bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated ACE2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication
Authors: Chen Mengfei , Shen Wenjuan , Rowan Nicholas R. , Kulaga Heather , Hillel Alexander , Ramanathan Murugappan , Lane Andrew P.
Published: May 2020

The site of SARS-CoV-2 entry and replication critically impacts strategies for COVID-19 diagnosis, transmission mitigation, and treatment. We determined the cellular location of the SARS-CoV-2 target receptor protein, ACE2, in the human upper airway, finding striking enrichment (200-700 folds) in the olfactory neuroepithelium relative to nasal respiratory or tracheal epithelial cells. This cellular tropism of SARS-CoV-2 may underlie its high transmissibility and association with olfactory dysfunction, while suggesting a viral reservoir potentially amenable to intranasal therapy.
The evolution of skin pigmentation associated variation in West Eurasia
Authors: Ju Dan , Mathieson Iain
Published: May 2020

Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans. It is unclear whether selection has operated on all the genetic variation associated with skin pigmentation as opposed to just a small number of large-effect variants. Here, we address this question using ancient DNA from 1158 individuals from West Eurasia covering a period of 40,000 years combined with genome-wide association summary statistics from the UK Biobank. We find a robust signal of directional selection in ancient West Eurasians on skin pigmentation variants ascertained in the UK Biobank, but find this signal is driven mostly by a limited number of large-effect variants. Consistent with this observation, we find that a polygenic selection test in present-day populations fails to detect selection with the full set of variants; rather, only the top five show strong evidence of selection. Our data allow us to disentangle the effects of admixture and selection. Most notably, a large-effect variant at SLC24A5 was introduced to Europe by migrations of Neolithic farming populations but continued to be under selection post-admixture. This study shows that the response to selection for light skin pigmentation in West Eurasia was driven by a relatively small proportion of the variants that are associated with present-day phenotypic variation.

Significance

Some of the genes responsible for the evolution of light skin pigmentation in Europeans show signals of positive selection in present-day populations. Recently, genome-wide association studies have highlighted the highly polygenic nature of skin pigmentation. It is unclear whether selection has operated on all of these genetic variants or just a subset. By studying variation in over a thousand ancient genomes from West Eurasia covering 40,000 years we are able to study both the aggregate behavior of pigmentation-associated variants and the evolutionary history of individual variants. We find that the evolution of light skin pigmentation in Europeans was driven by frequency changes in a relatively small fraction of the genetic variants that are associated with variation in the trait today.
VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data
Authors: Yasumizu Yoshiaki , Hara Atsushi , Sakaguchi Shimon , Ohkura Naganari
Published: May 2020

The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 763 viruses including herpesviruses, retroviruses, and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host gene expression profile of the cell. This bioinformatics method would be instrumental in addressing the possible effects of covertly infecting viruses on certain diseases and developing new treatments to target such viruses.

Availability and implementation

VIRTUS is implemented using Common Workflow Language and Docker under a CC-NC license. VIRTUS is freely available athttps://github.com/yyoshiaki/VIRTUS.

Supplementary information

Supplementary data are available at Bioinformatics online.
SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins
Authors: Chen Fan , Keleş Sündüz
Published: May 2020

Advances in high-throughput profiling of RNA binding proteins (RBPs) have resulted in CLIP-seq datasets coupled with transcriptome profiling by RNA-seq. However, analysis methods that integrate both types of data are lacking. We describe SURF, Statistical Utility for RBP Functions, for integrative analysis of large collections of CLIP-seq and RNA-seq data. We demonstrate SURF’s ability to accurately detect differential alternative transcriptional regulation events and associate them to local protein-RNA interactions. We apply SURF to ENCODE RBP compendium and carry out downstream analysis with additional reference datasets. The results of this application are browsable athttp://www.statlab.wisc.edu/shiny/surf/.
Genetic redundancy in iron and manganese transport in the metabolically versatile bacteriumRhodopseudomonas palustrisTIE-1
Authors: Singh Rajesh , Ranaivoarisoa Tahina Onina , Gupta Dinesh , Bai Wei , Bose Arpita
Published: May 2020

