bluuebunny/crossref_metadata_2025 huggingface dataset:
Ichnology of the Callovian-Oxfordian Rocks of the Katrol Hill Range, Kachchh, Western India
Authors: Solanki Paras M. , Bhatt Nishith Y. , Patel Satish J. , Patel Jagdish M.
Published: October 2017

On the basis of distinct lithologic features such as composition, grain size, bedding characteristics and sedimentary structures, six facies were identified in Callovian to Oxfordian rocks exposed southwest of Bhuj, Kachchh. They are interbedded calcareous shale-siltstone (ICSSF), limestone (LF), ferruginous sandstone (FerSF), felspathic sandstone (FelSF), grey shale (GSF) and oolitic limestone (OLF) facies. The rich and highly diversified trace fossils reveal a wide range of animal behaviours represented by dwelling, feeding, crawling and resting structures. Horizontal feeding structures are found abundantly in all lithofacies indicating low wave and current energy and deposition of poorly sorted muddy to sandy sediments. A few coarse layers containing Arenicolites, Ophiomorpha and Skolithos indicate the presence of opportunistic animals (due to their first appearance under harsh conditions) under -intermittently moderate wave and current energy or storm wave conditions (due to coarse grain size and dominance/presence of only vertical trace fossils) in the shoreface zone. Taenidium occurs mainly in the lower shoreface to transitional zone suggesting low to moderate energy conditions. Thalassinoides occurs in middle to lower shoreface settings under relatively low-energy conditions. Zoophycos represents offshore environment, where it occupies the deepest bioturbation levels.

The characteristic lithofacies and assemblages of trace fossils in the rocks of the Chari/Jumara Formation indicate a depositional environment fluctuating from the upper shoreface to offshore zone.
Groundwater Contamination in Parts of Nalgonda District, Telangana, India as Revealed by Trace Elemental Studies
Authors: Purushotham D. , Linga D. , Sagar Netramani , Mishra Sibasish , Vinod G. Naga , Venkatesham K. , Saikrishna K.
Published: October 2017

The present paper deals with major and trace elements geochemistry of the groundwater from Nalgonda district, Telangana. The study area is very important in terms of anthropogenic activity like rapid industrial, urban development, pesticides, pharmaceutical, granite polishing and agro based industries. Inductively coupled plasma mass spectrometer (ICPMS) was employed to determine the concentration of trace elements in collected groundwater samples (bore well). These probe elements were further categorized as toxic elements (Pb, As, Cd, and V), alkaline earths (Sr and Ba), alkali metals (Li, Rb), transition metals (Cr, Mo and Ni), metallic elements (Cu, Fe, Zn, Al, Co), and other non-metallic elements (Se and Si). The groundwater quality was examined in perspective of Indian as well as World Health Organization drinking water standards. Based on the analytical results, groundwater in the study area is found to be slightly alkaline in nature and very hard, the average abundance of the major cations and anions is in the order of Ca+>Na+>Mg+>K+ and Cl−>HCO3−> CO3->SO4->NO3->F- respectively. The dominant hydro chemical facies of groundwater is Na+ - HCO3− – Cl- and Na+ - Cl- – HCO3− types.

The results of trace elements shows that concentration of Pb, As, Cd, V in collected samples exceeding the desirable limits, and in the case of alkaline, alkali, transition, non-metallic elements, seventy per cent of the samples crossed the desirable limits, but all metallic elements viz. Cu, Fe, Zn, Al, Co is within the limits as per Indian as well as World Health Organizations drinking water standards. Factor analysis results shows that seven factors emerged as a significant contributor to the groundwater contamination is about 65.32 per cent. The spatial variation maps decipher trace elemental concentrations both geogenic and anthropogenic origin, by three zones i.e. ‘low’, ‘moderate’ and ‘high’ of the study area based on environment using Arc-GIS. High concentrations of trace elements are indicative of phenomenal rise in chemical composition and likely to have its origin from silicate weathering reactions and dissolution/precipitation processes supported by rainfall and anthropogenic activities, indiscriminate use of fertilizers/pesticides, and disposal of waste and sewage, release of reactive pollutants into the atmosphere by industries. Hence, this work is of immense societal benefit in terms of prevailing human health hazards in the study area with a direct relevance to such industrially populated regions elsewhere.
Sleep-Related Painful Erections—A Case Series of 24 Patients Regarding Diagnostics and Treatment Options
Authors: Vreugdenhil Sanne , Weidenaar Alida Cornelia , de Jong Igle Jan , van Driel Mels Frank
Published: October 2017

Background

Patients with sleep-related painful erections (SRPEs) have deep penile pain during nocturnal erection that wakes them up and disturbs their nights of sleep. This rare parasomnia is poorly recognized by general practitioners and by urologists and sexologists.

Aim

To gain more insight into diagnostics and therapeutic options.

Methods

Data from a series of 24 consecutive patients who presented with SRPEs at the outpatient clinic from 1996 to 2015 were retrospectively analyzed. Additional questionnaires were completed to complement data and to obtain information about follow-up. Long-term treatment efficacy of baclofen was assessed using the Wilcoxon signed rank test.

