bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) in early development: a wide-scope metabolomics assay in zebrafish embryos
Authors: Merino Carla , Casado Marta , Piña Benjamí , Vinaixa Maria , Ramírez Noelia
Published: June 2021

The tobacco-specific nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic and ubiquitous environmental pollutant which carcinogenic and cytotoxic activity has been thoroughly investigated in murine models and human tissues. However, its potential deleterious effects on vertebrate early development are yet poorly understood. In this work, we characterized the impact of NNK exposure during early developmental stages of zebrafish embryos, a known alternative model for mammalian toxicity studies. Embryos exposed to different NNK concentrations were monitored for lethality and for the appearance of malformations during the first five days after fertilization. LC/MS-based untargeted metabolomics was subsequently performed for a wide-scope assay of NNK-related metabolic alterations. Our results revealed the presence of not only the parental compound, but also of two NKK known metabolites, 4-Hydroxy-4-(3-pyridyl)-butyric acid (HPBA) and 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol (NNAL-N-oxide) in exposed embryos likely resulting from active CYP450-mediated α-hydroxylation and NNK detoxification pathways, respectively. This was paralleled by a disruption in purine and pyrimidine metabolisms and the activation of the base excision repair pathway. Our results confirm NNK as a harmful embryonic agent and demonstrate zebrafish embryos to be a suitable early development model to monitor NNK toxicity.
A biochemically-realisable relational model of the self-manufacturing cell
Authors: Hofmeyr Jan-Hendrik S.
Published: June 2021

As shown by Hofmeyr, the processes in the living cell can be divided into three classes of efficient causes that produce each other, so making the cell closed to efficient causation, the hallmark of an organism. They are the enzyme catalysts of covalent metabolic chemistry, the intracellular milieu that drives the supramolecular processes of chaperone-assisted folding and self-assembly of polypeptides and nucleic acids into functional catalysts and transporters, and the membrane transporters that maintain the intracellular milieu, in particular its electrolyte composition. Each class of efficient cause can be modelled as a relational diagram in the form of a mapping in graph-theoretic form, and a minimal model of a self-manufacturing system that is closed to efficient causation can be constructed from these three mappings using the formalism of relational biology. This Fabrication-Assembly or (F,A)-system serves as an alternative to Robert Rosen’s replicative Metabolism-Repair or (M,R)-system, which has been notoriously problematic to realise in terms of real biochemical processes. A key feature of the model is the explicit incorporation of formal cause, which arrests the infinite regress that plagues all relational models of the cell. The (F,A)-system is extended into a detailed relational model of the self-manufacturing cell that has a clear biochemical realisation. This (F,A) cell model allows the interpretation and visualisation of concepts such as the metabolism and repair components of Rosen’s (M,R)-system, John von Neumann’s universal constructor, Howard Pattee’s symbol-function split via the symbol-folding transformation, Marcello Barbieri’s genotype-ribotype-phenotype ontology, and Tibor Gánti’s chemoton.
Hypoxia is a dominant remodeler of the CD8+T cell surface proteome relative to activation and regulatory T cell-mediated suppression
Authors: Byrnes James R. , Weeks Amy M. , Shifrut Eric , Carnevale Julia , Kirkemo Lisa , Ashworth Alan , Marson Alexander , Wells James A.
Published: June 2021

Immunosuppressive factors in the tumor microenvironment (TME) impair T cell function and limit the anti-tumor immune response. T cell surface receptors that influence interactions and function in the TME are already proven targets for cancer immunotherapy. However, surface proteome remodeling of primary human T cells in response to suppressive forces in the TME has never been characterized systematically. Using a reductionist cell culture approach with primary human T cells and SILAC-based quantitative cell surface capture glycoproteomics, we examined how two immunosuppressive TME factors, regulatory T cells (Tregs) and hypoxia, globally affect the activated CD8+surface proteome (surfaceome). Surprisingly, the CD8+/Treg co-culture only modestly affected the CD8+surfaceome, but did reverse several activation-induced surfaceomic changes. In contrast, hypoxia dramatically altered the CD8+surfaceome in a manner consistent with both metabolic reprogramming and induction of an immunosuppressed state. The CD4+T cell surfaceome similarly responded to hypoxia, revealing a novel hypoxia-induced surface receptor program. Our findings are consistent with the premise that hypoxic environments create a metabolic challenge for T cell activation, which may underlie the difficulty encountered in treating solid tumors with immunotherapies. Together, the data presented here provide insight into how suppressive TME factors remodel the T cell surfaceome and represent a valuable resource to inform future therapeutic efforts to enhance T cell function in the TME.
Distribution and vulnerability of transcriptional outputs across the genome in Myc-amplified medulloblastoma cells
Authors: Yang Rui , Wang Wenzhe , Dong Meichen , Roso Kristen , Greer Paula , Bao Xuhui , Pirozzi Christopher J. , Bigner Darell D. , Yan Hai , Ashley David M. , Zhabotynsky Vasyl , Zou Fei , He Yiping
Published: June 2021

