bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling Cell Shape in 3D Structured Environments: A Quantitative Comparison with Experiments
Authors: Link Rabea , Jaggy Mona , Bastmeyer Martin , Schwarz Ulrich S. 
Published: August 2023

AbstractCell shape plays a fundamental role in many biological processes, including migration, division and tissue morphogenesis, but it is not clear which shape model best predicts three-dimensional cell shape in structured environments. Here, we compare different modelling approaches with experimental data. 3D scaffolds for cell adhesion were manufactured using 3D laser nanoprinting and the shapes of single mesenchymal NIH/3T3 cells were compared by a Fourier method with surfaces that minimize area under the given adhesion and volume constraints. For the minimized surface model, we found marked differences to the experimentally observed cell shapes, which necessitated the use of more advanced shape models. We used different variants of the cellular Potts model, which effectively includes both surface and bulk contributions. The simulations revealed that the Hamiltonian with linear area energy outperformed the elastic area constraint in accurately modeling the 3D shapes of cells in structured environments. Explicit modeling the nucleus did not improve the accuracy of the simulated cell shapes. Overall, our work identifies effective methods for accurately modeling cellular shapes in complex environments, which in the future will enable the rational design of scaffolds for desired cell shapes.Author summaryCell shape and forces have emerged as important determinants of cell function and thus their prediction is essential to describe and control the behaviour of cells in complex environments. While there exist well-established models for the two-dimensional shape of cells on flat substrates, it is less clear how cell shape should be modeled in three dimensions. Different from the philosophy of the vertex model often used for epithelial sheets, we find that models based only on cortical tension as a constant geometrical surface tension are not sufficient to describe the shape of single cells in 3D. Therefore, we employ different variants of the cellular Potts model, where either a target area is prescribed by an elastic constraint or the area energy is described with a linear surface tension. By comparing the simulated shapes to experimental images of cells in 3D scaffolds manufactured with direct laser writing, we can identify parameters that accurately model the 3D cell shape.
Detection and characterization of a novel bat filovirus (Dehong virus, DEHV) in fruit bats
Authors: He Biao , Hu Tingsong , Yan Xiaomin , Zhang Fuqiang , Tu Changchun 
Published: August 2023

AbstractAlthough bats are natural hosts of most filoviruses (FiVs), with the pathogenic ones frequently causing deadly haemorrhagic fevers in Africa, the viruses are difficult to trace. Recently, multiple divergent FiVs have been uncovered in China, raising concerns about their threat to public health. Here we report the detection of bat-borne FiVs at the interface of orchards between bats and humans, eventually resulting in the discovery of a novel FiV, Dehong virus (DEHV), fromRousettus leschenaultii(R. leschenaultii) bats. DEHV has the largest genome, and the phylogeny places it between the generaDianlovirusandMarburgvirus, suggesting its classification as a prototype of a new genus within the familyFiloviridae. Our study emphasizes the importance of further understanding the distribution and potential risk of FiVs in the region.
The circadian clock is a pacemaker of the axonal regenerative ability
Authors: Virgiliis Francesco De , Mueller Franziska , Palmisano Ilaria , Chadwick Jessica S , Gutierrez Lucía Luengo , Giarrizzo Angela , Yan Yuyang , Danzi Matt Christopher , Muñoz Carmen Picón , Zhou Luming , Kong Guiping , Serger Elisabeth , Hutson Thomas Haynes , Maldonado ines , Song Yayue , Scheiermann Christoph , Brancaccio Marco , Giovanni Simone Di 
Published: August 2023

SummaryPeripheral nervous system injuries lead to long-term neurological disability due to limited axonal regenerative ability. Injury-dependent and -independent physiological mechanisms have provided important molecular insight into neuronal regeneration. However, whether common molecular denominators underpin both injury-dependent and independent biological processes remain unclear. Here, we performed a comparative analysis of recently generated transcriptomic datasets associated with the regenerative ability of sciatic dorsal root ganglia (DRG). Surprisingly, circadian rhythms were identified as a the most significantly enriched biological process associated with regenerative capability. We demonstrate that DRG neurons possess an endogenous circadian clock with a 24h oscillations of circadian genes and that their regenerative ability displays a diurnal oscillation in a mouse model of sciatic nerve injury. Consistently, transcriptomic analysis of DRG neurons showed a significant time-of-day dependent enrichment for processes associated with axonal regeneration, development and growth, as well as circadian associated genes, including the core clock genesBmal1andClock. Indeed, DRG-specific ablation of the non-redundant clock geneBmal1showed that it is required for regenerative gene expression, neuronal intrinsic circadian regeneration and target reinnervation. Lastly, lithium, a chrono-active compound, enhanced nerve regeneration, in wildtype but not inBmal1andCry1/2-deficient mice. Together, these data demonstrate that daily rhythms and the molecular clock fine-tune the regenerative response of DRG neurons, and that chrono-active drugs, such as lithium, are a novel potential approach to nerve repair.
Structure of the human outer kinetochore KMN network complex
Authors: Yatskevich Stanislau , Yang Jing , Bellini Dom , Zhang Ziguo , Barford David 
Published: August 2023

