bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in marketing foods to children in Slovenian magazines: a content analysis
Authors: Lavriša Živa , Erjavec Karmen , Pravst Igor
Published: October 2018

Objective

Food marketing is an important factor influencing children’s food preferences. In Slovenia the use of magazines is widespread among children. We investigated food advertising in children’s and teens’ magazines (CTM) in 2013 and 2017. The penetration of food advertising was compared with magazines targeting the adult population.

Design

A repeated cross-sectional study. Magazines were searched for branded food references (BFR). All BFR were categorised and evaluated using the WHO Europe nutrient profile model.

Setting

Slovenia.

Subjects

All issues of CTM and a selected sample of issues of adult-targeting magazines and newspapers published in Slovenia in 2013 and 2017.

Results

One hundred and seventy-five issues of CTM (ninety-two in 2013, eighty-three in 2017) and 675 issues of adult-targeted magazines and newspapers were analysed (345 in 2013, 330 in 2017). In 2017, food advertising in CTM dropped notably but the opposite was found for adult-targeted magazines. Regular advertisements dominated in 2017 in CTM, while in 2013, 83 % of BFR types were games/puzzles, competitions and product placements. Chocolate and confectionery were the most advertised in CTM and food supplements in adults’ magazines. Most foods in CTM were classed as ‘not permitted’ in both years (98 % in 2013 and 100 % in 2017).

Conclusions

The advertisements in CTM still mostly refer to unhealthy foods. The extent of food advertising has dropped considerably since 2013. On the contrary, food advertising in printed media targeting adults has increased, chiefly referring to food supplements and foods that do not pass the WHO Europe nutrient profile model criteria.
Fruit and vegetable consumption is associated with improved mental and cognitive health in older adults from non-Western developing countries
Authors: Gehlich Kerstin H , Beller Johannes , Lange-Asschenfeldt Bernhard , Köcher Wolfgang , Meinke Martina C , Lademann Jürgen
Published: October 2018

Objectives

Consumption of fruits and vegetables has been shown to contribute to mental and cognitive health in older adults from Western industrialized countries. However, it is unclear whether this effect replicates in older adults from non-Western developing countries. Thus, the present study examined the contribution of fruit and vegetable consumption to mental and cognitive health in older persons from China, India, Mexico, Russia, South Africa and Ghana.

Design

Representative cross-sectional and cross-national study.

Setting/Subjects

We used data from the WHO Study on Global Ageing and Adult Health (SAGE), sampled in 2007 to 2010. Our final sample size included 28 078 participants.

Results

Fruit and vegetable consumption predicted an increased cognitive performance in older adults including improved verbal recall, improved delayed verbal recall, improved digit span test performance and improved verbal fluency; the effect of fruit consumption was much stronger than the effect of vegetable consumption. Regarding mental health, fruit consumption was significantly associated with better subjective quality of life and less depressive symptoms; vegetable consumption, however, did not significantly relate to mental health.

Conclusions

Consumption of fruits is associated with both improved cognitive and mental health in older adults from non-Western developing countries, and consumption of vegetables is associated with improved cognitive health only. Increasing fruit and vegetable consumption might be one easy and cost-effective way to improve the overall health and quality of life of older adults in non-Western developing countries.
Beverage consumption patterns and energy contribution from beverages per meal type: results from a national dietary survey in Sweden
Authors: Scander Henrik , Monteagudo Celia , Nilsen Bente , Tellström Richard , Yngve Agneta
Published: October 2018

Objective

Many studies of food intake have been performed and published in Sweden, but to our knowledge no studies have extensively explored the beverage consumption of the Swedish adult population. The present study aimed to describe the beverage consumption and the contribution of beverage energy (including alcohol energy) to total energy intake according to gender, region of living, meal type and day for a Swedish adult population.

Design

National dietary survey Riksmaten (2010–2011), collected by the Swedish National Food Agency.

Setting

Sweden.

Subjects

A total of 1682 participants (57 % women) reported dietary intake data during four consecutive days, specified by portion size, meal, time point, day of the week and venue. Meals were categorized as breakfast, lunch, dinner and ‘other’.

Result

The beverage reported to be consumed the most was water (ml/d), followed by coffee. Men had a higher consumption of juice, soft drinks, beer, spirits and low-alcohol beer, while the consumption of tea and water was higher for women. For both genders, milk contributed the most to beverage energy intake. Energy percentage from beverages was higher at lunch and dinner during weekends for both genders. Participants from the biggest cities in Sweden had a higher consumption of wine for both genders and tea for men than participants from other regions.

Conclusions

A considerable part of total energy intake was contributed by beverages, especially for men. Beverages can contribute to a more enjoyable diet, but at the same time provide energy, sugar and alcohol in amounts that do not promote optimal health.
Social Movements, Brexit and Social Policy
Authors: Ishkanian Armine
Published: October 2018

In this article, I examine the relationship between social movements, Brexit and social policy and consider how political and socio-economic developments since the 2008 financial crisis helped create a fertile ground for Brexit. I query the assumption that Brexit was simply a result of those left behind by globalisation and instead explore why and how actors from across the ideological spectrum supported Brexit and examine the sources of discontent which created the conditions from which Brexit emerged. To understand the relationship, role and impact of social movements and, more widely, civil society on social policy, I argue that it is important to critically examine how diverse actors within civil society are campaigning for the recognition of unmet needs and challenging systems of redistribution and the ways in which they interact and engage with governance institutions and policy processes.
What Business do Businesses Have with the Free Exercise of Religion?
Authors: Failer Judith Lynn
Published: October 2018

