bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 105 biological, socioeconomic, behavioural, and environmental factors on the risk of SARS-CoV-2 infection and a severe course of Covid-19: A prospective longitudinal study
Authors: Flegr Jaroslav , Flegr Pavel , Příplatová Lenka
Published: September 2021

The confirmed number of SARS-CoV-2 infections up to 30 August 2021 is 217 mil. worldwide but information about factors affecting the probability of infection or of a severe course of Covid-19 remains insufficient and often speculative. Only a small number of factors have been rigorously examined, mostly by retrospective or cross-sectional studies. We ran a preregistered study on 5,164 internet users who shared with us information about their exposure to 105 risk factors and reported being Covid negative before the beginning of the fourth wave of Covid-19 in the Czech Republic. After the fourth wave, in which 709 (13.7%) of participants were infected, we used a partial Kendall test controlled for sex, age, and urbanisation to compare the risk of infection and of a severe course of the disease in subjects who originally did and did not report exposure to particular risk factors. After the correction for multiple tests, we identified 13 factors – including male sex, lower age, blood group B, and the larger household size – that increased the risk of infection and 16 factors – including mask wearing, borreliosis in the past, use of vitamin D supplements, or rooibos drinking – that decreased it. We also identified 23 factors that increased the risk of a severe course of Covid-19 and 12 factors that decreased the risk.
The non-steroidal anti-inflammatory drug nimesulide kills Gyps vultures at concentrations found in the muscle of treated cattle
Authors: Galligan Toby. H. , Green Rhys. E. , Wolter Kerri. , Taggart Mark. A. , Duncan Neil. , Mallord John. W. , Alderson Dawn. , Li Yuan. , Naidoo Vinny.
Published: September 2021

Throughout South Asia, cattle are regularly treated with non-steroidal anti-inflammatory drugs (NSAIDs) and their carcasses are left for scavengers to consume. Residues of the NSAID diclofenac in cattle carcasses caused widespread mortality and catastrophic population declines in three species of Gyps vulture during the 1990s and 2000s. Diclofenac is now banned, but other NSAIDs are used in its place. Different lines of evidence, including safety testing in Gyps vultures, have shown that some of these other NSAIDs are toxic, or probably toxic, to vultures. The NSAID nimesulide is widely available and commonly used, and has been found in dead vultures with signs of renal failure (i.e. visceral gout) and without the presence of diclofenac and/or other vulture-toxic NSAIDs. Nimesulide is therefore probably toxic to vultures. Here, we report safety testing of nimesulide in Gyps vultures. In a controlled toxicity experiment, we gave two vultures the maximum likely exposure of nimesulide calculated from initial pharmacokinetic and residue experiments in cattle. Two other control birds were given an oral dose of water. Both vultures dosed with nimesulide died within 30 h, after showing outward signs of toxicity and increases in biochemical indicators of renal failure. Post-mortem examinations found extensive visceral gout in both vultures. Both control vultures survived without biochemical indicators of renal failure. With this evidence, we call for an immediate and comprehensive ban of nimesulide throughout South Asia to ensure the survival of the region’s Critically Endangered vultures. More generally, testing the impacts of drugs on non-target species should be the responsibility of the pharmaceutical industry, before their veterinary use is licensed.
Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback
Authors: Tervo Aino E. , Nieminen Jaakko O. , Lioumis Pantelis , Metsomaa Johanna , Souza Victor H. , Sinisalo Heikki , Stenroos Matti , Sarvas Jukka , Ilmoniemi Risto J.
Published: September 2021

Background

Transcranial magnetic stimulation (TMS) is widely used in brain research and treatment of various brain dysfunctions. However, the optimal way to target stimulation and administer TMS therapies, for example, where and in which electric field direction the stimuli should be given, is yet to be determined.

Objective

To develop an automated closed-loop system for adjusting TMS parameters (in this work, the stimulus orientation) online based on TMS-evoked brain activity measured with electroencephalography (EEG).

Methods

We developed an automated closed-loop TMS–EEG set-up. In this set-up, the stimulus parameters are electronically adjusted with multi-locus TMS. As a proof of concept, we developed an algorithm that automatically optimizes the stimulation orientation based on single-trial EEG responses. We applied the algorithm to determine the electric field orientation that maximizes the amplitude of the TMS– EEG responses. The validation of the algorithm was performed with six healthy volunteers, repeating the search twenty times for each subject.

Results

The validation demonstrated that the closed-loop control worked as desired despite the large variation in the single-trial EEG responses. We were often able to get close to the orientation that maximizes the EEG amplitude with only a few tens of pulses.

