bluuebunny/crossref_metadata_2025 huggingface dataset:
The complacency of legality: Constitutionalist vulnerabilities to populist constituent power
Authors: Scholtes Julian
Published: April 2019

What role do public law and liberal constitutionalism play in an era of political populism? This article approaches this question by exploring the concept of constituent power in the light of recent constitutional developments in countries with populist governments. It attempts to outline and contrast conceptions of constituent power as inherent in liberal constitutionalist and populist thinking, respectively. While constitutionalists draw heavily upon Kelsenian normativism in framing the way political power is generated, populists juxtapose this with a concept of constituent power that is inspired by Carl Schmitt’s ‘decisionist’ view. The complacency of legality inherent in liberal constitutionalist thinking is susceptible to a populist challenge that draws attention to the necessity for the social embeddedness of any legal order. Populism, it is argued, exposes a core tension inherent in constitutionalism: How do constitutionalists reconcile their democratic aspirations with the simultaneous preclusion of certain political choices from the democratic realm? Populists can attack constitutionalism also because of the deficient conception of constituent power that underlies the latter. The article concludes that, where challenged by populists, public law can at some point no longer rely on its own force to defend itself. Its authority needs to be re-established from an extra-legal, pre-positive perspective. In an era of political populism, constitutionalist public law becomes a discourse that can challenge populism by means of the powerful reasons that inhere in the former.
Molla Sali v. Greece (Eur. Ct. H.R.)
Authors: Cerna Christina M.
Published: April 2019

President Guido Raimondi, the president of the European Court of Human Rights (European Court), in his address on January 25, 2019, at the opening of the Court's judicial year, singled out the case of Molla Sali v. Greece, concerning the application of Sharia law by the Greek courts, as one of the leading judgments of 2018. The judgment, he noted, gave rise to erroneous interpretations, with some commentators suggesting that the Court wanted to pave the way for the application of Sharia law in Europe, when in his view, the judgment leads to precisely the opposite conclusion.
Navalnyy v. Russia (Eur. Ct. H.R.)
Authors: Heri Corina
Published: April 2019

On November 15, 2018, the European Court of Human Rights (ECtHR) issued its judgment in Navalnyy v. Russia. The applicant in the case argued that the Russian authorities had targeted him for arrest and administrative sanctions because of his political activism. In its judgment, the Grand Chamber confirmed its recent change in approach to Article 18 of the European Convention on Human Rights (ECHR), including the normalization of the provision's scope and burden of proof. However, it displayed continued uncertainty about how to deal with measures based on a mixture of legitimate and illegitimate purposes.
Stability analysis of a particle band on the fluid–fluid interface
Authors: Hooshanginejad Alireza , Druecke Benjamin C. , Lee Sungyon
Published: April 2019

We present experiments and theory for viscous fingering of a suspension of non-colloidal particles undergoing radial flow in a Hele-Shaw cell. As the suspension displaces air, shear-induced migration causes particles to move faster than the average suspension velocity and to accumulate on the suspension–air interface. The resultant particle accumulation generates a pattern in which low-concentration, low-viscosity suspension displaces high-concentration, high-viscosity suspension and is unstable due to the classic Saffman–Taylor instability mechanism. While the destabilising mechanism is well-understood, what remains unknown is the stabilising mechanism that suppresses fine fingers characteristic of miscible fingering. In this work, we demonstrate how the stable suspension–air interface interacts with the unstable miscible interface to set the critical wavelength. We present a linear stability analysis for the time-dependent radial flow and show that the wavenumber predicted by the analysis is in good agreement with parametric experiments investigating the effect of suspension concentration and gap thickness of the Hele-Shaw cell.
APARTMENT COMPOUNDS, HOUSEHOLDS, AND POPULATION IN THE ANCIENT CITY OF TEOTIHUACAN, MEXICO
Authors: Smith Michael E. , Chatterjee Abhishek , Huster Angela C. , Stewart Sierra , Forest Marion
Published: April 2019

We present three new analyses of existing data from past fieldwork at Teotihuacan. First, we confirm and refine the wealth-based housing typology of Millon's Teotihuacan Mapping Project (TMP). Second, we analyze the spatial configurations of excavated compounds, using network methods to identify the size and layout of individual dwellings within walled compounds. Third, we use those results to generate the first population estimate for the city based on measurements from the TMP map. We extrapolate the average sizes of dwellings from excavated compounds to the entire sample of mapped residences as depicted on the TMP map of the city. We generate a range of population estimates, of which we suggest that 100,000 persons is the most reasonable estimate for the Xolalpan-Metepec population of Teotihuacan. These analyses show that legacy data from fieldwork long past can be used to answer research questions that are relevant and important today.
The Effect of Ozone Shadowing on the D Region Ionosphere During Sunrise
Authors: Macotela Edith L. , Clilverd Mark A. , Manninen Jyrki , Thomson Neil R. , Newnham David A. , Raita Tero
Published: April 2019

