bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted delivery of galunisertib attenuates fibrogenesis in an integratedex vivorenal transplant and fibrosis model
Authors: van Leeuwen L. Leonie , Leuvenink Henri G.D. , Kessler Benedikt M. , Olinga Peter , Ruigrok Mitchel J.R.
Published: March 2022

Normothermic machine perfusion is an emerging preservation technique for kidney allografts to reduce post-transplant complications, including interstitial fibrosis and tubular atrophy. This technique, however, could be improved by adding antifibrotic molecules to perfusion solutions. We established Machine perfusion and Organ slices as a Platform for Ex vivo Drug delivery (MOPED), to explore fibrogenesis suppression strategies. We perfused porcine kidneysex vivowith galunisertib—a potent inhibitor of the transforming growth factor beta signaling pathway. To determine whether effects persisted, we also cultured precision-cut tissue slices prepared from the respective kidneys. Galunisertib supplementation improved the general viability, without negatively affecting renal function or elevating levels of injury markers or byproducts of oxidative stress. Galunisertib also reduced inflammation and more importantly, strongly suppressed the onset of fibrosis, especially when the treatment was continued in slices. Our results illustrate the value of targeted drug delivery, using isolated organ perfusion, for reducing post-transplant complications.

One Sentence Summary

Galunisertib supplementation during normothermic machine perfusion attenuates fibrogenesis without compromising renal function.
Information maximization explains state-dependent synaptic plasticity and memory reorganization during non-rapid eye movement sleep
Authors: Yoshida Kensuke , Toyoizumi Taro
Published: March 2022

Slow waves during the non-rapid eye movement (NREM) sleep reflect the alternating up and down states of cortical neurons; global and local slow waves promote memory consolidation and forgetting, respectively. Furthermore, distinct spike-timing-dependent plasticity (STDP) operates in these up and down states. The contribution of different plasticity rules to neural information coding and memory reorganization remains unknown. Here, we show that optimal synaptic plasticity for information maximization in a cortical neuron model provides a unified explanation for these phenomena. The model indicates that the optimal synaptic plasticity is biased towards depression as the baseline firing rate increases. This property explains the distinct STDP observed in the up and down states. Furthermore, it explains how global and local slow waves predominantly potentiate and depress synapses, respectively, if the background firing rate of excitatory neurons declines with the spatial scale of waves as the model predicts. The model provides a unifying account of the role of NREM sleep, bridging neural information coding, synaptic plasticity, and memory reorganization.
XY sex determination in a cnidarian
Authors: Chen Ruoxu , Sanders Steven M. , Ma Zhiwei , Paschall Justin , Chang E. Sally , Riscoe Brooke M. , Schnitzler Christine E. , Baxevanis Andreas D. , Nicotra Matthew L.
Published: March 2022

Sex determination occurs across animal species, but most of our knowledge about the mechanisms of sex determination comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used this map to determine that this species has an XX/XY sex determination system. We delineate the pseudoautosomal and non-recombining regions of the Y chromosome and show that the latter encodes a number of genes with male gonad-specific expression. These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination.

Significance Statement

What determines whether an animal is male or female? The answer depends on the species. Some rely on signals from their environment, while others take cues from their genome. Most of what we understand about sex determination comes from traditional model organisms (such as mice, flies, and worms) or groups of well-studied vertebrates and insects. Studying sex determination in other animals, especially those from phyla that diverged early in animal evolution, would allow us to better understand how sex has evolved across the animal kingdom and could reveal pathways present in the eumetazoan ancestor >600 million years ago. In this study, we show that the cnidarian Hydractinia symbiolongicarpus has XY sex determination, establishing this species as a model system for sex determination in an understudied group of animals.
Comparative analysis of genome-wide protein-DNA interactions across domains of life reveals unique binding patterns for hypersaline archaeal histones
Authors: Sakrikar Saaz , Hackley Rylee K. , Martinez-Pastor Mar , Darnell Cynthia L. , Vreugdenhil Angie , Schmid Amy K.
Published: March 2022

DNA-binding proteins with roles in chromatin architecture and transcriptional regulation are present in all three domains of life. Histones package DNA and regulate gene expression in eukaryotes, and find their evolutionary origin in the domain of life Archaea. Previously characterised archaeal histones have a somewhat conserved functional role in nucleosome formation and DNA packaging. However, previous research has indicated that the histone-like proteins of high salt-adapted archaea, or halophiles, appear to function differently. The sole histone protein encoded by the model halophilic species Halobacterium salinarum is non-essential, is involved in direct and indirect transcriptional regulation, and does not appear to package DNA. Here we use protein-DNA binding assays, computational analysis, and quantitative phenotyping to compare DNA binding patterns across halophilic histone proteins, bacterial and archaeal TFs, NAPs, and eukaryotic histones. Like TFs, halophilic histones bind the genome too sparsely to compact the genome. However, unlike TFs, binding occurs in both coding and intergenic regions. Unlike histones, halophilic histone occupancy is not depleted at the start sites of genes, and halophilic genomes lack the dinucleotide periodicity known to facilitate histone binding. We detect unique sequence preferences for histone binding in halophiles. Together these data suggest that the non-essentiality and genome-wide binding features of halophilic histone-like proteins are conserved across halophiles; they bind DNA in ways resembling both TFs and chromatin proteins, but do not appear to play a role in forming chromatin.