Conclusion

Optimizing stimulation with EEG feedback in a closed-loop manner is feasible and enables effective coupling to brain activity.
Preproteins couple the intrinsic dynamics of SecA to its ATPase cycle to translocate via a catch and release mechanism
Authors: Krishnamurthy Srinath , Sardis Marios-Frantzeskos , Eleftheriadis Nikolaos , Chatzi Katerina E. , Smit Jochem H. , Karathanou Konstantina , Gouridis Giorgos , Portaliou Athina G. , Bondar Ana-Nicoleta , Karamanou Spyridoula , Economou Anastassios
Published: September 2021

Protein machines undergo conformational motions to interact with and manipulate polymeric substrates. The Sec translocase promiscuously recognizes, becomes activated and secretes >500 non-folded preprotein clients across bacterial cytoplasmic membranes. Here, we reveal that the intrinsic dynamics of the translocase ATPase, SecA, and of preproteins combine to achieve translocation. SecA possesses an intrinsically dynamic preprotein clamp attached to an equally dynamic ATPase motor. Alternating motor conformations are finely controlled by the γ-phosphate of ATP, while ADP causes motor stalling, independently of clamp motions. Functional preproteins physically bridge these independent dynamics. Their signal peptide promotes clamp closing; their mature domain overcomes the rate limiting ADP release. While repeated ATP cycles shift the motor between unique states, multiple conformationally frustrated prongs in the clamp repeatedly ‘catch and release’ trapped preprotein segments until translocation completion. This universal mechanism allows any preprotein to promiscuously recognize the translocase, usurp its intrinsic dynamics and become secreted.
Molecular mechanisms of the CdnG-Cap5 antiphage defense system employing 3’,2’-cGAMP as the second messenger
Authors: Fatma Shirin , Chakravarti Arpita , Zeng Xuankun , Huang Raven H.
Published: September 2021

Cyclic-oligonucleotide-based antiphage signaling systems (CBASS) are diverse and abundant in bacteria. Here, we present biochemical and structural characterization of two CBASS systems, composed of CdnG and Cap5, from Asticcacaulis sp. and Lactococcus lactis. We show that CdnG from Asticcacaulis sp. synthesizes 3’,2’-cGAMP in vitro, and 3’,2’-cGAMP is the biological signaling molecule that activates Cap5 for DNA degradation. Crystal structures of Cap5, together with the SAVED domain in complex with 3’,2’-cGAMP, provide insight into the architecture of Cap5 as well as molecular recognition of 3’,2’-cGAMP by the SAVED domain of Cap5. Amino acid conservation of the SAVED domain of Cap5, together with mutational studies, led us to propose a novel mechanism of Back-to-Front stacking of two SAVED domains, mediated by 3’,2’-cGAMP, to activate HNH nuclease domain for DNA degradation. Our study of the most abundant CBASS system provides new insight into mechanisms employed by bacteria in their conflicts against phage.
The evolutionary origin of host association in an ancient bacterial clade
Authors: Schön Max E. , Martijn Joran , Vosseberg Julian , Köstlbacher Stephan , Ettema Thijs J. G.
Published: September 2021

The evolution of obligate host-association of bacterial symbionts and pathogens remains poorly understood. The Rickettsiales represent an order of obligate alphaproteobacterial endosymbionts and parasites that infect a wide variety of eukaryotic hosts, including humans, livestock, insects and protists. Induced by their host-associated lifestyle, Rickettsiales genomes have undergone reductive evolution, leading to small, AT-rich genomes with limited metabolic capacities. We describe several genomes of deep-branching, environmental alphaproteobacteria that branch basal to previously sampled Rickettsiales, and whose genome content are reminiscent of free-living and biofilm-associated lifestyles. Ancestral genome content reconstruction across the Rickettsiales tree revealed that the free-living to host-association transition of this group occurred more recently than previously anticipated, and likely involved the repurposing of a type IV secretion system.

One-Sentence Summary

Deep-branching Rickettsiales provide insights into the evolution of obligate host-associated lifestyle
Multimodal characterization of the murine neurovascular niche using a novel microvascular isolation protocol
Authors: Bjørnholm Katrine Dahl , Vanlandewijck Michael , Del Gaudio Francesca , Lendahl Urban , Nilsson Per , Karlström Helena , Betsholtz Christer
Published: September 2021

The blood-brain barrier (BBB) is central to separate blood from the extracellular fluids of the brain. To understand disease-related changes in the BBB is pivotal and such changes can increasingly be studied by single-cell RNA sequencing (scRNAseq), which provides high-resolution insight into gene expression changes related to the pathophysiological response of the vasculature. However, analysis of the vascular cells in the brain is challenging due to the low abundance of these cells relative to neuronal and glial cells, and improved techniques for enrichment of the vascular component is therefore warranted. The present study describes a method whereby panning with CD31-coated magnetic beads allows isolation of brain vasculature without the need for transgenic reporter lines or FACS sorting. The protocol was tested in three modalities: isolation of cells for scRNAseq, western blot (WB) analysis, and primary cell culture. For scRNAseq, a total of 22,515 single-cell transcriptomes were generated from 12-months old mice and separated into 23 clusters corresponding to all known vascular and perivascular cell types. The most abundant cell type was endothelial cells (EC) (Pecam1- and Cdh5-positive), which dispersed into clusters of arterial, capillary, and venous EC according to previously established BBB arterio-venous zonation markers. Furthermore, we identified clusters of microglia (Aif1-positive), one cluster of fenestrated endothelial cells (Plvap-positive; Cldn5-negative), a cluster of pericytes (Kcnj8- and Abcc9-positive) and a cluster of vascular smooth muscle cells (VSMC) (Acta2- and Tagln-positive). WB analysis using established markers for the different cell types (CD31 (EC), SM22 (VSMC), PDGFRB (pericytes), GFAP (astrocytes), and IBA1 (microglia) confirmed their presence in the isolated vascular component and suggests that the protocol is suitable for future proteomic analysis. Finally, we adapted the isolation protocol to accommodate primary culture of brain vascular cells. In conclusion, we have successfully established a simple and fast method for isolating microvasculature from the murine brain independent of cell sorting and alleviating the need to use reporter mouse lines. The protocol is suitable for a multitude of testing modalities, including single-cell analyses, WB and primary cell culture.
Simultaneous Detection of Dopamine and Serotonin with Carbon-based Electrodes
Authors: Khot Gaurang , Shirtcliffe Neil , Celikel Tansu
Published: September 2021

