bluuebunny/crossref_metadata_2025 huggingface dataset:
Not urbanization level but socioeconomic, physical and social neighbourhood characteristics are associated with presence and severity of depressive and anxiety disorders
Authors: Generaal Ellen , Timmermans Erik J. , Dekkers Jasper E. C. , Smit Johannes H. , Penninx Brenda W. J. H.
Published: March 2018

Background

Which neighbourhood factors most consistently impact on depression and anxiety remains unclear. This study examines whether objectively obtained socioeconomic, physical and social aspects of the neighbourhood in which persons live are associated with the presence and severity of depressive and anxiety disorders.

Methods

Cross-sectional data are from the Netherlands Study of Depression and Anxiety including participants (n = 2980) with and without depressive and anxiety disorders in the past year (based on DSM-based psychiatric interviews). We also determined symptom severity of depression (Inventory of Depression Symptomatology), anxiety (Beck Anxiety Inventory) and fear (Fear Questionnaire). Neighbourhood characteristics comprised socioeconomic factors (socioeconomic status, home value, number of social security beneficiaries and percentage of immigrants), physical factors (air pollution, traffic noise and availability of green space and water) and social factors (social cohesion and safety). Multilevel regression analyses were performed with the municipality as the second level while adjusting for individual sociodemographic variables and household income.

Results

Not urbanization grade, but rather neighbourhood socioecononomic factors (low socioeconomic status, more social security beneficiaries and more immigrants), physical factors (high levels of traffic noise) and social factors (lower social cohesion and less safety) were associated with the presence of depressive and anxiety disorders. Most of these neighbourhood characteristics were also associated with increased depressive and anxiety symptoms severity.

Conclusion

These findings suggest that it is not population density in the neighbourhood, but rather the quality of socioeconomic, physical and social neighbourhood characteristics that is associated with the presence and severity of affective disorders.
Written corrective feedback from sociocultural theoretical perspectives: A research agenda
Authors: Storch Neomy
Published: March 2018

Using key constructs from sociocultural theory and activity theory, this paper outlines three broad areas of future research on written corrective feedback (WCF) that may be of interest to second language (L2) researchers and practitioners. The first area uses the constructs of the Zone of Proximal Development (ZPD) and scaffolding to assess the nature and appropriateness of the feedback provided. The second area uses the construct of tools and considers learners’ responses to the means used to provide WCF, including automated feedback. The third, and perhaps most important area, views WCF as an activity, and examines context-related and individual factors that impact on the provision and response to WCF. The paper provides concrete examples of small-scale longitudinal studies in each of these areas, including recommendations as to the kind of data and measures to employ.
Using online media-sourced seizure data to assess the illegal wildlife trade in Siamese rosewood
Authors: SIRIWAT PENTHAI , NIJMAN VINCENT
Published: March 2018

The illegal wildlife trade is covert by nature, and thus is often challenging to study. Seizure data is traditionally the most common means to gain insight into the trade for many species. Online media-sourced seizure records were applied to study the illegal trade of Siamese rosewood (Dalbergia cochinchinensis), one of 33 timber species of hongmu (rosewood), which is logged to produce luxury products predominantly for Chinese markets. Despite recent international pressure to strengthen the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) regulations, illegal trade of Siamese rosewood is prevalent in its range states. This paper will explore seizure reports in Thai online media and analyse spatial, temporal and other factors that potentially explain the trade. Between January 2014 and April 2016, 835 independent seizures were reported in 37 of 76 provinces in Thailand. Seizures occurred mostly in the north-eastern and eastern provinces with higher numbers of seizures closer to the border. The number of seizure reports decreased over time, and the average number of logs seized per seizure was consistent over the 28-month study period. Inadequate domestic legislation is a key factor facilitating the trade. Improvements are needed to the legislation and enforcement ahead of implementing other regional timber-specific initiatives and regulations. In this specific context, CITES also appears to be unacknowledged and ineffective in hampering the Siamese rosewood trade. Importantly, we find that using media-sourced seizure data is highly apt in Thailand's context, considering Thailand's sensitive political state and the prevalence of trade in other non CITES-listed rosewood species. The approach demonstrated here is applicable to many other wildlife species.
In situ measurements of snow accumulation in the Amundsen Sea Embayment during 2016
Authors: Johnson Joanne S. , O’Donnell John P. , Thomas Elizabeth R.
Published: March 2018

Measurements of snow accumulation are critical for reliable prediction of future ice mass loss and hence projections of sea level change. However, there are currently very few published in situ measurements of snow accumulation in the Pine Island–Thwaites glacier catchment of the Amundsen Sea Embayment, and none from low elevation sites west of 100.77° longitude. Here measurements of snow accumulation over an 11 month period in 2016 are reported for six sites in the Pine Island–Thwaites glacier catchment. The average accumulation rates of 0.10±0.01 to 1.26±0.22 m w.e. yr-1 are comparable with those derived from airborne radar for the period 1985–2009, suggesting very high rates of snowfall, particularly in the vicinity of the grounding line.
Religion and Foreign Aid
Authors: Blackman Alexandra Domike
Published: March 2018

