bluuebunny/crossref_metadata_2025 huggingface dataset:
The robustness of a simple dynamic model of island biodiversity to geological and eustatic change
Authors: Neves Pedro Santos , Lambert Joshua W. , Valente Luis , Etienne Rampal S.
Published: July 2021

Aim

Biodiversity on islands is affected by various geo-physical processes and sea-level fluctuations. Oceanic islands (never connected to a landmass) are initially vacant with diversity accumulating via colonisation and speciation, followed by a decline as islands shrink. Continental islands have species upon formation (when disconnected from the mainland) and may have transient land-bridge connections. Theoretical predictions for the effects of these geo-processes on rates of colonisation, speciation and extinction have been proposed, but methods of phylogenetic inference assume only oceanic island scenarios without accounting for island ontogeny, sea-level changes or past landmass connections. Here, we analyse to what extent ignoring geodynamics affects the inference performance of a phylogenetic island model, DAISIE, when confronted with simulated data that violate its assumptions.

Location

Simulation of oceanic and continental islands.

Methods

We extend the DAISIE simulation model to include: area-dependent rates of colonisation and diversification associated with island ontogeny and sea-level fluctuations, and continental islands with biota present upon separation from the mainland, and shifts in rates to mimic temporary land-bridges. We quantify the error made when geo-processes are not accounted for by applying DAISIE’s inference method to geodynamic simulations.

Results

We find that the robustness of the model to dynamic island area is high (error is small) for oceanic islands and for continental islands that have been separated for a long time, suggesting that, for these island types, it is possible to obtain reliable results when ignoring geodynamics. However, for continental islands that have been recently or frequently connected, robustness of DAISIE is low, and inference results should not be trusted.

Main conclusions: This study highlights that under a large proportion of island biogeographic geo-scenarios (oceanic islands and ancient continental fragments) a simple phylogenetic model ignoring geodynamics is empirically applicable and informative. However, recent connection to the continent cannot be ignored, requiring development of a new inference model.
Resiniferatoxin hampers the nocifensive response ofCaenorhabditis elegansto noxious heat, and pathway analysis revealed that the Wnt signaling pathway is involved
Authors: Ben Salem Jennifer , Nkambeu Bruno , Arvanitis Dina N , Beaudry Francis
Published: July 2021

Resiniferatoxin (RTX) is a metabolite extracted fromEuphorbia resinifera. RTX is a potent capsaicin analog with specific biological activities resulting from its agonist activity with the transient receptor potential channel vanilloid subfamily member 1 (TRPV1). RTX has been examined as a pain reliever, and more recently, investigated for its ability to desensitize cardiac sensory fibers expressing TRPV1 to improve chronic heart failure (CHF) outcomes using validated animal models.Caenorhabditis elegans(C. elegans) expresses orthologs of vanilloid receptors activated by capsaicin, producing antinociceptive effects. Thus, we usedC. elegansto characterize the antinociceptive properties and performed proteomic profiling to uncover specific signaling networks. After exposure to RTX, wild-type (N2) and mutantC. eleganswere placed on petri dishes divided into quadrants for heat stimulation. The thermal avoidance index was used to phenotype each testedC. elegansexperimental group. The data revealed for the first time that RTX can hamper the nocifensive response ofC. elegansto noxious heat (32°C – 35°C). The effect was reversed 6 h after RTX exposure. Additionally, we identified the RTX target, theC. eleganstransient receptor potential channel OCR-3. The proteomics and pathway enrichment analysis results suggest that Wnt signaling is triggered by the agonistic effects of RTX onC. elegansvanilloid receptors.
AGO1 regulates pericentromeric regions in mouse embryonic stem cells
Authors: Müller Madlen , Fäh Tara , Schaefer Moritz , Hermes Victoria , Luitz Janina , Stalder Patrick , Arora Rajika , Ngondo Richard Patryk , Ciaudo Constance
Published: July 2021

Argonaute proteins (AGOs), that play an essential role in cytosolic post-transcriptional gene silencing, have been also reported to function in nuclear processes like transcriptional activation or repression, alternative splicing and, chromatin organization. As most of these studies have been conducted in human cancer cell lines, the relevance of AGOs nuclear functions in the context of mouse early embryonic development remains uninvestigated. Here, we examined a possible role of the AGO1 protein on the distribution of constitutive heterochromatin in mouse Embryonic Stem Cells (mESCs). We observed a specific redistribution of the repressive histone mark H3K9me3 and the heterochromatin protein HP1α, away from pericentromeric regions upon Ago1 depletion. Furthermore, we demonstrated that major satellite transcripts are strongly upregulated in Ago1_KO mESCs and that their levels are partially restored upon AGO1 rescue. We also observed a similar redistribution of H3K9me3 and HP1α in Drosha_KO mESCs, suggesting a role for microRNAs (miRNAs) in the regulation of heterochromatin distribution in mESCs. Finally, we showed that specific miRNAs with complementarity to major satellites can partially regulate the expression of these transcripts.

