bluuebunny/crossref_metadata_2025 huggingface dataset:
On a Reef Far, Far Away: Anthropogenic Impacts Following Extreme Storms Affect Sponge Health and Bacterial Communities
Authors: Shore Amanda , Sims Jordan A. , Grimes Michael , Howe-Kerr Lauren I. , Grupstra Carsten G.B. , Doyle Shawn M. , Stadler Lauren , Sylvan Jason B. , Shamberger Kathryn E.F. , Davies Sarah W. , Santiago-Vázquez Lory Z. , Correa Adrienne M.S.
Published: April 2020

Terrestrial runoff can negatively impact marine ecosystems through stressors including excess nutrients, freshwater, sediments, and contaminants. Severe storms, which are increasing with global climate change, generate massive inputs of runoff over short timescales (hours to days); such runoff impacted offshore reefs in the northwest Gulf of Mexico (NW GoM) following severe storms in 2016 and 2017. Several weeks after coastal flooding from these events, NW GoM reef corals, sponges, and other benthic invertebrates -185 km offshore experienced mortality (2016 only) and/or sub-lethal stress (both years). To assess the impact of storm-derived runoff on reef filter feeders, we characterized the bacterial communities of two sponges,Agelas clathrodesandXestospongia muta, from offshore reefs during periods of sub-lethal stress and no stress over a three-year period (2016-2018). Sponge-associated bacterial communities were altered during both flood years. Additionally, we found evidence of wastewater contamination (based on 16S rRNA gene libraries and quantitative PCR) in offshore sponges following these flood years, but not during the no-flood year. We show that flood events from severe storms have the capacity to reach offshore reef ecosystems and impact resident benthic organisms. Such impacts are most readily detected if baseline data on organismal physiology and associated microbiome composition are available. This highlights the need for molecular and microbial time series of benthic organisms in near- and offshore reef ecosystems, and the continued mitigation of stormwater runoff and climate change impacts.
Population dynamics analysis ofSaccharomyces cerevisiaedeletion library during fed-batch cultivation using Bar-seq
Authors: Wehrs Maren , Thompson Mitchell G. , Banerjee Deepanwita , Prahl Jan-Philip , Barcelos Carolina A. , Moon Jadie , Morella Norma M. , Costello Zak , Keasling Jay D. , Shih Patrick M. , Tanjore Deepti , Mukhopadhyay Aindrila
Published: April 2020

To understand the genetic basis of changes in strain physiology during industrial fermentation, and the corresponding roles these genes play in strain performance, we employed a barcoded yeast deletion library to assess genome-wide strain fitness across a simulated industrial fermentation regime. Our results demonstrate the utility of Bar-seq to assess fermentation associated stresses in yeast populations under industrial conditions. We find that mutant population diversity is maintained through multiple seed trains, enabling for large scale fermentation selective pressures to act upon the community. We identify specific deletion mutants that were enriched in all processes, independent of the cultivation conditions, which includeMCK1, RIM11, MRK1, andYGK3that encode homologues of mammalian glycogen synthase kinase 3 (GSK-3). Further, we show that significant changes in the population diversity during fed-batch cultivations reflect the presence of significant external stresses, such as the accumulation of the fermentative byproduct ethanol. The mutants that were lost during the time of most extreme population selection suggest that specific biological processes may be required to cope with these specific stresses. Overall our work highlights a promising avenue to identify genetic loci and biological stress responses required for fitness under industrial conditions.
Visualization and sequencing of accessible chromatin reveals cell cycle and post romidepsin treatment dynamics
Authors: Estève Pierre-Olivier , Vishnu Udayakumar S. , Chin Hang Gyeong , Pradhan Sriharsa
Published: April 2020

Chromatin accessibility is a predictor of gene expression, cell division and cell type specificity. NicE-viewSeq (NickingEnzyme assistedviewing andSequencing) allows accessible chromatin visualization and sequencing with overall lower mitochondrial DNA and duplicated sequences interference relative to ATAC-see. Using NicE-viewSeq, we interrogated the accessibility of chromatin in a cell cycle (G1, S and G2/M) - specific manner using mammalian cells. Despite DNA replication and subsequent condensation of chromatin to chromosomes, chromatin accessibility remained generally preserved with minimal subtle alterations. Genome-wide alteration of chromatin accessibility within TSS and enhancer elements gradually decreased as cells progressed from G1 to G2M, with distinct differential accessibility near consensus transcription factors sites. Inhibition of histone deacetylases promoted accessible chromatin within gene bodies, correlating with apoptotic gene expression. In addition, reduced chromatin accessibility for the MYC oncogene pathway correlated with down regulation of pertinent genes. Surprisingly, repetitive RNA loci expression remained unaltered following histone acetylation-mediated increased accessibility. Therefore, we suggest that subtle changes in chromatin accessibility is a prerequisite during cell cycle and histone deacetylase inhibitor mediated therapeutics.
New alignment-based sequence extraction software (ALiBaSeq) and its utility for deep level phylogenetics
Authors: Knyshov A. , Gordon E.R.L. , Weirauch C.
Published: April 2020

