bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression Signature and Molecular Mechanism of Redox Homeostasis in Colorectal Cancer
Authors: Piran Mehran , Darayee Maryam , Piran Mehrdad , Sepahi Neda , Rahimi Amir
Published: January 2020

Cellular redox homeostasis is the important tool for normal cell function and survival. Oxidants, reductants and antioxidants are the players to maintain cellular homeostasis balance. However, in some conditions like cancer, the concentration and activation of these players are disturbed. This study walks you through the molecular mechanism of redox homeostasis to describe how expression level of these players would help colorectal cancer (CRC) cells continue proliferation and survive in the hypoxic environment of tumor. We proposed that O2-concentration is not detrimentally high in CRC cells since expression level of MnSOD didn’t change noticeably. We also suggested that High proliferative CRC cells obtain their energy by oxidation of H2S in or Electron transport chain (ETC) and keep the adequate concentration of H2S by diminishing the expression level of enzymes involved in sulfide oxidation pathway. Reduction in hydrogen sulfide oxidation results in a decrease in the level of GSH. Glutathione peroxidase enzyme requires GSH to convert H2O2into oxygen and water. Therefore, Level of hydrogen peroxide stays high which leads to an increase in cell proliferation. Furthermore, we analyzed the expression level of transcription factors sensitive to redox messengers.
Decoding the contents of consciousness from prefrontal ensembles
Authors: Kapoor Vishal , Dwarakanath Abhilash , Safavi Shervin , Werner Joachim , Besserve Michel , Panagiotaropoulos Theofanis I. , Logothetis Nikos K.
Published: January 2020

Multiple theories attribute to the primate prefrontal cortex a critical role in conscious perception. However, opposing views caution that prefrontal activity could reflect other cognitive variables during paradigms investigating consciousness, such as decision-making, monitoring and motor reports. To resolve this ongoing debate, we recorded from prefrontal ensembles of macaque monkeys during a no-report paradigm of binocular rivalry that instigates internally driven transitions in conscious perception. We could decode the contents of consciousness from prefrontal ensemble activity during binocular rivalry with an accuracy similar to when these stimuli were presented without competition. Oculomotor signals, used to infer conscious content, were not the only source of these representations since visual input could be significantly decoded when eye movements were suppressed. Our results suggest that the collective dynamics of prefrontal cortex populations reflect internally generated changes in the content of consciousness during multistable perception.

One sentence summary

Neural correlates of conscious perception can be detected and perceptual contents can be reliably decoded from the spiking activity of prefrontal populations.
SynGAP splice isoforms differentially regulate synaptic plasticity and dendritic development
Authors: Araki Yoichi , Hong Ingie , Gamache Timothy R. , Ju Shaowen , Collado-Torres Leonardo , Shin Joo Heon , Huganir Richard L.
Published: January 2020

SynGAP is a synaptic Ras GTPase-activating protein (GAP) with four C-terminal splice variants: α1, α2, β, and γ. Although recent studies have implicatedSYNGAP1haploinsufficiency in ID/ASD pathogenesis, the degree to which each SynGAP isoform contributes to disease pathogenesis remains elusive. Here we demonstrate that individual SynGAP isoforms exhibit unique spatiotemporal expression and have distinct roles in neuronal and synaptic development. The SynGAP-α1 isoform, which undergoes robust liquid-liquid phase-separation with PSD-95 and is highly-enriched in synapses, is expressed late in development and disperses from synaptic spines in response to LTP-inducing synaptic activity to allow for AMPA receptor insertion and spine enlargement. In contrast, the SynGAP-β isoform, which undergoes less liquid-liquid phase-separation with PSD95 and is less synaptically targeted, is expressed early in development and promotes dendritic arborization. Interestingly, a SynGAP-α1 mutation that disrupts phase separation and synaptic targeting abolishes its function in plasticity and instead drives dendritic arbor development like the β isoform. These results demonstrate that distinct phase separation and synaptic targeting properties of SynGAP isoforms determine their function.

Highlights

SynGAP-α1, α2, β, γ isoforms have distinct spatiotemporal expression and function in the brain.

SynGAP-α1 is required for plasticity, while β is required for dendritic development.

Liquid-liquid phase separation of SynGAP-α1 is required for its role in plasticity.

SynGAP isoforms may differentially contribute to SYNGAP1 related human NDDs.
Integrated Analysis of Methylome and Transcriptome Following Developmental Atrazine Exposure in Zebrafish Reveals Aberrant Gene-Specific Methylation of Neuroendocrine and Reproductive Pathways
Authors: Bryan Chris , Lin Li , Xie Junkai , Ahkin Chin Tai Janiel , Horzmann Katharine A. , Wettschurack Kyle , Zhang Min , Freeman Jennifer , Yuan Chongli
Published: January 2020