IMPORTANCE

Most cells in eukaryotic species – from yeast to humans– possess histone proteins that pack and unpack DNA in response to environmental cues. These essential proteins regulate the genes necessary for important cellular processes, including development and stress protection. The domain of life Archaea represent the evolutionary progenitors of eukaryotes. The universal conservation of the primary sequences of histone proteins across archaeal lineages suggests that eukaryotic histones originated in the Archaea. However, archaeal histones lack N-terminal tails and, in some species, package DNA in a continuous helix with no linker DNA between nucleosomes. We recently discovered that histones in hypersaline adapted archaeal species do not package DNA, and can act like transcription factors (TFs) to regulate stress response gene expression. Here we compare hypersaline histone function to a variety of DNA binding proteins across the tree of life, revealing a mosaic of functions for hypersaline-adapted histones.
Computer-assisted analysis of polysomnographic recordings improves inter-scorer associated agreement and scoring times
Authors: Alvarez-Estevez Diego , Rijsman Roselyne M.
Published: March 2022

Study Objectives

To investigate inter-scorer agreement and scoring time differences associated with visual and computer-assisted analysis of polysomnographic (PSG) recordings.

Methods

A group of 12 expert scorers reviewed 5 PSGs that were independently selected in the context of each of the following tasks: (i) sleep stating, (ii) detection of EEG arousals, (iii) analysis of the respiratory activity, and (iv) identification of leg movements. All scorers independently reviewed the same recordings, hence resulting in 20 scoring exercises from an equal amount of different subjects. The procedure was repeated, separately, using the classical visual manual approach and a computer-assisted (semi-automatic) procedure. Resulting inter-scorer agreement and scoring times were examined and compared among the two methods.

Results

Computer-assisted sleep scoring showed a consistent and statistically relevant effect toward less time required for the completion of each of the PSG scoring tasks. Gain factors ranged from 1.26 (EEG arousals) to 2.41 (limb movements). Inter-scorer kappa agreement was also consistently increased with the use of supervised semi-automatic scoring. Specifically, agreement increased from K=0.76 to K=0.80 (sleep stages), K=0.72 to K=0.91 (limb movements), K=0.55 to K=0.66 (respiratory activity), and K=0.58 to K=0.65 (EEG arousals). Inter-scorer agreement on the examined set of diagnostic indices did also show a trend toward higher Interclass Correlation Coefficient scores when using the semi-automatic scoring approach.

Conclusions

Computer-assisted analysis can improve inter-scorer agreement and scoring times associated with the review of PSG studies resulting in higher efficiency and overall quality in the diagnosis sleep disorders.
CNV-ClinViewer: Enhancing the clinical interpretation of large copy-number variants online
Authors: Macnee Marie , Pérez-Palma Eduardo , Brünger Tobias , Klöckner Chiara , Platzer Konrad , Stefanski Arthur , Montanucci Ludovica , Bayat Allan , Radtke Maximilian , Collins Ryan L , Talkowski Michael , Blankenberg Daniel , Møller Rikke S , Lemke Johannes R , Nothnagel Michael , May Patrick , Lal Dennis
Published: March 2022

Purpose

Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype-phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts.

Methods

We developed a web-application combining >250,000 patient and population CNVs together with a large set of biomedical annotations and provide tools for CNV classification based on ACMG/ClinGen guidelines and gene-set enrichment analyses.

Results

Here, we introduce the CNV-ClinViewer (https://cnv-ClinViewer.broadinstitute.org), an open-source web-application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface.

Conclusion

Overall, this resource facilitates semi-automated clinical CNV interpretation and genomic loci exploration and, in combination with clinical judgment, enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators patient care and for basic scientists translational genomic research.
Statistical and functional convergence of common and rare variant risk for autism spectrum disorders at chromosome 16p
Authors: Weiner Daniel J. , Ling Emi , Erdin Serkan , Tai Derek J.C. , Yadav Rachita , Grove Jakob , Fu Jack M. , Nadig Ajay , Carey Caitlin E. , Baya Nikolas , Bybjerg-Grauholm Jonas ,   iPSYCH Consortium,   ASD Working Group of the Psychiatric Genomics Consortium,   ADHD Working Group of the Psychiatric Genomics Consortium, Berretta Sabina , Macosko Evan Z. , Sebat Jonathan , O’Connor Luke J. , Hougaard David M. , Børglum Anders D. , Talkowski Michael E. , McCarroll Steve A. , Robinson Elise B.
Published: March 2022