The purple non-sulfur bacteriumRhodopseudomonas palustrisTIE-1 can produce useful biochemicals such as bioplastics and biobutanol. Production of such biochemicals requires intracellular electron availability, which is governed by the availability and the transport of essential metals such as iron (Fe). Because of the distinct chemical properties of ferrous [Fe(II)] and ferric iron [Fe(III)], different transport systems are required for their transport and storage in bacteria. Although Fe(III) transport systems are well characterized, we know much less about Fe(II) transport systems except for the FeoAB system. Iron transporters can also import manganese (Mn). Here, we study Fe and Mn transport by five putative Fe transporters in TIE-1 under metal-replete, -deplete, oxic and anoxic conditions. We observe that by overexpressingfeoAB, efeU, andnramp1AB, the intracellular concentration of Fe and Mn can be enhanced in TIE-1, under oxic and anoxic conditions, respectively. The deletion of a single gene/operon does not attenuate Fe or Mn uptake in TIE-1 regardless of the growth conditions used. This indicates that genetically dissimilar yet functionally redundant Fe transporters in TIE-1 can complement each other. Relative gene expression analysis shows thatfeoABandefeUare expressed during Fe and Mn depletion under both oxic and anoxic conditions. The promoters of these transporter genes contain a combination of Fur and Fnr boxes suggesting that their expression is regulated by both Fe and oxygen availability. The findings from this study will help us modulate intracellular Fe and Mn concentration, ultimately improving TIE-1’s ability to produce desirable biomolecules.

IMPORTANCE

Rhodopseudomonas palustrisTIE-1 is a metabolically versatile bacterium that can use various electron donors including Fe(II) and poised electrodes for photoautotrophic growth. TIE-1 can produce useful biomolecules such as biofuels and bioplastics during various growth conditions. Production of such reduced biomolecules is controlled by intracellular electron availability, which in turn is mediated by various iron-containing proteins in the cell. Several putative Fe transporters exist in TIE-1’s genome. Some of these transporters can also transport Mn, part of several important cellular enzymes. Therefore, understanding the ability to transport and respond to varying levels of Fe and Mn under different conditions is important to improve TIE-1’s ability to produce useful biomolecules. Our data suggest that by overexpressing Fe transporter genes via plasmid-based expression, we can increase the import of Fe and Mn in TIE-1. Future work will leverage these data to improve TIE-1 as an attractive microbial chassis and future biotechnological workhorse.
The phylogenetic and global distribution of bacterial polyhydroxyalkanoate bioplastic degrading genes
Authors: Viljakainen V. R. , Hug L. A.
Published: May 2020

Polyhydroxyalkanoates (PHAs) are a family of microbially-made polyesters commercialized as biodegradable plastics. PHA production rates are predicted to increase as concerns around environmental plastic contamination and limited fossil fuel resources have increased the importance of biodegradable and bio-based plastic alternatives. Microbially-produced PHA depolymerases are the key enzymes mediating PHA biodegradation, but only a few PHA depolymerases have been well-characterized and screens employing metagenomic sequence data are lacking. Here, we used 3,078 metagenomes to analyze the distribution of PHA depolymerases in microbial communities from diverse aquatic, terrestrial and waste management systems. We significantly expand the recognized diversity of this protein family by screening 1,914 Gb of sequence data and identifying 13,869 putative PHA depolymerases in 1,295 metagenomes. Our results indicate that PHA depolymerases are unevenly distributed across environments. We predicted the highest frequency of PHA depolymerases in wastewater systems and the lowest in marine and thermal springs. In tandem, we screened 5,290 metagenome-assembled genomes to describe the phylogenetic distribution of PHA depolymerases, which is substantially broader compared to current cultured representatives. The Proteobacteria and Bacteroidota are key lineages encoding PHA depolymerases, but PHA depolymerases were predicted from members of the Bdellovibrionota, Methylomirabilota, Actinobacteriota, Firmicutes, Spirochaetota, Desulfobacterota, Myxococcota and Planctomycetota.

Originality/Significance Statement

Biodegradable plastics like polyhydroxyalkanoates (PHAs) are a hot topic, following ubiquitous environmental plastic contamination, government bans on single-use plastics, and a growing need for sustainable alternatives to petroleum-based plastics. Understanding the microbial conversion of PHAs in the environment and finding biomolecular tools that can act on PHAs is increasingly important as PHAs grow in popularity. In this study, we screened thousands of metagenomes and metagenome-assembled genomes (MAGs) to substantially increase the recognized diversity of PHA depolymerases, the key enzymes mediating PHA biodegradation. We use datasets from seven continents to provide a global summary of the distribution of PHA depolymerase genes in natural environments and waste-management systems. In tandem, we increase the number of described phylum-level lineages with PHA biodegradation potential. This work contributes a new understanding of the phylogenetic and environmental distribution of PHA depolymerases.
The CCCTC-binding factor CTCF represses hepatitis B virus Enhancer I and regulates viral transcription
Authors: D’Arienzo V , Ferguson J , Giraud G , Chapus F , Harris JM , Wing PAC , Claydon A , Begum S , Zhuang X , Balfe P , Testoni B , McKeating JA , Parish JL
Published: May 2020

