bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel carbon nanoparticles (CNPs) fromCatharanthus roseuspetals for metal ion sensing and root growth modulation
Authors: Omprabha Satya , Kaushal Charli , Gawande Nilesh D. , Barot Raviraj , Bhatia Dhiraj , Sankaranarayanan Subramanian 
Published: March 2024

AbstractNanoparticles are of major interest nowadays due to their distinctive properties. In this study, we present a microwave-assisted green synthesis of carbon nanoparticles from theCatharanthus roseuspetals. The nanoparticles exhibited a fluorescence emission in the 300 to 400 nm wavelength region and emitted a characteristic blue fluorescence. The extensive characterization using Bio-AFM showed that the size of nanoparticles was 25.38 nm. M-XRD and Zeta potential analysis confirmed that the nanoparticles were amorphous and exhibited a negative surface charge. The surface functional groups on the nanoparticles were highlighted by FTIR analysis. Metal sensing affinity of the synthesized CNPs and their effect on the plant growth was tested. These CNPs demonstrated the effective sequestration of metallic ions such as copper (Cu2+), iron (Fe2+), and nickel (Ni2+), indicating their potential to be used as biosensors in metal detection. It was found that the effect was proportionate to theCatharanthus roseuspetal nanoparticles (CRPNP) concentration, where it exhibits a great affinity for Fe2+.The effect of the nanoparticles analyzed on the root growth ofArabidopsis thalianashowed that CRPNP suppresses the primary root and lateral root numbers. These results demonstrate the use ofC. roseussynthesized CNPs in sustainable agriculture by targeting nutrient delivery.
Transcription factors ERα and Sox2 have differing multiphasic DNA and RNA binding mechanisms
Authors: Hemphill Wayne O. , Steiner Halley R. , Kominsky Jackson R. , Wuttke Deborah S. , Cech Thomas R. 
Published: March 2024

ABSTRACTMany transcription factors (TFs) have been shown to bind RNA, leading to open questions regarding the mechanism(s) of this RNA binding and its role in regulating TF activities. Here we use biophysical assays to interrogate the kon, koff, and Kdfor DNA and RNA binding of two model human transcription factors, ERα and Sox2. Unexpectedly, we found that both proteins exhibited multiphasic nucleic acid binding kinetics. We propose that Sox2 RNA and DNA multiphasic binding kinetics could be explained by a conventional model for sequential Sox2 monomer association and dissociation. In contrast, ERα nucleic acid binding exhibited biphasic dissociation paired with novel triphasic association behavior, where two apparent binding transitions are separated by a 10-20 min “lag” phase depending on protein concentration. We considered several conventional models for the observed kinetic behavior, none of which adequately explained all the ERα nucleic acid binding data. Instead, simulations with a model incorporating sequential ERα monomer association, ERα nucleic acid complex isomerization, and product “feedback” on isomerization rate recapitulated the general kinetic trends for both ERα DNA and RNA binding. Collectively, our findings reveal that Sox2 and ERα bind RNA and DNA with previously unappreciated multiphasic binding kinetics, and that their reaction mechanisms differ with ERα binding nucleic acids via a novel reaction mechanism.
Movement quality moderates the effect of spatially congruent cues on the stability of symmetric and asymmetric rhythmic bimanual finger movements
Authors: Denyer Ronan , Boyd Lara A. 
Published: March 2024