Diurnal very low frequency subionospheric radio wave phase measurements show a night‐to‐day transition pattern. During this sunrise transition a phase perturbation, which consist of a phase overshoot followed by a small phase recovery to normal daytime values, is often observed. The variability of the size of this sunrise phase perturbation and its maximum and end times were monitored to identify the associated physical causes. Very low frequency signal from the 22.1‐kHz UK transmitter (call sign GVT) recorded at Sodankylä, Finland, from 20 April 2010 to 31 December 2016 were used. The timing at the maximum of the phase perturbation period has an annual pattern that is well described by the seasonal variation of the sunrise time 28 km above the transmitter. Variations in ozone number density at 38–42‐km altitudes are better correlated (R = 0.7) with the sunrise phase perturbation variability than at any other altitudes below ~80 km, and exhibit higher correlation values than for atmospheric temperature. Our results show that the main characteristics of the observed very low frequency sunrise phase perturbation arise from shadowing of short‐wavelength solar UV flux from the D region ionosphere due to stratospheric ozone absorption.
STIL: a multi-function protein required for dopaminergic neural proliferation, protection, and regeneration
Authors: Li Lei , Liu Congcong , Carr Aprell L.
Published: April 2019

Degeneration of dopaminergic (DA) neurons in the brain is the major cause for Parkinson’s disease (PD). While genetic loci and cellular pathways involved in DA neuron proliferation have been well documented, the genetic and molecular and cellular basis of DA cell survival remains to be elucidated. Recently, studies aimed to uncover the mechanisms of DA neural protection and regeneration have been reported. One of the most recent discoveries, i.e., multi-function of human oncogene SCL/TAL interrupting locus (Stil) in DA cell proliferation, neural protection, and regeneration, created a new field for studying DA cells and possible treatment of PD. In DA neurons, Stil functions through the Sonic hedgehog (Shh) pathway by releasing the inhibition of SUFU to GLI1, and thereby enhances Shh-target gene transcription required for neural proliferation, protection, and regeneration. In this review article, we will highlight some of the new findings from researches relate to Stil in DA cells using zebrafish models and cultured mammalian PC12 cells. The findings may provide the proof-of-concept for the development of Stil as a tool for diagnosis and/or treatment of human diseases, particularly those caused by DA neural degeneration.
Reliability of colour and hardness clinical examinations in detecting dentine caries severity: a systematic review and meta-analysis
Authors: Hon Larry , Mohamed Ahmed , Lynch Edward
Published: April 2019

Dental caries is the most common human infectious disease and is caused by microorganisms producing acids, resulting in changes in dental tissue hardness and colour. However, the accuracy and reliability of dentine colour and hardness as indicators for carious lesion severity has never been assessed in a systematic review. By applying strict criteria, only seven papers (five randomized control trials and two diagnostic studies) were considered for full text qualitative and quantitative assessment. Only three studies produced high quality evidence and only four articles were considered for meta-analysis, as these provided log10 colony forming units (CFU) data from caries biopsies following colour and hardness clinical examinations. When comparing the amount of CFU isolated from carious biopsies from different colour and hardness categories, hardness clinical examination was found to be a statistically more discriminate test than colour clinical examination. Therefore, hardness clinical examination is more specific and reliable than colour to detect dentine carious lesion severity. Further large carefully designed clinical studies are needed to consolidate the findings of this systematic review.
Chemical variability of artificial stone powders in relation to their health effects
Authors: Di Benedetto Francesco , Giaccherini Andrea , Montegrossi Giordano , Pardi Luca A. , Zoleo Alfonso , Capolupo Ferdinando , Innocenti Massimo , Lepore Giovanni O. , d’Acapito Francesco , Capacci Fabio , Poli Carla , Iaia Tonina Enza , Buccianti Antonella , Romanelli Maurizio
Published: April 2019

The occurrence of highly severe silica-related diseases among the resin- and silica-based artificial stone workers was claimed, associated to an extremely short latency. High levels of exposure and intrinsic properties of AS are thought to modulate the development of silicosis and auto-immune diseases. This study compares parent materials and processed dusts, to shed light on changes of AS occurring in the manufacturing process, through an XRF, EPR and XAS investigation. We point out the extremely wide variability of the materials, the occurrence of chemical signatures impressed by the processing techniques, and the unprecedented generation of stable radicals associated to the lysis of the Si-O chemical bond inside the resin coated respirable crystalline silica. These results suggest that the AS processing in industrial stone workshops can create respirable dusts with peculiar physical and chemical properties, to be correlated to the observed clinical evidences.
Savanna in equatorial Borneo during the late Pleistocene
Authors: Wurster Christopher M. , Rifai Hamdi , Zhou Bin , Haig Jordahna , Bird Michael I.
Published: April 2019

Equatorial Southeast Asia is a key region for global climate change. Here, the Indo-Pacific Warm Pool (IPWP) is a critical driver of atmospheric convection that plays a dominant role in global atmospheric circulation. However, fluctuating sea-levels during the Pleistocene produced the most drastic land-sea area changes on Earth, with the now-drowned continent of Sundaland being exposed as a contiguous landmass for most of the past 2 million years. How vegetation responded to changes in rainfall that resulted from changing shelf exposure and glacial boundary conditions in Sundaland remains poorly understood. Here we use the stable carbon isotope composition (δ13C) of bat guano and High Molecular Weight n-alkanes, from Saleh Cave in southern Borneo to demonstrate that open vegetation existed during much the past 40,000 yrs BP. This location is at the southern equatorial end of a hypothesized ‘savanna corridor’ and the results provide the strongest evidence yet for its existence. The corridor would have operated as a barrier to east-west dispersal of rainforest species, and a conduit for north-south dispersal of savanna species at times of lowered sea level, explaining many modern biogeographic patterns. The Saleh Cave record also exhibits a strong correspondence with insolation and sea surface temperatures of the IPWP, suggesting a strong sensitivity of vegetation to tropical climate change on glacial/interglacial timeframes.
Barley yield formation under abiotic stress depends on the interplay between flowering time genes and environmental cues
Authors: Wiegmann Mathias , Maurer Andreas , Pham Anh , March Timothy J. , Al-Abdallat Ayed , Thomas William T. B. , Bull Hazel J. , Shahid Mohammed , Eglinton Jason , Baum Michael , Flavell Andrew J. , Tester Mark , Pillen Klaus
Published: April 2019

