bluuebunny/crossref_metadata_2025 huggingface dataset:
Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing
Authors: Wan Ji , Nie Zhongyi , Xu Jie , Zhang Zixuan , Yao Shenglian , Xiang Zehua , Lin Xiang , Lu Yuxing , Xu Chen , Zhao Pengcheng , Wang Yiran , Zhang Jingyan , Wang Yaozheng , Zhang Shaotong , Wang Jinzhuo , Man Weitao , Zhang Min , Han Mengdi
Published: November 2023

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors must rely on transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces the biocompatibility, or limits the portability. Here, we develop a set of millimeter-scale, chip-less and battery-less magnetic implants that can measure biophysical and biochemical signals wirelessly. In particular, the implants form two-way communications with a fully integrated wearable device, where the wearable device can induce a large-amplitude damped vibration of the magnetic implants and capture their subsequent motions in a wireless manner. Such damped vibrations reflect not only the biophysical conditions surrounding the implants movements, but also the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities in measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure (ICP), and CSF glucose levels. This miniaturized system opens possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.
Zinc finger homeobox-3 (ZFHX3) orchestrates genome-wide daily gene expression in the suprachiasmatic nucleus
Authors: Bafna Akanksha , Banks Gareth , Vasilyev Vadim , Dallmann Robert , Hastings Michael H. , Nolan Patrick M.
Published: November 2023

The mammalian suprachiasmatic nucleus (SCN), situated in the ventral hypothalamus, directs daily cellular and physiological rhythms across the body. The SCN clockwork is a self-sustaining transcriptional-translational feedback loop (TTFL) that in turn co-ordinates the expression of clock-controlled genes (CCGs) directing circadian programmes of SCN cellular activity. In the mouse, the transcription factor, ZFHX3 (zinc finger homeobox-3), is necessary for the development of the SCN and influences circadian behaviour in the adult. The molecular mechanisms by which ZFHX3 affects the SCN at transcriptomic and genomic levels are, however, poorly defined. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) to map the genomic localization of ZFHX3 binding sites in SCN chromatin. To test for function, we then conducted comprehensive RNA sequencing at six distinct times-of-day to compare the SCN transcriptional profiles of control and ZFHX3-conditional null mutants. We show that the genome-wide occupancy of ZFHX3 occurs predominantly around gene transcription start sites (TSS), co-localizing with known histone modifications, and preferentially partnering with clock transcription factors (CLOCK, BMAL1) to regulate clock gene(s) transcription. Correspondingly, we show that the conditional loss of ZFHX3 in the adult has a dramatic effect on the SCN transcriptome, including changes in the levels of transcripts encoding elements of numerous neuropeptide neurotransmitter systems while attenuating the daily oscillation of the clock TFBmal1. Furthermore, various TTFL genes and CCGs exhibited altered circadian expression profiles, consistent with an advanced in daily behavioural rhythms under 12h light-12h dark conditions. Together, these findings reveal the extensive genome-wide regulation mediated by ZFHX3 in the central clock that orchestrates daily timekeeping in mammals.
Eccentric exercise ≠ eccentric contraction
Authors: Tecchio Paolo , Raiteri Brent J. , Hahn Daniel
Published: November 2023

Whether eccentric exercise involves active fascicle stretch is unclear due to muscle-tendon unit (MTU) series elasticity. Therefore, this study investigated the impact of changing the activation timing and level (i.e., pre-activation) on muscle fascicle kinematics and kinetics of the human tibialis anterior during dynamometer-controlled maximal voluntary MTU-stretch-hold contractions. B-mode ultrasound and surface electromyography were employed to assess muscle fascicle kinematics and muscle activity levels, respectively. While joint kinematics were similar for MTU-stretch-hold contractions, increasing pre-activation increased fascicle shortening and stretch amplitudes (9.9 - 23.2 mm,p≤ 0.015). This led to increasing positive and negative fascicle work with increasing pre-activation. Despite significantly different fascicle kinematics, similar peak fascicle forces during stretch occurred at similar fascicle lengths and joint angles regardless of pre-activation. Similarly, residual force enhancement (rFE) following MTU stretch was not significantly affected (6.5–7.6 %,p= 0.559) by pre-activation, but rFE was strongly correlated with peak fascicle force during stretch (rrm= 0.62,p= 0.003). These findings highlight that apparent eccentric exercise causes shortening-stretch contractions at the fascicle level rather than isolated eccentric contractions. The constant rFE despite different fascicle kinematics and kinetics suggests that a passive element was engaged at a common muscle length among conditions (e.g., optimal fascicle length). Although it remains unclear whether different fascicle mechanics trigger different adaptations to eccentric exercise, this study emphasizes the need to consider MTU series elasticity to better understand the mechanical drivers of adaptation to exercise.