Hepatitis B virus (HBV) infection is of global importance with over 2 billion people exposed to the virus during their lifetime and at risk of progressive liver disease, cirrhosis and hepatocellular carcinoma. HBV is a member of thehepadnaviridaefamily that replicates via episomal copies of a covalently closed circular DNA (cccDNA) genome. The chromatinization of this small viral genome, with overlapping open reading frames and regulatory elements, suggests an important role for epigenetic pathways to regulate viral transcription. The chromatin-organising transcriptional insulator protein CCCTC-binding factor (CTCF) has been reported to regulate transcription in a diverse range of viruses. We identified two conserved CTCF binding sites in the HBV genome within Enhancer I and chromatin immunoprecipitation (ChIP) analysis demonstrated an enrichment of CTCF binding to integrated or episomal copies of the viral genome. siRNA knockdown of CTCF results in a significant increase in pre-genomic RNA levels inde novoinfected HepG2 cells and those supporting episomal HBV DNA replication. Furthermore, mutation of these sites in HBV DNA minicircles abrogated CTCF binding and increased pre-genomic RNA levels, providing evidence of a direct role for CTCF in repressing HBV transcription.

IMPORTANCE

Hepatitis B virus (HBV) is a global cause of liver disease. At least 300 million individuals are chronically infected with HBV, frequently leading to life-threatening liver cirrhosis and cancer. Following viral entry, HBV DNA enters the nucleus and is bound by histones that are subject to epigenetic modification. The HBV genome contains two enhancer elements that stimulate viral transcription but the interplay between the viral enhancers and promoters is not fully understood. We have identified the host cell protein CCCTC binding factor (CTCF) as a repressor of HBV gene expression. CTCF binds to the HBV genome within Enhancer I and represses transcription of pre-genomic RNA. These findings provide new insights into how HBV transcription is regulated and show a new role for CTCF as a transcriptional insulator by associating with the viral genome between Enhancer I and the downstream basal core promoter.
Integron Gene Cassettes Harboring Novel Variants of D-Alanine-D-Alanine Ligase Confer High-level Resistance to D-Cycloserine
Authors: Rahman Md. Ajijur , Kaiser Frank , Jamshidi Shirin , Rahman Khondaker Miraz , Mullany Peter , Roberts Adam P.
Published: May 2020

During a PCR-based screen of antibiotic resistance genes (ARGs) associated with integrons in saliva-derived metagenomic DNA of healthy human volunteers, two novel variants of genes encoding a D-alanine-D-alanine ligase (ddl6andddl7) located within gene cassettes in the first position of a reverse integron were identified.Treponema denticolawas identified as the likely host of theddlcassettes. Bothddl6andddl7conferred high level resistance to D-cycloserine when expressed inEscherichia coliwithddl7conferring four-fold higher resistance to D-cycloserine compared toddl6. A SNP was found to be responsible for this difference in resistance phenotype between bothddlvariants. Molecular dynamics simulations were used to explain the mechanism of this phenotypic change at the atomic scale. A hypothesis for the evolutionary selection ofddlcontaining integron gene cassettes is proposed, based on molecular docking of plant metabolites within the ATP and D-cycloserine binding pockets of Ddl.

Significance Statement

The drivers of antimicrobial resistance are varied and numerous. One such hypothesis is that compounds not normally considered to be antibiotics may be able to select for genes that can provide resistance to conventional antibiotics. Here we provide evidence that dietary flavonoids are likely to provide the selective pressure for two novel variants of theddlgene, encoding D-alanine-D-alanine ligases, to be maintained as the first gene cassette of a reverse integron detectable in the human oral cavities from both the UK and Bangladesh. We show that Ddl is functional, able to confer resistance to D-cycloserine and that the dietary flavonoids quercetin and apigenin are likely able to compete with both ATP and D-cycloserine within their Ddl binding sites.
CytofRUV: Removing unwanted variation to integrate multiple CyTOF datasets
Authors: Trussart Marie , Teh Charis E , Tan Tania , Leong Lawrence , Gray Daniel HD , Speed Terence P.
Published: May 2020

Mass cytometry (CyTOF) is a technology that has revolutionised single cell biology. One illuminating application of CyTOF has been in understanding the mechanisms of blood cancer resistance to therapy. Longitudinal studies of clinical cohorts during drug treatment provide a deeper understanding of the molecular changes that underlie sensitivity or resistance to treatment in each patient. However, understanding the biological impact of a cancer drug in such studies necessitates the integration of multiple CyTOF batches. To date, the integration of CyTOF datasets remains a challenge due to technical differences arising in multiple batches. To overcome this limitation, we developed an approach called CytofRUV for analysing multiple CyTOF batches which includes an R-Shiny application with diagnostics plots. CytofRUV can correct for batch effects and integrate data from large numbers of patients and conditions across batches, to confidently compare cellular changes and correlate these with clinically relevant outcomes.
Evolutionary history of inversions in the direction of architecture-driven mutational pressures in crustacean mitochondrial genomes
Authors: Zhang Dong , Zou Hong , Zhang Jin , Wang Gui-Tang , Jakovlić Ivan
Published: May 2020