Since Burwell v. Hobby Lobby (2014), federal and state religious freedom restoration acts now extend the right to free exercise of religion to businesses. But what does it mean for businesses to have such a right? In this paper, I identify three implications of these new rights: they shift the burden for fulfilling the right to private citizens, and they conflict with businesses’ both commercial and democratic obligations. To illustrate how they become problematic, I draw on the case of In re Wathen (2015) where the owners of a bed and breakfast cited their business's religion as their reason for refusing to host a wedding reception for a same-sex couple, even though state law specifically prohibited commercial businesses from discriminating based on sexual orientation.
Loving Kindness Meditation zur Behandlung der chronischen Depression
Authors: Schilling Viola N. L. S. , Lutz Wolfgang , Hofmann Stefan G. , Zimmermann Dirk , Wolter Kathinka , Stangier Ulrich
Published: October 2018

Zusammenfassung. Theoretischer Hintergrund: Chronische Depressionen gehen mit einer langwierigen Belastung einher und verursachen hohe Krankheitskosten. Ein möglicher Ansatz zur Behandlung könnte die Loving Kindness Meditation (LKM) sein. Methode: In dieser Pilot-Studie wurde ein LKM-Gruppenprogramm eingesetzt und bezüglich der Effektivität untersucht. N = 2207 Fälle aus Wartelistendaten wurden stufenweise zu der LKM-Gruppe (n = 12) zugeordnet. Zwei Kontrollgruppen (n = 134 und n = 12) wurden gebildet, indem zunächst die Ein-und Ausschlusskriterien angewandt wurden und dann die verbliebene Stichprobe basierend auf der Kovariatenverteilung mittels Propensity Score Matching (PSM) angepasst wurde. Die Gruppen wurden anhand des OQ-30 verglichen. Ergebnisse: Im Prä-Post-Vergleich zeigten sich im OQ-30 signifikante Verbesserungen. Allerdings zeigte sich das so nicht in den symptomspezifischen Instrumenten (BDI-II und HAM-D). Im Vergleich zu der gesamten Wartelistenstichprobe (n = 134) ergaben sich signifikante Verbesserungen im OQ-30. Verglichen mit der PSM-Wartelistenkontrollgruppe zeigten sich marginal signifikante Unterschiede im OQ-30, signifikante Unterschiede konnten bezüglich der Depressionsitems des OQ-30 nachgewiesen werden. In der Interventionsgruppe ergaben sich mehr reliable Verbesserungen im OQ-30 als in den Wartelistenkontrollgruppen. Schlussfolgerung: Die Pilotstudie zeigte eine geringere Abbruchquote als Vorgängerpilotstudien und eine gute Prä-Post Effektstärke im OQ-30, sowie im Vergleich zu den beiden Wartelistekontrollgruppen. Allerdings zeigten sich keine konsistenten Prä-Post Effekte in den Depressionsskalen. Eine weitere umfangreichere Studie mit aktiver Kontrollgruppe wäre nötig, um das Programm hinsichtlich seiner Effektivität, bezüglich des Abbruchs sowie der Heterogenität der Effekte in den Depressionsskalen weiter untersuchen zu können.
Constraining Aging Processes of Black Carbon in the Community Atmosphere Model Using Environmental Chamber Measurements
Authors: Wang Yuan , Ma Po‐Lun , Peng Jianfei , Zhang Renyi , Jiang Jonathan H. , Easter Richard C. , Yung Yuk L.
Published: October 2018

The direct radiative forcing of black carbon aerosol (BC) on the Earth system remains unsettled, largely due to the uncertainty with physical properties of BC throughout their lifecycle. Here we show that ambient chamber measurements of BC properties provide a novel constraint on the crude BC aging representation in climate models. Observational evidence for significant absorption enhancement of BC can be reproduced when the aging processes in the four‐mode version of the Modal Aerosol Module (MAM4) aerosol scheme in the Community Atmosphere Model version 5 are calibrated by the recent in situ chamber measurements. An observation‐based scaling method is developed in the aging timescale calculation to alleviate the influence of biases in the simulated model chemical composition. Model sensitivity simulations suggest that the different monolayer settings in the BC aging parameterization of MAM4 can cause as large as 26% and 24% differences in BC burden and radiative forcing, respectively. We also find that an increase in coating materials (e.g., sulfate and secondary organic aerosols) reduces BC lifetime by increasing the hygroscopicity of the mixture but enhances its absorption, resulting in a net increase in BC direct radiative forcing. Our results suggest that accurate simulations of BC aging processes as well as other aerosol species are equally important in reducing the uncertainty of BC forcing estimation.
β2-Adrenergic receptor modulates mitochondrial metabolism and disease progression in recurrent/metastatic HPV(+) HNSCC
Authors: Lucido Christopher T. , Callejas-Valera Juan L. , Colbert Paul L. , Vermeer Daniel W. , Miskimins W. Keith , Spanos William C. , Vermeer Paola D.
Published: October 2018