Despite many bioinformatic solutions for analyzing sequencing data, few options exist for targeted sequence retrieval from whole genomic sequencing (WGS) data. Available tools especially struggle at deep phylogenetic levels and necessitate amino-acid space searches, increasing rates of false positive results. Many such tools also suffer from difficult installation processes and lack adequate user resources. Here, we describe a program using freely available similarity search tools to find homologs in assembled WGS data with unparalleled freedom to modify parameters. We evaluate its performance as well as that of other utilized bioinformatics tools on two divergent insect species (>200 My) for which annotated genomes exist, as well as on one large set each of highly conserved and more variable loci. Our software is capable of retrieving orthologs from well-curated, low and high depth shotgun, and target capture assemblies as well or better than other software as assessed by finding the most genes with maximal coverage and with a low rate of false positives throughout all datasets. The software (implemented in Python), tutorials, and manual are freely available athttps://github.com/AlexKnyshov/alibaseq.
Testosterone induces a female ornament followed by enhanced territoriality in a tropical songbird
Authors: Boersma Jordan , Enbody Erik D. , Jones John Anthony , Nason Doka , Lopez-Contreras Elisa , Karubian Jordan , Schwabl Hubert
Published: April 2020

We know little of the proximate mechanisms underlying expression of signaling traits in female vertebrates. Across males the expression of sexual and competitive traits, including ornamentation and aggressive behavior, is often mediated by testosterone. In the White-shouldered Fairywren (Malurus alboscapulatus) of New Guinea, females of different subspecies differ in presence or absence of white shoulder patches and melanic plumage, while males are uniformly ornamented. Previous work has shown that ornamented females circulate more testosterone and exhibit more territorial aggression than do unornamented females. We investigated the degree to which testosterone regulates expression of ornamental plumage and territorial behavior by implanting free-living unornamented females with testosterone. Every testosterone-treated female produced a male-like cloacal protuberance, and 15 of 20 replaced plucked brown feathers with white shoulder patch feathers, but did not produce melanic plumage characteristic of ornamented females. Testosterone treatment did not elevate territorial behavior prior to production of the plumage ornament and exhaustion of the implant. However, females with experimentally induced ornamentation, but exhausted implants, increased the vocal components of territory defense relative to fully unornamented control and also to testosterone-implanted females. Our results suggest that testosterone induces partial acquisition of the ornamental plumage phenotype, and that ornament expression, rather than testosterone alone, results in elevated territorial behavior.

Lay Summary

Testosterone regulates expression of a suite of competitive traits in male organisms and could have similar function in females. Empirical tests are needed to determine the extent to which testosterone promotes production of ornamentation and competitive behaviors in female animals. We supplemented testosterone in unornamented females of a species where naturally occurring ornamented females circulate higher testosterone and are more territorially aggressive. Implanted females produced partial ornamentation, which was followed by increased territoriality that was apparently unrelated to testosterone circulation itself.
Implications of back-and-forth motion and powerful propulsion for spirochetal invasion
Authors: Abe Keigo , Kuribayashi Toshiki , Takabe Kyosuke , Nakamura Shuichi
Published: April 2020

The spirocheteLeptospiraspp. can move in liquid and on a solid surface using two periplasmic flagella (PFs), and its motility is an essential virulence factor for the pathogenic species. Mammals are infected with the spirochete through the wounded dermis, which implies the importance of behaviors on the boundary with such viscoelastic milieu; however, the leptospiral pathogenicity involving motility remains unclear. We used a glass chamber containing a gel area adjoining the leptospiral suspension to resemble host dermis exposed to contaminated water and analyzed the motility of individual cells at the liquid-gel border. Insertion of one end of the cell body to the gel increased switching of the swimming direction. Moreover, the swimming force ofLeptospirawas also measured by trapping single cells using an optical tweezer. It was found that they can generate ∼17 pN of force, which is ∼30 times of the swimming force ofEscherichia coli. The force-speed relationship suggested the load-dependent force enhancement and showed that the power (the work per unit time) for the propulsion is ∼3.1×10−16W, which is two-order of magnitudes larger than the propulsive power ofE. coli. The powerful and efficient propulsion ofLeptospirausing back-and-forth movements could facilitate their invasion.
Safety, pharmacokinetics, and liver-stagePlasmodium cynomolgieffect of high-dose ivermectin and chloroquine in Rhesus Macaques
Authors: Vanachayangkul Pattaraporn , Im-erbsin Rawiwan , Tungtaeng Anchalee , Kodchakorn Chanikarn , Roth Alison , Adams John , Chaisatit Chaiyaporn , Saingam Piyaporn , Sciotti Richard J. , Reichard Gregory A. , Nolan Christina K. , Pybus Brandon S. , Black Chad C. , Lugo Luis A. , Wegner Matthew D. , Smith Philip L. , Wojnarski Mariusz , Vesely Brian A. , Kobylinski Kevin C.
Published: April 2020