Inversions of the origin of replication (ORI) of mitochondrial genomes produce asymmetrical mutational pressures that can cause artefactual clustering in phylogenetic analyses. It is therefore an absolute prerequisite for all molecular evolution studies that use mitochondrial data to account for ORI events in the evolutionary history of their dataset. The number of ORI events in crustaceans remains unknown; several studies reported ORI events in some crustacean lineages on the basis of fully inversed (e.g. negative vs. positive) GC skew patterns, but studies of isolated lineages could have easily overlooked ORI events that produced merely a reduction in the skew magnitude. In this study, we used a comprehensive taxonomic approach to systematically study the evolutionary history of ORI events in crustaceans using all available mitogenomes and combining signals from lineage-specific skew magnitude and direction (+ or -), cumulative skew diagrams, and gene rearrangements. We inferred 24 putative ORI events (14 of which have not been proposed before): 17 with relative confidence, and 7 speculative. Most of these were located at lower taxonomic levels, but there are indications of ORIs that occurred at or above the order-level: Copepoda, Isopoda, and putatively in Branchiopoda and Poecilostomatida+Cyclopoida. Several putative ORI events did not result in fully inversed skews. In many lineages skew plots were not informative for the prediction of replication origin and direction of mutational pressures, but inversions of the mitogenome fragment comprising the ancestral CR (rrnS-CR-trnI) were rather good predictors of skew inversions. We also found that skew plots can be a useful tool to indirectly infer the relative strengths of mutational/purifying pressures in some crustacean lineages: when purifying pressures outweigh mutational, GC skew plots are strongly affected by the strand distribution of genes, and when mutational > purifying, GC skew plots can be even completely (apparently) unaffected by the strand distribution of genes. This observation has very important repercussions for phylogenetic and evolutionary studies, as it implies that not only the relatively rare ORI events, but also much more common gene strand switches and same-strand rearrangements can produce mutational bursts, which in turn affect phylogenetic and evolutionary analyses. We argue that such compositional biases may produce misleading signals not only in phylogenetic but also in other types of evolutionary analyses (dN/dS ratios, codon usage bias, base composition, branch length comparison, etc.), and discuss several such examples. Therefore, all studies aiming to study the evolution of mtDNA sequences should pay close attention to architectural rearrangements.
Coordinated crosstalk between microtubules and actin by a spectraplakin regulates lumen formation and branching
Authors: Ricolo Delia , Araújo Sofia J.
Published: May 2020

The establishment of branched structures by single cells involves complex cytoskeletal remodelling events. InDrosophila, epithelial tracheal system terminal cells (TCs) and dendritic arborisation neurons are models for these subcellular branching processes. During tracheal embryonic development, the generation of subcellular branches is characterized by extensive remodelling of the microtubule (MT) network and actin cytoskeleton, followed by vesicular transport and membrane dynamics. We have previously shown that centrosomes are key players in the initiation of subcellular lumen formation where they act as microtubule organizing centres (MTOCs). However, not much is known on the events that lead to the growth of these subcellular luminal branches or what makes them progress through a particular trajectory within the cytoplasm of the TC. Here, we have identified that the spectraplakinShort-stop(Shot) promotes the crosstalk between MTs and actin, which leads to the extension and guidance of the subcellular lumen within the TC cytoplasm. Shot is enriched in cells undergoing the initial steps of subcellular branching as a direct response to FGF signalling. An excess of Shot induces ectopic acentrosomal branching points in the embryonic and larval tracheal TC leading to cells with extra subcellular lumina. These data provide the first evidence for a role for spectraplakins in subcellular lumen formation and branching.
Central role and structure of the membrane pseudokinase YukC in the antibacterialBacillus subtilisType VIIb Secretion System
Authors: Tassinari Matteo , Doan Thierry , Bellinzoni Marco , Chabalier Maïalene , Ben-Assaya Mathilde , Martinez Mariano , Gaday Quentin , Alzari Pedro M. , Cascales Eric , Fronzes Rémi , Gubellini Francesca
Published: May 2020

