bluuebunny/crossref_metadata_2025 huggingface dataset:
Want to Interview a Politician? Ways to Prepare for Digital Vetting by Political Staffers
Authors: Esselment Anna Lennox , Marland Alex
Published: July 2019

This article outlines how the advent of digital-communications technology, particularly social media, has contributed to an increased wariness by political elites to grant interviews to researchers. Errant remarks, misquotes, and comments taken out of context can exact a heavy price. Thus, politicians and their gatekeepers are far more cautious and risk averse than in decades past, which puts qualitative research methods—and the rich data they produce—in peril. Insights drawn from 32 qualitative, semi-structured interviews with social scientists, political journalists, and political staffers in six countries revealed that academics who submit interview requests should expect to be subjected to online scrutiny—a vetting—by gatekeepers before any access is granted. Digital screening aims to assess the authenticity and objectivity of the researcher. Our findings suggest that scholars who want to pursue qualitative research with politicians must practice online reputation management and perhaps even delve into personal marketing.
Food literacy programmes in secondary schools: a systematic literature review and narrative synthesis of quantitative and qualitative evidence
Authors: Bailey Christopher J , Drummond Murray J , Ward Paul R
Published: July 2019

Objective:

The current review aimed to synthesise the literature on food literacy interventions among adolescents in secondary schools, the attitudes and perceptions of food literacy interventions in secondary schools, and their effects on dietary outcomes.

Design:

The systematic review searched five electronic databases from the earliest record to present.

Setting:

The studies selected for the review were from sixteen countries: Australia (n 10), Canada (n 1), China (n 1), France (n 1), Greece (n 2), Iran (n 1), South Africa (n 1), South India (n 1), Kenya (n 1), Norway (n 2), Portugal (n 1), Denmark (n 1), Northern Ireland (n 1), USA (n 17), UK (n 1) and Sweden (n 2).

Participants:

Adolescents aged 10–19 years.

Results:

Forty-four studies were eligible for inclusion. Adolescents with greater nutritional knowledge and food skills showed healthier dietary practices. Studies found a mixed association between food literacy and long-term healthy dietary behaviour. Two studies showed an improvement in adolescents’ cooking skills and food safety knowledge; six studies showed an improvement in overall food safety knowledge; six studies showed an improvement in overall food and nutritional knowledge; and two studies showed an improvement in short-term healthy dietary behaviour.

Conclusions:

Food literacy interventions conducted in a secondary-school setting have demonstrated a positive impact on healthy food and nutritional knowledge. However, there appears to be limited evidence supporting food literacy interventions and long-term dietary behaviours in adolescents. More evidence-based research is required to adequately measure all domains of food literacy and more age-specific food literacy interventions.
Needs of people with dementia and their informal caregivers concerning assistive technologies
Authors: Hirt Julian , Burgstaller Melanie , Zeller Adelheid , Beer Thomas
Published: July 2019

Abstract. Background and objective: Assistive technologies might be a suitable option for supporting people with dementia and their informal caregivers. To avoid “one-fits-all”-solutions and to design useful technologies, it is essential to consider the end-users’ needs. The objective of this review was to examine the needs of people with dementia and their informal caregivers with regard to assistive technologies. Methods: We conducted a scoping review based on a comprehensive literature search in databases, handsearching, and free web searching. Additionally, we performed citation tracking of included studies. We included all types of study designs. Two researchers independently selected the studies. The results were thematically categorised by two researchers. Results: The search yielded 7160 references. 18 of 24 included studies were qualitative. The studies had been conducted in 13 different countries, mostly in Europe. The sample size ranged between two and 270 participants. Most of the studies involved people with dementia as well as informal caregivers. The analysis resulted in eleven themes. The themes could be assigned to three domains: “needed technologies”, “characteristics of needed technologies”, and “information about technologies”. Conclusions: The results might guide future usage, development and research addressing end users’ needs with regard to assistive technologies.
Strategies to Improve Name Learning
Authors: Brédart Serge
Published: July 2019

Abstract. The following points emerge from the present review of strategies to improve the learning of proper names: (a) Face-name mnemonic techniques based on mental imagery have been shown to be efficient in laboratory settings in both young and older adults. Unfortunately, they are particularly effortful and require capacity for imagination, making them difficult to apply in a real conversational context. (b) Strategies based on spaced retrieval practice have been found to be efficient both in laboratory and more ecological settings, and both in young and older adults. (c) Techniques based on spaced retrieval practice appear to be more efficient than those based on mental imagery. (d) More recent research has proposed new perspectives, such as basing learning strategies on implicit, rather than explicit, memory processes such as hyper-binding. Finally, neuroscience research has started to investigate the possibility of using non-invasive electrical brain stimulation to improve name learning.
Drivers of Carbon Export Efficiency in the Global Ocean
Authors: Henson Stephanie , Le Moigne Fred , Giering Sarah
Published: July 2019

