bluuebunny/crossref_metadata_2025 huggingface dataset:
Relational and Fine-Grained Argument Mining
Authors: Trautmann Dietrich , Fromm Michael , Tresp Volker , Seidl Thomas , Schütze Hinrich
Published: June 2020

In our project ReMLAV, funded within the DFG Priority Program RATIO (http://www.spp-ratio.de/), we focus on relational and fine-grained argument mining. In this article, we first introduce the problems we address and then summarize related work. The main part of the article describes our research on argument mining, both coarse-grained and fine-grained methods, and on same-side stance classification, a relational approach to the problem of stance classification. We conclude with an outlook.
Choosing the Optimal Brain Target for Neuromodulation Therapies as Alcohol Addiction Progresses—Insights From Pre-Clinical Studies
Authors: Edemann-Callesen Henriette , Barak Segev , Hadar Ravit , Winter Christine
Published: June 2020

Purpose of the Review

Development of addiction involves a transition from reward-driven to habitual behavior, mediated by neuroplastic changes. Based on preclinical findings, this article article reviews the current knowledge on the use of neuromodulation therapies to target alcohol addiction and essentially reduce relapse.

Recent Findings

To date, only a limited number of preclinical studies have investigated the use of neuromodulation in alcohol addiction, with the focus being on targeting the brain reward system. However, as addiction develops, additional circuits are recruited. Therefore, a differential setup may be required when seeking to alter the chronic alcohol-dependent brain, as opposed to treating earlier phases of alcohol addiction.

To promote enduring relapse prevention, the choice of brain target should match the stage of the disorder. Further studies are needed to investigate which brain areas should be targeted by neuromodulating strategies, in order to sufficiently alter the behavior and pathophysiology as alcohol addiction progresses.
The older the better: a fourth-order adaptive network model for reward-driven choices of emotion regulation strategies over time
Authors: Ullah Nimat , Treur Jan
Published: June 2020

The choice of which emotion regulation strategy to use changes depending on context, which within Psychology is referred to as ‘flexibility’. Besides that, choices of emotion regulation strategies are prone to various other factors, ranging from culture to gender, expectations of their effect, age, etc. This paper considers the phenomenon where choices of emotion regulation strategies change adaptively with age. In addition, the choices within specific age frames are driven by some kind of reward that affects in an adaptive manner the learning of a specific emotion regulation strategy. These adaptive phenomena involve plasticity or metaplasticity of different orders. They have been modeled by a fourth-order adaptive mental network model where the choice of emotion regulation strategies is motivated by reward prediction, and different age phases have their own adaptive influences. Simulation results are discussed for evaluation of the adaptive network model. The fourth-order adaptive network model presented here extends a second-order adaptive network model previously addressed in a paper at the conference COMPLEX NETWORKS 2019.
The Gendered Religious Response to State Action on the Coronavirus Pandemic
Authors: Smothers Hannah , Burge Ryan , Djupe Paul
Published: June 2020

State action to curtail the spread of the coronavirus has meant advising, and sometimes mandating, houses of worship to close to in-person worship. While mostly cooperative, the religious response has been varied and has exposed a hardened, defiant core. Informed by gendered religious worldviews, religious defiance is led by men and disproportionately supported by men. In this article, we document the extent of the defiance as of late March 2020 with our survey data and then investigate how gendered religious worldviews serve to track men to public roles and women to private ones. We attempt to confirm the nature of these effects with a gendered nationalism item and parallel gender gaps in political participation.
Ventilation and Expansion of Intermediate and Deep Waters in the Southeast Pacific During the Last Termination
Authors: Haddam N. A. , Michel E. , Siani G. , Licari L. , Dewilde F.
Published: June 2020

We investigate the geometry and ventilation of the water masses within bathyal depths (~1,500 to ~2,500 m) of the Southeast Pacific (SEP), inferring the lower depth limit variations of the Antarctic Intermediate Water (AAIW) since ~22 kyr cal. BP. We use three cores collected at the upper limit of the Pacific deep waters, between 41°S and 49°S, and one core at a greater depth within this same water mass, at 46°S. The benthic foraminiferal assemblages and carbon and oxygen isotopes are used to show strong linkages between the timing of the deglacial Southern Ocean upwelling events and changes in the vertical extension and ventilation of the AAIW. In accordance with local/sublocal oxygen reconstructions, we propose at least three states of ventilation‐AAIW vertical extension: (i) the late glacial and the Antarctic Cold Reversal (ACR): AAIW depth‐limit shoals, as its formation zone moves northward; (ii) the deglaciation (excluding the ACR): the [O2] enrichment of the AAIW and the dominance of benthic species Trifarina angulosa indicate ventilated AAIW, along with a deepening of its lower limit; and (iii) the Holocene: enhanced influence of the Pacific deep water at bathyal depths (1,500–2,500 m) in the SEP north of ~46°S and the circumpolar deep water south of ~46°S.
Antarctic Circumpolar Current Dynamics at the Pacific Entrance to the Drake Passage Over the Past 1.3 Million Years
Authors: Toyos María H. , Lamy Frank , Lange Carina B. , Lembke‐Jene Lester , Saavedra‐Pellitero Mariem , Esper Oliver , Arz Helge W.
Published: June 2020

