bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Analysis of Self-Harm and Suicide in Sri Lankan Printed Newspapers
Authors: Brandt Sørensen Jane , Pearson Melissa , Armstrong Gregory , Andersen Martin Wolf , Weerasinghe Manjula , Hawton Keith , Konradsen Flemming
Published: May 2020

Abstract. Background: Media reporting may influence suicidal behavior. In-depth exploration of how self-harm and suicide are portrayed in newspaper articles in a middle-income country such as Sri Lanka is lacking. Aims: We aimed to explore how self-harm and suicide are portrayed in Sri Lankan printed newspapers. Method: Seven English- and Sinhala-language Sri Lankan newspapers were screened for articles reporting on self-harm and suicide (December 1, 2014 to January 31, 2015). A thematic analysis was conducted. Results: In the 78 articles identified for analysis, certain aspects were overemphasized (inappropriate behavior) and others underemphasized (alcohol and complexities of self-harm). Explanations of self-harm were one-sided and a suicide prevention narrative was lacking. Limitations: Another time-frame and inclusion of Tamil newspapers as well as social media and online publications would provide additional understanding. Conclusion: The study found an indication of simplistic reporting. Greater focus on prevention and a nuanced portrayal of self-harm could reduce stigma and imitative behavior.
Ocean Color Algorithms for Estimating Chlorophyll a, CDOM Absorption, and Particle Backscattering in the Arctic Ocean
Authors: Lewis K. M. , Arrigo K. R.
Published: May 2020

As the Arctic Ocean (AO) is increasingly altered by anthropogenic climate change, it is critical that we accurately assess ongoing changes in its capacity to support marine life. Ocean color remote sensing provides an effective tool to estimate phytoplankton biomass and net primary production in the remote and undersampled AO. However, standard algorithms have been parameterized using global data sets that severely underrepresent the AO. Because the optical properties of AO waters differ markedly from those of lower‐latitude waters, standard algorithms perform poorly in the AO. Here, we use the largest bio‐optical database ever assembled for AO waters to examine seasonal and regional patterns of AO optical properties and to quantify their impact on ocean color algorithms. We find that the standard algorithms fail to accurately retrieve the primary photosynthetic pigment chlorophyll a (Chl a) in the AO; it is overestimated at low phytoplankton biomass due to exceptionally high absorption of colored dissolved organic matter (CDOM), particularly on the interior shelves, and underestimated at high biomass due to the photoacclimation of phytoplankton growing in low light leading to high pigment packaging effect. Using this large bio‐optical database that includes in situ measurements from across the AO and through the entire growing season, we parameterize a new empirical (AOReg.emp) and semianalytical (AO.GSM) algorithm which represent the unique bio‐optical properties of the AO to successfully retrieve Chl a, CDOM absorption, and particle backscattering with better accuracy than any algorithm yet applied to the AO.
Surface Depression and Wetland Water Storage Improves Major River Basin Hydrologic Predictions
Authors: Rajib Adnan , Golden Heather E. , Lane Charles R. , Wu Qiusheng
Published: May 2020

Surface water storage in small yet abundant landscape depressions—including wetlands and other small waterbodies—is largely disregarded in conventional hydrologic modeling practices. No quantitative evidence exists of how their exclusion may lead to potentially inaccurate model projections and understanding of hydrologic dynamics across the world's major river basins. To fill this knowledge gap, we developed the first‐ever major river basin‐scale modeling approach integrating surface depressions and focusing on the 450,000‐km2 Upper Mississippi River Basin (UMRB) in the United States. We applied a novel topography‐based algorithm to estimate areas and volumes of ~455,000 surface depressions (>1 ha) across the UMRB (in addition to lakes and reservoirs) and subsequently aggregated their effects per subbasin. Compared to a “no depression” conventional model, our depression‐integrated model (a) improved streamflow simulation accuracy with increasing upstream abundance of depression storage, (b) significantly altered the spatial patterns and magnitudes of water yields across 315,000 km2 (70%) of the basin area, and (c) provided realistic spatial distributions of rootzone wetness conditions corresponding to satellite‐based data. Results further suggest that storage capacity (i.e., volume) alone does not fully explain depressions' cumulative effects on landscape hydrologic responses. Local (i.e., subbasin level) climatic and geophysical drivers and downstream flowpath‐regulating structures (e.g., reservoirs and dams) influence the extent to which depression storage volume in a subbasin causes hydrologic effects. With these new insights, our study supports the integration of surface depression storage and thereby catalyzes a reassessment of current hydrological modeling and management practices for basin‐scale studies.
The Impact of Wettability and Surface Roughness on Fluid Displacement and Capillary Trapping in 2‐D and 3‐D Porous Media: 1. Wettability‐Controlled Phase Transition of Trapping Efficiency in Glass Beads Packs
Authors: Geistlinger Helmut , Zulfiqar Bilal
Published: May 2020