Summary blurb

Depletion of AGO1 in mESCs leads to a redistribution of H3K9me3 and HP1α away from pericentromeric regions and is accompanied by an upregulation of major satellites transcripts.
Low affinity integrin states have faster binding kinetics than the high affinity state
Authors: Li Jing , Yan Jiabin , Springer Timothy A.
Published: July 2021

Integrin conformational ensembles contain two low-affinity states, bent-closed and extended-closed, and an active, high-affinity, extended-open state. It is widely thought that integrins must be activated before they bind ligand; however, one model holds that activation follows ligand binding. As ligand-binding kinetics are not only rate limiting for cell adhesion but also have important implications for the mechanism of activation, we measure them here for integrins α4β1 and α5β1 and show that the low-affinity states bind substantially faster than the high-affinity state. On and off-rate measurements are similar for integrins on cell surfaces and ectodomain fragments. Although the extended-open conformation’s on-rate is ∼20-fold slower, its off-rate is ∼25,000-fold slower, resulting in a large affinity increase. The tighter ligand-binding pocket in the open state may slow its on-rate. These kinetic measurements, together with previous equilibrium measurements of integrin conformational state affinity and relative free energy on intact cells, are key to a definitive understanding of the mechanism of integrin activation.
EXPRESSION OF A SECRETABLE, CELL-PENETRATING CDKL5 PROTEIN ENHANCES THE EFFICACY OF AAV VECTOR-MEDIATED GENE THERAPY FOR CDKL5 DEFICIENCY DISORDER
Authors: Medici Giorgio , Tassinari Marianna , Galvani Giuseppe , Bastianini Stefano , Gennaccaro Laura , Loi Manuela , Mottolese Nicola , Alvente Sara , Berteotti Chiara , Sagona Giulia , Lupori Leonardo , Baggett Helen Rappe , Zoccoli Giovanna , Giustetto Maurizio , Muotri Alysson , Pizzorusso Tommaso , Nakai Hiroyuki , Trazzi Stefania , Ciani Elisabetta
Published: July 2021

No therapy is currently available for CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although delivery of a wild-type copy of the mutated gene to cells represents the most curative approach for a monogenic disease, proof-of-concept studies highlight significant efficacy caveats for brain gene therapy. Herein, we used a secretable TATk-CDKL5 protein to enhance the efficiency of a gene therapy for CDD. We found that, although AAVPHP.B_Igk-TATk-CDKL5 and AAVPHP.B_CDKL5 vectors had similar brain infection efficiency, the AAVPHP.B_Igk-TATk-CDKL5 vector led to a higher CDKL5 protein replacement due to secretion and transduction of the TATk-CDKL5 protein into the neighboring cells. Importantly, Cdkl5 KO mice treated with the AAVPHP.B_Igk-TATk-CDKL5 vector showed a behavioral and neuroanatomical improvement in comparison with vehicle-treated Cdkl5 KO mice or Cdkl5 KO mice treated with the AAVPHP.B_CDKL5 vector, indicating that a gene therapy based on a secretable recombinant TATk-CDKL5 protein is more effective at compensating Cdkl5-null brain defects than gene therapy based on the expression of the native CDKL5.
EMDA: A Python package for Electron Microscopy Data Analysis
Authors: Warshamanage Rangana , Yamashita Keitaro , Murshudov Garib N.
Published: July 2021

An open-source Python library EMDA for cryo-EM map and model manipulation is presented with a specific focus on validation. The use of several functionalities in the library is presented through several examples. The utility of local correlation as a metric for identifying map-model differences and unmodeled regions in maps, and how it is used as a metric of map-model validation is demonstrated. The mapping of local correlation to individual atoms, and its use to draw insights on local signal variations are discussed. EMDA’s likelihood-based map overlay is demonstrated by carrying out a superposition of two domains in two related structures. The overlay is carried out first to bring both maps into the same coordinate frame and then to estimate the relative movement of domains. Finally, the map magnification refinement in EMDA is presented with an example to highlight the importance of adjusting the map magnification in structural comparison studies.
Quantitative Profiling of Adaptation to Cyclin E Overproduction
Authors: Limas Juanita C. , Littlejohn Amiee N. , House Amy M. , Kedziora Katarzyna M. , Mouery Brandon L. , Ma Boyang , Fleifel Dalia , Walens Andrea , Aleman Maria M. , Dominguez Daniel , Cook Jeanette Gowen
Published: July 2021