Outcomes

SRPEs were not associated with urologic, surgical, or psychiatric history or with serum testosterone levels. The mean doctors’ delay was 3.5 years. 14 of the 24 patients were treated with baclofen (10–75 mg). In 11 of them, complete remission was observed within a few weeks. 2 of the 3 remaining patients noticed a slight improvement of SPRE symptoms and only 1 patient experienced no effect at all. After an average follow-up of 4.5 years, only 41.6% of patients who had used baclofen were satisfied with their SRPEs. The others (58.4%) were dissatisfied, mostly owing to relapse of symptoms after the discontinuation of baclofen. Other treatment forms were applied sporadically, with strongly varying results.

Clinical Implications

This overview of SRPE contributes to a better clinical understanding and recognition of the phenomenon and provides new, more constructed advice about therapeutic implications, especially concerning the use of baclofen.

Strengths and Limitations

This study provides a systematic overview of a relatively large series of patients with SRPE, which provides substantiated treatment advice. However, treatment efficacy was based mainly on the patients’ subjective perception and it was not possible to compare the results of baclofen with other forms of pharmacologic treatment, because these alternative drugs were applied only sporadically. Nevertheless, this study is directional for future research.

Conclusions

This study confirmed a long doctors’ delay in patients with SRPE. There was no association between SRPEs and comorbidity and total serum testosterone levels. Treatment with baclofen proved successful and safe in the short term. Long-term feasibility needs further investigation.
Bayesian estimation of the lethargy coefficient for probabilistic fatigue life model
Authors: Doh Jaehyeok , Lee Jongsoo
Published: October 2017

In this study, a model for probabilistic fatigue life that is based on the Zhurkov model is suggested using stochastically and statistically estimated lethargy coefficients. The fatigue life model was derived using the Zhurkov life model, and it was deterministically validated using real fatigue life data as a reference. For this process, firstly, a lethargy coefficient that is related to the failure of materials must be obtained with rupture time and stress from a quasi-static tensile test. These experiments are performed using HS40R steel. However, the lethargy coefficient has discrepancies due to the inherent uncertainty and the variation of material properties in the experiments. The Bayesian approach was employed for estimating the lethargy coefficient of the fatigue life model using the Markov Chain Monte Carlo (MCMC) sampling method and considering its uncertainties. Once the samples are obtained, one can proceed to the posterior predictive inference of the fatigue life. This life model was shown to be reasonable when compared with experimental fatigue life data. As a result, predicted fatigue life was observed to significantly decrease in accordance with increasing relative stress conditions.

Highlights Zhurkov fatigue life model is deterministically validated with experiments. Prediction of the S-N curve using Zhurkov fatigue model and lethargy coefficients. Lethargy coefficients of Zhurkov fatigue model are estimated by Bayesian updating. Bayesian updating is useful for quantifying the uncertainty of unknown parameters.
Metabotyping for the development of tailored dietary advice solutions in a European population: the Food4Me study
Authors: O’Donovan Clare B. , Walsh Marianne C. , Woolhead Clara , Forster Hannah , Celis-Morales Carlos , Fallaize Rosalind , Macready Anna L. , Marsaux Cyril F. M. , Navas-Carretero Santiago , Rodrigo San-Cristobal S. , Kolossa Silvia , Tsirigoti Lydia , Mvrogianni Christina , Lambrinou Christina P. , Moschonis George , Godlewska Magdalena , Surwillo Agnieszka , Traczyk Iwona , Drevon Christian A. , Daniel Hannelore , Manios Yannis , Martinez J. Alfredo , Saris Wim H. M. , Lovegrove Julie A. , Mathers John C. , Gibney Michael J. , Gibney Eileen R. , Brennan Lorraine
Published: October 2017

Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
Colonic and systemic effects of extruded whole-grain sorghum consumption in growing Wistar rats
Authors: Llopart Emilce E. , Cian Raúl E. , López-Oliva Muñoz María Elvira , Zuleta Ángela , Weisstaub Adriana , Drago Silvina R.
Published: October 2017

Colonic effects of extruded whole-grain sorghum diets were evaluated using a model of growing rats. In all, twenty-four male Wistar rats were fed control (C), extruded white sorghum (EWS) or red sorghum (ERS). Consumption of sorghum diets showed satiety properties, with reduction of caecal pH, and lower activity ofβ-glucosidase andβ-glucuronidase enzymes. Decreased copper zinc superoxide dismutase and manganese superoxide dismutase and increased catalase and glutathione peroxidase levels were observed in colonic mucosa. The induction of antioxidant enzymes occurred through the activation of the nuclear factor erythroid 2-related factor 2 protein and its subsequent translocation into the nucleus. ERS was able to decrease the proliferation of proximal mucosa of colon, demonstrating a possible effect against colorectal tumourigenesis. EWS increased proliferation and also apoptosis, ensuring the re-establishment of homoeostasis of the colonic mucosa. No antioxidant systemic effect (serum or hepatic level) was observed. It is likely that despite the extrusion the low bioavailability of the phenolic compounds of sorghum diets caused them to exert mainly acute effects at the colon level. Extruded whole-grain sorghum is a good functional ingredient that might be promising in dietary prevention of intestinal diseases.
The influence of dietary and supplemental calcium on postprandial effects of a high-fat meal on lipaemia, glycaemia, C-reactive protein and adiponectin in obese women
Authors: Ferreira Thaís da S. , Antunes Vanessa P. , Leal Priscila M. , Sanjuliani Antonio F. , Klein Márcia R. S. T.
Published: October 2017

