bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources of information waste in neuroimaging: mishandling structures, thinking dichotomously, and over-reducing data
Authors: Chen Gang , Taylor Paul A. , Stoddard Joel , Cox Robert W. , Bandettini Peter A. , Pessoa Luiz
Published: May 2021

Neuroimaging relies on separate statistical inferences at tens of thousands of spatial locations. Such massively univariate analysis typically requires an adjustment for multiple testing in an attempt to maintain the family-wise error rate at a nominal level of 5%. First, we examine three sources of substantial information loss that are associated with the common practice under the massively univariate framework: (a) the hierarchical data structures (spatial units and trials) are not well maintained in the modeling process; (b) the adjustment for multiple testing leads to an artificial step of strict thresholding; (c) information is excessively reduced during both modeling and result reporting. These sources of information loss have far-reaching impacts on result interpretability as well as reproducibility in neuroimaging. Second, to improve inference efficiency, predictive accuracy, and generalizability, we propose a Bayesian multilevel modeling framework that closely characterizes the data hierarchies across spatial units and experimental trials. Rather than analyzing the data in a way that first creates multiplicity and then resorts to a post hoc solution to address them, we suggest directly incorporating the cross-space information into one single model under the Bayesian framework (so there is no multiplicity issue). Third, regardless of the modeling framework one adopts, we make four actionable suggestions to alleviate information waste and to improve reproducibility: 1) abandon strict dichotomization, 2) report full results, 3) quantify effects, and 4) model data hierarchies. We provide examples for all of these points using both demo and real studies, including the recent NARPS investigation.
Elucidating the diversity of microeukaryotes and epi-endophytes in the brown algal holobiome
Authors: Markussen Bjorbækmo Marit F. , Brodie Juliet , Krabberød Anders K. , Logares Ramiro , Attwood Stephanie , Fredriksen Stein , Fuss Janina , Wold-Dobbe Anders , Shalchian-Tabrizi Kamran , Bass David
Published: May 2021

Background

Brown algae (Phaeophyceae) are essential species in coastal ecosystems where they form kelp forests and seaweed beds that support a wide diversity of marine life. Host-associated microbial communities are an integral part of phaeophyte biology. The bacterial microbial partners of brown algae have received far more attention than microbial eukaryotes. To our knowledge, this is the first study to investigate brown algal-associated eukaryotes (the eukaryome) using broadly targeting ‘pan-eukaryotic’ primers and high throughput sequencing (HTS). Using this approach, we aimed to unveil the eukaryome of seven large common brown algal species. We also aimed to assess whether these macroalgae harbour novel eukaryotic diversity and to ascribe putative functional roles to the host-associated eukaryome, based on taxonomic affiliation and phylogenetic placement.

Results

Our sequence dataset was dominated by brown algal reads, from the host species and potential symbionts. We also detected a broad taxonomic diversity of eukaryotes in the brown algal holobiomes, with OTUs taxonomically assigned to ten of the eukaryotic major Kingdoms or supergroups. A total of 265 microeukaryotic and epi-endophytic operational taxonomic units (OTUs) were defined, using 97% similarity cut off during clustering, and were dominated by OTUs assigned to stramenopiles, Alveolata and Fungi. Almost one third of the OTUs we detected have not been found in previous molecular environmental surveys, and represented potential novel eukaryotic diversity. This potential novel diversity was particularly prominent in phylogenetic groups comprising heterotrophic and parasitic organisms, such as labyrinthulids and oomycetes, Cercozoa, and Amoebozoa.

Conclusions

Our findings provide important baseline data for future studies of seaweed-associated microorganisms, and demonstrate that microeukaryotes and epi-endophytic eukaryotes should be considered as an integral part of brown algal holobionts. The potential novel eukaryotic diversity we found and the fact that the vast majority of macroalgae in marine habitats remain unexplored, demonstrates that brown algae and other seaweeds are potentially rich sources for a large and hidden diversity of novel microeukaryotes and epi-endophytes.
Hyperinflammation evokes different antiviral TMPRSS2 and ADAM17 expression responses in human gut xenograft versus host mouse gut although overall genomic responses are similar
Authors: Morris Lorna , Nisim-Eliraz Einat , Schouten Iftach , Bergey François , Dyer Nigel , Momiji Hiroshi , Nir Eilam , Marsiano Noga , Tezerji Raheleh Sheibani , Yagel Simcha , Rosenstiel Philip , Rand David , dos Santos Vitor A.P. Martins , Shpigel Nahum Y. ,   SysmedIBD research consortium
Published: May 2021

