bluuebunny/crossref_metadata_2025 huggingface dataset:
MULTIPLE, REDUNDANT CARBOXYLIC ACID TRANSPORTERS SUPPORT MITOCHONDRIAL METABOLISM INPLASMODIUM FALCIPARUM
Authors: Rajaram Krithika , Rangel Gabriel W. , Munro Justin T. , Nair Sethu C. , Llinás Manuel , Prigge Sean T.
Published: November 2024

The mitochondrion of the deadliest human malaria parasite,Plasmodium falciparum,is an essential source of cellular acetyl-CoA during the asexual blood-stage of the parasite life cycle. Blocking mitochondrial acetyl-CoA synthesis leads to a hypoacetylated proteome and parasite death. We previously determined that mitochondrial acetyl-CoA is primarily synthesized from glucose-derived pyruvate by α-ketoacid dehydrogenases. Here, we asked if inhibiting the import of glycolytic pyruvate across the mitochondrial inner membrane would affect acetyl-CoA production and, thus, could be a potential target for antimalarial drug development. We selected the two predicted mitochondrial pyruvate carrier proteins (PfMPC1 andPfMPC2) for genetic knockout and isotopic metabolite tracing via HPLC-MS metabolomic analysis. Surprisingly, we observed that asexual blood-stage parasites could survive the loss of either or bothPfMPCs with only minor growth defects, despite a substantial reduction in the amount of glucose-derived isotopic labelling into acetyl-CoA. Furthermore, genetic deletion of two additional mitochondrial carboxylic acid transporters – DTC (di/tricarboxylic acid carrier) and YHM2 (a putative citrate/α-ketoglutarate carrier protein) – only mildly affected asexual blood-stage replication, even in the context ofPfMPC deficiency. Although we observed no added impact on the incorporation of glucose carbon into acetyl-CoA in these quadruple knockout mutants, we noted a large decrease in glutamine-derived label in tricarboxylic acid cycle metabolites, suggesting that DTC and YHM2 both import glutamine derivatives into the mitochondrion. Altogether, our results expose redundant routes used to fuel the blood-stage malaria parasite mitochondrion with imported carbon from two major sources – glucose and glutamine.

SIGNIFICANCE

The mitochondrion of malaria parasites generates key molecules, such as acetyl-CoA, that are required for numerous cellular processes. To support mitochondrial biosynthetic pathways, the parasites must transport carbon sources into this organelle. By studying how the mitochondrion obtains pyruvate, a molecule derived from glucose, we have uncovered redundant carbon transport systems that ensure parasite survival in red blood cells. This metabolic redundancy poses a challenge for drug development, as it enables the parasite to adapt and survive by relying on alternative pathways when one is disrupted.
Anatomy, histology and ultrastructure of the adult human olfactory peduncle: blood vessel andcorpora amylaceaassessment
Authors: Raspeño-García JF. , González-Granero S. , Herranz-Pérez V. , Cózar-Cuesta A. , Artacho-Pérula E. , Insausti R. , García-Verdugo JM. , de la Rosa-Prieto C.
Published: November 2024

The mammalian olfactory system is responsible for processing volatile chemical stimuli and is composed of several structures including the olfactory epithelium, olfactory bulb, olfactory peduncle (OP), and olfactory cortices. Despite the critical role played by the OP in the transport of information it has remained understudied. In this work, optical, confocal, and electron microscopy were employed to examine the anatomy, histology, and ultrastructure of six human OP specimens (ages 37–84 years). Three concentric layers were identified in coronal sections: the external layer (EL), the axonal layer (AL), and the internal layer (IL). Immunohistochemistry revealed the distribution of neurons and glial cells throughout the OP. Two neuronal morphologies were observed: granule cells and larger pyramidal cells, the latter associated with projection neurons of the anterior olfactory nucleus. Astrocytes were uniformly distributed with a more radial morphology in the EL. Oligodendrocytes were mainly located in the AL. Blood vessels (BVs) were evenly distributed along the OP, with a mean luminal area of 82.9 µm² and a density of 1.26 %, with a significant increase in the IL. CA were abundant, with an average size of 49.3 µm² and a density of 3.23 %. CA clustered near BVs, particularly at tissue edges, with both size and density increasing with age. Notably, CA showed strong associations with astrocytes. This study provides the first detailed qualitative and quantitative data on the internal organization of the human OP, which may contribute to a better understanding of the pathophysiology of some neuropathological disorders.
A comparative study of rigid-body registration algorithms for the alignment of longitudinal structural MRI of the brain
Authors: Jouryabi Yazdan Rezaee , Lashgari Reza , Ardekani Babak A. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2024