The Antarctic Circumpolar Current (ACC) is the world's largest current system connecting all three major basins of the global ocean. Our knowledge of glacial‐interglacial changes in ACC dynamics in the southeast Pacific is not well constrained and presently only based on reconstructions covering the last glacial cycle. Here we use a combination of mean sortable silt grain size of the terrigenous sediment fraction (10–63 μm,
) and X‐ray fluorescence scanner‐derived Zr/Rb ratios as flow strength proxies to examine ACC variations at the Pacific entrance to the Drake Passage (DP) in the vicinity of the Subantarctic Front. Our results indicate that at the DP entrance, ACC strength varied by ~6–16% on glacial‐interglacial time scales, yielding higher current speeds during interglacial times and reduced current speeds during glacials. We provide evidence that previous observations of a reduction in DP throughflow during the last glacial period are part of a consistent pattern extending for at least the last 1.3 Ma. The orbital‐scale cyclicity follows well‐known global climate changes from prevailing ca. 41‐kyr cycles in the early part of the record (1.3 Ma to 850 ka; marine isotope stage 21) across the mid‐Pleistocene transition into the middle and late Pleistocene 100‐kyr world. A comparison to a bottom water flow record from the deep western boundary current off New Zealand (Ocean Drilling Program Site 1123) reveals anti‐phased changes between the two sites. The enhanced supply of deep water along the DP and into the Atlantic Ocean during interglacials corresponds to a weakened flow of the SW Pacific deep western boundary current.
Great Basin Paleoclimate and Aridity Linked to Arctic Warming and Tropical Pacific Sea Surface Temperatures
Authors: Lachniet Matthew S. , Asmerom Yemane , Polyak Victor , Denniston Rhawn
Published: June 2020

The arid southwestern United States is susceptible to sustained droughts that impact water resources and economic activity for millions of residents. Previous work has not systematically investigated the structure, timing, and possible forcings of Holocene Great Basin sub‐orbital hydroclimate changes, impeding our ability to understand the potential future controls on Southwestern aridity. The objective of this paper is to constrain the potential forcings on Holocene aridity and temperature, via comparison of new high‐resolution speleothem data, an Aridity Index synthesizing hydroclimate records, and linkages of Southwestern paleoclimate to other regions. The high‐resolution data from Leviathan Cave provide a paleoclimate record since 13,400 yr ago: A cool Younger Dryas was followed by two pronounced Middle Holocene aridity intervals between 9,850 and 5,310 yr B2k characterized by low growth rates and high δ18O and δ13C values. Subsequently, stalagmite δ18O values show near‐modern levels for the last four millennia during which time growth rates were high and δ13C values were low in response to wetter conditions. The regional Aridity Index documents that Middle Holocene drying coincided with a warm Arctic and decreased sea ice extent, a warm western tropical Pacific, and a large sea surface temperature gradient across the tropical Pacific, all of which likely responded to northern hemisphere summer insolation forcing. Our data suggest that extreme Middle Holocene aridity is more severe than the short medieval droughts evident in the tree ring record, and such extreme aridity may represent a worst‐case analog for future climate.
How Does a Greening Arctic Affect Groundwater Recharge?
Authors: Wheeling Kate
Published: June 2020

New research examines how shifts in aboveground ecology influence belowground hydrology in the Arctic.
Tectono‐Stratigraphic and Thermal Evolution of the Western Betic Flysch: Implications for the Geodynamics of South Iberian Margin and Alboran Domain
Authors: Daudet Maxime , Mouthereau Frédéric , Brichau Stéphanie , Crespo‐Blanc Ana , Gautheron Cécile , Angrand Paul
Published: June 2020

The Betic‐Rif orogen is a key region to understand the evolution of the plate boundary between Africa and Iberia/Europe. This study focuses on the Flysch Complex, which is considered the sedimentary cover of a domain originally positioned between the Iberian and Alboran margins. Based on stratigraphic and depositional evolution constraints, evidence for salt tectonics, combined with new apatite fission‐tracks (AFT) and (U‐Th‐Sm)/He ages from the Flysch Complex and the Subbetic Zone, we propose a geodynamic interpretation for the formation of the Betic Cordillera, accounting for moderate N‐directed transport of the Flysch Complex and synchronous exhumation between External and Internal Zones of the Betic. Early contraction between Africa and Iberia/Europe is reflected in the Cretaceous Flysch basin by a prolonged period of residence in the partial annealing zone for AFT and onset of foreland subsidence at 50 Ma. This stage lasted until the Early to Middle Miocene (20–15 Ma), marked by the rapid succession, in less than 5 Ma, of the deposition of Cenozoic flysch and their rapid exhumation. This event is interpreted to reflect the W‐directed retreating mantle delamination between Africa and Iberia margins at the origin of the collapse of the proto‐Betic orogenic domain and formation of the Alboran domain.
Active Extension in a Foreland Trapped Between Two Contractional Chains: The South Apulia Fault System (SAFS)
Authors: Maesano F. E. , Volpi V. , Civile D. , Basili R. , Conti A. , Tiberti M. M. , Accettella D. , Conte R. , Zgur F. , Rossi G.
Published: June 2020