Since the dawn of agriculture, crop yield has always been impaired through abiotic stresses. In a field trial across five locations worldwide, we tested three abiotic stresses, nitrogen deficiency, drought and salinity, using HEB-YIELD, a selected subset of the wild barley nested association mapping population HEB-25. We show that barley flowering time genes Ppd-H1, Sdw1, Vrn-H1 and Vrn-H3 exert pleiotropic effects on plant development and grain yield. Under field conditions, these effects are strongly influenced by environmental cues like day length and temperature. For example, in Al-Karak, Jordan, the day length-sensitive wild barley allele of Ppd-H1 was associated with an increase of grain yield by up to 30% compared to the insensitive elite barley allele. The observed yield increase is accompanied by pleiotropic effects of Ppd-H1 resulting in shorter life cycle, extended grain filling period and increased grain size. Our study indicates that the adequate timing of plant development is crucial to maximize yield formation under harsh environmental conditions. We provide evidence that wild barley alleles, introgressed into elite barley cultivars, can be utilized to support grain yield formation. The presented knowledge may be transferred to related crop species like wheat and rice securing the rising global food demand for cereals.
Insight into the microbial world of Bemisia tabaci cryptic species complex and its relationships with its host
Authors: Wang Hua-Ling , Lei Teng , Xia Wen-Qiang , Cameron Stephen L. , Liu Yin-Quan , Zhang Zhen , Gowda Maruthi M. N. , De Barro Paul , Navas-Castillo Jesús , Omongo Christopher A. , Delatte Hélène , Lee Kyeong-Yeoll , Patel Mitulkumar V. , Krause-Sakate Renate , Ng James , Wu San-Ling , Fiallo-Olivé Elvira , Liu Shu-Sheng , Colvin John , Wang Xiao-Wei
Published: April 2019

The 37 currently recognized Bemisia tabaci cryptic species are economically important species and contain both primary and secondary endosymbionts, but their diversity has never been mapped systematically across the group. To achieve this, PacBio sequencing of full-length bacterial 16S rRNA gene amplicons was carried out on 21 globally collected species in the B. tabaci complex, and two samples from B. afer were used here as outgroups. The microbial diversity was first explored across the major lineages of the whole group and 15 new putative bacterial sequences were observed. Extensive comparison of our results with previous endosymbiont diversity surveys which used PCR or multiplex 454 pyrosequencing platforms showed that the bacterial diversity was underestimated. To validate these new putative bacteria, one of them (Halomonas) was first confirmed to be present in MED B. tabaci using Hiseq2500 and FISH technologies. These results confirmed PacBio is a reliable and informative venue to reveal the bacterial diversity of insects. In addition, many new secondary endosymbiotic strains of Rickettsia and Arsenophonus were found, increasing the known diversity in these groups. For the previously described primary endosymbionts, one Portiera Operational Taxonomic Units (OTU) was shared by all B. tabaci species. The congruence of the B. tabaci-host and Portiera phylogenetic trees provides strong support for the hypothesis that primary endosymbionts co-speciated with their hosts. Likewise, a comparison of bacterial alpha diversities, Principal Coordinate Analysis, indistinct endosymbiotic communities harbored by different species and the co-divergence analyses suggest a lack of association between overall microbial diversity with cryptic species, further indicate that the secondary endosymbiont-mediated speciation is unlikely to have occurred in the B. tabaci species group.
Efficient message passing for cascade size distributions
Authors: Burkholz Rebekka
Published: April 2019

How big is the risk that a few initial failures of networked nodes amplify to large cascades that endanger the functioning of the system? Common answers refer to the average final cascade size. Two analytic approaches allow its computation: (a) (heterogeneous) mean field approximation and (b) belief propagation. The former applies to (infinitely) large locally tree-like networks, while the latter is exact on finite trees. Yet, cascade sizes can have broad and multi-modal distributions that are not well represented by their average. Full distribution information is essential to identify likely events and to estimate the tail risk, i.e. the probability of extreme events. We therefore present an efficient message passing algorithm that calculates the cascade size distribution in finite networks. It is exact on finite trees and for a large class of cascade processes. An approximate version applies to any network structure and performs well on locally tree-like networks, as we show with several examples.
Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson’s disease
Authors: Foti Sandrine C. , Hargreaves Iain , Carrington Stephanie , Kiely Aoife P. , Houlden Henry , Holton Janice L.
Published: April 2019

