments from all over the tumor can be collected using an ultrasonic aspirator during surgery, thus assembling a “global tumor biopsy”. Usually, this ultrasonic aspirate (UA) sample is considered as biological waste after operations. Here, we show that UA samples offer a large and reliable source of live cells. Similar to core biopsies, UA samples enriched for GSCs that differentiated into neural lineages, showed inter-individual variation of GSC markers, and induced tumors. Molecular profiling showed that UA samples cover tumor heterogeneity better than core biopsies. These results suggest that UA samples can be used to establish large scale cultures for therapeutic applications.
Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones
Authors: Cama Jehangir , Schaich Michael , Al Nahas Kareem , Hernández-Ainsa Silvia , Pagliara Stefano , Keyser Ulrich F.
Published: September 2016

Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug – we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community.
Simultaneous spatiotemporal mapping of in situ pH and bacterial activity within an intact 3D microcolony structure
Authors: Hwang Geelsu , Liu Yuan , Kim Dongyeop , Sun Victor , Aviles-Reyes Alejandro , Kajfasz Jessica K. , Lemos Jose A. , Koo Hyun
Published: September 2016

Biofilms are comprised of bacterial-clusters (microcolonies) enmeshed in an extracellular matrix. Streptococcus mutans can produce exopolysaccharides (EPS)-matrix and assemble microcolonies with acidic microenvironments that can cause tooth-decay despite the surrounding neutral-pH found in oral cavity. How the matrix influences the pH and bacterial activity locally remains unclear. Here, we simultaneously analyzed in situ pH and gene expression within intact biofilms and measured the impact of damage to the surrounding EPS-matrix. The spatiotemporal changes of these properties were characterized at a single-microcolony level following incubation in neutral-pH buffer. The middle and bottom-regions as well as inner-section within the microcolony 3D structure were resistant to neutralization (vs. upper and peripheral-region), forming an acidic core. Concomitantly, we used a green fluorescent protein (GFP) reporter to monitor expression of the pH-responsive atpB (PatpB::gfp) by S. mutans within microcolonies. The atpB expression was induced in the acidic core, but sharply decreased at peripheral/upper microcolony regions, congruent with local pH microenvironment. Enzymatic digestion of the surrounding matrix resulted in nearly complete neutralization of microcolony interior and down-regulation of atpB. Altogether, our data reveal that biofilm matrix facilitates formation of an acidic core within microcolonies which in turn activates S. mutans acid-stress response, mediating both the local environment and bacterial activity in situ.
Effects of density dependence in a temperate forest in northeastern China
Authors: Yao Jie , Zhang Xinna , Zhang Chunyu , Zhao Xiuhai , von Gadow Klaus
Published: September 2016

Negative density dependence may cause reduced clustering among individuals of the same species, and evidence is accumulating that conspecific density-dependent self-thinning is an important mechanism regulating the spatial structure of plant populations. This study evaluates that specific density dependence in three very large observational studies representing three successional stages in a temperate forest in northeastern China. The methods include standard spatial point pattern analysis and a heterogeneous Poisson process as the null model to eliminate the effects of habitat heterogeneity. The results show that most of the species exhibit conspecific density-dependent self-thinning. In the early successional stage 11 of the 16 species, in the intermediate successional stage 18 of the 21 species and in the old growth stage all 21 species exhibited density dependence after removing the effects of habitat heterogeneity. The prevalence of density dependence thus varies among the three successional stages and exhibits an increase with increasing successional stage. The proportion of species showing density dependence varied depending on whether habitat heterogeneity was removed or not. Furthermore, the strength of density dependence is closely related with species abundance. Abundant species with high conspecific aggregation tend to exhibit greater density dependence than rare species.
Nematodes enhance plant growth and nutrient uptake under C and N-rich conditions
Authors: Gebremikael Mesfin T. , Steel Hanne , Buchan David , Bert Wim , De Neve Stefaan
Published: September 2016