Fluid invasion, displacement of one fluid by another in porous media, is important in a large number of industrial and natural processes. Of special interest is the trapping of gas and oil clusters. We study the impact of wettability on fluid pattern formation and capillary trapping in three‐dimensional glass beads packs (dmean = 1 mm) during fluid invasion at capillary numbers of 10−7 using μ‐CT. The invading fluid was water, and the defending fluid was air. The contact angle of the glass beads was altered between 5° and 115° using Piranha cleaning and silanization. We analyzed the front morphology of the invading fluid, the residual gas saturation, the fluid occupation frequency of pores, and the morphology and statistics of the trapped gas clusters. We found a sharp transition (crossover) at a critical contact angle θc = 96°. Below θc the morphology of the displacement front was flat and compact caused by the strong smoothing effect of cooperative filling. Above θc the morphology of the displacement front was fractal and ramified caused by single bursts (Haines jumps). Across this dynamical phase transition the trapping efficiency changes from no trapping to maximal trapping. For θ > θc the experimental results show that invasion percolation governs the fluid displacement. Strong indicators are the universal scaling behavior of the size distribution of large clusters (relative data error εdata < 1%) and their linear surface‐volume relationship (R2 = 0.99).
Drought‐Induced Soil Desiccation Cracking Behavior With Consideration of Basal Friction and Layer Thickness
Authors: Zeng Hao , Tang Chao‐Sheng , Cheng Qing , Zhu Cheng , Yin Li‐Yang , Shi Bin
Published: May 2020

Drought‐induced cracking of soils is of great concern with the advent of global climate change. The cracking process accelerates the evaporation rate of pore water, lowers the water retention capacity, and degrades the hydraulic‐mechanical properties of soils. Basal friction and layer thickness are two important aspects affecting the subsurface cracking. To explore their detailed effects on soils under drying, we conduct a series of desiccation tests on twelve slurry soil bars and select four types of base materials with different roughness levels and three kinds of layer thicknesses. We track the dynamic cracking process in various samples and adopt the noncontact optical technique—digital image correlation—for the motion of soil particles. Experimental results validate that the coupled effects of basal conditions and soil layer thickness play a key role in governing the soil cracking behavior. The presence of rough bottom surface induces the onset and propagation of desiccation cracks at both top and bottom surfaces. Some of the cracks initiated at the bottom do not propagate through the soil profile. Increasing layer thickness weakens the effect of basal friction on the soil top surface shrinkage but increases the frictional force acting on the base and results in more crack initiations at the bottom. The digital image correlation results further reveal that cracks initiated on the bottom surface and propagated upward vertically are dominated by tensile stresses, while those propagated upward obliquely are dominated by the joint action of shear and tensile stresses.
The β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 axis promotes hepatocellular carcinoma metastasis
Authors: Huang Wei-Juan , Tian Xiao-Peng , Bi Si-Xue , Zhang Si-Rui , He Ting-Sha , Song Li-Yan , Yun Jing-Ping , Zhou Zhong-Guo , Yu Rong-Min , Li Mei
Published: May 2020

Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Cancer Genome Atlas (TCGA) and Sun Yat-sen University Cancer Center (SYSUCC) dataset. MiR-1258 expression negatively correlated with recurrence-free survival and overall survival of HCC patients. MiR-1258 overexpression inhibited migration and invasion of HCC cells both in vitro and in vivo, whereas miR-1258 downregulation promoted cell metastasis. Luciferase assays verified direct binding of miR-1258 to Smad2 and Smad3, thereby attenuating TGF-β/Smad signaling. We further established that lncRNA LINC01278 was a negative regulator of miR-1258. In vivo and in vitro assays demonstrated that LINC01278-mediated HCC metastasis was dependent on miR-1258 expression. Furthermore, miR-1258 downregulation in turn increased LINC01278 expression. We also observed that TCF-4 could bind to the LINC01278 promoter site. In addition, LINC01278 downregulation decreased migration and invasion of HCC cells induced by β-catenin and TGF-β1 both in vitro and in vivo. We uncovered a novel mechanism for β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 feedback loop activation in HCC metastasis, and the study indicated that LINC01278 could serve as a therapeutic target for HCC metastasis.
Analysis of different characteristics of smile
Authors: Khan Mehwish , Kazmi Syed Murtaza Raza , Khan Farhan Raza , Samejo Imran
Published: May 2020

Introduction

Analysis of smile is imperative in the diagnosis and treatment planning phases of aesthetic dentistry.

Aim

To evaluate the components of smile among students of a dental institution.

Methods

Frontal view digital photographs with posed smile of 157 dental students were assessed using Adobe Photoshop7.0. Smile characteristics evaluated included; smile line, smile arc, smile design, upper lip curvature, labiodental relationship and number of teeth displayed. Data were analyzed using SPSS version 23.0. Pearson chi-square test was used to determine the gender based differences for various parameters.

Results

Average smile line (43.3%), consonant smile arcs (45.2%), cuspid smiles (45.9%), upward lip curvature (43.9%), maxillary anterior teeth not covered by lower lip (60.5%) and teeth displayed up to first premolars (35.7%). Gender based differences were not statistically significant except for smile arc (pvalue = 0.02) and number of teeth displayed (pvalue < 0.001). There was a significant relationship between lip curvature and smile pattern (pvalue < 0.001) and lip curvature and smile arc (pvalue = 0.01) revealing that upward lip curvature was associated with commissure type smiles and consonant smile arcs.