Non-fasting hypertriacylglycerolaemia is a risk factor for CVD and the amount of fat in a meal seems to be the main factor influencing postprandial lipaemia. Although several studies suggest that Ca can increase faecal fat excretion, it is not known whether Ca can decrease postprandial TAG. This study aimed to evaluate the influence of dietary Ca (DC) and supplemental Ca (SC) on lipaemia, glucose metabolism, C-reactive protein (CRP) and adiponectin during postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20–50 years were randomly assigned to receive three test meals (approximately 2900 kJ; 48 % fat): high DC (547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (42 mg DC). Blood samples were collected in the fasting period and at minutes 120 and 240 after meals to evaluate total cholesterol and fractions, TAG, glucose, insulin, high-sensitivity CRP and adiponectin. Serum levels of TAG and insulin increased significantly after all test meals. Only after HSCM total cholesterol did not present a significant increase and LDL-cholesterol had a significant decrease. Postprandial glucose, HDL-cholesterol, CRP and adiponectin did not present significant changes after the three test meals. The comparative analysis of the effects of the three test meals on serum lipids, glucose, insulin, CRP and adiponectin revealed no significant meal-by-time interaction. These results suggest that in obese women challenged with a high-fat meal DC and SC do not interfere with postprandial lipaemia, glucose metabolism, CRP and adiponectin.
Morphological awareness and visual processing of derivational morphology in high-functioning adults with dyslexia: An avenue to compensation?
Authors: LAW JEREMY M. , VEISPAK ANNELI , VANDERAUWERA JOLIJN , GHESQUIÈRE POL
Published: October 2017

This study examined the processing of derivational morphology and its association with measures of morphological awareness and literacy outcomes in 30 Dutch-speaking high-functioning dyslexics, and 30 controls, matched for age and reading comprehension. A masked priming experiment was conducted where the semantic overlap between morphologically related pairs was manipulated as part of a lexical decision task. Measures of morphological awareness were assessed using a specifically designed sentence completion task. Significant priming effects were found in each group, yet adults with dyslexia were found to benefit more from the morphological structure than the controls. Adults with dyslexia were found to be influenced by both form (morpho-orthographic) and meaning (morphosemantic) properties of morphemes while controls were mainly influenced by morphosemantic properties. The reports suggest that morphological processing is intact in high-functioning dyslexics and a strength when compared to controls matched for reading comprehension and age. Thus, reports support morphological processing as a potential factor in the reading compensation of adults with dyslexia. However, adults with dyslexia performed significantly worse than controls on morphological awareness measures.
Sustainable intensification amongst Ghana's pineapple farmers: the complexity of an innovation determines the effectiveness of its training
Authors: Wuepper David , Sauer Johannes , Kleemann Linda
Published: October 2017

To foster the adoption of sustainable intensification practices amongst Ghana's farmers, they are widely promoted through training sessions provided by development organizations, companies, and the public extension service. We investigate whether these training sessions are effective and find that they are effective only for the diffusion of organic fertilizers but not for mulching. We suggest that this comes from the complexity of the innovations. Mulching is one of the simplest sustainable intensification technologies. It diffuses easily through peer learning and, after an initial training delivered to a critical mass of farmers, does not require training anymore. The use of organic fertilizers, in contrast, requires more specific knowledge and adaptation, which limits the effectiveness of peer learning and increases the effectiveness of training. This suggests that to achieve a widespread diffusion of sustainable intensification amongst Ghana's farmers, training sessions should focus on those practices that are complex and thus difficult to learn from peers.
A DIRECT SEARCH QUASI-NEWTON METHOD FOR NONSMOOTH UNCONSTRAINED OPTIMIZATION
Authors: PRICE C. J.
Published: October 2017

A direct search quasi-Newton algorithm is presented for local minimization of Lipschitz continuous black-box functions. The method estimates the gradient via central differences using a maximal frame around each iterate. When nonsmoothness prevents progress, a global direction search is used to locate a descent direction. Almost sure convergence to Clarke stationary point(s) is shown, where convergence is independent of the accuracy of the gradient estimates. Numerical results show that the method is effective in practice.
Anti-imperialism: The Leninist Legacy and the Fate of World Revolution
Authors: Friedman Jeremy , Rutland Peter
Published: October 2017

The most important of Lenin's writings was, arguably,Imperialism: the Highest Stage of Capitalism.That work shifted the focus from workers’ struggles within one country to the dynamics of capitalism as a global system. The Leninist project thereby inextricably linked the causes of economic justice and national liberation, a fateful step in light of the transformation of the world wrought by decolonization. As capitalism stumbles through yet another global crisis today, what parts of Lenin's fevered vision remain relevant 100 years later?
Violence to Velvet: Revolutions—1917 to 2017
Authors: Markwick Roger D.
Published: October 2017