The role of soil fauna in crucial ecosystem services such as nutrient cycling remains poorly quantified, mainly because of the overly reductionistic approach adopted in most experimental studies. Given that increasing nitrogen inputs in various ecosystems influence the structure and functioning of soil microbes and the activity of fauna, we aimed to quantify the role of the entire soil nematode community in nutrient mineralization in an experimental set-up emulating nutrient-rich field conditions and accounting for crucial interactions amongst the soil microbial communities and plants. To this end, we reconstructed a complex soil foodweb in mesocosms that comprised largely undisturbed native microflora and the entire nematode community added into defaunated soil, planted withLolium perenneas a model plant, and amended with fresh grass-clover residues. We determined N and P availability and plant uptake, plant biomass and abundance and structure of the microbial and nematode communities during a three-month incubation. The presence of nematodes significantly increased plant biomass production (+9%), net N (+25%) and net P (+23%) availability compared to their absence, demonstrating that nematodes link below- and above-ground processes, primarily through increasing nutrient availability. The experimental set-up presented allows to realistically quantify the crucial ecosystem services provided by the soil biota.
The Extrinsic Coagulation Pathway: a Biomarker for Suicidal Behavior in Major Depressive Disorder
Authors: Yang Yongtao , Chen Jin , Liu Chengyu , Fang Liang , Liu Zhao , Guo Jing , Cheng Ke , Zhou Chanjuan , Zhan Yuan , Melgiri Narayan D. , Zhang Liang , Zhong Jiaju , Chen Jianjun , Rao Chenglong , Xie Peng
Published: September 2016

Although an association between major depressive disorder (MDD) and suicide exists, most depressed patients never attempt suicide. An improved understanding of the factors contributing to suicidal risk in MDD can provide direction for suicide predictor development. In MDD suicide attempters (MDD-SA), MDD non-attempters (MDD-NA), and healthy controls (HC) (n = 12 each group), complementary plasma proteomics identified 45 differential proteins mapped to coagulation and inflammation, 25 of which underwent Western blotting. In another cohort including antidepressant-treated patients (n = 49 each group), seven additional extrinsic pathway proteins were selected for ELISA. Two inflammatory proteins and eight coagulatory proteins demonstrated alterations in MDD-SA relative to MDD-NA and HC. Applying a relative mass-action ratio, MDD-SA subjects displayed a higher relative prothrombinase activity than MDD-NA subjects, while healthy controls displayed higher relative prothrombinase activity than both MDD-SA and MDD-NA subjects. Consistent with our human findings, we found that heparin treatment significantly increased forced swimming test (FST) immobility time in rodents. MDD, independent of suicidality, is associated with a proinflammatory state accompanied by a hypothrombotic state. Suicidal behavior in MDD is associated with a more pronounced proinflammatory and prothrombotic phenotype accompanied by extrinsic pathway activation, revealing an extrinsic pathway biomarker that can be applied in predicting and monitoring suicidal risk.
Incomplete immune response to coxsackie B viruses associates with early autoimmunity against insulin
Authors: Ashton Michelle P. , Eugster Anne , Walther Denise , Daehling Natalie , Riethausen Stephanie , Kuehn Denise , Klingel Karin , Beyerlein Andreas , Zillmer Stephanie , Ziegler Anette-Gabriele , Bonifacio Ezio
Published: September 2016

Viral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely defined by different binding to VP1 or VP2. Antibody responses that were anti-VP2 competent but anti-VP1 deficient were unable to neutralize CVB, and were characteristic of children who developed early insulin-targeting autoimmunity, suggesting an impaired ability to clear CVB in early childhood. In contrast, children who developed a GAD-targeting autoimmunity had robust VP1 and VP2 antibody responses to CVB. We further found that 20% of memory CD4+ T cells responding to the GAD65247-266 peptide share identical T cell receptors to T cells responding to the CVB4 p2C30-51 peptide, thereby providing direct evidence for the potential of molecular mimicry as a mechanism for GAD autoimmunity. Here, we highlight functional immune response differences between children who develop insulin-targeting and GAD-targeting autoimmunity, and suggest that children who lose B cell tolerance to insulin within the first years of life have a paradoxical impaired ability to mount humoral immune responses to coxsackie viruses.
Correction: Corrigendum: Composite alginate gels for tunable cellular microenvironment mechanics
Authors: Khavari Adele , Nydén Magnus , Weitz David A. , Ehrlicher Allen J.
Published: September 2016