Conclusions

The smile characteristics should be considered before beginning the aesthetic treatment of the patient to obtain adequate results in oral rehabilitation.
Clinical utility of serial analysis of circulating tumour cells for detection of minimal residual disease of metastatic nasopharyngeal carcinoma
Authors: Ko Josephine Mun-Yee , Vardhanabhuti Vince , Ng Wai-Tong , Lam Ka-On , Ngan Roger Kai-Cheong , Kwong Dora Lai-Wan , Lee Victor Ho-fun , Lui Yun-Hoi , Yau Chun-Chung , Kwan Chung-Kong , Li Wing-Sum , Yau Stephen , Guo Chen , Choi Sheyne Sta Ana , Lei Lisa Chan , Chan Kenneth Chun-Ho , Lam Candy Chi-Shan , Chan Candy King-Chi , Dai Wei , Khong Pek-Lan , Lung Maria Li
Published: May 2020

Background

Nasopharyngeal carcinoma (NPC) is an important cancer in Hong Kong. We aim to utilise liquid biopsies for serial monitoring of disseminated NPC in patients to compare with PET-CT imaging in detection of minimal residual disease.

Method

Prospective serial monitoring of liquid biopsies was performed for 21 metastatic patients. Circulating tumour cell (CTC) enrichment and characterisation was performed using a sized-based microfluidics CTC chip, enumerating by immunofluorescence staining, and using target-capture sequencing to determine blood mutation load. PET-CT scans were used to monitor NPC patients throughout their treatment according to EORTC guidelines.

Results

The longitudinal molecular analysis of CTCs by enumeration or NGS mutational profiling findings provide supplementary information to the plasma EBV assay for disease progression for good responders. Strikingly, post-treatment CTC findings detected positive findings in 75% (6/8) of metastatic NPC patients showing complete response by imaging, thereby demonstrating more sensitive CTC detection of minimal residual disease. Positive baseline, post-treatment CTC, and longitudinal change of CTCs significantly associated with poorer progression-free survival by the Kaplan–Meier analysis.

Conclusions

We show the potential usefulness of application of serial analysis in metastatic NPC of liquid biopsy CTCs, as a novel more sensitive biomarker for minimal residual disease, when compared with imaging.
I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo
Authors: Liu Zhengjun , Li Ping , Yang Yong-qiang , Cai Shang , Lin Xiangwei , Chen Min-bin , Guo Hailei
Published: May 2020

Bromodomain-containing protein 4 (BRD4) is a potential therapeutic target of skin squamous cell carcinoma (SCC). I-BET726 is a novel BRD4 inhibitor. Its potential effect in skin SCC cells was tested in the present study. We show that I-BET726 potently inhibited survival, proliferation, cell cycle progression, and migration in established (A431/SCC-9/SCC-12/SCC-13 lines) and primary human skin SCC cells. I-BET726 induced significant apoptosis activation in skin SCC cells. It was more efficient in inhibiting skin SCC cells than known BRD4 inhibitors (JQ1, CPI203, and AZD5153). I-BET726 not only downregulated BRD4-regulated proteins (c-Myc, Bcl-2, and cyclin D1), but also inhibited sphingosine kinase 1 (SphK1) and Akt signalings in SCC cells. Restoring Akt activation, by a constitutively active S473D mutant Akt1 (“caAkt1”), partially inhibited I-BET726-induced cytotoxicity in A431 cells. In vivo, I-BET726 oral administration potently inhibited A431 xenograft growth in severe combined immunodeficient mice. Downregulation of BRD4-regulated proteins and inhibition of the SphK1-Akt signaling were detected in I-BET726-treated A431 xenograft tumor tissues. Together, I-BET726 inhibits skin SCC cell growth in vitro and in vivo.
Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2
Authors: Peng Yi , Zhao Ji-Ling , Peng Zhi-Yong , Xu Wei-Fang , Yu Guo-Long
Published: May 2020

Mesenchymal stem cell (MSC) therapy is a promising approach against myocardial infarction (MI). Studies have demonstrated that MSCs can communicate with other cells by secreting exosomes. In the present study, we aimed to identify exosomal microRNAs that might contribute to MSC-mediated cardioprotective effects. Primary cardiomyocytes were deprived of oxygen and glucose to mimic MI in vitro. For the animal model of MI, the left anterior descending artery was ligated for 1 h, followed by reperfusion for 12 h. MSC-derived exosomes were used to treat primary cardiomyocytes or mice. Cardioprotection-related microRNAs were determined, followed by target gene identification and functional studies with quantitative PCR, western blotting, MTT assay, flow cytometry assay, chromatin immunoprecipitation and dual-luciferase assay. We found that MSC co-culture reduced OGD-induced cardiomyocyte apoptosis and inflammatory responses. Cardioprotection was also observed upon treatment with MSC-derived exosomes in vitro and in vivo. In line with this, exosome uptake led to a significant increase in miR-25-3p in cardiomyocytes. Depletion of miR-25-3p in MSCs abolished the protective effects of exosomes. Mechanistically, miR-25-3p directly targeted the pro-apoptotic genes FASL and PTEN and reduced their protein levels. Moreover, miR-25-3p decreased the levels of EZH2 and H3K27me3, leading to derepression of the cardioprotective gene eNOS as well as the anti-inflammatory gene SOCS3. Inhibition of EZH2 or overexpression of miR-25-3p in cardiomyocytes was sufficient to confer cardioprotective effects in vitro and in vivo. We concluded that exosomal miR-25-3p from MSCs alleviated MI by targeting pro-apoptotic proteins and EZH2.
Nestin protects podocyte from injury in lupus nephritis by mitophagy and oxidative stress
Authors: Tian Yuexin , Guo Huifang , Miao Xinyan , Xu Jie , Yang Ran , Zhao Lu , Liu Jinxi , Yang Lin , Gao Fan , Zhang Wei , Liu Qingjuan , Sun Shaoguang , Tian Yu , Li Hongbo , Huang Jie , Gu Cunyang , Liu Shuxia , Feng Xiaojuan
Published: May 2020