Abstract

The incidence of human papillomavirus-associated head and neck squamous cell carcinoma (HPV[ + ] HNSCC) is rapidly increasing. Although clinical management of primary HPV( + ) HNSCC is relatively successful, disease progression, including recurrence and metastasis, is often fatal. Moreover, patients with progressive disease face limited treatment options and significant treatment-associated morbidity. These clinical data highlight the need to identify targetable mechanisms that drive disease progression in HPV( + ) HNSCC to prevent and/or treat progressive disease. Interestingly, β-adrenergic signaling has recently been associated with pro-tumor processes in several disease types. Here we show that an aggressive murine model of recurrent/metastatic HPV( + ) HNSCC upregulates β2-adrenergic receptor (β2AR) expression, concordant with significantly heightened mitochondrial metabolism, as compared with the parental model from which it spontaneously derived. β-Adrenergic blockade effectively inhibits in vitro proliferation and migratory capacity in this model, effects associated with an attenuation of hyperactive mitochondrial respiration. Importantly, propranolol, a clinically available nonselective β-blocker, significantly slows primary tumor growth, inhibits metastatic development, and shows additive benefit alongside standard-of-care modalities in vivo. Further, via CRISPR/Cas9 technology, we show that the hyperactive mitochondrial metabolic profile and aggressive in vivo phenotype of this recurrent/metastatic model are dependent on β2AR expression. These data implicate β2AR as a modulator of mitochondrial metabolism and disease progression in HPV( + ) HNSCC, and warrant further investigation into the use of β-blockers as low cost, relatively tolerable, complementary treatment options in the clinical management of this disease.
Genome-scale fitness profile of Caulobacter crescentus grown in natural freshwater
Authors: Hentchel Kristy L , Reyes Ruiz Leila M , Curtis Patrick D , Fiebig Aretha , Coleman Maureen L , Crosson Sean
Published: October 2018

Bacterial genomes evolve in complex ecosystems and are best understood in this natural context, but replicating such conditions in the lab is challenging. We used transposon sequencing to define the fitness consequences of gene disruption in the bacterium Caulobacter crescentus grown in natural freshwater, compared with axenic growth in common laboratory media. Gene disruptions in amino-acid and nucleotide sugar biosynthesis pathways and in metabolic substrate transport machinery impaired fitness in both lake water and defined minimal medium relative to complex peptone broth. Fitness in lake water was enhanced by insertions in genes required for flagellum biosynthesis and reduced by insertions in genes involved in biosynthesis of the holdfast surface adhesin. We further uncovered numerous hypothetical and uncharacterized genes for which disruption impaired fitness in lake water, defined minimal medium, or both. At the genome scale, the fitness profile of mutants cultivated in lake water was more similar to that in complex peptone broth than in defined minimal medium. Microfiltration of lake water did not significantly affect the terminal cell density or the fitness profile of the transposon mutant pool, suggesting that Caulobacter does not strongly interact with other microbes in this ecosystem on the measured timescale. Fitness of select mutants with defects in cell surface biosynthesis and environmental sensing were significantly more variable across days in lake water than in defined medium, presumably owing to day-to-day heterogeneity in the lake environment. This study reveals genetic interactions between Caulobacter and a natural freshwater environment, and provides a new avenue to study gene function in complex ecosystems.
EVI1 overexpression reprograms hematopoiesis via upregulation of Spi1 transcription
Authors: Ayoub Edward , Wilson Michael P. , McGrath Kathleen E. , Li Allison J. , Frisch Benjamin J. , Palis James , Calvi Laura M. , Zhang Yi , Perkins Archibald S.
Published: October 2018

Inv(3q26) and t(3:3)(q21;q26) are specific to poor-prognosis myeloid malignancies, and result in marked overexpression of EVI1, a zinc-finger transcription factor and myeloid-specific oncoprotein. Despite extensive study, the mechanism by which EVI1 contributes to myeloid malignancy remains unclear. Here we describe a new mouse model that mimics the transcriptional effects of 3q26 rearrangement. We show that EVI1 overexpression causes global distortion of hematopoiesis, with suppression of erythropoiesis and lymphopoiesis, and marked premalignant expansion of myelopoiesis that eventually results in leukemic transformation. We show that myeloid skewing is dependent on DNA binding by EVI1, which upregulates Spi1, encoding master myeloid regulator PU.1. We show that EVI1 binds to the −14 kb upstream regulatory element (−14kbURE) at Spi1; knockdown of Spi1 dampens the myeloid skewing. Furthermore, deletion of the −14kbURE at Spi1 abrogates the effects of EVI1 on hematopoietic stem cells. These findings support a novel mechanism of leukemogenesis through EVI1 overexpression.
Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex
Authors: Calabrese David R. , Chen Xiang , Leon Elena C. , Gaikwad Snehal M. , Phyo Zaw , Hewitt William M. , Alden Stephanie , Hilimire Thomas A. , He Fahu , Michalowski Aleksandra M. , Simmons John K. , Saunders Lindsey B. , Zhang Shuling , Connors Daniel , Walters Kylie J. , Mock Beverly A. , Schneekloth John S.
Published: October 2018

G-quadruplexes (G4s) are noncanonical DNA structures that frequently occur in the promoter regions of oncogenes, such as MYC, and regulate gene expression. Although G4s are attractive therapeutic targets, ligands capable of discriminating between different G4 structures are rare. Here, we describe DC-34, a small molecule that potently downregulates MYC transcription in cancer cells by a G4-dependent mechanism. Inhibition by DC-34 is significantly greater for MYC than other G4-driven genes. We use chemical, biophysical, biological, and structural studies to demonstrate a molecular rationale for the recognition of the MYC G4. We solve the structure of the MYC G4 in complex with DC-34 by NMR spectroscopy and illustrate specific contacts responsible for affinity and selectivity. Modification of DC-34 reveals features required for G4 affinity, biological activity, and validates the derived NMR structure. This work advances the design of quadruplex-interacting small molecules to control gene expression in therapeutic areas such as cancer.
POH1 deubiquitinates pro-interleukin-1β and restricts inflammasome activity
Authors: Zhang Li , Liu Yun , Wang Boshi , Xu Guiqin , Yang Zhaojuan , Tang Ming , Ma Aihui , Jing Tiantian , Xu Xiaoli , Zhang Xiaoren , Liu Yongzhong
Published: October 2018

