bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal stromal cells affect CD8 naïve to memory subsets polarization by down-modulating IL12Rβ1 and IL2Rα signaling pathways
Authors: Papait Andrea , Vertua Elsa , Signoroni Patrizia Bonassi , Cargnoni Anna , Magatti Marta , Stefani Francesca Romana , Romoli Jacopo , Silini Antonietta Rosa , Parolini Ornella
Published: March 2023

Adaptive immunity is typified by specificity and memory. Immune memory protects from subsequent infection and relies on functional, fully activated, T lymphocytes. Mesenchymal stromal cells (MSC) have been investigated for their potential therapeutic applications in a variety of diseases in which a dysregulated immune response plays a central role in pathogenesis or progression. Notably, for adaptive immunity, MSC can reduce the activation and cytotoxic activity of CD8+T lymphocytes as well as the polarization of CD4+T lymphocytes toward inflammatory subsets while favoring polarization toward the T regulatory subset. Although MSC have been widely reported to impact CD4 T cell proliferation and polarization, how MSC affect T-cell commitment toward memory subsets is still not known. Here, we report for the first time that MSC isolated from the amniotic membrane of human term placenta (hAMSC) determine T cell fate. We show that hAMSC influence naïve CD8+T cell activation and differentiation by downregulating mTOR pathway activation and modulating the expression of Tbet and Eomes, master regulators of the commitment of naïve CD8+T cells toward memory precursor effector cells (MPECs). This effect can be partly attribute to the ability of hAMSC to reduce the phosphorylation of STAT4 and STAT5, two transcriptional factors downstream IL-12Rβ1 and IL-2Rα receptors. Our results unravel a novel feature of MSC, offering new mechanistic insights into the effects of MSC in the treatment of diseases characterized by an altered activation of memory subsets, such as autoimmune diseases and graft versus host disease.
Triggering blood-lipid-profile by immunomodulatory and antimicrobial molecules for cross-evaluation of early detection of cancer
Authors: Prakash Om , Khan Feroz
Published: March 2023

Background

Al-guided mapping establishes relationship between gene-signature and phenotype. Since, Immunomodulatory & antimicrobial molecules, both show anticancer as well as their relation with lipid; therefore, can be further used for cross-validation or enrichment analysis for early detection of cancer. Considering the information, a study was performed on the influence of Immunomodulatory and antimicrobial molecules on blood lipid profile at the early stage of cancer.

Materials and Method

Present study established a relationship between small molecule-vs-genotype to phenotype. Genotypic features extracted through RNAseq analysis for stomach adenocarcinoma, which was further mapped with blood lipid profile. RNA-seq expression, from a population, was collected as gene expression profile of transcriptome. Gene signature was identified through in-house processing. Blood lipid profile was as: Total Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, Non-HDL-C, and TG to HDL ratio.

Results

To evaluate the Immunomodulatory and antimicrobial molecules for anticancer activity in terms of their influence on blood lipid-profile, computational models were established for developing relationships between small molecules-vs-genotype. Immunomodulatory and antimicrobial activity showed significant impact on genotypic expression at cancerous conditions.

Conclusion

It was concluded that usage of Immunomodulatory small molecules & antibiotics showed their impact on blood lipid profile. These results may support cross-checking the possibility of cancer during the early detection of cancer. Furthermore, suggested the use of immunomodulatory and antimicrobial small molecules for cross evaluation of early disease prediction of different cancer types.
Are 150 km of open sea enough? Gene flow and population differentiation in a bat-pollinated columnar cactus
Authors: Arenas Sebastián , Búrquez Alberto , Bustamante Enriquena , Scheinvar Enrique , Eguiarte Luis E.
Published: March 2023

Genetic differentiations and phylogeographical patterns are controlled by the interplay between spatial isolation and gene flow. To test the extent of gene flow across an oceanic barrier, we explored the effect of the separation of the peninsula of Baja California on the evolution of mainland and peninsular populations of the long-lived columnar cactusStenocereus thurberi. We analyzed twelve populations throughout the OPC distribution range to assess genetic diversity and structure using chloroplast DNA sequences. Genetic diversity was higher (Hd=0.81), and genetic structure was lower (GST=0.143) in mainland populations vs peninsular populations (Hd=0.71,GST=0.358 respectively). Genetic diversity was negatively associated with elevation but positively with rainfall. Two mainland and one peninsular ancestral haplotypes were reconstructed. Peninsular populations were as isolated among them as with mainland populations. Peninsular haplotypes formed a group with one mainland coastal population, and populations across the gulf shared common haplotypes giving support to regular gene flow across the Gulf. Gene flow is likely mediated by bats, the main pollinators and seed dispersers. Niche modeling suggests that during the Last Glacial Maximum (c. 130 ka), OPC populations shrank to southern locations. Currently, Stenocereus thurberi populations are expanding, and the species is under population divergence despite ongoing gene flow. Ancestral populations are located on the mainland and although vicariant peninsular populations cannot be ruled out, they are likely the result of gene flow across the seemingly formidable barrier of the Gulf of California. Still, unique haplotypes occur in the peninsula and the mainland, and peninsular populations are more structured than these on the mainland.
CellBin: a highly accurate single-cell gene expression processing pipeline for high-resolution spatial transcriptomics
Authors: Li Mei , Liu Huanlin , Kang Qiang , Fang Shuangsang , Li Min , Zhang Jiajun , Teng Fei , Wang Dan , Cen Weixuan , Li Zepeng , Feng Ning , Guo Jing , He Qiqi , Wang Leying , Zheng Tiantong , Li Shengkang , Bai Yinqi , Xie Min , Bai Yong , Liao Sha , Chen Ao , Zhang Yong , Brix Susanne , Xu Xun , Li Yuxiang
Published: March 2023