The response of continental forelands to subduction and collision is a widely investigated topic in geodynamics. The deformation occurring within a foreland shared by two opposite‐verging chains, however, is uncommon and poorly understood. The Apulia Swell in the southern end of the Adria microplate (Africa‐Europe plate boundary, central Mediterranean Sea) represents one of these cases, as it is the common foreland of the SW verging Albanides‐Hellenides and the NE verging Southern Apennines merging into the SSE verging Calabrian Arc. We investigated the internal deformation of the Apulia Swell using multiscale geophysical data: multichannel seismic profiles recording up to 12‐s two‐way time (TWT) for a consistent image of the upper crust; high‐resolution multichannel seismic profiles, high‐resolution multibeam bathymetry, and CHIRP profiles acquired by R/V OGS Explora to constrain the Quaternary geological record. The results of our analyses characterize the geometry of the South Apulia Fault System (SAFS), a 100‐km‐long and 12‐km‐wide structure attesting an extensional (and possibly transtensional) response of the foreland to the two contractional fronts. The SAFS consists of two NW‐SE right‐stepping master faults and several secondary structures. The SAFS activity spans from the Early Pleistocene through the Holocene, as testified by the bathymetric and high‐resolution seismic data, with long‐term slip rates in the range of 0.2–0.4 mm/yr. Considering the position within an area with few or none other active faults in the surroundings, the dimension, and the activity rates, the SAFS can be a candidate causative fault of the 20 February 1743, M 6.7, earthquake.
Gap junction-mediated cell-to-cell communication in oral development and oral diseases: a concise review of research progress
Authors: Liu Wenjing , Cui Yujia , Wei Jieya , Sun Jianxun , Zheng Liwei , Xie Jing
Published: June 2020

Homoeostasis depends on the close connection and intimate molecular exchange between extracellular, intracellular and intercellular networks. Intercellular communication is largely mediated by gap junctions (GJs), a type of specialized membrane contact composed of variable number of channels that enable direct communication between cells by allowing small molecules to pass directly into the cytoplasm of neighbouring cells. Although considerable evidence indicates that gap junctions contribute to the functions of many organs, such as the bone, intestine, kidney, heart, brain and nerve, less is known about their role in oral development and disease. In this review, the current progress in understanding the background of connexins and the functions of gap junctions in oral development and diseases is discussed. The homoeostasis of tooth and periodontal tissues, normal tooth and maxillofacial development, saliva secretion and the integrity of the oral mucosa depend on the proper function of gap junctions. Knowledge of this pattern of cell–cell communication is required for a better understanding of oral diseases. With the ever-increasing understanding of connexins in oral diseases, therapeutic strategies could be developed to target these membrane channels in various oral diseases and maxillofacial dysplasia.
Histone chaperone FACT is essential to overcome replication stress in mammalian cells
Authors: Prendergast Laura , Hong Erin , Safina Alfiya , Poe Dante , Gurova Katerina
Published: June 2020

The histone chaperone FACT is upregulated during mammary tumorigenesis and necessary for the viability and growth of breast tumor cells. We established that only proliferating tumor cells are sensitive to FACT knockdown, suggesting that FACT functions during DNA replication in tumor cells but not in normal cells. We hypothesized that the basal level of replication stress defines the FACT dependence of cells. Using genetic and chemical tools, we demonstrated that FACT is needed to overcome replication stress. In the absence of FACT during replication stress, the MCM2-7 helicase dissociates from chromatin, resulting in the absence of ssDNA accumulation, RPA binding, and activation of the ATR/CHK1 checkpoint response. Without this response, stalled replication forks are not stabilized, and new origin firing cannot be prevented, leading to the accumulation of DNA damage and cell death. Thus, we propose a novel role for FACT as a factor preventing helicase dissociation from chromatin during replication stress.
Overview of lethal human coronaviruses
Authors: Chen Bin , Tian Er-Kang , He Bin , Tian Lejin , Han Ruiying , Wang Shuangwen , Xiang Qianrong , Zhang Shu , El Arnaout Toufic , Cheng Wei
Published: June 2020

Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus–host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment.
Deep learning in mental health outcome research: a scoping review
Authors: Su Chang , Xu Zhenxing , Pathak Jyotishman , Wang Fei
Published: June 2020

Mental illnesses, such as depression, are highly prevalent and have been shown to impact an individual’s physical health. Recently, artificial intelligence (AI) methods have been introduced to assist mental health providers, including psychiatrists and psychologists, for decision-making based on patients’ historical data (e.g., medical records, behavioral data, social media usage, etc.). Deep learning (DL), as one of the most recent generation of AI technologies, has demonstrated superior performance in many real-world applications ranging from computer vision to healthcare. The goal of this study is to review existing research on applications of DL algorithms in mental health outcome research. Specifically, we first briefly overview the state-of-the-art DL techniques. Then we review the literature relevant to DL applications in mental health outcomes. According to the application scenarios, we categorize these relevant articles into four groups: diagnosis and prognosis based on clinical data, analysis of genetics and genomics data for understanding mental health conditions, vocal and visual expression data analysis for disease detection, and estimation of risk of mental illness using social media data. Finally, we discuss challenges in using DL algorithms to improve our understanding of mental health conditions and suggest several promising directions for their applications in improving mental health diagnosis and treatment.
Circular RNA circZNF566 promotes hepatocellular carcinoma progression by sponging miR-4738-3p and regulating TDO2 expression
Authors: Li Shanbao , Weng Junyong , Song Fangbin , Li Lei , Xiao Chao , Yang Weiqiang , Xu Junming
Published: June 2020

