bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1
Authors: Dwivedi Devashish , Harry Daniela , Meraldi Patrick 
Published: September 2022

AbstractA tight synchrony between the DNA and centrosome cycle is essential for genomic integrity. Centriole disengagement, which licenses centrosomes for duplication, occurs normally during mitotic exit. We recently demonstrated that mild DNA replication stress in untransformed human cells causes premature centriole disengagement at mitotic entry, leading to transient multipolar spindles that favour chromosome mis-segregation. How mild replication stress accelerate the centrosome cycle at the molecular level remained, however, unclear. Using expansion microscopy, we show that mild replication stress already induces premature centriole disengagement in G2 via the ATR-Chk1 axis of the DNA damage repair pathway. We demonstrate that this results in a subcritical Plk1 kinase activity that is insufficient for rapid mitotic entry. Nevertheless, it primes the pericentriolar matrix for Separase-dependent disassembly causing premature centriole disengagement in G2. We postulate that the differential requirement of Plk1 activity in the DNA and centrosome cycles explains how mild replication stress disrupts the synchrony between both processes and contributes to genomic instability.
YAP1 is essential for self-organized differentiation of pluripotent stem cells
Authors: Zeevaert Kira , Goetzke Roman , Elsafi Mabrouk Mohamed H. , Schmidt Marco , Maaßen Catharina , Henneke Ann-Christine , He Chao , Gillner Arnold , Zenke Martin , Wagner Wolfgang 
Published: September 2022

AbstractThe Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway and essential mechanotransducer. It has been suggested to play a crucial role for early embryo development, but the relevance for early germ layer commitment of human induced pluripotent stem cells (iPSCs) remains largely unclear. To gain better insight into the function of YAP1 in these early cell-fate decisions, we generated iPSC lines with YAP1 knockout (YAP-/-) with CRISPR/Cas9 technology and analyzed transcriptomic and epigenetic modifications. In YAP-/- iPSCs the expression of several YAP1 targets changed and NODAL, which is an important regulator of cell differentiation, was upregulated. Furthermore, YAP1 deficiency evoked global DNA methylation changes. Directed differentiation of adherent iPSC colonies toward endoderm, mesoderm, and ectoderm could be induced, albeit endodermal and ectodermal differentiation showed transcriptomic and epigenetic changes in YAP-/- lines. Notably, in self-organized embryoid bodies (EBs) germ layer specification was clearly impaired. This phenotype was rescued via lentiviral overexpression of YAP1 and in tendency also by NODAL inhibitors. Our results demonstrate that YAP1 plays an important role during early germ layer specification of iPSCs, particularly for the non-directed self-organization of EBs, and this is at least partly attributed to activation of the NODAL pathway.
Cellular Factors Involved in Transcriptome Dynamics in Early Zebrafish Embryogenesis
Authors: Rauwerda Han , Pagano Johanna F.B. , de Leeuw Wim C. , Ensink Wim , van Olst Marina , Nehrdich Ulrike , Jonker Martijs J. , Spaink Herman P. , Breit Timo M. 
Published: September 2022

AbstractAt gastrulation in the zebrafish embryogenesis, the embryonic genome is switched on to produce transcripts that are used for the maintenance and development of the embryo. In a previous study from late blastula to mid gastrula on the transcriptomes of 179 individual embryos, we capture the transcriptome dynamics via ten gene-expression types. Here we study the factors that regulate these transcriptome dynamics by in extensive silico analyses and two small-RNA sequencing experiments. We analyzed mechanisms that would make it possible for the embryo to achieve the tight regulation of gene expression that was observed, not only during development, but also when individual embryos were compared. We found that many of the gene-expression regulatory factors that are available to the embryo are operational in the different gene-expression types and act concurrently with not one mechanism prevailing in this developmental phase. We also saw that at least one of the regulatory mechanisms, the expression of members of the miRNA-430 family again is very tightly regulated, both during development as well as when miRNA expression from individual embryos is compared.
The BeMoBIL Pipeline for automated analyses of multimodal mobile brain and body imaging data
Authors: Klug M. , Jeung S. , Wunderlich A. , Gehrke L. , Protzak J. , Djebbara Z. , Argubi-Wollesen A. , Wollesen B. , Gramann K. 
Published: September 2022