Podocyte injury is the main cause of proteinuria in lupus nephritis (LN). Nestin, an important cytoskeleton protein, is expressed stably in podocytes and is associated with podocyte injury. However, the role of nestin in the pathogenesis of proteinuria in LN remains unclear. The correlations among nestin, nephrin and proteinuria were analyzed in LN patients and MRL/lpr lupus-prone mice. The expression of nestin in mouse podocyte lines (MPCs) and MRL/lpr mice was knocked down to determine the role of nestin in podocyte injury. Inhibitors and RNAi method were used to explore the role of mitophagy and oxidative stress in nestin protection of podocyte from damage. There was a significantly negative correlation between nestin and proteinuria both in LN patients and MRL/lpr mice, whereas the expression of nephrin was positively correlated with nestin. Knockdown of nestin resulted in not only the decrease of nephrin, p-nephrin (Y1217) and mitophagy-associated proteins in cultured podocytes and the podocytes of MRL/lpr mice, but also mitochondrial dysfunction in podocytes stimulated with LN plasma. The expression and phosphorylation of nephrin was significantly decreased by reducing the level of mitophagy or production of reactive oxygen species (ROS) in cultured podocytes. Our findings suggested that nestin regulated the expression of nephrin through mitophagy and oxidative stress to protect the podocytes from injury in LN.
Economic motivation for raising coastal flood defenses in Europe
Authors: Vousdoukas Michalis I. , Mentaschi Lorenzo , Hinkel Jochen , Ward Philip J. , Mongelli Ignazio , Ciscar Juan-Carlos , Feyen Luc
Published: May 2020

Extreme sea levels (ESLs) in Europe could rise by as much as one metre or more by the end of this century due to climate change. This poses significant challenges to safeguard coastal communities. Here we present a comprehensive analysis of economically efficient protection scenarios along Europe’s coastlines during the present century. We employ a probabilistic framework that integrates dynamic simulations of all ESL components and flood inundation, impact modelling and a cost-benefit analysis of raising dykes. We find that at least 83% of flood damages in Europe could be avoided by elevating dykes in an economically efficient way along 23.7%-32.1% of Europe’s coastline, specifically where high value conurbations exist. The European mean benefit to cost ratio of the investments varies from 8.3 to 14.9 while at country level this ranges between 1.6 and 34.3, with higher efficiencies for a scenario with high-end greenhouse gas emissions and strong socio-economic growth.
Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations
Authors: Navas-Olive Andrea , Valero Manuel , Jurado-Parras Teresa , de Salas-Quiroga Adan , Averkin Robert G. , Gambino Giuditta , Cid Elena , de la Prida Liset M.
Published: May 2020

Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioral sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type-specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase preference of individual CA1 pyramidal cells recorded in mice and rats not engaged in any particular memory task. We applied unbiased and hypothesis-free approaches to identify effects of intrinsic and synaptic factors, as well as cell morphology, in determining phase preference. We found that perisomatic inhibition delivered by complementary populations of basket cells interacts with input pathways to shape phase-locked specificity of deep and superficial pyramidal cells. Somatodendritic integration of fluctuating glutamatergic inputs defined cycle-by-cycle by unsupervised methods demonstrated that firing selection is tuneable across sublayers. Our data identify different mechanisms of phase-locking selectivity that are instrumental for flexible dynamical representations of theta sequences.
A high-resolution description of β1-adrenergic receptor functional dynamics and allosteric coupling from backbone NMR
Authors: Grahl Anne , Abiko Layara Akemi , Isogai Shin , Sharpe Timothy , Grzesiek Stephan
Published: May 2020

Signal transmission and regulation of G-protein-coupled receptors (GPCRs) by extra- and intracellular ligands occurs via modulation of complex conformational equilibria, but their exact kinetic details and underlying atomic mechanisms are unknown. Here we quantified these dynamic equilibria in the β1-adrenergic receptor in its apo form and seven ligand complexes using 1H/15N NMR spectroscopy. We observe three major exchanging conformations: an inactive conformation (Ci), a preactive conformation (Cp) and an active conformation (Ca), which becomes fully populated in a ternary complex with a G protein mimicking nanobody. The Ci ↔ Cp exchange occurs on the microsecond scale, the Cp ↔ Ca exchange is slower than ~5 ms and only occurs in the presence of two highly conserved tyrosines (Y5.58, Y7.53), which stabilize the active conformation of TM6. The Cp→Ca chemical shift changes indicate a pivoting motion of the entire TM6 that couples the effector site to the orthosteric ligand pocket.
Segregation of an MSH1 RNAi transgene produces heritable non-genetic memory in association with methylome reprogramming
Authors: Yang Xiaodong , Sanchez Robersy , Kundariya Hardik , Maher Tom , Dopp Isaac , Schwegel Rosemary , Virdi Kamaldeep , Axtell Michael J. , Mackenzie Sally A.
Published: May 2020