Longitudinal structural MRI (sMRI) may be used to characterize brain morphological changes over time. A key requirement for this approach is accurate rigid-body alignment of longitudinal sMRI. We have recently developed the automatic temporal registration algorithm (ATRA) for this purpose. ATRA is a landmark-based approach capable of registering dozens of serial sMRI simultaneously in an unbiased manner. The aim of the research presented in this paper was to evaluate the accuracy and inverse-consistency of ATRA in comparison to three commonly used sMRI alignment methods: FSL, FreeSurfer, and ANTS. In the absence of a ground truth, it is only possible to quantitatively determine the degree of discrepancy between two algorithms. We propose that if the discrepancy exceeds a certain threshold, the relative accuracy of the two algorithms could be determined visually. We computed the discrepancy between ATRA and each of the three other methods for the alignment of 150 pairs of sMRI taken roughly one year apart. We visually rated the accuracy of alignments in cases where the discrepancy was greater than .5 mm while the rater was agnostic to the registration method. In those instances, ATRA was considered more accurate than FSL in 46 out of 48 cases, more accurate than FreeSurfer in 6 out of 7 cases, and more accurate than ANTS in all 6 cases. ATRA was also the most inverse-consistent method. In addition to being capable of performing unbiased group-wise registration, ATRA is the most accurate algorithm in comparison to several commonly used rigid-body alignment methods.
Association between COVID-19 Disease Severity and T Cell Receptor Repertoire
Authors: Chen Xinyi , Su Yapeng , Dai Chloe , Goldman Jason D. , Heath James R. , Liu Si , Sun Wei
Published: November 2024

During the COVID-19 pandemic, while most infected individuals experienced mild to moderate symptoms, a significant subset developed severe illness. A clinical test distinguishing between mild and severe cases could inform effective treatment strategies. Toward the latter stages of the pandemic, it became evident that vaccination or prior infection cannot entirely prevent reinfection. However, they are crucial in reducing the risk of severe disease by inducing T-cell memory. T cell receptors (TCRs), which can be obtained from human blood, serve as valuable biomarkers for monitoring T cell responses to SARS-CoV-2 infection. In this study, we investigated the associations between TCR metrics and COVID-19 severity and found significant associations. Furthermore, such associations could depend on the subset of TCRs used (e.g., TCRs from CD8+ T or CD4+ T cells) and when the TCRs were collected.
Human Herpes Virus-8 Oral Shedding Heterogeneity is Due to Varying Rates of Reactivation from Latency and Immune Containment
Authors: Swan David A , Krantz Elizabeth M , Byrne Catherine , Okuku Fred , Nankoma Janet , Mutyaba Innocent , Phipps Warren , Schiffer Joshua T.
Published: November 2024

Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission. The mechanistic drivers of different HHV-8 shedding patterns in infected individuals are unknown. We applied stochastic mathematical models to a longitudinal study of HHV-8 oral shedding in 295 individuals in Uganda who were monitored daily with oral swabs. Participants were divided into four groups based on whether they were HIV-negative or positive as well as KS-negative or positive. In all groups, we observed a wide variance of shedding patterns, including no shedding, episodic low viral load shedding, and persistent high viral load shedding. Our model closely replicates patterns in individual data and attributes higher shedding rates to increased rates of viral reactivation, and lower median viral load values to more rapid and effective engagement of cytolytic immune responses. Our model provides a framework for understanding different shedding patterns observed in individuals with HHV-8 infection.

Keypoints

HHV8 shedding rate is mosty determined by rate of reactivation from latency while viral loads is mostly dteremined by peripheral immune responses.

DAS performed all mathematical modeling and editied the paper; EMK performed statistical analysis and edited the paper; CB assisted with modeling; FO, JN and IM designed and implemented the clinical protocols; WP designed and implemented the clinical protocols and edited the paper; JTS conceived the study and write the paper.
Glucose alters the evolutionary response to gentamicin in uropathogenicEscherichia coli
Authors: Choudhary Shalini , Smith Jacob A. , McNally Alan , Hall Rebecca J.
Published: November 2024

Urinary tract infections (UTI) are a major health and economic concern. UropathogenicEscherichia coli(UPEC) are the leading cause of UTI, and antibiotic resistant UPEC are increasingly common. The microenvironment of the urinary tract is metabolically distinct, and there is growing interest in understanding the extent to which metabolism may influence UPEC infection and response to antibiotics, and how this varies between individuals. Diabetes, characterised in part by glycosuria, is a known risk factor for UTI and is associated with more severe infections. The role that glucose plays in driving UPEC evolution is unclear. Here, we found that a pathologically-relevant glucose concentration reduced the efficacy of the antibiotic gentamicin against a UPEC strain. Through experimental evolution, we identified mutations in the RNA polymerase sigma factorrpoSassociated with long-term glucose exposure. We found that the presence of gentamicin resulted in mutations in genes includingtrkH, encoding a potassium ion uptake system and linked previously to aminoglycoside resistance, and in the autotransporterhyxB. Strikingly, these mutations were not present in populations exposed to a combination of both glucose and gentamicin. Together, this suggests that whilst glucose may reduce growth inhibition by gentamicin, it may also influence mutation acquisition, providing new avenues for understanding the evolution and treatment of UPEC-mediated UTI in high-risk individuals.
The Integrator complex prevents premature neuronal differentiation through global control of transcription elongation
Authors: Somsen Hedda B. , Eigenhuis Kristel N. , Kuijpers-Korporaal Anne L. , Pelicano de Almeida Mariana , Montoro Ferrer Roberto , Kats Kelsey , Dekker Mike R. , Zuidweg Thuur , Azmani Zakia , van den Hout Mirjam C.G.N. , van IJcken Wilfred F.J. , Huylebroeck Danny , Fornerod Maarten , Poot Raymond A. , van den Berg Debbie L.C.
Published: November 2024