Previously, ivermectin (1–10 mg/kg) was shown to inhibit liver-stage development ofPlasmodium bergheiin orally dosed mice. Here, ivermectin showed inhibition of thein vitrodevelopment ofPlasmodium cynomolgischizonts (IC50= 10.42 μM) and hypnozoites (IC50= 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for seven consecutive days was evaluated for prophylaxis or radical cure ofPlasmodium cynomolgiliver-stages in Rhesus macaques. No inhibition or delay to blood-stageP. cynomolgiparasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for seven days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)in vitro. Further ivermectin and chloroquine trials in humans are warranted to evaluate their role inPlasmodium vivaxcontrol and as adjunctive therapies against COVID-19 infections.
Loss of the extracellular matrix molecule tenascin-C leads to absence of reactive gliosis and promotes anti-inflammatory cytokine expression in an autoimmune glaucoma mouse model
Authors: Wiemann Susanne , Reinhard Jacqueline , Reinehr Sabrina , Cibir Zülal , Joachim Stephanie C. , Faissner Andreas
Published: April 2020

Previous studies demonstrated that retinal damage correlates with a massive remodeling of extracellular matrix (ECM) molecules and reactive gliosis. However, the functional significance of the ECM in retinal neurodegeneration is still unknown. In the present study, we used an intraocular pressure (IOP) independent experimental autoimmune glaucoma (EAG) mouse model to examine the role of the ECM glycoprotein tenascin-C (Tnc).

Wild type (WT ONA) and Tnc knockout (KO ONA) mice were immunized with an optic nerve antigen (ONA) homogenate and control groups (CO) obtained sodium chloride (WT CO, KO CO). IOP was measured weekly and electroretinographies were recorded at the end of the study. 10 weeks after immunization, we analyzed retinal ganglion cells (RGCs), glial cells and the expression of different cytokines in retina and optic nerve tissue in all four groups.

IOP and retinal function was comparable in all groups. Although less severe in KO ONA, WT and KO mice displayed a significant loss of RGCs after immunization. Compared to KO ONA, a significant reduction of βIII-tubulin stained axons and oligodendrocyte markers was noted in the optic nerve of WT ONA. In retinal and optic nerve slices, we found an enhanced GFAP+staining area of astrocytes in immunized WT. In retinal flat-mounts, a significantly higher number of Iba1+microglia was found in WT ONA, while a lower number of Iba1+cells was observed in KO ONA. Furthermore, an increased expression of the glial markersGfap, Iba1, Nos2andCd68was detected in retinal and optic nerve tissue of WT ONA, whereas comparable levels were observed in KO ONA post immunization. In addition, pro-inflammatoryTnfaexpression was upregulated in WT ONA, but downregulated in KO ONA. Vice versa, a significantly increased anti-inflammatoryTgfbexpression was measured in KO ONA animals.

Collectively, this study revealed that Tnc plays an important role in glial and inflammatory response during retinal neurodegeneration. Our results provide evidence that Tnc is involved in glaucomatous damage by regulating retinal glial activation and cytokine release. Thus, this transgenic EAG mouse model offers for the first time the possibility to investigate IOP-independent glaucomatous damage in direct relation to ECM remodeling.
Bistability in oxidative stress response determines the migration behavior of phytoplankton in turbulence
Authors: Carrara Francesco , Sengupta Anupam , Behrendt Lars , Vardi Assaf , Stocker Roman
Published: April 2020

Turbulence is an important determinant of phytoplankton physiology, often leading to cell stress and damage. Turbulence affects phytoplankton migration, both by transporting cells and by triggering switches in migratory behavior, whereby vertically migrating cells can invert their direction of migration upon exposure to turbulent cues. However, a mechanistic link between single-cell physiology and vertical migration of phytoplankton in turbulence is currently missing. Here, by combining physiological and behavioral experiments with a mathematical model of stress accumulation and dissipation, we show that the mechanism responsible for the switch in the direction of migration in the marine raphidophyteHeterosigma akashiwois the integration of reactive oxygen species (ROS) signaling generated by turbulent cues. Within timescales as short as tens of seconds, the emergent downward-migrating subpopulation exhibited a two-fold increase of ROS, an indicator of stress, 15% lower photosynthetic efficiency, and 35% lower growth rate over multiple generations compared to the upward-migrating subpopulation. The origin of the behavioral split in a bistable oxidative stress response is corroborated by the observation that exposure of cells to exogenous stressors (H2O2, UV-A radiation or high irradiance), in lieu of turbulence, caused comparable ROS accumulation and an equivalent split into the two subpopulations. By providing a mechanistic link between single-cell physiology, population-scale migration and fitness, these results contribute to our understanding of phytoplankton community composition in future ocean conditions.