Type VIIb Secretion System (T7SSb) has been recently identified in Firmicutes resembling the mycobacterial T7SSa. Despite limited sequence homology, T7SSa and T7SSb have substrates with striking structural similarities, the WXG100 proteins. Recent advances inStaphylococcus spp. proposed that T7SSb is involved in intra-species competition. However, the architecture and mechanism of action of this secretion complex remain largely obscure. Here, we investigate the T7SSb ofBacillus subtilisas a model system. We report the first evidence ofB. subtilisability to mediate intra- and inter-species antibacterial activity in a T7SSb-dependent manner. Then, we present the first systematic investigation of the T7SSb protein-protein network, revealing novel interactions and highlighting the central role of the pseudokinase subunit YukC in the assembly of the system. Its direct interaction with a T7SSb-secreted toxin supports its role in recruiting substrates to the secretion machinery. Finally, we solved the crystal structure of full-length transmembrane YukC defining novel structural motifs and suggesting that intrinsic flexibility modulates the orientation of the pseudokinase domains and YukC function. Overall, our results provide a better understanding on the role and molecular organisation of the T7SSb, opening new perspectives for the comprehension of this poorly characterized molecular machine.
Phototaxis of the unicellular red algaCyanidioschyzon merolaeis mediated by novel actin-driven tentacles
Authors: Maschmann Sascha , Ruban Karin , Wientapper Johanna , Walter Wilhelm J.
Published: May 2020

Phototaxis – which is the ability to move towards or away from a light source autonomously – is a common mechanism of unicellular algae. It evolved multiple times independently in different plant lineages1. As of yet, algal phototaxis has been mainly linked to the presence of cilia, the only known locomotive organelle in unicellular algae. Consequently, phototaxis was believed to be largely absent in red algae (Rhodophyta) that lack cilia in all stages of their life cycle1. Remarkably, the unicellular red algaCyanidioschyzon merolae(C. merolae) is able to move towards the light. However, it has remained unclear howC. merolaecan achieve movement, and the presence of a completely new mechanism was suggested2.

Here we show that the basis of this movement are novel retractable projections that were termed tentacles due to their distinct morphology. The tentacles could be reproducibly induced within 20 minutes by increasing the salt concentration of the culture medium. Electron microscopy revealed filamentous structures inside the tentacles that we identified to be actin filaments. This is surprising asC. merolae’s single actin gene was previously published to not be expressed3,4. Based on our findings, we propose a model forC. merolae’s actin-driven but myosin-independent motility. To our knowledge, the described tentacles represent a novel motility mechanism.
Fungi are colder than their surroundings
Authors: Cordero Radames JB , Mattoon Ellie Rose , Casadevall Arturo
Published: May 2020

Fungi play essential roles in global ecology and economy, but their thermal biology is widely unknown. Mushrooms were previously noticed to be colder than surrounding air via evaporative cooling or evapotranspiration. Here we applied infrared imaging to reveal that not just mushrooms, but also molds and yeasts maintain colder temperatures than their surroundings via evapotranspiration. On average, fungal specimens are ~2.5 °C colder than the surrounding temperature. The relatively cold temperature of mushrooms can be observed throughout the whole fruiting process and at the level of mycelium. The mushroom’s hymenium appeared the coldest and different areas of thePleurotus ostreatusmushroom appear to dissipate heat differently. Evapotranspiration in yeast and mold biofilms can be measured from the accumulation of condensed water droplets above biofilms; which is significantly higher than the surrounding agar. We also present a mushroom-based air-cooling system (MycoCooler™) capable of passively reducing the temperature of a closed compartment by approximately 10 °C in 25 minutes. These findings suggest that the fungal kingdom is characteristically cold. Since fungi make up ~2% of Earth biomass, their evapotranspiration may contribute to planetary temperatures in local environments. This study present new research avenues in fungal biology, biomedicine, microclimate, and sustainable energy.
Irisin Directly Stimulates Osteoclastogenesis and Bone ResorptionIn VitroandIn Vivo
Authors: Estell Eben G. , Le Phuong T. , Vegting Yosta , Kim Hyeonwoo , Baron Roland , Spiegelman Bruce , Rosen Clifford J.
Published: May 2020

The myokine irisin facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In the current study we investigated whether irisin also directly regulates osteoclasts.In vitro, irisin (2-10 ng/mL) increased osteoclast differentiation in C57BL/6J bone marrow progenitors; this increase was blocked by a neutralizing antibody to integrin αVβ5. Irisin also increased resorption on several substratesin situ. RNAseq revealed differential gene expression induced by irisin including upregulation of markers for osteoclast differentiation and resorption, as well as osteoblast-stimulating ‘clastokines’.In vivo, forced expression of the irisin precursorFndc5in murine muscle resulted in low bone mass and increased number of osteoclasts. Taken together, our work demonstrates that irisin acts directly on cultured osteoclast progenitors to increase differentiation and promote bone resorption. These actions support the tenet that irisin not only stimulates bone remodeling but may also be an important counter-regulatory hormone during exercise.
ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection
Authors: Zhou Lingli , Xu Zhenhua , Castiglione Gianni M. , Soiberman Uri S. , Eberhart Charles G. , Duh Elia J.
Published: May 2020

Purpose

Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.