Foreign aid allocations represent one of several important economic policy tools used by governments to realize their foreign policy objectives. Using a conjoint survey of respondents in the United States, this paper shows that recipient country religion is a significant determinant of individual-level foreign aid preferences. In particular, respondents express a preference for giving to Christian-majority countries in contrast to Muslim- or Buddhist-majority countries. This effect is comparable with that of other important determinants of support for foreign aid, such as a country's status as a U.S. ally or trade partner. Importantly, the preference for Christian recipient countries is especially pronounced among Christian, and most notably Evangelical Christian, respondents. This paper explores two potential mechanisms for the effect of religion: country religion as a heuristic and an individual-level preference for giving to co-religionists.
A Possible Twin: The 1960s Twin Study Revisited/Twin Research: Twin-to-Twin Heart Transplantation; Distinguishing Monozygotic Twins; Twin Conceptions via Oocyte Donation; Factors Affecting Craniofacial Traits/In the Media: Triplet Delivery in the UK; Conjoined Twins and the Concept of Self; Colombian Twin Trainers; Skin Grafting to Save an Identical Co-Twin; Lack of Physical Flaws in Dolly the Cloned Sheep; Possible Conjoined Twins of Opposite-Sex; Passing of the Remaining Twin From the World's Longest Separated Pair
Authors: Segal Nancy L.
Published: March 2018

This article begins with the story of a 51-year-old Los Angeles, California man, Justin Goldberg, whose daughter caught a glimpse of his striking look-alike at a popular market. Many people have so-called doppelgängers, but this occurrence is especially intriguing — the individual in question, born in New York City in the mid-1960s to an unwed mother, was an adoptee placed by the Louise Wise Adoption Agency. This agency, under the guidance of a prominent psychiatrist, decided to place twins in separate homes. Some of these twin children were part of a controversial child development study that was hidden from them and their parents. Next, recent and current twin research on heart transplantation, distinguishing monozygotic co-twins, twin conceptions via oocyte donation and factors affecting craniofacial traits are summarized. The article concludes with highlights on twins in the media, specifically, a triplet delivery in the United Kingdom, self-concept and consciousness in conjoined twins, Colombian twin trainers, skin grafting to save an identical co-twin, lack of physical flaws in Dolly the cloned sheep, possible opposite-sex conjoined twins, and the passing of the remaining twin from the world's longest separated pair.
Lower Levels of Resistance to Change (but not Opposition to Equality) Is Related to Analytic Cognitive Style
Authors: Yilmaz Onurcan , Saribay S. Adil
Published: March 2018

Abstract. In recent years, there has been increasing research attention to cognitive style differences between liberals and conservatives. While some studies have found a negative relation between conservatism and analytic thinking tendency, others have not observed such a relation. None of these studies has measured the core motives underlying conservative ideology and investigated their relation with analytic cognitive style (ACS). We predicted that ACS is related to only one of the core motives underlying conservatism (resistance to change), but not the other (opposition to equality). This hypothesis was supported in three non-Western samples (total n = 1,552). This finding may clarify why some studies found a relation between cognitive style and conservatism, while others did not.
The elusive abnormal CO2 insertion enabled by metal-ligand cooperative photochemical selectivity inversion
Authors: Schneck Felix , Ahrens Jennifer , Finger Markus , Stückl A. Claudia , Würtele Christian , Schwarzer Dirk , Schneider Sven
Published: March 2018

Direct hydrogenation of CO2 to CO, the reverse water–gas shift reaction, is an attractive route to CO2 utilization. However, the use of molecular catalysts is impeded by the general reactivity of metal hydrides with CO2. Insertion into M–H bonds results in formates (MO(O)CH), whereas the abnormal insertion to the hydroxycarbonyl isomer (MC(O)OH), which is the key intermediate for CO-selective catalysis, has never been directly observed. We here report that the selectivity of CO2 insertion into a Ni–H bond can be inverted from normal to abnormal insertion upon switching from thermal to photochemical conditions. Mechanistic examination for abnormal insertion indicates photochemical N–H reductive elimination as the pivotal step that leads to an umpolung of the hydride ligand. This study conceptually introduces metal-ligand cooperation for selectivity control in photochemical transformations.
Elementary steps in electrical doping of organic semiconductors
Authors: Tietze Max L. , Benduhn Johannes , Pahner Paul , Nell Bernhard , Schwarze Martin , Kleemann Hans , Krammer Markus , Zojer Karin , Vandewal Koen , Leo Karl
Published: March 2018