Significance Statement

Turbulence has long been known to drive phytoplankton fitness and species succession: motile species dominate in calmer environments and non-motile species in turbulent conditions. Yet, a mechanistic understanding of the effect of turbulence on phytoplankton migratory behavior and physiology is lacking. By combining a method to generate turbulent cues, quantification of stress accumulation and physiology, and a mathematical model of stress dynamics, we show that motile phytoplankton use their mechanical stability to sense the intensity of turbulent cues and integrate these cues in time via stress signaling to trigger switches in migratory behavior. The stress-mediated warning strategy we discovered provides a paradigm for how phytoplankton cope with turbulence, thereby potentially governing which species will be successful in a changing ocean.
Self-reported sleep problems are related to cortical thinning in aging but not memory decline and amyloid-β accumulation – results from the Lifebrain consortium
Authors: Fjell Anders M. , Sørensen Øystein , Amlien Inge K. , Bartrés-Faz David , Brandmaier Andreas M. , Buchmann Nikolaus , Demuth Ilja , Drevon Christian A , Düzel Sandra , Ebmeier Klaus P. , Ghisletta Paolo , Idland Ane-Victoria , Kietzmann Tim C. , Kievit Rogier A. , Kühn Simone , Lindenberger Ulman , Magnussen Fredrik , Macià Didac , Mowinckel Athanasia M. , Nyberg Lars , Sexton Claire E. , Solé-Padullés Cristina , Pudas Sara , Roe James M. , Sederevicius Donatas , Suri Sana , Vidal-Piñeiro Didac , Wagner Gerd , Watne Leiv Otto , Westerhausen René , Zsoldos Enikő , Walhovd Kristine B. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2020

Background

Older persons with poor sleep are more likely to develop neurodegenerative disease, but the causality underlying this association is unclear. To move towards explanation, we examine whether sleep quality and quantity are similarly associated with brain changes across the adult lifespan.

Methods

Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index;PSQI) and longitudinal cortical change were tested using five samples from theLifebrainconsortium (n=2205, 4363 MRIs, 18-92 years). Analyses were augmented by considering episodic memory change, gene expression from the Allen Human Brain Atlas, and amyloid-beta (Aβ) accumulation (n=1980).

Results

PSQI components sleep problems and low sleep quality were related to thinning of the right lateral temporal cortex. The association with sleep problems emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. BMI and symptoms of depression had negligible effects. Sleep problems were neither related to longitudinal change in episodic memory function nor to Aβ accumulation, suggesting that sleep-related cortical changes were independent of AD neuropathology and cognitive decline.

Conclusion

Worse self-reported sleep in later adulthood was associated with more cortical thinning in regions of high expression of genes related to oligodendrocytes and S1 pyramidal neurons, but not to Aβ accumulation or memory decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes, except for a few restricted regions, indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
GeneTEFlow: A Nextflow-based pipeline for analysing gene and transposable elements expression from RNA-Seq data
Authors: Liu Xiaochuan , Bienkowska Jadwiga R , Zhong Wenyan
Published: April 2020

Transposable elements (TEs) are mobile genetic elements in eukaryotic genomes. Recent research highlights the important role of TEs in the embryogenesis, neurodevelopment, and immune functions. However, there is a lack of a one-stop and easy to use computational pipeline for expression analysis of both genes and locus-specific TEs from RNA-Seq data. Here, we present GeneTEFlow, a fully automated, reproducible and platform-independent workflow, for the comprehensive analysis of gene and locus-specific TEs expression from RNA-Seq data employing Nextflow and Docker technologies. This application will help researchers more easily perform integrated analysis of both gene and TEs expression, leading to a better understanding of roles of gene and TEs regulation in human diseases. GeneTEFlow is freely available athttps://github.com/zhongw2/GeneTEFlow.
Mosquito defensins enhance Japanese encephalitis virus infection by facilitating virus adsorption and entry within mosquito
Authors: Liu Ke , Xiao Changguang , Xi Shumin , hameed Muddassar , Wahaab Abdul , Shao Donghua , Li Zongjie , Li Beibei , Wei Jianchao , Qiu Yafeng , Miao Denian , Zhu Huaimin , Ma Zhiyong
Published: April 2020

Japanese encephalitis virus (JEV) is a viral zoonosis which can cause viral encephalitis, death and disability.Culexis the main vector of JEV, but little is known about JEV transmission by this kind of mosquito. Here, we found that mosquito defensin facilitated the adsorption of JEV on target cells via both direct and indirect pathways. Mosquito defensin bound the ED III domain of viral E protein and directly mediated efficient virus adsorption on the target cell surface, Lipoprotein receptor-related protein 2 expressed on the cell surface is the receptor affecting defensin dependent adsorption. Mosquito defensin also indirectly down-regulated the expression of an antiviral protein, HSC70B. As a result, mosquitos defensin enhances JEV infection in salivary gland while increasing the possibility of viral transmission by mosquito. These findings demonstrate that the novel effects of mosquito defensin in JEV infection and the mechanisms through which the virus exploits mosquito defensin for infection and transmission.
Extensive 5’-Surveillance Guards Against Non-Canonical NAD-Caps of Nuclear mRNAs in Yeast
Authors: Zhang Yaqing , Kuster David , Schmidt Tobias , Kirrmaier Daniel , Nübel Gabriele , Ibberson David , Benes Vladimir , Hombauer Hans , Knop Michael , Jäschke Andres
Published: April 2020