Transcription pause-release constitutes a key step in the regulation of gene expression. Pathogenic variants in various pausing regulators have been identified in neurodevelopmental disorders, but how transcription pause-release regulates neural development remains largely unknown. Here we show that a patient-specific in-frame deletion in Integrator subunit 8 (INTS8) that prevents association of this subunit with the Integrator complex results in a global increase in nascent transcription and precocious expression of neuronal genes in progenitor cells. Consequently, differentiating neural progenitors fail to sustain a proliferating progenitor cell population during cortical neuronal network formation, resulting in network collapse. We show that attenuation of RNApol2 pause-release by targeted degradation of BRD4 can revert neuronal gene activation and prevent premature progenitor cell loss. Our data demonstrate that a fine-tuned balance between RNApol2 pausing and elongation is crucial for normal neuronal development and suggest transcription pause-release as a druggable target for neurological defects in developmental disorders.
The oxidative stress response-related peroxiredoxin Tsa1b ofCandida aurisfunctions as a virulence factor that promotes infection
Authors: Areitio Maialen , Rodriguez-Erenaga Oier , Aparicio-Fernandez Leire , Abio-Dorronsoro Lucía , Martin-Souto Leire , Perez-Cuesta Uxue , Buldain Idoia , Zaldibar Beñat , Ruiz-Gaitan Alba , Pemán Javier , Leibundgut-Landmann Salomé , Rementeria Aitor , Antoran Aitziber , Ramirez-Garcia Andoni
Published: November 2024

The difficulty of accurately identifyingCandida aurisand the high resistance rates presented have increased the concern in the healthcare setting. Due to this, the aim of this study was to analyse the fungal response to oxidative stress. To achieve this goal, gene and protein expression were examined using qPCR and two-dimensional electrophoresis, respectively, peroxiredoxin Tsa1b being discovered to be overexpressed under oxidative stress. Besides, its antigenicity was also confirmed by western blotting. Subsequently, the significance of Tsa1b was next investigated by creating and characterizing theC. auris ΔTSA1BandC. auris ΔTSA1B::TSA1Bstrains using CRISPR-Cas9. The findings demonstrated that theΔTSA1Bstrain was more susceptible to oxidative and cell wall stressors than the wild-type strain, which was consistent with an increase in the cell wall β-glucan amounts when grown in the presence of oxidative stress. Furthermore, theΔTSA1Bstrain was also more vulnerable to the presence of dendritic cells and bone marrow-derived macrophages. Finally,in vivoinfections performed inGalleria mellonellaand mice showed a slower progression of the disease in those animals infected with the mutant strain. In conclusion, the peroxiredoxin Tsa1b has been identified as an important protein for theC. aurisresponse to oxidative stress and as a virulence factor, allowing for a more thorough knowledge of the pathobiology of this yeast. This study points out the potential that this protein may have for the development of new diagnostic and therapeutic approaches.

HIGHLIGHTS

Several metabolic proteins are implicated inC. aurisresponse to oxidative stress

C. aurisresponse to oxidative stress is influenced by the Tsa1b peroxiredoxin

Lack of Tsa1b generates more susceptibility to stresses and an altered cell wall

C. aurisTsa1b is involved in the fungal interaction with host immune cells

The Tsa1b ofC. auriscontributes to the progression of the infectionin vivo
Neurogenetic evidence for oscillatory behavior of Lgr3-positive growth control interneurons inDrosophila
Authors: Zanini Rebeca , Pereirinha Joana , Fernandez-Acosta Magdalena , Casimiro Andreia P. , Pinho Mariana , Garelli Andres , Herédia Fabiana , Gontijo Alisson M.
Published: November 2024

The ability of animals to achieve a species-specific size and proportion even in the face of developmental or environmental perturbations is termed developmental stability. InDrosophila, the relaxin/insulin-like peptide 8 (Dilp8) mediates interorgan growth coordination during larval development acting upstream of the neuronal relaxin-like Leucine-rich repeat-containing G protein-coupled receptor (Lgr3). Previous reports have led to a model where Dilp8-dependent Lgr3 activation in two bilateral brain interneurons termedpars intercerebralisLgr3-positive/growth-coordinating Lgr3 (PIL/GCL) neurons leads to their depolarization, which then triggers a neuroendocrine cascade that promotes developmental stability by delaying the larval-to-pupal transition and reducing organ growth concomitantly. However, many fundamental aspects of this model remained to be experimentally proven, most notably the specific requirement of Lgr3 and depolarization in PIL/GCL neurons for developmental stability. Here, we confirm the first part of the model regarding the specific requirement of Lgr3 in PIL/GCL neurons using improved genetic drivers, but, in contrast to the model predictions, we find that both hyper-and depolarized states of these neurons are required for their developmental delay-promoting activity in response to Dilp8. The simplest explanation for this finding is that Lgr3 activation by Dilp8 triggers oscillatory activity of PIL/GCL neurons, and that this is required for the Dilp8-dependent developmental delay. Whether or not such oscillatory behavior would arise from intrinsically pacemaker activity or from network connectivity properties such as feedback inhibition remains to be defined, although we present evidence that both could be involved. Namely, PIL/GCL neurons are positive for Cyclin A, which has been linked with sleep time coordination in adult postmitotic neurons. On the other hand, the neuroanatomy of PIL/GCL neurons is consistent with reciprocally-innervating loop-forming neurons, a common architecture in oscillating circuits and central pattern generators. Finally, we demonstrate through clonal analyses that PIL/GCL neurons represent two distinct neuronal types–a local and a projection neuron–instead of a homogeneous neuronal population as previously thought, revealing a new complexity layer in the developmental stability circuit. Our findings highlight the importance of cell-type specific neurogenetic manipulation, detailed neuroanatomical characterization, and reveal a critical and unanticipatedly complex role for PIL/GCL neurons in the Dilp8-dependent developmental stability pathway.
Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from chronic binge alcohol
Authors: McNair Elizabeth , Dawkins Lamar , Ross Grace , Barnett Alexandra , Nakala Puja , Qin Liya , Zou Jian , Nikolova Viktoriya , Moy Sheryl , Coleman Leon G.
Published: November 2024