Atrazine (ATZ) is one of the most commonly used herbicides in the United States. Previous studies have hypothesized the role of ATZ as an endocrine disruptor (EDC), and developmental exposure to ATZ has been shown to lead to behavioral and morphological alterations. Specific epigenetic mechanisms responsible for these alterations, however, are yet to be elucidated. In this study, we exposed zebrafish embryos to 0.3, 3, and 30 ppb (µg/L) of ATZ for 72 hours post fertilization. We performed whole-genome bisulfite sequencing (WGBS) to assess the effects of developmental ATZ exposure on DNA methylation in female fish brains. The number of differentially methylated genes (DMG) increase with increasing dose of treatments. DMGs are enriched in neurological pathways with extensive methylation changes consistently observed in neuroendocrine and reproductive pathways. To assess the effects of DNA methylation on gene expression, we integrated our data with transcriptomic data. Four genes, namely CHD9, FRAS1, PID1, and PCLO, were differentially expressed and methylated in each dose. Overall, this study identifies specific genes and pathways with aberrant methylation and expression following ATZ exposure as targets to elucidate the molecular mechanisms of ATZ toxicity and presents ATZ-induced site-specific DNA methylation as a potential mechanism driving aberrant gene expression.
Epithelial morphogenesis in the perinatal mouse uterus
Authors: Vue Zer , Behringer Richard R.
Published: January 2020

Background

The uterus is the location where multiple events occur that are required for the start of new life in mammals. The adult uterus contains endometrial or uterine glands that are essential for female fertility. In the mouse, uterine glands are located in the lateral and anti-mesometrial regions of the uterine horn. Previous 3D-imaging of the adult uterus, its glands, and implanting embryos has been performed by multiple groups, using fluorescent microscopy. Adenogenesis, the formation of uterine glands, initiates after birth. Recently, we created a 3D-staging system of mouse uterine gland development at postnatal time points, using light sheet fluorescent microscopy. Here, using a similar approach, we examine the morphological changes in the epithelium of the perinatal mouse uterus.

Results

The uterine epithelium exhibits mesometrial-antimesometrial (dorsoventral) patterning as early as three days after birth (P3), marked by the presence of the mesometrially-positioned developing uterine rail. Uterine gland buds are present beginning at P4. Novel morphological epithelial structures, including a ventral ridge and uterine segments were identified.

Conclusions

The perinatal mouse uterine luminal epithelium develops mesometrial-antimesometrial (dorsal-ventral) morphologies at 3-4 days post-partum. Between 5-6 days post-partum uterine epithelial folds form, defining alternating left-right segments.

Bullet points

Morphological patterning events in the perinatal uterine epithelium are not well described.

Light sheet microscopy was used to generate volumetric reconstructions of the perinatal mouse uterine epithelium.

At postnatal day 3 (P3), the uterine epithelium shows the first signs of dorsoventral pattern, with the presence of the forming mesometrially-positioned uterine rail.

The first morphological indication of uterine adenogenesis begins at P4.

Novel morphological structures were identified from volumetric reconstructions, including the presence of a ventral ridge (another sign of dorsoventral pattern) and uterine segmentation.
The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription
Authors: Castañeda Angelica F. , Didychuk Allison L. , Louder Robert K. , McCollum Chloe O. , Davis Zoe H. , Nogales Eva , Glaunsinger Britt A.
Published: January 2020

β- and γ-herpesviruses include the oncogenic human viruses Kaposi’s sarcoma-associated virus (KSHV) and Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV), which is a significant cause of congenital disease. Near the end of their replication cycle, these viruses transcribe their late genes in a manner distinct from host transcription. Late gene transcription requires six virally-encoded proteins, one of which is a functional mimic of host TATA-box-binding protein (TBP) that is also involved in recruitment of RNA polymerase II (Pol II) via unknown mechanisms. Here, we applied biochemical protein interaction studies together with electron microscopy-based imaging of a reconstituted human preinitiation complex to define the mechanism underlying Pol II recruitment. These data revealed that the herpesviral TBP, encoded by ORF24 in KSHV, makes a direct protein-protein contact with the C-terminal domain of host RNA polymerase II (Pol II), which is a unique feature that functionally distinguishes viral from cellular TBP. The interaction is mediated by the N-terminal domain (NTD) of ORF24 through a conserved motif that is shared in its β- and γ-herpesvirus homologs. Thus, these herpesviruses employ an unprecedented strategy in eukaryotic transcription, wherein promoter recognition and polymerase recruitment are facilitated by a single transcriptional activator with functionally distinct domains.

SIGNIFICANCE STATEMENT

The β- and γ-herpesviruses mediate their late gene transcription through a set of viral transcriptional activators (vTAs). One of these vTAs, ORF24 in Kaposi’s sarcoma-associated herpesvirus (KSHV), is a mimic of host TATA-box-binding protein (TBP). We demonstrate that the N-terminal domain of ORF24 and its homologs from other β- and γ-herpesviruses directly bind the unstructured C-terminal domain (CTD) of RNA Pol II. This functionally distinguishes the viral TBP mimic from cellular TBP, which does not bind Pol II. Thus, herpesviruses encode a transcription factor that has the dual ability to directly interact with promoter DNA and the polymerase, a property which is unique in eukaryotic transcription and is conceptually akin to prokaryotic transcription factors.
Litterbox - A gnotobiotic zeolite-clay system to investigate Arabidopsis-microbe interactions
Authors: Miebach Moritz , Schlechter Rudolf , Clemens John , Jameson Paula E. , Remus-Emsermann Mitja N.P.
Published: January 2020

