bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct roles of α- and β-tubulin C-terminal tails for ciliary function as revealed by a CRISPR/Cas9 mediated gene editing inChlamydomonas
Authors: Kubo Tomohiro , Tani Yuma , Yanagisawa Haru-Aki , Kikkawa Masahide , Oda Toshiyuki 
Published: February 2023

Abstractα- and β-tubulin have an unstructured glutamate-rich region at their C-terminal tails (CTT). The function of this region in cilia/flagella is still unclear, except that glutamates in CTT act as the sites for posttranslational modifications that affect ciliary motility. A unicellular algaChlamydomonaspossesses only two α-tubulin genes and two β-tubulin genes, each pair encoding an identical protein. This simple gene organization may enable a complete replacement of the wild-type tubulin with its mutated version. Here, using CRISPR/Cas9, we generated mutants expressing tubulins with modified CTTs. We found that the mutant whose four glutamate residues in the α-tubulin CTT have been replaced by alanine almost completely lacked polyglutamylated tubulin and displayed paralyzed cilia. In contrast, the mutant lacking the glutamate-rich region of the β-tubulin CTT assembled short cilia without the central apparatus. This phenotype is similar to the mutants harboring a mutation in a subunit of katanin, whose function has been shown to depend on the β-tubulin CTT. Therefore, our study reveals distinct and important roles of α- and β-tubulin CTT in the formation and function of cilia.Summary statementChlamydomonasmutants were produced by CRISPR/Cas9 mediated gene editing to investigate ciliary function of tubulin C-terminal tails (CTTs). We found that α- and β-tubulin CTTs are essential for ciliary motility and assembly.
Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation
Authors: Jin Shijie , Chen Xuan , Tian Yang , Jarvis Rachel , Promes Vanessa , Yang Yongjie 
Published: February 2023

AbstractDeveloping astroglia play important roles in regulating synaptogenesis through secreted and contact signals. Whether they regulate postnatal axon growth is unknown. By selectively isolating exosomes using size-exclusion chromatography (SEC) and employing cell-type specific exosome reporter mice, our current results define a secreted astroglial exosome pathway that can spread long-rangein vivoand stimulate axon growth of cortical pyramidal neurons. Subsequent biochemical and genetic studies found that surface expression of glial HepaCAM protein essentially and sufficiently mediates the axon-stimulating effect of astroglial exosomes. Interestingly, apolipoprotein E (ApoE), a major astroglia-secreted cholesterol carrier to promote synaptogenesis, strongly inhibits the stimulatory effect of astroglial exosomes on axon growth. Developmental ApoE deficiency also significantly reduces spine density of cortical pyramidal neurons. Together, our study suggests a surface contact mechanism of astroglial exosomes in regulating axon growth and its antagonization by ApoE, which collectively coordinates early postnatal pyramidal neuronal axon growth and dendritic spine formation.
Physiological reprogrammingin vivomediated by Sox4 pioneer factor activity
Authors: Katsuda Takeshi , Sussman Jonathan , Ito Kenji , Katznelson Andrew , Yuan Salina , Li Jinyang , Merrell Allyson J. , Takenaka Naomi , Cure Hector , Li Qinglan , Rasool Reyaz Ur , Asangani Irfan A. , Zaret Kenneth S. , Stanger Ben Z. 
Published: February 2023

AbstractTissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors mediate “reprogramming” by opening new chromatin sites for expression that can attract transcription factors from the starting cell’s enhancers. Here we report that Sox4 is sufficient to initiate hepatobiliary metaplasia in the adult liver. In lineage-traced cells, we assessed the timing of Sox4-mediated opening of enhancer chromatin versus enhancer decommissioning. Initially, Sox4 directly binds to and closes hepatocyte regulatory sequences via a motif it overlaps with Hnf4a, a hepatocyte master regulator. Subsequently, Sox4 exerts pioneer factor activity to open biliary regulatory sequences. The results delineate a hierarchy by which gene networks become reprogrammed under physiological conditions, providing deeper insight into the basis for cell fate transitions in animals.
Whole-brain, gray and white matter time-locked functional signal changes with simple tasks and model-free analysis
Authors: Schilling Kurt G , Li Muwei , Rheault Francois , Gao Yurui , Cai Leon , Zhao Yu , Xu Lyuan , Ding Zhaohua , Anderson Adam W , Landman Bennett A , Gore John C 
Published: February 2023