AbstractAdvancements in hardware technology and analysis methods allow more and more mobility in electroencephalography (EEG) experiments. Mobile Brain/Body Imaging (MoBI) studies may record various types of data such as motion or eye tracking in addition to neural activity. Although there are options available to analyze EEG data in a standardized way, they do not fully cover complex multimodal data from mobile experiments. We thus propose the BeMoBIL Pipeline, an easy-to-use pipeline in MATLAB that supports the time-synchronized handling of multimodal data. It is based on EEGLAB and fieldtrip and consists of automated functions for EEG preprocessing and subsequent source separation. It also provides functions for motion data processing and extraction of event markers from different data modalities, including the extraction of eye-movement and gait-related events from EEG using independent component analysis. The pipeline introduces a new robust method for region-of-interest-based group-level clustering of independent EEG components. Finally, the BeMoBIL Pipeline provides analytical visualizations at various processing steps, keeping the analysis transparent and allowing for quality checks of the resulting outcomes. All parameters and steps are documented within the data structure and can be fully replicated using the same scripts. This pipeline makes the processing and analysis of (mobile) EEG and body data more reliable and independent of the prior experience of the individual researchers, thus facilitating the use of EEG in general and MoBI in particular. It is an open-source project available for download at https://github.com/BeMoBIL/bemobil-pipeline which allows for community-driven adaptations in the future.
Atmospheric nitrogen fixation by eukaryotes: Should we reconsider the nitrogen cycle in nature?
Authors: Arapitsas Nikolaos , Christakis Christos A. , Angelakis George , Maragkoudakis Aristeidis , Kotzabasis Kiriakos , Sarris Panagiotis F. 
Published: September 2022

AbstractNitrogen is the most abundant element in our planet’s atmosphere. Approximately 78% of the atmosphere is made up of nitrogen gas (N2). It is essential for organisms, as a major component of biomolecules and cellular biochemistry. Until today, atmospheric N2 assimilation in eukaryotic organisms has been reported to occur only through specific symbiotic N2-fixing bacterial groups that make it available to plants, the base of the food chain.In this work, using Gas Chromatography with Thermal Conductivity Detection, we proved the direct consumption of atmospheric N2 by eukaryotic organisms. Three yeast species: Debaryomyces hansenii, Metschnikowia reukaufii and model-species Saccharomyces cerevisiae are able to directly assimilate atmospheric nitrogen in various conditions, with a yet unknown mechanisms that are not based on the presence of known N2-fixation enzymes. Our findings could change the way we consider the N2-assimilation in nature, laying the basis for future focused studies on the molecular mechanism underling the biological phenomenon of eukaryotic N2-assimilation.
The paradoxical relationship between CRISPR-Cas and phage susceptibility in Pseudomonas aeruginosa
Authors: Lood Cédric , Verkinderen Emma , Fabijan Aleksandra Petrovic , Iredell Jonathan R. , Ceyssens Pieter-Jan , Lavigne Rob , van Noort Vera 
Published: September 2022

AbstractCRISPR-Cas systems are part of the pan-immune system of Pseudomonas aeruginosa and have been shown to limit horizontal gene transfers in that species. Indeed, isolates equipped with these systems tend to have smaller genomes and CRISPR spacers targeting integrative conjugative elements, phages, and plasmids. In this work, we investigate the genomic effects and phenotypic consequences of CRISPR-Cas systems in P. aeruginosa. First, we establish that the population structure is a confounding factor of the relation between genome sizes and the presence of CRISPR-Cas systems in P. aeruginosa as isolates from group II are, on average, 200 kbp larger than those from group I, and have a lower likelihood of possessing CRISPR-Cas systems. Second, we show that the impact on the genome size of CRISPR deactivation by anti-CRISPR proteins differs between the various CRISPR-Cas types found in this species (I-C, I-E, and I-F). Finally, we highlight a paradoxical, positive correlation between the presence of CRISPR-Cas systems and the chances of the host being infected by a set of distinct, strictly virulent Pseudomonas phages. We propose that this increased phage susceptibility in the presence of CRISPR-Cas is linked to a depletion of other accessory defense system genes in isolates with CRISPR-Cas systems.Note: This manuscript was published as a chapter in the doctoral dissertation of Cédric Lood [72]
Concomitant Vascular Calsequestrin 2 overexpression and leukocytes transmigration in a rat model of skeletal muscle traumatic inflammatory injury
Authors: Khalaf Noureddine Ben , Al-Mehatab Dalal , Fathallah Dahmani M. 
Published: September 2022