Multiple system atrophy (MSA) is a neurodegenerative disease characterised by glial cytoplasmic inclusions (GCIs), containing α-synuclein. Mutated COQ2, encoding an enzyme essential for co-enzyme Q10 (CoQ10) biosynthesis, has been associated with MSA. CoQ10 is an electron carrier in the mitochondrial electron transport chain (ETC) and antioxidant. It has been shown to be deficient in MSA brain tissue, thus implicating mitochondrial dysfunction in MSA. To investigate mitochondrial dysfunction in MSA further we examined ETC activity in MSA and control brain tissue, compared with Parkinson’s disease (PD) where mitochondrial dysfunction is known to be important. Using cerebellar and occipital white matter ETC complex I, II/III and IV activities were measured spectrophotometrically, selected individual components of the ETC were assessed by immunoblotting and cellular complex IV activity was analysed by enzyme histochemistry. We show decreased complex II/III activity with increased complex I and IV activity in MSA cerebellar white matter. This corresponds with the deficit in CoQ10 previously described in MSA and reflects the high regional pathological burden of GCIs. This study highlights mitochondrial dysfunction in MSA pathogenesis, suggests an influence on selective regional vulnerability to disease and points to shared disease mechanisms in α-synucleinopathies.
Manganese-induced cellular disturbance in the baker’s yeast, Saccharomyces cerevisiae with putative implications in neuronal dysfunction
Authors: Hernández Raúl Bonne , Moteshareie Houman , Burnside Daniel , McKay Bruce , Golshani Ashkan
Published: April 2019

Manganese (Mn) is an essential element, but in humans, chronic and/or acute exposure to this metal can lead to neurotoxicity and neurodegenerative disorders including Parkinsonism and Parkinson’s Disease by unclear mechanisms. To better understand the effects that exposure to Mn2+ exert on eukaryotic cell biology, we exposed a non-essential deletion library of the yeast Saccharomyces cerevisiae to a sub-inhibitory concentration of Mn2+ followed by targeted functional analyses of the positive hits. This screen produced a set of 43 sensitive deletion mutants that were enriched for genes associated with protein biosynthesis. Our follow-up investigations demonstrated that Mn reduced total rRNA levels in a dose-dependent manner and decreased expression of a β-galactosidase reporter gene. This was subsequently supported by analysis of ribosome profiles that suggested Mn-induced toxicity was associated with a reduction in formation of active ribosomes on the mRNAs. Altogether, these findings contribute to the current understanding of the mechanism of Mn-triggered cytotoxicity. Lastly, using the Comparative Toxicogenomic Database, we revealed that Mn shared certain similarities in toxicological mechanisms with neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s and Huntington’s diseases.
Low-Dose Tacrolimus Prevents Dysregulated Peri-Conceptional Ovarian and Systemic Immune Cellular Homeostasis in Subjects with PCOS
Authors: Albaghdadi Ahmad J. H. , Feeley Carolyn Ann , Kan Frederick W. K.
Published: April 2019

Polycystic ovary syndrome (PCOS) is characterized by failure of ovulation and is associated with obesity and chronic inflammation. Recent evidence suggests that anomalous activation of ovarian macrophages and numerical and functional deficits in the Th17 (CD4+IL17A+) and the CD4+CD25+CD127lowTregs plays crucial role in PCOS. We have shown that the pre-pregnancy use of tacrolimus prevents adverse reproductive outcomes in a mouse model of PCOS. Here we used the HFD-NONcNZO mice to test a hypothesized beneficial use of tacrolimus relative to metformin in favorably influencing the ovarian and systemic immune milieux conducive to gestational success in subjects with PCOS. Compared to normative controls, our data revealed an aberrant peri-conceptional suppression of the CD4+CD25+CD127lowTregs together with an overexpression of the Th17 T cells and lack of coordinated activation of ovarian macrophages in untreated HFD-dNONcNZO mice. Significant variances in treatment outcomes favoured the use of tacrolimus over metformin in treated mice. Consistent with the human fertility studies, this investigation reveals a beneficial systemic use of tacrolimus (0.1 mg/kg) in promoting early pregnancy in individuals with PCOS and suggests the need for further research into the selective inhibition of IL17A as a plausibly alternative immunotherapeutic approach in the clinical management of infertile individuals with PCOS.
Ocular biometry and refractive outcomes using two swept-source optical coherence tomography-based biometers with segmental or equivalent refractive indices
Authors: Omoto Miki Kamikawatoko , Torii Hidemasa , Masui Sachiko , Ayaki Masahiko , Tsubota Kazuo , Negishi Kazuno
Published: April 2019

This study compared the axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), mean anterior corneal radius of curvature (Rm), and postoperative refractive outcomes obtained from two different swept-source optical coherence biometers, the ARGOS (Movu, Aichi, Japan), which uses the segmental refractive index for each segment, and the IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany), which uses an equivalent refractive index for the entire eye. One hundred and six eyes of 106 patients with cataracts were included. The refractive outcomes using the Barrett Universal II, Haigis, Hoffer Q, and SRK/T formulas were evaluated. The mean AL, CCT, ACD, and Rm differed significantly (P < 0.001) with the IOLMaster 700 (25.22 mm, 559 µm, 3.23 mm, and 7.69 mm) compared with the ARGOS (25.14 mm, 533 µm, 3.33 mm, and 7.66 mm). The mean LTs did not differ significantly. The percentages of eyes within ±0.50 and ±1.00 diopter of the predicted refraction did not differ significantly (P > 0.05). The accuracy of the intraocular lens power calculations was clinically acceptable with both biometers, although the ocular biometry using these two biometers exhibited certain differences.
Environmental DNA metabarcoding to detect pathogenic Leptospira and associated organisms in leptospirosis-endemic areas of Japan
Authors: Sato Yukuto , Mizuyama Masaru , Sato Megumi , Minamoto Toshifumi , Kimura Ryosuke , Toma Claudia
Published: April 2019