Proinflammatory microglial activation and hyperkatifeia during withdrawal are key features or Alcohol Use Disorder (AUD) as well as in rodent models of binge alcohol. However, it is unclear the role microglia play in the development of AUD behavioral phenotypes, particularly negative affect or hyperkatifeia. We hypothesized proinflammatory microglia promote neuronal death and hyperkatifeia during withdrawal and prolonged abstinence. METHODS: Inflammatory and affective responses were measured in adult mice 24h or 4 weeks after 4 or 10 daily binge ethanol exposures (5g/kg/d, i.g.). RT-PCR was used to measure expression of pro-inflammatory genes. FosB immunohistochemistry was measured in stress circuitry central amygdala (CeA), BNST, and infralimbic cortex (IL) as a proxy for neuronal activity. Behavioral testing was performed in additional cohorts to measure anxiety-like behavior (center time in the open field), hyperarousal (acoustic startle), and inflexible negative affect (conditioned fear memory with extinction). To determine the role of proinflammatory microglia, Gi DREADDs were activated in microglia (CX3CR1.CreERT2.hm4di+/-EtOH +/- CNO). RESULTS: Binge ethanol increased pro-inflammatory gene activation both 24h after EtOH and lasting weeks into withdrawal (type I IFNs). Ten ethanol binges increased FosB in stress circuitry during withdrawal while simultaneously reducing BDNF persistently in the dBNST and CeA. Ethanol-treated mice spent less time in the center of the open field (anxiety-like behavior), had increased magnitude of acoustic startle reflex (hyperarousal) during withdrawal with reduced extinction of conditioned fear memory (PTSD phenotype) 4-5 weeks into abstinence. Gi-DREADD inhibition of microglia during alcohol treatment blocked persistent increases in proinflammatory cytokines, prevented ethanol-induced neuronal death (TUNEL), and prevented ethanol-induced hyperkatifeia including anxiety-like behavior and persistent conditioned fear memory. CONCLUSION: These data find a causative role for microglia in the development of negative affect behaviors during alcohol withdrawal. The prevention of these pro-inflammatory effects and behaviors by microglial inhibition reveals the integral role microglia play in the acute and lasting effects of ethanol on behavior in AUD pathogenesis.
Calcium-mediated amyloid co-aggregation of S100A1 and S100A8 proteins
Authors: Karalkevičiūtė Viktorija , Baronaitė Ieva , Peštenytė Aistė , Veiveris Dominykas , Usevičius Gediminas , Šimėnas Mantas , Žiaunys Mantas , Smirnovas Vytautas , Šulskis Darius
Published: November 2024

The S100 family consists of calcium binding proteins that are largely known for their contribution to the neuroinflammatory processes. They are associated with various cardiac and neurological functions as well as related diseases. A few S100 proteins can form unspecific or amyloid aggregates in neuropathologies and thus play a part in dementia pathogenesis. Among all S100 proteins, S100B and S100A9 aggregation properties are the most investigated, however, there is a lack of studies regarding other S100 members. In particular, S100A1 and S100A8 are also associated with neuropathies, but their interactions or aggregation are poorly understood. Therefore, in this study, we explored whether S100A1 and S100A8 proteins can form heterodimers, interact or co-aggregate.

Our results revealed that S100A1 and S100A8 interactions and amyloid aggregation are driven by calcium ions. We observed that while S100A1 remains mostly stable, S100A8 forms various types of spherical or unspecific aggregates. While they do not form stable heterodimers like calprotectin, their transient interactions facilitate the formation of worm-like amyloid fibrils and the process is regulated by different calcium ion concentrations. At calcium ions saturation, both proteins are stabilized leading to inhibition of aggregation. Overall, by employing a diverse range of techniques from amyloid and protein-specific fluorescence detection to electron-electron double resonance spectroscopy, we elucidated interactions between S100 proteins that might otherwise be overlooked, enhancing our understanding of their aggregation behaviour.
Uncovering the electrical synapse proteome in retinal neurons viain vivoproximity labeling
Authors: Tetenborg Stephan , Shihabeddin Eyad , Kumar Elizebeth Olive Akansha Manoj , Sigulinsky Crystal L. , Dedek Karin , Lin Ya-Ping , Echeverry Fabio A. , Hoff Hannah , Pereda Alberto E. , Jones Bryan W. , Ribelayga Christophe P. , Ebnet Klaus , Matsuura Ken , O’Brien John
Published: November 2024