AbstractSpatially congruent cues increase the speed of bimanual reach decisions compared to abstract symbolic cues, particularly for asymmetric reaches. Asymmetric rhythmic bimanual movements are less stable than symmetric rhythmic movements, but it is not well understood if spatially congruent cues similarly increase the stability of asymmetric rhythmic bimanual movements. To address this question, inExperiment 1, participants performed symmetric and asymmetric bimanual rhythmic finger tapping movements at different movement frequencies in time with flickering spatially congruent and abstract symbolic stimuli. As expected, symmetric movements were more stable. Spatially congruent cues similarly increased the stability of symmetric and asymmetric movements compared to abstract symbolic cues. The benefits of spatial congruence and movement symmetry were restricted to high movement frequencies (>2 hertz). To better understand if the emergence of these effects at high movement frequencies was driven by a change in movement strategy, inExperiment 2, video of the hands was concurrently recorded during task performance. Markerless motion tracking software revealed that participants switched from discontinuous to continuous movement strategies with increasing movement frequency. Since discontinuous and continuous movements are thought to be controlled by distinct neuro-cogntive systems, this might explain why the beneficial effects of spatial congruence and response symmetry emerged only at high movement frequencies. Overall, results from the current study indicate that the perceptual quality of the stimulus use to cue movement frequency can have powerful effects on the stability of rhythmic bimanual movements, but that these effects may depend on whether discontinuous or continuous movement strategies are selected.
Structural diversity and clustering of bacterial flagellar outer domains
Authors: Fields Jessie Lynda , Zhang Hua , Bellis Nathan F. , Petersen Holly A. , Halder Sajal K. , Rich-New Shane T. , Wu Hui , Wang Fengbin 
Published: March 2024

AbstractSupercoiled flagellar filaments function as mechanical propellers within the bacterial flagellum complex, playing a crucial role in motility. Flagellin, the building block of the filament, features a conserved inner D0/D1 core domain across different bacterial species. In contrast, approximately half of the flagellins possess additional, highly divergent outer domain(s), suggesting varied functional potential. In this study, we elucidate atomic structures of flagellar filaments from three distinct bacterial species:Cupriavidus gilardii,Stenotrophomonas maltophilia, andGeovibrio thiophilus. Our findings reveal that the flagella from the facultative anaerobicG. thiophiluspossesses a significantly more negatively charged surface, potentially enabling adhesion to positively charged minerals. Furthermore, we analyzed all AlphaFold predicted structures for annotated bacterial flagellins, categorizing the flagellin outer domains into 682 structural clusters. This classification provides insights into the prevalence and experimental verification of these outer domains. Remarkably, two of the flagellar structures reported herein belong to a previously unexplored cluster, indicating new opportunities on the study of the functional diversity of flagellar outer domains. Our findings underscore the complexity of bacterial flagellins and open up possibilities for future studies into their varied roles beyond motility.
Human spermatogonial stem cells retain states with a foetal-like signature
Authors: Bush Stephen J. , Nikola Rafail , Han Seungmin , Suzuki Shinnosuke , Yoshida Shosei , Simons Benjamin D. , Goriely Anne 
Published: March 2024

AbstractSpermatogenesis involves a complex process of cellular differentiation maintained by spermatogonial stem cells (SSCs). Being critical to male reproduction, it is generally assumed that spermatogenesis starts and ends in equivalent transcriptional states in related species. Based on single-cell gene expression profiling it has been proposed that undifferentiated human spermatogonia can be sub-classified into four heterogenous subtypes, termed states 0, 0A, 0B, and 1. To increase the resolution of the undifferentiated compartment and trace the origin of the spermatogenic trajectory, we re-analysed the single-cell (sc)RNA-seq libraries of 34 post-pubescent human testes to generate an integrated atlas of germ cell differentiation. We then used this atlas to perform comparative analyses of the putative SSC transcriptome both across human development (using 28 foetal and pre-pubertal scRNA-seq libraries) and across species (including data from sheep, pig, buffalo, rhesus and cynomolgus macaque, rat and mouse).Alongside its detailed characterisation, we show that the transcriptional heterogeneity of the undifferentiated spermatogonial cell compartment varies not only between species but across development. Our findings associate ‘state 0B’ with a suppressive transcriptomic program that, in adult humans, acts to functionally oppose proliferation and maintain cells in a ready-to-react state. Consistent with this conclusion, we show that human foetal germ cells – which are mitotically arrested – can be characterised solely as state 0B. While germ cells with a state 0B signature are also present in foetal mouse (and are likely conserved at this stage throughout mammals), they are not maintained into adulthood. We conjecture that in rodents, the foetal-like state 0B differentiates at birth into the renewing SSC population, whereas in humans it is maintained as a reserve population, supporting testicular homeostasis over a longer reproductive life while reducing mutagenic load. Together, these results suggest that SSCs adopt differing evolutionary strategies across species to ensure fertility and genome integrity over vastly differing life histories and reproductive timeframes.
Multiplexed DNA-PAINT Imaging of the Heterogeneity of Late Endosome/Lysosome Protein Composition
Authors: Bond Charles , Hugelier Siewert , Xing Jiazheng , Sorokina Elena M. , Lakadamyali Melike 
Published: March 2024

