bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo whole-genome assembly ofChrysanthemum makinoi, a key wild ancestor to hexaploid Chrysanthemum
Authors: van Lieshout N. , van Kaauwen M. , Kodde L. , Arens P. , Smulders M.J.M. , Visser R.G.F. , Finkers R.
Published: July 2021

Chrysanthemum is among the top ten cut, potted and perennial garden flowers in the world. Despite this, to date, only the genomes of two wild diploid chrysanthemums have been sequenced and assembled. Here we present the most complete and contiguous chrysanthemumde novoassembly published so far, as well as a correspondingab initioannotation. The wild diploidChrysanthemum makinoiis thought to be one of the ancestors of the cultivated hexaploid varieties which are currently grown all around the world. Using a combination of Oxford Nanopore long reads, Pacific Biosciences long reads, Illumina short reads, Dovetail sequences and a genetic map, we assembled 3.1 Gb of its sequence into 9 pseudochromosomes, with an N50 of 330 Mb and BUSCO complete score of 92.1%. Ourab initioannotation pipeline predicted 95 074 genes and marked 80.0% of the genome as repetitive. This genome assembly ofC. makinoiprovides an important step forward in understanding the chrysanthemum genome, evolution and history.
Sleep Medicine Knowledge Among Graduating Medical Students in Lebanon During an Economic and Political Crisis
Authors: Aoun Raissa , Zibara Victor , Costanian Christy , Attarian Hrayr , Bahous Sola Aoun
Published: July 2021

Objectives

Sleep disorders are prevalent and underrecognized during both economic and political crises. They are a major reason for poor overall health and decreased quality of life. Sleep medicine education is limited at most medical schools, resulting in limited awareness of this important aspect of healthcare. The aim of the study is to assess sleep medicine knowledge of graduating medical students in Lebanon and to assess their readiness to tackle sleep health issues in a country during an unprecedented crisis.

Methods

Final-year medical students at 7 medical schools in Lebanon were invited to fill a survey between January 2020 and March 2021. The Assessment of Sleep Knowledge in Medical Education survey was used to assess their knowledge in sleep medicine. The curriculum organizers at the medical schools were also surveyed. Student’s t-test was used for analysis.

Results

158 and 58 students completed the survey during 2020 and 2021, with a mean overall score on sleep knowledge of was 17.5 and 15.9 /30, respectively. There was no difference in mean knowledge scores by gender, age, American versus European medical school systems, and between medical schools that included sleep medicine in their curriculum versus those that did not.

Conclusions

Presence of sleep medicine education in the curriculum was associated with higher scores on ASKME among graduating Lebanese medical students. Overall, the new crop of physicians in Lebanon possesses a relatively good knowledge base in sleep medicine. Nevertheless, more effort should be made to uniformly maintain this level of sleep education.
Antisense oligonucleotides targeting UBE3A-ATS restore expression of UBE3A by relieving transcriptional interference
Authors: Germain Noelle D. , Gorka Dea , Drennan Ryan , Jafar-nejad Paymaan , Whipple Amanda , Core Leighton , Levine Eric S. , Rigo Frank , Chamberlain Stormy J.
Published: July 2021

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A allele. In neurons, the paternal allele of UBE3A is silenced in cis by the long noncoding RNA, UBE3A-ATS. Unsilencing paternal UBE3A by reducing UBE3A-ATS is a promising therapeutic approach for the treatment of AS. Here we show that targeted cleavage of UBE3A-ATS using antisense oligonucleotides (ASOs) restores UBE3A and rescues electrophysiological phenotypes in human AS neurons. We demonstrate that cleavage of UBE3A-ATS results in termination of its transcription by displacement of RNA Polymerase II. Reduced transcription of UBE3A-ATS allows transcription of UBE3A to proceed to completion, providing definitive evidence for the transcriptional interference model of paternal UBE3A silencing. These insights into the mechanism by which ASOs restore UBE3A inform the future development of nucleotide-based approaches for the treatment of AS, including alternative strategies for cleaving UBE3A-ATS that can be developed for long-term restoration of UBE3A function.
Inhibitory proteins block substrate access by occupying the active site cleft of Bacillus subtilis intramembrane protease SpoIVFB
Authors: Olenic Sandra , Heo Lim , Feig Michael , Kroos Lee
Published: July 2021

Intramembrane proteases function in numerous signaling pathways that impact health, but knowledge about regulation of intramembrane proteolysis is limited. We examined inhibition of intramembrane metalloprotease SpoIVFB by proteins BofA and SpoIVFA. We found that BofA residues in and near a predicted transmembrane segment are required for SpoIVFB inhibition, and cross-linking experiments indicated that this transmembrane segment occupies the SpoIVFB active site cleft. SpoIVFA is also required for SpoIVFB inhibition. The inhibitory proteins block access of the substrate N-terminal Proregion to the membrane-embedded SpoIVFB active site, based on additional cross-linking experiments; however, the inhibitory proteins did not prevent interaction between the substrate C-terminal region and the SpoIVFB soluble domain. A structural model was built of SpoIVFB in complex with BofA and parts of SpoIVFA and substrate, using partial homology and constraints from cross-linking and co-evolutionary analyses. The model predicts that conserved BofA residues interact to stabilize a transmembrane segment and a membrane-embedded C-terminal region. SpoIVFA is predicted to bridge the BofA C-terminal region and SpoIVFB, forming a membrane-embedded inhibition complex. Our results reveal a novel mechanism of intramembrane protease inhibition with clear implications for relief from inhibition in vivo and design of inhibitors as potential therapeutics.
A Phosphorus-Limitation Induced, Functionally Conserved DUF506 Protein is a Repressor of Root Hair Elongation in Arabidopsis thaliana
Authors: Ying Sheng , Blancaflor Elison B. , Liao Fuqi , Scheible Wolf-Rüdiger
Published: July 2021