Myc plays a central role in tumorigenesis by orchestrating the expression of genes essential to numerous cellular processes1-4. While it is well established that Myc functions by binding to its target genes to regulate their transcription5, the distribution of the transcriptional output across the human genome in Myc-amplified cancer cells, and the susceptibility of such transcriptional outputs to therapeutic interferences remain to be fully elucidated. Here, we analyze the distribution of transcriptional outputs in Myc-amplified medulloblastoma (MB) cells by profiling nascent total RNAs within a temporal context. This profiling reveals that a major portion of transcriptional action in these cells was directed at the genes fundamental to cellular infrastructure, including rRNAs and particularly those in the mitochondrial genome (mtDNA). Notably, even when Myc protein was depleted by as much as 80%, the impact on transcriptional outputs across the genome was limited, with notable reduction mostly only in genes involved in ribosomal biosynthesis, genes residing in mtDNA or encoding mitochondria-localized proteins, and those encoding histones. In contrast to the limited direct impact of Myc depletion, we found that the global transcriptional outputs were highly dependent on the activity of Inosine Monophosphate Dehydrogenases (IMPDHs), rate limiting enzymes for de novo guanine nucleotide synthesis and whose expression in tumor cells was positively correlated with Myc expression. Blockage of IMPDHs attenuated the global transcriptional outputs with a particularly strong inhibitory effect on infrastructure genes, which was accompanied by the abrogation of MB cell’s proliferation in vitro and in vivo. Together, our findings reveal a real time action of Myc as a transcriptional factor in tumor cells, provide new insight into the pathogenic mechanism underlying Myc-driven tumorigenesis, and support IMPDHs as a therapeutic vulnerability in cancer cells empowered by a high level of Myc oncoprotein.
Genome wide association mapping ofPyrenophora teresf.maculataandPyrenophora teresf.teresresistance loci utilizing natural Turkish wild and landrace barley populations
Authors: Clare Shaun J. , Oğuz Arzu Çelik , Effertz Karl , Poudel Roshan Sharma , See Deven , Karakaya Aziz , Brueggeman Robert S.
Published: June 2021

Unimproved landraces and wild relatives of crops are sources of genetic diversity that were lost post domestication in modern breeding programs. To tap into this rich resource, genome wide association studies in large plant genomes have enabled the rapid genetic characterization of desired traits from natural landrace and wild populations. Wild barley (Hordeum spontaneum), the progenitor of domesticated barley (H. vulgare), is dispersed across Asia and North Africa, and has co-evolved with the ascomycetous fungal pathogensPyrenophora teresf.teresandP. teresf.maculata, the casual agents of the diseases net form of net blotch and spot form of net blotch, respectively. Thus, these wild and local adapted barley landraces from the region of origin of both the host and pathogen represent a diverse gene pool to identify new sources of resistance, due to millions of years of co-evolution. The barley -P. terespathosystem is governed by complex genetic interactions with dominant, recessive, and incomplete resistances and susceptibilities, with many isolate-specific interactions. Here we provide the first genome wide association study of wild and landrace barley from the Fertile Crescent for resistance to both forms ofP. teres. A total of 14 loci, four againstP. teresf.maculataand ten againstPyrenophora teresf.teres,were identified in both wild and landrace populations, showing that both are genetic reservoirs for novel sources of resistance. We also highlight the importance of using multiple algorithms to both identify and validate additional loci.
Blocking antibodies against integrin-α3, -αM, and -αMβ2 de-differentiate myofibroblasts and reverse lung and kidney fibroses
Authors: White Michael JV , Ozkan Melis , Gomez-Medellin Jorge Emiliano , Rączy Michal M , Koss Kyle M , Solanki Ani , Zhang Zheng Jenny , Alpar Aaron T. , Naved Bilal , Wertheim Jason , Hubbell Jeffrey A
Published: June 2021

Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse the progression of the disease. Myofibroblasts are key to the progression and maintenance of fibrosis. We investigated features of cell adhesion necessary for monocytes to differentiate into myofibroblasts, seeking to identify pathways key to myofibroblast differentiation. Blocking antibodies against integrins α3, αM, and αMβ2 de-differentiate myofibroblasts in vitro, lower the pro-fibrotic secretome of myofibroblasts, and reverse lung and kidney fibrosis in vivo. Decorin’s collagen-binding peptide directs blocking antibodies (against integrins-α3, -αM, -αMβ2) to both fibrotic lungs and fibrotic kidneys, reducing the dose of antibody necessary to reverse fibrosis. This targeted immunotherapy blocking key integrins may be an effective therapeutic for the treatment and reversal of fibrosis.