MSH1 is a plant-specific protein. RNAi suppression of MSH1 results in phenotype variability for developmental and stress response pathways. Segregation of the RNAi transgene produces non-genetic msh1 ‘memory’ with multi-generational inheritance. First-generation memory versus non-memory comparison, and six-generation inheritance studies, identifies gene-associated, heritable methylation repatterning. Genome-wide methylome analysis integrated with RNAseq and network-based enrichment studies identifies altered circadian clock networks, and phytohormone and stress response pathways that intersect with circadian control. A total of 373 differentially methylated loci comprising these networks are sufficient to discriminate memory from nonmemory full sibs. Methylation inhibitor 5-azacytidine diminishes the differences between memory and wild type for growth, gene expression and methylation patterning. The msh1 reprogramming is dependent on functional HISTONE DEACETYLASE 6 and methyltransferase MET1, and transition to memory requires the RNA-directed DNA methylation pathway. This system of phenotypic plasticity may serve as a potent model for defining accelerated plant adaptation during environmental change.
Mutualist and pathogen traits interact to affect plant community structure in a spatially explicit model
Authors: Schroeder John W. , Dobson Andrew , Mangan Scott A. , Petticord Daniel F. , Herre Edward Allen
Published: May 2020

Empirical studies show that plant-soil feedbacks (PSF) can generate negative density dependent (NDD) recruitment capable of maintaining plant community diversity at landscape scales. However, the observation that common plants often exhibit relatively weaker NDD than rare plants at local scales is difficult to reconcile with the maintenance of overall plant diversity. We develop a spatially explicit simulation model that tracks the community dynamics of microbial mutualists, pathogens, and their plant hosts. We find that net PSF effects vary as a function of both host abundance and key microbial traits (e.g., host affinity) in ways that are compatible with both common plants exhibiting relatively weaker local NDD, while promoting overall species diversity. The model generates a series of testable predictions linking key microbial traits and the relative abundance of host species, to the strength and scale of PSF and overall plant community diversity.
Zika virus noncoding RNA suppresses apoptosis and is required for virus transmission by mosquitoes
Authors: Slonchak Andrii , Hugo Leon E. , Freney Morgan E. , Hall-Mendelin Sonja , Amarilla Alberto A. , Torres Francisco J. , Setoh Yin Xiang , Peng Nias Y. G. , Sng Julian D. J. , Hall Roy A. , van den Hurk Andrew F. , Devine Gregor J. , Khromykh Alexander A.
Published: May 2020

Flaviviruses, including Zika virus (ZIKV), utilise host mRNA degradation machinery to produce subgenomic flaviviral RNA (sfRNA). In mammalian hosts, this noncoding RNA facilitates replication and pathogenesis of flaviviruses by inhibiting IFN-signalling, whereas the function of sfRNA in mosquitoes remains largely elusive. Herein, we conduct a series of in vitro and in vivo experiments to define the role of ZIKV sfRNA in infected Aedes aegypti employing viruses deficient in production of sfRNA. We show that sfRNA-deficient viruses have reduced ability to disseminate and reach saliva, thus implicating the role for sfRNA in productive infection and transmission. We also demonstrate that production of sfRNA alters the expression of mosquito genes related to cell death pathways, and prevents apoptosis in mosquito tissues. Inhibition of apoptosis restored replication and transmission of sfRNA-deficient mutants. Hence, we propose anti-apoptotic activity of sfRNA as the mechanism defining its role in ZIKV transmission.
Author Correction: Chiral recognition and enantiomer excess determination based on emission wavelength change of AIEgen rotor
Authors: Hu Ming , Yuan Ying-Xue , Wang Weizhou , Li Dong-Mi , Zhang Hong-Chao , Wu Bai-Xing , Liu Minghua , Zheng Yan-Song
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration
Authors: Kim Yeonjoo , Lee Jiyoung , Seppala Maisa , Cobourne Martyn T. , Kim Soo-Hyun
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Predicting synthesizable multi-functional edge reconstructions in two-dimensional transition metal dichalcogenides
Authors: Hu Guoxiang , Fung Victor , Sang Xiahan , Unocic Raymond R. , Ganesh P.
Published: May 2020

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) have attracted tremendous interest as functional materials due to their exceptionally diverse and tunable properties, especially in their edges. In addition to the conventional armchair and zigzag edges common to hexagonal 2D materials, more complex edge reconstructions can be realized through careful control over the synthesis conditions. However, the whole family of synthesizable, reconstructed edges remains poorly studied. Here, we develop a computational approach integrating ensemble-generation, force-relaxation, and electronic-structure calculations to systematically and efficiently discover additional reconstructed edges and screen their functional properties. Using MoS2 as a model system, we screened hundreds of edge-reconstruction to discover over 160 reconstructed edges to be more stable than the conventional ones. More excitingly, we discovered nine new synthesizable reconstructred edges with record thermodynamic stability, in addition to successfully reproducing three recently synthesized edges. We also find our predicted reconstructed edges to have multi-functional properties—they show near optimal hydrogen evolution activity over the conventional edges, ideal for catalyzing hydrogen-evolution reaction (HER) and also exhibit half-metallicity with a broad variation in magnetic moments, making them uniquely suitable for nanospintronic applications. Our work reveals the existence of a wide family of synthesizable, reconstructed edges in 2D TMDCs and opens a new materials-by-design paradigm of ‘intrinsic’ edge engineering multifunctionality in 2D materials.
Towards clinically actionable digital phenotyping targets in schizophrenia
Authors: Henson Philip , Barnett Ian , Keshavan Matcheri , Torous John
Published: May 2020