The export of organic carbon from the surface ocean forms the basis of the biological carbon pump, an important planetary carbon flux. Typically, only a small fraction of primary productivity (PP) is exported (quantified as the export efficiency: export/PP). Here we assemble a global data synthesis to reveal that very high export efficiency occasionally occurs. These events drive an apparent inverse relationship between PP and export efficiency, which is opposite to that typically used in empirical or mechanistic models. At the global scale, we find that low PP, high export efficiency regimes tend to occur when macrozooplankton and bacterial abundance are low. This implies that a decoupling between PP and upper ocean remineralization processes can result in a large fraction of PP being exported, likely as intact cells or phytoplankton‐based aggregates. As the proportion of PP being exported declines, macrozooplankton and bacterial abundances rise. High export efficiency, high PP regimes also occur infrequently, possibly associated with nonbiologically mediated export of particles. A similar analysis at a biome scale reveals that the factors affecting export efficiency may be different at regional and global scales. Our results imply that the whole ecosystem structure, rather than just the phytoplankton community, is important in setting export efficiency. Further, the existence of low PP, high export efficiency regimes imply that biogeochemical models that parameterize export efficiency as increasing with PP may underestimate export flux during decoupled periods, such as at the start of the spring bloom.
An Updated Crustal Thickness Map of Central South America Based on Receiver Function Measurements in the Region of the Chaco, Pantanal, and Paraná Basins, Southwestern Brazil
Authors: Rivadeneyra‐Vera Carolina , Bianchi Marcelo , Assumpção Marcelo , Cedraz Victoria , Julià Jordi , Rodríguez Martín , Sánchez Leda , Sánchez Gerardo , Lopez‐Murua Luciana , Fernandez Gonzalo , Fugarazzo Rafael ,   The “3‐Basins” Project Team
Published: July 2019

Previous compilation of crustal structure in South America had large unsampled areas including the thin crust in the Sub‐Andean lowlands, largely estimated by gravity data, and the sparsely sampled Amazon Craton. A deployment of 35 seismic stations in Brazil, Bolivia, Paraguay, Argentina, and Uruguay improved the coverage of the Pantanal Basin in Western Brazil, the intracratonic Paraná and the Chaco Basins. Crustal thicknesses and Vp/Vs ratios were estimated with a modified H‐k method by producing three stacked traces to enhance the three Moho conversions (the direct Ps and the two multiples Ppps and Ppss). This modified method gives lower uncertainties than previous studies and shows more regional consistency between nearby stations. The temporary stations and the Brazilian Network (RSBR) have characterized the crustal structure as follows. The Paraná Basin has a thick crust 40–45 km and average Vp/Vs ratio (1.71–1.77), while the Chaco Basin has a slightly thinner crust (35–40 km) and higher Vp/Vs ratio (1.75–1.79). This confirms the lack of widespread magmatic underplating in the Paraná Basin that could be related to the origin of the flood basalts during the South Atlantic opening. A belt of thin crust (30–35 km) with low Vp/Vs (<1.74) is confined to the eastern edge of the Pantanal Basin. Normal crust (38–43 km) is observed along the western edge of the Pantanal, from the southern part of the Amazon craton to the Rio Apa cratonic block. This study, combined with other published data, provides an updated crustal thickness map of South America.
The Case for Combining a Large Low‐Band Very High Frequency Transmitter With Multiple Receiving Arrays for Geospace Research: A Geospace Radar
Authors: Hysell D. L. , Chau J. L. , Coles W. A. , Milla M. A. , Obenberger K. , Vierinen J.
Published: July 2019

We argue that combining a high‐power, large‐aperture radar transmitter with several large‐aperture receiving arrays to make a geospace radar—a radar capable of probing near‐Earth space from the upper troposphere through to the solar corona—would transform geospace research. We review the emergence of incoherent scatter radar in the 1960s as an agent that unified early, pioneering research in geospace in a common theoretical, experimental, and instrumental framework, and we suggest that a geospace radar would have a similar effect on future developments in space weather research. We then discuss recent developments in radio‐array technology that could be exploited in the development of a geospace radar with new or substantially improved capabilities compared to the radars in use presently. A number of applications for a geospace radar with the new and improved capabilities are reviewed including studies of meteor echoes, mesospheric and stratospheric turbulence, ionospheric flows, plasmaspheric and ionospheric irregularities, and reflection from the solar corona and coronal mass ejections. We conclude with a summary of technical requirements.
Fireballs Could Provide Clues to an Outstanding Meteor Mystery
Authors: Redd Nola
Published: July 2019

Fireballs in the summer sky may signify a chance to probe their mysterious origin.
Effects of Variability in Atlantic Ocean Circulation
Authors: Zhang Rong , Sutton Rowan , Danabasoglu Gokhan , Kwon Young-Oh , Marsh Robert , Yeager Stephen , Amrhein Daniel , Little Christopher
Published: July 2019

There is strong evidence that the Atlantic meridional overturning circulation plays an essential role in Atlantic multidecadal variability and associated climate impacts.
Giant non-linear susceptibility of hydrogenic donors in silicon and germanium
Authors: Le Nguyen H. , Lanskii Grigory V. , Aeppli Gabriel , Murdin Benedict N.
Published: July 2019

Implicit summation is a technique for the conversion of sums over intermediate states in multiphoton absorption and the high-order susceptibility in hydrogen into simple integrals. Here, we derive the equivalent technique for hydrogenic impurities in multi-valley semiconductors. While the absorption has useful applications, it is primarily a loss process; conversely, the non-linear susceptibility is a crucial parameter for active photonic devices. For Si:P, we predict the hyperpolarizability ranges from χ(3)/n3D = 2.9 to 580 × 10−38 m5/V2 depending on the frequency, even while avoiding resonance. Using samples of a reasonable density, n3D, and thickness, L, to produce third-harmonic generation at 9 THz, a frequency that is difficult to produce with existing solid-state sources, we predict that χ(3) should exceed that of bulk InSb and χ(3)L should exceed that of graphene and resonantly enhanced quantum wells.
Evolution in action: habitat transition from sediment to the pelagial leads to genome streamlining in Methylophilaceae
Authors: Salcher Michaela M , Schaefle Daniel , Kaspar Melissa , Neuenschwander Stefan M , Ghai Rohit
Published: July 2019