Blocking antibodies against integrins-α3, -αM, and -αMβ2 can be targeted to sites of fibrosis, reverse lung and kidney fibroses, and offer the potential to bring immunotherapy to fibrosis
Bioelectromagnetic platform for stimulation
Authors: Ashbaugh Ryan C , Udpa Lalita , Israeli Ron R. , Gilad Assaf A. , Pelled Galit
Published: June 2021

Magnetogenetics is a new field that utilizes electromagnetic fields to remotely control cellular activity. In addition to the development of the biological genetic tools, this approach requires designing hardware with a specific set of demands for the electromagnets used to provide the desired stimulation for electrophysiology and imaging experiments. Here we present a universal stimulus delivery system comprised of four magnet designs compatible with electrophysiology, fluorescence and luminescence imaging, microscopy, and freely behaving animal experiments. The overall system includes a low-cost stimulation controller which enables rapid switching between active and sham stimulation trials as well as precise control of stimulation delivery.
An extension of Wang’s protein design model using Blosum62 substitution matrix
Authors: Rahmani Amin , Mirakabad Fatemeh Zare
Published: June 2021

Humans life depends on the functionality of molecules in the body. One of these essential molecules is the protein that plays a vital role in our life, such that its malfunction can cause severe damages. Such roles make protein structure and its functionality necessary to understand. One of the problems that help us understand the relation between protein structure is the well-known protein design problem which attempts to find an amino acid sequence that can fold into a desired tertiary structure. However, despite having an acceptable accuracy in protein design, this accuracy is an identical percentage of amino acid retrieving. At the same time, it is well-known that amino acids can replace each other in evolution while the function and structure of protein stay the same. Thus the designed sequence does not have the opportunity to be close to the target in the evolutionary aspect. This paper presents an extension to Wang’s deep learning model, which uses evolutionary information in the Blosum62 substitution matrix to take amino acid replacement probability into account while designing a sequence.
Strain-Programmable Patch for Diabetic Wound Healing
Authors: Theocharidis Georgios , Yuk Hyunwoo , Roh Heejung , Wang Liu , Mezghani Ikram , Wu Jingjing , Kafanas Antonios , Chen Lihong , Guo Chuan Fei , Jayaswal Navin , Katopodi Xanthi-Leda , Nabzdyk Christoph S. , Vlachos Ioannis S. , Veves Aristidis , Zhao Xuanhe
Published: June 2021

Chronic wounds with impaired healing capability such as diabetic foot ulcers (DFU) are devastating complications in diabetic patients, inflicting rapidly growing clinical and economic burdens in aging societies. Despite recent advances in therapeutic approaches, limited benefits of the existing solutions highlight the critical need for novel therapeutic solutions for diabetic wound healing. Here we propose a strain-programmable patch capable of rapid robust adhesion on and programmable mechanical contraction of wet wounded tissues over days to offer a new therapeutic platform for diabetic wounds. The strain-programmable patch, consisting of a dried bioadhesive layer and a pre-stretched elastomer backing, implements a hydration-based shape-memory mechanism to achieve both uniaxial and biaxial contractions and stress remodeling of wet wounds in a programmable manner. We develop theoretical and numerical models to rationally guide the strain-programming and mechanical modulation of wounds. In vivo rodent and ex vivo human skin culture models validate the programmability and efficacy of the proposed platform and identify mechanisms of action for accelerated diabetic wound healing.

One Sentence Summary

A strain-programmable bioadhesive patch is developed for accelerated closure and healing of wounds in diabetic mice and human skin.
Nutrient profiling reveals extracellular uridine as a fuel for pancreatic cancer through uridine phosphorylase 1
Authors: Ward Matthew H. , Nwosu Zeribe C. , Poudel Pawan , Kasperek Steven , Tolstyka Zach , Menjivar Rosa E. , Ragulan Chanthirika , Nyamundanda Gift , Zhang Li , Andren Anthony , Halbrook Christopher J. , Carpenter Eileen S. , di Magliano Marina Pasca , Sadanandam Anguraj , Lyssiotis Costas A.
Published: June 2021

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease characterized by high invasiveness, therapeutic resistance, and metabolic aberrations. Although altered metabolism drives PDA growth and survival, the complete spectrum of metabolites used as nutrients by PDA remains largely unknown. Here, we aimed to determine novel nutrients utilized by PDA. We assessed how >175 metabolites impacted metabolic activity in 19 PDA cell lines under nutrient-restricted conditions. This analysis identified uridine as a novel metabolite driver of PDA survival in glucose-deprived conditions. Uridine utilization strongly correlated with expression of the enzyme uridine phosphorylase 1 (UPP1). Metabolomics profiling, notably13C-stable isotope tracing, revealed that uridine-derived ribose is the relevant component supporting redox balance, survival, and proliferation in glucose-deprived PDA cells. We demonstrate that UPP1 catabolizes uridine, shunting its ribose component into central carbon metabolism to support glycolysis, the tricarboxylic acid (TCA) cycle and nucleotide biosynthesis. Compared to non-tumoral tissues, we show that PDA tumors express highUPP1, which correlated with poor overall survival in multiple patient cohorts. Further, uridine is enriched in the pancreatic tumor microenvironment, and we demonstrate that this may be provided in part by tumor associated macrophages. Finally, we found that inhibition ofUPP1restricted the ability of PDA cells to use uridine, and thatUPP1knockout impairs tumor growthin vivo. Our data identifies uridine catabolism as a critical aspect of compensatory metabolism in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy.
Presynaptic FMRP and local protein synthesis support structural and functional plasticity of glutamatergic axon terminals
Authors: Monday Hannah R. , Kharod Shivani C. , Yoon Young J. , Singer Robert H. , Castillo Pablo E.
Published: June 2021

Learning and memory critically rely on long-lasting, synapse-specific modifications. While postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis contributes to presynaptic changes remains unclear. Here, we examined the hippocampal mossy fiber (MF)-CA3 synapse which expresses both structural and functional presynaptic plasticity. We report that MF boutons synthesize protein locally and contain ribosomes. Long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with translation-dependent enlargement of MF boutons. Moreover, increasing in vitro and in vivo MF activity enhanced protein synthesis in MFs. Remarkably, deletion of presynaptic Fragile X mental retardation protein (FMRP), an RNA-binding protein expressed in MF boutons and previously implicated in local postsynaptic protein synthesis-dependent plasticity, blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic function. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature brain.