Methods

We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.

Results

Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.

Conclusions

Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.
Labeling subcellular structures in living specimens using live-cell incompatible dyes with excellent optical properties
Authors: Han Yubing , Zhang Zhimin , Liu Wenjie , Yao Yuanfa , Chen Yuchen , Luo Xin , Wang Wensheng , Xu Yingke , Liu Xu , Kuang Cuifang , Hao Xiang
Published: May 2020

Despite the urgent needs of imaging living specimens for cutting-edge biological research, most of the existing fluorescent labeling methods suffer from either poor optical properties or complicated operations to realize cell-permeability and specificity. Here, we introduce a method to overcome this tradeoff by incubating living cells and tissues with fluorescent dyes, no matter if they are cell-permeable or not, at particular conditions (concentration and temperature) without physical cell-penetration or chemical modifications. Based on this method, the mitochondrial labeling capability of Atto dyes, especially Atto 647N with extraordinary optical properties, together with interesting interactions between organelles is revealed. These results indicate the great potential of using dyes, which are normally considered “live-cell incompatible”, to capture the morphology and dynamics of subcellular structures in living specimens.
Loss of clathrin heavy chain enhances actin-dependent stiffness of mouse embryonic stem cells
Authors: Mote Ridim D , Yadav Jyoti , Singh Surya Bansi , Tiwari Mahak , Patil Shivprasad , Subramanyam Deepa
Published: May 2020

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cell stiffness, and specific responses to features of the underlying substratum. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking the clathrin heavy chain (Cltc), display higher Young’s modulus, indicative of greater cellular stiffness, in comparison to WT mESCs. We have previously shown that mESCs lackingCltcdisplay a loss of pluripotency, and an initiation of differentiation. The increased stiffness observed in these cells was accompanied by the presence of actin stress fibres and accumulation of the inactive, phosphorylated, actin binding protein, Cofilin. Treatment ofCltcknockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young’s modulus, to values similar to those obtained with WT mESCs. However, the expression profile of pluripotency factors was not rescued. This indicates that a restoration of mechanical properties, through modulation of the actin cytoskeleton, may not always be accompanied by a change in the expression of critical transcription factors that regulate the state of a stem cell, and that this may be dependent on the presence of active endocytosis in a cell.
From organizing to organizations: a typological scale of human relations management outside the legal world
Authors: Neumann Martin
Published: May 2020

Purpose

The article examines strategies of human resource management in the absence of institutional hedging by norm-enforcing institutions such as a state monopoly of violence by using case studies of criminal organizations. This condition provides a test-bed for studying the effects of human relations management strategies on organizational performance.

Design/methodology/approach

For this purpose, a case study methodology is applied. Three cases are selected to build a scale from complete plasticity of an undifferentiated network via a status differentiated gang to a hierarchical organization that provides social positions. The case studies are analysed by qualitative content analysis, network analysis and agent-based simulation.

Findings

An undifferentiated network based on informal trust lacks mechanisms for conflict resolution. This is a highly vulnerable organizational structure. While a status differentiated gang is more resilient towards internal conflicts, its activities remain dependent on individually accumulated social capital. This organizational structure is not resilient over generations of actors. A hierarchical organization provides highest degree of structural resilience up to a level of a system of self-organized criticality.

Originality/value

The study of human relations management outside the legal world provides insights into the basic mechanisms and functional effects of organizational activity.
Digital curation practices in institutional repositories in South India: a study
Authors: C. Shajitha
Published: May 2020

Purpose

The purpose of this study was to identify the digital curation practices in institutional repositories (IRs) in South India.

Design/methodology/approach

A voluntary survey was conducted among the IR managers of 23 South Indian IRs, and the response rate was 87%.

Findings

This study found that the active participation of South Indian IRs was only seen in a few digital curation activities. However, of the 33 digital curation activities analyzed, the active participation of repositories was only seen in ten digital curation activities. The performance of preservation activities was extremely low, and disagreements were recorded by the survey participants toward several digital curation activities. The most disagreed digital curation activities were emulation and cease data curation. All the participants had assigned metadata and allowed file downloads in their repositories. Raman Research Institute had provided a good number of digital curation services in their IR.

Originality/value

This is an in-depth study investigating the digital curation practice currently underway in South Indian IRs, and the researcher could not find similar studies in this niche.
Enhancing teachers' relational competence: a teacher lesson study
Authors: Plantin Ewe Linda
Published: May 2020

Purpose

The purpose of this paper is to contribute with innovative knowledge about how lesson study as a method can be used as a tool for increasing in-service teachers' professional development. More specifically, the aim is to test in what way one single lesson study cycle, where teachers' way of perceiving teacher–student interactions was tested before and after, contributes to teachers' increased understanding of relational competence. The study is a pilot preparing for an upcoming main study.