From their inception, the 1917 Russian Revolutions, specifically the October Revolution, have been synonymous with Bolshevik violence. In the course of the last century, almost all observers have believed that violence was inherent in the Russian revolutions and revolutions generally. Such views have obscured what a revolution actually is. Closer examination of the October Revolution confirms violence was not its defining feature. Further, the Bolsheviks conceived October as the opening salvo of international, socialist revolution; expectations largely crushed by overwhelming counter-revolutionary violence. The discrediting of war and political violence since World War II has seen the conception of revolution as a “velvet” process of political transformation emerge, particularly in Latin America, the US, Britain, and Europe. While such movements rarely look back to the Russian Revolutions, they echo the democratic, egalitarian, and emancipatory impulses bequeathed by 1917, and raise the possibility of near non-violent socialist revolutions.
Women and Gender in 1917
Authors: Ruthchild Rochelle Goldberg
Published: October 2017

This paper argues for greater integration of considerations of women and gender in the history of the 1917 Russian Revolutions. Two key issues have long been discussed by historians: the spontaneity/consciousness paradigm, and the role of class in the revolution. Neither has been adequately analyzed in relation to gender. Women's suffrage has been largely neglected despite the fact that it was a significant issue throughout the year and represented a pioneering advance won by a countrywide coalition of women and men from the working class and intelligentsia, and from almost all political parties. In this centennial year, accounts of the Revolution remain one-dimensional; women remain the other.
1917: Revolution as Demobilization and State Collapse
Authors: Lohr Eric , Sanborn Joshua
Published: October 2017

Our essay proposes that while the predominant concept of revolution as driven by the mobilization of social, political, and cultural forces has value, at least as important for understanding the revolutions of 1917 was the dramatic demobilization of army, police, state, and society. We suggest that revolutions often see a conflict between affective mobilization (in which some portion of the citizenry becomes much more enthusiastic about particular social and political projects) and structural demobilization (in which the failure of major state institutions and economic enterprises makes positive social and political change nearly impossible). In early 1917, affective mobilization on behalf of the war and the regime was in decline, but structural mobilization was at its peak. The February Revolution brought a sudden radical structural demobilization. This structural demobilization both made it possible for relatively modest numbers of revolutionary forces to succeed in October 1917 and made the emergence of widespread apathy and disillusionment in 1918 much more likely.
DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment
Authors: Mathot P , Grandin M , Devailly G , Souaze F , Cahais V , Moran S , Campone M , Herceg Z , Esteller M , Juin P , Mehlen P , Dante R
Published: October 2017

Breast cancer-associated fibroblasts (CAFs) have a crucial role in tumor initiation, metastasis and therapeutic resistance by secreting various growth factors, cytokines, protease and extracellular matrix components. Soluble factors secreted by CAFs are involved in many pathways including inflammation, metabolism, proliferation and epigenetic modulation, suggesting that CAF-dependent reprograming of cancer cells affects a large set of genes. This paracrine signaling has an important role in tumor progression, thus deciphering some of these processes could lead to relevant discoveries with subsequent clinical implications. Here, we investigated the mechanisms underlying the changes in gene expression patterns associated with the cross-talk between breast cancer cells and the stroma. From RNAseq data obtained from breast cancer cell lines grown in presence of CAF-secreted factors, we identified 372 upregulated genes, exhibiting an expression level positively correlated with the stromal content of breast cancer specimens. Furthermore, we observed that gene expression changes were not mediated through significant DNA methylation changes. Nevertheless, CAF-secreted factors but also stromal content of the tumors remarkably activated specific genes characterized by a DNA methylation pattern: hypermethylation at transcription start site and shore regions. Experimental approaches (inhibition of DNA methylation, knockdown of methyl-CpG-binding domain protein 2 and chromatin immunoprecipitation assays) indicated that this set of genes was epigenetically controlled. These data elucidate the importance of epigenetics marks in the cancer cell reprogramming induced by stromal cell and indicated that the interpreters of the DNA methylation signal have a major role in the response of the cancer cells to the microenvironment.
Erratum: Self-assembly of ordered graphene nanodot arrays
Authors: Camilli Luca , Jørgensen Jakob H. , Tersoff Jerry , Stoot Adam C. , Balog Richard , Cassidy Andrew , Sadowski Jerzy T. , Bøggild Peter , Hornekær Liv
Published: October 2017

Change History: A correction to this article has been published and is linked from the HTML version of this article.
Real-time observation of polymerase-promoter contact remodeling during transcription initiation
Authors: Meng Cong A. , Fazal Furqan M. , Block Steven M.
Published: October 2017

Critical contacts made between the RNA polymerase (RNAP) holoenzyme and promoter DNA modulate not only the strength of promoter binding, but also the frequency and timing of promoter escape during transcription. Here, we describe a single-molecule optical-trapping assay to study transcription initiation in real time, and use it to map contacts formed between σ70 RNAP holoenzyme from E. coli and the T7A1 promoter, as well as to observe the remodeling of those contacts during the transition to the elongation phase. The strong binding contacts identified in certain well-known promoter regions, such as the −35 and −10 elements, do not necessarily coincide with the most highly conserved portions of these sequences. Strong contacts formed within the spacer region (−10 to −35) and with the −10 element are essential for initiation and promoter escape, respectively, and the holoenzyme releases contacts with promoter elements in a non-sequential fashion during escape.
Hydrogen substituted graphdiyne as carbon-rich flexible electrode for lithium and sodium ion batteries
Authors: He Jianjiang , Wang Ning , Cui Zili , Du Huiping , Fu Lin , Huang Changshui , Yang Ze , Shen Xiangyan , Yi Yuanping , Tu Zeyi , Li Yuliang
Published: October 2017