Leptospires, which cause the zoonotic disease leptospirosis, persist in soil and aqueous environments. Several factors, including rainfall, the presence of reservoir animals, and various abiotic and biotic components interact to influence leptospiral survival, persistence, and pathogenicity in the environment. However, how these factors modulate the risk of infection is poorly understood. Here we developed an approach using environmental DNA (eDNA) metabarcoding for detecting the microbiome, vertebrates, and pathogenic Leptospira in aquatic samples. Specifically, we combined 4 sets of primers to generate PCR products for high-throughput sequencing of multiple amplicons through next-generation sequencing. Using our method to analyze the eDNA of leptospirosis-endemic areas in northern Okinawa, Japan, we found that the microbiota in each river shifted over time. Operating taxonomic units corresponding to pathogenic L. alstonii, L. kmetyi, and L. interrogans were detected in association with 12 nonpathogenic bacterial species. In addition, the frequencies of 11 of these species correlated with the amount of rainfall. Furthermore, 10 vertebrate species, including Sus scrofa, Pteropus dasymallus, and Cynops ensicauda, showed high correlation with leptospiral eDNA detection. Our eDNA metabarcoding method is a powerful tool for understanding the environmental phase of Leptospira and predicting human infection risk.
A systematic approach re-analyzing the effects of temperature disturbance on the microbial community of mesophilic anaerobic digestion
Authors: Shaw Grace Tzun-Wen , Weng Chieh-Yin , Chen Cheng-Yu , Weng Francis Cheng-Hsuan , Wang Daryi
Published: April 2019

Microbial communities are key drivers of ecosystem processes, but their behavior in disturbed environments is difficult to measure. How microbial community composition and function respond disturbances is a common challenge in biomedical, environmental, agricultural, and bioenergy research. A novel way to solve this problem is to use a systems-level perspective and describe microbial communities as networks. Based on a mesophilic anaerobic digestion system of swine manure as a tool, we propose a simple framework to investigate changes in microbial communities via compositions, metabolic pathways, genomic properties and interspecies relationships in response to a long-term temperature disturbance. After temperature disturbance, microbial communities tend towards a competitive interaction network with higher GC content and larger genome size. Based on microbial interaction networks, communities responded to the disturbance by showing a transition from acetotrophic (Methanotrichaceae and Methanosarcinaceae) to methylotrophic methanogens (Methanomassiliicoccaceae and Methanobacteriaceae) and a fluctuation in rare biosphere taxa. To conclude, this study may be important for exploring the dynamic relationships between disturbance and microbial communities as a whole, as well as for providing researchers with a better understanding of how changes in microbial communities relate to ecological processes.
Discovery of selective activators of PRC2 mutant EED-I363M
Authors: Suh Junghyun L. , Barnash Kimberly D. , Abramyan Tigran M. , Li Fengling , The Juliana , Engelberg Isabelle A. , Vedadi Masoud , Brown Peter J. , Kireev Dmitri B. , Arrowsmith Cheryl H. , James Lindsey I. , Frye Stephen V.
Published: April 2019

Many common disease-causing mutations result in loss-of-function (LOF) of the proteins in which they occur. LOF mutations have proven recalcitrant to pharmacologic intervention, presenting a challenge for the development of targeted therapeutics. Polycomb repressive complex 2 (PRC2), which contains core subunits (EZH2, EED, and SUZ12), regulates gene activity by trimethylation of histone 3 lysine 27. The dysregulation of PRC2 catalytic activity by mutations has been implicated in cancer and other diseases. Among the mutations that cause PRC2 malfunction, an I363M LOF mutation of EED has been identified in myeloid disorders, where it prevents allosteric activation of EZH2 catalysis. We describe structure-based design and computational simulations of ligands created to ameliorate this LOF. Notably, these compounds selectively stimulate the catalytic activity of PRC2-EED-I363M over wildtype-PRC2. Overall, this work demonstrates the feasibility of developing targeted therapeutics for PRC2-EED-I363M that act as allosteric agonists, potentially correcting this LOF mutant phenotype.
Radiative transfer modelling reveals why canopy reflectance follows function
Authors: Kattenborn Teja , Schmidtlein Sebastian
Published: April 2019

Optical remote sensing is potentially highly informative to track Earth’s plant functional diversity. Yet, causal explanations of how and why plant functioning is expressed in canopy reflectance remain limited. Variation in canopy reflectance can be described by radiative transfer models (here PROSAIL) that incorporate plant traits affecting light transmission in canopies. To establish causal links between canopy reflectance and plant functioning, we investigate how two plant functional schemes, i.e. the Leaf Economic Spectrum (LES) and CSR plant strategies, are related to traits with relevance to reflectance. These traits indeed related to both functional schemes, whereas only traits describing leaf properties correlated with the LES. In contrast, traits related to canopy structure showed no correlation to the LES, but to CSR strategies, as the latter integrates both plant economics and size traits, rather than solely leaf economics. Multiple optically relevant traits featured comparable or higher correspondence to the CSR space than those traits originally used to allocate CSR scores. This evidences that plant functions and strategies are directly expressed in reflectance and entails that canopy ‘reflectance follows function’. This opens up new possibilities to understand differences in plant functioning and to harness optical remote sensing data for monitoring Earth´s functional diversity.
Predicting Growth and Carcass Traits in Swine Using Microbiome Data and Machine Learning Algorithms
Authors: Maltecca Christian , Lu Duc , Schillebeeckx Constantino , McNulty Nathan P. , Schwab Clint , Shull Caleb , Tiezzi Francesco
Published: April 2019