Digital phenotyping has potential to quantify the lived experience of mental illness and generate real-time, actionable results related to recovery, such as the case of social rhythms in individuals with bipolar disorder. However, passive data features for social rhythm clinical targets in individuals with schizophrenia have yet to be studied. In this paper, we explore the relationship between active and passive data by focusing on temporal stability and variance at an individual level as well as large-scale associations on a population level to gain clinically actionable information regarding social rhythms. From individual data clustering, we found a 19% cluster overlap between specific active and passive data features for participants with schizophrenia. In the same clinical population, two passive data features in particular associated with social rhythms, “Circadian Routine” and “Weekend Day Routine,” and were negatively associated with symptoms of anxiety, depression, psychosis, and poor sleep (Spearman ρ ranged from −0.23 to −0.30, p < 0.001). Conversely, in healthy controls, more stable social rhythms were positively correlated with symptomatology (Spearman ρ ranged from 0.20 to 0.44, p < 0.05). Our results suggest that digital phenotyping in schizophrenia may offer clinically relevant information for understanding how daily routines affect symptomatology. Specifically, negative correlations between smartphone reported anxiety, depression, psychosis, and poor sleep in individuals with schizophrenia, but not in healthy controls, offer an actionable clinical target and area for further investigation.
Genome sequence analysis of multidrug-resistant Mycobacterium tuberculosis from Malaysia
Authors: Tan Joon Liang , Simbun Alfred , Chan Kok-Gan , Ngeow Yun Fong
Published: May 2020

Mycobacterium tuberculosis (MTB) is commonly used as a model to study pathogenicity and multiple drug resistance in bacteria. These MTB characteristics are highly dependent on the evolution and phylogeography of the bacterium. In this paper, we describe 15 new genomes of multidrug-resistant MTB (MDRTB) from Malaysia. The assessments and annotations on the genome assemblies suggest that strain differences are due to lineages and horizontal gene transfer during the course of evolution. The genomes show mutations listed in current drug resistance databases and global MTB collections. This genome data will augment existing information available for comparative genomic studies to understand MTB drug resistance mechanisms and evolution.
Atypical responses of a large catchment river to the Holocene sea-level highstand: The Murray River, Australia
Authors: Helfensdorfer Anna M. , Power Hannah E. , Hubble Thomas C. T.
Published: May 2020

Three-dimensional numerical modelling of the marine and fluvial dynamics of the lower Murray River demonstrate that the mid-Holocene sea-level highstand generated an extensive central basin environment extending at least 140 kilometres upstream from the river mouth and occupying the entire one to three kilometre width of the Murray Gorge. This unusually extensive, extremely low-gradient backwater environment generated by the two metre sea-level highstand captured most, if not all, of the fine-grained sediment discharged from the 1.06 million square kilometre Murray-Darling catchment. This material was sequestered within a >60 kilometre long, >10 metre thick valley-wide deposit of finely laminated mud. This previously unrecognised sediment trap persisted from 8,518 to 5,067 cal yr BP preventing sediment delivery to the marine environment. Its identification requires that mid-Holocene climate reconstructions for southeastern Australia based on fluctuations in the delivery of fine-grained sediment to the ocean offshore the lower Murray River’s mouth must be re-evaluated.
Computational Assessment of Thermokinetics and Associated Microstructural Evolution in Laser Powder Bed Fusion Manufacturing of Ti6Al4V Alloy
Authors: Pantawane Mangesh V. , Ho Yee-Hsien , Joshi Sameehan S. , Dahotre Narendra B.
Published: May 2020

Although most of the near non-equilibrium microstructures of alloys produced by laser powder bed fusion (LPBF) additive manufacturing (AM) are being reported at a rapid rate, the accountable thermokinetics of the entire process have rarely been studied. In order to exploit the versatility of this AM process for the desired properties of built material, it is crucial to understand the thermokinetics associated with the process. In light of this, a three-dimensional thermokinetic model based on the finite element method was developed to correlate with the microstructure evolved in additively manufactured Ti6Al4V alloy. The computational model yielded the thermal patterns experienced at given location while building a single layer through multiple laser scans and a whole part through multiple layers above it. X-ray analysis of the resultant microstructure confirmed the presence of acicular martensitic (α′) phase of (002) texture within the build-plane. Computationally predicted magnitude of the thermal gradients within the additively manufactured Ti6Al4V alloy in different directions (X, Y, and Z) facilitated the understanding about the evolution of grain morphology and orientation of acicular martensite in prior β grains. The scanning electron microscopy observations of the alloy revealed the distinct morphology of phase precipitated within the martensitic phase, whose existence was, in turn, understood through predicted thermal history.
Genomic differentiation and intercontinental population structure of mosquito vectors Culex pipiens pipiens and Culex pipiens molestus
Authors: Yurchenko Andrey A. , Masri Reem A. , Khrabrova Natalia V. , Sibataev Anuarbek K. , Fritz Megan L. , Sharakhova Maria V.
Published: May 2020