Inflammasome activation is essential for host defence against invading pathogens, but is also involved in various forms of inflammatory diseases. The processes that control inflammasome activity are thus important for averting excessive immune responses and tissue damage. Here we show that the deubiquitinase POH1 negatively regulates the immune response triggered by inflammasome activation. POH1 deficiency in macrophages enhances mature IL-1β production without significant alterations in inflammasome priming and ASC-caspase-1 activation. In WT macrophages, POH1 interacts with and deubiquitinates pro-IL-1β by decreasing the K63-linked polyubiquitin chains, as well as decreases the efficacy of pro-IL-1β cleavage. Furthermore, myeloid cell-specific deletion of POH1 aggravates lipopolysaccharide-induced systemic inflammation and alum-induced peritonitis inflammatory responses in vivo. Our study thereby reveals that POH1-mediated deubiquitination of pro-IL-1β is an important regulatory event that restrains inflammatory responses for the maintenance of immune homeostasis.
DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells
Authors: Yamamoto Takeshi , Endo Yusuke , Onodera Atsushi , Hirahara Kiyoshi , Asou Hikari K. , Nakajima Takahiro , Kanno Toshio , Ouchi Yasuo , Uematsu Satoshi , Nishimasu Hiroshi , Nureki Osamu , Tumes Damon J. , Shimojo Naoki , Nakayama Toshinori
Published: October 2018

ST2hi memory-type Th2 cells are identified as a pathogenic subpopulation in eosinophilic airway inflammation. These ST2hi pathogenic Th2 cells produce large amount of IL-5 upon T cell receptor stimulation, but not in response to IL-33 treatment. By contrast, IL-33 alone induces cytokine production in ST2+ group 2 innate lymphoid cells (ILC2). Here we show that a MAPK phosphatase Dusp10 is a key negative regulator of IL-33-induced cytokine production in Th2 cells. In this regard, Dusp10 is expressed by ST2hi pathogenic Th2 cells but not by ILC2, and Dusp10 expression inhibits IL-33-induced cytokine production. Mechanistically, this inhibition is mediated by DUSP10-mediated dephosphorylation and inactivation of p38 MAPK, resulting in reduced GATA3 activity. The deletion of Dusp10 renders ST2hi Th2 cells capable of producing IL-5 by IL-33 stimulation. Our data thus suggest that DUSP10 restricts IL-33-induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-GATA3 activity.
Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions
Authors: Fornasiero Eugenio F. , Mandad Sunit , Wildhagen Hanna , Alevra Mihai , Rammner Burkhard , Keihani Sarva , Opazo Felipe , Urban Inga , Ischebeck Till , Sakib M. Sadman , Fard Maryam K. , Kirli Koray , Centeno Tonatiuh Pena , Vidal Ramon O. , Rahman Raza-Ur , Benito Eva , Fischer André , Dennerlein Sven , Rehling Peter , Feussner Ivo , Bonn Stefan , Simons Mikael , Urlaub Henning , Rizzoli Silvio O.
Published: October 2018

The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult to obtain in vivo. They are readily measured in vitro by feeding cells with isotopically labeled amino acids, followed by mass spectrometry analyses. In vivo proteins are generated from at least two sources: labeled amino acids from the diet, and non-labeled amino acids from the degradation of pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously with a workflow that combines mouse in vivo isotopic labeling, mass spectrometry, and mathematical modeling. We also established several independent approaches to test and validate the results. This enabled us to measure the accurate lifetimes of ~3500 brain proteins. The high precision of our data provided a large set of biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along with a comprehensive catalog of extremely long-lived proteins (ELLPs).
Photonic thermal management of coloured objects
Authors: Li Wei , Shi Yu , Chen Zhen , Fan Shanhui
Published: October 2018

The colours of outdoor structures, such as automobiles, buildings and clothing, are typically chosen for functional or aesthetic reasons. With a chosen colour, however, one must control the radiative thermal load for heating or cooling purposes. Here we provide a comprehensive calculation of the tunable range of radiative thermal load for all colours. The range exceeds 680 Wm−2for all colours, and can be as high as 866 Wm−2, resulting from effects of metamerism, infrared solar absorption and radiative cooling. We experimentally demonstrate that two photonic structures with the same pink colour can have their temperatures differ by 47.6 °C under sunlight. These structures are over 20 °C either cooler or hotter than a commercial paint with a comparable colour. Furthermore, the hotter pink structure is 10 °C hotter than a commercial black paint. These results elucidate the fundamental potentials of photonic thermal management for coloured objects.
Cortical population activity within a preserved neural manifold underlies multiple motor behaviors
Authors: Gallego Juan A. , Perich Matthew G. , Naufel Stephanie N. , Ethier Christian , Solla Sara A. , Miller Lee E.
Published: October 2018