The most abundant aquatic microbes are small in cell and genome size. Genome-streamlining theory predicts gene loss caused by evolutionary selection driven by environmental factors, favouring superior competitors for limiting resources. However, evolutionary histories of such abundant, genome-streamlined microbes remain largely unknown. Here we reconstruct the series of steps in the evolution of some of the most abundant genome-streamlined microbes in freshwaters (“Ca. Methylopumilus”) and oceans (marine lineage OM43). A broad genomic spectrum is visible in the family Methylophilaceae (Betaproteobacteria), from sediment microbes with medium-sized genomes (2–3 Mbp genome size), an occasionally blooming pelagic intermediate (1.7 Mbp), and the most reduced pelagic forms (1.3 Mbp). We show that a habitat transition from freshwater sediment to the relatively oligotrophic pelagial was accompanied by progressive gene loss and adaptive gains. Gene loss has mainly affected functions not necessarily required or advantageous in the pelagial or is encoded by redundant pathways. Likewise, we identified genes providing adaptations to oligotrophic conditions that have been transmitted horizontally from pelagic freshwater microbes. Remarkably, the secondary transition from the pelagial of lakes to the oceans required only slight modifications, i.e., adaptations to higher salinity, gained via horizontal gene transfer from indigenous microbes. Our study provides first genomic evidence of genome reduction taking place during habitat transitions. In this regard, the family Methylophilaceae is an exceptional model for tracing the evolutionary history of genome streamlining as such a collection of evolutionarily related microbes from different habitats is rare in the microbial world.
In-operando high-speed microscopy and thermometry of reaction propagation and sintering in a nanocomposite
Authors: Wang Haiyang , Kline Dylan J. , Zachariah Michael R.
Published: July 2019

An important proposed mechanism in nanothermites reactions — reactive sintering — plays a significant role on the combustion performance of nanothermites by rapidly melting and coalescing aggregated metal nanoparticles, which increases the initial size of the reacting composite powders before burning. Here, we demonstrate a high-speed microscopy/thermometry capability that enables ~ µs time and ~ µm spatial resolution as applied to highly exothermic reaction propagation to directly observe reactive sintering and the reaction front at high spatial and temporal resolution. Experiments on the Al+CuO nanocomposite system reveal a reaction front thickness of ~30 μm and temperatures in excess of 3000 K, resulting in a thermal gradient in excess of 107 K m−1. The local microscopic reactive sintering velocity is found to be an order of magnitude higher than macroscale flame velocity. In this observed mechanism, propagation is very similar to the general concept of laminar gas reaction theory in which reaction front velocity ~ (thermal diffusivity x reaction rate)1/2.
Noncovalently fused-ring electron acceptors with near-infrared absorption for high-performance organic solar cells
Authors: Huang Hao , Guo Qingxin , Feng Shiyu , Zhang Cai’e , Bi Zhaozhao , Xue Wenyue , Yang Jinjin , Song Jinsheng , Li Cuihong , Xu Xinjun , Tang Zheng , Ma Wei , Bo Zhishan
Published: July 2019

Non-fullerene fused-ring electron acceptors boost the power conversion efficiency of organic solar cells, but they suffer from high synthetic cost and low yield. Here, we show a series of low-cost noncovalently fused-ring electron acceptors, which consist of a ladder-like core locked by noncovalent sulfur–oxygen interactions and flanked by two dicyanoindanone electron-withdrawing groups. Compared with that of similar but unfused acceptor, the presence of ladder-like structure markedly broadens the absorption to the near-infrared region. In addition, the use of intramolecular noncovalent interactions avoids the tedious synthesis of covalently fused-ring structures and markedly lowers the synthetic cost. The optimized solar cells displayed an outstanding efficiency of 13.24%. More importantly, solar cells based on these acceptors demonstrate very low non-radiative energy losses. This research demonstrates that low-cost noncovalently fused-ring electron acceptors are promising to achieve high-efficiency organic solar cells.
Paternal-age-related de novo mutations and risk for five disorders
Authors: Taylor Jacob L. , Debost Jean-Christophe P. G. , Morton Sarah U. , Wigdor Emilie M. , Heyne Henrike O. , Lal Dennis , Howrigan Daniel P. , Bloemendal Alex , Larsen Janne T. , Kosmicki Jack A. , Weiner Daniel J. , Homsy Jason , Seidman Jonathan G. , Seidman Christine E. , Agerbo Esben , McGrath John J. , Mortensen Preben Bo , Petersen Liselotte , Daly Mark J. , Robinson Elise B.
Published: July 2019

There are established associations between advanced paternal age and offspring risk for psychiatric and developmental disorders. These are commonly attributed to genetic mutations, especially de novo single nucleotide variants (dnSNVs), that accumulate with increasing paternal age. However, the actual magnitude of risk from such mutations in the male germline is unknown. Quantifying this risk would clarify the clinical significance of delayed paternity. Using parent-child trio whole-exome-sequencing data, we estimate the relationship between paternal-age-related dnSNVs and risk for five disorders: autism spectrum disorder (ASD), congenital heart disease, neurodevelopmental disorders with epilepsy, intellectual disability and schizophrenia (SCZ). Using Danish registry data, we investigate whether epidemiologic associations between each disorder and older fatherhood are consistent with the estimated role of dnSNVs. We find that paternal-age-related dnSNVs confer a small amount of risk for these disorders. For ASD and SCZ, epidemiologic associations with delayed paternity reflect factors that may not increase with age.
Discovery of new materials using combinatorial synthesis and high-throughput characterization of thin-film materials libraries combined with computational methods
Authors: Ludwig Alfred
Published: July 2019