AbstractFaithful chromosome segregation requires robust, load-bearing attachments of chromosomes to the mitotic spindle, a function accomplished by large macromolecular complexes termed kinetochores. In most eukaryotes, the constitutive centromere-associated network (CCAN) complex of the inner kinetochore recruits to centromeres the ten-subunit outer kinetochore KMN network, which comprises the KNL1C, MIS12C and NDC80C complexes. The KMN network directly attaches CCAN to microtubules through MIS12C and NDC80C. Here, we determined a high-resolution cryo-EM structure of the human KMN network. This showed an intricate and extensive assembly of KMN subunits, with the central MIS12C forming rigid interfaces with NDC80C and KNL1C. The redundancy and strength of inter-subunit connections explains how KMN withstands strong forces applied during chromosome segregation. We also observed that unphosphorylated MIS12C exists in an auto-inhibited state that suppresses its capacity to interact with CCAN. Ser100 and Ser109 of the N-terminal segment of the MIS12C subunit Dsn1, two key targets of Aurora B kinase, directly stabilize this auto-inhibition. Our work provides a molecular mechanism for how selectively relieving this auto-inhibition through Ser100 and Ser109 phosphorylation would restrict outer kinetochore assembly to functional centromeres during cell division.
Effects of ageing and frailty on circulating monocyte and dendritic cell subsets
Authors: Reitsema Rosanne D. , Kumawat Ashok K. , Hesselink Bernd-Cornèl , van Baarle Debbie , van Sleen Yannick 
Published: August 2023

AbstractAgeing is associated with dysregulated immune responses, resulting in impaired resilience against infections and a low-grade inflammation known as inflammageing. Frailty is a measurable condition in older adults characterized by decreased health and physical impairment. Dendritic cells (DCs) and monocytes play a crucial role in initiating and steering immune responses. To assess whether their frequencies and phenotypes in the blood are affected by ageing or frailty, we performed a flow cytometry study (14 markers) on monocyte and DC subsets in an immune ageing cohort (SENEX).Participants were divided into three groups (n=15 each): healthy young controls (HYC, median age 29 years), healthy older controls (HOC, 73 years) and Frail older controls (76 years). Frailty status was based on Tilburg Frailty Index scores. Among HLA-DR+/CD19-cells, monocyte subsets (classical, intermediate, non-classical) were identified by CD14 and CD16 expression, and DC subsets (conventional (c)DC1, cDC2, plasmacytoid (p)DC) by CD11c, CD1c, CD141 and CD303 expression.Using unsupervised and conventional gating strategies, we observed a substantially lower proportion of pDCs in the HOC compared to the HYC. Additionally, we observed higher expression of activation markers on classical and intermediate monocytes and on cDC2 in HOC compared to HYC. Comparing the Frail to the age-matched HOC group, we observed only one important difference: a higher expression of CD40 on classical and non-classical monocytes in Frail individuals.In this cross-sectional study, we document a substantial effect of ageing on monocytes and DCs. The reduction of pDCs in older people may underly their impaired ability to counter viral infections, whereas the enhanced expression of activation markers could indicate a state of inflammageing. Future studies could elucidate the functional consequences of CD40 upregulation with frailty.
TOM20 Gates PINK1 Activity And Mediates Its Tethering Of The TOM And TIM23 Translocases Upon Mitochondrial Stress
Authors: Eldeeb Mohamed A. , Bayne Andrew N. , Fallahi Armaan , Goiran Thomas , MacDougall Emma J. , Soumbasis Andrea , Zorca Cornelia E. , Tabah Jace-Jones , Thomas Rhalena A. , Karpilovsky Nathan , Mathur Meghna , Durcan Thomas M. , Trempe Jean-François , Fon Edward A. 
Published: August 2023