Plants are colonised by millions of microorganisms representing thousands of species with varying effects on plant growth and health. The microbial communities found on plants are compositionally consistent and their overall positive effect on the plant is well known. However, the effects of individual microbiota members on plant hosts andvice versa, as well as the underlying mechanisms remain largely unknown. Here, we describe ‘Litterbox’, a highly controlled system to investigate plant-microbe interactions. Plants were grown gnotobiotically on zeolite-clay, an excellent soil replacement that retains enough moisture to avoid subsequent watering. Plants grown on zeolite phenotypically resemble plants grown under environmental conditions. Further, bacterial densities on leaves in the Litterbox system resembled those in temperate environments. A PDMS sheet was used to cover the zeolite, thereby significantly lowering the bacterial load in the zeolite and rhizosphere. This reduced the likelihood of potential systemic responses in leaves induced by microbial rhizosphere colonisation. We present results of example experiments studying the transcriptional responses of leaves to defined microbiota members and the spatial distribution of bacteria on leaves. We anticipate that this versatile and affordable plant growth system will promote microbiota research and help in elucidating plant-microbe interactions and their underlying mechanisms.
Genetic diversity and evolution of Hantaan virus in China and its neighbors
Authors: Li Naizhe , Li Aqian , Liu Yang , Wu Wei , Li Chuan , Yu Dongyang , Zhu Yu , Li Jiandong , Li Dexin , Wang Shiwen , Liang Mifang
Published: January 2020

Backgroud

Hantaan virus(HTNV), as one of the pathogenic hantaviruses of HFRS, has raised serious concerns in Eurasia. China and its neighbors, especially Russia and South Korea, are seriously suffered HTNV infections. Recent studies reported genetic diversity and phylogenetic features of HTNV in different parts of China, but the analyses from the holistic perspective are rare.

Methodology and Principal Findings

To better understand HTNV genetic diversity and dynamics, we analyzed all available complete sequences derived from the S and M segments with bio-informatic tools. Our study revealed 11 phylogroups and sequences showed obvious geographic clustering. We found 42 significant amino acid variants sites and 18 of them located in immune epitopes. Nine recombination events and seven reassortment isolates were deteced in our study. Sequences from Guizhou were highly genetic divergent, characterized by the emergence of multiple lineages, recombination and reassortment events. We found that HTNV probably emerged in Zhejiang about 1,000 years ago and the population size expanded from 1980s to 1990s. Bayesian stochastic search variable selection analysis revealed that Heilongjiang, Shaanxi and Guizhou played important roles in HTNV evolution and migration.

Conclusions/Significance

These findings reveal the original and evolution features of HTNV which might assist in understanding Hantavirus epidemics and would be useful for disease prevention and control.

Author summary

Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS) are endemic zoonotic infectious diseases caused by hantaviruses that belong to the Family Bunyaviridae. Hantaviruses have gained worldwide attention as etiological agents of emerging zoonotic diseases, with fatality rates ranging from <10% up to 60%. However, our knowledge about the emergence and evolution of HTNV is limited. To get more information about HTNV genetic diversity and phylogenetic features in holistic perspective, we investigated the genetic diversity and spatial distribution of HTNV using all available whole genomic sequences of S and M segments. We also gain insights into the genetic diversity and spatial-temporal dynamics of HTNV. These data can augment traditional approach to infectious disease surveillance and control.
Localization of neutral evolution: selection for mutational robustness and the maximal entropy random walk
Authors: Smerlak Matteo
Published: January 2020

If many mutations confer no immediate selective advantage, they can pave the way for the discovery of fitter phenotypes and their subsequent positive selection. Understanding the reach of neutral evolution is therefore a key problem linking diversity, robustness and evolvability at the molecular scale. While this process is usually described as a random walk in sequence space with clock-like regularity, new effects can arise in large microbial or viral populations where new mutants arise before old ones can fix. Here I show that the clonal interference of neutral variants shuts off the access to neutral ridges and thus induces localization within the robust cores of neutral networks. As a result, larger populations can be less effective at exploring sequence space than smaller ones—a counterintuitive limitation to evolvability which invalidates analogies between evolution and percolation. I illustrate these effects by revisiting Maynard Smith’s word-game model of protein evolution. Interestingly, the phenomenon of neutral interference connects evolutionary dynamics to a Markov process known in network science as the maximal-entropy random walk; its special properties imply that, when many neutral variants interfere in a population, evolution chooses mutational paths—not individual mutations—uniformly at random.
Oct4 regulates embryonic pluripotency via metabolic mechanisms and Stat3 signalling
Authors: Stirparo Giuliano Giuseppe , Kurowski Agata , Strawbridge Stanley Eugene , Stuart Hannah , Boroviak Thorsten Edwin , Yanagida Ayaka , Nichols Jennifer
Published: January 2020

