bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Macroevolutionary Signature of Asymmetric Inheritance at Speciation
Authors: Gaboriau Théo , Tobias Joseph A. , Silvestro Daniele , Salamin Nicolas 
Published: March 2023

AbstractPopular 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

ABSTRACTMammalian 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

AbstractIncreased 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 statementPeripheral 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

AbstractObjects 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

SummaryHypercapnia, 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

AbstractThere 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

AbstractThein 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

ABSTRACTThere 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

PurposeTransition 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/approachA 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.FindingsAfter 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/implicationsA 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 implicationsMental 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/valueThis 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

Abstract

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.
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

AbstractDysnatremia 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

AbstractAimTo identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm.Materials and MethodsData 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.ResultsData 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.ConclusionsQ‐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.