The ubiquitous redox coenzyme nicotinamide adenine dinucleotide (NAD) acts as a non-canonical cap structure on prokaryotic and eukaryotic ribonucleic acids. Here we find that in budding yeast, NAD-RNAs are abundant (>1400 species), short (<170 nt), and mostly correspond to mRNA 5’-ends. The modification percentage is low (<5%). NAD is incorporated during the initiation step by RNA polymerase II, which uses distinct promoters with a YAAG core motif for this purpose. Most NAD-RNAs are 3’-truncated. At least three decapping enzymes, Rai1, Dxo1, and Npy1, guard against NAD-RNA at different cellular locations, targeting overlapping transcript populations. NAD-mRNAs do not support translationin vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.

In Brief

In budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.

Graphical Abstract

Highlights

Yeast cells have thousands of short NAD-RNAs related to the 5’-ends of mRNAs

RNA polymerase II prefers a YAAG promoter motif for NAD incorporation into RNA

NAD-RNA is strongly guarded against by Rai1, Dxo1, and Npy1 decapping enzymes at different subcellular sites

In vitro, NAD-mRNAs are rejected from translation
MicroRNA composition delineates cardiosphere-derived cell and mesenchymal stem cell extracellular vesicles
Authors: Walravens Ann-Sophie , Smolgovsky Sasha , Li Liang , Kelly Lauren , Antes Travis , Peck Kiel , Quon Tanner , Marbán Linda , Berman Benjamin , -Borlado Luis R. , de Couto Geoffrey
Published: April 2020

Cell therapy limits ischemic injury following myocardial infarction (MI) by limiting cell death, modulating the immune response, and promoting tissue regeneration. The therapeutic efficacy of cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs) is associated with extracellular vesicle (EV) release. Despite differences in cell origin, it is unclear why EVs elicit differences in therapeutic potency between cell types. Here, we compare EVs derived from multiple MSC and CDC donors. We reveal that EV membrane protein and microRNA (miR) composition are reflective of their parent cell. Small RNA-sequencing revealed enrichment of miR-10b in MSC EVs. Our data support the hypothesis that CDC EVs are distinct from MSC-EVs and is reflected by their miR composition.
Field-deployable molecular diagnostic platform for arbovirus andWolbachiadetection inAedes aegypti
Authors: Rutkowski Natalie N. , Dong Yuemei , Dimopoulos George
Published: April 2020

Background

Surveillance of mosquito infection status is critical for planning and deployment of proper mosquito control initiatives. Concurrently,Wolbachiais being widely used as a control method for arboviral transmission. Point-of-care (POC) detection assays are necessary for monitoring the infection prevalence and geographic range of viruses as well asWolbachiain mosquito vector populations. We therefore assessed the novel qPCR bCUBE molecular diagnostic system as a tool for virus andWolbachiadetection.

Results

We developed a reliable, specific, and sensitive diagnostic assay for detecting Zika virus and dengue virus serotype 2 using the real-time qPCR platform bCUBE. With bCUBE-based qRT-PCR, bothWolbachiabacterium and virus RNA could be reliably detected in individually infectedAe. aegyptimosquitoes and in pools of 5, 10, or 15 mosquitoes.

Conclusions

The portable qPCR bCUBE diagnostic platform is capable of detecting Zika and dengue virus as well asWolbachiain mosquitoes and therefore has potential as a practical field-deployable diagnostic test for vector-borne disease surveillance programs.
Using Expansion Microscopy to visualize and characterize the morphology of mitochondrial cristae
Authors: Kunz Tobias C. , Götz Ralph , Gao Shiqiang , Sauer Markus , Kozjak-Pavlovic Vera
Published: April 2020

Mitochondria are double membrane bound organelles indispensable for biological processes such as apoptosis, cell signalling, and the production of many important metabolites, which includes ATP that is generated during the process known as oxidative phosphorylation (OXPHOS). The inner membrane contains folds called cristae, which increase the membrane surface and thus the amount of membrane-bound proteins necessary for the OXPHOS. These folds have been of great interest not only because of their importance for energy conversion, but also because changes in morphology have been linked to a broad range of diseases from cancer, diabetes, neurodegenerative diseases, to ageing and infection. With a distance between opposing cristae membranes often below 100 nm, conventional fluorescence imaging cannot provide a resolution sufficient for resolving these structures. For this reason, various highly specialized super-resolution methods includingdSTORM, PALM, STED and SIM have been applied for cristae visualisation.