Electrical synapses containing Connexin 36 (Cx36) represent the main means for communication in the mammalian nervous system. However, little is known about the protein complexes that constitute these synapses. In the present study, we applied different BioID strategies to screen the interactomes of Connexin 36 the major neuronal connexin and its zebrafish orthologue Cx35b in retinal neurons. Forin vivoproximity labeling in mice, we took advantage of the Cx36-EGFP strain and expressed a GFP-nanobody-TurboID fusion construct selectively in AII amacrine cells. Forin vivoBioID in zebrafish, we generated a transgenic line expressing a Cx35b-TurboID fusion under control of the Cx35b promoter. Both strategies allowed us to capture a plethora of molecules that were associated with electrical synapses and showed a high degree of evolutionary conservation in the proteomes of both species. Besides known interactors of Cx36 such as ZO-1 and ZO-2 we have identified more than 50 new proteins, such as scaffold proteins, adhesion molecules and regulators of the cytoskeleton. Moreover, we determined the subcellular localization of these proteins in AII amacrine and tested potential binding interactions with Cx36. Amongst these new interactors, we identified signal induced proliferation associated 1 like 3 (SIPA1L3), a protein that has been implicated in cell junction formation and cell polarity as a new scaffold of electrical synapses. Interestingly, SIPA1L3 was able to interact with ZO-1, ZO-2 and Cx36, suggesting a pivotal role in electrical synapse function. In summary, our study provides the first detailed view of the electrical synapse proteome in retinal neurons, which is likely to apply to electrical synapses elsewhere.
Quantitative mapping of pseudouridines in bacteria RNA
Authors: Sharma Shikha , Woodworth Brendan , Yang Bin , Duan Ning , Pheko Mannuku , Moutsopoulos Niki , Emiola Akintunde
Published: November 2024

RNA pseudouridylation is one of the most prevalent post-transcriptional modifications, occurring universally across all organisms. Although pseudouridines have been extensively studied in bacterial tRNAs and rRNAs, their presence and role in bacterial mRNA remain poorly characterized. Here, we used a bisulfite-based sequencing approach to provide a comprehensive and quantitative measurement of bacteria pseudouridines. As a proof of concept inE.coli, we identified 1,954 high-confidence sites in 1,331 transcripts, covering almost 30% of the transcriptome. Furthermore, pseudouridine mapping enabled the detection of differentially expressed genes associated with stress response that were unidentified using conventional RNA-seq approach. We also demonstrate that in addition to pseudouridine profiling, our approach can facilitate the discovery of previously unidentified transcripts. As an example, we identified a small RNA transcribed from the antisense strand of tRNA-Tyr which represses expression of distal genes. Finally, we mapped pseudouridines in oral microbiome samples of human subjects, demonstrating the broad applicability of our approach in complex microbiomes. Altogether, our work highlights the advantages of mapping bacterial pseudouridines and provides a tool to study posttranscription regulation in microbial communities.
Hepatic HKDC1 Deletion Alleviates Western Diet-Induced MASH in Mice
Authors: Xu Kai , Corona-Avila Irene , Frutos Maria Dolores , Nunez-Sanchez Maria Angeles , Makhanasa Dhruvi , Shah Pratham Viral , Guzman Grace , Ramos-Molina Bruno , Priyadarshini Medha , Khan Md. Wasim
Published: November 2024

The global prevalence of Metabolic dysfunction-associated steatohepatitis (MASH) has been rising sharply, closely mirroring the increasing rates of obesity and metabolic syndrome. MASH exhibits a strong sexual dimorphism where females are affected with more severe forms after menopause. Hexokinase domain-containing protein 1 (HKDC1) has recently been recognized for its role in liver diseases, where its expression is minimal under normal conditions but significantly increases in response to metabolic stressors like obesity and liver injury. This selective upregulation suggests HKDC1s potential specialization in hepatic glucose and lipid dysregulation, linking it closely to the progression of MASLD and MASH. This study aims to clarify the role of HKDC1 in Western diet-induced MASH in female mice by examining its impact on hepatic glucose and lipid metabolism, offering insights into its potential as a therapeutic target and addressing the need for sex-specific research in liver disease. This study reveals that HKDC1 expression is elevated in obese women with MASH and correlates with liver pathology. In a mouse model, liver-specific HKDC1 knockout (HKDC1LKO) protected against Western diet-induced obesity, glucose intolerance, and MASH features, including steatosis, inflammation, and fibrosis. Transcriptomic analysis showed that HKDC1 deletion reduced pro-inflammatory and pro-fibrotic gene expression, while gut microbiome analysis indicated a shift toward MASH-protective bacteria. These findings suggest that HKDC1 may exacerbate MASH progression through its role in metabolic and inflammatory pathways, making it a potential therapeutic target.
On-shell effective field theory and quantum transport for hard photons
Authors: Comadran Marc , Manuel Cristina
Published: November 2024

We develop an effective field theory for the description of high energetic or hard photons, the on-shell effective theory (OSEFT). The OSEFT describes the so-called eikonal or semiclassical optical limit, allowing for corrections organized in a systematic expansion on inverse powers of the photon energy. We derive the OSEFT from the Maxwell Lagrangian and study its different properties, such as the gauge symmetry and reparametrization invariance. The theory can be finally formulated in terms of a gauge invariant vector gauge field, without the need to introduce gauge-fixing. We then use the OSEFT to compute corrections to the Wigner photon function and derive its associated side jump effect from reparametrization invariance. Finally, we discuss how to properly define the Stokes parameters from transport theory once quantum effects are considered, so as to preserve their well-defined properties under Lorentz transformations.