Populations of cortical neurons flexibly perform different functions; for the primary motor cortex (M1) this means a rich repertoire of motor behaviors. We investigate the flexibility of M1 movement control by analyzing neural population activity during a variety of skilled wrist and reach-to-grasp tasks. We compare across tasks the neural modes that capture dominant neural covariance patterns during each task. While each task requires different patterns of muscle and single unit activity, we find unexpected similarities at the neural population level: the structure and activity of the neural modes is largely preserved across tasks. Furthermore, we find two sets of neural modes with task-independent activity that capture, respectively, generic temporal features of the set of tasks and a task-independent mapping onto muscle activity. This system of flexibly combined, well-preserved neural modes may underlie the ability of M1 to learn and generate a wide-ranging behavioral repertoire.
Perceptual learning of fine contrast discrimination changes neuronal tuning and population coding in macaque V4
Authors: Sanayei Mehdi , Chen Xing , Chicharro Daniel , Distler Claudia , Panzeri Stefano , Thiele Alexander
Published: October 2018

Perceptual learning, the improvement in perceptual abilities with training, is thought to be mediated by an alteration of neuronal tuning. It remains poorly understood how tuning properties change as training progresses, whether improved stimulus tuning directly links to increased behavioural readout of sensory information, or how population coding mechanisms change with training. Here, we recorded continuously from multiple neuronal clusters in area V4 while macaque monkeys learned a fine contrast categorization task. Training increased neuronal coding abilities by shifting the steepest point of contrast response functions towards the categorization boundary. Population coding accuracy of difficult discriminations resulted largely from an increased information coding of individual channels, particularly for those channels that in early learning had larger ability for easy discriminations, but comparatively small encoding abilities for difficult discriminations. Population coding was also enhanced by specific changes in correlations. Neuronal activity became more indicative of upcoming choices with training.
An engineered thermal-shift screen reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins
Authors: Nji Emmanuel , Chatzikyriakidou Yurie , Landreh Michael , Drew David
Published: October 2018

Membrane bilayers are made up of a myriad of different lipids that regulate the functional activity, stability, and oligomerization of many membrane proteins. Despite their importance, screening the structural and functional impact of lipid–protein interactions to identify specific lipid requirements remains a major challenge. Here, we use the FSEC-TS assay to show cardiolipin-dependent stabilization of the dimeric sodium/proton antiporter NhaA, demonstrating its ability to detect specific protein-lipid interactions. Based on the principle of FSEC-TS, we then engineer a simple thermal-shift assay (GFP-TS), which facilitates the high-throughput screening of lipid- and ligand- interactions with membrane proteins. By comparing the thermostability of medically relevant eukaryotic membrane proteins and a selection of bacterial counterparts, we reveal that eukaryotic proteins appear to have evolved to be more dependent to the presence of specific lipids.
Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia
Authors: Latham Sharissa L. , Ehmke Nadja , Reinke Patrick Y. A. , Taft Manuel H. , Eicke Dorothee , Reindl Theresia , Stenzel Werner , Lyons Michael J. , Friez Michael J. , Lee Jennifer A. , Hecker Ramona , Frühwald Michael C. , Becker Kerstin , Neuhann Teresa M. , Horn Denise , Schrock Evelin , Niehaus Indra , Sarnow Katharina , Grützmann Konrad , Gawehn Luzie , Klink Barbara , Rump Andreas , Chaponnier Christine , Figueiredo Constanca , Knöfler Ralf , Manstein Dietmar J. , Di Donato Nataliya
Published: October 2018

Germline mutations in the ubiquitously expressed ACTB, which encodes β-cytoplasmic actin (CYA), are almost exclusively associated with Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF). Here, we report six patients with previously undescribed heterozygous variants clustered in the 3′-coding region of ACTB. Patients present with clinical features distinct from BWCFF, including mild developmental disability, microcephaly, and thrombocytopenia with platelet anisotropy. Using patient-derived fibroblasts, we demonstrate cohort specific changes to β-CYA filament populations, which include the enhanced recruitment of thrombocytopenia-associated actin binding proteins (ABPs). These perturbed interactions are supported by in silico modeling and are validated in disease-relevant thrombocytes. Co-examination of actin and microtubule cytoskeleton constituents in patient-derived megakaryocytes and thrombocytes indicates that these β-CYA mutations inhibit the final stages of platelet maturation by compromising microtubule organization. Our results define an ACTB-associated clinical syndrome with a distinct genotype-phenotype correlation and delineate molecular mechanisms underlying thrombocytopenia in this patient cohort.
Astrocytes detect and upregulate transmission at inhibitory synapses of somatostatin interneurons onto pyramidal cells
Authors: Matos Marco , Bosson Anthony , Riebe Ilse , Reynell Clare , Vallée Joanne , Laplante Isabel , Panatier Aude , Robitaille Richard , Lacaille Jean-Claude
Published: October 2018

Astrocytes are important regulators of excitatory synaptic networks. However, astrocytes regulation of inhibitory synaptic systems remains ill defined. This is particularly relevant since GABAergic interneurons regulate the activity of excitatory cells and shape network function. To address this issue, we combined optogenetics and pharmacological approaches, two-photon confocal imaging and whole-cell recordings to specifically activate hippocampal somatostatin or paravalbumin-expressing interneurons (SOM-INs or PV-INs), while monitoring inhibitory synaptic currents in pyramidal cells and Ca2+ responses in astrocytes. We found that astrocytes detect SOM-IN synaptic activity via GABABR and GAT-3-dependent Ca2+ signaling mechanisms, the latter triggering the release of ATP. In turn, ATP is converted into adenosine, activating A1Rs and upregulating SOM-IN synaptic inhibition of pyramidal cells, but not PV-IN inhibition. Our findings uncover functional interactions between a specific subpopulation of interneurons, astrocytes and pyramidal cells, involved in positive feedback autoregulation of dendritic inhibition of pyramidal cells.
Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites
Authors: Fang Hanwei , Gomes Ana Rita , Klages Natacha , Pino Paco , Maco Bohumil , Walker Eloise M. , Zenonos Zenon A. , Angrisano Fiona , Baum Jake , Doerig Christian , Baker David A. , Billker Oliver , Brochet Mathieu
Published: October 2018