Fermi level control by doping is established since decades in inorganic semiconductors and has been successfully introduced in organic semiconductors. Despite its commercial success in the multi-billion OLED display business, molecular doping is little understood, with its elementary steps controversially discussed and mostly-empirical-materials design. Particularly puzzling is the efficient carrier release, despite a presumably large Coulomb barrier. Here we quantitatively investigate doping as a two-step process, involving single-electron transfer from donor to acceptor molecules and subsequent dissociation of the ground-state integer-charge transfer complex (ICTC). We show that carrier release by ICTC dissociation has an activation energy of only a few tens of meV, despite a Coulomb binding of several 100 meV. We resolve this discrepancy by taking energetic disorder into account. The overall doping process is explained by an extended semiconductor model in which occupation of ICTCs causes the classically known reserve regime at device-relevant doping concentrations.
A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues
Authors: Wan Hao , Yue Jingying , Zhu Shoujun , Uno Takaaki , Zhang Xiaodong , Yang Qinglai , Yu Kuai , Hong Guosong , Wang Junying , Li Lulin , Ma Zhuoran , Gao Hongpeng , Zhong Yeteng , Su Jessica , Antaris Alexander L. , Xia Yan , Luo Jian , Liang Yongye , Dai Hongjie
Published: March 2018

Fluorescence imaging of biological systems in the second near-infrared (NIR-II, 1000–1700 nm) window has shown promise of high spatial resolution, low background, and deep tissue penetration owing to low autofluorescence and suppressed scattering of long wavelength photons. Here we develop a bright organic nanofluorophore (named p-FE) for high-performance biological imaging in the NIR-II window. The bright NIR-II >1100 nm fluorescence emission from p-FE affords non-invasive in vivo tracking of blood flow in mouse brain vessels. Excitingly, p-FE enables one-photon based, three-dimensional (3D) confocal imaging of vasculatures in fixed mouse brain tissue with a layer-by-layer imaging depth up to ~1.3 mm and sub-10 µm high spatial resolution. We also perform in vivo two-color fluorescence imaging in the NIR-II window by utilizing p-FE as a vasculature imaging agent emitting between 1100 and 1300 nm and single-walled carbon nanotubes (CNTs) emitting above 1500 nm to highlight tumors in mice.
RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia
Authors: Cheng Jason X. , Chen Li , Li Yuan , Cloe Adam , Yue Ming , Wei Jiangbo , Watanabe Kenneth A. , Shammo Jamile M. , Anastasi John , Shen Qingxi J. , Larson Richard A. , He Chuan , Le Beau Michelle M. , Vardiman James W.
Published: March 2018

The roles of RNA 5-methylcytosine (RNA:m5C) and RNA:m5C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure. In contrast, NSUN1 binds BRD4 and RNA-polymerase-II to form an active chromatin structure that is insensitive to 5-AZA, but hypersensitive to the BRD4 inhibitor JQ1 and to the downregulation of NSUN1 by siRNAs. Both 5-AZA-resistant leukaemia cell lines and clinically 5-AZA-resistant myelodysplastic syndrome and acute myeloid leukaemia specimens have a significant increase in RNA:m5C and NSUN1-/BRD4-associated active chromatin. This study reveals novel RNA:m5C/RCMT-mediated chromatin structures that modulate 5-AZA response/resistance in leukaemia cells, and hence provides a new insight into treatment of leukaemia.
Difluoromethylation of (hetero)aryl chlorides with chlorodifluoromethane catalyzed by nickel
Authors: Xu Chang , Guo Wen-Hao , He Xu , Guo Yin-Long , Zhang Xue-Ying , Zhang Xingang
Published: March 2018

Relatively low reactivity hinders using chlorodifluoromethane (ClCF2H) for general difluoromethylation with organic molecules, despite its availability as an inexpensive industrial chemical. To date, transformations of ClCF2H are very limited and most of them involve difluorocarbene intermediate. Here, we describe a strategy for difluoromethylation of aromatics through nickel-catalyzed cross-coupling of ClCF2H with readily accessible (hetero)aryl chlorides. The reaction proceeds under mild reaction conditions with high efficiency and features synthetic simplicity without preformation of arylmetals and broad substrate scope, including a variety of heteroaromatics and commercially available pharmaceuticals. The reliable practicability and scalability of the current nickel-catalyzed process has also been demonstrated by several 10-g scale reactions without loss of reaction efficiency. Preliminary mechanistic studies reveal that the reaction starts from the oxidative addition of aryl chlorides to Ni(0) and a difluoromethyl radical is involved in the reaction, providing a route for applications of ClCF2H in organic synthesis and related chemistry.
Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control
Authors: Yang Jin-Yu , Deng Xiang-Yu , Li Yi-Sheng , Ma Xian-Cai , Feng Jian-Xiong , Yu Bing , Chen Yang , Luo Yi-Ling , Wang Xi , Chen Mei-Ling , Fang Zhi-Xin , Zheng Fu-Xiang , Li Yi-Ping , Zhong Qian , Kang Tie-Bang , Song Li-Bing , Xu Rui-Hua , Zeng Mu-Sheng , Chen Wei , Zhang Hui , Xie Wei , Gao Song
Published: March 2018

Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N′-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3′-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family.
Operando tribochemical formation of onion-like-carbon leads to macroscale superlubricity
Authors: Berman Diana , Narayanan Badri , Cherukara Mathew J. , Sankaranarayanan Subramanian K. R. S. , Erdemir Ali , Zinovev Alexander , Sumant Anirudha V.
Published: March 2018

Stress-induced reactions at the sliding interface during relative movement are known to cause structural or chemical modifications in contacting materials. The nature of these modifications at the atomic level and formation of byproducts in an oil-free environment, however, remain poorly understood and pose uncertainties in predicting the tribological performance of the complete tribosystem. Here, we demonstrate that tribochemical reactions occur even in dry conditions when hydrogenated diamond-like carbon (H-DLC) surface is slid against two-dimensional (2D) molybdenum disulfide along with nanodiamonds in dry nitrogen atmosphere. Detailed experimental studies coupled with reactive molecular dynamics simulations reveal that at high contact pressures, diffusion of sulfur from the dissociated molybdenum disulfide led to amorphization of nanodiamond and subsequent transformation to onion-like carbon structures (OLCs). The in situ formation of OLCs at the sliding interface provide reduced contact area as well as incommensurate contact with respect to the H-DLC surface, thus enabling successful demonstration of superlubricity
nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer
Authors: Ahn Ji-Hye , Lee Hyun-Sung , Lee Ju-Seog , Lee Yeon-Su , Park Jong-Lyul , Kim Seon-Young , Hwang Jung-Ah , Kunkeaw Nawapol , Jung Sung Yun , Kim Tae Jin , Lee Kwang-Soo , Jeon Sung Ho , Lee Inhan , Johnson Betty H. , Choi Jung-Hye , Lee Yong Sun
Published: March 2018

Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways.
Adsorption-induced slip inhibition for polymer melts on ideal substrates
Authors: Ilton Mark , Salez Thomas , Fowler Paul D. , Rivetti Marco , Aly Mohammed , Benzaquen Michael , McGraw Joshua D. , Raphaël Elie , Dalnoki-Veress Kari , Bäumchen Oliver
Published: March 2018

Hydrodynamic slip, the motion of a liquid along a solid surface, represents a fundamental phenomenon in fluid dynamics that governs liquid transport at small scales. For polymeric liquids, de Gennes predicted that the Navier boundary condition together with polymer reptation implies extraordinarily large interfacial slip for entangled polymer melts on ideal surfaces; this Navier-de Gennes model was confirmed using dewetting experiments on ultra-smooth, low-energy substrates. Here, we use capillary leveling—surface tension driven flow of films with initially non-uniform thickness—of polymeric films on these same substrates. Measurement of the slip length from a robust one parameter fit to a lubrication model is achieved. We show that at the low shear rates involved in leveling experiments as compared to dewetting ones, the employed substrates can no longer be considered ideal. The data is instead consistent with a model that includes physical adsorption of polymer chains at the solid/liquid interface.
Author Correction: Efficient green light-emitting diodes based on quasi-two-dimensional composition and phase engineered perovskite with surface passivation
Authors: Yang Xiaolei , Zhang Xingwang , Deng Jinxiang , Chu Zema , Jiang Qi , Meng Junhua , Wang Pengyang , Zhang Liuqi , Yin Zhigang , You Jingbi
Published: March 2018

The original version of this Article omitted an acknowledgement to the source of Fig. 1a. The following has been added to the end of the caption to Fig. 1: ‘Figure 1a adapted from ref. 13 (copyright 2016 Macmillan Publishers)’. This has been corrected in the PDF and HTML versions of the Article.
Bismuth and antimony-based oxyhalides and chalcohalides as potential optoelectronic materials
Authors: Ran Zhao , Wang Xinjiang , Li Yuwei , Yang Dongwen , Zhao Xin-Gang , Biswas Koushik , Singh David J. , Zhang Lijun
Published: March 2018

In the last decade the ns2 cations (e.g., Pb2+ and Sn2+)-based halides have emerged as one of the most exciting new classes of optoelectronic materials, as exemplified by for instance hybrid perovskite solar absorbers. These materials not only exhibit unprecedented performance in some cases, but they also appear to break new ground with their unexpected properties, such as extreme tolerance to defects. However, because of the relatively recent emergence of this class of materials, there remain many yet to be fully explored compounds. Here, we assess a series of bismuth/antimony oxyhalides and chalcohalides using consistent first principles methods to ascertain their properties and obtain trends. Based on these calculations, we identify a subset consisting of three types of compounds that may be promising as solar absorbers, transparent conductors, and radiation detectors. Their electronic structure, connection to the crystal geometry, and impact on band-edge dispersion and carrier effective mass are discussed.
Quantitative perfusion imaging of neoplastic liver lesions: A multi-institution study
Authors: Pahwa Shivani , Liu Hao , Chen Yong , Dastmalchian Sara , O’Connor Gregory , Lu Ziang , Badve Chaitra , Yu Alice , Wright Katherine , Chalian Hamid , Rao Shengxiang , Fu Caixia , Vallines Ignacio , Griswold Mark , Seiberlich Nicole , Zeng Mengsu , Gulani Vikas
Published: March 2018