Published by the American Physical Society
2024
Coping with a protracted crisis: a case study of IT-Integrator in Ukraine
Authors: Kukuruza Oksana , Golovkina Nataliya , Omelchenko Nadiia
Published: November 2024

Learning outcomes

This case study offers the following learning opportunities for students: to identify and assess how a management team can establish effective working relationships to build a cohesive team during times of severe crisis and to prepare business for the restoration period; and to find alternative ways aimed at restoring the company’s operations and suggest ways of adapting to the new, normal situation.

Case overview/synopsis

This case study examines the strategic decisions of IT-Integrator, a Ukrainian IT company, during the Russian invasion of Ukraine in 2022. It highlights the leadership of vice president Nadiia Omelchenko in navigating the crisis, focusing on initial chaos, the development of a business continuity plan and efforts to restore operations and ensure employee safety. Despite warnings, the outbreak of war on February 24, 2022, was unexpected, with no established emergency protocols. Companies independently decided on measures for safety and business continuity, especially those critical to infrastructure and banking. In 2021, IT-Integrator faced reluctance within its executive team regarding resource allocation for wartime scenarios. Omelchenko’s push for a comprehensive business continuity plan proved crucial. Despite the plan’s effectiveness, unpreparedness for the crisis’s scale hindered recovery efforts. During the early days of the invasion, Omelchenko managed the dual challenge of safeguarding the business and its employees amid uncertainty and workforce reduction. Each decision had significant implications, requiring a balance between immediate survival and future stability. The case of IT-Integrator underscores the importance of proactive crisis management, strategic planning and resilient leadership. Omelchenko’s experience offers valuable lessons for businesses facing similar crises, emphasizing preparedness, adaptability and a focus on both immediate and long-term recovery.

Complexity academic level

This case study is suitable for MBA and executive development programs.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 6: human resource management.
Regulatory fragmentation and management earnings forecasts
Authors: Xu Hongkang
Published: November 2024

Purpose

This study examines the impact of regulatory fragmentation on the issuance and width of management earnings forecasts (MEFs) in US firms, exploring how the presence of multiple regulatory bodies influences corporate disclosure and transparency.

Design/methodology/approach

Using data from the Federal Register from 2004 to 2019, the study employs a measure of regulatory fragmentation to analyze its effect on the likelihood and width of MEFs.

Findings

The research finds that heightened regulatory fragmentation is associated with an increased likelihood of firms issuing MEFs and a wider range of forecasted earnings, indicating a strategic use of MEFs to manage regulatory complexity.

Originality/value

The study offers a unique perspective by contrasting with literature that predominantly views regulatory fragmentation negatively, providing detailed insights into its complex effects on corporate communication. It suggests the strategic use of MEFs amid regulatory challenges, enhancing our understanding of how regulatory environments shape corporate communication strategies.
Ethical reasoning in technology: using computational approaches to integrate ethics into AI systems
Authors: Sholla Sahil , Reshi Iraq Ahmad
Published: November 2024

Purpose

This paper does not concern with the “why” of ethics. Such questions are typically of interest to philosophers and are outside the scope of this work. In the next section, the authors offer a look into “what” of ethics, i.e. various types and subtypes of ethics. Subsequently, the authors explore “how” of ethics, by summarising various computational approaches to ethical reasoning offered by researchers in the field.

Design/methodology/approach

The approaches are classified based on the application domain, ethical theory, agent type and design paradigm adopted. Moreover, promising research directions towards ethical reasoning are also presented.

Findings

Since the field is essentially interdisciplinary in nature, collaborative research from such areas as neuroscience, psychology, artificial intelligence, law and social sciences is necessary. It is hoped that this paper offers much needed insight into computational approaches for ethical reasoning paving way for researchers to further engage with the question.

Originality/value

In this paper, the authors discussed vaious computational approaches proposed by researchers to implement ethics. Although none of the approaches adequately answer the question, it is necessary to engage with the research effort to make a substantial contribution to the emerging research area. Though some effort has been made in the design of logic-based systems, they are largely in stages of infancy and merit considerable research.
Impact of market classifications on the innovative use of financing and dividend techniques: a global review of survey papers
Authors: Addico Nene Lartey , Amewu Godfred , Owusu-Ansah Anthony , Daniels Edward
Published: November 2024

Purpose

This study aims to investigate the belief that the innovative/skilled use of financing and dividend policy decision techniques depends on the firm’s host market classifications (frontier, emerging and developed markets).