As a recently discovered noncoding RNA, circular RNAs (circRNAs) have been identified to play key roles in cancer biology; however, the detailed functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unclarified. RNA-seq analysis was used to screen the expression profiles of circRNAs in HCC. CircZNF566 expression in HCC tissues and cell lines was detected by qRT-PCR. In vitro CCK-8, colony formation, wound healing, transwell migration, and invasion assays and in vivo tumorigenesis and metastasis assays were conducted to determine the functions of circZNF566. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed to confirm the relationship between circZNF566 and miR-4738-3p. Bioinformatics analysis and luciferase reporter assays were employed to determine whether miR-4738-3p regulates tryptophan 2,3-dioxygenase (TDO2) expression. Finally, immunohistochemistry (IHC) was used to detect the level of TDO2 and determine its prognostic value. CircZNF566 was significantly upregulated in HCC tissues and cell lines. High circZNF566 expression in HCC tissues was positively correlated with clinicopathological features and poor prognosis. Functionally, in vitro experiments showed that circZNF566 promoted HCC cell migration, invasion, and proliferation, whereas in vivo experiments showed that circZNF566 promoted tumorigenesis and metastasis. Mechanistically, circZNF566 acted as a miR-4738-3p sponge to relieve the repressive effect of miR-4738-3p on its target TDO2. In addition, miR-4738-3p suppressed HCC cell migration, invasion, and proliferation, while TDO2 was positively correlated with pathological features and poor prognosis and promoted cell migration, invasion, and proliferation in HCC. CircZNF566 is a novel tumor promoter in HCC and functions through the circZNF566/ miR-4738-3p /TDO2 axis; in addition, circZNF566 may serve as a novel diagnostic marker, prognostic indicator, and target for the treatment of HCC.
Intracellular virus sensor MDA5 exacerbates vitiligo by inducing the secretion of chemokines in keratinocytes under virus invasion
Authors: Zhuang Tongtian , Yi Xiuli , Chen Jianru , Kang Pan , Chen Xuguang , Chen Jiaxi , Cui Tingting , Chang Yuqian , Ye Zhubiao , Ni Qingrong , Wang Yinghan , Du Pengran , Li Baizhang , Liu Ling , Jian Zhe , Li Kai , Gao Tianwen , Li Shuli , Li Chunying
Published: June 2020

Vitiligo is a disfiguring disease featuring chemokines-mediated cutaneous infiltration of autoreactive CD8+ T cells that kill melanocytes. Copious studies have indicated that virus invasion participates in the pathogenesis of vitiligo. IFIH1, encoding MDA5 which is an intracellular virus sensor, has been identified as a vitiligo susceptibility gene. However, the specific role of MDA5 in melanocyte death under virus invasion is not clear. In this study, we first showed that the expression of anti-CMV IgM and MDA5 was higher in vitiligo patients than healthy controls. Then, by using Poly(I:C) to imitate virus invasion, we clarified that virus invasion significantly activated MDA5 and further potentiated the keratinocyte-derived CXCL10 and CXCL16 which are the two vital chemokines for the cutaneous infiltration of CD8+ T cells in vitiligo. More importantly, IFN-β mediated by the MDA5-MAVS-NF-κB/IRF3 signaling pathway orchestrated the secretion of CXCL10 via the JAK1-STAT1 pathway and MDA5-meidiated IRF3 transcriptionally induced the production of CXCL16 in keratinocytes under virus invasion. In summary, our results demonstrate that MDA5 signaling orchestrates the aberrant skin immunity engaging in melanocyte death via mediating CXCL10 and CXCL16 secretion, which supports MDA5 as a potential therapeutic target for vitiligo under virus invasion.
MAPK-dependent hormonal signaling plasticity contributes to overcoming Bacillus thuringiensis toxin action in an insect host
Authors: Guo Zhaojiang , Kang Shi , Sun Dan , Gong Lijun , Zhou Junlei , Qin Jianying , Guo Le , Zhu Liuhong , Bai Yang , Ye Fan , Wu Qingjun , Wang Shaoli , Crickmore Neil , Zhou Xuguo , Zhang Youjun
Published: June 2020

The arms race between entomopathogenic bacteria and their insect hosts is an excellent model for decoding the intricate coevolutionary processes of host-pathogen interaction. Here, we demonstrate that the MAPK signaling pathway is a general switch to trans-regulate differential expression of aminopeptidase N and other midgut genes in an insect host, diamondback moth (Plutella xylostella), thereby countering the virulence effect of Bacillus thuringiensis (Bt) toxins. Moreover, the MAPK cascade is activated and fine-tuned by the crosstalk between two major insect hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH) to elicit an important physiological response (i.e. Bt resistance) without incurring the significant fitness costs often associated with pathogen resistance. Hormones are well known to orchestrate physiological trade-offs in a wide variety of organisms, and our work decodes a hitherto undescribed function of these classic hormones and suggests that hormonal signaling plasticity is a general cross-kingdom strategy to fend off pathogens.
Sub-nanowatt microfluidic single-cell calorimetry
Authors: Hong Sahngki , Dechaumphai Edward , Green Courtney R. , Lal Ratneshwar , Murphy Anne N. , Metallo Christian M. , Chen Renkun
Published: June 2020