New & Noteworthy

Apparent eccentric exercises do not result in isolated eccentric contractions, but shortening-stretch contractions at the fascicle level. The amount of fascicle shortening and stretch depend on the pre-activation during the exercise andcannotbe estimated from the muscle-tendon unit or joint kinematics. As different fascicle mechanics might trigger different adaptations to eccentric exercise, muscle-tendon unit series elasticity and muscle pre-activation need to be considered when eccentric exercise protocols and designed and evaluated.
Personality and behavioral syndromes in two species of fruit bats (Chiroptera: Phyllostomidae)
Authors: Miguel Pedro Henrique , Batisteli Augusto F. , Cruz-Neto Ariovaldo P.
Published: November 2023

Personality indicates consistency in individual behavioral responses across different contexts, and different personality traits may be correlated in behavioral syndromes. Studies on personality have important consequences for conservation ecology and, despite the ecological relevance of fruit bats, rare studies have tested the existence of personality and behavior syndromes in this group. In this context, this study aims to test whether the Neotropical fruit batsArtibeus lituratusandCarollia perspicillatapresent (1) individual repeatability (i.e. personality) related to the behaviors: activity, aggressiveness and boldness and (2) correlation between these personality axes, constituting behavioral syndromes. For each species, 27 adult males were captured and immediately placed in cloth bags individually, and we measured aggressiveness as the time they struggled in the bag within a 180-second interval. Bats were then kept in individual cages in a climate-controlled room for 48-h, after which we filmed them for 30 min in a flight tent as an activity test. In the boldness test, we quantified the latency to each animal to start feeding in front of an observer, assuming that bolder individuals had lower latency to feed. All tests were repeated after 48-h to analyze repeatability. We found high individual repeatability of aggressiveness, activity and boldness for both species, but different behavioral syndromes for each of them. ForC. perspicillata, the three behaviors were correlated to each other, with the most aggressive individuals being bolder and more active. ForA. lituratus, aggressiveness and boldness were also positively correlated, but activity did not correlate with the other two behaviors. Considering these different syndromes, our results suggest thatC. perspicillatahas less variation in behavioral profiles thanA. lituratusprobably as a result of species-specific selective pressures. The existence of behavioral syndromes in these frugivorous bats contributes to understanding the importance of individual variation on the ecological functions provided by seed dispersers.
Sex differences in intrinsic functional cortical organization reflect differences in network topology rather than cortical morphometry
Authors: Serio Bianca , Hettwer Meike D. , Wiersch Lisa , Bignardi Giacomo , Sacher Julia , Weis Susanne , Eickhoff Simon B. , Valk Sofie L.
Published: November 2023

Brain size robustly differs between sexes. However, the consequences of this anatomical dimorphism on sex differences in intrinsic brain function remain unclear. We investigated the extent to which sex differences in intrinsic cortical functional organization may be explained by differences in cortical morphometry, namely brain size, microstructure, and the geodesic distances of connectivity profiles. For this, we computed a low dimensional representation of functional cortical organization, the sensory-association axis, and identified widespread sex differences. Contrary to our expectations, observed sex differences in functional organization were not fundamentally associated with differences in brain size, microstructural organization, or geodesic distances, despite these morphometric properties beingper seassociated with functional organization and differing between sexes. Instead, functional sex differences in the sensory-association axis were associated with differences in functional connectivity profiles and network topology. Collectively, our findings suggest that sex differences in functional cortical organization extend beyond sex differences in cortical morphometry.

Teaser

Investigating sex differences in functional cortical organization and their association to differences in cortical morphometry.
Kinexinfers causal kinases from phosphoproteomics data
Authors: Valeanu Alexandra , Golz Verena , Avila David W. , Tzouros Manuel , Siebourg-Polster Juliane , Badi Laura , Zhang Jitao David
Published: November 2023

Motivation

Phosphoproteomics data are essential for characterising signalling pathways, identifying drug targets, and evaluating efficacy and safety profiles of drug candidates. Emerging resources, including a substrate-specificity atlas and drug-induced phosphoproteomics profiles, may transform the inference of causal kinases. However, there is currently no open-source software that leverages insights derived from these resources.

Results

We introduceKinex,a workflow implemented in the same-name Python package, which infers causal serine/threonine kinases from phosphoproteomics data. Kinex allows users to score kinase-substrate interactions, perform enrichment analysis, visualise candidates of causal regulators, and query similar profiles in a database of drug-induced kinase activities. Analysing seven published studies and one newly generated dataset, we demonstrate that analysis with Kinex recovers causal effects of perturbations and reveals novel biological insights. We foresee that Kinex will become an indispensable tool for basic and translational research including drug discovery.