Highlights

Mossy fiber boutons (MFBs) synthesize protein locally and contain ribosomes

Local presynaptic translation is increased by in vitro and in vivo GC activity

MFB structural plasticity relies on de novo protein synthesis.

Presynaptic FMRP is required for MF-CA3 structural and functional plasticity

In Brief

Monday et al. report that FMRP and protein synthesis in hippocampal mossy fiber boutons mediate functional and structural presynaptic plasticity.
DRUG-seq Provides Unbiased Biological Activity Readouts for Drug Discovery
Authors: Li Jingyao , Ho Daniel J. , Henault Martin , Yang Chian , Neri Marilisa , Ge Robin , Renner Steffen , Mansur Leandra , Lindeman Alicia , Tumkaya Tayfun , Russ Carsten , Hild Marc , Keller Caroline Gubser , Jenkins Jeremy L. , Worringer Kathleen A. , Sigoillot Frederic D. , Ihry Robert J.
Published: June 2021

Unbiased transcriptomic RNA-seq data has provided deep insights about biological processes. However, its impact in drug discovery has been narrow given high costs and low throughput. Proof-of-concept studies with Digital RNA with pertUrbation of Genes (DRUG)-seq demonstrated the potential to address this gap. We extended the DRUG-seq platform by subjecting it to rigorous testing and by adding an open-source analysis pipeline. The results demonstrate high reproducibility and ability to resolve the mechanism(s) of action for a diverse set of compounds. Overall, the protocol and open-source analysis pipeline are a step towards industrializing RNA-seq for high complexity transcriptomics studies performed at a saturating scale.
Cool temperature limit Zika virus genome replication
Authors: Tesla Blanka , Powers Jenna S. , Barnes Yvonne , Lakhani Shamil , Acciani Marissa D. , Murdock Courtney C. , Brindley Melinda A.
Published: June 2021

Zika virus is a mosquito-borne flavivirus known to cause severe birth defects and neuroimmunological disorders. We have previously demonstrated that mosquito transmission of Zika virus decreases with temperature. While transmission was optimized at 29°C, it was limited at cool temperatures (< 22°C) due to poor virus establishment in the mosquitoes. Temperature is one of the strongest drivers of vector-borne disease transmission due to its profound effect on ectothermic mosquito vectors, viruses, and their interaction. Although there is substantial evidence of temperature effects on arbovirus replication and dissemination inside mosquitoes, little is known about whether temperature affects virus replication directly or indirectly through mosquito physiology. In order to determine the mechanisms behind temperature-induced changes in Zika virus transmission potential, we investigated different steps of the virus replication cycle in mosquito cells (C6/36) at optimal (28°C) and cool (20°C) temperatures. We found that cool temperature did not alter Zika virus entry or translation but reduced the amount of double-stranded RNA replication intermediates. If replication complexes were first formed at 28°C and the cells were subsequently shifted to 20°C, the late steps in the virus replication cycle were efficiently completed. These data suggest that cool temperature decreases the efficiency of Zika virus genome replication in mosquito cells. This phenotype was observed in the Asian-lineage of Zika virus, while the African-lineage Zika virus was less restrictive at 20°C.

Importance

With half of the human population at risk, arboviral diseases represent a substantial global health burden. Zika virus, previously known to cause sporadic infections in humans, emerged in the Americas in 2015 and quickly spread worldwide. There was an urgent need to better understand the disease pathogenesis, develop therapeutics and vaccines, as well as to understand, predict, and control virus transmission. In order to efficiently predict the seasonality and geography for Zika virus transmission, we need a deeper understanding of the host-pathogen interactions and how they can be altered by environmental factors such as temperature. Identifying the step in the virus replication cycle that is inhibited in cool conditions can have implications in modeling the temperature suitability for arbovirus transmission as global environmental patterns change. Understanding the link between pathogen replication and environmental conditions can potentially be exploited to develop new vector control strategies in the future.
Systematic review of Economic studies of Partner Notification and management interventions for sexually transmitted infections including HIV in men who have sex with men
Authors: Okeke Ogwulu CB , Abdali Z , Williams EV , Estcourt CS , Howarth AR , Copas A , Mapp F , Woode-Owusu M , Roberts TE
Published: June 2021

Objectives

Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). Partner notification (PN) to identify, test and treat sex partners of MSM with bacterial STIs is challenging because MSM often report larger numbers of sex partners and a higher proportion of one-off partners who may be difficult to engage. However, one-off partners contribute disproportionately to onward transmission. Economic research on PN has typically focused on heterosexual people and evidence of effectiveness of PN in MSM is scant. We conducted a systematic review of economic studies of PN interventions in MSM to inform the development of a novel PN intervention for MSM with one-off partners.