Organic electrodes are potential alternatives to current inorganic electrode materials for lithium ion and sodium ion batteries powering portable and wearable electronics, in terms of their mechanical flexibility, function tunability and low cost. However, the low capacity, poor rate performance and rapid capacity degradation impede their practical application. Here, we concentrate on the molecular design for improved conductivity and capacity, and favorable bulk ion transport. Through an in situ cross-coupling reaction of triethynylbenzene on copper foil, the carbon-rich frame hydrogen substituted graphdiyne film is fabricated. The organic film can act as free-standing flexible electrode for both lithium ion and sodium ion batteries, and large reversible capacities of 1050 mAh g−1 for lithium ion batteries and 650 mAh g−1 for sodium ion batteries are achieved. The electrode also shows a superior rate and cycle performances owing to the extended π-conjugated system, and the hierarchical pore bulk with large surface area.
Aromatic C-H addition of ketones to imines enabled by manganese catalysis
Authors: Zhou Bingwei , Hu Yuanyuan , Liu Ting , Wang Congyang
Published: October 2017

Selectivity control of varied C–H bonds in a complex molecule is a long-standing goal and still a great challenge in C–H activation field. Most often, such selectivity is achieved by the innate reactivity of different C–H bonds. In this context, the classic Mannich reaction of acetophenone derivatives and imines is ascribed to the more reactive C(sp3)–H bonds α to the carbonyl, with the much less reactive aromatic C(sp2)–H bonds remaining intact. Herein we report an aromatic C(sp2)–H addition of ketones to imines enabled by manganese catalysis, which totally reverses the innate reactivity of C–H bonds α to the carbonyl and those on the aromatic ring. Diverse products of ortho-C–H aminoalkylated ketones, cyclized exo-olefinic isoindolines, and three-component methylated isoindolines can be successfully accessed under mild reaction conditions, which significantly expands the synthetic utilities of ketones as simple bulk chemicals.
Inequality in genetic cancer risk suggests bad genes rather than bad luck
Authors: Stensrud Mats Julius , Valberg Morten
Published: October 2017

Heritability is often estimated by decomposing the variance of a trait into genetic and other factors. Interpreting such variance decompositions, however, is not straightforward. In particular, there is an ongoing debate on the importance of genetic factors in cancer development, even though heritability estimates exist. Here we show that heritability estimates contain information on the distribution of absolute risk due to genetic differences. The approach relies on the assumptions underlying the conventional heritability of liability model. We also suggest a model unrelated to heritability estimates. By applying these strategies, we describe the distribution of absolute genetic risk for 15 common cancers. We highlight the considerable inequality in genetic risk of cancer using different metrics, e.g., the Gini Index and quantile ratios which are frequently used in economics. For all these cancers, the estimated inequality in genetic risk is larger than the inequality in income in the USA.
Bioluminescence imaging of G protein-coupled receptor activation in living mice
Authors: Kono Mari , Conlon Elizabeth G. , Lux Samantha Y. , Yanagida Keisuke , Hla Timothy , Proia Richard L.
Published: October 2017

G protein-coupled receptors (GPCRs), a superfamily of cell-surface receptors involved in virtually all physiological processes, are the major target class for approved drugs. Imaging GPCR activation in real time in living animals would provide a powerful way to study their role in biology and disease. Here, we describe a mouse model that enables the bioluminescent detection of GPCR activation in real time by utilizing the clinically important GPCR, sphingosine-1-phosphate receptor 1 (S1P1). A synthetic S1P1 signaling pathway, designed to report the interaction between S1P1 and β-arrestin2 via the firefly split luciferase fragment complementation system, is genetically encoded in these mice. Upon receptor activation and subsequent β-arrestin2 recruitment, an active luciferase enzyme complex is produced, which can be detected by in vivo bioluminescence imaging. This imaging strategy reveals the dynamics and spatial specificity of S1P1 activation in normal and pathophysiologic contexts in vivo and can be applied to other GPCRs.
Taxonomic and functional turnover are decoupled in European peat bogs
Authors: Robroek Bjorn J. M. , Jassey Vincent E. J. , Payne Richard J. , Martí Magalí , Bragazza Luca , Bleeker Albert , Buttler Alexandre , Caporn Simon J. M. , Dise Nancy B. , Kattge Jens , Zając Katarzyna , Svensson Bo H. , van Ruijven Jasper , Verhoeven Jos T. A.
Published: October 2017