In malaria parasites, evolution of parasitism has been linked to functional optimisation. Despite this optimisation, most members of a calcium-dependent protein kinase (CDPK) family show genetic redundancy during erythrocytic proliferation. To identify relationships between phospho-signalling pathways, we here screen 294 genetic interactions among protein kinases in Plasmodium berghei. This reveals a synthetic negative interaction between a hypomorphic allele of the protein kinase G (PKG) and CDPK4 to control erythrocyte invasion which is conserved in P. falciparum. CDPK4 becomes critical when PKG-dependent calcium signals are attenuated to phosphorylate proteins important for the stability of the inner membrane complex, which serves as an anchor for the acto-myosin motor required for motility and invasion. Finally, we show that multiple kinases functionally complement CDPK4 during erythrocytic proliferation and transmission to the mosquito. This study reveals how CDPKs are wired within a stage-transcending signalling network to control motility and host cell invasion in malaria parasites.
Establishment of porcine enterocyte/myofibroblast co-cultures for the growth of porcine rota- and coronaviruses
Authors: Cui Tingting , Theuns Sebastiaan , Desmarets Lowiese M. B. , Xie Jiexiong , De Gryse Gaëtan M. A. , Yang Bo , Van den Broeck Wim , Nauwynck Hans J.
Published: October 2018

A stable culture of primary porcine enterocytes is necessary to study porcine enteric virus replication characteristics. Because the direct cultivation of primary porcine enterocytes is difficult, alternatives have to be considered. As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. First, it was demonstrated that the co-cultured ileocytes and colonocytes were susceptible to an archival rotavirus strain RVA/pig-tc/BEL/RV277/1977/G1P[7] and different other rotavirus genotypes (fecal samples containing G5P[7], G5P[13], G9P[23], G4P[6]). Next, the TGEV Purdue strain infected both ileocytes and colonocytes whereas the Miller strain only infected ileocytes. Last, the PEDV CV777 Vero adapted and non-adapted (fecal suspension) strains could infect co-cultured ileocytes but not colonocytes. The infectivity of the CV777 Vero adapted strain was higher when the cells were cultured without fetal bovine serum and the CV777 fecal suspension only infected the ileocytes cultured without fetal bovine serum. In conclusion, a novel co-culture of porcine enterocytes with myofibroblasts was established, which can be used for the investigation of the replication of enteric viruses.
Systematic investigation of the deformation mechanisms of a γ-TiAl single crystal
Authors: Jeong Byungkwan , Kim Jaemin , Lee Taegu , Kim Seong-Woong , Ryu Seunghwa
Published: October 2018

We propose a theoretical framework to predict the deformation mechanism of the γ-TiAl single crystal without lattice defects by combining the generalized stacking fault energy and the Schmid factor. Our theory is validated against an excellent testbed, the single crystal nanowire, by correctly predicting four major deformation mechanisms, namely, ordinary slip, super slip, twinning, and mixed slip/fracture observed during the tensile and compressive tests along 10 different orientations using molecular dynamics simulations. Interestingly, although lattice defects are not taken into account, the theoretical predictions match well with existing experiments on bulk specimen with only a few exceptions; the exceptions are discussed based on the size-dependent deformation mechanism in the presence of preexisting dislocation sources. We expect that the method in this paper can be generalized to study various ductile intermetallic crystals where conventional Schmid law does not hold well.
Super-resolution imaging via aperture modulation and intensity extrapolation
Authors: Xu Biao , Wang Zhiqiang , He Jinping
Published: October 2018

High-resolution telescopic imaging is of great importance in astronomy. Compared to the complexity and huge cost of constructing extremely-large telescopes, super-resolution technique which breaks the diffraction limit of the imaging system can enhance the spatial resolution with compact setup and low cost. In this paper, a novel super-resolution telescopic imaging method based on aperture modulation and intensity extrapolation is demonstrated, with both simulated and experimental studies performed. The simulation results show that the method can enhance the resolving power of a diffraction-limited telescopic imaging system by >5 times in noise-free case, and the improvement still reaches ~1.8 times with a signal-to-noise ratio of only ~10. The preliminary experimental results show a resolution enhancement of ~1.36 times for the limitations of the experimental setup. Better performance is possible with the images for reconstruction denoised and registered more precisely. The method is also useful in wide-field microscopy.
Selective DNAM-1 expression on small peritoneal macrophages contributes to CD4+ T cell costimulation
Authors: Takenaka Eri , Van Vo Anh , Yamashita-Kanemaru Yumi , Shibuya Akira , Shibuya Kazuko
Published: October 2018