We describe multi-institutional experience using free-breathing, 3D Spiral GRAPPA-based quantitative perfusion MRI in characterizing neoplastic liver masses. 45 patients (age: 48–72 years) were prospectively recruited at University Hospitals, Cleveland, USA on a 3 Tesla (T) MRI, and at Zhongshan Hospital, Shanghai, China on a 1.5 T MRI. Contrast-enhanced volumetric T1-weighted images were acquired and a dual-input single-compartment model used to derive arterial fraction (AF), distribution volume (DV) and mean transit time (MTT) for the lesions and normal parenchyma. The measurements were compared using two-tailed Student’s t-test, with Bonferroni correction applied for multiple-comparison testing. 28 hepatocellular carcinoma (HCC) and 17 metastatic lesions were evaluated. No significant difference was noted in perfusion parameters of normal liver parenchyma and neoplastic masses at two centers (p = 0.62 for AF, 0.015 for DV, 0.42 for MTT for HCC, p = 0.13 for AF, 0.97 for DV, 0.78 for MTT for metastases). There was statistically significant difference in AF, DV, and MTT of metastases and AF and DV of HCC compared to normal liver parenchyma (p < 0.5/9 = 0.0055). A statistically significant difference was noted in the MTT of metastases compared to hepatocellular carcinoma (p < 0.001*10-5). In conclusion, 3D Spiral-GRAPPA enabled quantitative free-breathing perfusion MRI exam provides robust perfusion parameters.
Dual role of E-cadherin in the regulation of invasive collective migration of mammary carcinoma cells
Authors: Elisha Yair , Kalchenko Vyacheslav , Kuznetsov Yuri , Geiger Benjamin
Published: March 2018

In this article, we explore a non-canonical form of collective cell migration, displayed by the metastatic murine mammary carcinoma cell line 4T1. We show here that in sparsely plated 4T1 cells, E-cadherin levels are moderately reduced (~50%), leading to the development of collective migration, whereby cells translocate in loose clusters, interconnected by thin membrane tethers. Knocking down E-cadherin blocked tether formation in these cells, leading to enhancement of migration rate and, at the same time, to suppression of lung metastases formation in vivo, and inhibition of infiltration into fibroblast monolayers ex vivo. These findings suggest that the moderate E-cadherin levels present in wild-type 4T1 cells play a key role in promoting cancer invasion and metastasis.
Virulence factors of Moraxella catarrhalis outer membrane vesicles are major targets for cross-reactive antibodies and have adapted during evolution
Authors: Augustyniak Daria , Seredyński Rafał , McClean Siobhán , Roszkowiak Justyna , Roszniowski Bartosz , Smith Darren L. , Drulis-Kawa Zuzanna , Mackiewicz Paweł
Published: March 2018

Moraxella catarrhalis is a common human respiratory tract pathogen. Its virulence factors associated with whole bacteria or outer membrane vesicles (OMVs) aid infection, colonization and may induce specific antibodies. To investigate pathogen-host interactions, we applied integrated bioinformatic and immunoproteomic (2D-electrophoresis, immunoblotting, LC-MS/MS) approaches. We showed that OMV proteins engaged exclusively in complement evasion and colonization strategies, but not those involved in iron transport and metabolism, are major targets for cross-reacting antibodies produced against phylogenetically divergent M. catarrhalis strains. The analysis of 31 complete genomes of M. catarrhalis and other Moraxella revealed that OMV protein-coding genes belong to 64 orthologous groups, five of which are restricted to M. catarrhalis. This species showed a two-fold increase in the number of OMV protein-coding genes relative to its ancestors and animal-pathogenic Moraxella. The appearance of specific OMV factors and the increase in OMV-associated virulence proteins during M. catarrhalis evolution is an interesting example of pathogen adaptation to optimize colonization. This precisely targeted cross-reactive immunity against M. catarrhalis may be an important strategy of host defences to counteract this phenomenon. We demonstrate that cross-reactivity is closely associated with the anti-virulent antibody repertoire which we have linked with adaptation of this pathogen to the host.
Intermittent dynamics in complex systems driven to depletion
Authors: Escobar Juan V. , Pérez Castillo Isaac
Published: March 2018