Root hairs (RHs) function in nutrient and water acquisition, root metabolite exudation, soil anchorage and plant-microbe interactions. Longer or more abundant RHs are potential breeding traits for developing crops that are more resource-use efficient and can improve soil health. RH elongation is controlled by both environmental and endogenous factors. While many genes are known to promote RH elongation, relatively little is known about genes and mechanisms that constrain RH growth. Here we demonstrate that a DOMAIN OF UNKNOWN FUNCTION 506 (DUF506) protein, AT3G25240, negatively regulates Arabidopsis thaliana RH growth. The AT3G25240 gene is strongly and specifically induced during P-limitation. Mutants of this gene, which we call REPRESSOR OF EXCESSIVE ROOT HAIR ELONGATION 1 (RXR1), have much longer RHs, while over-expression of the gene results in much shorter RHs. RXR1 physically interacts with a Rab-GTPase (RXR2), and an rxr2 mutant phenocopies the rxr1 mutant. Overexpression of a Brachypodium distachyon RXR1 homolog resulted in repression of RH elongation in Brachypodium. Taken together, our results reveal a DUF506-GTPase module with a prominent role in repression of RH elongation that is conserved in monocots and dicots.
Larval zebrafish exhibit collective motion behaviors in constrained spaces
Authors: Zaki Haider , Lushi Enkeleida , Severi Kristen E.
Published: July 2021

Collective behavior may be elicited or can spontaneously emerge by a combination of interactions with the physical environment and conspecifics moving within that environment. To investigate the relative contributions of these factors in a small millimeter-scale swimming organism, we observed larval zebrafish, interacting at varying densities under circular confinement. Our aim was to understand the biological and physical mechanisms acting on these larvae as they swim together inside circular confinements. If left undisturbed, larval zebrafish swim intermittently in a burst and coast manner and are socially independent at this developmental stage, before shoaling behavioral onset. We report here our analysis of a new observation for this well-studied species: in circular confinement and at sufficiently high densities, the larvae collectively circle rapidly alongside the boundary. This is a new physical example of self-organization of mesoscale living active matter driven by boundaries and environment geometry. We believe this is a step forward toward using a prominent biological model system in a new interdisciplinary context to advance knowledge of the physics of social interactions.
Mutations in Drosophila tRNA processing factors cause phenotypes similar to Pontocerebellar Hypoplasia
Authors: Schmidt Casey A. , Min Lucy Y. , McVay Michelle H. , Giusto Joseph D. , Brown John C. , Salzler Harmony R. , Matera A. Gregory
Published: July 2021

Mature tRNAs are generated by multiple RNA processing events, which can include the excision of intervening sequences. The tRNA splicing endonuclease (TSEN) complex is responsible for cleaving these intron-containing pre-tRNA transcripts. In humans, TSEN copurifies with CLP1, an RNA kinase. Despite extensive work on CLP1, its in vivo connection to tRNA splicing remains unclear. Interestingly, mutations in CLP1 or TSEN genes cause neurological diseases in humans that are collectively termed Pontocerebellar Hypoplasia (PCH). In mice, loss of Clp1 kinase activity results in premature death, microcephaly and progressive loss of motor function. To determine if similar phenotypes are observed in Drosophila, we characterized mutations in crowded-by-cid (cbc), the CLP1 ortholog, as well as in the fly ortholog of human TSEN54. Analyses of organismal viability, larval locomotion and brain size revealed that mutations in both cbc and Tsen54 phenocopy those in mammals in several details. In addition to an overall reduction in brain lobe size, we also found increased cell death in mutant larval brains. Ubiquitous or tissue-specific knockdown of cbc in neurons and muscles reduced viability and locomotor function. These findings indicate that we can successfully model PCH in a genetically-tractable invertebrate.
Development of a fluorescent quantitative real-time polymerase chain reaction assay for the detection of novel-goose parvovirus in vivo
Authors: Ma Haibin , Li Yahui , Yang Junzheng
Published: July 2021

Objectives

To develop a sensitive, highly specific fluorescent quantitative real-time PCR assay for accurate detection and quantification of novel-goose parvovirus (N-GPV) in vitro and in vivo.