Design/methodology/approach

Using survey studies with similar questions, the authors reviewed, tallied and compared firm characteristic subgroup mean values of 2.4 and above (≥ 60% usage rate) per technique per market classification for the financing decisions analysis. In the dividend policy analysis, the authors tabulated existing rank results per market classification.

Findings

Managers in Malaysia significantly issue stock based on whether the firm's recent profits have been sufficient to fund their activities; this technique is of low value to US and Ghanaian managers. Managers in Ghana significantly limit their debt so their customers/suppliers are not worried about the firm going out of business; this technique has low value for Malaysian and US managers. Managers in Malaysia significantly issue debt when it gives investors a better impression of their firm prospects than issuing stock; this technique is not valuable to Ghanaian and US managers. On dividends, Ghanaian and sanctioned Iranian managers significantly consider cash availability before a dividend decision; this has low value to emerging and developed market managers.

Practical implications

These findings suggest that managers must customise their sets of valuable financing and dividend techniques to reflect the business risks and hurdles per their firm’s host market classification – as markets may determine a technique’s usefulness. Also, the innovative/skilful use of financing and dividend techniques decreases as managers move from developed to frontier markets, possibly due to degrading market conditions.

Originality/value

A global comparative study of survey literature covering frontier, emerging and developed markets is rare in the literature.
Production system state analysis and improvement using VSM, simulation, and fuzzy logic
Authors: Noueihed Karim , Hamzeh Farook
Published: November 2024

Purpose

The paper aims to provide a door-to-door holistic perspective on the state of a production system based on several metrics and their relationships, to utilize a combination of tools and techniques and to develop a unique model for production system assessment. The study addresses the limitations of narrow approaches by proposing a new metric as a single indicator of the production system’s overall state.

Design/methodology/approach

The research methodology adopted is design science research. It proposes a framework that combines value stream mapping, simulation and fuzzy logic to study the impact of different lean interventions on the overall state. An offsite construction facility was used as a case study. Data were gathered using methods such as ethnography, interviews, time and motion studies, shopfloor observations, video surveillance and database exploration.

Findings

The paper highlights how some interventions can have local improvements but lead to negative impacts on the overall system state. It emphasizes the importance of having a holistic approach to analyze and improve the true state of a production system.

Research limitations/implications

The study excludes impacts of the supply chain and assumes the system to be confined within the shopfloor. Researchers are encouraged to include those variables in future studies.

Practical implications

The study presents a practical framework and tool that can be tailored to any production system and be used to improve its performance.

Originality/value

This paper proposes a unique framework and a new metric for system state assessment and improvement.
At the crossroads of inflation: analyzing Central Bank responses in noneconomic crises
Authors: Bajra Ujkan Q. , Gjeçi Ardit , Cadez Simon
Published: November 2024

Purpose

This study aims to thoroughly investigate the complexity of inflation dynamics in the context of two significant global crises, the COVID-19 pandemic and the ongoing geopolitical tensions in Ukraine. The primary goal is to examine the effects of several factors, such as interest rates, currency indices and unemployment, on inflation during extended periods of noneconomic crises.

Design/methodology/approach

This research uses a comprehensive data set spanning 75 months across the USA and the Euro Area, using the Generalized Method of Moments two-step regression methodology for analysis. The study examines the relationships between interest rates, currency indices, unemployment and inflation during extended noneconomic (financial) crises. This rigorous approach offers a nuanced understanding of how these factors interact and influence inflation.

Findings

The study highlights the crucial role of interest rates in controlling inflation during crises. Specifically, an interest rate increase of over 1.75% negatively impacts inflation, with more substantial rate hikes having a faster effect. The analysis reveals a minimal correlation between currency devaluation and inflation, emphasizing the predominant influence of interest rates. In addition, a notable negative correlation between unemployment and inflation is observed, indicating that higher unemployment rates tend to coincide with lower inflation levels.

Practical implications

The study’s findings offer valuable insights for central banks and policymakers tasked with managing inflation in times of crisis. By underscoring the effectiveness of interest rate adjustments and the limited influence of currency depreciation, this research provides critical guidance for formulating effective monetary policy during economic challenges.

Originality/value

This study contributes to existing literature by providing a comprehensive analysis of inflation dynamics during noneconomic crises, using a robust database and using advanced econometric techniques. The findings provide new insights into the role of interest rates, currency indices and unemployment in shaping inflation dynamics in times of noneconomic crises. These findings enhance the understanding of monetary policy strategies in challenging economic environments.
Integration and implementation of LSS 4.0 practices: a perspective from manufacturing and service sectors
Authors: Citybabu G. , Yamini S.
Published: November 2024

Purpose

Lean Six Sigma (LSS) is often perceived as a foundation for implementing Industry 4.0 (I4.0) within an organization, with the two strengthening each other in different ways. The purpose of this article is to examine the evolution, trends and motivation for merging LSS and I4.0 and to gain insights into LSS 4.0 in both manufacturing and service sectors. This article also explores the effective methods for integrating and implementing LSS 4.0 in both manufacturing and service sectors, along with conducting a Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis of LSS 4.0.