Design/methodology/approach

Participants were 19 lead teachers (swe: förstelärare) in a Swedish municipality. The study was based on a relational framework and methodological approach (Aspelin, 2017; Pianta, 1999). Data obtained through web-questionnaires and collaborative group reflections were analysed and compiled to find general patterns.

Findings

The majority of the participants (98.5%) considered their understanding of relational competence to be increased (Cohen's d 1.72) during the intervention. Additionally, there was a notable increase in participants' abilities to verbalise their understanding post-intervention.

Research limitations/implications

The lack of revised studies might have impacted the validity of this work. However, as this was a pilot study the result can be considered to fulfil the purpose.

Practical implications

The research suggests that lesson study as a method for in-service teachers as participating students can be used effectively to increase teachers' professional development.

Originality/value

The study aims to investigate how lesson study as a method can be used to develop in-service teacher learning.
Interfere! How Chinese subsidiaries manage their global headquarters
Authors: Metz Annette , Prange Christiane
Published: May 2020

Purpose

With the increasing dependence on the Chinese market, Chinese subsidiary managers rather than Western managers in the headquarters take responsibility for the overall success of the multinational company (MNC). This paper aims to argue that Chinese managers need to actively interfere to guarantee the survival of the MNC. Transaction analysis is suggested as a tool to rebalance the relationship.

Design/methodology/approach

Based on illustrative material and experience cases, the authors highlight why and how Chinese subsidiary managers have to engage in interference management.

Findings

Introducing different strategies within transaction analysis shows how Western managers can deal with Chinese interference management to improve relationships.

Practical implications

With the use of transaction analysis, Western managers can verify their communication strategies and behavior to better relate to Chinese subsidiaries on an “adult” level.

Originality/value

Interference management is based on counterintuitive thought that Chinese subsidiary managers rather than headquarters become responsible for the overall success of the MNC. Transaction analysis is used to uncover hidden assumptions, communication strategies and behavior in headquarters–subsidiary relationships.
Labour and Antisemitism: a Crisis Misunderstood
Authors: Gidley Ben , McGeever Brendan , Feldman David
Published: May 2020

In this article, we argue that Labour’s antisemitism crisis has been misunderstood. We suggest that a more accurate and sophisticated understanding of antisemitism offers a way forward. There are three elements to this claim. First, by drawing on existing data on attitudes towards Jews, we criticise the widespread focus on individual ‘antisemites’, rather than on the broader problem of antisemitism. In turn, we conceive of antisemitism not as a virus or poison, as in so many formulations, but rather, as a reservoir of readily available images and ideas that subsist in our political culture. Second, following on from this understanding, we offer five ways forward. Finally, we set this analysis in the context of a historical parting of the ways between anti‐racism and opposition to antisemitism. An anti‐racism defined solely by conceptions of whiteness and power, we argue, has proven unable to fully acknowledge and account for anti‐Jewish racism.
Factors associated with emergency medical service delays in suspected ST‐elevation myocardial infarction in Victoria, Australia: A retrospective study
Authors: Alrawashdeh Ahmad , Nehme Ziad , Williams Brett , Smith Karen , Stephenson Michael , Bernard Stephen , Cameron Peter , Stub Dion
Published: May 2020

Objective

To assess the effect of patient and system characteristics on emergency medical service (EMS) delays prior to arrival at hospital in suspected ST‐elevation myocardial infarction (STEMI).

Methods

This was a retrospective observational study of 1739 patients who presented with suspected STEMI to the EMS in Melbourne, Australia between October 2011 and January 2014. Our primary outcome measure was call‐to‐hospital time, defined as the time in minutes from emergency call to hospital arrival. We examined the association of patient and system characteristics on call‐to‐hospital time using multivariable linear regression.

Results

The mean call‐to‐hospital time was 60.1 min (standard deviation 20.5) and the median travel distance was 13.0 km (interquartile range 7.2–23.1). In the multivariable model, patient characteristics associated with longer call‐to‐hospital time were age ≥75 years (2.3 min; 95% confidence interval [CI] 0.6–4.0), female sex (1.9 min; 95% CI 0.3–3.4), pre‐existing mental health disorder (4.0 min; 95% CI 1.9–6.1) or musculoskeletal disease (2.7 min; 95% CI 1.0–4.4), absence of chest pain (3.0 min; 95% CI 1.1–4.8), and presentation with clinical complications. System factors associated with call‐to‐hospital time include lower dispatch priority (12.7 min; 95% CI 9.0–16.5) and non‐12‐lead electrocardiography (ECG) capable ambulance first on scene (4.5 min; 95% CI 3.1–5.8). Patients who were not initially attended by a 12‐lead capable ambulance were less likely to receive a 12‐lead ECG within 10 min (18.5% vs 71.0%, P < 0.001).