Understanding the population structure and mechanisms of taxa diversification is important for organisms responsible for the transmission of human diseases. Two vectors of West Nile virus,Culex pipiens pipiensandCx. p. molestus, exhibit epidemiologically important behavioral and physiological differences, but the whole-genome divergence between them was unexplored. The goal of this study is to better understand the level of genomic differentiation and population structures ofCx. p. pipiensandCx. p. molestusfrom different continents. We sequenced and compared the whole genomes of 40 individual mosquitoes from two locations in Eurasia and two in North America. Principal Component, ADMIXTURE, and neighbor joining analyses of the nuclear genomes identified two major intercontinental, monophyletic clusters ofCx. p. pipiensandCx. p. molestus. The level of genomic differentiation between the subspecies was uniform along chromosomes. The ADMIXTURE analysis determined signatures of admixture inCx. p. pipenspopulations but not inCx. p. molestuspopulations. Comparison of mitochondrial genomes among the specimens showed a paraphyletic origin of the major haplogroups between the subspecies but a monophyletic structure between the continents. Thus, our study identified thatCx. p. molestusandCx. p. pipiensrepresent different evolutionary units with monophyletic origin that have undergone incipient ecological speciation.
Using aircraft location data to estimate current economic activity
Authors: Miller Sam , Moat Helen Susannah , Preis Tobias
Published: May 2020

Aviation is a key sector of the economy, contributing at least 3% to gross domestic product (GDP) in the UK and the US. Currently, airline performance statistics are published with a three month delay. However, aircraft now broadcast their location in real-time using the Automated Dependent Surveillance Broadcast system (ADS-B). In this paper, we analyse a global dataset of flights since July 2016. We first show that it is possible to accurately estimate airline flight volumes using ADS-B data, which is available immediately. Next, we demonstrate that real-time knowledge of flight volumes can be a leading indicator for aviation’s direct contribution to GDP in both the UK and the US. Using ADS-B data could therefore help move us towards real-time estimates of GDP, which would equip policymakers with the information to respond to shocks more quickly.
Toward neuroprosthetic real-time communication from in silico to biological neuronal network via patterned optogenetic stimulation
Authors: Mosbacher Yossi , Khoyratee Farad , Goldin Miri , Kanner Sivan , Malakai Yenehaetra , Silva Moises , Grassia Filippo , Simon Yoav Ben , Cortes Jesus , Barzilai Ari , Levi Timothée , Bonifazi Paolo
Published: May 2020

Restoration of the communication between brain circuitry is a crucial step in the recovery of brain damage induced by traumatic injuries or neurological insults. In this work we present a study of real-time unidirectional communication between a spiking neuronal network (SNN) implemented on digital platform and an in-vitro biological neuronal network (BNN), generating similar spontaneous patterns of activity both spatial and temporal. The communication between the networks was established using patterned optogenetic stimulation via a modified digital light projector (DLP) receiving real-time input dictated by the spiking neurons’ state. Each stimulation consisted of a binary image composed of 8 × 8 squares, representing the state of 64 excitatory neurons. The spontaneous and evoked activity of the biological neuronal network was recorded using a multi-electrode array in conjunction with calcium imaging. The image was projected in a sub-portion of the cultured network covered by a subset of the all electrodes. The unidirectional information transmission (SNN to BNN) is estimated using the similarity matrix of the input stimuli and output firing. Information transmission was studied in relation to the distribution of stimulus frequency and stimulus intensity, both regulated by the spontaneous dynamics of the SNN, and to the entrainment of the biological networks. We demonstrate that high information transfer from SNN to BNN is possible and identify a set of conditions under which such transfer can occur, namely when the spiking network synchronizations drive the biological synchronizations (entrainment) and in a linear regime response to the stimuli. This research provides further evidence of possible application of miniaturized SNN in future neuro-prosthetic devices for local replacement of injured micro-circuitries capable to communicate within larger brain networks.
Transcriptome profiling reveals insertional mutagenesis suppressed the expression of candidate pathogenicity genes in honeybee fungal pathogen, Ascosphaera apis
Authors: Getachew Awraris , Abejew Tessema Aynalem , Wu Jiangli , Xu Jin , Yu Huimin , Tan Jing , Wu Pengjie , Tu Yangyang , Kang Weipeng , Wang Zheng , Xu Shufa
Published: May 2020