AbstractLate endosomes/lysosomes (LELs) are crucial for numerous physiological processes and their dysfunction is linked to many diseases. Proteomic analyses have identified hundreds of LEL proteins, however, whether these proteins are uniformly present on each LEL, or if there are cell-type dependent LEL sub-populations with unique protein compositions is unclear. We employed a quantitative, multiplexed DNA-PAINT super-resolution approach to examine the distribution of six key LEL proteins (LAMP1, LAMP2, CD63, TMEM192, NPC1 and LAMTOR4) on individual LELs. While LAMP1 and LAMP2 were abundant across LELs, marking a common population, most analyzed proteins were associated with specific LEL subpopulations. Our multiplexed imaging approach identified up to eight different LEL subpopulations based on their unique membrane protein composition. Additionally, our analysis of the spatial relationships between these subpopulations and mitochondria revealed a cell-type specific tendency for NPC1-positive LELs to be closely positioned to mitochondria. Our approach will be broadly applicable to determining organelle heterogeneity with single organelle resolution in many biological contexts.SummaryThis study develops a multiplexed and quantitative DNA-PAINT super-resolution imaging pipeline to investigate the distribution of late endosomal/lysosomal (LEL) proteins across individual LELs, revealing cell-type specific LEL sub-populations with unique protein compositions, offering insights into organelle heterogeneity at single-organelle resolution.
All-atom protein sequence design based on geometric deep learning
Authors: Liu Jiale , Guo Zheng , Zhang Changsheng , Lai Luhua 
Published: March 2024

AbstractThe development of advanced deep learning methods has revolutionized computational protein design. Although the success rate of design has been significantly increased, the overall accuracy ofde novodesign remains low. Many computational sequence design approaches are devoted to recover the original sequences for given protein structures by encoding the environment of the central residue without considering atomic details of side chains. This may limit the exploration of new sequences that can fold into the same structure and restrain function design that depends on interaction details. In this study, we proposed a novel deep learning frame-work, GeoSeqBuilder, to learn the relationship between protein structure and sequence based on rotational and translational invariance by extracting the information from relative locations. We utilized geometric deep learning to fetch the spatial local geometric features from protein backbones and explicitly incorporated three-body interactions to learn the inter-residue coupling information, and then determined the central residue type. Our model recovers over 50% native residue types and simultaneously gives highly accurate prediction of side-chain conformations which gives the atomic interaction details and circumvents the dependence of protein structure prediction tools. We used the likelihood confidence logPas scoring function for sequence and structure consistence evaluation which exhibits strong correlation with TM-score, and can be applied to recognize near-native structures from protein decoys pool in protein structure prediction. We have used GeoSeqBuilder to design sequences for two proteins, including thiore-doxin and ade novohallucinated protein. All of the 15 sequences experimentally tested can be expressed as soluble monomeric proteins with high thermal stability and correct secondary structures. We further solved one crystal structure for thioredoxin and two for the hallucinated structure and all the experimentally solved structures are in good agreement with the designed models. The two designed sequences for the hallucination structure are novel without any homologous sequences within the latest released database clust30. The ability of GeoSeqBuilder to design new sequences for given protein structures with atomic details makes it applicable, not only forde novosequence design, but also for protein-protein interaction and functional protein design.
Multi-omics analysis of aggregative multicellularity
Authors: Edelbroek Bart , Orzechowski Westholm Jakub , Bergquist Jonas , Söderbom Fredrik 
Published: March 2024

AbstractThe extent to which mRNA and protein levels or their regulation correlate remains obscure, especially during development. In particular, this is true for organisms that exhibit aggregative multicellularity, such as the social amoebaDictyostelium discoideum. The transcriptome ofD. discoideumhas been thoroughly studied during multicellular development, however the proteome and the correlation to the transcriptome during transition from uni- to multicellular life have not been analyzed in detail. Here, we present the first paired transcriptomics and proteomics developmental time series during aggregative multicellularity. The dataset reveals that mRNA and protein levels correlate highly during growth, but decrease when multicellular development is initiated. This accentuates that transcripts alone cannot accurately describe gene expression. This dataset can therefore be an important resource to study gene expression during aggregative multicellular development, in particular inD. discoideum.
The RNA-dependent interactions of phosphatidylinositol 4,5-bisphosphate with intrinsically disordered proteins contribute to nuclear compartmentalization
Authors: Sztacho Martin , Červenka Jakub , Šalovská Barbora , Antiga Ludovica , Hoboth Peter , Hozák Pavel 
Published: March 2024