Graphite-based materials, like pyrolyzed carbon electrodes, are widely used as implantable electrochemical sensors, for the detection of neurotransmitters, neuromodulators, and gaseous species, thanks to their strong mechanical properties, superior electron-transfer kinetics, and in-vivo stability. Electrochemical properties of graphite can be improved by coating them with carbon nanotubes (CNTs) which improves sensitivity, selectivity, and resistance to biofouling. Although several types of electrodes have been developed to detect biologically relevant targets like monoamines, multiplexed sensing of dopamine and serotonin is not yet widely available. Herein we introduce pyrolyzed carbon electrodes coated with CNTs for fast scan cyclic voltammetry for simultaneous detection of dopamine and serotonin with a sensitivity of 52±8nA/μM and 5±17nA/μM, respectively. Serotonin shows a broad oxidation peak at 0.68V±0.12V. When dopamine and serotonin are probed simultaneously at 10 Hz, dopamine oxidizes at 0.1V± 0.1 and serotonin oxidizes at 0.78V±0.12 and dopamine reduces at −0.35V±0.1 and serotonin at 0.1V±0.2 V. Thus the sensors shows discrimination between dopamine and serotonin and are suitable for simultaneous detection of these monoamines.
A comprehensive neural simulation of slow-wave sleep and highly responsive wakefulness dynamics
Authors: Goldman Jennifer S. , Kusch Lionel , Yalçinkaya Bahar Hazal , Depannemaecker Damien , Nghiem Trang-Anh E. , Jirsa Viktor , Destexhe Alain
Published: September 2021

Hallmarks of neural dynamics during healthy human brain states span spatial scales from neuromodulators acting on microscopic ion channels to macroscopic changes in communication between brain regions. Developing a scale-integrated understanding of neural dynamics has therefore remained challenging. Here, we perform the integration across scales using mean-field modeling of Adaptive Exponential (AdEx) neurons, explicitly incorporating intrinsic properties of excitatory and inhibitory neurons. We report that when AdEx mean-field neural populations are connected via structural tracts defined by the human connectome, macroscopic dynamics resembling human brain activity emerge. Importantly, the model can qualitatively and quantitatively account for properties of empirical spontaneous and stimulus-evoked dynamics in the space, time, phase, and frequency domains. Remarkably, the model also reproduces brain-wide enhanced responsiveness and capacity to encode information particularly during wake-like states, as quantified using the perturbational complexity index. The model was run using The Virtual Brain (TVB) simulator, and is open-access in EBRAINS. This approach not only provides a scale-integrated understanding of brain states and their underlying mechanisms, but also open access tools to investigate brain responsiveness, toward producing a more unified, formal understanding of experimental data from conscious and unconscious states, as well as their associated pathologies.
Sequential Transmission of Task-Relevant Information in Cortical Neuronal Networks
Authors: Francis Nikolas A. , Mukherjee Shoutik , Koçillari Loren , Panzeri Stefano , Babadi Behtash , Kanold Patrick O.
Published: September 2021

During auditory task performance, cortical processing of task-relevant information enables mammals to recognize sensory input and flexibly select behavioral responses. In mouse auditory cortex, small neuronal networks encode behavioral choice during a pure-tone detection task, but it is poorly understood how neuronal networks encode behavioral choice during a pure-tone discrimination task where tones have to be categorized into targets and non-targets. While the interactions between networked neurons are thought to encode behavioral choice, it remains unclear how patterns of neuronal network activity indicate the transmission of task-relevant information within the network. To this end, we trained mice to behaviorally discriminate target vs. non-target pure-tones while we used in vivo 2-photon imaging to record neuronal population activity in primary auditory cortex layer 2/3. We found that during task performance, a specialized subset of neurons transiently encoded intersection information, i.e., sensory information that was used to inform behavioral choice. Granger causality analysis showed that these neurons formed functional networks in which task-relevant information was transmitted sequentially between neurons. Differences in network structure between target and non-target sounds encoded behavioral choice. Correct behavioral choices were associated with shorter timescale communication between neurons. In summary, we find that specialized neuronal populations in auditory cortex form functional networks during auditory task performance whose structures depend on both sensory input and behavioral choice.
SMN controls neuromuscular junction integrity through U7 snRNP
Authors: Tisdale Sarah , Alstyne Meaghan Van , Simon Christian M. , Mentis George Z. , Pellizzoni Livio
Published: September 2021