Cyclin E/CDK2 drives cell cycle progression from G1 to S phase. Cyclin E overproduction is toxic to mammalian cells, although the gene encoding cyclin E (CCNE1) is overexpressed in some cancers. To gain insight into how cancer cells tolerate high cyclin E, we extensively characterized non-transformed epithelial cells throughout a time course of chronic cyclin E overproduction. Cells overproducing human cyclin E, but not cyclin D or cyclin A, briefly experienced truncated G1 phases, then endured a transient period of DNA replication origin underlicensing, replication stress, and severely impaired proliferation. Individual cells displayed substantial intercellular heterogeneity in cell cycle dynamics and CDK activity. Each phenotype improved rapidly despite maintaining high cyclin E-associated activity. Transcriptome analysis revealed that adapted cells downregulated a cohort of G1-regulated genes. Withdrawing cyclin E induction only partially reversed the intermediate licensing phenotype of adapted cells indicating that adaptation is at least partly independent of mutations. This study provides evidence that mammalian cyclin E/CDK inhibits origin licensing by an indirect mechanism through premature S phase onset and provides further insight into the relationship between CDK activity and licensing in mammals. It serves as an example of specific oncogene adaptation that may recapitulate molecular changes during tumorigenesis.
Barcoded reciprocal hemizygosity analysis via sequencing illuminates the complex genetic basis of yeast thermotolerance
Authors: Abrams Melanie B. , Chuong Julie N. , AlZaben Faisal , Dubin Claire A. , Skerker Jeffrey M. , Brem Rachel B.
Published: July 2021

Decades of successes in statistical genetics have revealed the molecular underpinnings of traits as they vary across individuals of a given species. But standard methods in the field can’t be applied to divergences between reproductively isolated taxa. Genome-wide reciprocal hemizygosity mapping (RH-seq), a mutagenesis screen in an inter-species hybrid background, holds promise as a method to accelerate the progress of interspecies genetics research. Here we describe an improvement to RH-seq in which mutants harbor barcodes for cheap and straightforward sequencing after selection in a condition of interest. As a proof of concept for the new tool, we carried out genetic dissection of the difference in thermotolerance between two reproductively isolated budding yeast species. Experimental screening identified dozens of candidate loci at which variation between the species contributed to the thermotolerance trait. Hits were enriched for mitosis genes and other housekeeping factors, and among them were multiple loci with robust sequence signatures of positive selection. Together, these results shed new light on the mechanisms by which evolution solved the problems of cell survival and division at high temperature in the yeast clade, and they illustrate the power of the barcoded RH-seq approach.
Interstitial and cerebrospinal fluid exchanging process revealed by phase alternate labeling with null recovery MRI
Authors: Li Anna M. , Xu Jiadi
Published: July 2021

Purpose

To develop Phase Alternate LAbeling with Null recovery (PALAN) MRI methods for the quantification of interstitial to cerebrospinal fluid flow (ICF) and cerebrospinal to interstitial fluid flow (CIF) in the brain.

Method

In both T1-PALAN and apparent diffusion coefficient (ADC)-PALAN MRI methods, the cerebrospinal fluid (CSF) signal was nulled, while the residual interstitial fluid (ISF) was labeled by alternating the phase of pulses. ICF was extracted from the difference between the recovery curves of CSF with and without labeling. Similarly, CIF was measured by the T2-PALAN MRI method by labeling CSF, which took advance of the significant T2 difference between CSF and parenchyma.

Results

Both T1-PALAN and ADC-PALAN observed a rapid occurrence of ICF at 67±56 ms and 13±2 ms interstitial fluid transit times, respectively. ICF signal peaked at 1.5 s for both methods. ICF was 1153±270 ml/100ml/min with T1-PALAN in the third and lateral ventricles, which was higher than 891±60 ml/100ml/min obtained by ADC-PALAN. The results of the T2-PALAN suggested the ISF exchanging from ependymal layer to the parenchyma was extremely slow.

Conclusion

The PALAN methods are suitable tools to study ISF and CSF flow kinetics in the brain.
Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling
Authors: Griffiths Samuel C. , Tan Jia , Wagner Armin , Blazer Levi , Adams Jarret J. , Srinivasan Srisathya , Moghisaei Shayan , Sidhu Sachdev S. , Siebold Christian , Ho Hsin-Yi Henry
Published: July 2021

The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, Brachydactyly B and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.
Determinants of the quality of external board evaluation in the UK
Authors: Sobhan Abdus , Adegbite Emmanuel
Published: July 2021

Purpose

This study aims to examine the influence of the following on the quality of externally facilitated board evaluation, namely, the timing of adoption of external board evaluation, type of evaluators and the independence of external facilitators.

Design/methodology/approach

The statements on board evaluation in annual reports of a sample of FTSE 350 companies were content analysed to measure the quality of externally facilitated board evaluation. This paper then used descriptive analysis and inferential statistics to demonstrate the possible association between the timing of adoption, as well as the type and independence of external facilitators and the quality of externally facilitated board evaluation.

Findings

Results reveal some effects of the timing of adoption, as well as the type and independence of external facilitators on the quality of externally facilitated board evaluation.

Practical implications

Shareholders should be aware of the timing of adoption, as well as consider the types and independence of external facilitators, given their influence on the quality of externally facilitated board evaluation. Regulatory authorities should provide more specific guidance on what types of professional organisations can be engaged as external facilitators and on the implementation of externally facilitated board evaluation, to promote its quality.