Methods

Specific primers was designed based on N-GPV inverted terminal repeats region; virus RNA (DFV, NDV, AIV, DHV-1, DHV-3) and virus DNA (MDPV, GPV, N-GPV) were extracted, cDNA (DFV, NDV, AIV, DHV-1, DHV-3) were prepared from viral RNAs using M-MLV Reverse Transcriptase, and prepared cDNA (DFV, NDV, AIV, DHV-1, DHV-3) and DNA (MDPV, GPV, N-GPV) amplified by real-time PCR; the sensitivity, specificity and reproducibility of established real-time PCR methods were evaluated, and finally we validated the reliability of real-time PCR methods in ducklings models in vivo.

Results

The standard curve of established real-time PCR had a good linearity (slope was −0.3098, Y-intercept was 37.865, efficiency of standard curve was 0.995); the detection limit of established real-time PCR for N-GPV was 10 copies/reaction. The sensitivity of real-time PCR was 10 copies/μL, which was 1000 times higher than conventional gel-based PCR assay. The results of intra-assay CVs (0.04-0.74%) and inter-assay CVs (0.16-0.53%) showed that the real-time PCR assay had an excellent repeatability. This method also could efficiently detect viral load in heart, liver, spleen, lung, kidney, pancreas, bursa of Fabricius, brain, blood and excrement from ducklings models after N-GPV infection from 6h to 28 days, which could provided us a dynamic distribution observation of N-GPV viral load using this real-time PCR assay in vivo.

Conclusion

In the study, we developed a high sensitive, specific and reproducible real-time PCR assay for N-GPV detection. The established real-time PCR assay was suitable for parvovirus detection and quantification simultaneously, no matter sample obtained from blood, internal organs or ileac contents; the present work may provide insight into the pathogenesis of N-GPV and will contributes to better understanding of this newly emerged novel GPV related virus in cherry valley ducks.
Differed cell division angle, position of cell proliferative area, and localization of ANGUSTIFOLIA3 in lateral organs
Authors: Kinoshita Ayaka , Naito Makiko , Tsukaya Hirokazu
Published: July 2021

Leaf meristem is a cell proliferative zone present in the lateral organ primordia. In this study, we investigated how the proliferative zone affects the final morphology of the lateral organs. We examined how cell proliferative zones differ in the primordia of planar floral organs and polar auxin transport inhibitor (PATI)-treated leaves from normal foliage leaf primordia of Arabidopsis thaliana with a focus on the spatial accumulation pattern of ANGUSTIFOLIA3 (AN3), a key element for leaf meristem positioning. We found that organ shape changes by PATI treatment were correlated to the angle of the cell division plane relative to the leaf primordia axis in the leaf meristem (cell division angle), but not with leaf-meristem positioning, size of the leaf meristem, or the localization pattern of AN3 protein. In contrast, different shapes between sepals and petals compared with foliage leaves were associated with both altered meristem position associated with altered AN3 expression patterns and different distributions of cell division angles. These results suggest that lateral organ shapes are regulated via two aspects: position of meristem and cell division angles

Summary statement

Different lateral organs with different morphology possess different properties of meristems; cell division angles, position of cell proliferative area and AN3 localization patterns.
Assessing the Effectiveness of Mycorrhizal Inoculation on the Biochemical Composition of the Different Species of Echinacea
Authors: Sharma Asha , Saini Ishan , Shankar Bandi Arpitha
Published: July 2021

The information regarding the effect of the mycorrhizal inoculation on different Echinacea species is not available in detail. Therefore, here we determined the changes in the biochemical composition of echinacea as a result of mycorrhizal inoculation. This experiment was undertaken to assess the effect of the mycorrhizal association on biochemical properties of different echinacea species (E. angustifolia,E. purpurea, E. pallida). Here various echinacea species were inoculated with mycorrhiza to examine the species richness in different traits. The results established that biological traits (plant dry matter, chlorophyll content, carotenoid, N content, P content, K content) and physiological and mycorrhization characteristics (Root essential oil, ABTS Antioxidant, Ferric-Reducing Antioxidant, Total phenolic, AM Spore No., AM Root Colonization) both are higher under mycorrhizal association than the control plants of different echinacea species. E. purpurea showed greater results than the E. angustifolia and E. pallida. Among biochemical properties chlorophyll content, carotenoid and N, P, K were significantly higher underE. Purpurea than the E. angustifolia and E.pallida. Total dry matter was higher under E. angustifolia (49.23 g) and minimum dry matter was found under E. pallida (40.07 g). Physiological and mycorrhizal traits were significantly higher under E. purpurea than the other species. E. purpurea showed higher AM Spore No., AM Root Colonization 231.30, 78.70% respectively. Lowest physiological and mycorrhization characteristics were found under E. pallida. The result of mycorrhizal association was very effective for plant growth and increased bio-physicochemical properties than the control plants.
Selective whole genome amplification as a tool to enrich specimens with lowTreponema pallidumgenomic DNA copies for whole genome sequencing
Authors: Thurlow Charles M. , Joseph Sandeep J. , Ganova-Raeva Lilia , Katz Samantha S. , Pereira Lara , Chen Cheng , Debra Alyssa , Vilfort Kendra , Workowski Kimberly , Cohen Stephanie E. , Reno Hilary , Sun Yongcheng , Burroughs Mark , Sheth Mili , Chi Kai-Hua , Danavall Damien , Philip Susan S. , Cao Weiping , Kersh Ellen N. , Pillay Allan
Published: July 2021

