bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epac activation reduces trans-endothelial migration of undifferentiated neuroblastoma cells and cellular differentiation with a CDK inhibitor further enhances Epac effect
Authors: Inuwa Rabiu , Moss Diana , Quayle John , Swadi Rasha 
Published: May 2024

AbstractNeuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessedin vitroin a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients.
Differences between barley and maize revealed in limitations of photosystems I and II under high temperature and low air humidity
Authors: Lysenko Eugene A. 
Published: May 2024

AbstractNon-photochemical quenching and limitations of the photosystem I and photosystem II activities were studied in C3-plant barley and C4-plant maize. Plants were undergone to prolonged heat stress under high and low air humidity. Both species decreased non-photochemical quenching under tolerated heat stress (37-42°C), while increased it under nearly lethal heat stress (46°C). Usually, limitation at the acceptor side of the photosystem I was minor, while at 46°C it appeared major limiting factor. A similar decrease of photosystem II activity at 46°C by lower air humidity was achieved through different mechanisms. In barley, photosystem II downregulated by the increase of non-photochemical quenching. In maize, photosystem II downregulated by the increase of limitation at the acceptor side. Analysis of transients also revealed differences between species. One second after a light induction, limitations flashes at the acceptor sides of both photosystems. Elevating temperature reduced the size of these flashes; acceptor-side limitations of both photosystems decreased proportional to each other. In maize, the decrease was simple: the size of flashes slightly decreased at 37°C and more reduced at 42-46°C. In barley, the decrease had complex pattern: the size of flashes greatly reduced at 37°C and gradually returned to the control level under the higher temperatures. Around the photosystem II, the flash was quenched by a later burst of non-photochemical quenching. In barley, the transient peaks of acceptor-side limitation and non-photochemical quenching were very similar at any temperature. This was not observed in maize. The ratios between limitations qC/Y(NA) and qC/Y(ND) were studied.HighlightsLight 1s induces instant limitations at acceptor-sides of PSII (qC) and PSI (Y(NA))Temperature reduced these flashes of qC and Y(NA) proportional to each otherThe pattern of reduction was different in barley and maizeFlash of qC was quenched by proportional flash of qN in barley but not in maizeStationary PSII activity was decreased by different mechanisms in barley and maize
State diagrams of type I collagen for the rational design of biomimetic materials
Authors: Martinier Isabelle , Deville Sylvain , Mosser Gervaise , Trichet Léa , Davidson Patrick , Fernandes Francisco M. 
Published: May 2024

AbstractIdeally, designing tissue engineering grafts and 3D cell culture materials should rely on mimicking the architecture and composition of the extracellular matrix, which is predominantly comprised of type I collagen. However, while collagen molecules are assembled into fibrils by cells in vivo, well-organized fibrils rarely form spontaneously in vitro. Indeed, the physico-chemical conditions for fibrillogenesis are still poorly understood and their influence on the formation and properties of fibrillar biomimetic materials remains elusive. Here, we establish state diagrams for type I collagen over an unprecedented range of concentration and temperature, showing the collagen denaturation limits, the emergence of fibrils in acidic conditions, and a new regime of collagen molecule/fibril coexistence. We also show how the state diagrams can be used to understand the formation of biomimetic materials by classical methods, as illustrated here by collagen freeze-casting. Therefore, these state diagrams will help to optimize the production of collagen-based biomimetic materials.
Clearance of DNA damage-arrested RNAPII is selectively impaired in Cockayne syndrome cells
Authors: van der Meer Paula J. , Yakoub George , Nakazawa Yuka , Ogi Tomoo , Luijsterburg Martijn S. 
Published: May 2024

AbstractArrest of elongating RNA polymerase II (RNAPII) at DNA lesions initiates transcription-coupled repair (TCR), involving the concerted action of specific TCR factors, followed by downstream nucleotide excision repair steps. Remarkedly, only congenital defects in the CSA or CSB genes cause the neurodegenerative disorder Cockayne syndrome, which is not observed with other TCR genes, despite their equal importance in TCR. An explanation for this discrepancy has been lacking. In this study, we developed an assay to track the fate of elongating RNAPII at sites of UV-induced DNA lesions. Employing this method on an isogenic collection of TCR knockout cells reveals a selective RNAPII clearance defect in cells defective in CSA or CSB, in contrast to knockouts of other TCR genes. Our findings provide evidence that a deficiency in RNAPII processing and prolonged transcription arrests in response to DNA damage, rather than compromised DNA repair, may underlie the Cockayne syndrome-like neurodegenerative phenotype.
Tagless LysoIP method for molecular profiling of lysosomal content in clinical samples
Authors: Saarela Daniel , Lis Pawel , Gomes Sara , Nirujogi Raja S. , Dong Wentao , Rawat Eshaan , Glendinning Sophie , Zeneviciute Karolina , Bagnoli Enrico , Fasimoye Rotimi , Lin Cindy , Nyame Kwamina , Boros Fanni A. , Zunke Friederike , Lamoliatte Frederic , Elshani Sadik , Jaconelli Matthew , Jans Judith J. M. , Huisman Margriet A. , Posern Christian , Westermann Lena M. , Schulz Angela , van Hasselt Peter M. , Alessi Dario R. , Abu-Remaileh Monther , Sammler Esther M. 
Published: May 2024