When complex systems are driven to depletion by some external factor, their non-stationary dynamics can present an intermittent behaviour between relative tranquility and burst of activity whose consequences are often catastrophic. To understand and ultimately be able to predict such dynamics, we propose an underlying mechanism based on sharp thresholds of a local generalized energy density that naturally leads to negative feedback. We find a transition from a continuous regime to an intermittent one, in which avalanches can be predicted despite the stochastic nature of the process. This model may have applications in many natural and social complex systems where a rapid depletion of resources or generalized energy drives the dynamics. In particular, we show how this model accurately describes the time evolution and avalanches present in a real social system.
A Comprehensive Physical Impedance Model of Polymer Electrolyte Fuel Cell Cathodes in Oxygen-free Atmosphere
Authors: Obermaier Michael , Bandarenka Aliaksandr S. , Lohri-Tymozhynsky Cyrill
Published: March 2018

Electrochemical impedance spectroscopy (EIS) is an indispensable tool for non-destructive operando characterization of Polymer Electrolyte Fuel Cells (PEFCs). However, in order to interpret the PEFC’s impedance response and understand the phenomena revealed by EIS, numerous semi-empirical or purely empirical models are used. In this work, a relatively simple model for PEFC cathode catalyst layers in absence of oxygen has been developed, where all the equivalent circuit parameters have an entire physical meaning. It is based on: (i) experimental quantification of the catalyst layer pore radii, (ii) application of De Levie’s analytical formula to calculate the response of a single pore, (iii) approximating the ionomer distribution within every pore, (iv) accounting for the specific adsorption of sulfonate groups and (v) accounting for a small H2crossover through ~15 μm ionomer membranes. The derived model has effectively only 6 independent fitting parameters and each of them has clear physical meaning. It was used to investigate the cathode catalyst layer and the double layer capacitance at the interface between the ionomer/membrane and Pt-electrocatalyst. The model has demonstrated excellent results in fitting and interpretation of the impedance data under different relative humidities. A simple script enabling fitting of impedance data is provided as supporting information.
Integrative analysis of large scale transcriptome data draws a comprehensive landscape of Phaeodactylum tricornutum genome and evolutionary origin of diatoms
Authors: Rastogi Achal , Maheswari Uma , Dorrell Richard G. , Vieira Fabio Rocha Jimenez , Maumus Florian , Kustka Adam , McCarthy James , Allen Andy E. , Kersey Paul , Bowler Chris , Tirichine Leila
Published: March 2018

Diatoms are one of the most successful and ecologically important groups of eukaryotic phytoplankton in the modern ocean. Deciphering their genomes is a key step towards better understanding of their biological innovations, evolutionary origins, and ecological underpinnings. Here, we have used 90 RNA-Seq datasets from different growth conditions combined with published expressed sequence tags and protein sequences from multiple taxa to explore the genome of the model diatom Phaeodactylum tricornutum, and introduce 1,489 novel genes. The new annotation additionally permitted the discovery of extensive alternative splicing in diatoms, including intron retention and exon skipping, which increase the diversity of transcripts generated in changing environments. In addition, we have used up-to-date reference sequence libraries to dissect the taxonomic origins of diatom genes. We show that the P. tricornutum genome is enriched in lineage-specific genes, with up to 47% of the gene models present only possessing orthologues in other stramenopile groups. Finally, we have performed a comprehensive de novo annotation of repetitive elements showing novel classes of transposable elements such as SINE, MITE and TRIM/LARD. This work provides a solid foundation for future studies of diatom gene function, evolution and ecology.
The evolutionarily conserved genes: Tex37, Ccdc73, Prss55 and Nxt2 are dispensable for fertility in mice
Authors: Khan Manan , Jabeen Nazish , Khan Teka , Hussain Hafiz Muhammad Jafar , Ali Asim , Khan Ranjha , Jiang Long , Li Tao , Tao Qizhao , Zhang Xingxia , Yin Hao , Yu Changping , Jiang Xiaohua , Shi Qinghua
Published: March 2018

There are more than 2300 genes that are predominantly expressed in mouse testes. The role of hundreds of these genes has been studied in mouse spermatogenesis but still there are many genes whose function is unknown. Gene knockout (KO) strategy in mice is widely used for in vivo study of gene function. The present study was designed to explore the function of the four genes: Tex37, Ccdc73, Prss55 and Nxt2, which were evolutionarily conserved in eutherians. We found that these genes had a testis-enriched expression pattern in mice except Nxt2. We knocked out these genes by CRISPR/Cas9 individually and found that all the KO mice had normal fertility with no detectable difference in testis/body weight ratios, epididymal sperm counts, as well as testicular and epididymal histology from wild type mice. Although these genes are evolutionarily conserved in eutherians including human and mouse, they are not individually essential for spermatogenesis, testis development and male fertility in mice in laboratory conditions. Our report of these fertile KO data could avoid the repetition and duplication of efforts which will help in prioritizing efforts to focus on genes that are indispensable for male reproduction.
Pupil size reflects successful encoding and recall of memory in humans
Authors: Kucewicz Michal T. , Dolezal Jaromir , Kremen Vaclav , Berry Brent M. , Miller Laura R. , Magee Abigail L. , Fabian Vratislav , Worrell Gregory A.
Published: March 2018