The global spread of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the pandemic outbreak of coronavirus disease 2019 (COVID-19), an inflammatory disease that is primarily affecting the respiratory system. However, gastrointestinal symptoms in COVID-19 patients suggests that the gut may present another viral target organ. Disease development and severity is dependent on viral interaction with two cell surface human proteins, ACE2 and TMPRSS2, and on antiviral response which may lead to systemic hyperinflammatory syndrome and multiorgan dysfunction. Understanding the host response to SARS-CoV-2 infection and the pathology of the disease will be greatly enhanced by the development of appropriate animal models. Laboratory mice have been the mainstay of therapeutic and vaccine development, however, the virus does not grow in wild type mice and only induced mild disease in transgenic animals expressing human ACE2. As there are known differences between immune response in laboratory mice and humans we evaluated the response of human gut developed as xenografts and host mouse gut following systemic LPS injections as a hyperinflammation model system. The orthologous gene expression levels in the mouse and human gut were highly correlated (Spearman’s rank correlation coefficient: 0.28–0.76) and gene set enrichment analysis of significantly upregulated human and mouse genes revealed that a number of inflammatory and immune response pathways are commonly regulated in the two species. However, species differences were also observed, most importantly, in the inflamed human gut but not in the mouse gut, there was clear upregulation of mRNAs coding for TMPRSS2, ADAM17 and for RIG-I-like receptors, which are involved in the recognition of viruses and in antiviral innate immune response. Moreover, using species-specific immunofluorescence microscopy, we demonstrated the expression and localization of human ACE2 and TMPRSS2 proteins, which are essential elements of the molecular machinery that enables SARS-CoV-2 to infect and replicate in human gut cells. Our findings demonstrate that the intestinal immune response to inflammation in humans and mice are generally very similar. However, certain human-specific diseases, such as COVID-19, can only be successfully studied in an experimental model of human tissue, such as the gut xenograft.
Investigating VCAM-1 Targeted Nanoparticles and Annexin A1 Therapy using Dysfunctional-endothelium-on-a-chip
Authors: Bazban-Shotorbani Salime , Kamaly Nazila
Published: May 2021

Atherosclerosis is an inflammation-driven disease of the arteries and one of the leading causes of global mortality. The initial pathological stage in atherosclerosis is dysfunctional endothelium (Dys-En), which results in loss of adherens-junctions between cells, thus enhancing permeability. Not only the enhanced permeability of Dys-En can be used as a nanoparticle targeting mechanism, but also the normalization and restoration of this phenomenon can be utilized as a potent anti-atherosclerotic therapy. This study aimed to recruit a robust biomicrofluidic model of Dys-En for 1) nanoparticle screening and 2) normalization assessments. The developed Dys-En-on-a-chip could successfully mimic the atherosclerotic flow condition, enhanced permeability, formation of actin stress fibers, and overexpression of vascular cell adhesion molecule 1 (VCAM-1), which are known as hallmarks of a Dys-En. The screening of VCAM-1 targeting nanoparticles with variable biophysicochemical properties showed that nanoparticle size plays the main role in nanoparticle targeting, and the design of nanoparticles in the range of 30-60 nm can highly increase their targeting to Dys-En. Moreover, treatment of Dys-En-on-a-chip with Annexin A1, as a novel pro-resolving mediator, resulted in restoration of adherens-junctions and normalization of the barrier integrity. This data validates the use of biomicrofluidic models for investigating treatment regimens with biologics and to identify optimal nanoparticle properties for effective atherosclerotic plaque targeting.
Tissue-specific transcriptomics reveal functional differences in maize floral development
Authors: Yang Hailong , Nukunya Kate , Ding Queying , Thompson Beth E.
Published: May 2021

Flowers are produced by floral meristems, groups of stem cells that give rise to floral organs. In grasses, including the major cereal crops, flowers (florets) are contained in spikelets, which contain one to many florets, depending on the species. Importantly, not all grass florets are developmentally equivalent, and one or more florets are often sterile or abort in each spikelet. Members of the Andropogoneae tribe, including maize, produce spikelets with two florets; the upper and lower florets are usually dimorphic and the lower floret greatly reduced compared to the upper floret. In maize ears, early development appears identical in both florets but the lower floret ultimately aborts. To gain insight into the functional differences between florets of different fates, we used laser capture microdissection coupled with RNA-seq to globally examine gene expression in upper and lower floral meristems in maize. Differentially expressed genes were involved in hormone regulation, cell wall, sugar and energy homeostasis. Furthermore, cell wall modifications and sugar accumulation differed between the upper and lower florets. Finally, we identified a novel boundary domain between upper and lower florets, which we hypothesize is important for floral meristem activity. We propose a model in which growth is suppressed in the lower floret by limiting sugar availability and upregulating genes involved in growth repression. This growth repression module may also regulate floret fertility in other grasses and potentially be modulated to engineer more productive cereal crops.