Availability

Kinex is released with the GNU General Public License and available athttps://github.com/bedapub/kinex.
IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections
Authors: Creusat Florent , Jouan Youenn , Gonzalez Loïc , Barsac Emilie , Ilango Guy , Lemoine Roxane , Soulard Daphnée , Boisseau Chloé , Guillon Antoine , Lin Qiaochu , de Amat Herbozo Carolina , Sencio Valentin , Winter Nathalie , Trottein François , Si-Tahar Mustapha , Briard Benoit , Mallevaey Thierry , Faveeuw Christelle , Baranek Thomas , Paget Christophe
Published: November 2023

Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of Programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1+neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1-counterpart. VRI-induced regulatory PD-L1+neutrophils were generated in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation and reduced expression of resolving factors. These findings suggest that PD-L1+neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.
Generation of site-specifically labelled fluorescent human XPA to investigate DNA binding dynamics during nucleotide excision repair
Authors: Kuppa Sahiti , Corless Elliot , Caldwell Colleen , Spies Maria , Antony Edwin
Published: November 2023

Nucleotide excision repair (NER) promotes genomic integrity by correcting bulky DNA adducts damage caused by external factors such as ultraviolet light. Defects in NER enzymes are associated with pathological conditions such as Xeroderma Pigmentosum, trichothiodystrophy, and Cockayne syndrome. A critical step in NER is the binding of the Xeroderma Pigmentosum group A protein (XPA) to the DNA adduct. To better capture the dynamics of XPA interactions with DNA during NER we have utilized the fluorescence enhancement through non-canonical amino acids (FEncAA) approach. 4-azido-L-phenylalanine (4AZP) was incorporated at Arg-153 in human XPA and conjugated to Cy3 using strain-promoted azide-alkyne cycloaddition. The resulting fluorescent human XPA protein (hXPACy3) shows no loss in DNA binding activity and generates a robust change in fluorescence upon binding to DNA. Here we describe methods to generate hXPACy3and detail experimental conditions required to stably maintain the protein during biochemical and biophysical studies.
Heritability of complex traits in sub-populations experiencing bottlenecks and growth
Authors: Taylor Cameron S. , Lawson Daniel J.
Published: November 2023

1

Populations that have experienced a bottleneck are regularly used in Genome Wide Association Studies (GWAS) to investigate variants associated with complex traits. It is generally understood that these isolated sub-populations may experience high frequency of otherwise rare variants with large effect size, and therefore provide a unique opportunity to study said trait. However, the demographic history of the population under investigation affects all SNPs that determine the complex trait genome-wide, changing its heritability and genetic architecture. We use a simulation-based approach to identify the impact of the demographic processes of drift, expansion, and migration on the heritability of complex trait. We show that demography has considerable impact on complex traits. We then investigate the power to resolve heritability of complex traits in GWAS studies subjected to demographic effects. We find that demography is an important component for interpreting inference of complex traits and has a nuanced impact on the power of GWAS. We conclude that demographic histories need to be explicitly modelled in order to properly quantify the history of selection on a complex trait.
Experience-dependent place-cell referencing in hippocampal area CA1
Authors: Qian Fish Kunxun , Li Yiding , Magee Jeffrey C.
Published: November 2023

CA1 hippocampal place cells (PCs) are known for using both self-centric (egocentric) and world-centric (allocentric) reference frames to support a cognitive map1,2. The mechanism of PC referencing and the role of experience in this process, however, remain poorly understood3–5. Here we longitudinally recorded the activity of CA1 PCs while mice performed a spatial learning task. In a familiar environment, the CA1 representation consisted of PCs that were referenced to either spatial locations (allocentric PCs) or mouse running (egocentric PCs) in approximately equal proportions. In a novel environment, however, the CA1 representation became predominately egocentrically referenced. Notably, individual allocentric PCs in a familiar environment adaptively switched reference frames to become egocentric in a novel environment. In addition, intracellular membrane potential recordings revealed that individual CA1 neurons simultaneously received both ego- and allo-centric synaptic inputs, and the ratio of these two input streams correlated with the level of individual PC referencing. Furthermore, behavioral timescale synaptic plasticity6,7(BTSP) was an active participant in shaping PC referencing through the rapid adjustment of synaptic weights on many PCs. Together, these results suggest that experience-dependent adjustment of synaptic input shapes ego and allocentric PC referencing to support a flexible cognitive map in CA1.
Genome-wide Quantification of Polycistronic Transcription inLeishmania major
Authors: Grünebast Janne , Lorenzen Stephan , Clos Joachim
Published: November 2023

Leishmania majoris a human-pathogenic, obligate parasite and the etiological agent of the most prevalent, cutaneous form of leishmaniasis, which is an important neglected, tropical disease with ∼1.2 Mio new infections per year.Leishmania, and the whole order Trypanosomatida, are early eukaryotes with highly diverged gene expression and regulation pathways, setting them apart from their mammalian hosts and from most other eukaryotes. Using precision run-on sequence analysis, we performed a genome-wide mapping and density analysis of RNA polymerases in isolated nuclei of the protozoan parasiteLeishmania major. We map transcription initiation sites within the chromosomes and correlate them with known sites of chromatin modifications. We confirm continuous, polycistronic RNA synthesis in all RNA polymerase II-dependent gene arrays but find varying RNA polymerase activities in polycistronic transcription units (PTUs), excluding gene-specific transcription regulation, but not PTU-specific variations as possible targets of modulatory pathways. Lastly, we find evidence for transcriptional pausing of all three RNA polymerase classes, hinting at a possible mechanism of transcriptional regulation.