The dominant human genetics paradigm for converting association to mechanism (“variant-to-function”) involves iteratively mapping individual associations to specific SNPs and to the proximal genes through which they act. In contrast, here we demonstrate the feasibility of extracting biological insight from a very large (>10Mb) region of the genome, and leverage this approach to derive insight into autism spectrum disorder (ASD). Using a novel statistical framework applied in an unbiased scan of the genome, we identified the 33Mb p-arm of chromosome 16 (16p) as harboring the greatest excess of common polygenic risk for ASD. This region includes the recurrent 16p11.2 copy number variant (CNV) – one of the largest single genetic risk factors for ASD, and whose pathogenic mechanisms are undefined. Analysis of bulk and single-cell RNA-sequencing data from post-mortem human brain samples revealed that common polygenic risk for ASD within 16p associated with decreased average expression of genes throughout this 33-Mb region. Similarly, analysis of isogenic neuronal cell lines with CRISPR/Cas9-mediated deletion of 16p11.2 revealed that the deletion also associated with depressed average gene expression across 16p. The effects of the rare deletion and diffuse common variation were correlated at the level of individual genes. Finally, analysis of chromatin contact patterns by Hi-C revealed patterns which may explain this transcriptional convergence, including elevated contact throughout 16p, and between 16p11.2 and a distal region on 16p (Mb 0-5.2) which showed the greatest gene expression changes in both the common and rare variant analyses. These results demonstrate that elevated 3D chromatin contact may coordinate genetic and transcriptional disease liability across large genomic regions, exemplifying a novel approach for extracting biological insight from genetic association data. As applied to ASD, our analyses highlight the 33Mb p-arm of chromosome 16 as a novel locus for ASD liability and provide insight into disease liability originating from the 16p11.2 CNV.
Phosphoprotein Phosphatase Activity Positively Regulates Oligomeric Pyrin to Trigger Inflammasome Assembly in Phagocytes
Authors: Malik Haleema S. , Magnotti Flora , Loeven Nicole A. , Delgado Jose M. , Kettenbach Arminja N. , Henry Thomas , Bliska James B.
Published: March 2022

Pyrin is a pattern-recognition receptor in phagocytes that triggers capase-1 inflammasome assembly in response to bacterial toxins and effectors that inactivate RhoA. Pyrin contains oligomerization domains and is negatively regulated by phosphorylation of two residues, S205 and S241 (murine) or S208 and S242 (human), via the kinases PKN1/2, which are activated by RhoA. Familial Mediterranean Fever (FMF) is caused by phagocyte production of pyrin gain of function variants, which have a lower threshold for inflammasome assembly upon RhoA-PKN axis inhibition. Inactivation of the RhoA-PKN axis removes negative regulation but a phosphoprotein phosphatase (PPP) is needed to positively regulate pyrin. No PPP that dephosphorylates pyrin has been identified, oligomerization of murine pyrin has not been studied, and the phosphorylation status of oligomeric pyrin is unknown. We used murine macrophages and FMF patient’s monocytes combined with the use of bacterial agonists and chemical inhibitors, native PAGE, phospho-specific antibodies and siRNA knockdowns to determine if a PPP positively regulates oligomeric pyrin. Results with broadly-specific inhibitors indicate that PPP activity is required to dephosphorylate murine and human pyrin in wild type or FMF patient’s phagocytes. Findings from native PAGE show that murine pyrin forms oligomers that are phosphorylated on S205 prior to RhoA inactivation. Inhibitors cause reduced mobility of murine pyrin on native PAGE and hyperphosphorylation of S242 in human pyrin, suggesting a PPP constitutively counterbalances PKN to keep the second site hypophosphorylated. Data from siRNA knockdown experiments implicate PP2A in dephosphorylation of S205 and positive regulation of pyrin in response to RhoA inactivation.

Key points

Murine pyrin is oligomeric and phosphorylated on S205 prior to inflammasome assembly

PPP activity positively regulates pyrin inflammasome assembly in mice and humans

The alpha and beta subunits of PP2A dephosphorylate murine pyrin S205 in macrophages
Stem cell homeostasis regulated by hierarchy and neutral competition
Authors: Nakamuta Asahi , Yoshido Kana , Naoki Honda
Published: March 2022

Tissue stem cells maintain themselves through self-renewal while constantly supplying differentiating cells. As a mechanism of stem cell homeostasis, two distinct models were proposed: the classical model states that there are hierarchy among stem cells and master stem cells provide stem cells by asymmetric divisions, whereas the recent model states that stem cells are equipotent and neutrally competing each other. However, its mechanism is still controversial in several tissues and species. Here, we developed a mathematical model linking these two models. Our theoretical analysis showed that the model with the hierarchy and neutral competition, called the hierarchical neutral competition (hNC) model, exhibited bursts in clonal expansion, unlike existing models. Furthermore, the scaling law in clone size distribution, thought to be a unique characteristic of the recent model, was satisfied in the hNC model. Based on these findings, we proposed a criterion for distinguishing the three models by experiments.
A multiple comorbidities mouse model to assess atherosclerosis progression following lung infection in ApoE deficient mice
Authors: Bartlett Benjamin , Lee Silvia , Ludewick Herbert P , Siew Teck , Verma Shipra , Waterer Grant , Corrales-Medina Vicente F. , Dwivedi Girish
Published: March 2022

Background

Inflammation is a risk factor for atherosclerosis progression. Hospitalisation for pneumonia is associated with increased risk of cardiovascular disease. Herein, we describe a multiple comorbidities murine model to study the impact of bacterial pneumonia on atherosclerosis.