AbstractThe network of molecular mediators involved in the transmigration of leukocytes to inflamed tissues has been expanding with the identification of new molecules involved in the inflammatory response. We have previously shown using a rat model that Protein Disulfide Isomerase PDIA4 (ERP72) is involved in the inflammatory response to skeletal muscle traumatic injury. In this paper, we report observations suggesting that calsequestrin 2 (CASQ2), another member of the thioredoxin/PDI family, might contribute to the inflammatory response that leads to adhesion and transmigration of leukocytes into injured skeletal muscle. Indeed, real time PCR assay showed that the expression level CASQ2 is significantly enhanced [p<0.01] in the mechanically injured muscle. Immunohistological and immunofluorescence analysis showed that CASQ2 but not CASQ1 is expressed in the vessels present in the muscle-injured area. In addition, CASQ2 overexpression and PMN transmigration to the inflamed muscle injury are concomitant. This overexpression occurs most likely in the smooth muscle of the inflamed vessel. These observations together with the known Ca2+ buffering role of CASQ2 suggest that the protein contributes to the inflammatory process by providing the Ca2+ needed to activate the inflammasome and the leukocytes adhesion molecules which enhances transmigration of inflammatory cells into the injured muscle.
RACK1 may participate in placental development via regulating proliferation and migration of trophoblast cell in pigs following intrauterine growth restriction
Authors: Wu Zhimin , Hu Guangling , Gong Ting , Hu Qun , Hong Linjun , Zhang Yiyu , Ao Zheng 
Published: September 2022

AbstractIntrauterine growth restriction (IUGR) is a severe complication in swine production. Placental insufficiency is responsible for inadequate fetal growth, but the specific etiology of placental dysfunction-induced IUGR in pigs remains poorly understood. In this work, placenta samples supplying the lightest-weight (LW) and mean-weight (MW) pig fetuses in the litter at day 65 (D65) of gestation were collected, and the relationship between fetal growth and placental morphologies and functions was investigated using histomorphological analysis, RNA sequencing, quantitative polymerase chain reaction, and in-vitro experiment in LW and MW placentas. Results showed that the folded structure of the epithelial bilayer of LW placentas followed a poor and incomplete development compared with that of MW placentas. A total of 632 differentially expressed genes (DEGs) were screened out between the LW and MW placentas, and RACK1 was found to be downregulated in LW placentas. The DEGs were mainly enriched in translation, ribosome, protein synthesis, and mTOR signaling pathway according to GO and KEGG enrichment analyses. In-vitro experiments indicated that the decreased RACK1 in LW placentas may be involved in abnormal development of placental folds (PFs) by inhibiting the proliferation and migration of porcine trophoblast cells. Taken together, these results revealed that RACK1 may be a vital regulator in the development of PFs via regulating trophoblast ribosome function, proliferation, and migration in pigs.
Cross-reactive single-domain antibodies to hemagglutinin stem region protect mice from group 1 influenza A virus infection
Authors: Voronina Darya V. , Bandelyuk Alina S. , Dzharullaeva Alina Sh. , Popova Olga , Kan Vladislav Yu. , Esmagambetov Ilias B. , Favorskaya Irina A. , Shcheblyakov Dmitry V. , Naroditskiy Boris S. , Gintsburg Aleksandr L. 
Published: September 2022

AbstractThe continued evolution of influenza viruses reduces the effectiveness of vaccination and antiviral drugs. The identification of novel and universal agents for influenza prophylaxis and treatment is an urgent need. We have previously described two potent single-domain antibodies (VHH), G2.3 and H1.2, which efficiently neutralize H1N1 and H5N2 influenza viruses in vivo. In this study, we modified these VHHs with Fc-fragment to enhance their antiviral activity. Reformatting of G2.3 into bivalent Fc-fusion molecule increased its in vitro neutralizing activity against H1N1 and H2N3 viruses up to 20-fold and, moreover, resulted in obtaining the ability to neutralize H5N2 and H9N2 subtypes. We demonstrated that a dose as low as 0.6 mg/kg of G2.3-Fc or H1.2-Fc administered systemically or locally before infection could protect mice from lethal challenges with both H1N1 and H5N2 viruses. Furthermore, G2.3-Fc reduced the lung viral load to an undetectable level. Both VHH-Fc showed in vivo therapeutic efficacy when delivered via systemic or local route. The findings support G2.3-Fc as a potential therapeutic agent for both prophylaxis and therapy of Group 1 influenza A infection.
Validity of Optical Heart Rate Measurement in Commercially Available Wearable Fitness Tracking Devices
Authors: Thomas Jason , Doyle Patrick , Doyle J. Andrew 
Published: September 2022