The neuromuscular junction (NMJ) is an essential synapse for animal survival whose loss is a key hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). While insights into the function of the causative genes implicate RNA dysregulation in NMJ pathogenesis, the RNA-mediated mechanisms controlling the biology of this specialized synapse that go awry in disease remain elusive. Here, we show that activity of the SMA-determining SMN protein in the assembly of U7 small nuclear ribonucleoprotein (snRNP), which functions in the 3’-end processing of replication-dependent histone mRNAs, is required for NMJ integrity. AAV9-mediated gene delivery of U7-specific Lsm10 and Lsm11 proteins selectively enhances U7 snRNP assembly, corrects histone mRNA processing defects, and rescues key structural and functional abnormalities of neuromuscular pathology in SMA mice - including NMJ denervation, reduced synaptic transmission, and skeletal muscle atrophy. Furthermore, U7 snRNP dysfunction induced by SMN deficiency drives selective loss of the synaptic organizing protein Agrin at NMJs innervating vulnerable axial muscles of SMA mice, revealing an unanticipated link between U7-dependent histone mRNA processing and motor neuron-derived expression of an essential factor for NMJ biology. Together, these findings establish a direct contribution of U7 snRNP dysfunction to the neuromuscular phenotype in SMA and the requirement of RNA-mediated histone gene regulation for maintaining functional synaptic connections between motor neurons and muscles.
An Arabidopsis root phloem pole cell atlas reveals PINEAPPLE genes as transitioners to autotrophy
Authors: Otero Sofia , Sevilem Iris , Roszak Pawel , Lu Yipeng , Vittori Valerio Di , Bourdon Matthieu , Kalmbach Lothar , Blob Bernhard , Heo Jung-ok , Peruzzo Federico , Laux Thomas , Fernie Alisdair R. , Tavares Hugo , Helariutta Yka
Published: September 2021

Single cell sequencing has recently allowed the generation of exhaustive root cell atlases. However, some cell types are elusive and remain underrepresented. Here, we use a second- generation single cell approach, where we zoom in on the root transcriptome sorting with specific markers to profile the phloem poles at an unprecedented resolution. Our data highlight the similarities among the developmental trajectories and gene regulatory networks communal to protophloem sieve element (PSE) adjacent lineages in relation to PSE enucleation, a key event in phloem biology.

As a signature for early PSE-adjacent lineages, we have identified a set of DNA-binding with one finger (DOF) transcription factors, the PINEAPPLEs (PAPL), that act downstream of PHLOEM EARLY DOF (PEAR) genes, and are important to guarantee a proper root nutrition in the transition to autotrophy.

Our data provide a holistic view of the phloem poles that act as a functional unit in root development.
Accounting for 16S rRNA copy number prediction uncertainty and its implications in bacterial diversity analyses
Authors: Gao Yingnan , Wu Martin
Published: September 2021

16S rRNA gene copy number (16S GCN) varies among bacterial species and this variation introduces potential biases to microbial diversity analyses using 16S rRNA read counts. To correct the biases, methods have been developed to predict 16S GCN. A recent study suggests that the prediction uncertainty can be so great that copy number correction is not justified in practice. Here we develop RasperGade16S, a novel method and software to better model and capture the inherent uncertainty in 16S GCN prediction. RasperGade16S implements a maximum likelihood framework of pulsed evolution model and explicitly accounts for intraspecific GCN variation and heterogeneous GCN evolution rates among species. Using cross validation, we show that our method provides robust confidence estimates for the GCN predictions and outperforms other methods in both precision and recall. We have predicted GCN for 592605 OTUs in the SILVA database and tested 113842 bacterial communities that represent an exhaustive and diverse list of engineered and natural environments. We found that the prediction uncertainty is small enough for 99% of the communities that 16S GCN correction should improve their compositional and functional profiles estimated using 16S rRNA reads. On the other hand, we found that GCN variation has limited impacts on beta-diversity analyses such as PCoA, PERMANOVA and random forest test.
Inheritance of Repressed Chromatin Domains during S-phase Requires the Histone Chaperone NPM1
Authors: Escobar Thelma M. , Yu Jia-Ray , Liu Sanxiong , Lucero Kimberly , Vasilyev Nikita , Nudler Evgeny , Reinberg Danny
Published: September 2021

The epigenetic process safeguards cell identity during cell division through the inheritance of appropriate gene expression profiles. We demonstrated previously that parental nucleosomes are inherited by the same chromatin domains during DNA replication only in the case of repressed chromatin. We now show that this specificity is conveyed by NPM1, a histone H3/H4 chaperone. Proteomic analyses of late S-phase chromatin revealed NPM1 in association with both H3K27me3, an integral component of facultative heterochromatin and MCM2, an integral component of the DNA replication machinery; moreover NPM1 interacts directly with PRC2 and with MCM2. Given that NPM1 is essential, the inheritance of repressed chromatin domains was examined anew using mESCs expressing an auxin-degradable version of endogenous NPM1. Upon NPM1 degradation, cells accumulated in S-phase of the cell-cycle and parental nucleosome inheritance from repressed chromatin domains was markedly compromised. Appropriate inheritance required the NPM1 acidic patches that function in chaperone activity, pointing to NPM1 being integral to the epigenetic process.