Methods

Firstly, a minimal infectious dose of Streptococcus pneumoniae (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 ApoE-/- mice were fed a high-fat diet prior to administering intranasally 105 colony forming units of TIGR4 or phosphate buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by MRI and PET. Mice were euthanised and investigated for changes in systemic inflammation and changes in lung morphology using ELISA, Luminex assay and real-time PCR.

Results

TIGR4 inoculated mice presented with varying degreess of lung infiltrate, pleural effusion and consolidation on MRI at all timepoints up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4 inoculated mice up to 28 days PI. Majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4 inoculated mice displayed significantly increased inflammatory gene expression (IL-1β & IL6) in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7- and 28-days PI respectively.

Conclusions

Our mouse model presents a discovery tool to understand the link between acute infections, including pneumonia, and increased cardiovascular disease risk in humans with inflammation as the mechanistic catalyst.

Graphical Abstract
Epigenetic and genetic population structure is coupled in a marine invertebrate
Authors: Silliman Katherine , Spencer Laura H. , White Samuel J. , Roberts Steven B.
Published: March 2022

Delineating the relative influence of genotype and the environment on DNA methylation is critical for characterizing the spectrum of organism fitness as driven by adaptation and phenotypic plasticity. In this study, we integrated genomic and DNA methylation data for two distinct Olympia oyster (Ostrea lurida) populations while controlling for within-generation environmental influences. In addition to providing the first characterization of genome-wide DNA methylation patterns in the oyster genusOstrea, we identified 3,963 differentially methylated loci between populations. Our results show a clear coupling between genetic and epigenetic patterns of variation, with 27% of variation in inter-individual methylation differences explained by genotype. Underlying this association are both direct genetic changes in CpGs (CpG-SNPs) and genetic variation with indirect influence on methylation (mQTLs). The association between genetic and epigenetic patterns breaks down when comparing measures of population divergence at specific genomic regions, which has implications for the methods used to study epigenetic and genetic coupling in marine invertebrates.

Significance statement

We know that genotype and epigenetic patterns are primarily responsible for phenotype, yet there is a lack of understanding to what degree the two are linked. Here we characterized the mechanisms and the degree by which genetic variation and DNA methylation variation are coupled in a marine invertebrate, with almost a third of the methylation variation attributable to genotype. This study provides a framework for future studies in environmental epigenetics to take genetic variation into account when teasing apart the drivers of phenotypic variation. By identifying methylation variation that cannot be attributed to genotype or environmental changes during development, our results also highlight the need for future research to characterize molecular mechanisms adjacent to genetic adaptation for producing long-term shifts in phenotype.
Proteomic analysis reveals microvesicles containing NAMPT as mediators of radiation resistance in glioma
Authors: Panizza Elena , Regalado Brandon D. , Wang Fangyu , Nakano Ichiro , Vacanti Nathaniel M. , Cerione Richard A. , Antonyak Marc A.
Published: March 2022

Glioma is a malignant brain tumor that is highly resistant to radiation and chemotherapy, where patients survive on average only 15 months after diagnosis. Furthering the understanding of mechanisms leading to radiation resistance of glioma is paramount to identify novel therapeutic targets. Previous studies have shown that glioma stem cells (GSCs) play an important role in promoting radiation resistance and disease recurrence. Herein we analyze the proteomic alterations occurring in patient-derived GSCs upon radiation treatment in order to identify molecular drivers of resistance. We show that proteome changes upon radiation accurately predict the resistance status of the cells, whereas resistance to radiation does not correlate with glioma transcriptional subtypes. We further show that the radio-resistant GSC-267 cell line sheds microvesicles (MVs) enriched in the metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT). These MVs can be transferred to recipient fibroblasts and radio-sensitive GSCs, enhancing their intracellular total NAD+ and NADH level, and their ability to proliferate when cultured in low serum, treated with a radio-mimetic drug or irradiated. The NAMPT enzymatic inhibitor FK-866 blocked the ability of MVs from GSC-267 cells to mediate these effects. Similarly, GSC-267 cells where NAMPT was knocked-down using shRNA, which produced MVs depleted of this enzyme, were unable to promote cell proliferation. Collectively, our findings demonstrates that proteome-level regulation can accurately predict the radio-resistance status of GSCs, and identifies NAMPT transfer via MVs as a mechanism for spreading radiation resistance within the glioma tumor microenvironment.