In peatland ecosystems, plant communities mediate a globally significant carbon store. The effects of global environmental change on plant assemblages are expected to be a factor in determining how ecosystem functions such as carbon uptake will respond. Using vegetation data from 56 Sphagnum-dominated peat bogs across Europe, we show that in these ecosystems plant species aggregate into two major clusters that are each defined by shared response to environmental conditions. Across environmental gradients, we find significant taxonomic turnover in both clusters. However, functional identity and functional redundancy of the community as a whole remain unchanged. This strongly suggests that in peat bogs, species turnover across environmental gradients is restricted to functionally similar species. Our results demonstrate that plant taxonomic and functional turnover are decoupled, which may allow these peat bogs to maintain ecosystem functioning when subject to future environmental change.
Multi-modal mechanophores based on cinnamate dimers
Authors: Zhang Huan , Li Xun , Lin Yangju , Gao Fei , Tang Zhen , Su Peifeng , Zhang Wenke , Xu Yuanze , Weng Wengui , Boulatov Roman
Published: October 2017

Mechanochemistry offers exciting opportunities for molecular-level engineering of stress-responsive properties of polymers. Reactive sites, sometimes called mechanophores, have been reported to increase the material toughness, to make the material mechanochromic or optically healable. Here we show that macrocyclic cinnamate dimers combine these productive stress-responsive modes. The highly thermally stable dimers dissociate on the sub-second timescale when subject to a stretching force of 1–2 nN (depending on isomer). Stretching a polymer of the dimers above this force more than doubles its contour length and increases the strain energy that the chain absorbs before fragmenting by at least 600 kcal per mole of monomer. The dissociation produces a chromophore and dimers are reformed upon irradiation, thus allowing optical healing of mechanically degraded parts of the material. The mechanochemical kinetics, single-chain extensibility, toughness and potentially optical properties of the dissociation products are tunable by synthetic modifications.
Montessori education: a review of the evidence base
Authors: Marshall Chloë
Published: October 2017

The Montessori educational method has existed for over 100 years, but evaluations of its effectiveness are scarce. This review paper has three aims, namely to (1) identify some key elements of the method, (2) review existing evaluations of Montessori education, and (3) review studies that do not explicitly evaluate Montessori education but which evaluate the key elements identified in (1). The goal of the paper is therefore to provide a review of the evidence base for Montessori education, with the dual aspirations of stimulating future research and helping teachers to better understand whether and why Montessori education might be effective.
Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells
Authors: Park Hae-Young , Tan Peck S. , Kavishna Ranmali , Ker Anna , Lu Jinhua , Chan Conrad E. Z. , Hanson Brendon J. , MacAry Paul A. , Caminschi Irina , Shortman Ken , Alonso Sylvie , Lahoud Mireille H.
Published: October 2017

Targeting model antigens (Ags) to Clec9A on DC has been shown to induce, not only cytotoxic T cells, but also high levels of Ab. In fact, Ab responses against immunogenic Ag were effectively generated even in the absence of DC-activating adjuvants. Here we tested if targeting weakly immunogenic putative subunit vaccine Ags to Clec9A could enhance Ab responses to a level likely to be protective. The proposed “universal” influenza Ag, M2e and the enterovirus 71 Ag, SP70 were linked to anti-Clec9A Abs and injected into mice. Targeting these Ags to Clec9A greatly increased Ab titres. For optimal responses, a DC-activating adjuvant was required. For optimal responses, a boost injection was also needed, but the high Ab titres against the targeting construct blocked Clec9A-targeted boosting. Heterologous prime-boost strategies avoiding cross-reactivity between the priming and boosting targeting constructs overcame this limitation. In addition, targeting small amounts of Ag to Clec9A served as an efficient priming for a conventional boost with higher levels of untargeted Ag. Using this Clec9A-targeted priming, conventional boosting strategy, M2e immunisation protected mice from infection with lethal doses of influenza H1N1 virus.
Dual Biomembrane Force Probe enables single-cell mechanical analysis of signal crosstalk between multiple molecular species
Authors: Ju Lining , Chen Yunfeng , Li Kaitao , Yuan Zhou , Liu Baoyu , Jackson Shaun P. , Zhu Cheng
Published: October 2017

Conventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter the molecules from their native state on the cell; 2) Long processing time before the final readout makes it difficult to capture transient signaling events (<1 min); 3) The experimental environments are force-free, therefore unable to visualize mechanical signals in real time. In contrast to these methods in biochemistry and cell biology that are usually population-averaged and non-real-time, here we introduce a novel single-cell based nanotool termed dual biomembrane force probe (dBFP). The dBFP provides precise controls and quantitative readouts in both mechanical and chemical terms, which is particularly suited for juxtacrine signaling and mechanosensing studies. Specifically, the dBFP allows us to analyze dual receptor crosstalk by quantifying the spatiotemporal requirements and functional consequences of the up- and down-stream signaling events. In this work, the utility and power of the dBFP has been demonstrated in four important dual receptor systems that play key roles in immunological synapse formation, shear-dependent thrombus formation, and agonist-driven blood clotting.
Postprandial Blood Glucose Outweighs Fasting Blood Glucose and HbA1c in screening Coronary Heart Disease
Authors: Jiang Jingjing , Zhao Lin , Lin Liu , Gui Minghui , Aleteng Qiqige , Wu Bingjie , Wang Shanshan , Pan Baishen , Ling Yan , Gao Xin
Published: October 2017