AbstractBackgroundWearable fitness tracking devices have risen in popularity for athletes and the general population and are increasingly integrated into smartwatch technology. Many devices incorporate optical heart rate (HR) measurement by photoplethysmography which provides data used to monitor and track exercise training intensities, progress, and other health and fitness related parameters.ObjectiveTo determine the validity of optical heart rate measurement in three fitness tracking devices while resting, walking, and running.MethodsTwenty subjects (10 male, 10 female) completed the research study based on the ANSI/CTI standards for physical activity monitoring of heart rate under 4 different conditions: sedentary (SED), treadmill walking (WLK), running (RUN), and dynamic running/walking (DYN). Subjects wore 3 optical heart rate devices: Polar OH1 (OH1) on the right forearm, Apple Watch 4 (AW4) on the right wrist and Garmin Forerunner 945 (FR945) on the left wrist. A Polar H10 (H10), a chest strap device, was the criterion HR measurement device. SED, WLK, and RUN were all 7-minute protocols with 1 minute of standing, 5 minutes of prescribed activity, and 1 final minute of standing. The DYN protocol was a 12-minute protocol with 1 minute of standing, 10 minutes of variable intensity walking and running, and 1 minute of standing. Raw HR data was extracted from each device and temporally aligned with the criterion H10 HR data for analysis.ResultsThe mean absolute deviation (MAD, measured in beats per minute) for the three experimental devices (OH1, AW4, FR945, respectively) for SED was 1.31, 1.33, and 2.03; for WLK was 2.79, 2.58, and 5.19; for RUN were 4.00, 4.29, and 6.51; and for DYN was 2.60, 2.44, and 2.44. The mean absolute percent error (MAPE) for the three experimental devices (OH1, AW4, FR945, respectively) for SED was 1.78%, 1.89%, and 2.81%; for WLK was 3.15%, 3.18%, and 5.93%; for RUN was 3.43%, 3.51%, and 5.25%; and for DYN was 2.05%, 1.95%, and 5.47%. The intraclass correlation for each device across all conditions was .991 (OH1), .984 (AW4), and .697 (FR945).ConclusionsAt rest, and during both steady-state and variable-speed treadmill walking and running, the Polar OH1, Garmin Forerunner 945, and Apple Watch 4 optical HR monitors demonstrated a level of accuracy well within that required by the ANSI/CTA Standard (2018) for physical activity monitoring devices for heart rate measurement (i.e., <10% Mean Absolute Percent Error). Therefore, consumers can have confidence that these devices provide HR data with accuracy that conforms to the performance criteria recommended for consumer electronics.
Nanoscale Friction of Biomimetic Hair Surfaces
Authors: Weiand Erik , Ewen James P. , Roiter Yuri , Koenig Peter H. , Page Steven H. , Rodriguez-Ropero Francisco , Angioletti-Uberti Stefano , Dini Daniele 
Published: September 2022

AbstractWe investigate the nanoscale friction between biomimetic hair surfaces using chemical colloidal probe atomic force microscopy experiments and nonequilibrium molecular dynamics simulations. In the experiments, friction is measured between water-lubricated silica surfaces functionalised with monolayers of either octadecyl or sulfonate groups, which are representative of the surfaces of virgin and ultimately bleached hair, respectively. In the simulations, friction is monitored between coarse-grained model hair surfaces with different levels of chemical damage, where different fractions of grafted lipid molecules are randomly replaced with sulfonate groups. The sliding velocity dependence of friction can be described using an extended stress-augmented thermally activation model. As the damage level increases, the friction generally increases, but its sliding velocity-dependence decreases. At low sliding speeds, which are closer to those encountered physiologically and experimentally, we observe a monotonic increase of friction with the damage ratio, which is consistent with our new experiments using biomimetic surfaces and previous ones using real hair. This observation demonstrates that modified surface chemistry, rather than roughness changes or subsurface damage, control the increase in nanoscale friction of damaged hair. We expect the experimental and computational model surfaces proposed here to be useful to screen the tribological performance of hair care formulations.
Influence of metal cations on the viscoelastic properties of Escherichia coli biofilms
Authors: Sarlet Adrien , Ruffine Valentin , Blank Kerstin G. , Bidan Cécile M. 
Published: September 2022