Expansion Microscopy (ExM) offers the possibility to perform super-resolution microscopy on conventional confocal microscopes by embedding the sample into a swellable hydrogel that is isotropically expanded by a factor of 4-4.5, improving the resolution to 60-70 nm on conventional confocal microscopes, which can be further increased to ∼ 30 nm laterally using SIM. Here, we demonstrate that the expression of the mitochondrial creatine kinase MtCK linked to marker protein GFP (MtCK-GFP), which localizes to the space between the outer and the inner mitochondrial membrane, can be used as a cristae marker. Applying ExM on mitochondria labelled with this construct enables visualization of morphological changes of cristae and localization studies of mitochondrial proteins relative to cristae without the need for specialized setups. For the first time we present the combination of specific mitochondrial intermembrane space labelling and ExM as a tool for studying internal structure of mitochondria.
Mammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males
Authors: Menon Debashish U. , Magnuson Terry
Published: April 2020

BRG1, a catalytic subunit of the mammalian SWI/SNF nucleosome remodeler is essential for male meiosis1. In addition to BRG1, multiple subunits (~10-14) some of which are mutually exclusive, constitute biochemically distinct SWI/SNF subcomplexes, whose functions in gametogenesis remain unknown. Here, we identify a role for the PBAF (Polybromo- Brg1AssociatedFactor) complex in the regulation of meiotic cell division. The germ cell-specific depletion of PBAF specific subunit, ARID2 resulted in a metaphase-I arrest.Arid2cKOmetaphase-I spermatocytes displayed defects in chromosome organization and spindle assembly. Additionally, mutant centromeres were devoid of Polo-like kinase1 (PLK1), a known regulator of the spindle assembly checkpoint (SAC)2. The loss of PLK1 coincided with an abnormal chromosome-wide expansion of centromeric chromatin modifications such as Histone H3 threonine3 phosphorylation (H3T3P) and Histone H2A threonine120 phosphorylation (H2AT120P) that are critical for chromosome segregation3,4. Consistent with the known role of these histone modifications in chromosome passenger complex (CPC) recruitment,Arid2cKOmetaphase-I chromosomes display defects in CPC association. We propose that ARID2 facilitates metaphase-I exit by regulating spindle assembly and centromeric chromatin.
Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin
Authors: Mycroft-West Courtney J. , Su Dunhao , Pagani Isabel , Rudd Timothy R. , Elli Stefano , Guimond Scott E. , Miller Gavin , Meneghetti Maria C. Z. , Nader Helena B. , Li Yong , Nunes Quentin M. , Procter Patricia , Mancini Nicasio , Clementi Massimo , Bisio Antonella , Forsyth Nicholas R. , Turnbull Jeremy E. , Guerrini Marco , Fernig David G. , Vicenzi Elisa , Yates Edwin A. , Lima Marcelo A. , Skidmore Mark A.
Published: April 2020

The dependence of the host on the interaction of hundreds of extracellular proteins with the cell surface glycosaminoglycan heparan sulphate (HS) for the regulation of homeostasis is exploited by many microbial pathogens as a means of adherence and invasion. The closely related polysaccharide heparin, the widely used anticoagulant drug, which is structurally similar to HS and is a common experimental proxy, can be expected to mimic the properties of HS. Heparin prevents infection by a range of viruses if added exogenously, including S-associated coronavirus strain HSR1. Heparin prevents infection by a range of viruses if added exogenously, including S-associated coronavirus strain HSR1. Here, we show that the addition of heparin to Vero cells between 6.25 - 200 μg.ml−1, which spans the concentration of heparin in therapeutic use, and inhibits invasion by SARS-CoV-2 at between 44 and 80%. We also demonstrate that heparin binds to the Spike (S1) protein receptor binding domain and induces a conformational change, illustrated by surface plasmon resonance and circular dichroism spectroscopy studies. The structural features of heparin on which this interaction depends were investigated using a library of heparin derivatives and size-defined fragments. Binding is more strongly dependent on the presence of 2-O or 6-O sulphation, and the consequent conformational consequences in the heparin structure, than on N-sulphation. A hexasaccharide is required for conformational changes to be induced in the secondary structure that are comparable to those that arise from heparin binding. Enoxaparin, a low molecular weight clinical anticoagulant, also binds the S1 RBD protein and induces conformational change. These findings have implications for the rapid development of a first-line therapeutic by repurposing heparin as well as for next-generation, tailor-made, GAG-based antiviral agents against SARS-CoV-2 and other members of theCoronaviridae.
7-Iodo-5-aza-7-deazaguanine ribonucleoside: crystal structure, physical properties, base-pair stability and functionalization
Authors: Kondhare Dasharath , Budow-Busse Simone , Daniliuc Constantin , Seela Frank
Published: April 2020