The objective of the present study is to assess the performance of fasting blood glucose (FBG), postprandial blood glucose (PBG), and glycated hemoglobin (HbA1c) as screening for coronary heart disease (CHD) in an inpatient population undergoing coronary angiography. 1852 consecutive patients scheduled for coronary angiography were classified into Normal Glucose Tolerance (NGT), Impaired Glucose Regulation (IGR), and diabetes, based on FBG, PBG, and HbA1c. Correlations of Gensini score with glucose metabolism and insulin resistance were analyzed. The associations between glycemic variables and Gensini score or the presence of CHD were analyzed by multiple linear regression and logistic regression, respectively. CHD was diagnosed in 488, 622, and 414 patients with NGT, IGR, and diabetes, respectively. Gensini score was positively correlated with FBG (r = 0.09, p < 0.01), PBG (r = 0.20, p < 0.01), and HbA1c (r = 0.19, p < 0.01). Gensini score was not correlated with fasting insulin (r = −0.081, p = 0.36), post-prandial insulin (r = −0.02, p = 0.61), or HOMAIR (r = −0.0059, p = 0.13). When FBG, PBG and HbA1c were pooled altogether, only PBG persisted in its association with Gensini score and the prevalence of CHD. The severity of CHD was associated with glucose rather than insulin resistance in this Chinese population. PBG was optimally correlated with the presence and severity of CHD.
Imaging Monitoring of Kupffer Cell Function and Hepatic Oxygen Saturation in Preneoplastic Changes During Cholangiocarcinogenesis
Authors: Lee Seunghyun , Kim Jung Hoon , Lee Jeong Hwa , Zen Yoh , Han Joon Koo
Published: October 2017

We investigated serial changes of the Kupffer cell (KC) function and hepatic oxygen saturation (sO2) using contrast-enhanced ultrasound imaging (CEUS) and photoacoustic imaging (PAI) in preneoplastic changes during cholangiocarcinogenesis induced by obstructive cholangitis and N-nitrosodimethylamine in a mouse model. The CEUS and PAI were performed to assess Sonazoid contrast agent uptake by KC and changes in the sO2 of liver parenchyma. An extensive bile ductular reaction, cystic dilatation, and epithelial hyperplasia with dysplastic changes were noted in the experimental group. During the preneoplastic changes, the parenchymal echogenicity on the Kupffer-phase of CEUS was continuously decreased in the experimental group, and which means that the Sonazoid phagocytosis by KC was decreased. The number of KCs was increased in the CD68 analysis, indicating functionally impaired KCs. There was a simultaneous serial decrease in sO2 on PAI measurement of the experimental group during the preneoplastic changes. The experimental group also showed significantly higher expression of hypoxia-inducible factor-1α and vascular endothelial growth factor protein. Our study demonstrated that KC dysfunction and hypoxic environmental changes were the factors influencing preneoplastic change during cholangiocarcinogenesis, and we could non-invasively monitor these changes using CEUS and PAI.
Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington’s disease mice
Authors: Bondulich Marie K. , Jolinon Nelly , Osborne Georgina F. , Smith Edward J. , Rattray Ivan , Neueder Andreas , Sathasivam Kirupa , Ahmed Mhoriam , Ali Nadira , Benjamin Agnesska C. , Chang Xiaoli , Dick James R. T. , Ellis Matthew , Franklin Sophie A. , Goodwin Daniel , Inuabasi Linda , Lazell Hayley , Lehar Adam , Richard-Londt Angela , Rosinski Jim , Smith Donna L. , Wood Tobias , Tabrizi Sarah J. , Brandner Sebastian , Greensmith Linda , Howland David , Munoz-Sanjuan Ignacio , Lee Se-Jin , Bates Gillian P.
Published: October 2017

Huntington’s disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Weekly administration from 5 to 11 weeks of age prevented body weight loss, skeletal muscle atrophy, muscle weakness, contractile abnormalities, the loss of functional motor units in EDL muscles and delayed end-stage disease. Inhibition of myostatin/activin A signaling activated transcriptional profiles to increase muscle mass in wild type and R6/2 mice but did little to modulate the extensive Huntington’s disease-associated transcriptional dysregulation, consistent with treatment having little impact on HTT aggregation levels. Modalities that inhibit myostatin signaling are currently in clinical trials for a variety of indications, the outcomes of which will present the opportunity to assess the potential benefits of targeting this pathway in HD patients.
Circulating Haptoglobin and Metabolic Syndrome in Renal Transplant Recipients
Authors: Minović Isidor , Eisenga Michele F. , Riphagen Ineke J. , van den Berg Else , Kootstra-Ros Jenny , Frenay Anne-Roos S. , van Goor Harry , Rimbach Gerald , Esatbeyoglu Tuba , Levy Andy P. , Gaillard Carlo A. J. M. , Geleijnse Johanna M. , Eggersdorfer Manfred L. , Navis Gerjan J. , Kema Ido P. , Bakker Stephan J. L.
Published: October 2017