This perspective provides an experimentalist’s view on materials discovery in multinary materials systems—from nanoparticles over thin films to bulk—based on combinatorial thin-film synthesis and high-throughput characterization in connection with high-throughput calculations and materials informatics. Complete multinary materials systems as well as composition gradients which cover all materials compositions necessary for verification/falsification of hypotheses and predictions are efficiently fabricated by combinatorial synthesis of thin-film materials libraries. Automated high-quality high-throughput characterization methods enable comprehensive determination of compositional, structural and (multi)functional properties of the materials contained in the libraries. The created multidimensional datasets enable data-driven materials discoveries and support efficient optimization of newly identified materials, using combinatorial processing. Furthermore, these datasets are the basis for multifunctional existence diagrams, comprising correlations between composition, processing, structure and properties, which can be used for the design of future materials.
Notch-mediated inhibition of neurogenesis is required for zebrafish spinal cord morphogenesis
Authors: Sharma Priyanka , Saraswathy Vishnu Muraleedharan , Xiang Li , Fürthauer Maximilian
Published: July 2019

The morphogenesis of the nervous system requires coordinating the specification and differentiation of neural precursor cells, the establishment of neuroepithelial tissue architecture and the execution of specific cellular movements. How these aspects of neural development are linked is incompletely understood. Here we inactivate a major regulator of embryonic neurogenesis - the Delta/Notch pathway - and analyze the effect on zebrafish central nervous system morphogenesis. While some parts of the nervous system can establish neuroepithelial tissue architecture independently of Notch, Notch signaling is essential for spinal cord morphogenesis. In this tissue, Notch signaling is required to repress neuronal differentiation and allow thereby the emergence of neuroepithelial apico-basal polarity. Notch-mediated suppression of neurogenesis is also essential for the execution of specific morphogenetic movements of zebrafish spinal cord precursor cells. In the wild-type neural tube, cells divide at the organ midline to contribute one daughter cell to each organ half. Notch signaling deficient animals fail to display this behavior and therefore form a misproportioned spinal cord. Taken together, our findings show that Notch-mediated suppression of neurogenesis is required to allow the execution of morphogenetic programs that shape the zebrafish spinal cord.
Optimal design of lattice structures for controllable extremal band gaps
Authors: Choi Myung-Jin , Oh Myung-Hoon , Koo Bonyong , Cho Seonho
Published: July 2019

This paper presents very large complete band gaps at low audible frequency ranges tailored by gradient-based design optimizations of periodic two- and three-dimensional lattices. From the given various lattice topologies, we proceed to create and enlarge band gap properties through controlling neutral axis configuration and cross-section thickness of beam structures, while retaining the periodicity and size of the unit cell. Beam neutral axis configuration and cross-section thickness are parameterized by higher order B-spline basis functions within the isogeometric analysis framework, and controlled by an optimization algorithm using adjoint sensitivity. Our optimal curved designs show much more enhanced wave attenuation properties at audible low frequency region than previously reported straight or simple undulated geometries. Results of harmonic response analyses of beam structures consisting of a number of unit cells demonstrate the validity of the optimal designs. A plane wave propagation in infinite periodic lattice is analyzed within a unit cell using the Bloch periodic boundary condition.
Reliability of Total Grain-Size Distribution of Tephra Deposits
Authors: Pioli L. , Bonadonna C. , Pistolesi M.
Published: July 2019

Total Grain-Size Distribution (TGSD) of tephra deposits is key to the characterization of explosive volcanism, plume-dispersal modeling, and magmatic fragmentation studies. Nonetheless, various aspects that includes deposit exposure and data fitting make its determination extremely complex and affect its representativeness. In order to shed some lights on the reliability of derived TGSDs, we examine a large TGSD dataset in combination with a sensitivity analysis of sampling strategies. These analyses are based both on a well-studied tephra deposit and on synthetic deposits associated with a variety of initial eruptive and atmospheric conditions. Results demonstrate that TGSDs can be satisfactorily fitted by four distributions (lognormal, Rosin-Rammler, and power-law based either on the absolute or cumulative number of particles) that capture different distribution features. In particular, the Rosin-Rammler distribution best reproduces both the median and the tails of the TGSDs. The accuracy of reconstructed TGSDs is strongly controlled by the number and distribution of the sampling points. We conclude that TGSDs should be critically assessed based on dedicated sampling strategies and should be fitted by one of the mentioned theoretical distributions depending on the specific study objective (e.g., tephra-deposit characterization, physical description of explosive eruptions, tephra-dispersal modeling).
Gate Tuning of Synaptic Functions Based on Oxygen Vacancy Distribution Control in Four-Terminal TiO2−x Memristive Devices
Authors: Nagata Zenya , Shimizu Takuma , Isaka Tsuyoshi , Tohei Tetsuya , Ikarashi Nobuyuki , Sakai Akira
Published: July 2019