Significance

The highly aggressive and deadly brain cancer glioma is commonly resistant to standard chemo- and radio-therapy. We used systems biology approaches to study patient-derived glioma stem cells (GSCs), which are known to be responsible for therapeutic resistance, and cell-to-cell communication mediated by extracellular vesicles (EVs), which plays an important role in tumor progression. Analysis of the proteome of GSCs and of the EVs they release led us to determine that the EV-mediated transfer of the metabolic enzyme nicotinamide phosphorybosyltransferase (NAMPT) from radio-resistant to less aggressive cells confers resistance to radiation. Our findings identify a mechanism of therapy resistance in glioma, and suggest that NAMPT inhibition could enhance the efficacy of radiation for the treatment of glioma.
Filter paper disks as a matrix for manipulation of recombinant proteins
Authors: Ball Eric H. , Basilone Nicoletta T.
Published: March 2022

Filter paper provides an excellent matrix for retention of proteins containing a cellulose binding domain. To use this capability for manipulating recombinant fusion proteins, binding and elution parameters were explored and procedures developed for small scale purification, modification and assay. Proteins were tagged with the cellulose binding domain from theC thermocellumCipB gene via a cleavable linker. Filter paper disks of 6mm diameter were able to bind up to 80 μg protein although there was a substantial dependence on molecular size. Different means of introducing fusion proteins to the disks allow either binding within 20 minutes from microliter volumes or slower binding from milliliter volumes. Elution with protease in small volumes yielded greater than 10 μg amounts with concentrations in the 1-2 mg/ml range. To demonstrate their utility, disks were used for small scale protein purification, covalent modification of protein, immunoprecipitation, and in a binding assay. These versatile methods allow parallel processing of multiple samples and may find many uses when only small amounts of protein are needed.
Agrobacterium mediated transformation and deciphering SNPs in TaLr67 gene homeologs for gene editing in wheat
Authors: Thiyagarajan Karthikeyan , Noguera Luis Miguel , Pacheco Mario , Govindan Velu , Vikram Prashant
Published: March 2022

Diseases adversely affect grain yield of crop plants. Leaf rust is a major disease of wheat. As race-specific resistance breaks down, introduction of newer sources of resistance often from older accessions is necessary. Linkage drag from the donor accessions adversely impacts grain yield. As a result, CIMMYT breeding effort has shifted to using durable resistance, also referred to as race non-specific host resistance, which allows slow rusting but maintains grain yield. One of the key genes for durable resistance is Lr67 and the resistant form of this gene is absent in CIMMYT elite lines. Hence, we have initiated efforts to convert the susceptible copy of Lr67 into its resistant form directly in these elite lines using gene editing. This would eliminate backcrossing and thus save time as well as eliminate linkage drag that would accompany the resistant copy of the gene if it were to be introgressed from an older accession. As first steps, we have isolated and sequenced the genomic copies from each of the A, B, and D genome of the Lr67 gene from three elite lines and an experimental line. Identification of more than 50 single nucleotide polymorphisms (SNPs) in the open reading frames (ORF) among these lines would be useful in designing the guide RNA molecules with precision. Further, we have streamlined genetic transformation of these elite lines, a prerequisite step for gene editing.
Bacteriophages Playing Nice: Lysogenic bacteriophage replication stable in the human gut microbiota
Authors: Sutcliffe Steven G. , Reyes Alejandro , Maurice Corinne F.
Published: March 2022

1.1.

The human gut is a dense microbial community, of which bacteria and bacteriophages are the majority. Bacteriophages, viruses of bacteria, exist stably, without major fluctuations in the gut of healthy individuals. This stability appears to be due to an absence of ‘kill-the-winner’ dynamics, and the existence of ‘piggy-back-the-winner’ dynamics, where lysogenic replication rather than lytic replication occurs. Revisiting the deep-viral sequencing data of a healthy individual studied over 2.4 years, we were able to improve our understanding of how these dynamics occur in healthy individuals. We assembled prophages from bacterial metagenomic data and show that these prophages were continually switching from lysogenic to lytic replication. Prophages were the source of a stable extracellular phage population continually present in low abundance, in comparison to the lytic-phage population, where taxonomic diversity diverged over 2.4 years. The switch to lytic replication, or prophage induction, appears to occur mostly through spontaneous prophage induction. The observed phage dynamics of regular spontaneous induction are ecologically important as they allow prophages to maintain their ability to replicate, avoiding degradation and their loss from the gut microbiota.

1.2.