The positional change of nitrogen-7 of the RNA constituent guanosine to the bridgehead position-5 leads to the base-modified nucleoside 5-aza-7-deazaguanosine. Contrary to guanosine, this molecule cannot form Hoogsteen base pairs and the Watson–Crick proton donor site N3—H becomes a proton-acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable `all-purine' DNA and DNA with silver-mediated base pairs. The present work reports the single-crystal X-ray structure of 7-iodo-5-aza-7-deazaguanosine, C10H12IN5O5(1). The iodinated nucleoside shows ananticonformation at the glycosylic bond and anNconformation (O4′-endo) for the ribose moiety, with an antiperiplanar orientation of the 5′-hydroxy group. Crystal packing is controlled by interactions between nucleobase and sugar moieties. The 7-iodo substituent forms a contact to oxygen-2′ of the ribose moiety. Self-pairing of the nucleobases does not take place. A Hirshfeld surface analysis of1highlights the contacts of the nucleobase and sugar moiety (O—H...O and N—H...O). The concept of pK-value differences to evaluate base-pair stability was applied to purine–purine base pairing and stable base pairs were predicted for the construction of `all-purine' RNA. Furthermore, the 7-iodo substituent of1was functionalized with benzofuran to detect motional constraints by fluorescence spectroscopy.
China’s green watch program: beyond greenwashing
Authors: Miller Van V. , Su Qi , Perez-Batres Luis A. , Pisani Michael J.
Published: April 2020

Purpose

This paper aims to provide a more inclusive perspective on corporate greenwashing. Major ideas from impression management and transaction cost theory (TCT) helped in evaluating the likelihood of greenwashing within the Chinese context.

Design/methodology/approach

The sample consists of 184 Chinese public companies – 104 participating and 80 not participating in China’s green watch (GW) program. Using logistic regression, the analysis illustrates the importance of impression management and TCT as indicators of GW participation.

Findings

GW participation reduced the likelihood of GW firms joining substantive codes of conduct outside the GW program, indicating an important role of impression management and power relationships; a higher level of firm risk is associated with greater GW participation, signaling a higher level of risk tolerance; and higher levels of asset intensity increase the likelihood of GW participation, indicating a TCT connection.

Research limitations/implications

These findings present a strong case for going beyond greenwashing and further exploring the organizations’ multiple motives for sustainability. They “force” the authors to study impression management and greenwashing from a more “human” perspective.

Practical implications

Besides establishing sustainability legitimacy, substantive codes of conduct enhance a firm’s ability to attract capital – impression management behavior falls within the rules of the game to achieve legitimacy and competitive advantage.

Originality/value

This paper provides a complementary explanation for firms engaging in sustainability acts, beyond that offered by the greenwashing concept. It is demonstrated that firms do not necessarily desire to deceive others, but to realistically impress and influence them, most likely in pursuit of corporate objectives.
A bi‐objective inventory routing problem with interval grey demand data
Authors: Kahraman Ömer Utku , Aydemir Erdal
Published: April 2020

Purpose

The purpose of this paper is to manage the demand uncertainty considered as lower and upper levels for a medium-scale industrial distribution planning problem in a biobjective inventory routing problem (IRP). In order to achieve this, the grey system theory is applied since no statistical distribution from the past data and incomplete information.

Design/methodology/approach

This study is investigated with optimizing the distribution plan, which involves 30 customers of 12 periods in a manufacturing company under demand uncertainty that is considered as lower and upper levels for a biobjective IRP with using grey demand parameters as a grey integer programming model. In the data set, there are also some missing demand values for the customers. So, the seven different grey models are developed to eliminat the effects on demand uncertainties in computational analysis using a piece of developed software considering the logistical performance indicators such as total deliveries, total cost, the total number of tours, distribution capacity, average remaining capacity and solution time.

Findings

Results show that comparing the grey models, the cost per unit and the maximum number of vehicle parameters are also calculated as the new key performance indicator, and then results were ranked and evaluated in detail. Another important finding is the demand uncertainties can be managed with a new approach via logistics performance indicators using alternative solutions.

Practical implications

The results enable logistics managers to understand the importance of demand uncertainties if more reliable decisions are wanted to make with obtaining a proper distribution plan for effective use of their expectations about the success factors in logistics management.

Originality/value

The study is the first in terms of the application of grey models in a biobjective IRP with using interval grey demand data. Successful implementation of the grey approaches allows obtaining a more reliable distribution plan. In addition, this paper also offers a new key performance indicator for the final decision.
Choosing mothering and entrepreneurship: a relational career-life process
Authors: Hudson Breen Rebecca , Leung Aegean
Published: April 2020

Purpose

To date, research on women’s entrepreneurship has largely been focused on how gender roles may constrain the venture process, or cause role conflicts for women pursuing an entrepreneurial career. While acknowledging the validity of such perspectives, the purpose of this paper is to apply a broader perspective of career-life development, answering the call for a more nuanced and embedded understanding of an entrepreneurial career.

Design/methodology/approach

This paper presents a constructionist, relational analysis of the experiences of 13 Canadian women who started their business following the life transition to motherhood. Interview data were coded using grounded theory methods.

Findings

The conceptual model captures the influence of the mothering role in shaping the transition into entrepreneurship, illuminating the reciprocal relational processes of context, choice and outcomes in the career-life development of mother entrepreneurs.