One-Sentence Summary

The histone H3/H4 chaperone, NPM1, fosters epigenetic inheritance from parental repressed chromatin during DNA replication.
A Useful Guide to Lectin Binding: Machine-Learning Directed Annotation of 57 Unique Lectin Specificities
Authors: Bojar Daniel , Meche Lawrence , Meng Guanmin , Eng William , Smith David F. , Cummings Richard D. , Mahal Lara K.
Published: September 2021

Glycans are critical to every facet of biology and medicine, from viral infections to embryogenesis. Tools to study glycans are rapidly evolving, however the majority of our knowledge is deeply dependent on binding by glycan binding proteins (e.g., lectins). The specificities of lectins, which are often naturally isolated proteins, have not been well- defined, making it difficult to leverage their full potential for glycan analysis. Herein, we use glycan microarray analysis of 116 commercially available lectins, including different preparations of the same lectin, to extract the specific glycan features required for lectin binding. Data was obtained using the Consortium for Functional Glycomics microarray (CFG v5.0) containing 611 glycans. We use a combination of machine learning algorithms to define lectin specificity, mapping inputs (glycan sequences) to outputs (lectin-glycan binding) for a large-scale evaluation of lectin-glycan binding behaviours. Our motif analysis was performed by integrating 68 manually defined glycan features with systematic probing of computational rules for significant binding motifs using mono- and disaccharides- and linkages. Using a combination of machine learning and manual annotation of the data, we created a detailed interpretation of glycan-binding specificity for 57 unique lectins, categorized by their major binding motifs: mannose, complex-type N-glycan, O-glycan, fucose, sialic acid and sulfate, GlcNAc and chitin, Gal and LacNAc, and GalNAc. Our work provides fresh insights into the complex binding features of commercially available lectins in current use, providing a critical guide to these important reagents.
Robust, data-driven bioregionalizations emerge from diversity concordance
Authors: Montalvo-Mancheno Cristian S. , Buettel Jessie C. , Ondei Stefania , Brook Barry W.
Published: September 2021

Aim

Despite the increasing interest in developing new bioregionalizations and assessing the most widely accepted biogeographic frameworks, no study to date has sought to systematically define a system of small bioregions nested within larger ones that better reflect the distribution and patterns of biodiversity. Here, we examine how an algorithmic, data-driven model of diversity patterns can lead to an ecologically interpretable hierarchy of bioregions.

Location

Australia.

Time period

Present.

Major taxa studied

Terrestrial vertebrates and vascular plants.

Methods

We compiled information on the biophysical characteristics and species occupancy of Australia’s geographic conservation units (bioregions). Then, using cluster analysis to identify groupings of bioregions representing optimal discrete-species areas, we evaluated what a hierarchical bioregionalization system would look like when based empirically on the within-and between-site diversity patterns across taxa. Within an information-analytical framework, we then assessed the degree to which the World Wildlife Fund’s (WWF) biomes and ecoregions and our suite of discrete-species areas are spatially associated and compared those results among bioregionalization scenarios.

Results

Information on biodiversity patterns captured was moderate for WWF’s biomes (50– 58% for birds’ beta, and plants’ alpha and beta diversity, of optimal discrete areas, respectively) and ecoregions (additional 4–25%). Our plants and vertebrate optimal areas retained more information on alpha and beta diversity across taxa, with the two algorithmically derived biogeographic scenarios sharing 86.5% of their within- and between-site diversity information. Notably, discrete-species areas for beta diversity were parsimonious with respect to those for alpha diversity.

Main conclusions

Nested systems of bioregions must systematically account for the variation of species diversity across taxa if biodiversity research and conservation action are to be most effective across multiple spatial or temporal planning scales. By demonstrating an algorithmic rather than subjective method for defining bioregionalizations using species-diversity concordances, which reliably reflects the distributional patterns of multiple taxa, this work offers a valuable new tool for systematic conservation planning.
Characterization of opposing responses to phenol by Bacillus subtilis chemoreceptors
Authors: Bodhankar Girija A. , Tohidifar Payman , Foust Zachary L. , Ordal George W. , Rao Christopher V.
Published: September 2021

Bacillus subtilis employs ten chemoreceptors to move in response to chemicals in its environment. While the sensing mechanisms have been determined for many attractants, little is known about the sensing mechanisms for repellents. In this work, we investigated phenol chemotaxis in B. subtilis. Phenol is an attractant at low, micromolar concentrations, and a repellent at high, millimolar concentrations. McpA was found to be the principal chemoreceptor governing the repellent response to phenol and other related aromatic compounds. In addition, the chemoreceptors McpC and HemAT were found to the govern the attractant response to phenol and related compounds. Using receptor chimeras, McpA was found to sense phenol using its signaling domain rather than its sensing domain. These observations were substantiated in vitro, where direct binding of phenol to the signaling domain of McpA was observed using saturation-transfer difference nuclear magnetic resonance. These results further advance our understanding of B. subtilis chemotaxis and demonstrate that the signaling domain of B. subtilis chemoreceptors can directly sense chemoeffectors.