Significance Statement

It has been eight years since Minot and colleagues published their landmark longitudinal study of phages in the gut. In the years following, the bioinformatic field improved in great strides, including the methods of bacterial-genome assembly, phage-identification, and prophage detection. We leveraged the unprecedented deep sequencing of phages in this dataset by adding bacterial assembly and prophage detection analyzes. We show clearly for the first time that ‘piggy-back-the-winner’ dynamics are maintained in the gut through spontaneous prophage induction, and not widespread triggered prophage induction. These dynamics play an important ecological role by creating a stable subpopulation of phages, which could help explain how phages are maintained over the 2.4 years timeframe that this individual was studied.
Achieve a better shape of life: how entrepreneurship gears up life-time well-being
Authors: Zhou Jinyi , Park Jong Gyu , Li Yawen
Published: March 2022

Purpose

An anomaly of entrepreneurship literature was that, despite serious efforts required to manage a business, few studies had investigated entrepreneurs' health conditions at the end of their careers. This study investigated whether one's entrepreneurship in a lifetime enhanced their health after a career plateau.

Design/methodology/approach

The authors tested the main effect and mediating effects of entrepreneurs' life habits and self-esteem, respectively, using two longitudinal representative examples with 8,984 and 12,686 participants.

Findings

Results indicated that entrepreneurship significantly improved individuals' general lifetime health condition. Moreover, life habits (e.g. vigorous activities or sports, light activities, drinking habits and diet habits) and self-esteem significantly mediated the relationship between entrepreneurship and lifetime health. Entrepreneurs tended to have better health due to healthier life habits and higher self-esteem than salaried employees. In this paper, the authors also discussed theoretical and practical implications.

Originality/value

The authors proposed and found that, to counter the harsh requirements of entrepreneurial actions, entrepreneurs need to seek personal physical and psychological resources, and these resources can benefit their health even after decades.
Understanding the transformation toward omnichannel logistics in grocery retail: a dynamic capabilities perspective
Authors: Eriksson Ebba , Norrman Andreas , Kembro Joakim
Published: March 2022

Purpose

Omnichannel (OC) logistics is undergoing a significant transformation in grocery retail. To shed light on this important but underresearched phenomenon, this study aims to investigate how grocery retailers transform and why some are more successful in transforming OC logistics.

Design/methodology/approach

Applying dynamic capabilities as a theoretical lens, a multiple case study was conducted with three grocery retailers at different stages of their transformation.

Findings

Six microfoundations of dynamic capabilities were identified as critical for enabling OC transformation. The study highlights important differences in dynamic capabilities, which can be attributed to investment decision-making, governance and creating co-specialization. Finally, the authors propose seven propositions for contextualization of dynamic capabilities for OC transformation in grocery retail.

Originality/value

This study is original by contextualizing microfoundations in grocery OC retailing. The study contributes to theory and practice by showing the value of dynamic capabilities, stressing the important interrelation among a retailer's governance structure, leadership and capability to make investment decisions, increase logistics coordination and co-specialize.
Predation risk can modify the foraging behaviour of frugivorous carnivores: Implications of rewilding apex predators for plant–animal mutualisms
Authors: Burgos Tamara , Fedriani Jose M. , Escribano‐Ávila Gema , Seoane Javier , Hernández‐Hernández Javier , Virgós Emilio
Published: March 2022

Apex predators play key roles in food webs and their recovery can trigger trophic cascades in some ecosystems. Intra‐guild competition can reduce the abundances of smaller predators and perceived predation risk can alter their foraging behaviour thereby limiting seed dispersal by frugivorous carnivores. However, little is known about how plant–frugivore mutualisms could be disturbed in the presence of larger predators.

We evaluated the top‐down effect of the regional superpredator, the Iberian lynx Lynx pardinus, on the number of visits and fruits consumed by medium‐sized frugivorous carnivores, as well as the foraging behaviour of identified individuals, by examining the consumption likelihood and the foraging time.

We carried out a field experiment in which we placed Iberian pear Pyrus bourgaeana fruits beneath fruiting trees and monitored pear removal by frugivorous carnivores, both inside and outside lynx ranges. Using camera traps, we recorded the presence of the red fox Vulpes vulpes, the Eurasian badger Meles meles and the stone marten Martes foina, as well as the number of fruits they consumed and their time spent foraging.

Red fox was the most frequent fruit consumer carnivore. We found there were fewer visits and less fruit consumed by foxes inside lynx ranges, but lynx presence did not seem to affect badgers. We did not observe any stone marten visits inside lynx territories. The foraging behaviour of red foxes was also altered inside lynx ranges whereby foxes were less efficient, consuming less fruit per unit of time and having shorter visits. Local availability of fruit resources, forest coverage and individual personality also were important variables to understand visitation and foraging in a landscape of fear.