Method

Six electronic databases were searched up to June 2020. Cost studies and full economic evaluations, which focused on PN and/or testing and treatment (in the context of PN) of sex partners of MSM with STIs, and/or HIV, were included. A two-stage categorisation process was used for study selection and a narrative synthesis was reported.

Results

Twenty-six studies of a possible 1909 met the selection criteria. Sixteen focused on MSM but only three of these were on PN. Few studies reported on patients’ characteristics and settings. Most studies were cost-utility analyses with outcomes reported as quality-adjusted life years (QALYs) which were derived from studies on heterosexual people.

Conclusions

None of the identified studies specifically addressed cost-effectiveness of PN in MSM. The few studies identified as potentially relevant relied on costs and QALYs data from studies in heterosexual people, which may be inappropriate given the different patterns of sexual partnerships reported by these two groups. The lack of evidence on efficient PN approaches for MSM, a group with a high burden of infection, supports the need for new interventions tailored to the needs and preferences of MSM with parallel economic evaluation.
Bayesian mapping of the striatal microcircuit reveals robust asymmetries in the probabilities and distances of connections
Authors: Cinotti François , Humphries Mark D.
Published: June 2021

The striatum’s complex microcircuit is made by connections within and between its D1- and D2-receptor expressing projection neurons and at least five species of interneuron. Precise knowledge of this circuit is likely essential to understanding striatum’s functional roles and its dysfunction in a wide range of movement and cognitive disorders. We introduce here a Bayesian approach to mapping neuron connectivity using intracellular recording data, which lets us simultaneously evaluate the probability of connection between neuron types, the strength of evidence for it, and its dependence on distance. Using it to synthesise a complete map of the mouse striatum, we find strong evidence for two asymmetries: a selective asymmetry of projection neuron connections, with D2 neurons connecting twice as densely to other projection neurons than do D1 neurons, but neither subtype preferentially connecting to another; and a length-scale asymmetry, with interneuron connection probabilities remaining non-negligible at more than twice the distance of projection neuron connections. We further show our Bayesian approach can evaluate evidence for wiring changes, using data from the developing striatum and a mouse model of Huntington’s disease. By quantifying the uncertainty in our knowledge of the microcircuit, our approach reveals a wide range of potential striatal wiring diagrams consistent with current data.
The impact of housing conditions on porcine mesenchymal stromal/stem cell populations differ between adipose tissue and skeletal muscle
Authors: Quéméner Audrey , Dessauge Frédéric , Perruchot Marie-Hélène , Le Floc’h Nathalie , Louveau Isabelle
Published: June 2021

Background

In pigs, the ratio between lean mass and fat mass in the carcass determines production efficiency and is strongly influenced by the number and size of cells in tissues. During growth, the increase in the number of cells results from the recruitment of different populations of multipotent mesenchymal stromal/stem cells (MSCs) residing in the tissues. We hypothesized that the impact of hygiene of housing conditions during growth on the proportions of MSCs in adipose tissue and skeletal muscle may differ between pigs with different residual feed intake (RFI), a measure of feed efficiency.

Methods

At the age of 12 weeks, Large White pigs from two lines divergently selected for low and high RFI were housed in two contrasting hygiene conditions (good vs poor). After six weeks, pigs were slaughtered (n = 30; 5-9/group). Samples of subcutaneous adipose tissue and longissimus skeletal muscle were collected, and cells from the stromal vascular fraction (SVF), which includes mesenchymal stromal/stem cell populations, were isolated from each tissue. Adipose and muscle cell populations from the SVF were phenotyped by flow cytometry using antibodies that targeted different cell surface markers (CD45 to separate hematopoietic cells from MSCs; CD34, CD38, CD56 and CD140a to identify MSC populations with adipogenic and/or myogenic potential).

Results

Adipose tissue and muscle shared some common MSC populations although MSC diversity was higher in muscle than in adipose tissue. In muscle, the CD45-CD56+CD34-CD140a+ and CD45-CD56+CD34+CD140a+ cell populations were abundant. Of these two cell populations, only the proportions of CD45-CD56+CD34+CD140a+ cells increased (P < 0.05) in pigs housed in poor hygiene as compared with pigs in good hygiene conditions. For the CD45-CD56-CD34- cell population, present in low proportion, there was an interaction between hygiene condition and genetic line (P < 0.05) with a decrease in low RFI pigs housed in poor hygiene conditions. In adipose tissue, the two abundant MSC populations were CD45-CD56-CD34- and CD45-CD56+CD34-. The proportion of CD45-CD56-CD34- cells increased (P < 0.05) whereas the proportion of CD45-CD56+CD34- tended to decrease (P < 0.1) in pigs housed in poor conditions. This study shows that the proportions of some MSC populations were affected by hygiene of housing conditions in a tissue-dependent manner in pigs of both RFI lines. It suggests that MSCs may play a significant role in adipose tissue and skeletal muscle homeostasis and may influence later growth and body composition in growing animals.
The wall-less bacterium Spiroplasma poulsonii builds a polymeric cytoskeleton composed of interacting MreB isoforms
Authors: Masson Florent , Pierrat Xavier , Lemaitre Bruno , Persat Alexandre
Published: June 2021