Significance Statement

Leishmaniaspp. are pathogens of humans and animals and cause one of the most important neglected tropical diseases. Regulation of gene expression inLeishmaniabut also in the relatedTrypanosomais radically different from all eukaryotic model organisms, dispensing with regulated, gene-specific transcription, and relying instead on highly regulated translation. Our work sheds light on the initiation, elongation and termination of transcription, maps unidirectional, polycistronic transcription units, provides evidence for transcriptional pausing at or near starting points of RNA synthesis, and quantifies the varying transcription rates of the polycistronic transcription units. Our results will further the understanding of these important pathogens and should provide a valuable ressource for researchers in the field of eukaryotic microbiology.
Kisspeptin modulates sex-like phenotypes in the neonatal period
Authors: Neves João R. , Castelo-Branco Miguel , Gonçalves Joana
Published: November 2023

In recent years, our understanding of the physiological role of kisspeptin (Kiss1) has evolved significantly, revealing its pivotal role in shaping sexual differentiation within the brain. Predominantly expressed in the hypothalamus, Kiss1 plays a crucial role in regulating release of the gonadotrophin-releasing hormone (GnRH). Kisspeptin 1 receptor (Kiss1R) exhibits sex-dependent expression in various brain regions, including the medial amygdala and preoptic area (POA) of the hypothalamus, regions underlying sexual development. Importantly, in the critical period for the sexual development in mammals occurs a synchronized surge of Kiss1 and testosterone, highlighting its importance in sexual dimorphism. It has been suggested that the neonatal Kiss1 surge is associated with the buildup of gender-linked social development. We investigated this hypothesis by testing the effect of neonatal blockage of Kiss1 signaling on the sex-like phenotype in rats. We postulate that Kiss1 actions are both time and region-dependent, particularly during the neonatal period, having lasting impact on social interactions.

For that we injected intracerebroventricular (ICV) a Kiss1R antagonist, Kp234, in the first 24h of life. Our data showed, that neonatal Kiss1 is determinant in modulating physiological responses, such as weight and testis development in males (N: males Veh = 10; males Kp234 = 10). Also, we document, for the first time, that Kiss1 modulates the testosterone surge in males and inhibits it in females (N: males Vehicle = 3; males Kp234 = 4; females Vehicle = 3; females Kp234 = 4). Furthermore, neonatal Kiss1 blockade modulated the sexual drive in, while the sexual performance in both sexes is maintained males (N: males Vehicle = 8; males Kp234 = 9; females Vehicle = 7; females Kp234 = 8).

In conclusion, this study underscores the significance of Kiss1 during the neonatal period, a critical phase for sexual differentiation and neuroplasticity. Neonatal Kiss1 emerges as a key player in the development of a sex-like phenotype in rats. Additionally, our findings show dimorphic patterns in Kiss1 influence. This work raises the intriguing possibility that the early influence of Kiss1 in brain circuitry is pivotal in the modulation of gender and plays a role in the social construction of the bimodality of gender identity.
Successful spread ofmcr-1-bearing IncX4 plasmids is associated with variant in replication protein of IncX4 plasmids
Authors: Yi Lingxian , Yu Kaiyang , Gao Guolong , Zhang Rongmin , Lv Luchao , Yu Daojin , Yang Jun , Liu Jian-Hua
Published: November 2023

IncX4 plasmids are one of the most epidemiologically successful vehicles formcr-1spread. Here we found that the IncX4 plasmids carried two different replication proteins encoded by genespir-1andpir-2, respectively, butmcr-1was only carried by IncX4 plasmid encodingpir-1. The copy number ofpir-2encoding plasmids (3.15±0.9 copies) are higher than that ofpir-1encoding plasmids (0.85±0.5 copies). Whenmcr-1was cloned into IncX4 plasmid encodingpir-2, the higher copy number of these plasmids resulted in increased expression ofmcr-1and a greater fitness burden on their host cells. However, these plasmids exhibited a lower rate of invasion into the bacterial population compared tomcr-1positive plasmids encoding thepir-1gene. These findings collectively explain the absence ofmcr-1in all IncX4 plasmids encodingpir-2. Our results further confirmed that low-copy numbers are important for the spread ofmcr-1plasmid from the perspective of natural evolution.
Rationale and Design of the BECA Project: Smartwatch-based Activation of the Chain of Survival for Out-of-Hospital Cardiac Arrest
Authors: Hup Roelof G. , Linssen Emma C. , Eversdijk Marijn , Verbruggen Bente , Bak Marieke A.R. , Habibovic Mirela , Kop Willem J. , Willems Dick L. , Dekker Lukas R.C. , Haakma Reinder , Vernooij Carlijn A. , Kooy Tom A. , Tan Hanno L. , Vullings Rik
Published: November 2023

Introduction

Out-of-hospital cardiac arrest (OHCA) is a major health problem, and the overall survival rate is low (4.6%-16.4%). The initiation of the current chain of survival depends on the presence of a witness of the OHCA, which is not present in 29.7%-63.4% of the cases. Furthermore, a delay in starting this chain is common in witnessed OHCA. This project aims to reduce morbidity and mortality due to OHCA by developing a smartwatch-based solution to expedite the chain of survival in the case of (un)witnessed OHCA.