OCT4 is a fundamental component of the molecular circuitry governing pluripotencyin vivoandin vitro. To determine how OCT4 protects the pluripotent lineage from differentiation into trophoblast, we used single cell transcriptomics and quantitative immunofluorescence on blastocysts and established differentially expressed genes and pathways between control and OCT4 null cells. Activation of most pluripotency-associated transcription factors in the early mouse inner cell mass appears independent of OCT4, whereas JAK/STAT signalling requires OCT4, via activation of IL6ST. Single cell deconvolution, diffusion component and trajectory inference dissected the process of differentiation of OCT4 null cells by activating specific gene-network and transcription factors. Downregulation of glycolytic and oxidative metabolism was observed. CHIPseq analysis suggests OCT4 directly targets rate-limiting glycolytic enzymes. Concomitant with significant disruption of the STAT3 pathway, oxidative respiration is significantly diminished in OCT4 null cells. Upregulation of the lysosomal pathway detected in OCT4 null embryos is likely attributable to aberrant metabolism.

Highlights and novelty

Major pluripotency-associated transcription factors are activated in OCT4-deficient early mouse ICM cells, coincident with ectopic expression of trophectoderm markers

JAK/STAT signalling is defective in OCT4 null embryos

OCT4 promotes expression of KATS enzymes by means of glycolytic production of Acetyl CoA to secure chromatin accessibility for acquisition of epiblast identity

OCT4 regulates the metabolic and biophysical processes required for establishment of embryonic pluripotency
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
Authors: Tian Xiaolong , Li Cheng , Huang Ailing , Xia Shuai , Lu Sicong , Shi Zhengli , Lu Lu , Jiang Shibo , Yang Zhenlin , Wu Yanling , Ying Tianlei
Published: January 2020

The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 800 laboratory-confirmed human infections, including 25 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS-CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. Therefore, CR3022 has the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g., m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, indicating that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.
Foveal pRF properties in the visual cortex depend on the extent of stimulated visual field
Authors: Prabhakaran Gokulraj , Carvalho Joana , Invernizzi Azzurra , Kanowski Martin , Renken Remco J. , Cornelissen Frans W. , Hoffmann Michael B.
Published: January 2020

Previous studies demonstrated that alterations in functional MRI derived receptive field (pRF) properties in cortical projection zones of retinal lesions can erroneously be mistaken for cortical large-scale reorganization in response to visual system pathologies. We tested, whether such confounds are also evident in the normal cortical projection zone of the fovea for simulated peripheral visual field defects. We applied fMRI-based visual field mapping of the central visual field at 3 Tesla in eight controls to compare the pRF properties of the central visual field of a reference condition (stimulus radius: 14°) and two conditions with simulated peripheral visual field defect, i.e., with a peripheral gray mask, stimulating only the central 7° or 4° radius. We quantified, for the cortical representation of the actually stimulated visual field, the changes in the position and size of the pRFs associated with reduced peripheral stimulation using conventional and advanced pRF modeling. We found foveal pRF-positions (≤3°) to be significantly shifted towards the periphery (p<0.05, corrected). These pRF-shifts were largest for the 4° condition [visual area (mean eccentricity shift): V1 (0.9°), V2 (0.9°), V3 (1.0°)], but also evident for the 7° condition [V1 (0.5°), V2 (0.5°), V3 (0.9°)]. Further, an overall enlargement of pRF-sizes was observed. These findings indicate the dependence of foveal pRF parameters on the spatial extent of the stimulated visual field. Consequently, our results imply that, previously reported similar findings in patients with actual peripheral scotomas need to be interpreted with caution and indicate the need for adequate control conditions in investigations of visual cortex reorganization.

Highlights

Foveal pRF properties change in controls with restricted peripheral stimulation

pRFs shift in position and enlarge in size for reduced stimulation extent

Alterations in pRF characteristics in patients should be interpreted with caution

Adequate control conditions needed in investigations of visual cortex plasticity
Creld2 function during unfolded protein response is essential for liver metabolism homeostasis
Authors: Kern Paul , Balzer Nora R. , Bender Franziska , Frolov Alex , Wunderling Klaus , Sowa Jan-Peter , Bonaguro Lorenzo , Ulas Thomas , Thiele Christoph , Schultze Joachim L. , Canbay Ali , Bauer Reinhard , Mass Elvira
Published: January 2020

The unfolded protein response (UPR) is associated with the hepatic metabolic function, yet it is not well understood how endoplasmic reticulum (ER) disturbance might influence metabolic homeostasis. Here, we describe the physiological function of Cysteine-rich with EGF-like domains 2 (Creld2), previously characterized as a downstream target of the ER-stress signal transducer Atf6. To this end we generatedCreld2-deficient mice and induced UPR by injection of tunicamycin. Creld2 augments protein folding and creates an interlink between the UPR axes through its interaction with proteins involved in UPR. Thereby, Creld2 promotes tolerance to ER stress and recovery from acute stress.Creld2-deficiency leads to a dysregulated UPR, and causes the development of hepatic steatosis during ER stress conditions. Moreover, Creld2 enhancement of the UPR assists in the regulation of energy expenditure. Furthermore, we observed a sex dimorphism in humans with fatty liver disease, with only males showing an accumulation of CRELD2 protein in the liver. These results reveal a Creld2 function at the intersection between UPR and metabolic homeostasis and suggest a mechanism in which chronic ER stress underlies fatty liver disease in males.
A mysterious 80 nm amoeba virus with a near-complete “ORFan genome” challenges the classification of DNA viruses
Authors: Boratto Paulo V. M. , Oliveira Graziele P. , Machado Talita B. , Andrade Ana Cláudia S. P. , Baudoin Jean-Pierre , Klose Thomas , Schulz Frederik , Azza Saïd , Decloquement Philippe , Chabrière Eric , Colson Philippe , Levasseur Anthony , La Scola Bernard , Abrahão Jônatas S.
Published: January 2020