A rigid cell wall defines the morphology of most bacteria. MreB, a bacterial homologue of actin, plays a major role in coordinating cell wall biogenesis and defining a cell’s shape. In contrast with most bacteria, the Mollicutes family is devoid of cell wall. As a consequence, many Mollicutes have undefined morphologies. Spiroplasma species are an exception as they robustly grow with a characteristic helical shape, but how they maintain their morphology remains unclear. Paradoxal to their lack of cell wall, the genome of Spiroplasma contains five homologues of MreB (SpMreBs). Since MreB is a homolog of actin and that short MreB filaments participate in its function, we hypothesize that SpMreBs form a polymeric cytoskeleton. Here, we investigate the function of SpMreB in forming a polymeric cytoskeleton by focusing on the Drosophila endosymbiont Spiroplasma poulsonii. We found that in vivo, Spiroplasma maintain a high concentration of all five MreB isoforms. By leveraging a heterologous expression system that bypasses the poor genetic tractability of Spiroplasma, we found that strong intracellular levels of SpMreb systematically produced polymeric filaments of various morphologies. Using co-immunoprecipitation and co-expression of fluorescent fusions, we characterized an interaction network between isoforms that regulate the filaments formation. Our results point to a sub-functionalization of each isoform which, when all combined in vivo, form a complex inner polymeric network that shapes the cell in a wall-independent manner. Our work therefore supports the hypothesis where MreB mechanically supports the cell membrane, thus forming a cytoskeleton.

Significance statement

Bacteria shape is determined by their cell wall. The actin homologue MreB essentially determines shape by organizing cell wall synthesis at the subcellular level. Despite their lack of cell wall, Spiroplasma robustly grow into long helical bacteria. Surprisingly, its genome retains five copies of mreB while it lost genes encoding canonical MreB interactors. We sought to delineate the exact function of Spiroplasma MreBs (SpMreBs). We leveraged in vivo data along with functional studies to systematically investigate MreB polymerization behavior. We uncovered that SpMreBs build into filaments, which structure it determined by a complex interaction network between isoforms. Our results support the hypothesis that MreB can mechanically support the membrane of Spiroplasma, hence acting as a load-bearing cytoskeletal protein.
Contrast – a lightweight Python framework for beamline orchestration and data acquisition
Authors: Björling Alexander , Weninger Clemens , Kahnt Maik , Kalbfleisch Sebastian , Johansson Ulf , Sala Simone , Lenrick Filip , Thånell Karina
Published: June 2021

The emergence of fourth-generation synchrotrons is prompting the development of new systems for experimental control and data acquisition. However, as general control systems are designed to cover a wide set of instruments and techniques, they tend to become large and complicated, at the cost of experimental flexibility. Here we present Contrast, a simple Python framework for interacting with beamline components, orchestrating experiments and managing data acquisition. The system is presented and demonstrated via its application at the NanoMAX beamline of the MAX IV Laboratory.
Public debt and economic growth: contemporary evidence from a developing economy
Authors: Hilton Sam Kris
Published: June 2021

Purpose

Considering the continuous rise in the public debt stock of developing countries (particularly Ghana) with the unstable economic growth rate for the past decades and the recent borrowing because of the impact of COVID 19, this paper aims to examine the causal relationships between public debt and economic growth over time.

Design/methodology/approach

The paper uses a dynamic multivariate autoregressive-distributed lag (ARDL)-based Granger-causality model to test the causal relationships between public debt and economic growth [gross domestic product (GDP)]. Annual time-series data that spanned 1978–2018 were sourced from the World Bank Development Indicator database and the IMF fiscal Affairs Department Database and WEO.

Findings

The results reveal that public debt has no causal relationship with GDP in the short-run but there is unidirectional Granger causality running from public debt to GDP in the long run. Again, investment spending has a negative bi-directional causal relationship with GDP in the short-run but they have a positive bi-directional causal relationship in the long run. Conversely, no short-run causal relationship exists between government consumption expenditure and GDP but long-run Granger causality runs from government consumption expenditure to GDP. Finally, public debt has a positive impact on the inflation rate in the short run.

Practical implications

The findings imply that government(s) must ensure high fiscal discipline to serve as a precursor for the effective and efficient use of recent borrowing, that is, the loans should be used for highly prioritized projects (preferably investment spending) that are well evaluated and self-sustained to add positively to the GDP.

Originality/value

This paper provides contemporary findings to augment extant literature on public debt and economic growth by using variables and empirical models, which prior studies could not sufficiently cover in a developing country perspective and affirms that public debt contributes to GDP only in the long run.
Enhancing users involvement in architectural design using mobile augmented reality
Authors: Shouman Bassam , Othman Ayman Ahmed Ezzat , Marzouk Mohamed
Published: June 2021

Purpose

Mobile augmented reality (MAR) is one of the advanced three-dimensional (3D) representation tools that has been recently utilized in the construction industry. This paper aims to assess a user’s involvement levels through MAR application that has been experimented against traditional involvement techniques through an existing facility, plan re-designing scenario.