Methods and analysis

Within the BECA (BEating Cardiac Arrest) project, we aim to develop a demonstrator product that can detect OHCA using photoplethysmography and accelerometer analysis, and autonomously alert emergency medical services. A target group study will be performed to determine who benefits the most from this product. Furthermore, several clinical studies will be conducted to capture or simulate data on OHCA cases, as to develop detection algorithms and validate their diagnostic performance. Volunteers will be asked to simulate OHCA by interrupting radial arterial and venous blood flow by blood pressure cuff inflation while lying still. Data will also be captured during cardiac electrophysiologic and implantable cardioverter defibrillator (ICD) testing procedures. In addition, patients at risk for OHCA are recruited to acquire measurements over a longer period. Moreover, studies on psychosocial and ethical acceptability will be conducted, consisting of surveys, focus groups, and interviews. These studies will focus on end-user preferences and needs, to ensure that important individual and societal values are respected in the design process.

Ethics and dissemination

Ethical approval or waivers will be sought from the research ethics committees of the different institutions. Written informed consent will be obtained from the participants of all studies. Study findings will be submitted to international peer-reviewed journals and will be presented at international scientific conferences.

STRENGTHS AND LIMITATIONS

Strengths

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This research project aims to develop unobtrusive technology that could save lives by autonomously alerting emergency medical services in case of out-of-hospital cardiac arrest.

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The project includes a broad range of aspects to maximize the technology’s chance of adoption: clinical, technical, psychological, and ethical.

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The project aims for the inclusion of a wide and diverse research sample and the involvement of different stakeholder groups to minimize bias and ensure accessibility for everyone in society.

Limitations

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Smartwatch-obtained data of OHCA cases is scarce and hard to acquire: the more realistic the data is, the more difficult its acquisition is.
Bilaterally suppressed EEG amplitudes predict death and poor functional outcomes in critically ill children
Authors: Paul Luisa , Greve Sandra , Hegemann Johanna , Gienger Sonja , Löffelhardt Verena , Della Marina Adela , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora
Published: November 2023

Background and objectives

Continuous full-channel EEG is the gold standard for electrocortical activity assessment in critically ill children, but its implementation faces challenges, leading to a growing use of amplitude-integrated EEG (aEEG). While suppressed aEEG amplitudes have been linked to adverse outcomes in preterm infants and adults after cardiac arrest, evidence for critically ill children remains limited. This retrospective study aimed to evaluate the association between suppressed aEEG amplitudes in critically ill children and death or poor functional neurological outcomes.

Methods

235 EEGs derived from individual patients < 18 years in the pediatric intensive care unit (PICU) at the University Hospital Essen (Germany) between 04/2014 and 07/2021 were retrospectively converted into aEEGs and amplitudes analyzed with respect to previously defined age-specific percentiles. Adjusted odds ratios for death and poor functional outcome at hospital discharge in patients with bilateral upper or lower amplitude suppression below the 10thpercentile were calculated accounting for neurological injuries, acute disease severity, sedation levels, and functional neurological status before acute critical illness.

Results

The median time from neurological insult to EEG recording was 2 days. PICU admission occurred due to neurological reasons in 43 % and patients had high overall disease severity. Thirty-three (14 %) patients died and 68 (29 %) had poor outcomes. Amplitude depression below the 10thpercentile was frequent (upper amplitude: 27 %, lower amplitude: 34 %) with suppression of only one amplitude less frequent than bilateral suppression. Multivariable regression analyses yielded odds between 6.63 and 15.22 for death, neurological death, and poor neurological outcomes if both upper or both lower amplitudes were suppressed. Model discrimination was excellent with areas under the curve above 0.92 for all models.

Discussion

This study found a high prevalence of suppressed aEEG amplitudes in critically ill children early after PICU admission, with suppression being highly associated with death and poor functional outcomes at hospital discharge. These findings emphasize the potential of early identification of high-risk PICU patients through aEEG monitoring if conventional EEG is unavailable, potentially guiding neuroprotective therapies and early neurorehabilitation.
Epstein Barr virus infection induces tissue-resident memory T cells in mucosal lymphoid tissues
Authors: Kirchmeier Daniel , Deng Yun , Rieble Lisa , Läderach Fabienne , Schuhmachers Patrick , Valencia-Camargo Alma Delia , Murer Anita , Caduff Nicole , Chatterjee Bithi , Chijioke Obinna , Zens Kyra , Münz Christian
Published: November 2023

Epstein Barr virus (EBV) contributes to around 2% of all tumors worldwide. Simultaneously, more than 90% of healthy human adults persistently carry EBV without clinical symptoms. In most EBV carriers it is thought that virus-induced tumorigenesis is prevented by cell-mediated immunity. Specifically, memory CD8+T cells recognize EBV-infected cells during latent and lytic infection.