Recent developments in artificial intelligence technology has facilitated advances in neuromorphic computing. Electrical elements mimicking the role of synapses are crucial building blocks for neuromorphic computers. Although various types of two-terminal memristive devices have emerged in the mainstream of synaptic devices, a hetero-synaptic artificial synapse, i.e., one with modulatable plasticity induced by multiple connections of synapses, is intriguing. Here, a synaptic device with tunable synapse plasticity is presented that is based on a simple four-terminal rutile TiO2−x single-crystal memristor. In this device, the oxygen vacancy distribution in TiO2−x and the associated bulk carrier conduction can be used to control the resistance of the device. There are two diagonally arranged pairs of electrodes with distinct functions: one for the read/write operation, the other for the gating operation. This arrangement enables precise control of the oxygen vacancy distribution. Microscopic analysis of the Ti valence states in the device reveals the origin of resistance switching phenomena to be an electrically driven redistribution of oxygen vacancies with no changes in crystal structure. Tuning protocols for the write and the gate voltage applications enable high precision control of resistance, or synaptic plasticity, paving the way for the manipulation of learning efficiency through neuromorphic devices.
Study of Gene Expression Profiles of Breast Cancers in Indian Women
Authors: Malvia Shreshtha , Bagadi Sarangadhara Appala Raju , Pradhan Dibyabhaba , Chintamani Chintamani , Bhatnagar Amar , Arora Deepshikha , Sarin Ramesh , Saxena Sunita
Published: July 2019

Breast cancer is the most common cancer among women globally. In India, the incidence of breast cancer has increased significantly during the last two decades with a higher proportion of the disease at a young age compared to the west. To understand the molecular processes underlying breast cancer in Indian women, we analysed gene expression profiles of 29 tumours and 9 controls using microarray. In the present study, we obtained 2413 differentially expressed genes, consisting of overexpressed genes such asCOL10A1,COL11A1,MMP1,MMP13,MMP11,GJB2, andCST1and underexpressed genes such asPLIN1,FABP4,LIPE,AQP7,LEP,ADH1A,ADH1B, andCIDEC. The deregulated pathways include cell cycle, focal adhesion and metastasis, DNA replication, PPAR signaling, and lipid metabolism. Using PAM50 classifier, we demonstrated the existence of molecular subtypes in Indian women. In addition, qPCR validation of expression of metalloproteinase genes,MMP1,MMP3,MMP11,MMP13,MMP14,ADAMTS1, andADAMTS5showed concordance with that of the microarray data; wherein we found a significant association ofADAMTS5down-regulation with older age (≥55 years) of patients. Together, this study reports gene expression profiles of breast tumours from the Indian subcontinent, throwing light on the pathways and genes associated with the breast tumourigenesis in Indian women.
Human menstrual blood-derived stromal/stem cells modulate functional features of natural killer cells
Authors: Shokri Mohammad-Reza , Bozorgmehr Mahmood , Ghanavatinejad Alireza , Falak Reza , Aleahmad Mehdi , Kazemnejad Somaieh , Shokri Fazel , Zarnani Amir-Hassan
Published: July 2019

Although natural killer (NK) cells play a crucial role in the maintenance of a successful pregnancy, their cytotoxic activity should be tightly controlled. We hypothesized that endometrial mesenchymal stromal/stem cells (eMSCs) could potentially attenuate the functional features of NK cells. Herein, we assessed immunomodulatory effects of menstrual blood-derived stromal/stem cells (MenSCs), as a surrogate for eMSCs, on NK cells function. Our results showed that MenSCs induced proliferation of NK cells. However, IFN-γ/IL-1β pretreated MenSCs significantly inhibited NK cell proliferation. Of 41 growth factors tested, MenSCs produced lower levels of insulin-like growth factor binding proteins (IGFBPs) 1–4, VEGF-A, β-NGF, and M-CSF compared to bone marrow-derived mesenchymal stem cells (BMSCs). MenSCs displayed high activity of IDO upon IFN-γ treatment. The antiproliferative potential of IFN-γ/IL-1β-pretreated MenSCs was mediated through IL-6 and TGF-β. MenSCs impaired the cytotoxic activity of NK cells on K562 cells, consistent with the lower expression of perforin, granzymes A, and B. We also observed that in vitro decidualization of MenSCs in the presence of IFN-γ reduced the inhibitory effect of MenSCs on NK cell cytotoxicity against K562 target cells. Additionally, MenSCs were found to be prone to NK cell-mediated lysis in an MHC-independent manner. Our findings imply that dysregulation of NK cells in such pregnancy-related disorders as miscarriage may stem from dysfunctioning of eMSCs.
Integrative multi-omic analysis identifies new drivers and pathways in molecularly distinct subtypes of ALS
Authors: Morello Giovanna , Guarnaccia Maria , Spampinato Antonio Gianmaria , Salomone Salvatore , D’Agata Velia , Conforti Francesca Luisa , Aronica Eleonora , Cavallaro Sebastiano
Published: July 2019

Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease. Increasing the chances of success for future clinical strategies requires more in-depth knowledge of the molecular basis underlying disease heterogeneity. We recently laid the foundation for a molecular taxonomy of ALS by whole-genome expression profiling of motor cortex from sporadic ALS (SALS) patients. Here, we analyzed copy number variants (CNVs) occurring in the same patients, by using a customized exon-centered comparative genomic hybridization array (aCGH) covering a large panel of ALS-related genes. A large number of novel and known disease-associated CNVs were detected in SALS samples, including several subgroup-specific loci, suggestive of a great divergence of two subgroups at the molecular level. Integrative analysis of copy number profiles with their associated transcriptomic data revealed subtype-specific genomic perturbations and candidate driver genes positively correlated with transcriptional signatures, suggesting a strong interaction between genomic and transcriptomic events in ALS pathogenesis. The functional analysis confirmed our previous pathway-based characterization of SALS subtypes and identified 24 potential candidates for genomic-based patient stratification. To our knowledge, this is the first comprehensive “omics” analysis of molecular events characterizing SALS pathology, providing a road map to facilitate genome-guided personalized diagnosis and treatments for this devastating disease.
Host–symbiont combinations dictate the photo-physiological response of reef-building corals to thermal stress
Authors: Hoadley Kenneth D. , Lewis Allison M. , Wham Drew C. , Pettay D. Tye , Grasso Chris , Smith Robin , Kemp Dustin W. , LaJeunesse Todd C. , Warner Mark E.
Published: July 2019

High sea surface temperatures often lead to coral bleaching wherein reef-building corals lose significant numbers of their endosymbiotic dinoflagellates (Symbiodiniaceae). These increasingly frequent bleaching events often result in large scale coral mortality, thereby devasting reef systems throughout the world. The reef habitats surrounding Palau are ideal for investigating coral responses to climate perturbation, where many inshore bays are subject to higher water temperature as compared with offshore barrier reefs. We examined fourteen physiological traits in response to high temperature across various symbiotic dinoflagellates in four common Pacific coral species, Acropora muricata, Coelastrea aspera, Cyphastrea chalcidicum and Pachyseris rugosa found in both offshore and inshore habitats. Inshore corals were dominated by a single homogenous population of the stress tolerant symbiont Durusdinium trenchii, yet symbiont thermal response and physiology differed significantly across coral species. In contrast, offshore corals harbored specific species of Cladocopium spp. (ITS2 rDNA type-C) yet all experienced similar patterns of photoinactivation and symbiont loss when heated. Additionally, cell volume and light absorption properties increased in heated Cladocopium spp., leading to a greater loss in photo-regulation. While inshore coral temperature response was consistently muted relative to their offshore counterparts, high physiological variability in D. trenchii across inshore corals suggests that bleaching resilience among even the most stress tolerant symbionts is still heavily influenced by their host environment.
HIV-1 tropism prediction by the XGboost and HMM methods
Authors: Chen Xiang , Wang Zhi-Xin , Pan Xian-Ming
Published: July 2019

Human Immunodeficiency Virus 1 (HIV-1) co-receptor usage, called tropism, is associated with disease progression towards AIDS. Furthermore, the recently developed and developing drugs against co-receptors CCR5 or CXCR4 open a new thought for HIV-1 therapy. Thus, knowledge about tropism is critical for illness diagnosis and regimen prescription. To improve tropism prediction accuracy, we developed two novel methods, the extreme gradient boosting based XGBpred and the hidden Markov model based HMMpred. Both XGBpred and HMMpred achieved higher specificities (72.56% and 72.09%) than the state-of-the-art methods Geno2pheno (61.6%) and G2p_str (68.60%) in a 10-fold cross validation test at the same sensitivity of 93.73%. Moreover, XGBpred had more outstanding performances (with AUCs 0.9483, 0.9464) than HMMpred (0.8829, 0.8774) on the Hivcopred and Newdb (created in this work) datasets containing larger proportions of hard-to-predict dual tropic samples in the X4-using tropic samples. Therefore, we recommend the use of our novel method XGBpred to predict tropism. The two methods and datasets are available via http://spg.med.tsinghua.edu.cn:23334/XGBpred/. In addition, our models identified that positions 5, 11, 13, 18, 22, 24, and 25 were correlated with HIV-1 tropism.
A dual-model SERS and RRS analytical platform for Pb(II) based on Ag-doped carbon dot catalytic amplification and aptamer regulation
Authors: Wang Haidong , Huang Xiaowei , Wen Guiqing , Jiang Zhiliang
Published: July 2019

Several carbon dots doping with diferent elements (Ca, Ag, Au) were fabricated and their catalytic properties had been investigated in this paper. It was found that the Ag-doped carbon dots (CDAg) had played a role of mimic enzyme on the reaction of HAuCl4-H2O2 and generated nanogold particles with surface enhanced Raman scattering (SERS) and resonance Rayleigh scattering (RRS) effects. The aptamer (Apt) can be adsorbed on the CDAg surface and cause the catalysis weakening. When the target Pb(II) was added, it would combine with the Apt to produce firm complexes Pb-Apt and desorb CDAg, which caused its catalytic effect restore. The formed nanogold had a strong RRS peak (at 375 nm) and a high SERS peak (at 1615 cm−1) in the presence of molecular probe (Victoria blue B, VBB). The dual-model signals of SERS and RRS increased linearly with Pb(II) concentration increase within the scope of 0.006–0.46 μmol/L and 0.01–0.46 μmol/L. And their detection limits respectively were 0.0032 μmol/L and 0.0048 μmol/L Pb(II).
Spatial variation of vector vortex beams with plasmonic metasurfaces
Authors: Zhang Yuchao , Gao Jie , Yang Xiaodong
Published: July 2019