Design/methodology/approach

Through reviewing related literature studies in the MAR field, an application has been developed that can superimpose real design alternatives on paper-based markers, allowing for flexible wall positioning, interior and exterior wall material application. As such, an enhanced user involvement experience is created. To measure user involvement levels, the application is experimented with 33 participants having the British University in Egypt’s library building as a case study, followed by survey questionnaires to gather and evaluate user responses.

Findings

The results of the analyzed data using SPSS indicated that MAR showed a positive impact on enhancing user involvement and better understanding of design projects. It also allowed users to produce different design alternatives in comparison to the traditional involvement approaches where users showed low design interaction and understanding.

Originality/value

The interactive features of the proposed application facilitate implementing ideas in design of construction projects that require user involvement.
Impact of personal values on customer satisfaction and word of mouth for luxury hotel service consumption in Confucian culture: evidence from Vietnam
Authors: Cam Le Nguyen Thi , Quy Vo Thi , Kim Quy Hoang Thi
Published: June 2021

Purpose

This research aims to investigate the effect of personal values on customer satisfaction and whether positive experiences lead to positive word of mouth (WOM) about the luxury hotel service from the Confucian perspective.

Design/methodology/approach

This research developed a structural equation model for testing. Research data collected from Confucian participants who have used luxury hotel services in Vietnam, where Confucianism is the dominant cultural paradigm.

Findings

The results show that there is a positive relationship between Confucian customer personal values and satisfaction, as well as between customer satisfaction and positive WOM; personal values had no effect on positive WOM.

Research limitations/implications

This research implies that the personal values of Confucian consumers constitute the lens through which they view the world, thus the service personal values reflect their priorities on luxury hotel service consumption. A key to success for luxury hotel service providers lies in providing services that enhance Confucian customer personal values, which allow service providers to intercommunicate with the Confucian consumers’ core.

Originality/value

This research is significant because there is little research on personal values from the cultural mechanism of Confucian culture. This research also comes up with a richer understanding of the relationship between customer personal values and behaviors within the luxury hotel segment.
Commitment profiles of nascent entrepreneurs: insights from an empirical taxonomy among French student entrepreneurs
Authors: Gabay-Mariani Laetitia , Boissin Jean-Pierre
Published: June 2021

Purpose

In line with an emerging body of literature questioning student entrepreneurs’ practices, and recent calls to bridge the intention-action gap, this contribution aims to identify profiles of commitment among nascent entrepreneurs, and their relationship with the performance of entrepreneurial behaviors.

Design/methodology/approach

Relying on Meyer and Allen's multidimensional model, the authors build an empirical taxonomy regarding affective and instrumental forms of commitment experienced by nascent entrepreneurs (n = 328) operating within French higher education.

Findings

The authors identify three commitment profiles – weak, affective and total – associated with distinct levels of advancement and investment in the entrepreneurial process. This analysis leads them to map out the entrepreneurial process followed by nascent entrepreneurs with three main thresholds: the initial threshold, the resonance threshold and the irreversibility threshold.

Research limitations/implications

The work contributes to an emerging field of research dedicated to student entrepreneurship. It highlights the existence of different trajectories among nascent entrepreneurs, but also to different ways of being tied to them. It also enriches more broadly the understanding of the entrepreneurial process, especially its volitional phase.

Practical implications

The results are also important to guide public action, especially to design relevant support programs accounting for nascent entrepreneurs' diversity.

Originality/value

This is the first research to identify profiles of nascent student entrepreneurs based on the way they feel tied to their project, but also to the broader project of becoming entrepreneurs.
Initial teacher education students' perceptions during a practicum in primary schools: a New Zealand experience
Authors: Fletcher Jo , Astall Chris , Everatt John
Published: June 2021

Purpose

This paper is about mentoring of initial teacher education (ITE) students whilst on their practicum.

Design/methodology/approach

Informed by a social constructivist theoretical framework, an online survey was used to capture the breadth of quantitative data and the richness of qualitative responses relating to factors that impact student teachers' experiences during practicum.

Findings

Quantitative data indicate that many student teachers were positive about the practicum, but this varied across the type of school in which they were placed. The qualitative data analyses showed a greater in-depth understanding of the range of issues that impacted how student teachers are treated in their role as a mentee by the mentor and the wider school community.

Practical implications

Better understanding the experiences of student teachers helps to inform ITE providers of the critical role that mentor teachers play in preparing student teachers. The practical implications are that strategies to develop deep and collaborative partnerships amongst ITE providers, mentor teachers and school leaders, which build stronger understandings of a mentor teacher's role, are critical in order to support student teachers.

Originality/value

This research study repositions the critical nature of effective mentoring of student teachers so that mentor teachers and ITE providers can be informed by the voices and lived realities of these student teachers. The mentoring relationship needs to be critically interrogated to provide a more even and supportive “playing field” for all student teachers.
CSR fit and organizational attractiveness for job applicants
Authors: Agnihotri Arpita , Bhattacharya Saurabh
Published: June 2021

Purpose

The purpose of this paper is to explore a conceptual model on the influence of corporate social responsibility (CSR) “fit” on organizational attractiveness among job applicants under the boundary conditions of chief executive officer (CEO) activism and CSR credibility.