Using a symptomatic primary infection model, similar to infectious mononucleosis (IM), we found EBV induced CD8+tissue resident memory T cells (TRMs) in mice with a humanized immune system. These human TRMs were preferentially established after intranasal EBV infection in nasal-associated lymphoid tissues (NALT), equivalent to tonsils, the primary site of EBV infection in humans. They expressed canonical TRM markers, including CD69, CD103 and BLIMP-1, as well as Granzyme B, CD107a and CCL5, while demonstrating reduced CD27 expression and proliferation by Ki-67 expression. Despite cytotoxic activity and cytokine productionex vivo, these TRMs failed to control EBV viral loads in the NALT during infection although effector memory T cells (TEMs) controlled viral titers in spleen and blood.

Overall, TRMs in mucosal lymphoid tissues are established by EBV infection, but primarily systemic CD8+T cell expansion seems to attenuate viral loads in the context of IM-like infection.
The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast
Authors: Chen Jennifer J. , Moy Calvin , Pagé Viviane , Monnin Cian , El-Hajj Ziad W. , Avizonis Daina Z. , Reyes-Lamothe Rodrigo , Tanny Jason C.
Published: November 2023

Abstract

RNA polymerase II (RNAPII) transcription elongation directs an intricate pattern of histone modifications. Formation of this pattern involves a highly conserved regulatory axis, key components of which are the elongation factor Rtf1, monoubiquitylation of histone H2B (H2Bub1), and methylation of histone H3 on lysine 4 (H3K4me). Direct contact between Rtf1 and the ubiquitylation complex Rad6-Bre1 stimulates H2Bub1, which in turn promotes H3K4me by stimulating the activity of the Set1C/COMPASS methyltransferase complex. Previous studies have defined the molecular basis for these regulatory relationships, but it remains unclear how they regulate chromatin and transcriptionin vivo. We found that mutations affecting multiple components of the Rtf1-H2Bub1-H3K4me axis in the model eukaryoteSchizosaccharomyces pombe(fission yeast) caused resistance to the ribonucleotide reductase inhibitor hydroxyurea (HU). Resistance correlated with a reduced effect of HU on dNTP pools, bypass of the S-phase checkpoint in the presence of HU, and blunting of the transcriptional response to HU treatment. Mutations in the C-terminal repeat domain (CTD) of the RNAPII large subunit Rpb1 led to a similar spectrum of phenotypes. Moreover, all the HU resistant mutants we identified also exhibited resistance to several azole class antifungal agents. Our results suggest a novel, shared gene regulatory function of the Rtf1-H2Bub1-H3K4me axis and the Rpb1 CTD in controlling fungal drug tolerance.
Nanopore and Illumina Sequencing Reveal Different Viral Populations from Human Gut Samples
Authors: Cook Ryan , Telatin Andrea , Hsieh Shen-Yuan , Newberry Fiona , Tariq Mohammad A. , Baker Dave J. , Carding Simon R. , Adriaenssens Evelien M.
Published: November 2023

The advent of viral metagenomics, or viromics, has improved our knowledge and understanding of global viral diversity. High-throughput sequencing technologies enable explorations of the ecological roles, contributions to host metabolism, and the influence of viruses in various environments including the human gut microbiome. However, the bacterial metagenomic studies frequently have the advantage. The adoption of advanced technologies like long-read sequencing has the potential to be transformative in refining viromics and metagenomics.

Here, we examined the effectiveness of long-read and hybrid sequencing by comparing Illumina short-read and Oxford Nanopore Technology (ONT) long-read sequencing technologies and different assembly strategies on recovering viral genomes from human faecal samples.

Our findings showed that if a single sequencing technology is to be chosen for virome analysis, Illumina was preferable due to its superior ability to recover fully resolved viral genomes and minimise erroneous genomes. While ONT assemblies were effective in recovering viral diversity, the challenges related to input requirements and the necessity for amplification made it less ideal as a standalone solution. However, using a combined, hybrid approach enabled a more authentic representation of viral diversity to be obtained within samples.

Impact Statement

Viral metagenomics, or viromics, has revolutionised our understanding of global viral diversity however long-read and hybrid approaches are not yet widespread in this field. Here, we compared the performance of Illumina short-read and Nanopore long-read assembly approaches for recovering fully resolved viral genomes from human faecal samples. We highlight Illumina’s short-read sequencing for recovering fully resolved viral genomes, while acknowledging Oxford Nanopore Technology’s long-read sequencing for capturing broader viral diversity. However, a hybrid approach, utilising both technologies, may mitigate the limitations of one technology alone.

Data Summary

All reads used in this study are available on European Nucleotide Archive (ENA) within the project PRJEB47625.
Microbial contamination and some chemical and physical properties of date fruits stored at room and refrigerator temperatures
Authors: Hamad Siddig Hussein
Published: November 2023

Purpose

The purpose of this article is to investigate on changes of the microbial load and the chemical and physical properties of date fruits stored for 6 months under two different temperatures.