Downstream next generation sequencing (NGS) of the syphilis spirocheteTreponema pallidumsubspeciespallidum(T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for theT. pallidumgenome, and the capture and removal of CpG-methylated host DNA using the NEBNext®Microbiome DNA Enrichment Kit followed by MDA with the REPLI-g Single Cell Kit as enrichment methods to improve the yields ofT. pallidumDNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93-98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit propagated isolates, containing >14T. pallidumgenomic copies/μl of sample for SWGA and >129 genomic copies/μl for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens, showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole genome sequencing (WGS) of specimens containing very low numbers ofT. pallidum, which have been challenging until now.

Importance

Syphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogenTreponema pallidumsubspeciespallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions, and if left untreated, can progress through multiple stages with varied clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past two decades, WGS data is needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of a SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers ofT. pallidum.
Screening and Identification of Lassa Virus Endonuclease-targeting Inhibitors from a Fragment-based Drug Development Library
Authors: Lan Xiaohao , Zhang Yueli , Liu Yang , Guo Jiao , Jia Xiaoying , Zhang Mengmeng , Cao Junyuan , Xiao Gengfu , Guo Yu , Wang Wei
Published: July 2021

Lassa virus (LASV) belongs to the Old World genus Mammarenavirus, family Arenaviridae, and order Bunyavirales. Arenavirus contains a segmented negative-sense RNA genome, which is in line with the bunyavirus and orthomyxoviruses. The segmented negative-sense RNA viruses utilize a cap-snatching strategy to provide primers cleavaged from the host capped mRNA for viral mRNA transcription. As a similar strategy and the conformational conservation shared with these viruses, the endonuclease (EN) would serve as an attractive target for developing broad-spectrum inhibitors. Using the LASV minigenome (MG) system, we screened a fragment-based drug development library and found three candidates (F1204, F1781, and F1597) inhibited MG activity. All three candidates also inhibited the prototype arenavirus Lymphocytic choriomeningitis virus (LCMV) MG activity. Furthermore, the investigation revealed that two benzotriazole compounds (F1204 and F1781) effectively inhibited authentic LCMV and severe fever with thrombocytopenia syndrome virus (SFTSV) infections. The combination of either compound with an arenavirus entry inhibitor had significant synergistic antiviral effects. Moreover, both F1204 and F1781 were found to exert the binding ability of LASV EN with binding affinity at the micromolar level. These findings provide a basis for developing benzotriazole compounds as potential candidates for the treatment of segmented negative-sense RNA virus infections.

Importance

Cap-snatching is the mRNA transcription strategy shared by all the segmented, negative-sense RNA viruses. Using a fragment-based drug development (FBDD) library, we tried to screen out the backbone compound to inhibit the endonuclease activity and thus block this kind of virus infection. Two benzotriazole compounds, F1204 and F1781, were identified to inhibit the Lassa virus (LASV) minigenome activity by targeting the LASV EN.
Tributyltin exposure leads to increased adiposity and reduced abundance of leptogenic bacteria in the zebrafish intestine
Authors: de la Torre Canny Sol Gómez , Mueller Olaf , Craciunescu Camil V. , Blumberg Bruce , Rawls John F.
Published: July 2021

The chemical obesogen tributyltin (TBT) is known to promote fat storage in adipose tissue through direct action on vertebrate cells. TBT also has direct toxic effects on microorganisms, raising the possibility that TBT may also promote fat storage in vertebrates by altering their microbiota. Here we show that exposure of conventionally-reared post-embryonic zebrafish to TBT results in increased adiposity, reduced body size, and altered intestinal microbiota composition including reduced relative abundance of Plesiomonas bacteria. To test if those microbiota alterations affected host adiposity, we exposed conventionally-reared zebrafish to intestinal bacterial strains representative of TBT-altered taxa. We found that introduction of a Plesiomonas strain into conventionally-reared zebrafish was sufficient to reduce adiposity and alter intestinal microbiota composition. Using new long-term gnotobiotic zebrafish husbandry methods, we found that colonization of germ-free zebrafish with Plesiomonas was sufficient to reduce host adiposity. Together these results show the leptogenic activity of Plesiomonas on zebrafish hosts, indicating that the ability of TBT to increase adiposity in vivo may be due in part to TBT-mediated modification of the abundance of leptogenic bacteria like Plesiomonas. These findings underscore how complex reciprocal interactions between animals and their microbial and chemical environments can influence energy balance and metabolic health.