Non-invasive and label-free calorimetry could become a disruptive technique to study single cell metabolic heat production without altering the cell behavior, but it is currently limited by insufficient sensitivity. Here, we demonstrate microfluidic single-cell calorimetry with 0.2-nW sensitivity, representing more than ten-fold enhancement over previous record, which is enabled by (i) a low-noise thermometry platform with ultralow long-term (10-h) temperature noise (80 μK) and (ii) a microfluidic channel-in-vacuum design allowing cell flow and nutrient delivery while maintaining a low thermal conductance of 2.5 μW K−1. Using Tetrahymena thermophila as an example, we demonstrate on-chip single-cell calorimetry measurement with metabolic heat rates ranging from 1 to 4 nW, which are found to correlate well with the cell size. Finally, we perform real-time monitoring of metabolic rate stimulation by introducing a mitochondrial uncoupling agent to the microchannel, enabling determination of the spare respiratory capacity of the cells.
Heterobilayers of 2D materials as a platform for excitonic superfluidity
Authors: Gupta Sunny , Kutana Alex , Yakobson Boris I.
Published: June 2020

Excitonic condensate has been long-sought within bulk indirect-gap semiconductors, quantum wells, and 2D material layers, all tried as carrying media. Here, we propose intrinsically stable 2D semiconductor heterostructures with doubly-indirect overlapping bands as optimal platforms for excitonic condensation. After screening hundreds of 2D materials, we identify candidates where spontaneous excitonic condensation mediated by purely electronic interaction should occur, and hetero-pairs Sb2Te2Se/BiTeCl, Hf2N2I2/Zr2N2Cl2, and LiAlTe2/BiTeI emerge promising. Unlike monolayers, where excitonic condensation is hampered by Peierls instability, or other bilayers, where doping by applied voltage is required, rendering them essentially non-equilibrium systems, the chemically-specific heterostructures predicted here are lattice-matched, show no detrimental electronic instability, and display broken type-III gap, thus offering optimal carrier density without any gate voltages, in true-equilibrium. Predicted materials can be used to access different parts of electron-hole phase diagram, including BEC-BCS crossover, enabling tantalizing applications in superfluid transport, Josephson-like tunneling, and dissipationless charge counterflow.
Non-thermal resistive switching in Mott insulator nanowires
Authors: Kalcheim Yoav , Camjayi Alberto , del Valle Javier , Salev Pavel , Rozenberg Marcelo , Schuller Ivan K.
Published: June 2020

Resistive switching can be achieved in a Mott insulator by applying current/voltage, which triggers an insulator-metal transition (IMT). This phenomenon is key for understanding IMT physics and developing novel memory elements and brain-inspired technology. Despite this, the roles of electric field and Joule heating in the switching process remain controversial. Using nanowires of two archetypal Mott insulators—VO2 and V2O3 we unequivocally show that a purely non-thermal electrical IMT can occur in both materials. The mechanism behind this effect is identified as field-assisted carrier generation leading to a doping driven IMT. This effect can be controlled by similar means in both VO2 and V2O3, suggesting that the proposed mechanism is generally applicable to Mott insulators. The energy consumption associated with the non-thermal IMT is extremely low, rivaling that of state-of-the-art electronics and biological neurons. These findings pave the way towards highly energy-efficient applications of Mott insulators.
Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity
Authors: Wang Lei , Pydi Sai P. , Zhu Lu , Barella Luiz F. , Cui Yinghong , Gavrilova Oksana , Bence Kendra K. , Vernochet Cecile , Wess Jürgen
Published: June 2020

Adipocyte dysfunction links obesity to insulin resistance and type 2 diabetes. Adipocyte function is regulated by receptor-mediated activation of heterotrimeric G proteins. Little is known about the potential in vivo metabolic roles of Gi-type G proteins expressed by adipocytes, primarily due to the lack of suitable animal models. To address this question, we generated mice lacking functional Gi proteins selectively in adipocytes. Here we report that these mutant mice displayed significantly impaired glucose tolerance and reduced insulin sensitivity when maintained on an obesogenic diet. In contrast, using a chemogenetic strategy, we demonstrated that activation of Gi signaling selectively in adipocytes greatly improved glucose homeostasis and insulin signaling. We also elucidated the cellular mechanisms underlying the observed metabolic phenotypes. Our data support the concept that adipocyte Gi signaling is essential for maintaining euglycemia. Drug-mediated activation of adipocyte Gi signaling may prove beneficial for restoring proper glucose homeostasis in type 2 diabetes.
3D sedimentary architecture showing the inception of an Ice Age
Authors: Løseth H. , Dowdeswell J. A. , Batchelor C. L. , Ottesen D.
Published: June 2020