Design/methodology/approach

A composite sample of 100 kg date fruits from the Khalas variety, season 2019, was collected from the local market in Al Ahsa Province, Saudi Arabia, packaged in 1 kg lots, stored at room and refrigerator temperatures and the microbial contamination and the chemical and physical properties monitored over a period of six months of storage. Total bacteria, lactic acid bacteria, Enterobacteriaceae, yeasts and molds were counted and representatives of yeast and mold contaminants were identified using morphological, physiological and molecular typing techniques. Changes in the color and texture of the samples were also monitored during storage.

Findings

The yeasts detected were two strains of each of Lachancea thermotolerans and Rhodosporidiobolus fluvialis and one strain of Cystofilobasidium lacus-mascardii. For molds, one strain of each of Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum and Aspergillus caespitosus have been detected. No significant growth of these microorganisms was observed, but enough load persisted during storage that makes the samples not meeting the microbiological standards. There were significant changes in the color and texture of the fruits during storage.

Originality/value

These findings add important information that can help producers and processors to improve quality and promote marketing of date fruits, especially to international markets.
Hydraulic loss characteristics of closed-loop piping system during start-up process of mixed-flow pump
Authors: Li Wei , Huang Yuxin , Ji Leilei , Ma Lingling , Agarwal Ramesh
Published: November 2023

Purpose

The purpose of this study is to explore the transient characteristics of mixed-flow pumps during startup process.

Design/methodology/approach

This study uses a full-flow field transient calculation method of mixed-flow pump based on a closed-loop model.

Findings

The findings show the hydraulic losses and internal flow characteristics of the piping system during the start-up process.

Research limitations/implications

Large computational cost.

Practical implications

Improve the accuracy of current numerical simulation results in transient process of mixed-flow pump.

Originality/value

Simplify the setting of boundary conditions in the transient calculation.
Al-Chef Cafeteria: dilemma of market expansion post-pandemic
Authors: Singh Deepak , Qadir Abdul
Published: November 2023

Learning outcomes

Upon completion of this case study, students will be able to identify the key changes in the marketing environment affecting the industry, demonstrate the elements of the marketing mix in the fast-food industry, illustrate the crucial elements of customer value-driven marketing strategy, critique relevant marketing strategies that are crucial for business development and formulate effective market expansion strategies for Al-Chef Cafetaria to achieve sustainable competitive advantage in the VUCA world.

Case overview/synopsis

The Al-Chef Cafeteria, established by Ali Arif, one of the partners, became one of the most happening quick service restaurants (QSRs) in Patna. However, the outbreak of the COVID-19 pandemic disrupted the once-thriving fast-food market in the city as the government imposed lockdowns to restrict the onslaught of the pandemic. The relentless waves of the pandemic in the subsequent months severely impacted India and worsened the economic challenges. Consumer behaviour towards outdoor eateries, especially QSRs, became uncertain, which led to the exit of several smaller players in the industry. In June 2021, because of an uncertain future, Arif was forced to contemplate different business trajectories for survival and growth. Arif’s resilience was highlighted, as he endeavoured to revive his dream cafe. To start the café, Arif had quit a stable job in the Middle East. His journey mirrored the broader narrative of businesses navigating uncharted waters as the cafe transformed from a flourishing enterprise to one reeling from adversity and looking forward to undergoing a strategist lens for revival. Against an uncertain business landscape and wavering consumer sentiment, Arif grappled with the question of whether a return to normalcy was possible or if a new-normal system would emerge. This case study highlighted the challenges and uncertainties faced by the Al-Chef Cafeteria post-pandemic and the strategies needed to rewire the previous business model to chart a new growth trajectory.

Complexity academic level

This case is suitable for postgraduate-level marketing management or sales management (business development) courses in any of the following programmes: MBA programme, PG diploma in marketing management/PG diploma in hospitality and tourism management/PG diploma in sales management/PG diploma in food and beverage service/PG diploma in service management, part-time diploma programmes in management and executive programmes in management.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing.
The impact of internal governance mechanisms on environmental performance of Saudi firms
Authors: Alwadani Neef , Al-Shaer Habiba , Albitar Khaldoon
Published: November 2023

Purpose

This study aims to explore whether firms that have a sustainability committee operating on the board, publish separate sustainability reports that are externally assured by an independent external audit and have large and active boards are more likely to be engaged in environmental practices and have better environmental performance.

Design/methodology/approach

Based on a sample of firms listed on the Saudi Stock Exchange, covering the period 2014–2021, this study applies panel data models to examine the research hypotheses.

Findings

The findings show significant positive associations between the existence of a sustainability committee, the publication of separate sustainability reports and the independent external assurance of these reports and environmental performance. This study also finds that the composite internal governance index is significant and positively associated with environmental performance.

Practical implications

Policymakers should support the creation of a sustainability committee on the boards of Saudi firms and review its role and responsibilities. The findings of this study inform regulators of the importance of the existence of independent external assurance of the sustainability reports of Saudi firms to enhance the credibility and reliability of these reports. Managers need to establish devoted committees committed to sustainability-related tasks that help coordinate communications between the firm and stakeholders.