Background

Owing to recent advances in resolution and field-of-view, spatially resolved transcriptomics sequencing, such as Stereo-seq, has emerged as a cutting-edge technology for the interpretation of large tissues at the single-cell level. To generate accurate single-cell spatial gene expression profiles from high-resolution spatial omics data, a powerful computational tool is required.

Findings

We present CellBin, an image-facilitated one-stop pipeline for high-resolution and large field-of-view spatial transcriptomic data of Stereo-seq. CellBin provides a comprehensive and systematic platform for generating high-confidence single-cell spatial gene expression profiles, which specifically includes image stitching, image registration, tissue segmentation, nuclei segmentation and molecule labeling. CellBin is user-friendly and does not require a specific level of omics and image analysis expertise.

Conclusions

During image stitching and molecule labeling, CellBin delivers better-performing algorithms to reduce stitching error and time, in addition to improving the signal-to-noise ratio of single-cell gene expression data, in comparison with existing methods. Additionally, CellBin has been shown to obtain highly accurate single-cell spatial data using mouse brain tissue, which facilitated clustering and annotation.
Cell-autonomous metabolic reprogramming and oxidative stress underlie endothelial dysfunction in acute myocardial infarction
Authors: Zodda Erika , Tura-Ceide Olga , Mills Nicholas L. , Tarragó-Celada Josep , Carini Marina , Thomson Timothy M , Cascante Marta
Published: March 2023

Compelling evidence has accumulated for the role of oxidative stress on the endothelial cell (EC) dysfunction underlying acute coronary syndromes. However, understanding the metabolic determinants of EC dysfunction has been hampered by the scarcity of appropriate cell models. Here, we have generated and phenotypically characterized EC derived from thrombectomy specimens in patients with acute myocardial infarction (AMI). We have found that AMI-derived endothelial cells (AMIECs), but not control EC from health coronary arteries, display impaired growth, migration and tubulogenesis. These phenotypic abnormalities were accompanied with metabolic abnormalities including augmentation of reactive oxygen species (ROS) and glutathione intracellular content, along with diminished glucose consumption coupled to increased lactate production. In AMIECs, the protein levels of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase type 3, PFKFB3, were downregulated, while those of PFKFB4 were upregulated, suggesting a shunting of glycolysis towards the pentose phosphate pathway (PPP) in the pathological ECs. PPP overactivation was further supported by upregulation of G6PD in AMIECs, the key enzyme in the oxidative branch of the PPP, which supplies the bulk of NADPH reducing equivalents necessary for the reduction/turnover and lipid synthesis.. Further, the glutaminolytic enzyme glutaminase (GLS) was upregulated in AMIECs, providing a mechanistic explanation for the observed increase in glutathione content. Finally, AMIECs had higher mitochondrial membrane potential than control ECs, which, together with high ROS levels, suggest a highly coupled mitochondrial activity in patient ECs. We suggest that high proton coupling underlies the abnormally high production of ROS, balanced by PPP-driven glutathione turnover, as a primary, cell-autonomous abnormality driving EC dysfunction in AMI.
BrainLine: An Open Pipeline for Connectivity Analysis of Heterogeneous Whole-Brain Fluorescence Volumes
Authors: Athey Thomas L. , Wright Matthew A. , Pavlovic Marija , Chandrashekhar Vikram , Deisseroth Karl , Miller Michael I. , Vogelstein Joshua T.
Published: March 2023

Whole-brain fluorescence images require several stages of computational processing to fully reveal the neuron morphology and connectivity information they contain. However, these computational tools are rarely part of an integrated pipeline. Here we present BrainLine, an open-source pipeline that interfaces with existing software to provide registration, axon segmentation, soma detection, visualization and analysis of results. By implementing a feedback based training paradigm with BrainLine, we were able to use a single learning algorithm to accurately process a diverse set of whole-brain images generated by light-sheet microscopy. BrainLine is available as part of our Python package brainlit:http://brainlit.neurodata.io/.
Exploring the Macroevolutionary Signature of Asymmetric Inheritance at Speciation
Authors: Gaboriau Théo , Tobias Joseph A. , Silvestro Daniele , Salamin Nicolas
Published: March 2023