Originality/value

Several studies have provided theoretical accounts on how board evaluation should be conducted to ensure its effectiveness. However, there is a dearth of empirical literature, which examines the quality of externally facilitated board evaluation. This study develops a quality measure for externally facilitated board evaluation and shows the effect of the timing of adoption, types and independence of external facilitators on its quality. The study forges ahead institutional theorising of external board evaluation.
Tolerance zones: a pragmatic approach to respond to problems related to open alcohol and drug scenes in Bremen/Germany
Authors: Prepeliczay Susanna , Schmidt-Semisch Henning
Published: July 2021

Purpose

This study aims to describe and analyse an approach in the city of Bremen (Germany) to establish streetwork-supported tolerance zones for local open drug and alcohol scenes to reduce related disorder and nuisance in public spaces.

Design/methodology/approach

The qualitative methodology included systematic participant observations at public sites of drug and alcohol use, and problem-centred interviews with different groups of respondents (residents, passers-by, trades people, drug users, experts from addiction help and police).

Findings

In residential districts, tolerance zones were well accepted by their target group and found to reduce perceived disorder and nuisance in public space. However, their success depends on the social and spatial conditions of the chosen location, its surrounding urban infrastructure, cooperation among local actors and characteristics of drug using groups.

Originality/value

Usually, policing of open drug scenes focuses on repression and law enforcement. The example of Bremen suggests that streetwork-supported tolerance zones dedicated to the drug scene can substantially reduce disorder and nuisance in public space.
The volatility characteristics of Vietnamese coffee export price and transmission mechanism of influencing factors: a Markov switching approach
Authors: Dang TrungTuyen , Caihong Zhang , Nguyen ThiHong , Nguyen NgocTrung , Tran Cuong
Published: July 2021

Purpose

This study aims to examine the transmission mechanism of factors on the characteristic fluctuation of Vietnamese coffee bean export price (PVN).

Design/methodology/approach

Applying Markov switching–vector autoregressive model.

Findings

Significantly, the empirical results showed that the transmission of independent variables on PVN is non-linear, and the fluctuation of PVN is affected by many factors, especially PVN in the previous period. In addition, the effect of Robusta coffee price was the greatest with coefficient is 0.28785, and the correlation between PVN and it was also the highest in both regimes with coefficients are 0.5317 and 0.3959, respectively.

Originality/value

These obtained results are in accordance with reality, as Vietnam is the largest exporter of Robusta coffee in the world.
Security and privacy of adolescents in social applications and networks: legislative aspects and legal practice of countering cyberbullying on example of developed and developing countries
Authors: Ghandour Ahmad , Shestak Viktor , Sokolovskiy Konstantin
Published: July 2021

Purpose

This paper aims to study the developed countries’ experience on the cyberbullying legal regulation among adolescents, to identify existing shortcomings in the developing countries’ laws and to develop recommendations for regulatory framework improvement.

Design/methodology/approach

The authors have studied the state regulatory practice of the UK, the USA, Canada, Malaysia, South Africa, Turkey, UAE and analyzed the statistics of 2018 on the cyberbullying manifestation among adolescents in these countries.

Findings

The study results can encourage countries to create separate cyberbullying legislation and periodically review and modify already existing legislation.

Originality/value

The study provides a list of the recommendations to regulate cybercrime in developing countries and prevent it as well. The results may contribute to creating laws related to the regulation of cyberbullying in countries where such legislation does not exist yet or existing regulatory legal acts do not bring the expected results, namely, in Post-Soviet countries and other developing countries of the world.
The influence of private family firm characteristics on audit fees: the family name as a red flag
Authors: Schierstedt Bennet , Corten Maarten
Published: July 2021

Purpose

This study aims to examine the relationship between family firm characteristics and audit fees. It also examines the extent to which the family name is considered a red flag during the risk assessment of these firm characteristics.

Design/methodology/approach

Using an external panel data set that includes 1,252 firm-year observations of 204 private German firms with a time series from 2010–2016, regression analyses were conducted to test the hypotheses.

Findings

This study’s results indicate that family involvement in management and the supervisory board are negatively related to audit fees, suggesting less demand and supply of audit effort due to lower Type I agency conflicts. Family ownership is found to be positively associated with audit fees due to higher Type II agency conflicts. Moreover, the negative effect of family involvement in management on audit fees becomes weaker if the firm name contains the family name, indicating that it is considered a red flag by auditors during their risk assessment.

Originality/value

Prior studies that examined audit fees in family firms mainly compared family firms to non-family firms. However, auditors are not likely to look at firms in a dichotomous way during their risk assessment, especially as there are numerous definitions of family firms. Instead, they will assess the underlying characteristics regarding management, ownership and governance, although a firm name containing the family name may influence this assessment. This study contributes to the literature by accounting for the heterogeneity of family firms and examining how auditors will assess this heterogeneity.
New Zealand Government’s budgetary response to the COVID-19 pandemic
Authors: Narayan Anil K. , Kommunuri John
Published: July 2021

Purpose

This paper aims to provide a commentary on how well the New Zealand (NZ) Government has used the budget as a tool to tackle the social and economic problems associated with the COVID-19 pandemic. The role of public budgeting as a political instrument is also critiqued.

Design/methodology/approach

An analysis was carried out of relevant documents that included government policy statements, budgets, news articles and website information on the pandemic. Meaningful interpretation of information and reflections helped provide the basis of the commentary.