IMPORTANCE

Bacterial chemotaxis is commonly thought to employ a sensing mechanism involving the extracellular sensing domain of chemoreceptors. Some ligands, however, appear to be sensed by the signaling domain. Phenolic compounds, commonly found in soil and root exudates, provide environmental cues for soil microbes like Bacillus subtilis. We show that phenol is sensed both as an attractant and a repellent. While mechanism for sensing phenol as an attractant is still unknown, we found that phenol is sensed as a repellent by the signaling domain of the chemoreceptor McpA. This study furthers our understanding of the unconventional sensing mechanisms employed by the B. subtilis chemotaxis pathway.
Selecting for and Checking Cells with HGPRT Deficiency for Hybridoma Production
Authors: Greenfield Edward A.
Published: September 2021

For drug-selective media to work for hybridoma selection, myeloma cells expressing a mutation abrogating the function of their HGPRT gene (and subsequently unable to produce purines for DNA biosynthesis) are used. HGPRT will recognize 8-AG as a substrate and convert it to the monophosphate nucleotide. The 8-AG-containing nucleotide is then processed further and incorporated into DNA and RNA, where it is toxic. Therefore, cells with a functional HGPRT enzyme grown in the presence of 8-AG will die. Cells that are deficient in HGPRTase cannot incorporate 8-AG in vivo and thus continue to grow. Cells that have been selected for resistance to 8-AG should be checked periodically to ensure that they maintain sensitivity to drugs that block the de novo synthesis of DNA. In addition, all myeloma cell lines should be checked periodically for reversion of their drug selection markers. Any line that is not killed completely by drug selection should either be reselected or replaced with a new line.
Does gender diversity on the board reduce agency cost? Evidence from Pakistan
Authors: Amin Ali , Ur Rehman Ramiz , Ali Rizwan , Ntim Collins G.
Published: September 2021

Purpose

This study aims to examine the effects of board gender diversity on agency costs in non-financial firms listed on the Pakistan Stock Exchange (PSX).

Design/methodology/approach

Multiple regression analysis is used to determine the impact of board gender diversity on agency cost. The research used panel data consisting of 2,062 firm-year observations of 226 non-financial firms listed on the PSX from 2008 to 2019 to test the proposed hypothesis. In addition, the Blau and the Shannon indices were used to checking for robustness.

Findings

The results indicate that female presence on the board significantly reduces the agency cost and, hence, mitigates the principal-agent conflict. Moreover, consistent with the critical mass theory, it was found that boards with three or more female directors have a stronger impact on reducing the agency cost, as compared to two or fewer female directors on the board.

Research limitations/implications

The sample was restricted to non-financial firms listed on the PSX only; therefore, the results reflect the attributes of Pakistan’s business environment. A similar analysis in the context of other countries may generate different results.

Practical implications

The findings imply that female directors play an important role in reducing agency conflicts between shareholders and managers by enhancing monitoring through effective governance mechanisms. The policymakers, therefore, should focus on female career development and encourage professional training programmes to generate a fair, competitive environment for senior female management.

Originality/value

This study attempts to fill the literature gap in that no similar study covers the non-financial firms’ listed firms in Pakistan. The paper supports the reforms made by the code of corporate governance by making the placement of female directors mandatory on Pakistani corporate boards. Overall, support is provided for the view that regulators should favour gender quotas regarding the composition of the board management team of listed firms to reduce agency conflicts and gain shareholder confidence.
Thermal performance analysis of hybrid nanofluid natural convection in a square cavity containing an elliptical obstacle under variable magnetic field
Authors: Belhaj Soufien , Ben-Beya Brahim
Published: September 2021

Purpose

This study aims to analyze entropy generation and magnetohydrodynamic (MHD) natural convection of hybrid nanofluid in a square cavity, with a heated elliptical block placed at the center, in presence of a periodic-variable magnetic field.

Design/methodology/approach

In this paper, simulations were performed with a FORTRAN home code. The numerical methodology used to solve Navier–Stokes, energy and entropy generation equations with corresponding boundary conditions, is essentially based on the finite volume method and full multigrid acceleration.

Findings

The cavity is filled with Ag–Tio2/Water hybrid nanofluid. The main objective of this investigation is to predict the effects of body’s size (6 cases), type of applied magnetic field (variable or uniform), the non-dimensional period number of the variable magnetic field (VMF) (0.2 ≤ Λ ≤ 0.8), the inclination angle of the VMF (0 ≤ χ ≤ 90), Rayleigh number (5 × 103 ≤ Ra ≥ 105) and Hartmann number (5 ≤ Ha ≥ 100) on thermal performance, heat transfer rate, entropy generation and flow patterns.

Originality/value

To the authors’ best knowledge, this paper is the first numerical investigation deals with the entropy generation and natural convection of hybrid nanofluid in a two-dimensional cavity, with specific thermal boundary conditions, containing an elliptical block under periodic-variable magnetic field. Different combinations between flow-governing parameters were made to find optimal thermal performance.
Prioritizing success factors for implementing total productive maintenance (TPM)
Authors: Singh Rajesh Kumar , Gurtu Amulya
Published: September 2021

Purpose

This paper aims to prioritize the factors for the successful implementation of total productive maintenance (TPM).

Design/methodology/approach

The technique used for prioritization is the analytical hierarchy process (AHP).