Design/methodology/approach

By conducting a systematic literature review in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, relevant literature from 2010 to 2023 was reviewed using appropriate keywords and research criteria. The objective was to identify, select and evaluate research articles related to LSS 4.0. Consequently, 159 relevant papers were located in databases, including Elsevier, Taylor and Francis Group, IEEE, Springer, Emerald Insights, Scopus and non-Scopus databases. Additionally, this review aimed to understand the progress of LSS 4.0 from the manufacturing and service sector context and to perform a SWOT analysis of LSS 4.0.

Findings

This review reveals a significant surge in the literature on LSS and I4.0 over the past three years. The research articles were categorized based on various themes, including the publisher, journals, types of articles and geographical factors such as country and continent. Additionally, the review examined the progress of LSS 4.0 in both manufacturing and service sectors. A SWOT analysis was also performed to identify the SWOT of LSS 4.0.

Originality/value

This is the first exclusive research work to conduct a SWOT analysis of LSS 4.0. This research article is highly valuable for academicians, researchers, policymakers and practitioners as it helps to identify the SWOT of LSS 4.0. Furthermore, it provides an overview of the progress of LSS 4.0 from both manufacturing and service sector perspectives, and significant case studies are discussed.
Lacticaseibacillus rhamnosus LRa05 alleviates cyclophosphamide‐induced immunosuppression and intestinal microbiota disorder in mice
Authors: Zhu Mingming , Yang Lvzhu , Kong Sufen , Bai Yuyuan , Zhao Bin
Published: November 2024

Probiotics play a crucial role in regulating the gut microbiota and enhancing immune response. Oral administration of probiotics modulates intestinal microbiota composition and immune homeostasis. In this study, we investigated the immunoregulatory effect of Lacticaseibacillus rhamnosus LRa05 on cyclophosphamide (CTX)‐induced immunosuppressive mice. The results showed that oral administration of LRa05 reduced weight loss, restored immune organ indices, and maintained the structural integrity of the intestinal tissue in CTX‐treated mice. Moreover, oral administration of LRa05 exhibited immune‐modulating properties by promoting the secretion of cytokines (tumor necrosis factor‐α, interleukin‐1β, interleukin‐10, and secretory immunoglobulin A) in serum. Moreover, the analysis of 16S rRNA amplicon sequencing revealed that LRa05 increased gut microbiota diversity and regulated its composition. In detail, LRa05 intervention restored the Firmicutes/Bacteroidota ratio and significantly increased the relative abundance of Lachnospiraceae_NK4A136_group, Oscillibacter, Alloprevotella, Parasutterella, and Roseburia in immunocompromised mice. Conversely, the abundances of Helicobacter, Bacteroides, and unclassified_Desulfovibrionaceae were significantly decreased after administration of LRa05. Based on these findings, orally administered LRa05 could effectively maintain intestinal microbiota homeostasis and regulate immunity, suggesting the potential of L. rhamnosus LRa05 as a candidate probiotic strain in the application of dietary supplement.

Practical Application

Supplement with L. rhamnosus LRa05 can improve immunity, regulate gut microbiota and promote body health.
Visual perceptual artefacts in cardiothoracic imaging: Implications for diagnostic accuracy and strategies for mitigation
Authors: Stirrat Thomas P , Chang Michael , Desai Anushka , Thiru Shankar , Chen Daniel T , Waller Joseph , Kamona Aws , Umair Muhammad
Published: November 2024

Visual perceptual artefacts are distortions or illusions in medical image interpretation arising from the human visual system rather than hardware or imaging acquisition processes. These artefacts, emerging at various visual processing stages, such as the retina, visual pathways, visual cortex, and cognitive interpretation stages, impact the interpretation of cardiothoracic images. This review discusses artefacts including Mach bands, Dark Rim, Background Effects, Ambiguous Figures, Subjective Contours, and the Parallax Effect. A thorough literature search was conducted using PubMed and Google Scholar. Search terms included ‘visual perceptual artifacts’, ‘cardiothoracic imaging’, ‘Mach bands’, ‘dark rim artifact’, ‘stress cardiac MRI’, and ‘radiology visual illusions’. Inclusion criteria encompassed studies focusing on visual perceptual artefacts in cardiothoracic imaging published in peer‐reviewed journals. Studies not addressing visual perceptual artefacts or those focusing on imaging technology, hardware, or software‐related artefacts were excluded. Duplicate studies were removed, and a final selection of 32 studies was analysed. Several key visual perceptual artefacts relevant to cardiothoracic imaging were identified. Mach bands, caused by lateral inhibition in the retina, create false contrasts at object boundaries, potentially mimicking pathologies such as fractures or pneumothoraces. The dark rim artefact observed on stress cardiac MRI, resulting from Gibbs ringing or truncation artefacts, can simulate perfusion defects and complicate diagnosis. Lateral inhibition can possibly accentuate the appearance of the dark rim artefact. Artefacts also fall under illusions of sensation, perception, and image formation. These illusions present both risks and benefits to diagnostic radiology. Recognizing visual perceptual artefacts is crucial for improving diagnostic accuracy and developing strategies to mitigate their impact. A comprehensive understanding and training on these artefacts are essential for radiologists to enhance interpretive skills, reduce diagnostic errors, and ultimately improve patient care in radiology.