IMPORTANCE

Obesogens are environmental chemicals that promote fat storage and are generally thought to exert this effect directly on animal cells. Using zebrafish, we show that the obesogen tributyltin can also promote fat storage by acting upon intestinal microbiota via reduction of bacteria that are sufficient to reduce fat storage.
Small RNA profiling inMycobacteriuminsights into stress adapt ability
Authors: Chen Yingyu , Zhai Wenjun , Zhang Kailun , Zhu Tingting , Su Li , Bermudez Luiz , Chen Huanchun , Guo Aizhen
Published: July 2021

Mycobacteria would encounter a number of environment changes during infection, and respond to it using different mechanisms. sRNA is a posttranscriptionally regulatory system for the function of genes and has been investigated in many other bacteria. Here, we usedMycobacterium tuberculosisandMycobacterium bovisBCG infection models and sequenced the whole bacterial RNAs before and after host cells infection. Comparison of differential expressed sRNAs, by using GO and KEGG, and target predication, was carried out. Six pathogenically relevant stresses, drug resistance test, growth rate and morphology were used for screening and identify sRNAs. From these data, we identified a subset of sRNAs that are differentially expressed in multiple infection groups and stress conditions. We found that many of them were associated with lipid metabolism. Among them, ncBCG427, was significantly down-regulated when BCG entered into macrophages, and was associated with increase of biofilm formation and changed in drug susceptibility. Then, reduction of virulence possibility depends on regulating lipid metabolism.
Molecular mechanisms of stress-induced reactivation in mumps virus condensates
Authors: Zhang Xiaojie , Sridharan Sindhuja , Zagoriy Ievgeniia , Oegema Christina Eugster , Ching Cyan , Pflaesterer Tim , Fung Herman K. H. , Poser Ina , Müller Christoph W. , Hyman Anthony A. , Savitski Mikhail M. , Mahamid Julia
Published: July 2021

Many viruses can establish long-term persistent infections in the human host and cause chronic diseases. Here we combine cell biology, whole-cell proteomics and cryo-electron tomography to uncover how cellular stress disrupts the host-virus equilibrium in persistent infection and induces viral replication, using a model of negative-stranded RNA viruses, the mumps virus. We show that phosphorylation of the largely disordered viral phosphoprotein coincides with increased partitioning of viral polymerase into pre-formed liquid-like condensates and the formation of a stable replication machinery. By obtaining the first atomic models for the authentic mumps virus nucleocapsid, we elucidate a concomitant conformational change that exposes the viral genome to its replication machinery. These events that occur within viral condensates upon stress, together with concerted down-regulation of the host antiviral defense, provide an environment that supports up-regulation of viral replication and constitute a stress-mediated switch that disrupts the host-virus equilibrium in persistent infection.

In Brief

A multi-scale approach uncovers molecular and structural basis of how cellular stress provokes activation of persistent viral infection mediated by biomolecular condensates.
A Massively Parallel Trafficking Assay Accurately Predicts Loss of Channel Function inKCNH2Variants
Authors: Ng Chai-Ann , Ullah Rizwan , Farr Jessica , Hill Adam P. , Kozek Krystian A. , Vanags Loren R. , Mitchell Devyn , Kroncke Brett M. , Vandenberg Jamie I.
Published: July 2021

High throughput genomics has greatly facilitated identification of genetic variants. However, determining which variants contribute to disease causation is challenging with more than half of all missense variants now classified asvariants of uncertain significance(VUS). A VUS leaves patients and their clinicians unable to utilize the variant information in clinical decision-making. In long QT syndrome type 2,KCNH2channel function is directly associated with disease presentation. Therefore, functional phenotypingof KCNH2variants can provide direct evidence to aid variant classification. Here, we investigated the expression of all codon variants in exon 2 ofKCNH2using a massively parallel trafficking assay and for a subset of 458 single nucleotide variants compared the results with peak tail current density and gating using automated patch clamp electrophysiology. Trafficking could correctly classify loss of peak tail current density variants with an AUC reaching 0.94 compared to AUCs of 0.75 to 0.8 forin silicovariant classifiers. We suggest massively parallel trafficking assays can provide prospective and accurate functional assessment for all missense variants inKCNH2and most likely many other ion channels and membrane proteins.
Functional analysis of Mmd2 and related PAQR genes during sex determination in mice
Authors: Zhao Liang , Thomson Ella , Ng Ee Ting , Longmuss Enya , Svingen Terje , Bagheri-Fam Stefan , Quinn Alexander , Harley Vincent R. , Harrison Leonard C. , Pelosi Emanuele , Koopman Peter
Published: July 2021