Pupil responses are known to indicate brain processes involved in perception, attention and decision-making. They can provide an accessible biomarker of human memory performance and cognitive states in general. Here we investigated changes in the pupil size during encoding and recall of word lists. Consistent patterns in the pupil response were found across and within distinct phases of the free recall task. The pupil was most constricted in the initial fixation phase and was gradually more dilated through the subsequent encoding, distractor and recall phases of the task, as the word items were maintained in memory. Within the final recall phase, retrieving memory for individual words was associated with pupil dilation in absence of visual stimulation. Words that were successfully recalled showed significant differences in pupil response during their encoding compared to those that were forgotten – the pupil was more constricted before and more dilated after the onset of word presentation. Our results suggest pupil size as a potential biomarker for probing and modulation of memory processing.
Plastic antibodies tailored on quantum dots for an optical detection of myoglobin down to the femtomolar range
Authors: Piloto Ana Margarida , Ribeiro David S. M. , Rodrigues S. Sofia M. , Santos Catarina , Santos João L. M. , Sales M. Goreti F.
Published: March 2018

A highly sensitive fluorescence detection probe was developed by tailoring plastic antibodies on the external surface of aqueous soluble quantum dots (QDs). The target was Myoglobin (Myo), a cardiac biomarker that quenched the intrinsic fluorescent emission of cadmium telluride (CdTe) QDs capped with mercaptopropionic acid (CdTe-MPA-QDs). The QDs were incubated with the target protein and further modified with a molecularly-imprinted polymer (MIP) produced by radical polymerization of acrylamide and bisacrylamide. The main physical features of the materials were assessed by electron microscopy, dynamic light scattering (DLS), UV/Vis spectrophotometry and spectrofluorimetry. The plastic antibodies enabled Myo rebinding into the QDs with subsequent fluorescence quenching. This QD-probe could detect Myo concentrations from 0.304 to 571 pg/ml (50.6 fM to 95 pM), with a limit of detection of 0.045 pg/ml (7.6 fM). The proposed method was applied to the determination of Myo concentrations in synthetic human serum. The results obtained demonstrated the ability of the modified-QDs to determine Myo below the cut-off values of myocardial infarction. Overall, the nanostructured MIP-QDs reported herein displayed quick responses, good stability and sensitivity, and high selectivity for Myo, offering the potential to be explored as new emerging sensors for protein detection in human samples.
Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease
Authors: Crowe J. Scott , Roberts Kevin J. , Carlton Timothy M. , Maggiore Luana , Cubitt Marion F. , Clare Simon , Harcourt Katherine , Reckless Jill , MacDonald Thomas T. , Ray Keith P. , Vossenkämper Anna , West Michael R.
Published: March 2018

TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised.
The generation mechanism of spike-and-slow wave discharges appearing on thalamic relay nuclei
Authors: Hu Bing , Guo Yu , Shi Feng , Zou Xiaoqiang , Dong Jing , Pan Long , Yu Min , Zhou Chaowei , Cheng Zhang , Tang Wanyue , Sun Haochen , Chen Luonan
Published: March 2018

In this paper, we use a model modified from classic corticothalamic network(CT) to explore the mechanism of absence seizures appearing on specific relay nuclei (SRN) of the thalamus. It is found that typical seizure states appear on SRN through tuning several critical connection strengths in the model. In view of previous experimental and theoretical works which were mainly on epilepsy seizure phenomena appearing on excitatory pyramidal neurons (EPN) of the cortex, this is a novel model to consider the seizure observed on thalamus. In particular, the onset mechanism is different from previous theoretical studies. Inspired by some previous clinical and experimental studies, we employ the external stimuli voltage on EPN and SRN in the network, and observe that the seizure can be well inhibited by tuning the stimulus intensity appropriately. We further explore the effect of the signal transmission delays on seizures, and found that the polyspike phenomenon appears only when the delay is sufficiently large. The experimental data also confirmed our model. Since there is a complex network in the brain and all organizations are interacting closely with each other, the results obtained in this paper provide not only biological insights into the regulatory mechanisms but also a reference for the prevention and treatment of epilepsy in future.
Novel crab predator causes marine ecosystem regime shift
Authors: Kotta J. , Wernberg T. , Jänes H. , Kotta I. , Nurkse K. , Pärnoja M. , Orav-Kotta H.
Published: March 2018