Here we report the discovery of Yaravirus, a new lineage of amoebal virus with a puzzling origin and phylogeny. Yaravirus presents 80 nm-sized particles and a 44,924 bp dsDNA genome encoding for 74 predicted proteins. More than 90% (68) of Yaravirus predicted genes have never been described before, representing ORFans. Only six genes had distant homologs in public databases: an exonuclease/recombinase, a packaging-ATPase, a bifunctional DNA primase/polymerase and three hypothetical proteins. Furthermore, we were not able to retrieve viral genomes closely related to Yaravirus in 8,535 publicly available metagenomes spanning diverse habitats around the globe. The Yaravirus genome also contained six types of tRNAs that did not match commonly used codons. Proteomics revealed that Yaravirus particles contain 26 viral proteins, one of which potentially representing a novel capsid protein with no significant homology with NCLDV major capsid proteins but with a predicted double-jelly roll domain. Yaravirus expands our knowledge of the diversity of DNA viruses. The phylogenetic distance between Yaravirus and all other viruses highlights our still preliminary assessment of the genomic diversity of eukaryotic viruses, reinforcing the need for the isolation of new viruses of protists.

Significance statement

Most of the known viruses of amoeba have been seen to share many features that eventually prompted authors to classify them into common evolutionary groups. Here we describe Yaravirus, an entity that could represent either the first isolated virus ofAcanthamoebaspp. out of the group of NCLDVs or, in alternative evolutive scenario, it is a distant and extremely reduced virus of this group. Contrary to what is observed in other isolated viruses of amoeba, Yaravirus is not represented by a large/giant particle and a complex genome, but at the same time carries an important number of previously undescribed genes, including one encoding a novel major capsid protein. Metagenomic approaches also testified for the rarity of Yaravirus in the environment.
Molecular characterization of a novel cytorhabdovirus with a unique genomic organization infecting yerba mate (Ilex paraguariensis) in Argentina
Authors: Bejerman Nicolás , Acevedo Raúl Maximiliano , de Breuil Soledad , Ruiz Oscar A. , Sansberro Pedro , Dietzgen Ralf G. , Nome Claudia , Debat Humberto
Published: January 2020

The genome of a novel rhabdovirus was detected in yerba mate (Ilex paraguariensisSt. Hil.). The newly identified virus, tentatively named yerba mate virus A (YmVA), has a genome of 14,961 nucleotides. Notably, eight open reading frames were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, including two novel accessory genes, in the order 3’-N-P-3-4-M-G-L-8-5’. Sequence identity of the encoded proteins as well as phylogenetic analysis suggest that YmVA is a new member of the genusCytorhabdovirus, familyRhabdoviridae. YmVA unique genomic organization and phylogenetic relationships indicate that this virus likely represents a distinct evolutionary lineage within the cytorhabdoviruses.
Deep neural networks for interpreting RNA-binding protein target preferences
Authors: Ghanbari Mahsa , Ohler Uwe
Published: January 2020

Deep learning has become a powerful paradigm to analyze the binding sites of regulatory factors including RNA-binding proteins (RBPs), owing to its strength to learn complex features from possibly multiple sources of raw data. However, the interpretability of these models, which is crucial to improve our understanding of RBP binding preferences and functions, has not yet been investigated in significant detail. We have designed a multitask and multimodal deep neural network for characterizing in vivo RBP targets. The model incorporates not only the sequence but also the region type of the binding sites as input, which helps the model to boost the prediction performance. To interpret the model, we quantified the contribution of the input features to the predictive score of each RBP. Learning across multiple RBPs at once, we are able to avoid experimental biases and to identify the RNA sequence motifs and transcript context patterns that are the most important for the predictions of each individual RBP. Our findings are consistent with known motifs and binding behaviors and can provide new insights about the regulatory functions of RBPs.
SHARP: hyperfast and accurate processing of single-cell RNA-seq data via ensemble random projection
Authors: Wan Shibiao , Kim Junil , Won Kyoung Jae
Published: January 2020