Originality/value

The Saudi Arabian Government has implemented a range of policies and initiatives aimed at improving environmental performance, which is a main focus of Saudi Vision 2030 to achieve environmental sustainability. Therefore, this study provides unique evidence and new insights on the impact of internal governance on corporate environmental performance in the Saudi context.
Assessing the barriers to lean manufacturing adoption in the furniture industry of Bangladesh: a fuzzy-DEMATEL study
Authors: Uday Rifath Mahmud , Salman Sheak , Karim Md. Rezaul , Ar Salan Md. Sifat , Islam Muzahidul , Shahriar Mustak
Published: November 2023

Purpose

The objective of this study is to investigate the barriers hindering the integration of lean manufacturing (LM) practices within the furniture industry of Bangladesh. The traditional operational paradigms in this sector have posed substantial challenges to the effective implementation of LM. In this study, the barriers of implementing LM in the furniture business are examined, aiming to provide a systematic understanding of the barriers that must be addressed for a successful transition.

Findings

The research reveals that “Fragmented Industry Structure,” “Resistance to Lean Practices” and “Inadequate Plant Layout and Maintenance”, emerged as the foremost barriers to LM implementation in the furniture industry. Additionally, “Insufficient Expert Management,” “Limited Technical Resources” and “Lack of Capital Investment” play significant roles.

Research limitations/implications

The outcomes of this study provide valuable insights into the furniture industry, enabling the development of strategies for effective LM implementation. One notable challenge in lean implementation is the tendency to revert to established practices when confronted with barriers. Therefore, this transition necessitates informed guidance and leadership. In addition to addressing these internal challenges, the scope of lean implementation should be broadened.

Originality/value

This study represents one of the initial efforts to systematically identify and assess the barriers to LM implementation within the furniture industry of Bangladesh, contributing to the emerging body of knowledge in this area.
The impact of economic policy uncertainty on sustainability (ESG) performance: the role of the firm life cycle
Authors: Qureshi Muhammad Azeem , Ahsan Tanveer , Gull Ammar Ali , Umar Zaghum
Published: November 2023

Purpose

This study investigates the impact of economic policy uncertainty (EPU) on corporate sustainability [environmental, social and governance (ESG)] performance and aims to explore whether uncertainty-induced sustainability performance is influenced by the firm's life cycle (LC).

Design/methodology/approach

The study uses data from European non-financial firms listed during the period from 2002 to 2022 to extend the nascent literature regarding EPU and sustainability performance while applying a dynamic panel data regression analysis (Generalized Method of Moments - GMM System) on 11,462 firm-year observations of 1,869 European firms.

Findings

The authors find overwhelming evidence that policy uncertainty affects the sustainability performance of European firms. The firms restrict their environmental and governance-related activities and address immediate issues to survive during periods of high EPU. Conversely, the firms increase their social engagements to decrease uncertainty-induced information asymmetry. The authors' results show that the intensity and type of sustainability performance are also influenced by the firm's LC. The results imply that board gender diversity (BGD) increases while power concentration with the chief executive officer (CEO) decreases sustainability performance.

Practical implications

These findings have important implications for policymakers, potential investors, firm management and other stakeholders given the firms' access to resources and preferences to encounter uncertainty vary across different LC stages.

Originality/value

To the best of the authors' knowledge, this is the first study that investigates the role of the firm's LC in the relationship between policy uncertainty and sustainability performance in the European context.
A qualitative exploration of immigrant’s experiences, practices and feelings about health‐care management, diet quality and food security issues, in Greece
Authors: Michalis Athanasios , Panagiotakos Demosthenes B. , Papadopoulos Apostolos , Costarelli Vassiliki
Published: November 2023

Purpose

The study aims to have adults discuss experiences, practices needs and feelings related to health management, diet and food security.

Design/methodology/approach

A total of 22 immigrants were recruited from the Open School of Immigrants in Piraeus, Attica, Greece, to participate in focus group discussions. The discussions were audio recorded and thematically analyzed. Three major themes were developed: pathways to health care, nutrition management and experiences related to food shortages.

Findings

Most of the participants identified internet as the most commonly used way to obtain health advice; they also stated that unexpected ill-health is usually accompanied by feelings of fear, anxiety and loneliness. Immigrants, who had visited a public hospital in Greece, identified the language barrier as the most challenging issue, followed by the long waiting lists. Fear and anxiety of hospital visits was an important factor in their decision to vaccinate against COVID-19. Lack of time, high cost of healthy food and lack of knowledge were the most common obstacles to a healthy diet. One in two immigrants reported that they have faced food insecurity issues in the past. Stress, psychological distress and irritation were reported, due to food shortages, especially during the first few years of arriving in Greece. The exclusion of some foods, reduced portion sizes and buying cheaper foods were among the coping strategies to address food shortages.

Originality/value

The study offers an insight into immigrant’s experiences, practices and feelings about managing health issues and could be useful for health-care practitioners, researchers and policymakers.