Northeast Atlantic climate shifted into the Quaternary Ice Age around 2.6 M yr ago. Until now, however, the detailed changes associated with this inception of an Ice Age have remained obscure. New high-quality three-dimensional seismic data reveal a detailed geological record of buried surfaces, landforms and sedimentary architecture over vast parts of the Norwegian North Sea. Here, we show the sequence of near-coast geological events spanning the Northeast Atlantic inception of an Ice Age. We identify the location of immediate pre-glacial fluvially derived sandy systems where rivers from the Norwegian mainland built marine deltas. The stratigraphic position of a large submarine channel, formed by enhanced meltwater from initial build-up of local glaciers, is also shown. Finally, we document the transition to full ice-sheet growth over Scandinavia from the ice sheet’s earliest position to the later pattern of debris-flow lobes reaching the present-day shelf edge.
CRISPR artificial splicing factors
Authors: Du Menghan , Jillette Nathaniel , Zhu Jacqueline Jufen , Li Sheng , Cheng Albert Wu
Published: June 2020

Alternative splicing allows expression of mRNA isoforms from a single gene, expanding the diversity of the proteome. Its prevalence in normal biological and disease processes warrant precise tools for modulation. Here we report the engineering of CRISPR Artificial Splicing Factors (CASFx) based on RNA-targeting CRISPR-Cas systems. We show that simultaneous exon inclusion and exclusion can be induced at distinct targets by differential positioning of CASFx. We also create inducible CASFx (iCASFx) using the FKBP-FRB chemical-inducible dimerization domain, allowing small molecule control of alternative splicing. Finally, we demonstrate the activation of SMN2 exon 7 splicing in spinal muscular atrophy (SMA) patient fibroblasts, suggesting a potential application of the CASFx system.
Oculomotor behavior tracks the effect of ideological priming on deception
Authors: Schepisi Michael , Porciello Giuseppina , Aglioti Salvatore Maria , Panasiti Maria Serena
Published: June 2020

The decision to lie to another person involves a conflict between one’s own and others’ interest. Political ideology may foster self-promoting or self-transcending values and thus may balance or fuel self vs. other related conflicts. Here, we explored in politically non-aligned participants whether oculomotor behavior may index the influence on moral decision-making of prime stimuli related to left and right-wing ideologies. We presented pictures of Italian politicians and ideological words in a paradigm where participants could lie to opponents with high vs. low socio-economic status to obtain a monetary reward. Results show that left-wing words decreased self-gain lies and increased other-gain ones. Oculomotor behavior revealed that gazing longer at politicians’ pictures led participants to look longer at opponent’s status-related information than at game’s outcome-related information before the decision. This, in turn, caused participants to lie less to low status opponents. Moreover, after lying, participants averted their gaze from high status opponents and maintained it towards low status ones. Our results offer novel evidence that ideological priming influences moral decision-making and suggest that oculomotor behavior may provide crucial insights on how this process takes place.
Knowledge, attitude and practice on dengue prevention and dengue seroprevalence in a dengue hotspot in Malaysia: A cross-sectional study
Authors: Selvarajoo Sivaneswari , Liew Jonathan Wee Kent , Tan Wing , Lim Xin Ying , Refai Wardha F. , Zaki Rafdzah Ahmad , Sethi Neha , Wan Sulaiman Wan Yusoff , Lim Yvonne Ai Lian , Vadivelu Jamuna , Vythilingam Indra
Published: June 2020

Dengue has become a global public health problem. Despite reactive efforts by the government in Malaysia, the dengue cases are on the increase. Adequate knowledge, positive attitude and correct practice for dengue control are essential to stamp out the disease. Hence, this study aims to assess the factors associated with dengue knowledge, attitude and practice (KAP), as well as the association with dengue IgM and IgG seropositivity. A community-based cross-sectional study was conducted in a closed, dengue endemic area with multi-storey dwellings . Five hundred individuals (aged 18 years and above) were approached for pre-tested KAP and seroprevalences assessment. The study showed only half of the total participants have good knowledge (50.7%) but they had insufficient knowledge about dengue during pregnancy. 53.2% of people had poor attitude and 50.2% reported poor practice for dengue control. Out of 85 respondents who agreed to participate in the dengue seroprevalence study, 74.1% (n = 63) were positive for dengue IgG and 7.1% (n = 6) were positive for dengue IgM. Among all sociodemographic variable, race is the only independent predicator for all KAP levels (P < 0.05). In conclusion, proactive and sustainable efforts are needed to bring a behavioural change among communities in order to fight dengue outbreaks in endemic areas.
Increasing incidence of group B streptococcus neonatal infections in the Netherlands is associated with clonal expansion of CC17 and CC23
Authors: Jamrozy Dorota , Bijlsma Merijn W. , de Goffau Marcus C. , van de Beek Diederik , Kuijpers Taco W. , Parkhill Julian , van der Ende Arie , Bentley Stephen D.
Published: June 2020