AbstractThe RNA content is crucial for the formation of nuclear compartments, such as nuclear speckles and nucleoli. Phosphatidylinositol 4,5-bisphosphate (PIP2) is found in nuclear speckles, nucleoli and nuclear lipid islets and is involved in RNA polymerase I/II transcription. Intriguingly, the nuclear localization of PIP2 was also shown to be RNA-dependent. We therefore investigated whether PIP2 and RNA cooperate in the establishment of nuclear architecture. In this study, we unveiled the RNA-dependent PIP2-associated (RDPA) nuclear proteome in human cells by mass spectrometry. We found that intrinsically disordered regions (IDRs) with polybasic PIP2-binding K/R motifs are prevalent features of RDPA proteins. Moreover, these IDRs of RDPA proteins exhibit enrichment for phosphorylation, acetylation and ubiquitination sites. Our findings reveal that RDPA protein BRD4 associates with PIP2 in an RNA-dependent manner via electrostatic interactions, and that elevated PIP2 levels increase the number of BRD4 protein nuclear foci. Thus, we propose that PIP2 spatiotemporally orchestrates nuclear processes through association with RNA and RDPA proteins and affects their ability to phase separate. This suggests pivotal role of PIP2 for the establishment of a functional nuclear architecture competent for gene expression.
Replication efficiencies of human cytomegalovirus-infected epithelial cells are dependent on source of virus production
Authors: Mokry Rebekah L. , Monti Christopher E. , Rosas-Rogers Suzette , Schumacher Megan L. , Dash Ranjan K. , Terhune Scott S. 
Published: March 2024

ABSTRACTHuman cytomegalovirus (HCMV) is a prevalent betaherpesvirus, and infection can lead to a range of symptomatology from mononucleosis to sepsis in immunocompromised individuals. HCMV is also the leading viral cause of congenital birth defects. Lytic replication is supported by many cell types with different kinetics and efficiencies leading to a plethora of pathologies. The goal of these studies was to elucidate HCMV replication efficiencies for viruses produced on different cell types upon infection of epithelial cells by combining experimental approaches with data-driven computational modeling. HCMV was generated from a common genetic background of TB40-BAC4, propagated on fibroblasts (TB40Fb) or epithelial cells (TB40Epi), and used to infect epithelial cells. We quantified cell-associated viral genomes (vDNA), protein levels (pUL44, pp28), and cell-free titers over time for each virus at different multiplicities of infection. We combined experimental quantification with data-driven simulations and determined that parameters describing vDNA synthesis were similar between sources. We found that pUL44 accumulation was higher in TB40Fbthan TB40Epi. In contrast, pp28 accumulation was higher in TB40Epiwhich coincided with a significant increase in titer for TB40Epiover TB40Fb. These differences were most evident during live-cell imaging, which revealed syncytia-like formation during infection by TB40Epi. Simulations of the late lytic replication cycle yielded a larger synthesis constant for pp28 in TB40Epialong with increase in virus output despite similar rates of genome synthesis. By combining experimental and computational modeling approaches, our studies demonstrate that the cellular source of propagated virus impacts viral replication efficiency in target cell types.IMPORTANCEHuman cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause serious disease under conditions of immunodeficiency and upon congenital infection. HCMV replicates in diverse cell types throughout the human body with tropism influenced by the source of the virus. Here, we investigated the contribution of viral sources to the kinetics of HCMV replication in epithelial cells using both experimental and mechanistic computational modeling approaches. These studies reveal that HCMV produced from epithelial cells exhibits a higher efficiency of replication despite similar viral DNA synthesis kinetics between viral sources. These differences likely involve a propensity of epithelial-derived virus to induce syncytia versus fibroblast-derived virus, and an accompanying higher synthesis rate of a late virion protein ultimately resulting in production of more extracellular infectious virus.
Molecular Mechanism of Condensin I Activation by KIF4A
Authors: Cutts Erin E. , Tetiker Damla , Kim Eugene , Aragon Luis 
Published: March 2024