Findings

The commitment and involvement of the top management, i.e. the leadership team, is the most critical success factor in the successful implementation of TPM. Employee training is another vital factor. Top management should also encourage a culture favorable for information flow, equipment ownership, the involvement of people and quality management throughout the organization.

Research limitations/implications

Manufacturing organizations interested in improving productivity through the implementation of TPM should first involve the leadership team and seek their full support and train all the employees in this philosophy. However, the findings cannot be generalized for global application due to the inputs taken from experts in AHP from limited geography.

Practical implications

Reducing production costs is a universal expectation of business leaders. TPM can be used as a long-term strategy to improve productivity by the organization.

Social implications

All employees have to be trained in this philosophy, and as part of the training and the implementation of TPM, they feel empowered and committed to the organization.

Originality/value

This study has illustrated the use of AHP for the prioritization of success factors. Prioritization of success factors will help in strategy formulation by management for effective maintenance. It will help in improving the productivity and performance of the organization.
Mixed emotions and credence service use: insights from at-risk gamblers
Authors: De Vos Svetlana , Crouch Roberta , Quester Pascale , Ilicic Jasmina
Published: September 2021

Purpose

This paper aims to explore the power of appeals based on fear mixed with challenge co-designed with vulnerable consumers in motivating the use of credence services.

Design/methodology/approach

A qualitative phase (Study 1), comprising focus groups of self-identified at-risk gamblers, revealed a series of conceptual themes for advertising stimuli that were then tested empirically (Study 2) on the likelihood to use credence services in a gambling context. Individual characteristics such as tolerance of ambiguity were also tested for their potential moderating influence.

Findings

In comparison to appeals based on single emotions, fear mixed with the challenge has a significantly stronger impact on intentions to use credence services in at-risk gamblers. Findings confirm the indirect positive impact of fear mixed with the challenge via sequential mediators of involvement with advertising and attitude towards credence service advertising. The moderating role of tolerance of ambiguity on credence service use intentions was confirmed.

Originality/value

The potential of a fear mixed with challenge appeal to motivate vulnerable consumers to seek credence services has not been investigated to date. The findings contribute to both the transformative service research and advertising literature streams by providing valuable insights into promotional campaigns aimed at vulnerable consumers such as at-risk gamblers.
A multi-criteria decision making method for vapor smoothening fused deposition modelling part
Authors: M. Sugavaneswaran , B. Prashanthi , A. John Rajan
Published: September 2021

Purpose

This paper aims to enhance the surface finish of the fused deposition modeling (FDM) part using the vapor smoothening (VS) post-processing method and to study the combined effect of FDM and VS process parameters on the quality of the part.

Design/methodology/approach

Analysis of variance method is used to understand the significance of the FDM and VS process parameters. Following this, the optimized parameter for multiple criteria response is reported using the technique for order preference by similarity to ideal solution. The process parameters alternatives are build orientation angle, build surface normal and exposure time and the criteria are surface roughness and dimensional error percentage.

Findings

The result observed contradicts the result reported on the independent parameter optimization of FDM and VS processes. There is a radical improvement in the surface finish on account of the coating process and an increase in the exposure time results in the decrease of the surface roughness. Minimum surface roughness of 0.11 µm is observed at 1,620 build angle and the least dimensional error of 0.01% is observed at build orientation angle 540. The impact of VS on the up-facing surface is different from the down-facing surface due to the removal of support material burrs and the exposure of the surface to vapor direction.

Originality/value

A study on the multi-criteria decision-making to ascertain the effect of post-processing on FDM component surface normal directed both to downward (build angle 0°–90°) and to upward (build angle 99°–180°) are reported for the first time in this article. The data reported for the post-processed FDM part at the build angle 0°–180° can be used as a guideline for selecting the optimal parameter and for assigning appropriate tolerance in the CAD model.
Reduced SMA‐M1 connectivity in older than younger adults measured using dual‐site TMS
Authors: Rurak Brittany K. , Rodrigues Julian P. , Power Brian D. , Drummond Peter D. , Vallence Ann‐Maree
Published: September 2021

With advancing age comes a decline in voluntary movement control. Growing evidence suggests that an age‐related decline in effective connectivity between the supplementary motor area and primary motor cortex (SMA‐M1) might play a role in an age‐related decline of bilateral motor control. Dual‐site transcranial magnetic stimulation (TMS) can be used to measure SMA‐M1 effective connectivity. In the current study, we aimed to (1) replicate previous dual‐site TMS research showing reduced SMA‐M1 connectivity in older than younger adults and (2) examine whether SMA‐M1 connectivity is associated with bilateral motor control in independent samples of younger (n = 30) and older adults (n = 30). SMA‐M1 connectivity was measured using dual‐site TMS with interstimulus intervals of 6, 7 and 8 ms, and bilateral motor control was measured using the Purdue Pegboard, Four Square Step Test and the Timed Up and Go task. Findings from this study showed that SMA‐M1 connectivity was reduced in older than in younger adults, suggesting that the direct excitatory connections between SMA and M1 had reduced efficacy in older than younger adults. Furthermore, greater SMA‐M1 connectivity was associated with better bimanual motor control in older adults. Thus, SMA‐M1 connectivity in older adults might underpin, in part, the age‐related decline in bilateral motor control. These findings contribute to our understanding of age‐related declines in motor control and provide a physiological basis for the development of interventions to improve bimanual and bilateral motor control.
Cholesterol dyshomeostasis in amyotrophic lateral sclerosis: cause, consequence, or epiphenomenon?
Authors: Hartmann Hannelore , Ho Wan Yun , Chang Jer‐Cherng , Ling Shuo‐Chien
Published: September 2021