AbstractBiofilms frequently cause complications in various areas of human life, e.g. in medicine and in the food industry. More recently, biofilms are discussed as new types of living materials with tuneable mechanical properties. In particular, Escherichia coli produces a matrix composed of amyloid-forming curli and phosphoethanolamine-modified cellulose fibres in response to suboptimal environmental conditions. It is currently unknown how the interaction between these fibres contributes to the overall mechanical properties of the formed biofilms and if extrinsic control parameters can be utilized to manipulate these properties. Using shear rheology, we show that biofilms formed by the E. coli K-12 strain AR3110 stiffen by a factor of two when exposed to the trivalent metal cations Al(III) and Fe(III) while no such response is observed for the bivalent cations Zn(II) and Ca(II). Strains producing only one matrix component did not show any stiffening response to either cation or even a small softening. No stiffening response was further observed when strains producing only one type of fibre were co-cultured or simply mixed after biofilm growth. These results suggest that the E. coli biofilm matrix is a uniquely structured composite material when both matrix fibres are produced from the same bacterium. While the exact interaction mechanism between curli, phosphoethanolamine-modified cellulose and trivalent metal cations is currently not known, our results highlight the potential of using extrinsic parameters to understand and control the interplay between biofilm structure and mechanical properties. This will ultimately aid the development of better strategies for controlling biofilm growth.Table of Contents Graphic
Emergent chirality in active solid rotation of pancreas spheres
Authors: Tan Tzer Han , Amiri Aboutaleb , Seijo-Barandiarán Irene , Staddon Michael F. , Materne Anne , Tomas Sandra , Duclut Charlie , Popović Marko , Grapin-Botton Anne , Jülicher Frank 
Published: September 2022

AbstractCollective cell dynamics play a crucial role in many developmental and physiological contexts. While two-dimensional (2D) cell migration has been widely studied, how three-dimensional (3D) geometry and topology interplay with collective cell behavior to determine dynamics and functions remains an open question. In this work, we elucidate the biophysical mechanism underlying rotation in spherical tissues, a phenomenon widely reported both in vivo and in vitro. Using murine pancreas-derived organoids as a model system, we find that epithelial spheres exhibit persistent rotation, rotational axis drift and rotation arrest. Using a 3D vertex model, we demonstrate how the interplay between traction force and polarity alignment can account for these distinct rotational dynamics. Furthermore, our analysis shows that the spherical tissue rotates as an active solid and exhibits spontaneous chiral symmetry breaking. Using a continuum model, we demonstrate how the types and location of topological defects in the polarity field underlie this symmetry breaking process. Altogether, our work shows that tissue chirality can arise via topological defects in the pattern of cell traction forces, with potential implications for left-right symmetry breaking processes in morphogenetic events.
Nazo, the Drosophila homolog of the NBIA-mutated protein – c19orf12, is required for triglyceride homeostasis
Authors: Sreejith Perinthottathil , Lolo Sara , Patten Kristen R. , Gunasinghe Maduka , More Neya , Pallanck Leo J. , Bharadwaj Rajnish 
Published: September 2022

SUMMARYLipid dyshomeostasis has been implicated in a variety of diseases ranging from obesity to neurodegenerative disorders such as NBIA. Here, we uncover the physiological role of Nazo, the Drosophila homolog of the NBIA-mutated protein – c19orf12, whose function has been elusive. Ablation of Drosophila c19orf12 homologs leads to dysregulation of multiple lipid metabolism genes. nazo mutants exhibit markedly reduced gut lipid droplet and whole-body triglyceride contents. Consequently, they are sensitive to starvation and oxidative stress. Nazo localizes to ER-lipid droplet contact sites and is required for maintaining normal levels of Perilipin2, an inhibitor of the lipase – Brummer. Concurrent knockdown of Brummer or overexpression of Perilipin2 rescues the nazo phenotype, suggesting that this defect may arise from diminished Perilipin2 on lipid droplets leading to aberrant Brummer-mediated lipolysis. Our findings provide novel insights into the role of c19orf12 as a possible link between lipid dyshomeostasis and neurodegeneration, particularly in the context of NBIA.