Abstract

Popular comparative phylogenetic models such as Brownian Motion, Ornstein-Ulhenbeck, and their extensions, assume that, at speciation, a trait value is inherited identically by the two descendant species. This assumption contrasts with models of speciation at the micro-evolutionary scale where phenotypic distributions of the descendants are sub-samples of the ancestral distribution. Various described mechanisms of speciation can lead to a displacement of the ancestral phenotypic mean among descendants and an asymmetric inheritance of the ancestral phenotypic variance. In contrast, even macro-evolutionary models that account for intraspecific variance assume symmetrically conserved inheritance of the ancestral phenotypic distribution at speciation. Here we develop an Asymmetric Brownian Motion model (ABM) that relaxes the hypothesis of symmetric and conserved inheritance of the ancestral distribution at the time of speciation. The ABM jointly models the evolution of both intra- and inter-specific phenotypic variation. It also allows the mode of phenotypic inheritance at speciation to be inferred, ranging from a symmetric and conserved inheritance, where descendants inherit the ancestral distribution, to an asymmetric and displaced inheritance, where descendants inherit divergent phenotypic means and variances. To demonstrate this model, we analyze the evolution of beak morphology in Darwin finches, finding evidence of character displacement at speciation. The ABM model helps to bridge micro- and macro-evolutionary models of trait evolution by providing a more robust framework for testing the effects of ecological speciation, character displacement, and niche partitioning on trait evolution at the macro-evolutionary scale.
Functional imaging of conduction dynamics in cortical and spinal axons
Authors: Radivojevic Milos , Punga Anna Rostedt
Published: March 2023

Mammalian axons are specialized for transmitting action potentials to targets within the central and peripheral nervous system. A growing body of evidence suggests that, besides signal conduction, axons play essential roles in neural information processing, and their malfunctions are common hallmarks of neurodegenerative diseases. The technologies available to study axonal function and structure integrally limit the comprehension of axon neurobiology. High-density microelectrode arrays (HD-MEAs) allow for accessing axonal action potentials at high spatiotemporal resolution, but provide no insights on axonal morphology. Here we demonstrate a method for electrical visualization of axonal morphologies based on extracellular action potentials recorded from cortical and motor neurons using HD-MEAs. The method enabled us to reconstruct up to 5-centimeter-long axonal arbors and directly monitor axonal conduction across thousands of recording sites. We reconstructed 1.86 meters of cortical and spinal axons in total and found specific features in their structure and function.
Blood neurofilament light chain levels are associated with disease progression in a transgenic SCA3 mouse model
Authors: Mengel David , Wellik Isabel G. , Schuster Kristen H. , Jarrah Sabrina I. , Wacker Madeleine , Ashraf Naila S. , Öz Gülin , Synofzik Matthis , Costa Maria do Carmo , McLoughlin Hayley S.
Published: March 2023

Increased neurofilament light (NfL) protein in biofluids is reflective of neurodegeneration and has gained interest as a biomarker across neurodegenerative diseases. In spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited ataxia, patients exhibit progressive NfL increases in peripheral blood when becoming symptomatic, remaining stably elevated throughout further disease course. However, progressive NfL changes are not yet validated in relevant preclinical SCA3 animal models, hindering its application as a biomarker during therapeutic development. We used ultra-sensitive single-molecule array (Simoa) to measure blood NfL over disease progression in the YACQ84 mouse, assessing relationships with measures of disease severity including age, CAG repeat size, and magnetic resonance spectroscopy. We show that YACQ84 mice exhibit increased blood NfL, concomitant with ataxia-related motor deficits and correlated with neurometabolite abnormalities. Our findings establish natural history progression of NfL increases in the preclinical YACQ84 mouse, further supporting the utility of blood NfL as a peripheral neurodegeneration biomarker and informing coinciding timelines of different measures of SCA3 pathogenesis.

Summary statement

Peripheral blood of SCA3 YACQ84 mice exhibits increased abundance of neuronal-specific NfL protein directly associating with disease progression, providing an accessible disease biofluid biomarker to interrogate in preclinical therapeutic studies.
Representing Multiple Visual Objects in the Human Brain and Convolutional Neural Networks
Authors: Mocz Viola , Jeong Su Keun , Chun Marvin , Xu Yaoda
Published: March 2023