Our results show a potential trophic cascade from apex predators to primary producers. The presence of lynx can reduce frugivorous carnivore numbers and induce shifts in their feeding behaviour that may modify the seed dispersal patterns with likely consequences for the demography of many fleshy‐fruited plant species. We conclude that knowledge of the ecological interactions making up trophic webs is an asset to design effective conservation strategies, particularly in rewilding programs.
The poly‐extreme tolerant black yeasts are prevalent under high ultraviolet light and climatic seasonality across soils of global biomes
Authors: Coleine Claudia , Selbmann Laura , Singh Brajesh K. , Delgado‐Baquerizo Manuel
Published: March 2022

Black yeasts are among the most stress‐tolerant organisms of the planet, thriving under all types of terrestrial habitats and extreme environments. Yet, their global patterns and ecology remain far less studied, limiting our capacity to identify the main environmental drivers of these important organisms across biomes. To fill this knowledge gap, we analysed topsoils from 235 terrestrial ecosystems across and within globally distributed climate groups (i.e. dry, temperate and continental). We found that soils are important repositories of black yeasts, and that ultraviolet light, fine soil texture, and precipitation seasonality are the most consistent environmental factors associated with their diversity across biomes. Finally, we identified Exophiala and Cladophialophora as the most dominant black yeasts genera in soils across the globe. These findings provide novel evidence of global distribution of black yeasts and their key environmental predictors, giving new insights for speculating the evolution and spreading of these extreme‐tolerant organisms throughout both natural and human associated extreme environments.
China's efficient urban bias
Authors: Rangazas Peter , Wang Xiaobing , Zou Yuxiang
Published: March 2022

This paper develops a dynamic general equilibrium model with endogenous rural–urban migration to analyse the provision of rural and urban government services in China, with special emphasis on the role of the household registration (hukou) system in shaping its urbanization process. It argues that China's urban bias policy, which is enabled by the hukou system restricting rural–urban migration, did not necessarily reduce economic efficiency. Rather, it might have only raised urban welfare at the expense of rural residents. As the hukou system also ties people to particular geographical locations, this paper argues that China's continuous bias towards coastal and big cities has started to cause economic inefficiency as well as inequality. It suggests that progressive hukou reform reducing barriers to cross‐region migration would improve economic efficiency and welfare.
Intergenerational social mobility and the Brexit vote: How social origins and destinations divide Britain
Authors: MCNEIL ANDREW , HABERSTROH CHARLOTTE
Published: March 2022

To explain political divisions within British society, the current scholarship highlights the importance of the ‘winners’ and ‘left‐behind’ of political economic transformations. Yet, the impact of widespread absolute intergenerational social mobility in the past half century, which resulted in socio‐economic gains or losses for many, has not been systematically addressed. Our paper assesses how intergenerationally mobile voters’ positions in the Brexit referendum differ from their non‐mobile counterparts. We differentiate between the effects of social origins, social mobility and destination position. To do so, we model data from Understanding Society with a diagonal reference model. We show that origins are nearly as important as current socio‐economic positions for predicting the probability of voting to ‘leave’ or ‘remain’ in the Brexit referendum. We find that a first‐generation graduate would be up to 10 percentage points less likely to vote ‘Remain’ than a graduate whose parents also went to university.
Validating strength‐of‐support conclusion scales for fingerprint, footwear, and toolmark impressions
Authors: Busey Thomas , Klutzke Morgan , Nuzzi Alyssa , Vanderkolk John
Published: March 2022

In the pattern comparison disciplines such as fingerprints, footwear, and toolmarks, the results of a comparison are communicated by examiners in the form of categorical conclusions such as Identification or Exclusion. These statements have been criticized as requiring knowledge of prior probabilities by the examiners and being overinterpreted by laypersons. Alternative statements based on strength‐of‐support language have been proposed. The current study compares traditional conclusion scales against strength‐of‐support scales to determine how these new statements might be used by examiners in casework. Each participant completed 60 comparisons within their discipline, which were designed to approximate casework conditions, using either a traditional or a strength‐of‐support conclusion scale. The scale used on each trial was randomly assigned, and participants knew the scale for that trial as they began the comparison. Fingerprint examiners were much less likely to use Extremely Strong Support for Common Source than Identification. Footwear examiners treated the traditional and strength‐of‐support scales similarly, but toolmark examiners were much less likely to use Extremely Strong Support for Common Source than Identification, similar to fingerprint examiners. A separate group of fingerprint examiners used Identification less often when an expanded scale was available. The results demonstrate that expanded scales may result in the highest conclusion category being used less often by examiners when other alternatives are possible, and the term “extremely strong support” may introduce risk aversion on the part of examiners.
Return visits to the paediatric emergency department
Authors: Hollaway William , Borland Meredith L
Published: March 2022

Objective

To determine the rate of unplanned return visits (uRVs) within 48 h to a paediatric ED over a 12‐month period and describe the factors associated with these uRV.

Methods

Retrospective review of electronic data regarding the initial and follow‐up visit at a tertiary paediatric hospital ED in Western Australia. The primary outcome was the number of patients who presented for uRV within 48 h of their initial ED visit.