AbstractRecent studies have revealed the production of time-locked blood oxygenation-level dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to a task, challenging the idea of sparse and localized brain functions, and highlighting the pervasiveness of potential false negative fMRI findings. In these studies, ‘whole-brain’ refers to gray matter regions only, which is the only tissue traditionally studied with fMRI. However, recent reports have also demonstrated reliable detection and analyses of BOLD signals in white matter which have been largely ignored in previous reports. Here, using model-free analysis and simple tasks, we investigate BOLD signal changes in both white and gray matters. We aimed to evaluate whether white matter also displays time-locked BOLD signals across all structural pathways in response to a stimulus. We find that both white and gray matter show time-locked activations across the whole-brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing very different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that the whole brain, including both white and gray matter, show time-locked activation to multiple stimuli, not only challenging the idea of sparse functional localization, but also the prevailing wisdom of treating white matter BOLD signals as artefacts to be removed.
Perinuclear damage from nuclear envelope deterioration elicits stress responses that contribute toLMNAcardiomyopathy
Authors: Sikder Kunal , Phillips Elizabeth , Zhong Zhijiu , Wang Nadan , Saunders Jasmine , Mothy David , Kossenkov Andrew , Schneider Timothy , Nichtova Zuzana , Csordas Gyorgy , Margulies Kenneth B. , Choi Jason C. 
Published: February 2023

AbstractMutations in theLMNAgene encoding nuclear lamins A/C cause a diverse array of tissue-selective diseases, with the heart being the most commonly affected organ. Despite progress in understanding the molecular perturbations emanating fromLMNAmutations, an integrative understanding of the pathogenesis leading to cardiac dysfunction remains elusive. Using a novel cell-type specificLmnadeletion mouse model capable of translatome profiling, we found that cardiomyocyte-specificLmnadeletion in adult mice led to rapid cardiomyopathy with pathological remodeling. Prior to the onset of cardiac dysfunction, lamin A/C-depleted cardiomyocytes displayed nuclear envelope deterioration, golgi dilation/fragmentation, and CREB3-mediated golgi stress activation. Translatome profiling identified upregulation of Med25, a transcriptional co-factor that can selectively dampen UPR axes. Autophagy is disrupted in the hearts of these mice, which can be recapitulated by disrupting the golgi or inducing nuclear damage by increased matrix stiffness. Systemic administration of pharmacological modulators of autophagy or ER stress significantly improved the cardiac function. These studies support a hypothesis wherein stress responses emanating from the perinuclear space contribute to the development ofLMNAcardiomyopathy.TeaserInterplay of stress responses underlying the development ofLMNAcardiomyopathy
SynEcoSys: a multifunctional platform of large-scale single-cell omics data analysis
Authors: Zhang Yan , Li Bingyu , Duan Jiachen , Chen Xuezhen , Zhang Xiaogang , Ye Jun , Veloso Ana , Fan Jue , Fang Nan 
Published: February 2023

AbstractNext generation sequencing technologies enable the analysis of the transcriptomes of individual cells, providing a higher resolution of gene expression and function at the single cell level. Various single-cell data are continuously generated every year, covering fields from scientific research to clinical development. The fast-growing public datasets are collected by distinctive platforms, which are designed to facilitate biological discoveries, disease diagnosis, and new treatments. However, these platforms are hard to meet the urgency of having a unified data integration pipeline to improve comparability between datasets. Here we present SynEcoSys, an online multifunctional platform for single-cell transcriptomic data analysis, visualization, and exploration. SynEcoSys by Singleron Biotechnologies currently provides a massive collection of publicly available single-cell sequencing dataset, involving 46,326,175 cells from 731 datasets across multiple platforms and species. All datasets are generated with a strict and uniform data analysis pipeline and cell marker-based manual annotation, thus facilitating more comprehensive and reliable data mining. SynEcoSys is available at:https://www.synecosys.com.
Signalling pathway crosstalk stimulated by L-proline drives differentiation of mouse embryonic stem cells to primitive-ectoderm-like cells
Authors: Glover Hannah J. , Holliday Holly , Shparberg Rachel A. , Winkler David , Day Margot , Morris Michael B. 
Published: February 2023

AbstractThe amino acid L-proline exhibits novel growth factor-like properties during development - from improving blastocyst development to driving neurogenesisin vitro. Addition of 400 μM L-proline to self-renewal medium drives mouse embryonic stem cells (ESCs) to a transcriptionally distinct pluripotent cell population - early primitive ectoderm-like (EPL) cells - which lies between the naïve and primed states. EPL cells retain expression of pluripotency genes, upregulate primitive ectoderm markers, undergo a morphological change and have increased cell number.These changes are facilitated by a complex signalling network hinging on the Mapk, Fgfr, Pi3k and mTor pathways. We use a factorial experimental design coupled with linear modelling and Bayesian regularised neural networks to understand which signalling pathways are involved in the transition between ESCs and EPL cells, and how they underpin changes in morphology, cell number, apoptosis, proliferation and gene expression. This approach allows for consideration of where pathways work antagonistically or synergistically.Modelling showed that most properties were affected by more than one inhibitor, and each inhibitor blocked specific aspects of differentiation. These mechanisms underpin both progression of stem cells across thein vitropluripotency continuum and serve as a model for pre-, peri- and post-implantation embryogenesis.Summary StatementL-proline acts as growth factor to modulate phosphorylation of the Mapk, Pi3k, Fgf and mTor signalling pathways to drive embryonic stem cells to primitive ectoderm-like cells.
Deep Learning Reveals Endogenous Sterols as Allosteric Modulators of the GPCR-Gα Interface
Authors: Mohanty Sanjay Kumar , Mittal Aayushi , Namra  , Gaur Aakash , Duari Subhadeep , Solanki Saveena , Sharma Anmol Kumar , Arora Sakshi , Kumar Suvendu , Gautam Vishakha , Dixit Nilesh Kumar , Subramanian Karthika , Ghosh Tarini Shankar , Sengupta Debarka , Gupta Shashi Kumar , Murugan Natarajan Arul , Sharma Deepak , Ahuja Gaurav 
Published: February 2023