Scientific Reports 6: Article number: 30854; published online: 03 August 2016; updated: 08 September 2016
Graphene-assisted multiple-input high-base optical computing
Authors: Hu Xiao , Wang Andong , Zeng Mengqi , Long Yun , Zhu Long , Fu Lei , Wang Jian
Published: September 2016

We propose graphene-assisted multiple-input high-base optical computing. We fabricate a nonlinear optical device based on a fiber pigtail cross-section coated with a single-layer graphene grown by chemical vapor deposition (CVD) method. An approach to implementing modulo 4 operations of three-input hybrid addition and subtraction of quaternary base numbers in the optical domain using multiple non-degenerate four-wave mixing (FWM) processes in graphene coated optical fiber device and (differential) quadrature phase-shift keying ((D)QPSK) signals is presented. We demonstrate 10-Gbaud modulo 4 operations of three-input quaternary hybrid addition and subtraction (A + B − C, A + C − B, B + C − A) in the experiment. The measured optical signal-to-noise ratio (OSNR) penalties for modulo 4 operations of three-input quaternary hybrid addition and subtraction (A + B − C, A + C − B, B + C − A) are measured to be less than 7 dB at a bit-error rate (BER) of 2 × 10−3. The BER performance as a function of the relative time offset between three signals (signal offset) is also evaluated showing favorable performance.
Purification, characterization, cytotoxicity and anticancer activities of L-asparaginase, anti-colon cancer protein, from the newly isolated alkaliphilic Streptomyces fradiae NEAE-82
Authors: El-Naggar Noura El-Ahmady , Deraz Sahar F. , Soliman Hoda M. , El-Deeb Nehal M. , El-Ewasy Sara M.
Published: September 2016

L-asparaginase is an important enzyme as therapeutic agents used in combination with other drugs in the treatment of acute lymphoblastic leukemia. A newly isolated actinomycetes strain, Streptomyces sp. NEAE-82, was potentially producing extracellular L-asparaginase, it was identified as Streptomyces fradiae NEAE-82, sequencing product was deposited in the GenBank database under accession number KJ467538. L-asparaginase was purified from the crude enzyme using ammonium sulfate precipitation, dialysis and ion exchange chromatography using DEAE Sepharose CL-6B. Further the kinetic studies of purified enzyme were carried out. The optimum pH, temperature and incubation time for maximum L-asparaginase activity were found to be 8.5, 40 °C and 30 min, respectively. The optimum substrate concentration was found to be 0.06 M. The Km and Vmax of the enzyme were 0.01007 M and 95.08 Uml−1min−1, respectively. The half-life time (T1/2) was 184.91 min at 50 °С, while being 179.53 min at 60 °С. The molecular weight of the subunits of L-asparaginase was found to be approximately 53 kDa by SDS–PAGE analysis. The purified L-asparaginase showed a final specific activity of 30.636 U/mg protein and was purified 3.338-fold. The present work for the first time reported more information in the production, purification and characterization of L-asparaginase produced by newly isolated actinomycetes Streptomyces fradiae NEAE-82.
Nedd4-2 haploinsufficiency causes hyperactivity and increased sensitivity to inflammatory stimuli
Authors: Yanpallewar Sudhirkumar , Wang Ting , Koh Dawn C. I. , Quarta Eros , Fulgenzi Gianluca , Tessarollo Lino
Published: September 2016

Nedd4-2 (NEDD4L in humans) is a ubiquitin protein ligase best known for its role in regulating ion channel internalization and turnover. Nedd4-2 deletion in mice causes perinatal lethality associated with increased epithelial sodium channel (ENaC) expression in lung and kidney. Abundant data suggest that Nedd4-2 plays a role in neuronal functions and may be linked to epilepsy and dyslexia in humans. We used a mouse model of Nedd4-2 haploinsufficiency to investigate whether an alteration in Nedd4-2 levels of expression affects general nervous system functions. We found that Nedd4-2 heterozygous mice are hyperactive, have increased basal synaptic transmission and have enhanced sensitivity to inflammatory pain. Thus, Nedd4-2 heterozygous mice provide a new genetic model to study inflammatory pain. These data also suggest that in human, SNPs affecting NEDD4L levels may be involved in the development of neuropsychological deficits and peripheral neuropathies and may help unveil the genetic basis of comorbidities.
Isolation, Co-Crystallization and Structure-Based Characterization of Anabaenopeptins as Highly Potent Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa)
Authors: Schreuder Herman , Liesum Alexander , Lönze Petra , Stump Heike , Hoffmann Holger , Schiell Matthias , Kurz Michael , Toti Luigi , Bauer Armin , Kallus Christopher , Klemke-Jahn Christine , Czech Jörg , Kramer Dan , Enke Heike , Niedermeyer Timo H. J. , Morrison Vincent , Kumar Vasant , Brönstrup Mark
Published: September 2016