Objects in the real world often appear with other objects. To recover the identity of an object whether or not other objects are encoded concurrently, in primate object-processing regions, neural responses to an object pair have been shown to be well approximated by the average responses to each constituent object shown alone, indicating the whole is equal to the average of its parts. This is present at the single unit level in the slope of response amplitudes of macaque IT neurons to paired and single objects, and at the population level in response patterns of fMRI voxels in human ventral object processing regions (e.g., LO). Here we show that averaging exists in both single fMRI voxels and voxel population responses in human LO, with better averaging in single voxels leading to better averaging in fMRI response patterns, demonstrating a close correspondence of averaging at the fMRI unit and population levels. To understand if a similar averaging mechanism exists in convolutional neural networks (CNNs) pretrained for object classification, we examined five CNNs with varying architecture, depth and the presence/absence of recurrent processing. We observed averaging at the CNN unit level but rarely at the population level, with CNN unit response distribution in most cases did not resemble human LO or macaque IT responses. The whole is thus not equal to the average of its parts in CNNs, potentially rendering the individual objects in a pair less accessible in CNNs during visual processing than they are in the human brain.
MyeloidZfhx3Deficiency Protects Against Hypercapnia-induced Suppression of Host Defense Against Influenza A Virus
Authors: Casalino-Matsuda S. Marina , Chen Fei , Gonzalez-Gonzalez Francisco J. , Matsuda Hiroaki , Nair Aisha , Abdala-Valencia Hiam , Budinger G. R. Scott , Dong Jin-Tang , Beitel Greg J. , Sporn Peter H. S.
Published: March 2023

Hypercapnia, elevation of the partial pressure of CO2in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions, and that elevated CO2increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMØs). We also show that zinc finger homeobox 3 (Zfhx3), mammalian ortholog of zfh2, which mediates hypercapnic immune suppression inDrosophila, is expressed in mouse and human MØs. Deletion ofZfhx3in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMØs and decreased viral replication, inflammatory lung injury and mortality in hypercapnic mice infected with influenza A virus. Our results establish Zfhx3 as the first known mammalian mediator of CO2effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung diseases.

Graphical abstract
Primary lung fibroblasts respond to IL-33, IL-13, and IL-17A by secreting factors that activate macrophages
Authors: Venezia Jarrett , Gour Naina , Loube Jeffrey , Mitzner Wayne , Scott Alan L.
Published: March 2023

There is mounting evidence that macrophage-fibroblast communication is key to the understanding of disease processes. To gain insights into these relationships in the context of progressive lung damage, we measured changes in protein and RNA expression of pulmonary macrophages and fibroblasts upon exposure to IL-33, IL-13, and IL-17A, which are three cytokines often implicated in pathways driving chronic lung remodeling and severe disease like emphysema. Applying anin vitroculture system, bulk-RNA sequencing, and protein assays, it was determined that IL-33, IL-13, and IL-17A used alone or in combination activated mouse alveolar macrophages to a modest extent with IL-13 inducing the most vigorous response. While lung fibroblasts also responded modestly to single and paired treatments with IL-33, IL-13, and IL-17A, simultaneous exposure to all three cytokines induced significant activation that was characterized by expression of genes associated with immune cell trafficking and activation, tissue remodeling, and maintenance of the extracellular matrix. Importantly, factors secreted by triple-treated lung fibroblasts resulted in the activation of macrophagesin vitro. In addition to being the first report describing the cooperative interactions of IL-33, IL-13, and IL-17A on lung fibroblasts, these findings provide additional evidence that fibroblast-macrophage communication is a key component to repair and remodeling in the lung, as well as mechanisms that drive progression of emphysema.
In vitrogeneration of megakaryocytes from engineered mouse embryonic stem cells
Authors: Lewis Mitchell R. , Deans Tara L.
Published: March 2023

Thein vitrodifferentiation of pluripotent stem cells into desired lineages enables mechanistic studies of cell transitions into more mature states that can provide insights into the design principles governing cell fate control. We are interested in reprogramming pluripotent stem cells with synthetic gene circuits to drive mouse embryonic stem cells (mESCs) down the hematopoietic lineage for the production of megakaryocytes, the progenitor cells for platelets. Here, we describe the methodology for growing and differentiating mESCs, in addition to inserting a transgene to observe its expression throughout differentiation. This entails four key methods: (1) growing and preparing mouse embryonic fibroblasts for supporting mESC growth and expansion, (2) growing and preparing OP9 feeder cells to support the differentiation of mESCs, (3) the differentiation of mESCs into megakaryocytes, and (4) utilizing an integrase mediated docking site to insert transgenes for their stable integration and expression throughout differentiation. Altogether, this approach demonstrates a streamline differentiation protocol that emphasizes the reprogramming potential of mESCs that can be used for future mechanistic and therapeutic studies of controlling cell fate outcomes.
Genetically Encoded Boronolectin as a Specific Red Fluorescent UDP-GlcNAc Biosensor
Authors: Zhang Jing , Li Zefan , Pang Yu , Fan Yichong , Ai Hui-wang
Published: March 2023