Results

Between August 2018 and July 2019, 2322 patients returned to the ED for a uRV comprising 3.4% of 68 352 ED presentations with more than 53% returning with infectious causes. Triage category 3 patients were most likely to represent (OR 1.11, P = 0.029) with 3‐month to 1‐year old (OR 1.37, P < 0.00001) and 1–5‐year old (OR 1.32, P < 0.00001) the commonest age groups. There was seasonal variation in uRVs demonstrating a greater number in the winter months. The percentage of uRVs to overall ED presentations was greater in the summer months (3.8–4.1%). There was a significant increase in uRVs occurring up to 2 weeks after the changeovers in middle‐grade ED doctors only.

Conclusions

The present study has demonstrated associations between uRV and initial‐visit triage category 3, age between 3 months and 5 years, and presentations because of infectious illness. Middle‐grade doctor changeover was also associated with an increase in uRVs.
Comparison of plasma separation using centrifugation or filtration for MONET lipoprotein apheresis in patients with cardiovascular disease and severe dyslipidemia
Authors: Waitz Grit , Atiye Saynab , Gauly Adelheid , Prophet Heinrich
Published: March 2022

Introduction

Homozygous or severe heterozygous familial hypercholesterolemia and elevated lipoprotein(a) levels may be treated with membrane filtration. The MONET system (Fresenius Medical Care, Bad Homburg, Germany) involves plasma separation by centrifugation or filtration.

Methods

Whether the method of plasma separation affects lipoprotein lowering and treatment safety was investigated in a single‐center retrospective study.

Results

The centrifugation‐based plasma separation achieved a higher plasma flow and shorter time to treat 1 L of plasma (46.2 ± 8.6 min), than the filtration‐based system (71.5 ± 40.0 min; p = 0.001). The mean reduction of LDL‐cholesterol was 69% and 67% with centrifugation and filtration and was 75% for lipoprotein(a) with both plasma separation methods. A reduction of IgM by more than 60%, of albumin and total protein by approximately 20% and low frequency of side effects was observed.

Conclusions

The efficacy of lowering atherogenic lipoproteins was comparable with both plasma separation methods. Centrifugation was more time‐efficient compared to filtration.
The therapeutic relationship between a client and dietitian: A systematic integrative review of empirical literature
Authors: Nagy Annaliese , McMahon Anne , Tapsell Linda , Deane Frank
Published: March 2022

Aim

Scientific evidence underpins dietetics practice; however, evidence of how the therapeutic relationship influences outcomes is limited. This integrative review aims to provide a comprehensive overview of the topic of the therapeutic relationship between clients and dietitians in the individual counselling context by summarising empirical literature into qualitative themes.

Methods

An electronic literature search of the Cumulative Index of Nursing and Allied Health Literature, PsychInfo, Scopus and Web of Science databases was conducted in October 2018 and repeated in February 2021. Studies were included if they explicitly referred to the therapeutic relationship (or associated terms), were based on study data and available in full text. Extracted data were checked by a second researcher and the methodological quality was evaluated independently by two researchers using the Mixed Methods Appraisal Tool. An iterative process of qualitatively coding, categorising and comparing data to examine recurring themes was applied.

Results

Seventy‐six studies met the inclusion criteria. Five themes were identified which showed the extent and nature of research in this area. Studies revealed the therapeutic relationship: (i) is valued within clinical dietetic practice, (ii) involves complex and multifactorial interactions, (iii) is perceived as having a positive influence, (iv) requires skills training and (v) is embedded in practice models and tools.

Conclusion

Studies show the therapeutic relationship is a valued and multifactorial component of clinical dietetic practice and is perceived to positively influence the client and dietitian. Observational data are needed to assess the extent to which the strength of the therapeutic relationship might contribute to clients' health outcomes.
Financial Reporting Consequences of Sovereign Wealth Fund Investment*
Authors: Godsell David
Published: March 2022

Sovereign wealth funds (SWFs) are government‐owned institutional investors pursuing political and financial investment objectives. With $8 trillion in assets, SWFs are geopolitical powerbrokers actively participating in global capital markets, yet we know little about the financial reporting consequences of SWF investment. I document evidence supporting the hypothesis that the simultaneous pursuit of political and financial investment objectives renders SWFs weak monitors. Using a staggered difference‐in‐differences research design, I document economically significant increases in discretionary accruals for SWF target firms after SWF investment, relative to an entropy‐balanced control group of non‐SWF target firms. Corroborating tests document that the effect of SWF investment on discretionary accruals strengthens with SWFs' equity stake and SWF target firms' earnings management incentives and weakens when regulators curb SWFs' pursuit of political objectives. I highlight SWFs' distinct monitoring effect by replicating my analyses after replacing SWF investment with conventional institutional investment, and document that conventional institutional investment instead reduces discretionary accruals. I further corroborate SWFs' distinct monitoring role among conventional institutional investors using a wide variety of robustness tests employing alternate specifications, samples, and financial reporting proxies. Overall, this study introduces an economically important and fundamentally distinct but little‐studied institutional investor to the accounting literature.