To process large-scale single-cell RNA-sequencing (scRNA-seq) data effectively without excessive distortion during dimension reduction, we present SHARP, an ensemble random projection-based algorithm that is scalable to clustering 10 million cells. Comprehensive benchmarking tests on 17 public scRNA-seq data sets show that SHARP outperforms existing methods in terms of speed and accuracy. Particularly, for large-size data sets (more than 40,000 cells), SHARP runs faster than other competitors while maintaining high clustering accuracy and robustness. To the best of our knowledge, SHARP is the only R-based tool that is scalable to clustering scRNA-seq data with 10 million cells.
Organ-level protein networks as a reference for the host effects of the microbiome
Authors: Mills Robert H. , Wozniak Jacob M. , Vrbanac Alison , Campeau Anaamika , Chassaing Benoit , Gewirtz Andrew , Knight Rob , Gonzalez David J.
Published: January 2020

Connections between the microbiome and health are rapidly emerging in a wide range of diseases. However, a detailed mechanistic understanding of how different microbial communities are influencing their hosts is often lacking. One method researchers have used to understand these effects are germ-free (GF) mouse models. Differences found within the organ systems of these model organisms may highlight generalizable mechanisms that microbiome dysbioses have throughout the host. Here, we applied multiplexed, quantitative proteomics on the brains, spleens, hearts, small intestines, and colons of conventionally raised and GF mice, identifying associations to colonization state in over 7000 proteins. Highly ranked associations were constructed into protein–protein interaction networks and visualized onto an interactive 3D mouse model for user-guided exploration. These results act as a resource for microbiome researchers hoping to identify host effects of microbiome colonization on a given organ of interest. Our results include validation of previously reported effects in xenobiotic metabolism, the innate immune system, and glutamate-associated proteins while simultaneously providing organism-wide context. We highlight organism-wide differences in mitochondrial proteins including consistent increases in NNT, a mitochondrial protein with essential roles in influencing levels of NADH and NADPH, in all analyzed organs of conventional mice. Our networks also reveal new associations for further exploration, including protease responses in the spleen, high-density lipoproteins in the heart, and glutamatergic signaling in the brain. In total, our study provides a resource for microbiome researchers through detailed tables and visualization of the protein-level effects of microbial colonization on several organ systems.
A lathe system for micrometre-sized cylindrical sample preparation at room and cryogenic temperatures
Authors: Holler Mirko , Ihli Johannes , Tsai Esther H. R. , Nudelman Fabio , Verezhak Mariana , van de Berg Wilma D. J. , Shahmoradian Sarah H.
Published: January 2020

A simple two-spindle based lathe system for the preparation of cylindrical samples intended for X-ray tomography is presented. The setup can operate at room temperature as well as under cryogenic conditions, allowing the preparation of samples down to 20 and 50 µm in diameter, respectively, within minutes. Case studies are presented involving the preparation of a brittle biomineral brachiopod shell and cryogenically fixed soft brain tissue, and their examination by means of ptychographic X-ray computed tomography reveals the preparation method to be mainly free from causing artefacts. Since this lathe system easily yields near-cylindrical samples ideal for tomography, a usage for a wide variety of otherwise challenging specimens is anticipated, in addition to potential use as a time- and cost-saving tool prior to focused ion-beam milling. Fast sample preparation becomes especially important in relation to shorter measurement times expected in next-generation synchrotron sources.
The incommensurately modulated structures of low-temperature labradorite feldspars: a single-crystal X-ray and neutron diffraction study
Authors: Jin Shiyun , Xu Huifang , Wang Xiaoping , Jacobs Ryan , Morgan Dane
Published: January 2020

Labradorite feldspars of the plagioclase solid solution series have been known for their complicated subsolidus phase relations and enigmatic incommensurately modulated structures. Characterized by the irrationally indexede-reflections in the diffraction pattern,e-labradorite shows the largest variation in the incommensurate ordering states among thee-plagioclase structures. The strongly ordered low-temperaturee-labradorite is one of the last missing pieces of thee-plagioclase puzzle. Nine plutonic and metamorphic labradorite feldspar samples from Canada, Ukraine, Minnesota (USA), Tanzania and Greenland with compositions ranging from An52.5to An68were studied with single-crystal X-ray diffraction. Two crystals from Labrador, Canada, and Duluth, MN, USA, with wide enough twin lamellae were analyzed with single-crystal neutron diffraction. The incommensurately modulated structures ofe-plagioclase are refined for the first time with neutron diffraction data, which confirmed that the T—O distance modulation in the low-temperaturee-plagioclase results from the Al–Si ordering in the framework. Detailed configurations of the M site are also observed in the structures refined from neutron diffraction data, which were not possible to see with X-ray diffraction data. The relation between theq-vectors and the mole% An composition is revealed for the entire compositional range ofe-plagioclase, from An25to An75. The previously proposed two-trend relation depending on the cooling rate and phase transition path is confirmed. A new classification ofe-plagioclase (eα,eβandeγ) is proposed based on theq-vector of the structure, which makes it an independent character from the presence/absence of density modulation. New parameters are proposed to quantify the ordering states of these complicated aperiodic structures ofe-plagioclases, such as the difference between 〈T1o—O〉 and 〈T1m—O〉 at phaset= 0.2 or the normalized intensity of the (071\bar 1) reflection.
A new heteroleptic phosphorescent cuprous complex supported by a BINAP ligand: synthesis, structure, luminescence properties and theoretical analyses
Authors: Wang Dan-Dan , Wang Jian-Teng , Song Li , Wang You-Yu , Chai Wen-Xiang
Published: January 2020