Conclusion

A range of patient and system factors may influence EMS delays in STEMI. However, optimising dispatch prioritisation and widespread availability of prehospital 12‐lead ECG could lead to substantial reduction in time to treatment.
No evidence of cardiac stunning or decoupling immediately after cardiopulmonary bypass for elective coronary surgery
Authors: Dybos Tannvik Tomas , Kiss Gabriel , Torp Hans , Eskeland Rimehaug Audun , Kirkeby‐Garstad Idar
Published: May 2020

Background

There is significant uncertainty regarding the timing of onset of cardiovascular stunning after cardiac surgery. Cardiovascular stunning is affecting both contractility (Ees) and arterial load. Arterial load may be represented by arterial elastance (Ea) and participates in ventriculo‐arterial coupling through the Ea/Ees ratio, giving information on efficiency and performance. An alternative approach to ventriculo‐arterial interaction is oscillatory power fraction (OPF). The aim of this study was to investigate the immediate beat‐to‐beat effects of on‐pump coronary artery bypass graft (CABG) surgery on contractility, cardiac power parameters, arterial load and ventriculo‐arterial coupling as well as classical haemodynamic parameters.

Methods

We included 41 patients scheduled for fast‐track CABG surgery. Measurements were taken before and after cardiopulmonary bypass. A flow and pressure curve were recorded from transoesophageal pulsed wave Doppler and a radial artery catheter, respectively. This enabled the calculation of stroke work, total cardiac energy delivery, OPF and Ea/Ees ratio. Routine haemodynamic monitoring provided the classical haemodynamic parameters.

Results

Immediately after cardiopulmonary bypass there was no firm evidence for alterations in contractility, stroke work, stroke volume or arterial elastance. Ea/Ees ratio and OPF remained unchanged.

Conclusions

There was no evidence for clinically relevant cardiac stunning or altered arterial load immediately after cardiopulmonary bypass for CABG surgery. The unchanged Ea/Ees ratio and OPF are indicating unchanged cardiac efficiency before and after cardiopulmonary bypass. This indicates that in elective CABG patients cardiovascular stunning is perhaps a phenomenon of inflammation and not immediate ischaemia–reperfusion injury or mechanical handling.
When We Come To It
Authors: Craig Sienna R.
Published: May 2020

Pasang awakes on April 25, 2015, in her New England college dorm room to news of a major earthquake in Nepal, where she and her family are from. She returns to Nepal that summer for a visit. In the wake of Earth's massive movements, Pasang navigates her family's ties to Mustang, Nepal, and makes a journey that at once troubles and affirms her sense of place and home.
Radiation therapy and the innate immune response: Clinical implications for immunotherapy approaches
Authors: Gómez Valentí , Mustapha Rami , Ng Kenrick , Ng Tony
Published: May 2020

Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double‐strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule‐targeted therapies and, in recent years, immunotherapy (IT).

Cancer‐cell apoptosis after radiation treatment causes an immunological reaction that contributes to eradicating the tumour via antigen presentation and subsequent T‐cell activation. By contrast, radiotherapy also contributes to the formation of an immunosuppressive environment that hinders the efficacy of the therapy. Innate immune cells from myeloid and lymphoid origin show a very active role in both acquired resistance and antitumourigenic mechanisms. Therefore, many efforts are being made in order to reach a better understanding of the innate immunity reactions after radiation therapy (RT) and the design of new combinatorial IT strategies focused in these particular populations.
Anti‐N‐methyl‐D‐aspartate receptor encephalitis unresponsive to early and aggressive immunotherapy in a young female: A case report
Authors: Kaur Harleen , Mittal Gaurav Kumar
Published: May 2020

Background

Acute encephalitis refers to inflammation of the brain that develops as a rapidly progressive encephalopathy. It usually has an infectious origin, but an increasing number of autoimmune etiologies have been identified recently. Keeping a high index of suspicion is of great importance, because delayed diagnosis and delayed initiation of appropriate therapy may lead to poor outcome.

Case presentation

This paper describes a case of anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis in a young female who presented with a short prodrome; had a rapidly progressive illness; and could not be saved even after early, optimal, and aggressive immunomodulatory therapy.

Conclusions

Despite early diagnosis, and prompt therapy, anti‐NMDAR encephalitis may progress and remain refractory to treatment. More studies are needed for further therapeutic avenues in treatment‐refractory cases of anti‐NMDAR encephalitis not responding even to cyclophosphamide as highlighted by our case.