There is great interest in developing boronolectins, which are synthetic lectin mimics containing a boronic acid functional group for reversible recognition of diol-containing molecules, such as glycans and ribonucleotides. However, it remains a significant challenge to gain specificity. Here, we present a genetically encoded boronolectin, which is a hybrid protein consisting of a noncanonical amino acid (ncAA) p-boronophenylalanine (pBoF), natural-lectin-derived peptide sequences, and a circularly permuted red fluorescent protein (cpRFP). The genetic encodability permitted a straightforward protein engineering process to derive a red fluorescent biosensor that can specifically bind uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an important nucleotide sugar involved in metabolic sensing and cell signaling. We further characterized the resultant boronic acid-and peptide-assisted UDP-GlcNAc sensor (bapaUGAc) both in vitro and in live mammalian cells. Because UDP-GlcNAc in the endoplasmic reticulum (ER) and Golgi apparatus plays essential roles in glycosylating biomolecules in the secretory pathway, we genetically expressed bapaUGAc in the ER and Golgi and validated the sensor for its responses to metabolic disruption and pharmacological inhibition. In addition, we combined bapaUGAc with UGAcS, a recently reported green fluorescent UDP-GlcNAc sensor based on an alternative sensing mechanism, to monitor UDP-GlcNAc level changes in the ER and cytosol simultaneously. We expect our work to facilitate the future development of specific boronolectins for carbohydrates. In addition, this newly developed genetically encoded bapaUGAc sensor will be a valuable tool for studying UDP-GlcNAc and glycobiology.
Hanfparade 2022: protest and participants’ views on cannabis legalization in Germany
Authors: Skliamis Kostas
Published: March 2023

Purpose

The purpose of this paper is twofold. First, it investigates the characteristics of Hanfparade 2022 – the biggest prolegalization festival in Germany – and its visitors, as well as the main reason for participation in Hanfparade. Findings are compared to those from Hanfparade 2016 to explore whether the main reason for festival attendance has changed since the legalization of medical cannabis in 2017 and since the announcement of plans for cannabis legalization. Second, this paper assesses Hanfparade participants’ views on cannabis legalization in Germany, in particular their opinions on and their preferences for retail supply options.

Design/methodology/approach

This study is a replication of a research conducted in 2016 at the same festival in Berlin, with a slightly adapted questionnaire. In this study, a combination of qualitative and quantitative research methods was used: observation at the festival, interviews before and after the festival with the organizer and a survey among festival attendees (n = 183).

Findings

Protest still looks relevant for the participants at Hanfparade, and the announcement of plans for legalization does not seem to downgrade this feeling. The participants have positive opinions about self-supply through home cultivation, noncommercial supply through Cannabis Social Clubs (CSCs) and commercial supply through stores similar to Dutch coffee shops. However, positive opinions do not necessarily reflect a personal preference, e.g. CSCs were very low in personal preferences. The options of home cultivation and CSCs were more popular among daily users.

Originality/value

This study contributes to the ongoing debate in Germany, focusing on views of cannabis users.
“It’s the discharge and what comes after that” – a phenomenological analysis of peer support workers’ lived experiences of transitioning from psychiatric care
Authors: Brenisin Kristina , Padilla Mc Stephen , Breen Kieran
Published: March 2023

Purpose

Transition from inpatient mental health care to community living can be very difficult, as people are at an increased risk of suicide, self-harm and ultimately readmission into hospital. There is little research conducted exploring peer support workers’ (PSWs) lived experiences that could provide insight into the key transitions of care, particularly the support required after discharge from inpatient mental health care. The purpose of this paper is thus to provide a particular insight into what it feels like being discharged from psychiatric care from a PSW’s perspective, how may support be improved post-discharge and what factors might impact the potential for readmission into inpatient care.

Design/methodology/approach

A qualitative, phenomenological approach was adopted to explore and describe PSWs’ lived experiences of transitioning from psychiatric care. Four PSWs who were employed by a UK secure mental health facility were recruited. PSW is a non-clinical role with their main duty to support patients, and they were considered for this type of the study for their experience in negotiating the discharge process to better carry out their job as a PSW.

Findings

After being discharged from psychiatric care, PSWs experienced issues that had either a negative impact on their mental wellbeing or even resulted in their readmission back into inpatient psychiatric care. This study identified three inter-related recurrent themes – continuity of support, having options and realisation, all concerning difficulties in adjusting to independent community life following discharge. The findings of the study highlighted the importance of ensuring that service users should be actively involved in their discharge planning, and the use of effective post-discharge planning processes should be used as a crucial step to avoid readmission.

Research limitations/implications

A deeper insight into the factors that impact on readmission to secure care is needed. The active involvement of service users in effective pre- and post-discharge planning is crucial to avoid readmission.

Practical implications

Mental health professionals should consider developing more effective discharge interventions in collaboration with service users; inpatient services should consider creating more effective post-discharge information care and support packages. Their lived experience empowers PSWs to play a key role in guiding patients in the discharge process.

Originality/value

This is the first study, to the best of the authors’ knowledge, to explore what it feels like being discharged from inpatient mental health care by interviewing PSWs employed at a forensic mental health hospital by adopting a phenomenological approach. This paper offers a deeper insight into the transition process and explores in detail what support is needed post discharge to avoid potential readmission from PSWs’ perspectives.
Behavioural defences against parasites across host social structures
Authors: Stockmaier Sebastian , Ulrich Yuko , Albery Gregory F. , Cremer Sylvia , Lopes Patricia C.
Published: March 2023

Animals exhibit a variety of behavioural defences against socially transmitted parasites. These defences evolved to increase host fitness by avoiding, resisting or tolerating infection.