Sex determination in eutherian mammals is controlled by the Y-linked gene Sry, which drives the formation of testes in male embryos. Despite extensive study, the genetic steps linking Sry action and male sex determination remain largely unknown. Here, we focused on Mmd2, a gene that encodes a member of the progestin and adipoQ receptor (PAQR) family. We show that Mmd2 is expressed during the sex-determining period in XY but not XX gonads, specifically in the Sertoli cell lineage which orchestrates early testis development. Analysis of knockout mice deficient in Sox9 and Sf1 revealed that Mmd2 operates downstream of these known sex-determining genes. However, when we used CRISPR to ablate Mmd2 in the mouse, fetal testis development appeared to progress normally. To determine if other genes might have compensated for the loss of Mmd2, we identified the closely related PAQR family members Paqr8 and Mmd as also being expressed during testis development. We used CRISPR to generate mouse strains deficient in Paqr8 and Mmd, but both knockout lines appeared phenotypically normal and fertile. Finally, we generated Mmd2;Mmd and Mmd2;Paqr8 double-null embryos and again observed normal testis development. These results may reflect functional redundancy among these factors. Our findings highlight the difficulties involved in identifying genes with a functional role in sex determination and gonadal development through expression screening and loss-of-function analyses of individual candidate genes, and may help to explain the paucity of genes in which variations have been found to cause human disorders/differences of sex development.
TGFβ signalling is required to maintain pluripotency of human naïve pluripotent stem cells
Authors: Osnato Anna , Brown Stephanie , Krueger Christel , Andrews Simon , Collier Amanda J. , Nakanoh Shota , Londoño Mariana Quiroga , Wesley Brandon T. , Muraro Daniele , Brumm Sophie , Niakan Kathy , Vallier Ludovic , Ortmann Daniel , Rugg-Gunn Peter J.
Published: July 2021

The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGFβ/Activin/Nodal signalling. In contrast, the signalling requirements of naïve human pluripotency have not been fully established. Here, we demonstrate that TGFβ signalling is required to maintain naïve hPSCs. The downstream effector proteins – SMAD2/3 – bind common sites in naïve and primed hPSCs, including shared pluripotency genes. In naïve hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naïve pluripotency genes. Inhibiting TGFβ signalling in naïve hPSCs causes the downregulation of SMAD2/3-target genes and pluripotency exit. Single-cell analyses reveal that naïve and primed hPSCs follow different transcriptional trajectories after inhibition of TGFβ signalling. Primed hPSCs differentiate into neuroectoderm cells, whereas naïve hPSCs transition into trophectoderm. These results establish that there is a continuum for TGFβ pathway function in human pluripotency spanning a developmental window from naïve to primed states.
Unconventional tonicity-regulated nuclear trafficking of NFAT5 mediated by KPNB1, XPOT and RUVBL2
Authors: Cheung Chris Y. , Huang Ting-Ting , Chow Ning , Zhang Shuqi , Zhao Yanxiang , Wong Catherine C.L. , Boassa Daniela , Phan Sebastien , Ellisman Mark H , Yates John R. , Xu SongXiao , Yu Zicheng , Zhang Yajing , Zhang Rui , Ng Ling Ling , Ko Ben C.B.
Published: July 2021

NFAT5 is the only known mammalian tonicity-responsive transcription factor functionally implicated in diverse physiological and pathological processes. NFAT5 activity is tightly regulated by extracellular tonicity but the underlying mechanisms remain elusive. We demonstrated that NFAT5 enters the nucleus via the nuclear pore complex. We also found that NFAT5 utilizes a non-canonical nuclear localization signal (NFAT5-NLS) for nuclear imports. siRNA screening revealed that karyopherin β1 (KPNB1) drives nuclear import of NFAT5 via directly interacting with NFAT5-NLS. Proteomics analysis and siRNA screening further revealed that nuclear export of NFAT5 under hypotonicity is mediated by Exportin-T, and that it requires RuvB-Like AAA type ATPase 2 (RUVBL2) as an indispensable chaperone. Our findings have identified KPNB1 and RUVBL2 as key molecules responsible for the unconventional tonicity-regulated nucleocytoplasmic shuttling of NFAT5. These findings offer an opportunity for developing novel NFAT5 targeting strategies that are potentially useful for the treatment of diseases associated with NFAT5 dysregulation.
Wideband circularly polarized antenna with metallic walls for L-band applications
Authors: Pourbagher Mohammad , Ghobadi Changiz , Nourinia Javad , Naderali Rahim
Published: July 2021

Purpose

To achieve right-hand circular polarization (RHCP), a 3-dB Wilkinson power divider with a λ/4 phase shifter is used. The crossed-dipoles are placed at almost λ/4 elevation on the ground plane and connected to two coaxial cables. Experiments show that the impedance bandwidth of 49.40% (913.7–1,513.1 MHz) and axial ratio bandwidth (ARBW) of 22.88% (1,145.8–1,441.8 MHz) are achieved.

Design/methodology/approach

In this study, a wideband crossed-dipole antenna with circularly polarized (CP) radiation for L-band satellite and radar applications is presented. The proposed CP antenna comprises two orthogonally placed printed dipoles, a quadrature coupler and a box-shaped ground plane.

Findings

Furthermore, by fixing the box-shaped ground plane under the radiators, 5.13 dBic RHCP peak gain at 1,300 MHz and maximum half-power beamwidth (HPBW) of 84.5° at 1,170 MHz are realized for the antenna.

Originality/value

Eight metallic walls are connected to four corners of the substrate to stabilize the radiation properties in this study. Results show that the ARBW and front-to-back ratio are improved and the maximum HPBW around 127° across the operating frequency band is achieved. The proposed CP antenna is a good candidate for Global Positioning System (GPS) L2 (1.227 GHz), GPS L5 (1.176 GHz) and air route surveillance radar system at 1,215–1,390 MHz frequency band.
The effect of physical work environment on creativity among artists’ residencies
Authors: Motalebi Ghasem , Parvaneh Avishan
Published: July 2021

Purpose

The purpose of this study is to investigate the role of the physical environment characteristics on artists’ creativity.