Group B streptococcus (GBS) is the leading cause of neonatal invasive disease worldwide. In the Netherlands incidence of the disease increased despite implementation of preventive guidelines. We describe a genomic analysis of 1345 GBS isolates from neonatal (age 0–89 days) invasive infections in the Netherlands reported between 1987 and 2016. Most isolates clustered into one of five major lineages: CC17 (39%), CC19 (25%), CC23 (18%), CC10 (9%) and CC1 (7%). There was a significant rise in the number of infections due to isolates from CC17 and CC23. Phylogenetic clustering analysis revealed that this was caused by expansion of specific sub-lineages, designated CC17-A1, CC17-A2 and CC23-A1. Dating of phylogenetic trees estimated that these clones diverged in the 1960s/1970s, representing historical rather than recently emerged clones. For CC17-A1 the expansion correlated with acquisition of a new phage, carrying gene encoding a putative cell-surface protein. Representatives of CC17-A1, CC17-A2 and CC23-A1 clones were identified in datasets from other countries demonstrating their global distribution.
Visuomotor deficiency in panx1a knockout zebrafish is linked to dopaminergic signaling
Authors: Safarian Nickie , Whyte-Fagundes Paige , Zoidl Christiane , Grigull Jörg , Zoidl Georg
Published: June 2020

Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play roles in the nervous system. The analysis of roles in both standard and pathological conditions benefits from a model organism with rapid development and early onset of behaviors. Such a model was developed by ablating the zebrafish panx1a gene using TALEN technology. Here, RNA-seq analysis of 6 days post fertilization larvae were confirmed by Real-Time PCR and paired with testing visual-motor behavior and in vivo electrophysiology. Results demonstrated that loss of panx1a specifically affected the expression of gene classes representing the development of the visual system and visual processing. Abnormal swimming behavior in the dark and the expression regulation of pre-and postsynaptic biomarkers suggested changes in dopaminergic signaling. Indeed, altered visuomotor behavior in the absence of functional Panx1a was evoked through D1/D2-like receptor agonist treatment and rescued with the D2-like receptor antagonist Haloperidol. Local field potentials recorded from superficial areas of the optic tectum receiving input from the retina confirmed abnormal responses to visual stimuli, which resembled treatments with a dopamine receptor agonist or pharmacological blocking of Panx1a. We conclude that Panx1a functions are relevant at a time point when neuronal networks supporting visual-motor functions undergo modifications preparing for complex behaviors of freely swimming fish.
An AgNP-deposited commercial electrochemistry test strip as a platform for urea detection
Authors: Liu Juanjuan , Siavash Moakhar Roozbeh , Sudalaiyadum Perumal Ayyappasamy , Roman Horia Nicolae , Mahshid Sara , Wachsmann-Hogiu Sebastian
Published: June 2020

We developed an inexpensive, portable platform for urea detection via electrochemistry by depositing silver nanoparticles (AgNPs) on a commercial glucose test strip. We modified this strip by first removing the enzymes from the surface, followed by electrodeposition of AgNPs on one channel (working electrode). The morphology of the modified test strip was characterized by Scanning Electron Microscopy (SEM), and its electrochemical performance was evaluated via Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). We evaluated the performance of the device for urea detection via measurements of the dependency of peak currents vs the analyte concentration and from the relationship between the peak current and the square root of the scan rates. The observed linear range is 1–8 mM (corresponding to the physiological range of urea concentration in human blood), and the limit of detection (LOD) is 0.14 mM. The selectivity, reproducibility, reusability, and storage stability of the modified test strips are also reported. Additional tests were performed to validate the ability to measure urea in the presence of confounding factors such as spiked plasma and milk. The results demonstrate the potential of this simple and portable EC platform to be used in applications such as medical diagnosis and food safety.
Bidirectional association between asthma and chronic rhinosinusitis: Two longitudinal follow-up studies using a national sample cohort
Authors: Ryu Gwanghui , Min Chanyang , Park Bumjung , Choi Hyo Geun , Mo Ji-Hun
Published: June 2020

The aim of this study was to evaluate an epidemiologic association of asthma and chronic rhinosinusitis (CRS) using a national sample cohort of the Korean population. We collected data from the Korean Health Insurance Review and Assessment Service-National Sample Cohort between 2002 and 2013, and two different case-control cohorts were designed (1st: asthmatic patients matched in a 1:1 ratio with 204,119 non-asthmatics as control I, 2nd: CRS patients matched in a 1:4 ratio with 124,020 non-CRS patients as control II). Bidirectional association was examined using Cox proportional hazard models stratified by age, sex, income, and region of residence. Patients with asthma had an increased risk of developing CRS [adjusted hazard ratio (95% confidence interval) = 1.74 (1.67–1.80)], both with nasal polyps [1.55 (1.36–1.78)], without nasal polyps [1.74 (1.67–1.81)]. In the second cohort, patients with CRS had increased risk of developing asthma [1.85 (1.80–1.91)] with similar results for those with and without nasal polyps. The strongest association for risk of CRS was in 20–39 years old men with asthma [2.41 (1.97–2.96)], while the strongest association for increased risk of asthma in those with CRS group was also seen in this same subgroup [2.40 (2.18–2.63)]. CRS and asthma had a bidirectional influence on each other. CRS increased the risk of asthma, and asthma increased the risk of CRS, especially in young men.
Crystal structures of Uso1 membrane tether reveal an alternative conformation in the globular head domain
Authors: Heo Yoonyoung , Yoon Hye-Jin , Ko Hanseo , Jang Soonmin , Lee Hyung Ho
Published: June 2020