AbstractLysosomes are implicated in a wide spectrum of human diseases including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models allowed major discoveries in the field, however studying lysosomal dysfunction in human patients remains challenging. Here, we report the development of the “tagless LysoIP method” to enable rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.g. induced Pluripotent Stem Cell (iPSCs) derived neurons). Isolated lysosomes are intact and suitable for subsequent multimodal omics analyses. To validate our approach, we employed the tagless LysoIP to enrich lysosomes from peripheral blood mononuclear cells (PBMCs) derived from fresh blood from patients with CLN3 disease, a neurodegenerative LSD. Metabolic profiling of isolated lysosomes showed massive accumulation of glycerophosphodiesters (GPDs) in patients’ lysosomes. Interestingly, a patient with a milder phenotype and genotype displayed lower accumulation of lysosomal GPDs, consistent with their potential role as disease biomarkers. Altogether, the tagless LysoIP provides a framework to study native lysosomes from patient samples, identify novel biomarkers and discover human-relevant disease mechanisms.
Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration
Authors: Alper Samuel R. , Vasudevan Deeptha , Wheeler Maya K. , Panahi Samin , Dorsky Richard I. 
Published: May 2024

ABSTRACTBackgroundIn humans and other mammals, spinal cord injury (SCI) can lead to a permanent loss of sensory and motor function, due to the inability of damaged neurons and axons to regenerate. However, other vertebrate species including zebrafish exhibit complete spinal cord regeneration and functional recovery after SCI. Wnt signaling is required for neurogenesis and axon regrowth in a larval zebrafish SCI model, but the genes regulated by this pathway and the cell types that express them remain largely unknown.ResultsIn this study, we used bulk RNA-sequencing (RNAseq) to identify candidate genes regulated by Wnt signaling that are expressed after SCI. Using this unbiased screen, we identified multiple genes previously unassociated with SCI in larval zebrafish, and confirmed by in situ hybridization that their expression is injury-responsive, Wnt-dependent, and localized to fibroblast-like cells surrounding the spinal cord.ConclusionsTogether, our data reveal potential novel gene targets and cell populations that may play important roles in spinal cord regeneration.
The chlamydial transcriptional regulator Euo is a key switch in cell form developmental progression but is not involved in the committed step to the formation of the infectious form
Authors: Appa Cody R. , Grieshaber Nicole A. , Yang Hong , Omsland Anders , McCormick Sean , Chiarelli Travis J. , Grieshaber Scott S. 
Published: May 2024

AbstractBacteria in the genusChlamydiaare a significant health burden world wide. They infect a wide range of vertebrate animals including humans and domesticated animals. In humans,C. psittacican cause zoonotic pneumonia whileC. pneumoniaecauses a variety of respiratory infections. Infections withC. trachomatiscause ocular or genital infections. All chlamydial species are obligate intracellular parasites of eukaryotic cells and are dependent on a complex infection cycle that depends on transitions between specific cell forms. This cycle consists of cell forms specialized for host cell invasion, the Elementary Body (EB), and a form specialized for intracellular replication, the Reticulate Body (RB). In addition to the EB and RB there is a transitionary cell form that mediates the transformation between the RB and the EB, the Intermediate Body (IB). In this study we ectopically expressed the regulatory protein Euo and showed that high levels of expression resulted in reversible arrest of the development cycle. The arrested chlamydial cells were trapped phenotypically at an early IB stage of the cycle. These cells had exited the cell cycle but had not shifted gene expression from RB-like to IB/EB-like. This arrested state was dependent on continued expression of Euo. When ectopic expression was reversed, Euo levels dropped in the arrested cells which led to the repression of native Euo expression and the resumption of the developmental cycle. Our data are consistent with a model where Euo expression levels impact IB maturation to the infectious EB but not the production of the IB form.ImportanceBacterial species in the Chlamydiales order infect a variety of vertebrate animals and are a global health concern. They cause various diseases in humans, including genitital and respiratory infections. The bacteria are obligate intracellular parasites that rely on a complex infectious cycle involving multiple cell forms. All species share the same life cycle, transitioning through different states to form the infectious elementary body (EB) to spread infections to new hosts. The Euo gene, encoding a DNA binding protein, is involved in regulating this cycle. This study showed that ectopic expression of Euo halted the cycle at an early stage. This arrest depended on continued Euo expression. When Euo expression was reversed, the developmental cycle resumed. Additionally, this study suggests that high levels of Euo expression affects the formation of the infectious EB, but not the production of the cell form committed to EB formation.
Mapping the Cerebrovascular Abnormality in Transgenic Alzheimer’s Disease (AD) Mice with deep-learning-based super-resolution cerebral blood volume (CBV)-MRI
Authors: Zhou Xiaoqing Alice , Liu Xiaochen , Li Hongwei Bran , Hike David , Jiang Yuanyuan , Rosen Matthew S. , Iglesias Juan Eugenio , Yu Xin 
Published: May 2024