Chalkbrood disease is caused by Ascosphaera apis which severely affects honeybee brood. Spore inoculation experiments shown pathogenicity varies among different strains and mutants, however, the molecular mechanism of pathogenicity is unclear. We sequenced, assembled and annotated the transcriptomes of wild type (SPE1) and three mutants (SPE2, SPE3 and SPE4) with reduced pathogenicity that were constructed in our previous study. Illumina sequencing generated a total of 394,910,604 clean reads and de novo Trinity-based assembled into 12,989 unigenes, among these, 9,598 genes were successfully annotated to known proteins in UniProt database. A total of 172, 3,996, and 650 genes were up-regulated and 4,403, 2,845, and 3,016 genes were down-regulated between SPE2-SPE1, SPE3-SPE1, and SPE4-SPE1, respectively. Overall, several genes with a potential role in fungal pathogenicity were detected down-regulated in mutants including 100 hydrolytic enzymes, 117 transcriptional factors, and 47 cell wall related genes. KEGG pathway enrichment analysis reveals 216 genes involved in nine pathways were down-regulated in mutants compared to wild type. The down-regulation of more pathways involved in pathogenicity in SPE2 and SPE4 than SPE3 supports their lower pathogenicity during in-vitro bioassay experiment. Expression of 12 down-regulated genes in mutants was validated by quantitative real time PCR. This study provides valuable information on transcriptome variation caused by mutation for further functional validation of candidate pathogenicity genes in A. apis.
Models suggest pathogen risks to wild fish can be mitigated by acquired immunity in freshwater aquaculture systems
Authors: Teixeira Alves Mickael , Taylor Nick G. H.
Published: May 2020

The interaction of pathogens between wild and farmed aquatic animal populations is a concern that remains unclear and controversial.Ichthyophthirius multifiliis, a ciliated protozoan parasite, is a pathogen of freshwater finfish species with geographic and host range that causes significant economic losses in aquaculture. Flow-through farming systems may facilitate the transfer of such a parasite with free-living stages between farmed and wild stocks. Here, experimental and field study infection data are used to describe the infection dynamics ofIchthyophthirius multifiliisin rainbow trout using a simple macroparasite model by including host resistance. The study considered flow-through farming systems with a single or two age-class compartments and simulated the transfer of the parasite between farmed and wild fish populations. Results suggest that aquaculture can promote the prevalence of the resistance in wild stocks by increasing the parasite population in the wild environment. At the same time, acquired resistance in the farmed fish population may protect the wild fish population from lethal effects of the parasite by reducing the total parasite population. This study offers a promising mathematical basis for understanding the effects of freshwater aquaculture in disease spread in wildlife, developing risk assessment modeling, and exploring new ways of aquaculture management.
The calcitonin-like system is an ancient regulatory system of biomineralization
Authors: Cardoso João C. R. , Félix Rute C. , Ferreira Vinícius , Peng MaoXiao , Zhang Xushuai , Power Deborah M.
Published: May 2020

Biomineralization is the process by which living organisms acquired the capacity to accumulate minerals in tissues. Shells are the biomineralized exoskeleton of marine molluscs produced by the mantle but factors that regulate mantle shell building are still enigmatic. This study sought to identify candidate regulatory factors of molluscan shell mineralization and targeted family B G-protein coupled receptors (GPCRs) and ligands that include calcium regulatory factors in vertebrates, such as calcitonin (CALC). In molluscs, CALC receptor (CALCR) number was variable and arose through lineage and species-specific duplications. The Mediterranean mussel (Mytilus galloprovincialis) mantle transcriptome expresses six CALCR-like and two CALC-precursors encoding four putative mature peptides. Mussel CALCR-like are activated in vitro by vertebrate CALC but only receptor CALCRIIc is activated by the mussel CALCIIa peptide (EC50 = 2.6 ×10−5 M). Ex-vivo incubations of mantle edge tissue and mantle cells with CALCIIa revealed they accumulated significantly more calcium than untreated tissue and cells. Mussel CALCIIa also significantly decreased mantle acid phosphatase activity, which is associated with shell remodelling. Our data indicate the CALC-like system as candidate regulatory factors of shell mineralization. The identification of the CALC system from molluscs to vertebrates suggests it is an ancient and conserved calcium regulatory system of mineralization.
Predictive engines based on pharmacokinetics modelling for tacrolimus personalized dosage in paediatric renal transplant patients
Authors: Prado-Velasco Manuel , Borobia Alberto , Carcas-Sansuan Antonio
Published: May 2020

The development of predictive engines based on pharmacokinetic-physiological mathematical models for personalised dosage recommendations is an immature field. Nevertheless, these models are extensively applied during the design of new drugs. This study presents new advances in this subject, through a stable population of patients who underwent kidney transplantation and were prescribed tacrolimus. We developed 2 new population pharmacokinetic models based on a compartmental approach, with one following the physiologically based pharmacokinetic approach and both including circadian modulation of absorption and clearance variables. One of the major findings was an improved predictive capability for both models thanks to the consideration of circadian rhythms, both in estimating the population and in Bayesian individual customisation. This outcome confirms a plausible mechanism suggested by other authors to explain circadian patterns of tacrolimus concentrations. We also discovered significant intrapatient variability in tacrolimus levels a week after the conversion from a fast-release (Prograf) to a sustained-release formulation (Advagraf) using adaptive optimisation techniques, despite high adherence and controlled conditions. We calculated the intrapatient variability through parametric intrapatient variations, which provides a method for quantifying the mechanisms involved. We present a first application for the analysis of bioavailability changes in formulation conversion. The 2 pharmacokinetic models have demonstrated their capability as predictive engines for personalised dosage recommendations, although the physiologically based pharmacokinetic model showed better predictive behaviour.