In this paper, we evaluated the power of microbiome measures taken at three time points over the growth test period (weaning, 15 and 22 weeks) to foretell growth and carcass traits in 1039 individuals of a line of crossbred pigs. We measured prediction accuracy as the correlation between actual and predicted phenotypes in a five-fold cross-validation setting. Phenotypic traits measured included live weight measures and carcass composition obtained during the trial as well as at slaughter. We employed a null model excluding microbiome information as a baseline to assess the increase in prediction accuracy stemming from the inclusion of operational taxonomic units (OTU) as predictors. We further contrasted performance of models from the Bayesian alphabet (Bayesian Lasso) as well machine learning approaches (Random Forest and Gradient Boosting) and semi-parametric kernel models (Reproducing Kernel Hilbert space). In most cases, prediction accuracy increased significantly with the inclusion of microbiome data. Accuracy was more substantial with the inclusion of microbiome information taken at weeks 15 and 22, with values ranging from approximately 0.30 for loin traits to more than 0.50 for back fat. Conversely, microbiome composition at weaning resulted in most cases in marginal gains of prediction accuracy, suggesting that later measures might be more useful to include in predictive models. Model choice affected predictions marginally with no clear winner for any model/trait/time point. We, therefore, suggest average prediction across models as a robust strategy in fitting microbiome information. In conclusion, microbiome composition can effectively be used as a predictor of growth and composition traits, particularly for fatness traits. The inclusion of OTU predictors could potentially be used to promote fast growth of individuals while limiting fat accumulation. Early microbiome measures might not be good predictors of growth and OTU information might be best collected at later life stages. Future research should focus on the inclusion of both microbiome as well as host genome information in predictions, as well as the interaction between the two. Furthermore, the influence of the microbiome on feed efficiency as well as carcass and meat quality should be investigated.
Impact of Percoll purification on isolation of primary human hepatocytes
Authors: Horner R. , Gassner J. G. M. V. , Kluge M. , Tang P. , Lippert S. , Hillebrandt K. H. , Moosburner S. , Reutzel-Selke A. , Pratschke J. , Sauer I. M. , Raschzok N.
Published: April 2019

Research and therapeutic applications create a high demand for primary human hepatocytes. The limiting factor for their utilization is the availability of metabolically active hepatocytes in large quantities. Centrifugation through Percoll, which is commonly performed during hepatocyte isolation, has so far not been systematically evaluated in the scientific literature. 27 hepatocyte isolations were performed using a two-step perfusion technique on tissue obtained from partial liver resections. Cells were seeded with or without having undergone the centrifugation step through 25% Percoll. Cell yield, function, purity, viability and rate of bacterial contamination were assessed over a period of 6 days. Viable yield without Percoll purification was 42.4 × 106 (SEM ± 4.6 × 106) cells/g tissue. An average of 59% of cells were recovered after Percoll treatment. There were neither significant differences in the functional performance of cells, nor regarding presence of non-parenchymal liver cells. In five cases with initial viability of <80%, viability was significantly increased by Percoll purification (71.6 to 87.7%, p = 0.03). Considering our data and the massive cell loss due to Percoll purification, we suggest that this step can be omitted if the initial viability is high, whereas low viabilities can be improved by Percoll centrifugation.
Adoptive transfer of Trichinella spiralis-activated macrophages can ameliorate both Th1- and Th2-activated inflammation in murine models
Authors: Kang Shin Ae , Park Mi-Kyung , Park Sang Kyun , Choi Jun Ho , Lee Da In , Song So Myong , Yu Hak Sun
Published: April 2019

Trichinella spiralisis a zoonotic nematode and food borne parasite and infection withT.spiralisleads to suppression of the host immune response and other immunopathologies. Alternative activated macrophages (M2) as well as Tregcells, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite. The precise mechanism by which helminths modulate host immune response is not fully understood. To determine the functions of parasite-induced M2 macrophages, we compared the effects of M1 and M2 macrophages obtained fromTrichinella spiralis-infected mice with those ofT.spiralisexcretory/secretory (ES) protein-treated macrophages on experimental intestinal inflammation and allergic airway inflammation.T.spiralisinfection induced M2 macrophage polarization by increasing the expression of CD206,ARG1, andFizz2. In a single application, we introduced macrophages obtained fromT.spiralis-infected mice andT.spiralisES protein-treated macrophages into mice tail veins before the induction of dextran sulfate sodium (DSS)-induced colitis, ovalbumin (OVA)-alum sensitization, and OVA challenge. Colitis severity was assessed by determining the severity of colitis symptoms, colon length, histopathologic parameters, and Th1-related inflammatory cytokine levels. Compared with the DSS-colitis group,T.spiralis-infected mice andT.spiralisES protein-treated macrophages showed significantly lower disease activity index (DAI) at sacrifice and smaller reductions of body weight and proinflammatory cytokine level. The severity of allergic airway inflammation was assessed by determining the severity of symptoms of inflammation, airway hyperresponsiveness (AHR), differential cell counts, histopathologic parameters, and levels of Th2-related inflammatory cytokines. Severe allergic airway inflammation was induced after OVA-alum sensitization and OVA challenge, which significantly increased Th2-related cytokine levels, eosinophil infiltration, and goblet cell hyperplasia in the lung. However, these severe allergic symptoms were significantly decreased inT. spiralis-infected mice andT. spiralisES protein-treated macrophages. Helminth infection and helminth ES proteins induce M2 macrophages. Adoptive transfer of macrophages obtained from helminth-infected mice and helminth ES protein-activated macrophages is an effective treatment for preventing and treating airway allergy in mice and is promising as a therapeutic for treating inflammatory diseases.
Evaluation of the Returned Electromagnetic Signal from Retro-reflectors in Turbid Media
Authors: Hassani nia Iman , Wheaton Skyler , Mohseni Hooman
Published: April 2019