Research limitations/implications

While this is a small sample, and findings are not generalizable, application of relational theory of career-life offers implications for supporting women’s transition to, and continued success in, entrepreneurship.

Practical implications

Career theory offers practical application to the management of mother entrepreneurs’ career-life development.

Originality/value

To date, there has been limited application of career theory to entrepreneurship, particularly to understanding the gendered, relational career-life experiences of mother entrepreneurs.
Drivers of housing purchasing decisions: a data-driven analysis
Authors: BuHamdan Samer , Alwisy Aladdin , Bouferguene Ahmed
Published: April 2020

Purpose

The purpose of this paper is to develop a clear understanding of the features that increase the probability of condos’ sale, with a focus on design-related features.

Design/methodology/approach

The present research uses survival analysis (SA) and the Cox proportional-hazards regression (CPHR) to analyze condo sales data provided by the REALTORS® Association of Edmonton (RAE) (Alberta, Canada).

Findings

The analysis of the provided data shows that the listed price, building age, appliances and condo fees have less effect on the time a condo spends on the market compared to the condo’s physical features, such as construction material, interior finishing and heating type and source.

Research limitations/implications

The data used in the present research comes from one geographical area (i.e. Edmonton, Canada). Furthermore, the data provided by the RAE does not include any real estate transactions not involving a realtor. Additionally, the present research, owing to its focus on design-related features, does not control features related to the external environment, such as community and transportation proximity.

Practical implications

The findings of the present research help construction practitioners (e.g. architects, builders and realtors) better understand the features that influence condo buyers’ decisions. This knowledge helps to develop designs and marketing strategies that increase the likelihood of selling and decrease the time listed condos spend on the market.

Originality/value

The present research expands our knowledge of the drivers influencing the purchasers’ decisions concerning the building’s physical features that can be controlled during the design stage. Also, analyzing the provided data by using SA and CPHR, as followed in this paper, facilitates the inclusion of records that are listed but not sold, which helps to overcome the survivorship bias and avoid the over-optimism that exists in the present literature.
Are you my mentor? A study of faculty mentoring relationships in US higher education and the implications for tenure
Authors: Etzkorn Karen B. , Braddock Ashton
Published: April 2020

Purpose

This study identifies (1) differences that exist between junior and senior faculty in their beliefs about the impact of mentoring; (2) interest among tenured and tenure-track faculty in participating in a mentoring relationship and (3) the extent to which faculty perceive mentoring as a critical component of the track to tenure.

Design/methodology/approach

Across a multicampus system of higher education, 1,017 faculty responded to an anonymous online survey that included both quantitative and open-ended items (response rate 51%).

Findings

Although all faculty perceive mentoring as valuable, there are significant differences among junior and senior faculty in their beliefs and perceptions about mentoring, as well as their participation in mentoring relationships.

Research limitations/implications

All five participating campuses operate in the same state under the same governing board, so the findings are not necessarily generalizable to other institutions or populations of faculty.

Practical implications

To support effective mentoring, it is necessary that higher education organizations institutionalize mentoring and develop a purposeful program in which they train/support mentors and allow for flexibility; it is also critical to solicit input from the faculty at various stages.

Originality/value

This study considered multiple aspects of tenure from multiple institution types within a system of higher education. Furthermore, this study compares junior and senior faculty perceptions and outcomes, which few previous studies have done.
Associate teachers' learning networks: a figurational analysis of initial teacher education
Authors: Jones Luke , Tones Steven , Foulkes Gethin
Published: April 2020

Purpose

The aim of this paper is to use the lens of figurational sociology to analyse the learning networks of physical education (PE) associate teachers (ATs) in England. More specifically, it aims to develop a more adequate understanding of who is involved in the learning networks and how they influence ATs during their one-year postgraduate initial teacher education (ITE) programme.

Design/methodology/approach

A total of 35 ATs within a university ITE partnership took part in the study during the final phase of their postgraduate programme. Questionnaires and semi-structured interviews were used to examine the nature and impact of the interdependent relationships that they had developed with other individuals and groups. A process of content analysis was used to identify and analyse patterns in the data.

Findings

Mentors have the most influence over ATs. They support the inclusion of the ATs within the PE department, but elements of the mentors' role are contradictory and can unintentionally hinder the ATs' teaching. Mentors, teachers and tutors also share a common social habitus that ensures a degree of conformity within the PE community. New experiences tend to reinforce ATs' existing beliefs about the nature and practice of teaching PE.

Practical implications

These findings have implications for providers of ITE in deciding who is involved in mentor training and how it is approached. If ATs are to be introduced to more innovative teaching approaches that promote change, then tutors need to collaborate with mentors and teachers to develop awareness of their often-unplanned influence.

Originality/value

Applying the distinctive, and more generally sociological, concepts that make up the figurational perspective helped to develop a more adequate understanding of the ATs' learning networks. It provided an insight into the changing relationships that ATs have with their mentors and other individuals who work within the school and university context.