AbstractTo measure the brain-wide vascular density (VD) alteration in degenerated brains with Alzheimer’s Disease (AD), deep learning-based super-resolution approach was developed to assist the segmentation of micro-vessels from the Monocrystalline Iron Oxide Nanoparticle (MION)-based CBV MRI images of transgenic mouse brains. Iron-induced T2* amplification effect well separated micro-vessels with tens of microns from capillary-enriched parenchyma voxels, enabling vascular compartment-specific VD differential analysis between AD and wildtype control mice. The differential maps based on segmented micro-vessels identified decreased VD in the anterior cingulate cortex (ACC) and medial entorhinal cortex (mEC) and increased VD in several highlighted brain regions, including dentate gyrus (DG) of the hippocampus, central and geniculate thalamus, medial septal area (MS), ventral tegmental area (VTA), and lateral entorhinal cortex (lEC). In contrast, the T2*-weighted capillary density mapping from parenchyma voxels showed increased VD in several cortical regions, including somatosensory and visual cortex, retrosplenial cortex, as well as piriform area and lEC in AD brains. However, dramatic capillary VD decrease was observed in the subcortical areas including hippocampus, thalamus, hypothalamus, and pontine areas. These high-resolution MION-based CBV MRI elucidates altered vascular compartments in degenerated AD brains, reconciling the various region-specific vascular impairment and angiogenesis in functional areas critical for cognitive decline of AD.
Bursts from the past: Intrinsic properties link a network model to zebra finch song
Authors: Medina Nelson D. , Margoliash Daniel 
Published: May 2024

AbstractNeuronal intrinsic excitability is a mechanism implicated in learning and memory that is distinct from synaptic plasticity. Prior work in songbirds established that intrinsic properties (IPs) of premotor basal-ganglia-projecting neurons (HVCX) relate to learned song. Here we find that temporal song structure is related to specific HVCXIPs: HVCXfrom birds who sang longer songs including longer invariant vocalizations (harmonic stacks) had IPs that reflected increased post-inhibitory rebound. This suggests a rebound excitation mechanism underlying the ability of HVCXneurons to integrate over long periods of time and represent sequence information. To explore this, we constructed a network model of realistic neurons showing how in-vivo HVC bursting properties link rebound excitation to network structure and behavior. These results demonstrate an explicit link between neuronal IPs and learned behavior. We propose that sequential behaviors exhibiting temporal regularity require IPs to be included in realistic network-level descriptions.
Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids
Authors: Scuderi Soraya , Kang Tae-Yun , Jourdon Alexandre , Yang Liang , Wu Feinan , Nelson Alex , Anderson George M. , Mariani Jessica , Sarangi Vivekananda , Abyzov Alexej , Levchenko Andre , Vaccarino Flora M. 
Published: May 2024

SummaryThe repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain. Morphogens crosstalk translated into early patterns of gene expression programs predicting the generation of specific brain lineages. Human iPSC lines from six different genetic backgrounds showed substantial differences in response to morphogens, suggesting that interindividual genomic and epigenomic variations could impact brain lineages formation. Morphogen gradients promise to be a key approach to model the brain in its entirety.
KAT3 mutations impair neural crest migration through EMT regulatorssnai1b andsnai2in Rubinstein Taybi Syndrome
Authors: Verma Shweta , Dalabehera Sujit , Gowda Subhash , Chandrasekaran Koushika , Singh Dayanidhi , Prasher Bhavana , Bapat Sharmila , Ramalingam Sivaprakash , Sachidanandan Chetana 
Published: May 2024