Findings

Public budgeting has a prominent role in addressing a major global crisis. Budgets need to quickly respond to the needs of the moment in saving lives and sustaining people’s well-being, businesses and the economy. In a crisis situation, the social, political and economic factors become crucial determinants of budgetary policy measures. Although strong political leadership is required to deliver budgets under unimaginable circumstances, the ideology of the political party in government can be a powerful predictor of fiscal policies. Crisis budgeting will result in mounting budget deficits and public debts that will take many years for future generations to pay back.

Practical implications

This paper provides a significant learning for other nations. These lessons will guide budget policymakers to prepare better for potential crisis in the future.

Originality/value

This paper is original and based on the NZ Government’s budgetary response to the COVID-19 pandemic. It will be valuable in formulating budget policies and public funding decisions in a major crisis.
Application of total interpretive structural modeling for analyzing factors of additive manufacturing and industry 4.0 integration
Authors: Wankhede Vishal Ashok , S. Vinodh
Published: July 2021

Purpose

The purpose of this paper is to develop a model based on the total interpretive structural modeling (TISM) approach for analysis of factors of additive manufacturing (AM) and industry 4.0 (I4.0) integration.

Design/methodology/approach

AM integration with I4.0 is attributed due to various reasons such as developing complex shapes with good quality, real-time data analysis, augmented reality and decentralized production. To enable the integration of AM and I4.0, a structural model is to be developed. TISM technique is used as a solution methodology. TISM approach supports establishing a contextual relationship-based structural model to recognize the influential factors. Cross-impact matrix multiplication applied to classification (MICMAC) analysis has been used to validate the TISM model and to explore the driving and dependence power of each factor.

Findings

The derived structural model indicated the dominant factors to be focused on. Dominant factors include sensor integration (F9), resolution (F12), small build volumes (F19), internet of things and lead time (F14). MICMAC analysis showed the number of driving, dependent, linkage and autonomous factors as 3, 2, 12 and 3, respectively.

Research limitations/implications

In the present study, 20 factors are considered. In the future, additional factors could be considered based on advancements in I4.0 technologies.

Practical implications

The study has practical relevance as it had been conducted based on inputs from industry practitioners. The industry decision-makers and practitioners may use the developed TISM model to understand the inter-relationship among the factors to take appropriate measures before adoption.

Originality/value

The study on developing a structural model for analysis of factors influencing AM and I4.0 is the original contribution of the authors.
Impact of consumption values on consumers’ purchase of organic food and green environmental concerns
Authors: Mohd Suki Norazah , Majeed Abdul , Mohd Suki Norbayah
Published: July 2021

Purpose

This study aims to examine the impact of consumption values on consumers’ purchase of organic food and green environmental concerns. Additionally, the relationships between green environmental concerns and consumers’ purchase of organic food are investigated.

Design/methodology/approach

A self-administered questionnaire was distributed to 500 consumers with experience in purchasing organic food in Pakistan. The covariance-based structural equation modeling (CB-SEM) technique was used for the data analysis using the Analysis of Moments Structure software version 23. The CB-SEM technique allows for the simultaneous estimation of all relationships.

Findings

The CB-SEM technique reveals that of the 11 hypotheses tested, social value heavily influences consumers’ green environmental concerns. Moreover, consumers’ purchase of organic food is greatly impacted by conditional value. Consumers purchase organic food for their daily needs because they feel responsible for preserving and protecting the environment against global warming and its associated threats. This green purchasing behavior actually leads to better social approval, through its ability to impress others.

Practical implications

Organizations and business owners should address green environmental concerns by seriously applying organic methods in the process of production, processing, packaging and selling of organic food products. Such organic practices would enable organizations and business owners to produce organic food products that are free from chemicals.

Originality/value

The inclusion of consumption values strengthens the explanatory power of the proposed model in the context of Pakistani consumers’ purchase of organic food and green environmental concerns simultaneously. This study therefore adds new and substantial insights into the marketing theory.
Efficacy of bath‐psoralen and ultraviolet A therapy for mycosis fungoides – retrospective analysis of 62 cases
Authors: Shintani Yoichi , Nishida Emi , Furuhashi Takuya , Muramatsu Shinnosuke , Kubo Ryoji , Nakamura Motoki , Watanabe Shoichi , Masuda Hideyuki , Ikumi Kyoko , Matsumoto Kazuhiko , Yamazaki Sayuri , Morita Akimichi
Published: July 2021