SummaryDuring mitosis, the condensin I and II complexes compact chromatin into chromosomes. Loss of the chromokinesin, KIF4A, results in reduced condensin I chromosome association. However, the molecular mechanism behind this phenotype is unknown. Here, we show that KIF4A binds directly to condensin I HAWK subunit, NCAPG, via a conserved disordered short linear motif (SLiM) found in its C-terminal tail. KIF4A binding directly competes with two auto-inhibitory interactions in condensin I, mediated by SLiMs found in the N-terminus of NCAPH and the C-terminus of NCAPD2, which bind sites that overlap with KIF4A binding on NCAPG. Addition of the KIF4A SLiM peptide alone is sufficient to stimulate condensin’s ATPase and DNA loop extrusion activity. We also identify SLiMs in known yeast condensin interactors, Sgo and Lrs4, that bind yeast Ycg1, the HAWK equivalent to NCAPG. Our findings, together with previous work on condensin II and cohesin, demonstrate that SLiMs binding to HAWK subunits is a conserved mechanism of regulation in SMC complexes.
Optimising project outcomes in complex environments: empirical insights on agile practices and stakeholder dynamics
Authors: Nguyen Tuan Son , Mohamed Sherif , Mostafa Sherif 
Published: March 2024

PurposeThis study delves into the dynamics between Agile Response to Change (AR), Adaptive Scoping (AS), Stakeholder Engagement (SE) and Project Performance (PP), with a special focus on the moderating influence of Project Complexity (PC). The research, grounded in a thorough literature review, identifies critical gaps in these areas and examines the extent to which PC moderates the effects of AR, AS and SE on PP, offering new perspectives for managing complex projects.Design/methodology/approachThe research develops a conceptual model based on a critical analysis of existing literature. A comprehensive questionnaire was designed, incorporating 28 items to measure AR, AS, SE, PP and PC. Data was collected from 136 project managers across various industries, and the responses were analysed using structural equation modelling (SEM) to explore the complex interplay between these variables.FindingsThe analysis revealed that internal AR (ARint) significantly enhances both quantitative (PPqt) and qualitative aspects of PP (PPql). AS and SE were found to positively influence PPql, but their impact on PPqt was not significant. Interestingly, PC was observed to negatively moderate the relationship between ARint and PPql, while its moderating effect on the relationship between ARint and PPql was not significant. The study also notes that PC does not significantly alter the positive correlations between AS, SE and PPql.Originality/valueThis research contributes to the existing body of knowledge by elucidating the relationships between ARint, AS, SE and different dimensions of PP. It uniquely explores the role of PC as a moderating variable in these relationships, offering valuable insights for practitioners and researchers in the field of complex project management.
Corporate diplomacy: the dimensional structure and outcomes
Authors: Jiang Sihan , Teng Wenbo , Huang Yuanyuan , Zhang Xiao 
Published: March 2024

PurposeGiven the great upheaval in the international situation and the increasing operating risk in international business, research on corporate diplomacy is thriving. However, it still lacks clear conceptualization and operationalization. Based on social capital theory, our study conceptualizes corporate diplomacy as a three-dimensional construct and quantifies its distinct and combined impacts on multinational enterprises’ (MNE) subsidiary performance.Design/methodology/approachThis research analyzes 134 responses collected from a questionnaire survey among key informants in Chinese MNEs using the regression method.FindingsThis research finds that corporate diplomacy is positively correlated with MNEs’ subsidiary performance. Specifically, compatriot-oriented diplomacy is the most effective, followed sequentially by host-partner-oriented and host-regulator-oriented diplomacy. In addition, compatriot-oriented diplomacy substitutes for host-partner-oriented diplomacy but complements host-regulator-oriented diplomacy in enhancing subsidiary performance.Originality/valueOur research enriches the conceptualization and operationalization of corporate diplomacy and provides a nuanced view of its distinct and combined effects on MNEs’ subsidiary performance.