Mouse peritoneal macrophages consist of two subsets: large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), defined as CD11bhiF4/80hiand CD11b+F4/80locells, respectively. We reveal that SPMs, but not LPMs, have the ability to present antigens to naïve CD4+T cells. Coculture of SPMs with naïve ovalbumin (OVA) specific CD4+T cells (OT-II) in the presence of OVA peptide effectively induced CD4+T cells priming. SPMs, but not LPMs, strongly express DNAM-1, an activating immunoreceptor. Although antigen uptake and processing were comparable between WT and DNAM-1-deficient SPMs, deficiency of DNAM-1 on SPMs or blockade of DNAM-1 and its ligand interaction impaired CD4+T cells priming by SPMs. Furthermore, T and B cell responses in mediastinal lymph nodes of mice intraperitoneally immunized with trinitrophenyl (TNP)–OVA protein in Alum adjuvant were enhanced by intraperitoneally transferred wild-type, but not DNAM-1-deficient, SPMs. We propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays a costimulatory role in antigen presentation by SPMs.
Degradation kinetics of Ti-Cu compound layer in transient liquid phase bonded graphite/copper joints
Authors: Lin Jincheng , Huang Mei , Yang Weiqi , Xing Lili
Published: October 2018

The continuous Ti-Cu compound layer produced in brazing of graphite to copper with Ti foil is found to be seriously detrimental to joint properties due to its brittleness. In this work, a transient liquid phase (TLP) bonding method with a diffusion process below melting point is developed to realize a Ti-Cu compound layer free joint. The degradation of Ti-Cu compound layer depends on two simultaneously occurring processes, namely flow of titanium atoms to copper substrate and that to TiC layer on graphite. The latter is determined by growth kinetics of TiC layer based on carbon diffusion process. A degradation model is proposed and applied to optimize the TLP bonding. The improved graphite/copper joints without Ti-Cu compound layer show 20.8% higher in shear strength compared with that of brazing joints.
Severity of local inflammation does not impact development of fibrosis in mouse models of intestinal fibrosis
Authors: Hünerwadel A. , Fagagnini S. , Rogler G. , Lutz C. , Jaeger S. U. , Mamie C. , Weder B. , Ruiz P. A. , Hausmann M.
Published: October 2018

Intestinal fibrosis is thought to be a consequence of excessive tissue repair, and constitutes a common problem in patients with Crohn’s disease (CD). While fibrosis seems to require inflammation as a prerequisite it is unclear whether the severity or persistence of inflammation influences the degree of fibrosis. Our aim was to investigate the role of sustained inflammation in fibrogenesis. For the initiation of fibrosisin vivothe models ofIl10−/−spontaneous colitis, dextran sodium sulfate (DSS)-induced chronic colitis and heterotopic transplantation were used. InIl10−/−mice, we determined a positive correlation between expression of pro-inflammatory factors (Il1β,Tnf,Ifnγ,Mcp1andIl6). We also found a positive correlation between the expression of pro-fibrotic factors (Col3a1 Col1a1,TgfβandαSma). In contrast, no significant correlation was determined between the expression of pro-inflammatoryTnfand pro-fibroticαSma,Col1a1,Col3a1, collagen layer thickness and the hydroxyproline (HYP) content. Results from the DSS-induced chronic colitis model confirmed this finding. In the transplantation model for intestinal fibrosis a pronounced increase inMcp1,inosandIl6inIl10−/−as compared to WT grafts was observed, indicating more severe inflammation inIl10−/−grafts. However, the increase of collagen over time was virtually identical in bothIl10−/−and WT grafts. Severity of inflammation during onset of fibrogenesis did not correlate with collagen deposition. Although inflammation might be a pre-requisite for the initiation of fibrosis our data suggest that it has a minor impact on the progression of fibrosis. Our results suggest that development of fibrosis and inflammation may be disconnected. This may be important for explaining the inefficacy of anti-inflammatory treatments agents in most cases of fibrotic inflammatory bowel diseases (IBD).
Impact of the astronomical lunar 18.6-yr tidal cycle on El-Niño and Southern Oscillation
Authors: Yasuda Ichiro
Published: October 2018

Even though El-Niño and Southern Oscillation (ENSO) has a tremendous impact on global climate and society, its long-term forecast remains difficult. In this study, we discovered a statistically significant relationship between ENSO timing and the 18.6-year period lunar tidal cycle in the mature-phase (December–February) ENSO time-series during 1867–2015 and extending back to 1706 with proxy data. It was found that El-Niño tended to occur in the 1st, 10th, and 13th years after the maximum diurnal tide in the 18.6-yr cycle, and La-Niña tended to occur in the 3rd, 12th, and 16th years. These tendencies were also confirmed by corresponding sea-surface temperature (SST) and sea-level pressure (SLP) distributions; particularly Pacific SST and SLP spatial patterns in the third La-Niña and the tenth El-Niño year well resemble those of Pacific Decadal Oscillation (PDO). These findings contribute to understanding and forecasting long-term ENSO variability.
Showcasing the role of seawater in bacteria recruitment and microbiome stability in sponges
Authors: Turon Marta , Cáliz Joan , Garate Leire , Casamayor Emilio O. , Uriz Maria J.
Published: October 2018

We studied the core bacterial communities of 19 sponge species from Nha Trang Bay (Central Vietnam), with particular emphasis on the contribution of planktonic seawater bacteria to the sponge core microbiomes. To ensure consistent sponge-microbe associations and accurate identification of planktonic bacteria transmitted from seawater, we were very restrictive with the definition of the sponge core microbiomes (present in all the replicates), and with the identification of valid biological 16S rRNA gene sequences (100% sequence identity) that belonged to potentially different bacterial taxa. We found a high overlap (>50% relative abundance) between the sponge species core microbiome and the seawater bacterial core in ca. a half of the studied species, including representatives of both, HMA and LMA sponges. From our restrictive analysis, we point to horizontal transmission as a relevant way of symbiont acquisition in sponges. Some species-specific recognition mechanisms may act in sponges to enrich specific seawater bacteria in their tissues. These mechanisms would allow the maintenance of bacterial communities in a species across geographical ranges. Moreover, besides contrasting preferences in bacteria selection from seawater, divergent physiological traits may also account for the different microbiomes in species of HMA and LMA sponges.
Near-absolute polarization insensitivity in graphene based ultra-narrowband perfect visible light absorber
Authors: Yildirim Deniz Umut , Ghobadi Amir , Ozbay Ekmel
Published: October 2018