ABSTRACTMutations in PTEN-induced putative kinase 1 (PINK1) cause autosomal recessive early onset Parkinson disease (PD). PINK1 is a Ser/Thr kinase that regulates mitochondrial quality control by triggering mitophagy mediated by the ubiquitin ligase Parkin. Upon mitochondrial damage, PINK1 accumulates on the outer mitochondrial membrane (OMM) forming a high molecular weight complex with the translocase of the outer membrane (TOM). PINK1 then phosphorylates ubiquitin, which enables recruitment and activation of Parkin followed by autophagic clearance of the damaged mitochondrion. Thus, Parkin-dependent mitophagy hinges on the stable accumulation of PINK1 on the TOM complex. Yet, the mechanism linking mitochondrial stressors to PINK1 accumulation and whether the translocases of the inner membrane (TIMs) are also involved, remain unclear. Herein, we demonstrate that mitochondrial stress induces the formation of a PINK1-TOM-TIM23 supercomplex in human cultured cell lines, dopamine neurons, and midbrain organoids. Moreover, we show that PINK1 is required to stably tether the TOM to TIM23 complexes in response to stress, such that the supercomplex fails to accumulate in cells lacking PINK1. This tethering is dependent on an interaction between the PINK1 NT-CTE module and the cytosolic domain of the Tom20 subunit of the TOM complex, the disruption of which, by either designer or PD-associated PINK1 mutations, inhibits downstream mitophagy. Together, the findings provide key insight into how PINK1 interfaces with the mitochondrial import machinery, with important implications for the mechanisms of mitochondrial quality control and PD pathogenesis.
Can Prediction Error Explain Predictability Effects on the N1 during Picture-Word Verification?
Authors: Taylor Jack E. , Rousselet Guillaume A. , Sereno Sara C. 
Published: August 2023

AbstractDo early effects of predictability in visual word recognition reflect prediction error? Electrophysiological research investigating word processing has demonstrated predictability effects in the N1, or first negative component of the event-related potential (ERP). However, findings regarding the magnitude of effects and potential interactions of predictability with lexical variables have been inconsistent. Moreover, past studies have typically used categorical designs with relatively small samples and relied on by-participant analyses. Nevertheless, reports have generally shown that predicted words elicit less negative-going (i.e., lower amplitude) N1s, a pattern consistent with a simple predictive coding account. In our preregistered study, we tested this account via the interaction between prediction magnitude and certainty. A picture-word verification paradigm was implemented in which pictures were followed by tightly matched picture-congruent or picture-incongruent written nouns. The predictability of target (picture-congruent) nouns was manipulated continuously based on norms of association between a picture and its name. ERPs from 68 participants revealed a pattern of effects opposite to that expected under a simple predictive coding framework.
SIN-3 transcriptional coregulator maintains mitochondrial homeostasis and polyamine flux
Authors: Giovannetti M. , Fabrizio P. , Nicolle O. , Bedet C. , Rodríguez-Palero MJ. , Michaux G. , Artal-Sanz M. , Witting M. , Palladino F 
Published: August 2023

AbstractMitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important becauseSIN3haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays an important role in tumor biology. Here we show that loss ofC. elegansSIN-3 results in transcriptional deregulation of mitochondrial- and nuclear encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function,sin-3mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) andin vivoimaging, and altered oxygen consumption. Metabolomic analysis ofsin-3mutant animals identifies a signature of mitochondria stress, and deregulation of methionine flux resulting in decreased S-adenosyl methionine (SAM), and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.
VmPFC supports persistence during goal pursuit through selective attention
Authors: Holton Eleanor , Grohn Jan , Ward Harry , Manohar Sanjay , O’Reilly Jill , Kolling Nils 
Published: August 2023

AbstractStriking the balance between persistence with a goal and flexibility in the face of better options is critical for effectively organizing behaviour across time. While people are often biased towards completing their current goal (e.g. ‘sunk cost’ biases), it is unclear how these biases occur at a mechanistic level, still allowing for some flexibility for goal abandonment. We propose that ventromedial prefrontal cortex (vmPFC) plays a critical role in orienting attention towards a current goal, prioritising goal completion but allowing for abandonment, particularly when the current goal fails. We developed a novel incremental goal pursuit task to study goal-directed attention and action in healthy individuals with functional magnetic resonance imaging (fMRI), and in an independent group of individuals with brain lesions. The task required participants to make sequential decisions between continuing to persist with a current goal (commitment), versus abandoning progress for a better alternative goal (flexibility). We show that individuals who persist more show greater goal-oriented attention outside the decision period. Increasing attentional capture by the current goal is also revealed in decision-making: people remain more likely to abandon from ‘frustration’ (collapse of value of the current goal) than from ‘temptation’ (attraction from valuable alternative goals). Strikingly, we find that our stable inter-individual metrics of persistence and goal-oriented attention were both predicted by baseline activity in vmPFC, tracking goal progress. We present converging evidence from an independent lesion patient study demonstrating the causal involvement of vmPFC in goal persistence: damage to the vmPFC reduces biases to over-persist with the current goal, leading to a performance benefit in our task.
Stress response of fire salamander larvae differs between habitat types
Authors: Schulte Laura , Oswald Pia , Mühlenhaupt Max , Ossendorf Edith , Kruse Sabine , Kaiser Sylvia , Caspers Barbara A. 
Published: August 2023