Design/methodology/approach

Based on mixed-method of research the data was collected through questionnaires and interviews with 40 artists. The parameters of the physical environment characteristics included light, object design, color, window, the possibility of communication, flexibility and the existence of personal space.

Findings

The effect of these factors used simply and naturally on artists’ creativity was evaluated to be positive. It was found that if these factors were not present and only a simple, non-inspiring space was designed, the results would be simpler and less creative. It was suggested that designers need to design a space according to the artists’ individual and social needs and their perceptions.

Research limitations/implications

This study is mostly limited to Iranian artists; however, it is a starting point for broader implications.

Originality/value

The main contribution of this research is providing environmental characteristics, which can assist in creating an appropriate workspace for artists.
Fuel consumption in mining industry using partial least squares structural equation modeling approach
Authors: Yousefi Nejad Attari Mahdi , Farrashzadeh Miandoab Tohid , Ejlali Babak , Torkayesh Ali Ebadi
Published: July 2021

Purpose

Consumption of fossil fuels due to their non-renewability has always been one of the fundamental problems among energy-related issues. Major dependence of mining equipment and activities on energy, fuel and adequate fuel allocation has become of great importance in fuel consumption of mines. Therefore, this study aims to propose a model for optimal fuel allocation for mining industry.

Design/methodology/approach

In this study, partial least squares structural equation modeling (PLS-SEM), as one of the well-known statistical methods, is used to model and analyze fuel consumption pattern in mine industry.

Findings

To show the applicability of the proposed model, the study investigates the model for a real mine in Iran. In this regard, real data of important factors affecting mine fuel consumption are collected. Results of statistical models construct a general formula to calculate the fuel consumption based on three main variables.

Originality/value

Policymaking is one of the important tasks in energy-related organizations. One of the main sectors that uses noticeable amount of fossil fuels is mining industry. Despite the government subsidy for mining in Iran, there is a significant price difference between the price of allocated fuel for mine and the price of the same fuel in the open market. Therefore, this study implements PLS-SEM approach to formulate the fuel consumption pattern under all possible fuel consumption indicators to enable policymakers to make reliable decision for future purposes.
The European Union oil dependency: a threat to economic growth and diplomatic freedom
Authors: Acevedo Rafael Alexis , Lorca-Susino Maria
Published: July 2021

Purpose

This paper provides a general review of the current energy dependency of the European Union (EU) and the possible threat that it poses to economic growth and diplomatic freedom.

Design/methodology/approach

Systematic literature review with a narrative approach to analyze historical data, statistics and energy policies and determine if the EU oil dependency represents a threat to economic growth and diplomatic freedom. In addition, a review of the US policy “America first” is also included to analyze its impact on the EU.

Findings

The energy dependency rate of the EU increased 12 percentage points from 1990 to 2018. Russia has become the largest oil supplier for the EU tripling Norway, the largest supplier in the 1990s. The oil dependency of the EU on Russia is a difficult situation where guaranteed energy supply and diplomatic freedom becomes a national political controversy. Even though the USA is currently a top world exporter of oil, the EU does not rely on the USA. The findings suggest that the EU needs to secure a reliable energy supplier to guarantee economic growth, reduce energy scarcity and enhance diplomatic freedom.

Originality/value

This paper provides a historical examination of the EU oil dependency considering its impact on economic growth and diplomatic freedom.
Corporate ethical behavior and the cost of equity capital: evidence from the world’s most ethical companies
Authors: Zouari-Hadiji Rim , Chouaibi Yamina
Published: July 2021

Purpose

This paper aims to examine the effect of the corporate ethical approach on the cost of equity capital. This study is conducted on a large international sample on behalf of the world’s most engaged firms from an ethical point of view in 2015.

Design/methodology/approach

The multivariate linear regression model is used to meet the purpose of this study and research hypotheses are also examined using a sample of 80 of most ethical firms in the world during the year 2015. Moreover, three variables (i.e. business ethics, corporate social responsibility and executive compensation based on the achievement of sustainable development goals) are used to reflect the corporate ethical approach and the implied cost of equity capital is used for estimating the cost of equity. In this regard, equity cost estimation is the most appropriate approach to test the effect of business ethics on the cost of financing firms.

Findings

Based on a sample of 80 firms emerging as the world’s most ethical firms in 2015, the results revealed that firms with better ethics scores are significantly associated with a reduced cost of equity capital. This paper also demonstrates that the executive incentive pays that are based on the objectives of sustainable development are able to explain different outcomes regarding the relation between corporate ethical behaviors and the cost of equity. These findings support arguments in the literature that firms with socially responsible practices have a higher valuation and lower risk.