One sentence summary

Floret-specific differences in cell wall composition and sugar accumulation likely contribute to growth suppression in the lower floret of maize spikelets.
The SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia
Authors: Polyanskaya Sofya A. , Moreno Rosamaria Y. , Lu Bin , Feng Ruopeng , Yao Yu , Irani Seema , Klingbeil Olaf , Yang Zhaolin , Wei Yiliang , Demerdash Osama E. , Benjamin Lukas A. , Weiss Mitchell J. , Zhang Yan Jessie , Vakoc Christopher R.
Published: May 2021

Acute myeloid leukemia (AML) cells rely on phospho-signaling pathways to gain unlimited proliferation potential. Here, we used domain-focused CRISPR screening to identify the nuclear phosphatase SCP4 as a dependency in AML, yet this enzyme is dispensable in normal hematopoietic progenitor cells. Using CRISPR exon scanning and gene complementation assays, we show that the catalytic function of SCP4 is essential in AML. Through mass spectrometry analysis of affinity-purified complexes, we identify the kinase paralogs STK35 and PDIK1L as binding partners and substrates of the SCP4 phosphatase domain. We show that STK35 and PDIK1L function catalytically and redundantly in the same pathway as SCP4 to maintain AML proliferation and to support amino acid biosynthesis and transport. We provide evidence that SCP4 regulates STK35/PDIK1L through two distinct mechanisms: catalytic removal of inhibitory phosphorylation and by promoting kinase stability. Our findings reveal a phosphatase-kinase signaling complex that supports the pathogenesis of AML.
Revealing RNA virus diversity and evolution in unicellular algae transcriptomes
Authors: Charon Justine , Murray Shauna , Holmes Edward C.
Published: May 2021

Remarkably little is known about the diversity and evolution of RNA viruses in unicellular eukaryotes. We screened a total of 570 transcriptomes from the Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP) project that encompasses a wide diversity of microbial eukaryotes, including most major photosynthetic lineages (i.e. the microalgae). From this, we identified 30 new and divergent RNA virus species, occupying a range of phylogenetic positions within the overall diversity of RNA viruses. Approximately one-third of the newly described viruses comprised single-stranded positive-sense RNA viruses from the order Lenarviricota associated with fungi, plants and protists, while another third were related to the order Ghabrivirales, including members of the protist and fungi-associated Totiviridae. Other viral species showed sequence similarity to positive-sense RNA viruses from the algae-associated Marnaviridae, the double-stranded RNA Partitiviridae, as well as a single negative-sense RNA virus related to the Qinviridae. Importantly, we were able to identify divergent RNA viruses from distant host taxa, revealing the ancestry of these viral families and greatly extending our knowledge of the RNA viromes of microalgal cultures. Both the limited number of viruses detected per sample and the low sequence identity to known RNA viruses imply that additional microalgal viruses exist that could not be detected at the current sequencing depth or were too divergent to be identified using sequence similarity. Together, these results highlight the need for further investigation of algal-associated RNA viruses as well as the development of new tools to identify RNA viruses that exhibit very high levels of sequence divergence.
Modelling collective navigation via nonlocal communication
Authors: Johnston Stuart T , Painter Kevin J
Published: May 2021

Collective migration occurs throughout the animal kingdom, and demands both the interpretation of navigational cues and the perception of other individuals within the group. Navigational cues orient individuals toward a destination, while it has been demonstrated that communication between individuals enhances navigation through a reduction in orientation error. We develop a mathematical model of collective navigation that synthesises navigational cues and perception of other individuals. Crucially, this approach incorporates the uncertainty inherent to cue interpretation and perception in the decision making process, which can arise due to noisy environments. We demonstrate that collective navigation is more efficient than individual navigation, provided a threshold number of other individuals are perceptible. This benefit is even more pronounced in low navigation information environments. In navigation ''blindspots'', where no information is available, navigation is enhanced through a relay that connects individuals in information-poor regions to individuals in information-rich regions. As an expository case study, we apply our framework to minke whale migration in the North East Atlantic Ocean, and quantify the decrease in navigation ability due to anthropogenic noise pollution.
Concurrent circulation of dengue serotype 1, 2 and 3 among acute febrile patients in Cameroon
Authors: Tchetgna Huguette Simo , Yousseu Francine S. , Kamgang Basile , Tedjou Armel , McCall Philip J. , Wondji Charles
Published: May 2021

Acute febrile patients presenting at hospitals in Douala, Cameroon between July and December 2020, were screened for dengue infections using RT-PCR on fragments of the 5’ and 3’ UTR genomic regions. In total, 12.8% (41/320) of cases examined were positive for dengue. Dengue virus 3 (DENV-3) was the most common serotype found (68.3%), followed by DENV-2 (19.5%) and DENV-1 (4.9%). Co-infections of DENV-3 and DENV-2 were found in 3 cases. Jaundice and headache were the most frequent clinical signs associated with infection and 176 cases (55%) were co-infections with malaria. Phylogenetic analysis of the envelope gene identified DENV-1 as belonging to genotype V, DENV-2 to genotype II and DENV-3 to genotype III. The simultaneous occurrence of three serotypes in Douala reveals dengue as a serious public health threat for Cameroon and highlights the need for further epidemiological studies in the major cities of this region.
Differences in progression by surgical specialty: a national cohort study
Authors: Hope Carla , Lund Jonathan , Griffiths Gareth , Humes David J
Published: May 2021

The aim of surgical training across the ten surgical specialties is to produce competent day one consultants. Progression through training is assessed by the Annual Review of Competency Progression (ARCP).