We provide first-principle theoretical and numerical simulations using the coherent Transfer Matrix Approach (TMA) to describe the behavior of the three main class of the optical beacons namely phase conjugators, reflectors, and retroreflectors within a turbid medium. Our theory describes the extraordinary enhancement (about 5 dB) offered by retroreflectors compared to reflectors in our detailed experiments and shows that they effectively act as local optical phase conjugators. Moreover, the performance of retroreflectors shows little degradation for increased light incident angles in turbid media, while the performance of reflectors degrades drastically. These results may find applications for detection of the echoes of electromagnetic radiation in turbid media.
Plasma exosomes exacerbate alcohol- and acetaminophen-induced toxicity via CYP2E1 pathway
Authors: Rahman Mohammad A. , Kodidela Sunitha , Sinha Namita , Haque Sanjana , Shukla Pradeep K. , Rao Radhakrishna , Kumar Santosh
Published: April 2019

Cellular CYP2E1 is well-known to mediate alcohol- (ALC) and acetaminophen- (APAP) induced toxicity in hepatic and extra-hepatic cells. Although exosomes have been gaining importance in understanding mechanism of intra- and inter-cellular communication, the functional role of drug metabolizing cytochrome P450 (CYP) enzymes in human plasma exosomes are yet to be explored. In our previous study, we reported that human plasma-derived exosomes contain substantial level of functional CYP2E1. In the current project, we investigated the potential role of plasma exosomal CYP2E1 in mediating ALC- and APAP-induced toxicity. We treated hepatic and extra-hepatic (monocytic) cells with exosomes ± ALC/APAP. We observed that the plasma exosomes containing CYP2E1 cargo further exacerbate ALC- and APAP-induced toxicity in both hepatic and monocytic cells. Further, both exosomes- and ALC/APAP-induced toxicity was reduced/abolished by a selective inhibitor of CYP2E1 enzyme activity (diallyl ether). However, only ALC-, but not exosome-induced toxicity was reduced/abolished by CYP2E1 siRNA. These findings suggest that ALC/APAP-induced toxicity in the presence of exosomes are mediated, at least in part, by CYP2E1 enzyme. To validate these in vitro findings, we characterized plasma exosomal contents in a binge-drinking animal model and their effect on ALC/APAP-induced toxicity in monocytic cells. Our results showed that ALC exposure caused a significant induction of the plasma exosomal CYP2E1 level in a binge drinking murine model. These exosomes containing increased levels of CYP2E1 caused significant toxicity in monocytic cells compared to exosomes derived from control mice. Overall, our results showed an important role of exosomal CYP2E1 in exacerbating ALC- and APAP-induced toxicity. The study is significant in terms of understanding the role of exosomal CYP2E1 in cell-cell interactions, and their effects on drug-induced toxicity.
Synapse loss and progress of Alzheimer’s disease -A network model
Authors: Kashyap G. , Bapat D. , Das D. , Gowaikar R. , Amritkar R. E. , Rangarajan G. , Ravindranath V. , Ambika G.
Published: April 2019

We present observational evidence from studies on primary cortical cultures from AD transgenic mice, APPSwe/PS1ΔE9 (APP/PS1) mice, for significant decrease in total spine density at DIV-15 and onward. This indicates reduction in potential healthy synapses and strength of connections among neurons. Based on this, a network model of neurons is developed, that explains the consequent loss of coordinated activity and transmission efficiency among neurons that manifests over time. The critical time when structural connectivity in the brain undergoes a phase-transition, from initial robustness to irreparable breakdown, is estimated from this model. We also show how the global efficiency of signal transmission in the network decreases over time. Moreover, the number of multiple paths of high efficiency decreases rapidly as the disease progresses, indicating loss of structural plasticity and inefficiency in choosing alternate paths or desired paths for any pattern of activity. Thus loss of spines caused by β-Amyloid (Aβ) peptide results in disintegration of the neuronal network over time with consequent cognitive dysfunctions in Alzheimer’s Disease (AD).
Clinical efficacy of laminectomy with instrumented fixation in treatment of adjacent segmental disease following ACCF surgery: a retrospective observational study of 48 patients
Authors: Yang Sidong , Yang Dalong , Ma Lei , Wang Hui , Ding Wenyuan
Published: April 2019