Luminescent cuprous complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The heteroleptic cuprous complex solvaterac-(acetonitrile-κN)(3-aminopyridine-κN)[2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl-κ2P,P′]copper(I) hexafluoridophosphate dichloromethane monosolvate, [Cu(C5H6N2)(C2H3N)(C44H32P2)]PF6·CH2Cl2, conventionally abbreviated as [Cu(3-PyNH2)(CH3CN)(BINAP)]PF6·CH2Cl2, (I), where BINAP and 3-PyNH2represent 2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl and 3-aminopyridine, respectively, is described. In this complex solvate, the asymmetric unit consists of a cocrystallized dichloromethane molecule, a hexafluoridophosphate anion and a complete racemic heteroleptic cuprous complex cation in which the cuprous centre, in a tetrahedral CuP2N2coordination, is coordinated by two P atoms from the BINAP ligand, one N atom from the 3-PyNH2ligand and another N atom from a coordinated acetonitrile molecule. The UV–Vis absorption and photoluminescence properties of this heteroleptic cuprous complex have been studied on polycrystalline powder samples, which had been verified by powder X-ray diffraction before recording the spectra. Time-dependent density functional theory (TD-DFT) calculations and a wavefunction analysis reveal that the orange–yellow phosphorescence emission should originate from intra-ligand (BINAP) charge transfer mixed with a little of the metal-to-ligand charge transfer3(IL+ML)CT excited state.
Phase of Pendellösung oscillations in X-ray dynamical diffraction for perfect crystals
Authors: Saka Takashi
Published: January 2020

Formulations are given for the intensities of transmitted and diffracted waves in the Laue case of a perfect crystal. This is applicable irrespective of the magnitudes of both the real and imaginary parts of the Fourier components of the crystal polarizability. The phase shift of the Pendellösung oscillations of the transmitted and diffracted waves is analyzed in detail for a symmetrical Laue case. The phase is determined to shift continuously from out of phase to in phase for absorbing crystals.
Simulation based optimal evacuation plan in vertical ship lift: a case study
Authors: Wang Jian-Ping , Wang Mei-Ru , Zhou Jian-Lan , Zuo Qing-Jun , Shi Xun-Xian
Published: January 2020

Purpose

The purpose of this study is to develop optimal evacuation plan to provide valuable theoretical and practical insight in the fire evacuation work of similar structures, by proposing a systematic simulation-based guided-evacuation agent-based model (GAM) and a three-stage mathematical evacuation model to investigate how to simulate, assess and improve the performance efficiency of the evacuation plan.

Design/methodology/approach

The authors first present the self-evacuation and guided-evacuation models to determine the optimal evacuation plan in ship chamber. Three key performance indicators are put forward to quantitatively assess the evacuation performance within the two fire scenarios. The evacuation model in tower is built to obtain the dividing points of the three different fire evacuation plans.

Findings

The study shows that the optimal evacuation plan determined by the GAM considering social relationships effectively relieves the congestion or collision of evacuees and improves the evacuation uniformity. The optimal evacuation plan not only solves the crush caused by congestion or collision of evacuees but also can greatly shorten the evacuation time for passenger ship fire.

Originality/value

This study establishes the GAM considering the interactive evacuee characteristics and the proportion of evacuees guided by the crew members to make the optimal evacuation plan more time-efficient. The self-evacuation process is simulated to assess the performance of the guided-evacuation strategies, which are used to verify the effectiveness and feasibility of the optimal evacuation plan in this research.
Exploring the missing link between top management team characteristics and megaproject performance
Authors: Yun Le , Wan Jingyuan , Wang Ge , Bai Ju , Zhang Bing
Published: January 2020

Purpose

The purpose of this paper is to analyze the relationship between the demographic characteristics of top management teams (TMTs) (i.e. age, gender, administrative level, senior management experience and educational background) and megaproject performance, with respect to schedule, cost, quality, safety and technological innovation. The results shed new light on the effectiveness of different types of TMT.

Design/methodology/approach

This paper collected secondary and objective data from 208 TMT members in 42 megaprojects and employed hierarchical regression analysis to test the research hypotheses.

Findings

The findings revealed that age has a significant influence on schedule performance; gender has a significant influence on safety performance; senior management experience has a significant influence on cost performance; and educational background has a significant influence on both schedule and technological innovation performance. However, this study did not find evidence of a significant relationship between the administrative level and megaproject performance.

Research limitations/implications

This paper mainly focused on China’s megaprojects, most of which are globally influential (e.g. Hong Kong–Zhuhai–Macao Bridge and Shanghai Expo), however this sampling approach still limits the generalizability of research findings to other contexts.

Originality/value

The results of this paper contribute to a better understanding of how management team capabilities translate into better project achievements. This paper also provides implications on the criteria for selecting top megaproject managers to optimize the composition of the TMT and realize better performance.
Application of stochastic linear programming in managerial accounting
Authors: Wu Di , Choi Yong , Li Ji
Published: January 2020

Purpose

This paper aims to focus on applications of stochastic linear programming (SLP) to managerial accounting issues by providing a theoretical foundation and practical examples. SLP models may have more implications – and broader ones – in industry practice than deterministic linear programming (DLP) models do.