Photochemotherapy with psoralen and ultraviolet A (PUVA) is widely used for refractory skin diseases. Bathwater delivery of 8‐methoxypsoralen (8‐MOPS) with subsequent UVA irradiation (bath‐PUVA) or oral administration of 8‐MOPS with UVA is used to treat mycosis fungoides. We retrospectively analyzed 62 patients with mycosis fungoides (8 stage IA, 30 stage IB, 5 stage IIB, 18 stage IIIA, and 1 stage IVA2) treated with bath‐PUVA at the Dermatology Clinic of Nagoya City University Hospital from November 2004 to December 2013. A complete response was achieved in 37 (59.7%) patients, a partial response was achieved in 16 (25.8%), and stable disease was achieved in 6 (9.7%). Progressive disease was observed in 3 (4.8%) patients. Almost all patients in stage IA/IB achieved a complete response. Of the 5 stage IIB patients, 2 achieved a partial response, 1 achieved stable disease, and 2 had progressive disease. The serum concentrations of soluble interleukin‐2 receptor and lactate dehydrogenase decreased significantly following treatment with bath‐PUVA (p < 0.001). We examined the risk factors of patients whose stage progressed despite PUVA treatment. A multivariate Cox regression analysis of risk factors associated with stage progression yielded a hazard ratio of 28.5 for stage IIb. Treatment with bath‐PUVA is highly effective in the early stages of mycosis fungoides, and partially effective in advanced stages.
Frequencies and mechanisms of pesticide resistance in Tetranychus urticae field populations in China
Authors: Zhang Yan , Xu Dandan , Zhang Youjun , Wu Qingjun , Xie Wen , Guo Zhaojiang , Wang Shaoli
Published: July 2021

The two‐spotted spider mite Tetranychus urticate is an important agricultural pest worldwide. It is extremely polyphagous and has developed resistance to many pesticides. Here, we assessed the pesticide resistance of seven field populations of T. urticae in China, their target site mutations and the activities of their detoxification enzymes. The results showed that abamectin and the traditional pesticides pyridaben, profenofos and bifenthrin had higher resistance or lower toxicity than more recently developed pesticides including chlorfenapyr, spinetoram, cyflumetofen, cyenopyrafen, bifenazate and B‐azolemiteacrylic. The frequency of point mutations related to abamectin resistance, G314D in the glutamate‐gated chloride channel 1 (GluCl1) and G326E in GluCl3, ranged 47%–70% and 0%–97%, respectively. The frequency of point mutations in A1215D and F1538I of the voltage‐gated sodium channel gene (VGSC), which may increase resistance to pyrethroids, ranged 88%–100% and 10%–100%, respectively. For target sites related to organophosphate resistance, mutation frequencies ranged 25%–92% for G119S and 0%–23% for A201S in the acetycholinesterase gene (Ace). Mutation G126S in the bifenazate resistance‐related cytochrome b gene (Cytb) was observed in three of the seven T. urticae populations. Higher activities of detoxification enzymes (P450, GST, CarEs and UGTs) were observed in two T. urticae populations, with significant difference in the XY‐SX population. These results provide useful information on the status of pesticide resistance of T. urticae in China and suggest that T. urticae field populations may have multiple resistance mechanisms.
Enhancement of edeine production in Brevibacillus brevis X23 via in situ promoter engineering
Authors: Liu Qingshu , Zhang Liang , Wang Yunsheng , Zhang Cuiyang , Liu Tianbo , Duan Caichen , Bian Xiaoying , Guo Zhaohui , Long Qingshan , Tang Ying , Du Jie , Liu Aiyu , Dai Liangying , Li Dingjun , Chen Wu
Published: July 2021

Edeines, a group of cationic antimicrobial peptides produced by the soil bacterium Brevibacillus, have broad biological effects, such as antimicrobial, anticancer and immunosuppressive activities. However, the yield of edeines in wild‐type (WT) Brevibacillus is extremely low, and chemical synthesis of edeines is a time‐consuming process. Genetic engineering has proven to be an effective approach to produce antibiotics with high yield. In this study, the edeine biosynthetic gene cluster (ede BGC), which is involved in edeine production, was identified and characterized in Brevibacillus brevis X23. To improve edeine production in B. brevis X23, the ede BGC promoter was replaced with six different promoters, Pmwp, Pspc, PxylA, Pshuttle‐09, Pgrac or P43, through double‐crossover homologous recombination. The new promoters significantly increased the expression of the ede BGC as well as edeine production by 2.9 ± 0.4 to 20.5 ± 1.2‐fold and 3.6 ± 0.1to 8.7 ± 0.7‐fold respectively. The highest yield of edeines (83.6 mg l−1) was obtained in B. brevis X23 with the Pmwp promoter. This study provides a practical approach for producing high yields of edeines in B. brevis.
A newly developed PCR‐based method revealed distinct Fusobacterium nucleatum subspecies infection patterns in colorectal cancer
Authors: Bi Dexi , Zhu Yin , Gao Yaohui , Li Hao , Zhu Xingchen , Wei Rong , Xie Ruting , Wei Qing , Qin Huanlong
Published: July 2021