Amyotrophic lateral sclerosis (ALS), the most common adult‐onset motor neuron disease, is characterized by the selective degeneration of motor neurons leading to paralysis and eventual death. Multiple pathogenic mechanisms, including systemic dysmetabolism, have been proposed to contribute to ALS. Among them, dyslipidemia, i.e., abnormal level of cholesterol and other lipids in the circulation and central nervous system (CNS), has been reported in ALS patients, but without a consensus. Cholesterol is a constituent of cellular membranes and a precursor of steroid hormones, oxysterols, and bile acids. Consequently, optimal cholesterol levels are essential for health. Due to the blood–brain barrier (BBB), cholesterol cannot move between the CNS and the rest of the body. As such, cholesterol metabolism in the CNS is proposed to operate autonomously. Despite its importance, it remains elusive how cholesterol dyshomeostasis may contribute to ALS. In this review, we aim to describe the current state of cholesterol metabolism research in ALS, identify unresolved issues, and provide potential directions.
Sclerosing stromal tumour: a clinicopathological study of 100 cases of a distinctive benign ovarian stromal tumour typically occurring in the young
Authors: Devins Kyle M , Young Robert H , Watkins Jaclyn C
Published: September 2021

Aims

Since the sclerosing stromal tumour (SST) of the ovary was first described in 1973, few studies have expanded upon its histological features or overlap with other tumours. We thus investigate these aspects based on our experience with 100 cases.

Methods and results

The patients, 14 of whom were pregnant, ranged from 12 to 63 years (median = 26 years). Ten patients had hormonal manifestations (seven oestrogenic, three androgenic). Bilateral ovarian involvement was present in two cases. Size ranged from 1 to 23 cm (mean = 8.4 cm). Most tumours were solid and white with focal yellow areas; oedema with cystic degeneration (seen in 25 cases) resulted in eight being predominantly cystic. On microscopic examination, alternating cellular and paucicellular areas (pseudolobulation) were prominent in 94 cases but seen to a limited degree in the remaining neoplasms. Admixed spindled and luteinised cells were present in all tumours, but 13 demonstrated mainly spindled cells and 19 demonstrated mainly lutein cells; 14 of the latter were from pregnant patients. The stroma was typically oedematous or collagenous, but in 14 cases was prominently hyalinised and, in four, myxoid. Prominent vascularity was present in most cases. The mitotic rate ranged from 0 to 8/10 high‐power fields (HPF), but most demonstrated <1/10 HPF.

Conclusions

The differential diagnosis of SST is broad, including fibromas, thecomas, solitary fibrous tumours, pregnancy luteomas, myxomas, other ovarian sex cord‐stromal tumours with sclerosis and, rarely, Krukenberg tumours. Strict adherence to the requirement of pseudolobulation, prominent (usually ectatic) vessels, and lutein cells and fibroblasts admixed in a jumbled manner, will distinguish the neoplasm from others in the differential.
Co‐ordination of brain and heart oscillations during non‐rapid eye movement sleep
Authors: Mikutta Christian , Wenke Marion , Spiegelhalder Kai , Hertenstein Elisabeth , Maier Jonathan G. , Schneider Carlotta L. , Fehér Kristoffer , Koenig Julian , Altorfer Andreas , Riemann Dieter , Nissen Christoph , Feige Bernd
Published: September 2021

Oscillatory activities of the brain and heart show a strong variation across wakefulness and sleep. Separate lines of research indicate that non‐rapid eye movement (NREM) sleep is characterised by electroencephalographic slow oscillations (SO), sleep spindles, and phase–amplitude coupling of these oscillations (SO–spindle coupling), as well as an increase in high‐frequency heart rate variability (HF‐HRV), reflecting enhanced parasympathetic activity. The present study aimed to investigate further the potential coordination between brain and heart oscillations during NREM sleep. Data were derived from one sleep laboratory night with polysomnographic monitoring in 45 healthy participants (22 male, 23 female; mean age 37 years). The associations between the strength (modulation index [MI]) and phase direction of SO–spindle coupling (circular measure) and HF‐HRV during NREM sleep were investigated using linear modelling. First, a significant SO–spindle coupling (MI) was observed for all participants during NREM sleep, with spindle peaks preferentially occurring during the SO upstate (phase direction). Second, linear model analyses of NREM sleep showed a significant relationship between the MI and HF‐HRV (F = 20.1, r2 = 0.30, p < 0.001) and a tentative circular‐linear correlation between phase direction and HF‐HRV (F = 3.07, r2 = 0.12, p = 0.056). We demonstrated a co‐ordination between SO–spindle phase–amplitude coupling and HF‐HRV during NREM sleep, presumably related to parallel central nervous and peripheral vegetative arousal systems regulation. Further investigating the fine‐graded co‐ordination of brain and heart oscillations might improve our understanding of the links between sleep and cardiovascular health.