Originality/value

This study provides implications for global regulators and policymakers when setting social reporting standards, suggesting that corporate ethical engagement reduces the cost of equity capital by decreasing the information asymmetry and thereby reducing the firms’ risk. Therefore, the findings may be informative to international managers and investors when considering the effect of business ethics on the firm’s ex-ante cost of equity. In this perspective, the voluntary disclosure of information makes it possible to mitigate the problems of asymmetry of information and conflict of interest between the firm and its main providers of capital, which could reduce the cost of equity.
Trade-based money laundering (TBML) empowers criminals to run free post-Brexit
Authors: Marzouk Mariola Jolanta
Published: July 2021

Purpose

This paper aims to provide unique empirical findings exploring the impact of the UK’s post-Brexit Economic Strategy to boost trade with developing countries on the UK banking sector’s ability to manage trade-based money laundering risks.

Design/methodology/approach

Exploratory research design that used structured literature review, followed by semi-structured interviews with key subject matter experts employed by large UK banks.

Findings

Both banks and law enforcement struggle to prioritise trade-based money laundering (TBML) intelligence discovery due to deficient skills, resources, technology and lack of strong regulatory stimulus. The regulated sector calls for the UK anti-money laundering (AML) reform that would better incentivise TBML deterrence, yet the Government underestimates the money laundering risks while trading with high-risk jurisdictions post-Brexit.

Research limitations/implications

The findings are based on a small sample of six semi-structured interviews with difficult to access population of key subject matter experts. Despite the small sample, participants provided well-articulated and informed insights.

Practical implications

The UK’s post-Brexit Economic Strategy to boost trade with developing countries downplays the TBML risks it carries. The findings should alert UK banks, law enforcement and the Government who will collectively bear the responsibility to effectively manage TBML while enabling smooth trading.

Originality/value

The research provides unique perceptions of UK banks’ senior subject matter experts on managing TBML threats from opportunistic criminals.
Examining organization‐public relationships in crises: A thematic meta‐analysis of updated literature from 1997 to 2019
Authors: Cheng Yang , Funkhouser Caroline , Raabe Tessa , Cross Rebecca
Published: July 2021

In crises, relationships between organizations and publics are under pressure. Building or managing relationships in crises has attracted heated discussions among scholars in the field of public relations and business communication over the past few decades. To provide an updated systematic analysis of this area, this study presents a review of 131 published journal articles from 1997 to 2019. Findings identified theoretical and methodological trends in current relationship management research in crises. In addition, five themes of relationships in crises were demonstrated. These included the antecedents, outcomes, mediating/moderating role, networks and the process of relationships. Results also indicated that crisis communication strategies, crisis types and prior crisis history were key precursors of (re‐)building relationships in the literature. Theoretical and practical implications were discussed.
Debriefing immediately after intubation in a children's emergency department is feasible and contributes to measurable improvements in patient safety
Authors: Cincotta Domenic R , Quinn Nuala , Grindlay Joanne , Sabato Stefano , Fauteux‐Lamarre Emmanuelle , Beckerman David , Carroll Terry , Long Elliot
Published: July 2021

Objective

In 2013, our intubations highlighted a safety gap – only 49% achieved first‐pass success without hypoxia or hypotension. NAP4 recommended debriefing after intubation, but limited published methods existed. Primary aim is to implement a feasible process for immediate debriefing and feedback for emergency airway management. Secondary aims are to contribute to reduced frequency of adverse intubation‐related events and implement qualitative improvements in patient safety through team reflection and feedback.

Methods

A component of a prospective quality improvement (QI) study over 4 years in the ED of the Royal Children's Hospital, Melbourne, Australia. Debrief and feedback after intubation was one of seven study interventions. Targeted staff training and involvement of departmental leaders occurred. A post‐intervention cohort was audited in 2016. Analysis included the Team Emergency Assessment Measure.

Results

Immediate post‐event debriefing occurred in 39 (85%) of 46 intubations. Debriefing was short (median duration 5 min, interquartile range [IQR] 5–10) and soon after (median time 20 min, IQR 5–60). Commonest location was the resuscitation room (92%), led by the team leader (97%). Commonest barrier preventing immediate debriefing was excessive workload. Two QI process measures were assessed during debriefing (adequate resuscitation, airway plan) and case summaries distributed for 100% of intubations. Performance outcomes included contribution to 78% first‐pass success without hypoxia or hypotension. Team reflection prompted changes to environment (signage, stickers), training (skill drills), teamwork and process (communication, clinical event debriefing).

Conclusion

Structured and targeted debriefing after intubating children in the ED is feasible and contributes to measurable and qualitative improvements in patient safety.
The role of professional identity in HRM implementation: Evidence from a case study of job redesign
Authors: Chen Yaru , Currie Graeme , McGivern Gerry
Published: July 2021

How and why do employees from heterogeneous professional and occupational groups respond to the same HR practice differently—job redesign—and what is the implication of this for human resource management (HRM) implementation? Drawing upon a qualitative case study of job redesign in the English health and social care sector, affecting three distinct groups of employees, we highlight the different ways these employees respond to the implementation of job redesign over time. We contribute to a nascent literature discussing employees' role in HRM implementation. We also show that different types of professionals (occupational professionals, paraprofessionals, and organisational professionals) respond to job redesign differently, depending on its impact on their professional identity, which, in turn, affects its implementation.