Design/methodology/approach

The study is based on archival research, largely reviewing extant in CSR and drawing propositions based on existing theory.

Findings

Paper draws propositions based on CSR fit, credibility and CEO activism. The paper asserts the influence of CSR fit on organizational attractiveness among job applicants. It further explains moderated mediating mechanism through which CSR fit influences organizational attractiveness among job applicants.

Originality/value

Recruitment has primarily explored the role of CSR in attracting potential job candidates. This paper presents the role of CSR “fit,” an aspect not explored before in recruitment. This paper also introduces the role of CEO activism in recruitment.
Intraday analysis of regulation change in microstructure: evidence from an emerging market
Authors: Kadioglu Eyup
Published: June 2021

Purpose

This study investigates the impact of simultaneously replacing both midday single-price call auction and lunch break with multi-price continuous trading on intraday volatility–volume patterns as well as the intraday volatility–volume nexus.

Design/methodology/approach

The analysis utilises 150 m tick-by-tick transaction data related to 333 stocks traded on Borsa Istanbul Equity Market covering a period of 2 months prior to and following the change. In addition to graphic comparisons, the study uses difference in mean tests, panel-fixed generalized least squares (GLS), panel-random GLS and random-effects linear models with AR(1) disturbance regression estimations.

Findings

The results show that intraday volatility and trading volume form an inverse J-shape and are positively correlated. It is observed that the implementation of the regulation change decreased intraday volatility and increased trading volume. Additionally, the results indicate a negative volatility–liquidity and a positive volume–liquidity relationship, supporting the mixture of distribution hypothesis.

Research limitations/implications

Enhanced market efficiency provides greater opportunity for investment and risk management. Investors can benefit from the findings on the intraday volatility–volume nexus, which is an indicator of informed trading, and regulatory authorities can use volume to oversight volatility.

Originality/value

This very rare regulation change of the simultaneous replacement of the lunch break and midday call auction with continuous trading is investigated in the context of intraday volume and volatility. This study also expands upon some important findings on the volume–volatility nexus for the Turkish Stock Market.
Tribo-performance analysis of HVOF sprayed 86WC-10Co4Cr & Ni-Cr2O3on AISI 316L steel using DOE-ANN methodology
Authors: Singh Jashanpreet
Published: June 2021

Purpose

The purpose of this paper is to carry out erosion wear investigation on high-velocity oxy-fuel (HVOF)-deposited 86WC-10Co4Cr and synergistic Ni/Chromia powder (i.e. 80Ni-20Cr2O3) on AISI 316L.

Design/methodology/approach

Design of experiments-artificial neural network (DOE-ANN) methodology was adopted to calculate the erosion wear. Taguchi’s orthogonal array L16 (42) was used to perform set-of-erosion experiments followed by lower-the-better rule. The artificial neural network (ANN) model is used on erosion wear data obtained from the experiments.

Findings

Experimental results indicate that 86WC-10Co4Cr provided better erosion wear resistance as compared to Ni/Chromia. The erosion wear of 86WC-10Co4Cr and synergistic Ni/Chromia coatings increases with an increase in time duration, solid concentration and time. The magnitude of erosion generated by ashes was comparatively lower than sand. The arithmetic mean roughness (Ra) of finished AISI 316L, 86WC-10Co4Cr and Ni/Chromia coating was found as 0.46 ± 0.13, 6.50 ± 0.16 and 7.04 ± 0.23 µm, respectively. Surface microhardness of AISI 316L, 86WC-10Co4Cr and Ni/Chromia coating was found as 197 ± 18, 1,156 ± 18 and 1,021± 21 HV, respectively.

Practical implications

The present results can be useful for estimation of erosion wear in slurry pumps used in mining industry for the conveying of sand and in thermal power plants for the conveying of ashes to the dyke area.

Originality/value

The erosion wear of HVOF-sprayed 86WC-10Co4Cr and Synergistic Ni/Chromia powders was studied experimentally as well as predicted by the ANN model, and wear mechanisms are well discussed by scanning electron micrographs.
The impact of empowerment-focused human resource management on relationship learning and innovation
Authors: Zhang Huiying , Yang Man , Huo Baofeng
Published: June 2021

Purpose

In the field of innovation, there is growing interest in exploring the factors that determine the extent to which firms can learn from external sources. However, most previous studies neglect the role of human factors. Little is known about which employee behaviors are desirable for boundary-spanning learning activities and which human resource management (HRM) practices are appropriate to respond to external knowledge transfer across boundaries. To fill this gap, the authors investigate the role of empowerment-focused HRM in interfirm learning and explore the integration of external inputs from the perspective of employees.

Design/methodology/approach

Based on empirical survey data collected from different countries, the authors test the proposed model with structural equation modeling.

Findings

The authors’ findings indicate that empowerment-focused HRM practices, including job enrichment, job autonomy, teamwork and cross-functional communication, are positively associated with relationship learning.

Originality/value

In this study, the authors present a theoretical explanation for how empowerment-focused HRM may influence firm's innovation through relationship learning process and provide empirical evidence regarding the specific HRM practices that can have different effects on the different phases of relationship learning.