Because they can occur in both infected individuals and their uninfected social partners, these defences often have important consequences for the social group.

Here, we discuss the evolution and ecology of anti‐parasite behavioural defences across a taxonomically wide social spectrum, considering colonial groups, stable groups, transitional groups and solitary animals.

We discuss avoidance, resistance and tolerance behaviours across these social group structures, identifying how social complexity, group composition and interdependent social relationships may contribute to the expression and evolution of behavioural strategies.

Finally, we outline avenues for further investigation such as approaches to quantify group‐level responses, and the connection of the physiological and behavioural response to parasites in different social contexts.

Read the free Plain Language Summary for this article on the Journal blog.
Introduction
Authors: Borland Jeff
Published: March 2023

This article introduces the Policy Forum. It contains: (i) a brief overview of the fiscal policies introduced to deal with COVID‐19 and their impact on Australia's economic performance; (ii) summaries of the articles in the Forum; and (iii) suggested learnings for policymaking in future crises.
Plague God Image in the Clinic1
Authors: Xu Jun
Published: March 2023

This paper selects four dreams before and during COVID‐19 which constellated the Plague God image in Chinese culture. The author argues that this shows evidence that the origins of the modern psyche, although hidden, are preserved and living within the ancient anima mundi.
Postoperative free water administration is associated with dysnatremia after congenital heart disease surgery in infants
Authors: Kronborg Jonas Rønne , Lindhardt Rasmus Bo , Vejlstrup Niels , Holst Line Marie , Juul Klaus , Smerup Morten Holdgaard , Gjedsted Jakob , Ravn Hanne Berg
Published: March 2023

Dysnatremia after congenital heart disease (CHD) surgery is common. European guidelines on intraoperative fluid therapy in children recommend isotonic solutions to avoid hyponatremia, but prolonged cardiopulmonary bypass and administration of high sodium‐containing solutions (i.e., blood products and sodium bicarbonate) are associated with postoperative hypernatremia. The aim of the study was to describe fluid composition prior to and during the development of postoperative dysnatremia. A retrospective observational, single‐center study including infants undergoing CHD surgery. Demographics and clinical characteristics were registered. Highest and lowest plasma sodium values were recorded and associations with perioperative fluid administration, blood products, crystalloids, and colloids were explored in relation to three perioperative periods. Postoperative dysnatremia occurred in nearly 50% of infants within 48 h after surgery. Hypernatremia was mainly associated with administration of blood products (median [IQR]: 50.5 [28.4–95.5] vs. 34.5 [18.5–61.1] mL/kg; p = 0.001), and lower free water load (1.6 [1.1–2.2] mL/kg/h; p = 0.01). Hyponatremia was associated with a higher free water load (2.3 [1.7–3.3] vs. 1.8 [1.4–2.5] mL/kg/h; p = 0.001) and positive fluid balance. On postoperative day 1, hyponatremia was associated with higher volumes of free water (2.0 [1.5–2.8] vs. 1.3 [1.1–1.8] mL/kg/h; p < 0.001) and human albumin, despite a larger diuresis and more negative daily fluid balance. Postoperative hyponatremia occurred in 30% of infants despite restrictive volumes of hypotonic maintenance fluid, whereas hypernatremia was mainly associated with blood product transfusion. Individualized fluid therapy, with continuous reassessment to reduce the occurrence of postoperative dysnatremia is mandatory in pediatric cardiac surgery. Prospective studies to evaluate fluid therapy in pediatric cardiac surgery patients are warranted.
Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm
Authors: Ibald‐Mulli Angela , Seufert Jochen , Grimsmann Julia M. , Laimer Markus , Bramlage Peter , Civet Alexandre , Blanchon Margot , Gosset Simon , Templier Alexandre , Paar W. Dieter , Zhou Fang Liz , Lanzinger Stefanie
Published: March 2023

Aim

To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm.

Materials and Methods

Data from adults and children with type 1 diabetes and more than two diabetes‐related visits were analysed from the Diabetes Prospective Follow‐up Registry. Q‐Finder, a supervised non‐parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk. DKA was defined as pH less than 7.3 during a hospitalization event.

Results

Data for 108 223 adults and children, of whom 5609 (5.2%) had DKA, were studied. Q‐Finder analysis identified 11 profiles associated with an increased risk of DKA: low body mass index standard deviation score; DKA at diagnosis; age 6‐10 years; age 11‐15 years; an HbA1c of 8.87% or higher (≥ 73 mmol/mol); no fast‐acting insulin intake; age younger than 15 years and not using a continuous glucose monitoring system; physician diagnosis of nephrotic kidney disease; severe hypoglycaemia; hypoglycaemic coma; and autoimmune thyroiditis. Risk of DKA increased with the number of risk profiles matching patients’ characteristics.