AbstractDifferent habitats can impose varying selection pressures on individuals of the same species. Larvae of the European fire salamander (Salamandra salamandra) can inhabit two different habitats: streams and ponds. Streams are characterised by lower predation risk and intraspecific density and higher food availability than ponds. Thus, ponds are considered a less suitable habitat. To investigate the differential impacts of the two habitats on larval physiology, we measured the stress response of larvae living in the two different habitats. After successfully validating the measure of water-borne corticosterone (CORT) concentrations in fire salamander larvae, we measured the baseline and stress-induced CORT of 64 larvae from two pond and two stream locations in the field. We found larvae in ponds to be more stressed than larvae in streams. Additionally, we performed a reciprocal transplant experiment and tested whether larvae can adapt their stress response to changing habitat conditions. After two weeks of transfer, we did not find an increase in CORT when comparing stress-induced CORT values with baseline CORT values in larvae transferred into ponds. However, larvae transferred into streams exhibited an increase in the stress-induced CORT response. Moreover, transfer into ponds as well as larvae originating from ponds showed reduced growth rates, indicating that ponds might be the more stressful habitat, as it negatively affected larval physiology. These results show that noninvasive hormone measurements can provide information on habitat quality and potential adaptation and thus emphasis the potential for its use in conservation efforts.
Transcriptional pathways across colony biofilm models in the symbiontVibrio fischeri
Authors: Griend Jacob A. Vander , Isenberg Ruth Y. , Kotla Ketan R. , Mandel Mark J. 
Published: August 2023

ABSTRACTBeneficial microbial symbionts that are horizontally acquired by their animal hosts undergo a lifestyle transition from free-living in the environment to associated with host tissues. In the model symbiosis between the Hawaiian bobtail squid and its microbial symbiontVibrio fischeri,one mechanism used to make this transition during host colonization is the formation of biofilm-like aggregates in host mucosa. Previous work identified factors that are sufficient to induceV. fischeribiofilm formation, yet much remains unknown regarding the breadth of target genes induced by these factors. Here, we probed two widely-usedin vitromodels of biofilm formation to identify novel regulatory pathways in the squid symbiontV. fischeriES114. We discovered a shared set of 232 genes that demonstrated similar patterns in expression in both models. These genes comprise multiple exopolysaccharide loci that are upregulated and flagellar motility genes that are downregulated, with a consistent decrease in measured swimming motility.Furthermore, we identified genes regulated downstream of the key sensor kinase RscS that are induced independent of the response regulator SypG. Our data suggest that putative response regulator VpsR plays a strong role in expression of at least a subset of these genes. Overall, this study adds to our understanding of the genes involved inV. fischeribiofilm regulation, while revealing new regulatory pathways branching from previously characterized signaling networks.IMPORTANCETheV. fischeri-squid system provides an opportunity to study biofilm development both in the animal host and in culture-based biofilm models that capture key aspects ofin vivosignaling. In this work, we report the results of the transcriptomic profiling of twoV. fischeribiofilm models followed by phenotypic validation and examination of novel signaling pathway architecture. Remarkable consistency between the models provides a strong basis for future studies using either–or both–approaches. A subset of the factors identified by the approaches were validated in the work, and the body of transcriptomic data provides a number of leads for future studies in culture and during animal colonization.
The two plant-specific DREAM components FLIC and FLAC repress floral transition inArabidopsis
Authors: Lang Lucas , Böwer Franziska , Elbaşı Hasibe Tunçay , Eeckhout Dominique , Marschlich Nick , de Jaeger Geert , Heese Maren , Schnittger Arp 
Published: August 2023

AbstractThe DREAM complex is a key transcriptional regulator especially involved in the control of the cell cycle and development. Here, we characterise two novel plant- specific DREAM components, FLIC and FLAC, which we identified through tandem affinity purification experiments as interactors of conserved core DREAM constituents. We demonstrate that plants lacking both FLIC and FLAC exhibit pleiotropic phenotypes, including stunted growth and reduced fertility. Notably,flic flacdouble mutants show an early-flowering phenotype, an aspect that we found to be shared with mutants of the core DREAM component LIN37, with which FLIC and FLAC interact in binary protein-protein interaction assays. Performing reverse affinity purification experiments, we detected the JMJ14/NAC050/NAC052 module, known for its involvement in flowering repression, in the interactome of both FLIC and FLAC. Subsequent binary interaction studies then link the JMJ14/NAC050/NAC052 module via LIN37 to the DREAM complex providing a mechanistic framework on how flowering time could be transcriptionally controlled by the DREAM complex.Summary blurbThis study identifies two plant-specific members of the DREAM complex, explores their roles by mutant analysis and protein interaction investigation, and links them and additional DREAM complex components to the regulation of floral transition.