Design/methodology/approach

This paper introduces both DLP and SLP methods. In addition, continuous and discrete SLP models are explained. Applications are demonstrated using practical examples and simulations.

Findings

This research work extends the current knowledge of SLP, especially concerning managerial accounting issues. Through numerical examples, SLP demonstrates its great ability of hedging against all scenarios.

Originality/value

This study serves as an addition to building a cumulative tradition of research on SLP in managerial accounting. Only a few SLP studies in managerial accounting have focused on the development of such an instrument. Thus, the measurement scales in this research can be used as the starting point for further refining the instrument of optimization in managerial accounting.
Variable snap-off study for 3D additive screen printing
Authors: Wang Yacheng , Li Peibo , Liu Yuegang , Sun Yize , Su Liuyuan
Published: January 2020

Purpose

In 3D additive screen printing with constant snap-off, the inhomogeneous screen counterforce will influence the printing force and reduce the printing quality. The purpose of this paper is to study the relationship between scraper position, snap-off and screen counterforce and develop a variable snap-off curve for 3D additive screen printing to improve the printing quality.

Design/methodology/approach

An experiment was carried out; genetic algorithm (GA) optimization theoretical model, backpropagation neural network regression model and least square support vector machine regression model were established to study the relationship between scraper position, snap-off and screen counterforce. The absolute errors of counterforce of three models with the experiment results were less than 1.5 N, which was tolerated and the three models were considered valid. The comparison results showed that GA optimization theoretical model performed best.

Findings

The results suggest that GA optimization theoretical model performed best to represent the relationship, and it was used to develop a variable snap-off curve. With the variable snap-off curve in 3D additive screen printing, the inhomogeneous screen counterforce was weakened and the printing quality was improved.

Originality/value

In printing production, the variable snap-off curve in 3D additive screen printing helps improve the printing quality; this study is of prime importance to the 3D additive screen printing.
Improving expatriate adjustment: a social network perspective
Authors: Pustovit Sasha
Published: January 2020

Purpose

While the value of connections with host-country nationals (HCNs) for expatriate adjustment is well established, there is little guidance regarding which HCNs stand to benefit expatriates most. The purpose of this paper is to utilize a social network perspective to build theory to explain how and why expatriates who are connected to a central HCN are more likely to adjust. This study offers explicit guidance for steps parent country management can take to assist expatriates in the development of valuable connections with HCNs, even while thousands of miles away from the expatriate’s new locale.

Design/methodology/approach

This study takes a social network approach to build theory that will improve understanding of the expatriate experience.

Findings

Because central individuals tend to be embedded in the organization, their embeddedness is likely to spread to expatriates with whom they are in close contact with. Links to central HCNs are posited to contribute to improved work adjustment by enabling expatriates to attain a better understanding of workplace requirements and workplace norms.

Practical implications

Management can take steps to identify central HCNs using social network analysis and introduce expatriates to highly central HCNs to help improve expatriate adjustment.

Originality/value

This study answers explicit calls in the literature for a greater exploration of social interaction of expatriates in understanding the expatriate experience, as well as calls for taking a more active role in the management of informal relationships. This study is the first to discuss implications of the HCN’s network to expatriate outcomes.
Comparative analysis between global sukuk and bond indices: value-at-risk approach
Authors: Bhuiyan Rubaiyat Ahsan , Puspa Maya , Saiti Buerhan , Ghani Gairuzazmi Mat
Published: January 2020

Purpose

Sukuk is an innovative financial instrument with a flexible structure based on Islamic financial contracts, unlike a bond which is based on the structure of a loan imposed with interest. With the notion that sukuk differs considerably from the conventional bonds in terms of risks related to investment, this study aims to examine whether the sukuk market is different from conventional bond markets based on the value-at-risk (VaR) approach.

Design/methodology/approach

The VaR of a portfolio consists of sukuk and bond indices and is undertaken to determine whether there is any reduction in the VaR amount through the inclusion of the sukuk index in the portfolio. The analysis is undertaken based on the developed and emerging market bond and sukuk indices from January 2010 to December 2015.

Findings

This paper examines whether the VaR of sukuk market differs from conventional bond markets by using fundamental techniques. It was observed that the VaR amount of sukuk indices is comparatively much lower than the VaR of bond indices in all the cases. Including the sukuk index with each bond index can reduce the VaR of the portfolio by around 30 to 50 per cent for all the developed and emerging market bond indices.

Research limitations/implications

This research is limited to covering six years of data. Nonetheless, it is able to provide findings which are believed to be useful for the market players.

Practical implications

This study unveils attractive opportunities in terms of diversification benefits of sukuk indices for international fixed-income portfolios.

Originality/value

The VaR method is a useful risk management tool. This study uses this method to emphasise the significant reduction of risks and diversification benefits that sukuk investment could offer by including it in the investment portfolio.