Objective

This study aimed to examine variation in ARCP outcomes within surgical training and identify differences between specialties.

Design

A national cohort study using data from United Kingdom Medical Education Database (UKMED) was performed. ARCP outcome was the primary outcome measure. Multi-level ordinal regression analyses were performed, with ARCP outcomes nested within trainees.

Participants

Higher surgical trainees (ST3-ST8) from 9 UK surgical specialties were included (vascular surgery was excluded due to insufficient data). All surgical trainees across the UK with an ARCP outcome between 2010 to 2017 were included.

Results

Eight thousand two hundred and twenty trainees with an ARCP outcome awarded between 2010 and 2017 were included, comprising 31,788 ARCP outcomes. There was substantial variation in the proportion of non-standard outcomes recorded across specialties with general surgery trainees having the highest proportion of non-standard outcomes (22.5%) and urology trainees the fewest 12.4%. After adjustment, general surgery trainees were 1.3 times more likely to receive a non-standard ARCP outcome compared to trainees in T&O (OR 1.33 95%CI 1.21-1.45). Urology trainees were 36% less likely to receive a non-standard outcome compared to T&O trainees (OR 0.64 95%CI 0.54-0.75). Female trainees and older age were associated with non-standard outcomes (OR 1.11 95%CI 1.02-1.22; OR 1.04 95%CI 1.03-1.05).

Conclusion

There is wide variation in the training outcome assessments across surgical specialties. General surgery has higher rates of non-standard outcomes compared to other surgical specialities. Across all specialities, female sex and older age were associated with non-standard outcomes.

Article summary

Strengths and limitations

This is the first study investigating factors affecting ARCP outcome across all surgical specialities.

The major strength of the study is the large sample size comprising all higher surgical trainees between 2010 and 2017.

Unlike previous studies this study uses data from reliable sources and is not dependent on survey data.

Limitations include the inability to investigate the causes behind our findings due to the nature of the analysis.
Individual Level Differential Expression Analysis for Single Cell RNA-seq data
Authors: Zhang Mengqi , Liu Si , Miao Zhen , Han Fang , Gottardo Raphael , Sun Wei
Published: May 2021

Bulk RNA-seq data quantify the expression of a gene in an individual by one number (e.g., fragment count). In contrast, single cell RNA-seq (scRNA-seq) data provide much richer information: the distribution of gene expression across many cells. To assess differential expression across individuals using scRNA-seq data, a straightforward solution is to create “pseudo” bulk RNA-seq data by adding up the fragment counts of a gene across cells for each individual, and then apply methods designed for differential expression using bulk RNA-seq data. This pseudo-bulk solution reduces the distribution of gene expression across cells to a single number and thus loses a good amount of information. We propose to assess differential expression using the gene expression distribution measured by cell level data. We find denoising cell level data can substantially improve the power of this approach. We apply our method, named IDEAS (Individual level Differential Expression Analysis for scRNA-seq), to study the gene expression difference between autism subjects and controls. We find neurogranin-expressing neurons harbor a high proportion of differentially expressed genes, and ERBB signals in microglia are associated with autism.
Sugar units, not chilling units, control endodormancy duration in plants – potato tuber as a case study
Authors: Danieli Raz , Assouline Shmuel , Salam Bolaji Babajide , Teper-Bamnolker Paula , Belausov Eduard , Friedmann Yael , Granot David , Eshel Dani
Published: May 2021

Endodormancy (ED) is a crucial stage in the life cycle of many perennial plants, regulated by genetic and environmental factors. Chilling units, growth regulators, and nutrient supply are considered inducers of ED release, but the mechanism governing ED duration is poorly understood. The potato tuber has been used as a model system to study metabolic processes associated with ED release. Cold-induced sweetening is a well-known response of the tuber to chilling. Here, we found that cold stress induces an increase in sugar units in association with plasmodesmatal closure in the dormant bud cells. Tuber sweetening was associated with shortened ED duration after cooling. Heat exposure also caused sugar unit accumulation followed by faster ED release. A logistic function was developed to predict ED duration based on sugar unit measurements. We discovered that ED release is better correlated with the accumulation of sugar units compared to chilling units. CRISPR/Cas9 knockout of the vacuolar invertase gene (StVInv) induced longer ED, but only in cultivars in which the mutation modified the level sugar units. Our results suggest that sugar units are better predictors of vegetative bud ED duration than chilling units.
Neural correlates of individual differences in aversion to risk and choice inconsistency
Authors: Jaquerod Manon E. , Lintas Alessandra , Gratton Gabriele , Low Kathy A. , Tobler Philippe N. , Villa Alessandro E. P.
Published: May 2021