AbstractRubinstein Taybi syndrome, a rare congenital disease is caused by mutation in KAT3 genes,EP300andCREBBP. A subset of tissues affected in RSTS have their origin in neural crest cells, prompting our exploration into the role of KAT3 in neural crest development. Our zebrafish RSTS models generated by knocking down or mutatingep300aandcbpagenes, reveal defects in neural crest migration and its derived tissues when KAT3 genes are perturbed. We also demonstrate that the effects on neural crest can be reversed by HDAC inhibition in in morphant embryos. KAT3 knockdown causes downregulation of EMT regulators,snai1bandsnai2. Snai2 is known to represscdh6bin neural crest cells facilitating their delamination from neural tube and migration. We generated RSTS patient-derived iPSC line and differentiated them into neural crest cells in vitro. We show that role of KAT3 proteins in neural crest migration is conserved in human iPSC derived neural crest cells. Our findings make a case for classifying RSTS as a neurocristopathy.HighlightsPerturbation of KAT3 gene expression in zebrafish recapitulates the Rubinstein Taybi patient defectsThe zebrafish model of Rubinstein Taybi model reveals defects in neural crest cell migrationKAT3 proteins regulatesnai2, snai1band cdh6, genes important for neural crest migrationThe neural crest migration defects in the zebrafish model can be partially rescued by modulating the global acetylation levelsStudy of RSTS patient-derived neural crest cells reveals that the role of KAT3 in neural crest migration is conserved across vertebratesGraphical Abstract
Wall modes and the transition to bulk convection in rotating Rayleigh-Bénard convection
Authors: Zhang Xuan , Reiter Philipp , Shishkina Olga , Ecke Robert E. 
Published: May 2024

We investigate states of rapidly rotating Rayleigh-Bénard convection in a cylindrical cell over a range of Rayleigh numbers 3×105≤Ra≤5×109 and Ekman numbers 10−6≤Ek≤10−4 for Prandtl number Pr=0.8 and aspect ratios 1/5≤Γ≤5 using direct numerical simulations. We characterize, for perfectly insulating sidewall boundary conditions, the first transition to convection via wall mode instability and the nonlinear growth and instability of the resulting wall mode states, including a secondary transition to time dependence. We show how the radial structure of the vertical velocity uz and the temperature T is captured well by the linear eigenfunctions of the wall mode instability where the radial width of uz is δuz∼Ek1/3r/H whereas δT∼e−kr (k is the wave number of a laterally infinite wall mode state). The disparity in spatial scales for Ek=10−6 means that the heat transport is dominated by the radial structure of uz since T varies slowly over the radial scale δuz. We further describe how the transition to a state of bulk convection is influenced by the presence of the wall mode states. We use temporal and spatial scales as measures of the local state of convection and the Nusselt number Nu as representative of global transport. Our results elucidate the evolution of the wall state of rotating convection and confirm that wall modes are strongly linked with the boundary zonal flow being the robust remnant of nonlinear wall mode states. We also show how the heat transport (Nu) contributions of wall modes and bulk modes are related and discuss approaches to disentangling their relative contributions.

Published by the American Physical Society
2024
Ethical leadership in the Netherlands: testing the broader conceptualization and measurement scale
Authors: Shakeel Fahad , Kruyen Peter Mathieu , Van Thiel Sandra 
Published: May 2024

PurposeThis paper aims to validate a broader conceptualization of ethical leadership and a matching measurement scale (BELS) using survey data from 909 public servants in leadership positions in the Netherlands.Design/methodology/approachThe confirmatory factor analysis (CFA) (using AMOS) and exploratory factor analysis were carried out with repeated CFA. A social desirability scale was used to check for model fitness.FindingsOur findings support the notion that ethical leadership is broader in conceptualization and hence reject the theories that limit the role of ethical leaders within the confines of organizations. This study confirms that attributes like sustainability, leadership learning, ethical competency, diversity and resilience are part of ethical leadership. Such characteristics could not be measured with previous scales for ethical leadership. Also, ethical leadership is not separate from associated leadership styles.Research limitations/implicationsA self-assessment scale for leaders was used for this study. Although there is no indication of social desirability bias, future research can also focus on follower assessments of their leaders. This study only focuses on the public sector context only.Practical implicationsOur results suggest that ethical leadership contains more subvalues than in the seminal definition. This study has, therefore, corroborated a broader definition of ethical leadership.Originality/valueThis study indicates the need for ethical leadership to be studied and assessed using a broader conceptualization and measurement scale.