The spatial variation of vector vortex beams with arbitrary polarization states and orbital angular momentum (OAM) values along the beam propagation is demonstrated by using plasmonic metasurfaces with the initial geometric phase profiles determined from the caustic theory. The vector vortex beam is produced by the superposition of deflected right- and left-handed circularly polarized component vortices with different helical phase charges, which are simultaneously generated off-axially by the single metasurface. Besides, the detailed evolution processes of intensity profile, polarization distribution and OAM value along the beam propagation distance is analyzed. The demonstrated arbitrary space-variant vector vortex beam will pave the way to many promising applications related to spin-to-orbital angular momentum conversion, spin-orbit hybrid entanglement, particle manipulation and transportation, and optical communication.
Disease-causing mutations in subunits of OXPHOS complex I affect certain physical interactions
Authors: Barshad Gilad , Zlotnikov-Poznianski Nicol , Gal Lihi , Schuldiner Maya , Mishmar Dan
Published: July 2019

Mitochondrial complex I (CI) is the largest multi-subunit oxidative phosphorylation (OXPHOS) protein complex. Recent availability of a high-resolution human CI structure, and from two non-human mammals, enabled predicting the impact of mutations on interactions involving each of the 44 CI subunits. However, experimentally assessing the impact of the predicted interactions requires an easy and high-throughput method. Here, we created such a platform by cloning all 37 nuclear DNA (nDNA) and 7 mitochondrial DNA (mtDNA)-encoded human CI subunits into yeast expression vectors to serve as both ‘prey’ and ‘bait’ in the split murine dihydrofolate reductase (mDHFR) protein complementation assay (PCA). We first demonstrated the capacity of this approach and then used it to examine reported pathological OXPHOS CI mutations that occur at subunit interaction interfaces. Our results indicate that a pathological frame-shift mutation in the MT-ND2 gene, causing the replacement of 126 C-terminal residues by a stretch of only 30 amino acids, resulted in loss of specificity in ND2-based interactions involving these residues. Hence, the split mDHFR PCA is a powerful assay for assessing the impact of disease-causing mutations on pairwise protein-protein interactions in the context of a large protein complex, thus offering a possible mechanistic explanation for the underlying pathogenicity.
Phosphoproteomics analysis of male and female Schistosoma mekongi adult worms
Authors: Simanon Nattapon , Adisakwattana Poom , Thiangtrongjit Tipparat , Limpanont Yanin , Chusongsang Phiraphol , Chusongsang Yupa , Anuntakarun Songtham , Payungporn Sunchai , Ampawong Sumate , Reamtong Onrapak
Published: July 2019

Schistosoma mekongi is one of the major causative agents of human schistosomiasis in Southeast Asia. Praziquantel is now the only drug available for treatment and there are serious concerns about parasite resistance to it. Therefore, a dataset of schistosome targets is necessary for drug development. Phosphorylation regulates signalling pathways to control cellular processes that are important for the parasite’s growth and reproduction. Inhibition of key phosphoproteins may reduce the severity of schistosomiasis. In this research, we studied the phosphoproteomes of S. mekongi male and female adult worms by using computational and experimental approaches. Using a phosphoproteomics approach, we determined that 88 and 44 phosphoproteins were male- and female-biased, respectively. Immunohistochemistry using anti-phosphoserine antibodies demonstrated phosphorylation on the tegument and muscle of male S. mekongi worms and on the vitelline gland and gastrointestinal tract of female worms. This research revealed S. mekongi sex-dependent phosphoproteins. Our findings provide a better understanding of the role of phosphorylation in S. mekongi and could be integrated with information from other Schistosoma species to facilitate drug and vaccine development.
Differential expression of individual transcript variants of PD-1 and PD-L2 genes on Th-1/Th-2 status is guaranteed for prognosis prediction in PCNSL
Authors: Takashima Yasuo , Kawaguchi Atsushi , Sato Ryuichi , Yoshida Kenichi , Hayano Azusa , Homma Jumpei , Fukai Junya , Iwadate Yasuo , Kajiwara Koji , Ishizawa Shin , Hondoh Hiroaki , Nakano Masakazu , Ogawa Seishi , Tashiro Kei , Yamanaka Ryuya
Published: July 2019

In current molecular medicine, next-generation sequencing (NGS) for transcript variant detection and multivariable analyses are valid methods for evaluating gene expression, cancer mechanisms, and prognoses of patients. We conducted RNA-sequencing on samples from patients with primary central nervous system lymphoma (PCNSL) using NGS and performed multivariable analysis on gene expression data and correlations focused on Th-1/Th-2 helper T cell balance and immune checkpoint to identify diagnosis/prognosis markers and cancer immune pathways in PCNSL. We selected 84 transcript variants to limit the analysis range for Th-1/Th-2 balance and stimulatory and inhibitory checkpoints in 31 PCNSLs. Of these, 21 highly-expressed transcript variants were composed of the formulas for prognoses based on Th-1/Th-2 status and checkpoint activities. Using formulas, Th-1low, Th-2high, and stimulatory checkpointhigh resulted in poor prognoses. Further, Th-1highTh-2low was associated with good prognoses. On the other hand, CD40-001high and CD70-001high as stimulatory genes, and LAG3-001high, PDCD1 (PD-1)-001/002/003high, and PDCD1LG2 (PD-L2)-201low as inhibitory genes were associated with poor prognoses. Interestingly, Th-1highTh-2low and Th-1lowTh-2high were correlated with stimulatory checkpointlow as CD70-001low and inhibitory checkpointlow as HAVCR2 (TIM-3)-001low and PDCD1LG2-001/201low, respectively. Focused on the inhibitory checkpoint, specific variants of CD274 (PD-L1)-001 and PDCD1-002 served severe hazard ratios. In particular, PDCD1-002high by a cut off score was associated with poor prognoses, in addition to PDCD1-001/003high, PDCD1LG2-201low, and LAG3-001high. These results mainly suggest that expression of transcript variants of PDCD1 and PDCD1LG2 on the Th-1/Th-2 balance enable prognostic prediction in PCNSL. This study provides insights for development of molecular target therapies and identification of diagnosis/prognosis markers in PCNSL.
Human DC-SIGN and CD23 do not interact with human IgG
Authors: Temming A. Robin , Dekkers Gillian , van de Bovenkamp Fleur S. , Plomp H. Rosina , Bentlage Arthur E. H. , Szittner Zoltán , Derksen Ninotska I. L. , Wuhrer Manfred , Rispens Theo , Vidarsson Gestur
Published: July 2019