Strong light-graphene interaction is essential for the integration of graphene to nanophotonic and optoelectronic devices. The plasmonic response of graphene in terahertz and mid-infrared regions enhances this interaction, and other resonance mechanisms can be adopted in near-infrared and visible ranges to achieve perfect light absorption. However, obtaining near-absolute polarization insensitivity with ultra-narrow absorption bandwidth in the visible and near-infrared regimes remains a challenge. In this regard, we numerically propose a graphene perfect absorber, utilizing the excitation of guided-modes of a dielectric slab waveguide by a novel sub-wavelength dielectric grating structure. When the guided-mode resonance is critically coupled to the graphene, we obtain perfect absorption with an ultra-narrow bandwidth (full-width at half-maximum) of 0.8 nm. The proposed design not only preserves the spectral position of the resonance, but also maintains >98% absorption at all polarization angles. The spectral position of the resonance can be tuned as much as 400 nm in visible and near-infrared regimes by tailoring geometrical parameters. The proposed device has great potential in efficient, tunable, ultra-sensitive, compact and easy-to-fabricate advanced photodetectors and color filters.
High conductivity of ultrathin nanoribbons of SrRuO3 on SrTiO3 probed by infrared spectroscopy
Authors: Falsetti E. , Kalaboukhov A. , Nucara A. , Ortolani M. , Corasaniti M. , Baldassarre L. , Roy P. , Calvani P.
Published: October 2018

SrRuO3 (SRO) is a perovskite increasingly used in oxide-based electronics both for its intrinsic metallicity, which remains unaltered in thin films and for the ease of deposition on dielectric perovskites like SrTiO3, (STO) to implement SRO/STO microcapacitors and other devices. In order to test the reliability of SRO/STO also as high-current on-chip conductor, when the SRO dimensions are pushed to the nanoscale, here we have measured the electrodynamic properties of arrays of nanoribbons, fabricated by lithography starting from an ultrathin film of SRO deposited on a STO substrate. The nanoribbons are 6 or 4 nm thick, 400, 200 and 100 nm wide and 5 mm long. The measurements have been performed by infrared spectroscopy, a non-contact weakly perturbing technique which also allows one to separately determine the carrier density and their scattering rate or mobility. Far-infrared reflectivity spectra have been analyzed by Rigorous Coupled-Wave Analysis (RCWA) and by an Effective Medium Theory, obtaining consistent results. With the radiation polarized along the nanoribbons, we obtain a carrier density similar to that of a flat film used as reference, which in turn is similar to that of bulk SRO. Moreover, in the nanoribbons the carrier scattering rate is even smaller than in the unpatterned film by about a factor of 2. This shows that the transport properties of SRO deposited on STO remain at least unaltered down to nanometric dimensions, with interesting perspectives for implementing on-chip nano-interconnects in an oxide-based electronics. When excited in the perpendicular direction, the nanoribbons appear instead virtually transparent to the radiation field, as predicted by RCWA.
Superior proapoptotic activity of curcumin-loaded mixed block copolymer micelles with mitochondrial targeting properties
Authors: Momekova Denitsa , Ugrinova Iva , Slavkova Marta , Momekov Georgi , Grancharov Georgy , Gancheva Valeria , Petrov Petar D.
Published: October 2018

Multifunctional micelles based on two co-assembled block copolymers are proven to effectively accumulate and deliver curcumin in mitochondria, thus, inducing a much higher proapoptotic activity than single copolymer micelles.
Solvent-free thiophene-based electrolytes: synthesis of new liquid-crystalline ionic conductors for batteries: part I
Authors: Bogdanowicz Krzysztof Artur , Gancarz Pawel , Filapek Michal , Pociecha Damian , Marzec Monika , Chojnacka Ida , Iwan Agnieszka
Published: October 2018

We report the synthesis of new liquid crystalline thiophene esters, ThBz1 and ThBz2, for use in lithium-ion batteries as new, safe, solvent-free ionic conductors.
The protective effects of Poria cocos-derived polysaccharide CMP33 against IBD in mice and its molecular mechanism
Authors: Liu Xiaofei , Yu Xiuting , Xu Xiaofei , Zhang Xiaojun , Zhang Xuewu
Published: October 2018

In this study, the protective effects of a carboxymethyl polysaccharide CMP33 fromPoria cocosagainst inflammatory bowel disease (IBD) were investigated using TNBS-induced colitis in mice.
How to design more efficient hole-transporting materials for perovskite solar cells? Rational tailoring of the triphenylamine-based electron donor
Authors: Xu Yu-Lin , Ding Wei-Lu , Sun Zhu-Zhu
Published: October 2018

Continuously adjustable HOMO levels and high hole mobility are obtained by the structural tailoring of auxiliary TPA-donors.
Multicolor nanobubbles for FRET/ultrasound dual-modal contrast imaging
Authors: Zhang Xiaoting , Liu Renfa , Dai Zhifei
Published: October 2018

Nanobubbles doped with three fluorescent dyes were prepared and showed great potential for multicolor fluorescence/ultrasound dual-modal imaging.