Membrane tethers play a critical role in organizing the complex molecular architecture of eukaryotic cells. Uso1 (yeast homolog of human p115) is essential for tethering in vesicle transport from ER to Golgi and interacts with Ypt1 GTPase. The N-terminal globular head domain of Uso1 is responsible for Ypt1 binding; however, the mechanism of tethering between ER transport vesicles and Golgi is unknown. Here, we determined two crystal structures for the Uso1 N-terminal head domain in two alternative conformations. The head domain of Uso1 exists as a monomer, as confirmed using size-exclusion chromatography coupled to multi-angle light scattering and analytical gel filtration. Although Uso1 consists of a right-handed α-solenoid, like that in mammalian homologs, the overall conformations of both Uso1 structures were not similar to previously known p115 structures, suggesting that it adopts alternative conformations. We found that the N- and C-terminal regions of the Uso1 head domain are connected by a long flexible linker, which may mediate conformational changes. To analyse the role of the alternative conformations of Uso1, we performed molecular docking of Uso1 with Ypt1, followed by a structural comparison. Taken together, we hypothesize that the alternative conformations of Uso1 regulate the precise docking of vesicles to Golgi.
First Principles Calculation for Photocatalytic Activity of GaAs Monolayer
Authors: Rouzhahong Yilimiranmu , Wushuer Mariyemu , Mamat Mamatrishat , Wang Qing , Wang Qian
Published: June 2020

Solar energy hydrogen production is one of the best solutions for energy crisis. Therefore, finding effective photocatalytic materials that are able to split water under the sunlight is a hot topic in the present research fields. In addition, theoretical prediction is a present low-cost important method to search a new kind of materials. Herein, with the aim of seeking efficient photocatalytic material we investigated the photocatalytic activity of GaAs monolayer by the first principles calculation. According to the obtained electronic and optical properties, we primarily predicted the photocatalytic water splitting activity of GaAs monolayer, which the result further confirmed by the calculated reaction free energy. More remarkably, predicted carrier mobility of GaAs monolayer 2838 cm2V−1s−1is higher than 200 cm2V−1s−1of MoS2. Our finding provides a promising material for the development of renewable energy conversion and a new outlook for better designing of a superior photocatalyst for water splitting.
Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma
Authors: Addie Ruben D. , Kostidis Sarantos , Corver Willem E. , Oosting Jan , Aminzadeh-Gohari Sepideh , Feichtinger René G. , Kofler Barbara , Aydemirli Mehtap Derya , Giera Martin , Morreau Hans
Published: June 2020

Hürthle cell carcinoma (HCC) is a recurrent subtype of non-medullary thyroid cancer. HCC is characterized by profound whole-chromosome instability (w-CIN), resulting in a near-homozygous genome (NHG), a phenomenon recently attributed to reactive oxygen species (ROS) generated during mitosis by malfunctioning mitochondria. We studied shared metabolic traits during standard and glucose-depleted cell culture in thyroid cancer cell lines (TCCLs), with or without a NHG, using quantitative analysis of extra and intracellular metabolites and ROS production following inhibition of complex III with antimycin A. We found that the XTC.UC1 and FTC-236 cell lines (both NHG) are functionally impaired in complex I and produce significantly more superoxide radicals than SW579 and BHP 2–7 (non-NHG) after challenge with antimycin A. FTC-236 showed the lowest levels of glutathione and SOD2. XTC.UC1 and FTC-236 both exhibited reduced glycolytic activity and utilization of alternative sources to meet energy demands. Both cell lines also shared low levels of α-ketoglutarate and high levels of creatine, phosphocreatine, uridine diphosphate-N-acetylglucosamine, pyruvate and acetylcarnitine. Furthermore, the metabolism of XTC.UC1 was skewed towards the de novo synthesis of aspartate, an effect that persisted even in glucose-free media, pointing to reductive carboxylation. Our data suggests that metabolic reprogramming and a subtle balance between ROS generation and scavenging/conversion of intermediates may be involved in ROS-induced w-CIN in HCC and possibly also in rare cases of follicular thyroid cancer showing a NHG.
The development of a scoring and ranking strategy for a patient-tailored adverse drug reaction prediction in polypharmacy
Authors: Valeanu Andrei , Damian Cristian , Marineci Cristina Daniela , Negres Simona
Published: June 2020

Only few applications are currently dealing with personalized adverse drug reactions (ADRs) prediction in case of polypharmacy. The study aimed to develop a patient-tailored ADR web application, considering characteristics from 734 drugs and relevant patient related factors. The application was designed in Python using a scoring and ranking system based on frequency and severity, computed for each ADR and expressed through an online platform. A neural networks algorithm was used for predicting the severity of ADRs. The application inputs are: age, gender, drugs, relevant pathologies. The outputs are: an overall severity profile (hospitalization and mortality risk), a stratified risk on specific ADR groups and a sorted list of the most important ADRs depending on frequency and severity. The Severity prediction model validation resulted in 79.7–85.1% Area Under the Receiver Operating Characteristic Curve Score, which lies in the good cut-off of 75–90%. The program offers a complex view regarding the ADR profile of a given patient and could be used by the physician and clinical pharmacist during patient safety monitoring, for a coherent therapy choice or medication adjustment, due to the good therapy coverage and the inclusion of relevant patient comorbidities.