Conclusions

Q‐Finder confirmed common risk profiles identified by conventional statistical methods and allowed the generation of new profiles that may help predict patients with type 1 diabetes who are at a greater risk of experiencing DKA.
Test–retest reliability of electroencephalographic and magnetoencephalographic measures elicited during language tasks: A literature review
Authors: Cocquyt Elissa‐Marie , Van Laeken Heleen , van Mierlo Pieter , De Letter Miet
Published: March 2023

Electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings during language processing can provide relevant insights on neuroplasticity in clinical populations (including patients with aphasia). To use EEG and MEG in a longitudinal way, the outcome measures should be consistent across time in healthy individuals. Therefore, the current study provides a review on the test–retest reliability of EEG and MEG measures elicited during language paradigms in healthy adults. PubMed, Web of Science and Embase were searched for relevant articles based on specific eligibility criteria. In total, 11 articles were included in this literature review. The test–retest reliability of the P1, N1 and P2 is systematically considered to be satisfactory, whereas findings are more variable for event‐related potentials/fields occurring later in time. The within subject consistency of EEG and MEG measures during language processing can be influenced by multiple variables such as the stimulus presentation mode, the offline reference choice and the required amount of cognitive resources during the task. To conclude, most of the available results are favourable regarding the longitudinal use of EEG and MEG measures elicited during language paradigms in healthy young individuals. In view to the use of these techniques in patients with aphasia, future research should focus on whether the same findings apply to different age groups.
Human nature, history, and the limits of critique
Authors: Setiya Kieran
Published: March 2023

This essay defends a form of ethical naturalism in which ethical knowledge is explained by human nature. Human nature, here, is not the essence of the species but its natural history as socially and historically determined. The argument does not lead to social relativism, but it does place limits on the scope of ethical critique. As society becomes “total”, critique can only be immanent; to this extent, Adorno and the Frankfurt School are right.
MAEL facilitates metabolic reprogramming and breast cancer progression by promoting the degradation of citrate synthase and fumarate hydratase via chaperone‐mediated autophagy
Authors: Zhou Lin , Ou Shuobo , Liang Ting , Li Meiling , Xiao Pei , Cheng Jiaxin , Zhou Jianlin , Yuan Liqin
Published: March 2023

Metabolic reprogramming is a hallmark of cancer. Several studies have shown that inactivation of Krebs cycle enzymes, such as citrate synthase (CS) and fumarate hydratase (FH), facilitates aerobic glycolysis and cancer progression. MAEL has been shown to play an oncogenic role in bladder, liver, colon, and gastric cancers, but its role in breast cancer and metabolism is still unknown. Here, we demonstrated that MAEL promoted malignant behaviours and aerobic glycolysis in breast cancer cells. Mechanistically, MAEL interacted with CS/FH and HSAP8 via its MAEL domain and HMG domain, respectively, and then enhanced the binding affinity of CS/FH with HSPA8, facilitating the transport of CS/FH to the lysosome for degradation. MAEL‐induced degradation of CS and FH could be suppressed by the lysosome inhibitors leupeptin and NH4Cl, but not by the macroautophagy inhibitor 3‐MA or the proteasome inhibitor MG132. These results suggested that MAEL promoted the degradation of CS and FH via chaperone‐mediated autophagy (CMA). Further studies showed that the expression of MAEL was significantly and negatively correlated with CS and FH in breast cancer. Moreover, overexpression of CS or/and FH could reverse the oncogenic effects of MAEL. Taken together, MAEL promotes a metabolic shift from oxidative phosphorylation to glycolysis by inducing CMA‐dependent degradation of CS and FH, thereby promoting breast cancer progression. These findings have elucidated a novel molecular mechanism of MAEL in cancer.
Transcriptomic and proteomic studies suggest the establishment of advanced zonation‐like profiles in human‐induced pluripotent stem cell‐derived liver sinusoidal endothelial cells and carboxypeptidase M‐positive liver progenitor cells cocultured in a fluidic microenvironment
Authors: Danoy Mathieu , Poulain Stéphane , Jellali Rachid , Scheidecker Benedikt , Tauran Yannick , Leduc Marjorie , Bruce Johanna , Kim Soo Hyeon , Kido Taketomo , Miyajima Atsushi , Sakai Yasuyuki , Leclerc Eric
Published: March 2023

Aim

Hepatic zonation is a physiological feature of the liver, known to be key in the regulation of the metabolism of nutrients and xenobiotics and the biotransformation of numerous substances. However, the reproduction of this phenomenon remains challenging in vitro as only part of the processes involved in the orchestration and maintenance of zonation are fully understood. The recent advances in organ‐on‐chip technologies, which allow for the integration of multicellular 3D tissues in a dynamic microenvironment, could offer solutions for the reproduction of zonation within a single culture vessel.

Methods

An in‐depth analysis of zonation‐related mechanisms observed during the coculture of human‐induced pluripotent stem cell (hiPSC)‐derived carboxypeptidase M‐positive liver progenitor cells and hiPSC‐derived liver sinusoidal endothelial cells within a microfluidic biochip was carried out.