Mature thrombin activatable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help to prevent thrombosis. Applying a lead finding approach based on literature-mining, we discovered that anabaenopeptins, cyclic peptides produced by cyanobacteria, were potent inhibitors of TAFIa with IC50 values as low as 1.5 nM. We describe the isolation and structure elucidation of 20 anabaenopeptins, including 13 novel congeners, as well as their pronounced structure-activity relationships (SAR) with respect to inhibition of TAFIa. Crystal structures of the anabaenopeptins B, C and F bound to the surrogate protease carboxypeptidase B revealed the binding modes of these large (~850 Da) compounds in detail and explained the observed SAR, i.e. the strong dependence of the potency on a basic (Arg, Lys) exocyclic residue that addressed the S1’ binding pocket, and a broad tolerance towards substitutions in the pentacyclic ring that acted as a plug of the active site.
Higher-dimensional performance of port-based teleportation
Authors: Wang Zhi-Wei , Braunstein Samuel L.
Published: September 2016

Port-based teleportation (PBT) is a variation of regular quantum teleportation that operates without a final unitary correction. However, its behavior for higher-dimensional systems has been hard to calculate explicitly beyond dimension d = 2. Indeed, relying on conventional Hilbert-space representations entails an exponential overhead with increasing dimension. Some general upper and lower bounds for various success measures, such as (entanglement) fidelity, are known, but some become trivial in higher dimensions. Here we construct a graph-theoretic algebra (a subset of Temperley-Lieb algebra) which allows us to explicitly compute the higher-dimensional performance of PBT for so-called “pretty-good measurements” with negligible representational overhead. This graphical algebra allows us to explicitly compute the success probability to distinguish the different outcomes and fidelity for arbitrary dimension d and low number of ports N, obtaining in addition a simple upper bound. The results for low N and arbitrary d show that the entanglement fidelity asymptotically approaches N/d2 for large d, confirming the performance of one lower bound from the literature.
Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency
Authors: Jung Hae Hyun , Lee Soo-Hyeon , Kim Ji-Yeon , Ahn Jin Seok , Park Yeon Hee , Im Young-Hyuck
Published: September 2016

We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfectedDUSP4. We demonstrated thatETS1mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) andDUSP4mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4.
Exploration and detection of potential regulatory variants in refractive error GWAS
Authors: Liao Xuan , Lan ChangJun , Liao Dan , Tian Jing , Huang XiuQi
Published: September 2016

Refractive error (RE) is a complex multifactorial disease. Genome-wide association studies (GWAS) have provided significant insight into the genetic architecture and identified plenty of robust genetic variations or single nucleotide polymorphisms (SNPs) associated with complex disease. A major current challenge is to convert those resources into causal variants and target genes. We used RegulomeDB and HaploReg to annotate regulatory information onto associated SNPs derived from the two largest RE GWAS, and additional SNPs in linkage disequilibrium (LD) with GWAS significant SNPs. Overall 868 SNPs were investigated, out of which 662 returned RegulomeDB scores of 1 to 6. It was observed that 36 out of those SNPs show strong evidence of regulatory effects with a RegulomeDB score of 1, while only four of them were GWAS significant SNPs (CD55/rs1652333, CNDP2/rs12971120, RDH5/rs3138142 and rs3138144). The results encourage us to explore those putative pathogenic variants, both GWAS significant SNPs as well as the SNPs in LD, for future discernment of functional consequence. This study offers the attractive approach for prioritizing potential functional variants by combining ENCODE data and GWAS information, and provide further insights into the pathogenesis and mechanism and ultimately therapeutics.