Abstract

When making financial choices, most people prefer smaller but more certain gains to larger but more uncertain ones with the same expected value (risk aversion). However, attitudes toward risk may vary greatly also within individuals (choice inconsistency). To examine the brain dynamics implementing risky and inconsistent decisions, we recorded event-related brain potentials (ERPs) from 24 adults engaged in a task requiring choices between certain but smaller gains and uncertain but larger ones. Choice consistency and risk aversion were quantified for each individual. Participants were classified into three groups according to their attitude toward risk. Relative neutrality to risk was accompanied by a higher consistency across trials than risk aversion or proneness. Choice consistency was related to the amplitude of the positive ERP peaking near 200 ms after stimulus onset (P200), while risk aversion was related to modulation of the medial frontal negativity (MFN) and to the amplitude of a late positive potential (LPP). Late ERP activity was related to the modulation of value signals by risk levels and associated with individual differences in behavior. Overall, this study suggests that individual differences in attitude toward risk and choice consistency are associated with distinct brain dynamics.
Coordinated regulation of WNT/β-catenin, c-Met, and Integrin signalling pathways by miR-193b controls triple negative breast cancer metastatic traits
Authors: Giacomelli Chiara , Jung Janine , Wachter Astrid , Ibing Susanne , Will Rainer , Uhlmann Stefan , Mannsperger Heiko , Sahin Özgür , Yarden Yosef , Beißbarth Tim , Korf Ulrike , Körner Cindy , Wiemann Stefan
Published: May 2021

Background

Triple Negative Breast Cancer (TNBC) is the most aggressive subtype of Breast Cancer (BC). Treatment options for TNBC patients are limited and further insights into disease aetiology are needed to develop better therapeutic approaches. microRNAs’ ability to regulate multiple targets could hold a promising discovery approach to pathways relevant for TNBC aggressiveness. Thus, we address the role of miRNAs in controlling signalling pathways and phenotypes relevant to the biology of TNBC.

Methods

To identify miRNAs regulating WNT/β-catenin, c-Met, and integrin signalling pathways, we performed a high-throughput targeted proteomic approach, investigating the effect of 800 miRNAs on the expression of 62 proteins in the MDA-MB-231 TNBC cell line. We then developed a novel network analysis, Pathway Coregulatory (PC) score, to detect miRNAs regulating the three pathways. Usingin vitroassays for cell growth, migration, apoptosis, and stem-cell content, we validated the function of candidate miRNAs. Bioinformatic analyses using BC patients’ datasets were employed to assess expression of miRNAs as well as their pathological relevance in TNBC patients.

Results

We identified six candidate miRNAs coordinately regulating the three signalling pathways. Quantifying cell growth of three TNBC cell lines upon miRNA gain-of-function experiments, we characterised miR-193b as a strong and consistent repressor of this phenotype. Importantly, the effects of miR-193b were stronger than chemical inhibition of the individual pathways. We further demonstrated that miR-193b induced apoptosis, repressed migration, and regulated stem-cell markers in MDA-MB-231 cells. Furthermore, miR-193b expression was the lowest in patients classified as TNBC or Basal compared to other subtypes when classified by PAM50 signatures. Gene Set Enrichment Analysis showed that miR-193b expression was significantly associated with reduced activity of of WNT/β-catenin and c-Met signalling pathways in TNBC patients.

Conclusions

Integrating miRNA-mediated effects and protein functions on networks, we show that miRNAs predominantly act in a coordinated fashion to activate or repress signalling pathways responsible for metastatic traits in TNBC. We further demonstrate that our top candidate, miR-193b, regulates these phenotypes to an extent stronger than individual pathway inhibition, thus proving that its effect on TNBC aggressiveness is mediated by repressing multiple interconnected pathways.
Three ParA dimers cooperatively assemble on type Ia partition promoters
Authors: Boudsocq François , Salhi Maya , Barbe Sophie , Bouet Jean-Yves
Published: May 2021

Accurate DNA segregation is essential for faithful inheritance of genetic material. In bacteria, this process is mainly ensured by a partition system (Par) composed of two proteins, ParA and ParB, and a centromere site. The auto-regulation of Par operon expression is important for efficient partitioning, and is primarily mediated by ParA for type Ia plasmid partition systems. For the plasmid F, four ParAF monomers were proposed to bind to four repeated sequences in the promoter region. By contrast, using quantitative surface plasmon resonance, we showed that three ParAF dimers bind to this region. We uncovered that one perfect inverted repeat (IR) motif, consisting of two hexamer sequences spaced by 28-bp, constitutes the primary ParAF DNA binding site. A similar but degenerated motif overlaps the former. ParAF binding to these motifs is well supported by biochemical and modeling analyses. In addition, molecular dynamics simulations predict that the winged-HTH domain displays high flexibility, which may favor the cooperative ParA binding to the promoter region. We propose that three ParAF dimers bind cooperatively to overlapping motifs thus covering the promoter region. A similar organization is found on both closely related and distant plasmid partition systems, suggesting that such promoter organization for auto-regulated Par operons is widespread and may have evolved from a common ancestor.
Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
Authors: Thapa Dibesh , Sousa Valente João de , Barrett Brentton , Argunhan Fulye , Lee Sheng Y. , Nikitochkina Sofya , Kodji Xenia , Brain Susan D.
Published: May 2021

Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor receptor in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.
Site-occupancy scheme in disordered Ca3RE2(BO3)4: a dependence on rare-earth (RE) ionic radius
Authors: Kosyl Katarzyna M. , Paszkowicz Wojciech , Minikayev Roman , Shekhovtsov Alexey N. , Kosmyna Miron B. , Chrunik Maciej , Fitch Andrew N.
Published: May 2021

The structures of polycrystalline Ca3RE2(BO3)4(RE = La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Y; space groupPnma) orthoborates were determined using powder X-ray diffraction. Trends in the unit-cell dimensions and yet unreported trends in other structural properties (interatomic distances and the fractional occupation of three Ca/RE sites) for these compounds are demonstrated as a function of RE ionic radius. The unit-cell volume andaunit-cell parameter present a linear dependence, while thebandcunit-cell parameters change in a nonlinear manner. For the whole series, the RE atoms are present at all three cationic sites (labelled asM1,M2 andM3), but the fractional occupancies depend on the RE ionic radius. The small rare-earth atoms tend to enter mainly theM3 site; for the larger rare earths, the occupancy of this site decreases sharply. The occupancy of theM1 site by RE atoms is around 0.5 and tends to increase with increasing RE ionic radius. TheM2 site is the least preferentially occupied by RE ions, but the occupancy discernibly increases with rising radius as well. These findings are assembled with properties of isostructural strontium and barium borates, allowing prediction of occupancy schemes for not yet investigated compounds from theA3RE2(BO3)4(A= Ca, Ba, Sr).
Crystal structure of Z-DNA in complex with the polyamine putrescine and potassium cations at ultra-high resolution
Authors: Drozdzal Pawel , Gilski Miroslaw , Jaskolski Mariusz
Published: May 2021

The X-ray crystal structure of the d(CGCGCG)2/putrescine(2+)/K+ complex has been determined at 0.60 Å resolution. Stereochemical restraints were used only for the putrescinium dication, and 23 bonds and 18 angles of the Z-DNA nucleotides with dual conformation. The N atoms of the putrescine(2+) dication form three direct hydrogen bonds with the N7_G atoms of three different Z-DNA molecules, plus three water-mediated hydrogen bonds with cytosine, guanine and phosphate acceptors. A unique potassium cation was also unambiguously identified in the structure, albeit at a ∼0.5 occupation site shared with a water molecule, providing the first example of such a complex with Z-DNA. The K+ cation has coordination number of eight and an irregular coordination sphere, formed by four water molecules and four O atoms from two phosphate groups of the Z-DNA, including ligands present at fractional occupancy. The structural disorder of the Z-DNA duplex is manifested by the presence of alternate conformations along the DNA backbone. Comparison of the position and interactions of putrescine(2+) in the present structure with other ultra-high-resolution structures of Z-DNA in complexes with Mn2+ and Zn2+ ions shows that the dicationic putrescinium moiety can effectively substitute these metal ions for stabilization of Z-type DNA duplexes. Furthermore, this comparison also suggests that the spermine(4+) tetracation has a higher affinity for Z-DNA than K+.
Creating the digital citizen: students’ co-construction of meaning for global citizenship during online discussions
Authors: Myers John P.
Published: May 2021

Purpose

This study examines whether online asynchronous discussion forums support student’s meaning-making about citizenship in a globalizing world. Citizenship is an increasingly contested identity for young people, yet they have few opportunities in traditional civic education to consider their own citizenship. Although online discussions are considered effective spaces for increasing dialogue and critical thinking between diverse students, there has been little research to understand how effective they are for helping students to construct new understandings of citizenship.

Design/methodology/approach

A content analysis approach was used to analyze and code 89 discussion board posts. The Interaction Analysis Model (IAM) coding scheme was used to describe and analyze the quality of knowledge construction that occurred across the posts focusing on different aspects of global citizenship.

Findings

The findings demonstrate that the discussion boards produced substantive talks about the meaning of citizenship that in some instances reached the level of new knowledge construction. The students considered different meanings for global citizenship and negotiated positions on key issues. However, the highest levels of knowledge construction were rarely reached.

Practical implications

A major implication is the need to organize and cue discussion boards to support knowledge construction in addition to fostering dialogue.

Originality/value

This study contributes to the role that technology can play in supporting students’ knowledge construction about global citizenship that go beyond the scripted meanings conveyed in civics classes.
Civics education in Malaysia: a clash between ethics, religion and cultural norms
Authors: Balakrishnan Vishalache
Published: May 2021

Purpose

To showcase the importance of digital citizenship in the current era. This article compares the nine features of digital citizen provided by Ribble and Bailey (2007) with a case study conducted in a multicultural setting and identifies the tensions between ethics, religion and cultural norms in that environment.