This study was designed to investigate the clinical efficacy of laminectomy with instrumented fixation in treatment of adjacent segmental diseases following anterior cervical corpectomy and fusion (ACCF) surgery. Between January 2008 and December 2015, 48 patients who underwent laminectomy with instrumented fixation to treat adjacent segmental diseases following ACCF surgery, were enrolled into this study. The patients were followed up at least 2 years. Pain assessment was determined by visual analogue scale (VAS) score and Neck Disability Index (NDI) score; neurological impairment was evaluated by Japanese Orthopaedic Association (JOA) score; and radiographic parameters were also compared. All comparisons were determined by paired t test with appropriate Bonferronni correction. VAS score preoperatively and at last follow-up was 5.28 ± 2.35 vs 1.90 ± 1.06 (P < 0.001). JOA score preoperatively and at last follow-up was 8.2 ± 3.6 vs 14.5 ± 1.1 (P < 0.001). NDI score preoperatively and at last follow-up was 30.5 ± 12.2 vs 10.6 ± 5.8 (P < 0.001). Moreover, the losses of cervical lordosis and C2-C7 range of motion after laminectomy were significant (both P < 0.005), but not sagittal vertical axis distance. Postoperative complications were few or mild. In conclusion, clinical effectiveness and safety can be guaranteed when the patients undergo laminectomy with instrumented fixation to treat adjacent segmental diseases following ACCF surgery.
Epigenomic profiling of retinal progenitors reveals LHX2 is required for developmental regulation of open chromatin
Authors: Zibetti Cristina , Liu Sheng , Wan Jun , Qian Jiang , Blackshaw Seth
Published: April 2019

Retinal neurogenesis occurs through partially overlapping temporal windows, driven by concerted actions of transcription factors which, in turn, may contribute to the establishment of divergent genetic programs in the developing retina by coordinating variations in chromatin landscapes. Here we comprehensively profile murine retinal progenitors by integrating next generation sequencing methods and interrogate changes in chromatin accessibility at embryonic and post-natal stages. An unbiased search for motifs in open chromatin regions identifies putative factors involved in the developmental progression of the epigenome in retinal progenitor cells. Among these factors, the transcription factor LHX2 exhibits a developmentally regulated cis-regulatory repertoire and stage-dependent motif instances. Using loss-of-function assays, we determine LHX2 coordinates variations in chromatin accessibility, by competition for nucleosome occupancy and secondary regulation of candidate pioneer factors.
The interactions of an Aβ protofibril with a cholesterol-enriched membrane and involvement of neuroprotective carbazolium-based substances
Authors: Karimi Hedayat , Heydari Dokoohaki Maryam , Zolghadr Amin Reza , Ghatee Mohammad Hadi
Published: April 2019

The molecular dynamics simulations indicate that the cholesterol content of the membrane could not play a substantial role in the emergence of Alzheimer's disease. However, the strong interactions between the polar residue of Aβ and the POPC molecules lead to a large perturbation on the membrane bilayer. The simulation results disclose the neuroprotective property of P7C3-S243 molecule.
Intermolecular dynamics of ultraconfined interlayer water in tobermorite: influence on mechanical performance
Authors: Mitra Nilanjan , Sarkar Prodip Kumar , Prasad Dipak
Published: April 2019

Ultraconfined interlayer water within the tobermorite molecular structure is responsible for changes in the uniaxial tensile and compressive response of the family of tobermorites: 9, 11 and 14 Å.
First-principles calculations of thermal transport properties in MoS2/MoSe2 bilayer heterostructure
Authors: Ma Jiang-Jiang , Zheng Jing-Jing , Zhu Xue-Liang , Liu Peng-Fei , Li Wei-Dong , Wang Bao-Tian
Published: April 2019

The van der Waals interaction in a MoS2/MoSe2 bilayer heterostructure has a significant effect on its lattice thermal conductivity.
TiO2 mesoporous thin film architecture as a tool to control Au nanoparticles growth and sensing capabilities
Authors: Steinberg Paula Y. , Zalduendo M. Mercedes , Giménez Gustavo , Soler-Illia Galo J. A. A. , Angelomé Paula C.
Published: April 2019

Pore size and ordering in mesoporous TiO2 thin films define the Au nanoparticle growth through and inside the pores.
Three new metal chalcogenide open frameworks built through co-assembly and/or hybrid assembly from supertetrahedral T5-InOS and T3-InS nanoclusters
Authors: Zhang Jiaxu , Liu Xiaoshuang , Ding Yayun , Xue Chaozhuang , Wu Tao
Published: April 2019

Reported here are three new metal chalcogenide open frameworks built from supertetrahedral T5-InOS (or o-T5) and T3-InS nanoclusters via co-assembly and/or hybrid assembly modes.
In situ generation of Ph3PO in cyanido-bridged heterometallic {FeIIILnIII}2 molecular squares (Ln = Eu, Sm)
Authors: Alexandru Maria-Gabriela , Visinescu Diana , Braun-Cula Beatrice , Shova Sergiu , Lloret Francesc , Julve Miguel
Published: April 2019

Two new examples of cyanido-bridged {FeIII2(Eu/Sm)III2} molecular squares that exhibit weak antiferromagnetic interactions between 3d and 4f centers are reported.
3D hierarchical porous amidoxime fibers speed up uranium extraction from seawater
Authors: Xu Xiao , Zhang Hongjun , Ao Junxuan , Xu Lu , Liu Xiyan , Guo Xiaojing , Li Jingye , Zhang Lan , Li Qingnuan , Zhao Xiaoyan , Ye Bangjiao , Wang Deli , Shen Fei , Ma Hongjuan
Published: April 2019

The development of high specific surface area amidoxime-based polymeric (H-ABP) fibers presents a new technology for the synthesis of highly efficient adsorbents for uranium extraction from seawater (UES), thus opening a whole new means of nuclear fuel production from the ocean.
A binder-free electrode architecture design for lithium–sulfur batteries: a review
Authors: Guo Junling , Liu Jinping
Published: April 2019

Binder-free structures offering structural and kinetic advantages for constructing high performance sulfur cathodes and dendrite-free Li metal anodes are reviewed.