The escalating spread of invasive species increases the risk of disrupting the pathways of energy flow through native ecosystems, modify the relative importance of resource (‘bottom-up’) and consumer (‘top-down’) control in food webs and thereby govern biomass production at different trophic levels. The current lack of understanding of interaction cascades triggered by non-indigenous species underscores the need for more basic exploratory research to assess the degree to which novel species regulate bottom-up and/or top down control. Novel predators are expected to produce the strongest effects by decimating consumers, and leading to the blooms of primary producers. Here we show how the arrival of the invasive crab Rhithropanopeus harrisii into the Baltic Sea – a bottom-up controlled ecosystem where no equivalent predators ever existed – appeared to trigger not only strong top-down control resulting in a decline in richness and biomass of benthic invertebrates, but also an increase in pelagic nutrients and phytoplankton biomass. Thus, the addition of a novel interaction – crab predation – to an ecosystem has a potential to reduce the relative importance of bottom-up regulation, relax benthic-pelagic coupling and reallocate large amounts of nutrients from benthic to pelagic processes, resulting in a regime shift to a degraded ecosystem state.
The transcriptional profiles and functional implications of long non-coding RNAs in the unfolded protein response
Authors: Quan Hongyang , Fan Qianqian , Li Chuang , Wang Yan-ying , Wang Lin
Published: March 2018

The unfolded protein response (UPR) is activated, when the folding capacity is compromised in the endoplasmic reticulum (ER). To date, most studies focused on the coding genes and microRNAs in UPR. Other non-coding RNAs affected by UPR and their roles in UPR have not been systematically studied. Long noncoding RNAs (lncRNAs) are increasingly recognized as powerful epigenetic regulators. In this study, we transcriptomically profiled the lncRNAs and mRNAs from mouse embryonic fibroblasts under ER stress, and identified many differentially expressed lncRNAs and mRNAs. Genomic location and mRNA-lncRNA co-expression analyses predicted a number of lncRNAs, which potentially regulate the expression of UPR genes. In particular, FR229754, an exonic sense lncRNA, is significantly up-regulated in UPR. FR229754 overlaps with Sel1l, and their expressions correlated with each other. Sel1l is involved in the ER-associated protein degradation. Silencing of FR229754 did not much affect the expression of Sel1l, but markedly reduced the levels of BiP/GRP78/Hspa5, a major ER chaperon up-regulated in UPR. Probing with pathway-specific inhibitors showed that up-regulation of FR229754 and Sel1 depended on the activation of PERK. Together, our study identified a number of candidate lncRNAs and paved the way for future characterization of their functions in UPR.
Using high-amplitude and focused transcranial alternating current stimulation to entrain physiological tremor
Authors: Khatoun Ahmad , Breukers Jolien , Op de Beeck Sara , Nica Ioana Gabriela , Aerts Jean-Marie , Seynaeve Laura , Haeck Tom , Asamoah Boateng , Mc Laughlin Myles
Published: March 2018

Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that can entrain physiological tremor in healthy volunteers. We conducted two experiments to investigate the effectiveness of high-amplitude and focused tACS montages at entraining physiological tremor. Experiment 1 used saline-soaked sponge electrodes with an extra-cephalic return electrode and compared the effects of a motor (MC) and prefrontal cortex (PFC) electrode location. Average peak-amplitude was 1.925 mA. Experiment 2 used gel-filled cup-electrodes in a 4 × 1 focused montage and compared the effects of MC and occipital cortex (OC) tACS. Average peak-amplitude was 4.45 mA. Experiment 1 showed that unfocused MC and PFC tACS both produced phosphenes and significant phase entrainment. Experiment 2 showed that focused MC and OC tACS produced no phosphenes but only focused MC tACS caused significant phase entrainment. At the group level, tACS did not have a significant effect on tremor amplitude. However, with focused tACS there was a significant correlation between phase entrainment and tremor amplitude modulation: subjects with higher phase entrainment showed more tremor amplitude modulation. We conclude that: (1) focused montages allow for high-amplitude tACS without phosphenes and (2) high amplitude focused tACS can entrain physiological tremor.
Haplotype Heritability Mapping Method Uncovers Missing Heritability of Complex Traits
Authors: Shirali Masoud , Knott Sara A. , Pong-Wong Ricardo , Navarro Pau , Haley Chris S.
Published: March 2018

We propose a novel approach to analyze genomic data that incorporates haplotype information for detecting rare variants within a regional heritability mapping framework. The performance of our approach was tested in a simulation study based on human genotypes. The phenotypes were simulated by generating regional variance using either SNP(s) or haplotype(s). Regional genomic relationship matrices, constructed with either a SNP-based or a haplotype-based estimator, were employed to estimate the regional variance. The results from the study show that haplotype heritability mapping captures the regional effect, with its relative performance decreasing with increasing analysis window size. The SNP-based regional mapping approach often misses the effect of causal haplotype(s); however, it has a greater power to detect simulated SNP-based-variants. Heritability estimates suggest that the haplotype heritability mapping estimates the simulated regional heritability accurately for all phenotypes and analysis windows. However, the SNP-based analysis overestimates the regional heritability and performs less well than our haplotype-based approach for the simulated rare haplotype-based-variant. We conclude that haplotype heritability mapping is a useful tool to capture the effect of rare variants, and explain a proportion of the missing heritability.