Fusobacterium nucleatum, which has four subspecies (nucleatum, animalis, vincentii and polymorphum), plays an important role in promoting colorectal cancer (CRC). However, as there is no efficient method of differentiating these subspecies in the context of a rich gut microbiota, the compositions in CRC remain largely unknown. In this study, a PCR‐based differentiation method enabling profiling of F. nucleatum infection in CRC at the subspecies level was developed. Based on the analysis of 53 F. nucleatum genomes, we identified genetic markers specific to each subspecies and designed primers for the conserved sequences of those markers. The PCR performance of the primers was tested with F. nucleatum and non‐nucleatum Fusobacterium strains, and complete consistence with taxonomy was achieved. Additionally, no non‐specific amplification occurred when using human DNA. The method was then applied to faecal (n = 58) and fresh‐frozen tumour tissue (n = 100) samples from CRC patients, and wide heterogeneity in F. nucleatum subspecies compositions in the gut microbiota among CRC patients was observed. Single‐subspecies colonization was common, whereas coexistence of four subspecies was rare. Subspecies animalis was most prevalent, while nucleatum was not frequently detected. The results of this study contribute to our understanding of the pathogenicity of F. nucleatum at the subspecies level and the method developed has potential for clinical and epidemiological use.
Species density models from opportunistic citizen science data
Authors: Ver Hoef Jay M. , Johnson Devin , Angliss Robyn , Higham Matt
Published: July 2021

With the advent of technology for data gathering and storage, opportunistic citizen science data are proliferating. Species distribution models (SDMs) aim to use species occurrence or abundance for ecological insights, prediction and management. We analysed a massive opportunistic dataset with over 100,000 records of incidental shipboard observations of marine mammals. Our overall goal was to create maps of species density from massive opportunistic data by using spatial regression for count data with an effort offset. We illustrate the method with two marine mammals in the Gulf of Alaska and Bering Sea.

We counted the total number of animals in 11,424 hexagons based on presence‐only data. To decrease bias, we first estimated a spatial density surface for ship‐days, which was our proxy variable for effort. We used spatial considerations to create pseudo‐absences, and left some hexagons as missing values. Next, we created SDMs that used modelled effort to create pseudo‐absences, and included the effort surface as an offset in a second stage analysis of two example species, northern fur seals and Steller sea lions.

For both effort and species counts, we used spatial count regression with random effects that had a multivariate normal distribution with a conditional autoregressive (CAR) covariance matrix, providing 2.5 million Markov chain Monte Carlo (MCMC) samples (1,000 were retained) from the posterior distribution. We used a novel MCMC scheme that maintained sparse precision matrices for observed and missing data when batch sampling from the multivariate normal distribution. We also used a truncated normal distribution to stabilize estimates, and used a look‐up table for sampling the autocorrelation parameter. These innovations allowed us to draw several million samples in just a few hours.

From the posterior distributions of the SDMs, we computed two functions of interest. We normalized the SDMs and then applied an overall abundance estimate obtained from the literature to derive spatially explicit abundance estimates, especially within subsetted areas. We also created ‘certain hotspots’ that scaled local abundance by standard deviation and using thresholds. Hexagons with values above a threshold were deemed as hotspots with enough evidence to be certain about them.
A blinded randomized study comparing intubating conditions after either rocuronium 0.6 mg·kg−1 or remifentanil 2 µg·kg−1 in elderly patients
Authors: Vested Matias , Sørensen Anne Marie , Bjerring Cecilie , Christensen Rasmus E. , Dinesen Felicia , Vang Malene , Gilvanoff Alexander , Hansen Thea Ellehammer , Nielsen Tatiana , Rasmussen Lars S.
Published: July 2021

Background

To facilitate tracheal intubation, either a neuromuscular blocking agent or a bolus dose of remifentanil can be administered. We hypothesized that rocuronium 0.6 mg·kg−1 provided a larger proportion of excellent intubating conditions compared to remifentanil 2 µg·kg−1 in patients above 80 years.

Methods

A total of 78 patients were randomized to either rocuronium 0.6 mg·kg−1 or remifentanil 2 µg·kg−1. General anaesthesia was initiated with fentanyl and propofol. Two minutes after the administration of either rocuronium or remifentanil, tracheal intubating conditions were evaluated using the Fuchs‐Buder scale by a blinded investigator, and our primary outcome was the proportion of patients presenting intubating conditions deemed as excellent. Further outcomes included the Intubating Difficulty Scale (IDS), hoarseness or sore throat 24 h postoperatively, and intervention against hypotension.

Results

No difference in the occurrence of excellent intubating conditions was found comparing the rocuronium group with the remifentanil group; 10 (28%) versus 15 (39%) (p = .29), respectively, relative risk = 0.72. Interventions against hypotension were used in 24 (67%) versus 28 (74%) (p = .51), respectively. Hoarseness and sore throat 24 h postoperatively were found in 37% versus 35% p = .86, and 14% versus 5% p = .20, respectively. The IDS score was 2 versus 2 p = .48.

Conclusion

No difference in intubating conditions was found 2 min after the administration of either rocuronium 0.6 mg·kg−1 or remifentanil 2 µg·kg−1 in patients aged above 80 years. Intubation conditions were less than optimal in a large proportion of this patient population.

Clinical trials registration

NCT04287426.
Cerebrovascular disease hospitalizations following emergency department headache visits: A nested case–control study
Authors: Liberman Ava L. , Hassoon Ahmed , Fanai Mehdi , Badihian Shervin , Rupani Hetal , Peterson Susan M. , Sebestyen Krisztian , Wang Zheyu , Zhu Yuxin , Lipton Richard B. , Newman‐Toker David E.
Published: July 2021

Background

Delayed diagnosis of cerebrovascular disease (CVD) among patients can result in substantial harm. If diagnostic process failures can be identified at emergency department (ED) visits that precede CVD hospitalization, interventions to improve diagnostic accuracy can be developed.