Results

Hepatic phenotypes were confirmed in terms of albumin secretion, glycogen storage, CYP450 activity, and expression of specific endothelial markers such as PECAM1, RAB5A, and CD109. Further characterization of the patterns observed in the comparison of the transcription factor motif activities, the transcriptomic signature, and the proteomic profile expressed at the inlet and the outlet of the microfluidic biochip confirmed the presence of zonation‐like phenomena within the biochips. In particular, differences related to Wnt/β‐catenin, transforming growth factor‐β, mammalian target of rapamycin, hypoxia‐inducible factor‐1, and AMP‐activated protein kinase signaling, to the metabolism of lipids, and cellular remolding were observed.

Conclusions

The present study shows the interest in combining cocultures of hiPSC‐derived cellular models and microfluidic technologies for reproducing in vitro complex mechanisms such as liver zonation and further incites the use of those solutions for accurate reproduction of in vivo situations.
Decisions about adopting novel COVID‐19 vaccines among White adults in a rural state, USA: A qualitative study
Authors: Kohut Mike , Scharnetzki Liz , Pajka Joseph , Jacobs Elizabeth A. , Fairfield Kathleen M.
Published: March 2023

Purpose

Many people, especially in rural areas of the United States, choose not to receive novel COVID‐19 vaccinations despite public health recommendations. Understanding how people describe decisions to get vaccinated or not may help to address hesitancy.

Methods

We conducted semistructured interviews with 17 rural inhabitants of Maine, a sparsely populated state in the northeastern US, about COVID‐19 vaccine decisions during the early rollout (March–May 2021). We used the framework method to compare responses, including between vaccine Adopters and Non‐adopters.

Findings

Adopters framed COVID‐19 as unequivocally dangerous, if not personally, then to other people. Describing their COVID concerns, Adopters emphasized disease morbidities. By contrast, Non‐adopters never mentioned morbidities, referencing instead mortality risk, which they perceived as minimal. Instead of risks associated with the disease, Non‐adopters emphasized risks associated with vaccination. Uncertainty about the vaccine development process, augmented by social media, bolstered concerns about the long‐term unknown risks of vaccines. Vaccine Adopters ultimately described trusting the process, while Non‐adopters expressed distrust.

Conclusion

Many respondents framed their COVID vaccination decision by comparing the risks between the disease and the vaccine. Associating morbidity risks with COVID‐19 diminishes the relevance of vaccine risks, whereas focusing on low perceived mortality risks heightens their relevance. Results could inform efforts to address COVID‐19 vaccine hesitancy in the rural US and elsewhere.

Patient or Public Contribution

Members of Maine rural communities were involved throughout the study. Leaders of community health groups provided feedback on the study design, were actively involved in recruitment, and reviewed findings after analysis. All data produced and used in this study were co‐constructed through the participation of community members with lived experience.
Talking Trials: An arts‐based exploration of attitudes to clinical trials amongst minority ethnic members of the South Riverside Community of Cardiff
Authors: Bridges Sarah , Lamont‐Robinson Catherine , Herbert Allan , Din Mashmooma , Smith Carl , Ahmed Nasra , Ali Arafa , Bandyopadhyay Sudipta , Bibi Saleema , Canu Rossana , Correia Mariama N. G. , Djalo Mamadu S. , Hayan Kense , Horne Alka , Mita Ayesha , Svobodova Martina
Published: March 2023

Introduction

Clinical trials must include diverse participants to ensure the wide applicability of results. However, people from ethnic minorities are included in clinical trials at rates lower than expected given their share of the population. Working with South Riverside Community Development Centre (SRCDC), Talking Trials used public engagement to foster discussions around the underrepresentation of those from minority ethnic communities in clinical trials and to identify and address concerns surrounding trial participation.

Methods

We conducted three workshops with 13 co‐researchers from minority ethnic backgrounds. We explored perceptions and understanding of clinical trials alongside participatory art activities to help move away from verbocentric methods of communication. These artworks formed an exhibition that was presented to the community, prompting further discussions and engagement.

Findings

Co‐production workshops were an effective tool to introduce the public to trial research. With little knowledge of clinical trials at the beginning of the process, our co‐researchers formed a cohesive group, sharing initial fears and mistrust towards trials. As conversations progressed these attitudes clearly shifted. Artwork produced during the workshops was incorporated into an exhibition. Quotes and creative pieces from the group were included to reflect the themes identified. Presenting the exhibition at Riverside Festival enabled further engagement with a wider diverse community. The focus on co‐production helped build a network of individuals new to research and keen to become involved further.

Conclusion

Inclusive and democratic co‐production, enriched by participatory art practices, provided a powerful means of enabling our group to create new insights and foster new relationships. Projects like Talking Trials can diversify the research process itself—for example, four co‐researchers have commenced lay research partner roles on trial management groups and a lay advisory group is in development.

Patient or Public Contribution

Three members of staff at SRCDC were on the project delivery group and involved in the initial project design, subsequently helping to connect us with members of the Riverside community to work as co‐researchers. Two of the SRCDC staff are co‐authors of this manuscript. The project had 13 public co‐researchers guiding the direction of this research and creating the artwork displayed in the art exhibition.