The precise mechanisms underlying anti-inflammatory effects of intravenous immunoglobulin (IVIg) therapies remain elusive. The sialylated IgG fraction within IVIg has been shown to be therapeutically more active in mouse models. Functionally, it has been suggested that IgG undergoes conformational changes upon Fc-sialylation which sterically impede binding to conventional FcγRs, but simultaneously allow binding to human DC-SIGN (SIGN-R1 in mice) and also CD23. These latter C-type lectins have been proposed responsible for the immunomodulatory effects in mouse models. However, there is conflicting evidence supporting direct interactions between sialylated human IgG and CD23/DC-SIGN. While cells expressing human CD23 and DC-SIGN in their native configuration bound their natural ligands IgE and ICAM-3, respectively, no IgG binding was observed, regardless of Fc-glycan sialylation in any context (with or without bisection and/or fucosylation) or presence of sialylated Fab-glycans. This was tested by both by FACS and a novel cellular Surface Plasmon Resonance imaging (cSPRi) approach allowing for monitoring low-affinity but high-avidity interactions. In summary, we find no evidence for human CD23 or DC-SIGN being bona fide receptors to human IgG, regardless of IgG Fc- or Fab-glycosylation status. However, these results do not exclude the possibility that either IgG glycosylation or C-type lectins affect IVIg therapies.
Generation and characterization of a stable cell line persistently replicating and secreting the human hepatitis delta virus
Authors: Ni Yi , Zhang Zhenfeng , Engelskircher Lisa , Verch Georg , Tu Thomas , Lempp Florian A. , Urban Stephan
Published: July 2019

Human hepatitis delta virus (HDV) causes the most severe form of viral hepatitis. Approximately 15–25 million people are chronically infected with HDV. As a satellite virus of the human hepatitis B virus (HBV), HDV uses the HBV-encoded envelope proteins for egress from and de novo entry into hepatocytes. So far, in vitro production of HDV particles is restricted to co-transfection of cells with HDV/HBV encoding cDNAs. This approach has several limitations. In this study, we established HuH7-END cells, which continuously secrete infectious HDV virions. The cell line was generated through stepwise stable integration of the cDNA of the HDV antigenome, the genes for the HBV envelope proteins and the HBV/HDV receptor NTCP. We found that HuH7-END cells release infectious HDV particles up to 400 million copies/milliliter and support virus spread to co-cultured cells. Due to the expression of NTCP, HuH7-END cells are also susceptible to de novo HDV entry. Virus production is stable for >16 passages and can be scaled up for preparation of large HDV virus stocks. Finally, HuH7-END cells are suitable for screening of antiviral drugs targeting HDV replication. In summary, the HuH7-END cell line provides a novel tool to study HDV replication in vitro.
Label propagation method based on bi-objective optimization for ambiguous community detection in large networks
Authors: Luo Junhai , Ye Lei
Published: July 2019

Community detection is of great significance because it serves as a basis for network research and has been widely applied in real-world scenarios. It has been proven that label propagation is a successful strategy for community detection in large-scale networks and local clustering coefficient can measure the degree to which the local nodes tend to cluster together. In this paper, we try to optimize two objects about the local clustering coefficient to detect community structure. To avoid the trend that merges too many nodes into a large community, we add some constraints on the objectives. Through the experiments and comparison, we select a suitable strength for one constraint. Last, we merge two objectives with linear weighting into a hybrid objective and use the hybrid objective to guide the label update in our proposed label propagation algorithm. We perform amounts of experiments on both artificial and real-world networks. Experimental results demonstrate the superiority of our algorithm in both modularity and speed, especially when the community structure is ambiguous.
A ubiquitin-like domain is required for stabilizing the N-terminal ATPase module of human SMCHD1
Authors: Pedersen Lars C. , Inoue Kaoru , Kim Susan , Perera Lalith , Shaw Natalie D.
Published: July 2019

Variants in the gene SMCHD1, which encodes an epigenetic repressor, have been linked to both congenital arhinia and a late-onset form of muscular dystrophy called facioscapulohumeral muscular dystrophy type 2 (FSHD2). This suggests that SMCHD1 has a diversity of functions in both developmental time and space. The C-terminal end of SMCHD1 contains an SMC-hinge domain which mediates homodimerization and chromatin association, whereas the molecular architecture of the N-terminal region, which harbors the GHKL-ATPase domain, is not well understood. We present the crystal structure of the human SMCHD1 N-terminal ATPase module bound to ATP as a functional dimer. The dimer is stabilized by a novel N-terminal ubiquitin-like fold and by a downstream transducer domain. While disease variants map to what appear to be critical interdomain/intermolecular interfaces, only the FSHD2-specific mutant constructs we tested consistently abolish ATPase activity and/or dimerization. These data suggest that the full functional profile of SMCHD1 has yet to be determined.