Methods

We conducted a nested case–control study using a cohort of adult ED patients discharged from a single medical center with a benign headache diagnosis from October 1, 2015 to March 31, 2018. Hospitalizations for CVD within 1 year of index ED visit were identified using a regional health information exchange. Patients with subsequent CVD hospitalization (cases) were individually matched to patients without subsequent hospitalization (controls) using patient age and visit date. Demographic, clinical, and ED process characteristics were assessed via detailed chart review. McNemar's test for categorical and paired t‐test for continuous variables were used with statistical significance set at ≤0.05.

Results

Of the 9157 patients with ED headache visits, 57 (0.6%, 95% confidence interval [CI] = 0.5–0.8) had a subsequent CVD hospitalization. Median time from ED visit to hospitalization was 107 days. In 25 patients (43.9%, 25/57) the CVD hospitalization and the index ED visit were at different hospitals. Fifty‐three cases and 53 matched controls were included in the final study analysis. Cases and controls had similar baseline demographic and headache characteristics. Cases more often had a history of stroke (32.1% vs. 13.2%, p = 0.02) and neurosurgery (13.2% vs. 1.9%, p = 0.03) prior to the index ED visit. Cases more often had less than two components of the neurologic examination documented (30.2% vs. 11.3%, p = 0.03).

Conclusion

We found that 0.6% of patients with an ED headache visit had subsequent CVD hospitalization, often at another medical center. ED visits for headache complaints among patients with prior stroke or neurosurgical procedures may be important opportunities for CVD prevention. Documented neurologic examinations were poorer among cases, which may represent an opportunity for ED process improvement.
Newly defined allergens in the WHO/IUIS Allergen Nomenclature Database during 01/2019‐03/2021
Authors: Sudharson Srinidhi , Kalic Tanja , Hafner Christine , Breiteneder Heimo
Published: July 2021

The WHO/IUIS Allergen Nomenclature Database (http://allergen.org) provides up‐to‐date expert‐reviewed data on newly discovered allergens and their unambiguous nomenclature to allergen researchers worldwide. This review discusses the 106 allergens that were accepted by the Allergen Nomenclature Sub‐Committee between 01/2019 and 03/2021. Information about protein family membership, patient cohorts, and assays used for allergen characterization is summarized. A first allergenic fungal triosephosphate isomerase, Asp t 36, was discovered in Aspergillus terreus. Plant allergens contained 1 contact, 38 respiratory, and 16 food allergens. Can s 4 from Indian hemp was identified as the first allergenic oxygen‐evolving enhancer protein 2 and Cic a 1 from chickpeas as the first allergenic group 4 late embryogenesis abundant protein. Among the animal allergens were 19 respiratory, 28 food, and 3 venom allergens. Important discoveries include Rap v 2, an allergenic paramyosin in molluscs, and Sal s 4 and Pan h 4, allergenic fish tropomyosins. Paramyosins and tropomyosins were previously known mainly as arthropod allergens. Collagens from barramundi, Lat c 6, and salmon, Sal s 6, were the first members from the collagen superfamily added to the database. In summary, the addition of 106 new allergens to the previously listed 930 allergens reflects the continuous linear growth of the allergen database. In addition, 17 newly described allergen sources were included.
A comparative study of strabismus surgery with retained or removed scleral explant after retinal detachment surgery
Authors: Christakopoulos Christos E. , Larson Scott A. , Vinding Troels , Buch Hesgaard Helena
Published: July 2021

Purpose

To compare, in a larger study population, the outcomes of strabismus surgery in patients who either had the scleral explant (EX) retained or removed after surgery for retinal detachment.

Methods

A comparative retrospective study includes data from 2 centres. Surgical outcome, motor success, sensory success, the number of secondary operations for strabismus and complications were compared between the two groups. Motor success was defined as horizontal deviation of ≤6 prism diopters (PD) and vertical deviation of ≤6PD. Sensory success was defined as no diplopia without use of prism.

Results

Forty‐seven patients were included in the study; 70% had retained the EX and 74% had vertical strabismus. Horizontally, the final alignment was equal between the 2 groups, 4 PD vs.5 PD in the EX removed group. The patients with retained EX were referred with a significant lower mean vertical deviation and had a significant lower post‐operative mean vertical deviation of 2 PD vs. 3 PD in the EX‐removed group. The rates of motor success (76% vs. 71%) and sensory success (79% vs. 93%) did not differ significantly between the EX‐retained and EX‐removed groups. No patients underwent more than 2 operations. Two complications occurred in the EX‐retained group: a subconjunctival cyst and an exposed EX. In the EX‐removed group, 2 patients with retinal re‐detachment were found in the follow‐up period.

Conclusion

Good surgical outcomes including high motor and sensory success were obtained regardless of the presence of the EX. Retinal re‐detachment was observed in two patients with previously removed EX.