Design/methodology/approach

A case study approach has been used in this research. Why case study? Because it is unique and provides in-depth, unique and invaluable findings. Case studies researchers have contributed to the development of case study research from diverse disciplines. Historical examples of case studies go back as far as the nineteenth century with the biography of Charles Darwin (Stewart, 2014). The dominance of positivism in science in the late 1940 and 1950s in social science sidelined qualitative approaches such as case studies. Although case study research was often criticized for its inability to support generalizations, and thus, provided limited validity and value as a research design (Merriam, 2009; Stewart, 2014), case study research provides intensive analysis of an issue. A Case study is intrinsic, instrumental and collective (Stake, 1995, 2006). Case study research encourages the detailed enquiry of a unit of analysis within its context.

Findings

Findings show that current society needs to be educated on the nine aspects of digital citizenship. In the current era, changes are so rapid that every now and then, there must be collaboration and cooperation between different agencies to ensure that the tension between religiosity, cultural norms and ethics would be able to find some common ground. With more knowledge and wisdom on human rights, sustainability education and project-based learning in Civics Education, teachers, students, parents and community should often meet to decide on controversial issues and find ways to ensure that each one in society has the knowledge, skills and values for digital citizenship to grow and flourish.

Originality/value

The article is original in nature and has much social impact.
The impact of the international crisis on the entrepreneurial intentions of refugees
Authors: Welsh Dianne H.B. , Othman Dalia , Alserhan Baker , Zeqiri Jusuf , Al-Madadha Amro , Ramadani Veland
Published: May 2021

Purpose

We investigate the entrepreneurial intentions of a population under crisis — namely, recent Syrian refugees in Jordan — and Jordanian citizens to start small businesses during the COVID-19 pandemic.

Design/methodology/approach

Using a structured two-part survey, data were collected through online self-reported questionnaires in which respondents subjectively reported self-perceptions. The first part dealt with respondents’ characteristics and the second with their entrepreneurial intentions. The survey took place in Jordan, sampling Jordanian citizens and Syrian refugees. A nonprobability sampling technique was used to collect the data.

Findings

The results show that net desirability for self-employment, tolerance for risk and self-efficacy are related to entrepreneurial intentions. We find significant differences between the Syrian refugees and the Jordanian citizens in terms of risk-taking and self-efficacy as determinants of engagement in entrepreneurial activities.

Originality/value

This study offers guidance to institutions working with refugees during times of crisis. Implications are discussed.
DLC coated spur gears – Part II: coating properties and potential for industrial use
Authors: Bobzin Kirsten , Brögelmann Tobias , Kalscheuer Christian , Thiex Matthias , Schwarz Andreas , Ebner Martin , Lohner Thomas , Stahl Karsten
Published: May 2021

Purpose

This paper aims to address the coating and compound analysis of diamond-like carbon (DLC) on steel, to understand the frictional behavior in tribological gear systems presented in paper Part I. Here, the Ti and Zr modified DLC coating architectures are analyzed regarding their chemical, mechanical and thermophysical properties. The results represent a systematic analysis of the thermal insulating effect in tribological contact of DLC coated gears.

Design/methodology/approach

The approach was to evaluate the effect of the substitution of Zr through Ti at the reference coating ZrCg to TiCg and the effect on thermophysical properties. Furthermore, the influence of different carbon and hydrogen contents on the coating and compound properties was analyzed. Therefore, different discrete Ti or Zr containing DLC coatings were deposited on an industrial coating machine. Thereby the understanding of the microstructure and chemical composition of the reference coatings is increased.

Findings

Results prove comparable mechanical properties of metal modified DLC independent of differences in chemical compositions. Moreover, the compound adhesion between TiCg/16MnCr5E was improved compared to ZrCg/16MnCr5E. The effect of hydrogen content Ψ and carbon content xc on the thermophysical properties is limited by Ψ = 18 at.% and xc = 90 at.%.

Practical implications

The findings of the combined papers Part I and II show a high potential for industrial application of DLC on gears. Based on the results DLC coatings and gears can be tailored to each other.

Originality/value

Systematic analysis of DLC coatings were conducted to evaluate the effect of titanium, carbon and hydrogen on thermophysical properties.
The impact of locus of control and motivations in predicting entrepreneurial intentions among farmers: a field research
Authors: Pliakoura Alexandra Panagiotis , Beligiannis Grigorios N. , Chatzitheodoridis Fotios , Kontogeorgos Achilleas
Published: May 2021

Purpose

The purpose of this paper is to explain the impact of locus of control (LOC) and motivations on entrepreneurial intentions (EIs) among agri-entrepreneurs in the region of Western Greece.

Design/methodology/approach

The study was conducted in 2019 in the Western Greece region. Primary data were collected through a survey. A researcher-administered questionnaire was the data collection instrument while the individual farmer was the unit of analysis. Many data analysis methods were applied: a validity and reliability test, exploratory factor analysis, regression analysis, Kruskal–Wallis test and correlations.