Haptoglobin (Hp) is an acute phase protein that has recently been linked to components of the metabolic syndrome (MetS). We aimed to evaluate Hp as marker of MetS, and to assess its association with long-term outcome in renal transplant recipients (RTR). We measured plasma Hp in a prospective cohort of 699 stable RTR and 149 healthy controls. Median plasma Hp concentration in RTR was 1.4 [interquartile range (IQR), 1.0–1.8] g/L, which was higher compared to 1.1 [0.9–1.4] g/L in controls (P < 0.001). Hp was independently associated with the MetS (β = 0.10) (P = 0.005). During follow-up of 5.4 [4.8–6.1] years, 150 (21%) recipients died, of whom 60 (9%) due to cardiovascular causes, and 83 (12%) RTR developed graft failure. High (≥2.0 g/L) and low (≤0.9 g/L) plasma Hp were associated with increased risk of mortality (HR’s 2.3 [1.3–4.1] and 1.9 [1.0–3.5], resp.), predominantly cardiovascular. The association of high Hp lost significance upon adjustment for inflammation markers (HR 1.5 [0.8–2.7]), while low Hp was independently associated with mortality (HR 2.2 [1.2–4.0]). Hp was not associated with graft failure (P = 0.49). In conclusion, plasma Hp is independently associated with MetS in RTR. Importantly, high and low Hp are associated with increased mortality risk, independent of MetS.
Norrin protects optic nerve axons from degeneration in a mouse model of glaucoma
Authors: Leopold Stephanie A. , Zeilbeck Ludwig F. , Weber Gregor , Seitz Roswitha , Bösl Michael R. , Jägle Herbert , Fuchshofer Rudolf , Tamm Ernst R. , Ohlmann Andreas
Published: October 2017

Norrin is a secreted signaling molecule activating the Wnt/β-catenin pathway. Since Norrin protects retinal neurons from experimental acute injury, we were interested to learn if Norrin attenuates chronic damage of retinal ganglion cells (RGC) and their axons in a mouse model of glaucoma. Transgenic mice overexpressing Norrin in the retina (Pax6-Norrin) were generated and crossed with DBA/2J mice with hereditary glaucoma and optic nerve axonal degeneration. One-year old DBA/2J/Pax6-Norrin animals had significantly more surviving optic nerve axons than their DBA/2J littermates. The protective effect correlated with an increase in insulin-like growth factor (IGF)-1 mRNA and an enhanced Akt phosphorylation in DBA/2J/Pax6-Norrin mice. Both mouse strains developed an increase in intraocular pressure during the second half of the first year and marked degenerative changes in chamber angle, ciliary body and iris structure. The degenerations were slightly attenuated in the chamber angle of DBA/2J/Pax6-Norrin mice, which showed a β-catenin increase in the trabecular meshwork. We conclude that high levels of Norrin and the subsequent constitutive activation of Wnt/β-catenin signaling in RGC protect from glaucomatous axonal damage via IGF-1 causing increased activity of PI3K-Akt signaling. Our results identify components of a protective signaling network preventing degeneration of optic nerve axons in glaucoma.
Fluorescence-based cell-specific detection for laser-capture microdissection in human brain
Authors: Rocco Brad R. , Oh Hyunjung , Shukla Rammohan , Mechawar Naguib , Sibille Etienne
Published: October 2017

Cell-specific molecular investigations of the human brain are essential for understanding the neurobiology of diseases, but are hindered by postmortem conditions and technical challenges. To address these issues we developed a multi-label fluorescence in situ hybridization protocol and a novel optical filter device to identify cell types and control for tissue autofluorescence. We show that these methods can be used with laser-capture microdissection for human brain tissue cell-specific molecular analysis.
Comparative analysis of mitochondrial genomes of geographic variants of the gypsy moth, Lymantria dispar, reveals a previously undescribed genotypic entity
Authors: Djoumad Abdelmadjid , Nisole Audrey , Zahiri Reza , Freschi Luca , Picq Sandrine , Gundersen-Rindal Dawn E. , Sparks Michael E. , Dewar Ken , Stewart Don , Maaroufi Halim , Levesque Roger C. , Hamelin Richard C. , Cusson Michel
Published: October 2017

The gypsy moth, Lymantria dispar L., is one of the most destructive forest pests in the world. While the subspecies established in North America is the European gypsy moth (L. dispar dispar), whose females are flightless, the two Asian subspecies, L. dispar asiatica and L. dispar japonica, have flight-capable females, enhancing their invasiveness and warranting precautionary measures to prevent their permanent establishment in North America. Various molecular tools have been developed to help distinguish European from Asian subspecies, several of which are based on the mitochondrial barcode region. In an effort to identify additional informative markers, we undertook the sequencing and analysis of the mitogenomes of 10 geographic variants of L. dispar, including two or more variants of each subspecies, plus the closely related L. umbrosa as outgroup. Several regions of the gypsy moth mitogenomes displayed nucleotide substitutions with potential usefulness for the identification of subspecies and/or geographic origins. Interestingly, the mitogenome of one geographic variant displayed significant divergence relative to the remaining variants, raising questions about its taxonomic status. Phylogenetic analyses placed this population from northern Iran as basal to the L. dispar clades. The present findings will help improve diagnostic tests aimed at limiting risks of AGM invasions.