Findings

The results show that the proposed model explains almost 33% of the variance for the EI. Internal LOC and pull motivations have a positive relationship with the intention of entrepreneurship. EI in the agricultural sector is more dependent on LOC, motivations, age and level of education than gender and type of holding.

Research limitations/implications

The findings of this study provide several theoretical and practical contributions, which can be useful for other researchers.

Originality/value

This research study adds to the existing literature of the EI by using a different type of sample compared to previous contributions. Mostly EI studies used student sample to measure intentions. The present study extends the antecedents of intention by using a sample of existing agri-entrepreneurs. Farmers are one of the best potential segments, and as a result, this research will help predicting how the intention process of existing entrepreneurs works, especially in the primary sector.
Owner-manager when death do us part – roles of a widow in sudden succession in family firms
Authors: Almlöf Hanna , Sjögren Hans
Published: May 2021

Purpose

This study sheds light on a hitherto understudied group in family business literature: widows. We explore the roles a widow may take following the unexpected death of her owner-manager spouse when she had no salient role in the business prior to the death.

Design/methodology/approach

We used a qualitative approach to research, to study inductively the roles considered and taken by three widows who unexpectedly succeeded as owners of Swedish privately held family firms. We conducted semi-structured interviews with widows and children in top management.

Findings

We construct a typology of four main roles a widow can take and analyse the underlying dimensions that they represent. We also analyse to which extent the choice of role widow can be explained by psychological ownership and double-loss theory. The typology can be used as a tool for family business owners and their advisors as the basis of an open and non-prejudiced discussion of the choices available to a widow.

Originality/value

We have investigated the factors that influence a widow's decision whether to take over the business or not, as suggested in previous research by, for example, Martinez et al. (2009). We explore the roles a widow can consider and adopt. The study advances our understanding of how businesses can remain as family firms also in the event of the unexpected death of an owner-manager (De Massis et al., 2008). We hereby contribute to the literature on sudden successions and on women in family businesses.
Approaches to learning in the context of work – workplace learning and human resources
Authors: Brandi Ulrik , Iannone Rosa Lisa
Published: May 2021

Purpose

With the purpose of promoting cross-field dialogue, this paper aims to review workplace learning (WPL) and human resource (HR) literature. The authors endeavour a conceptual examination and discussion of the bridges that link both research fields in relation to learning, in an effort to establish an integrated understanding of learning in workplaces.

Design/methodology/approach

This paper uses a scoping review focused on how learning is approached in WPL and HR studies. An analysis of the selected literature reveals fundamental themes and dimensions that further our understanding of learning in the context of work.

Findings

Overall, there are three learning dimensions where WPL and HR conceptually interrelate, namely, skills, incentives and work design. The scoping review also shows that HR is output-oriented and looks to learning as capital for enterprises, especially in light of enterprise performance for competence development. WPL centres more upon socio-cultural and practice-based configurations and the individual. It encompasses the human dimension of learning as something enriching the whole of life, including work life.

Originality/value

This paper contributes with a unique inquiry into the interrelations between WPL and HR approaches to learning, highlighting the complementarity between WPL theoretical features and HR practices. At the core of our findings is that WPL becomes analytically visible through how HR learning strategies are designed and deployed in the forms of skill development, incentive structures and work design, referring to both workplace structure and cultural features.
The impact of green bonds on corporate environmental and financial performance
Authors: Yeow Kim Ee , Ng Sin-Huei
Published: May 2021

Purpose

As investors' expectations shift toward corporate sustainability, many corporations have jumped on the bandwagon of being “green” by issuing green bonds. However, as a recent green financing tool, little attention has been paid on the value that green bonds actually deliver. This causes the problem of greenwashing, in which firms pretend to be environmentally responsible when in reality they are not. This study therefore aims to explore green bonds' impact on issuers' corporate environmental and financial performance.

Design/methodology/approach

The sample is collected from among the green bond and conventional bond issues between 2015 and 2019 issued by corporations from various countries. Using the propensity score matching (PSM) and then difference-in-difference (DiD) approaches, two sub-groups (green bond and conventional bond issuers) were generated for comparison. Changes in environmental and financial performance over time between the sub-groups are then examined.

Findings

The overall results show that green bonds are effective in improving environmental performance, but only when they are certified by third parties. Additionally, green bonds do not have an impact on financial performance. The findings imply that green bonds' dependency on external certification may be a consequence of an underdeveloped green bond market, where weak governance still dominates the green bond market. Because of this, corporations tend to take advantage of green finance's growing popularity, causing the greenwashing problem.

Originality/value

Green bonds are an extremely new area of research. Few research studies focus on the effectiveness of green bonds in impacting corporate financial and environmental performance. Therefore, this study strives to fill this research gap. It sheds light on the effectiveness of green bonds in supporting the development of green projects and provides a reference point for decision-making in strengthening transparency and accountability in environmental disclosure and helps regulating authorities develop tighter regulatory controls.