ABSTRACTEndogenous intracellular allosteric modulators of GPCRs remain largely unexplored, with limited binding and phenotype data available. This gap arises from the lack of robust computational methods for unbiased cavity identification, cavity-specific ligand design, synthesis, and validation across GPCR topology. Here, we developed Gcoupler, an AI-driven generalized computational toolkit that leverages an integrative approach combiningde novoligand design, statistical methods, Graph Neural Networks, and Bioactivity-based ligand prioritization for rationally predicting high-affinity ligands. Using Gcoupler, we interrogated intracellular metabolites that target and regulate the GPCR-Gα interface (Ste2p-Gpa1p), affecting pheromone-induced programmed cell death in yeast. Our computational analysis, complemented by experimental validations, including genetic screening, multi-omics, site-directed mutagenesis, biochemical assays, and physiological readouts, identified endogenous hydrophobic metabolites, notably sterols, as direct intracellular allosteric modulators of Ste2p. Molecular simulations coupled with biochemical signaling assessment in site-directed Ste2p mutants further confirmed metabolites binding to GPCR-Gα obstruct downstream signaling, possibly via cohesive effect. Finally, by utilizing isoproterenol-induced, GPCR-mediated human and neonatal rat cardiac hypertrophy models, we observed elevated metabolite levels attenuate hypertrophic response, reinforcing the evolutionary relevance of this mechanism.
In search of the Goldilocks zone for hybrid speciation II: hard times for hybrid speciation?
Authors: Blanckaert Alexandre , Sriram Vedanth , Bank Claudia 
Published: February 2023

AbstractHybridization opens a unique window for observing speciation mechanisms and is a potential engine of speciation. One controversially discussed outcome of hybridization is homoploid hybrid speciation by reciprocal sorting, where a hybrid population maintains a mixed combination of the parental genetic incompatibilities, preventing further gene exchange between the newly formed population and the two parental sources. Previous work showed that, for specific linkage architectures (i.e., the genomic location and order of hybrid incompatibilities), reciprocal sorting could reliably result in hybrid speciation. Yet, the sorting of incompatibilities creates a risk of population extinction. To understand how demographic consequences of the purging of incompatibilities interact with the formation of a hybrid species, we model an isolated hybrid population resulting from a single admixture event. We study how population size, linkage architecture and the strength of the incompatibility affect survival of the hybrid population, resolution/purging of the genetic incompatibilities and the probability of observing hybrid speciation. We demonstrate that the extinction risk is highest for intermediately strong hybrid incompatibilities. In addition, the linkage architecture displaying the highest hybrid speciation probabilities changes drastically with population size. Overall, this indicates that population dynamics can strongly affect the outcome of hybridization and the hybrid speciation probability.
The imperfections of employee involvement: harnessing the consequences of involvement practices on psychosocial risks at work
Authors: Palumbo Rocco , Hinna Alessandro , Decastri Maurizio 
Published: February 2023

Purpose
Involving employees in making management decisions is a powerful way to enhance organizational performance. However, employee involvement (EI) might exacerbate psychosocial stress at work. This paper aims to investigate this issue, illuminating the implications of EI on work-related stress.

Design/methodology/approach
Secondary data were collected from the third wave of the European Survey of Enterprises on New and Emerging Risks. A conditional process analysis based on ordinary least square regression and bootstrap sampling was accomplished to obtain evidence of the implications of EI on psychosocial risks (PSR) at work, taking into consideration the mediating role of organizational health promotion initiatives (HPI).

Findings
EI increased the sources of psychosocial stress at work, adding to individual job demands. Involving employees was positively related to a greater organizational concern for HPI, which, in turn, lessened psychosocial strain.

Practical implications
Although it contributes to organizational performance, EI propels work-related stress, which undermines individual and collective wellbeing. Involvement practices should be coupled with tailored HPI to address the PSR at work triggered by involvement, empowering people to cope with strain.

Originality/value
Scientific literature emphasizes the positive implications of EI on organizational performance, but little is known about its side effects on work-related stress. The paper provides original insights into this topic, arguing that HPI are necessitated to address the drawback of involvement on work-related stress.
Stalking: Issues of deterrence “When I was stalking, I was so dedicated to it. Nothing would stop me. It was my focus.”
Authors: Wheatley Rachael , Henley Sara , Farnham Frank 
Published: February 2023

PurposeThis paper aims to present issues of deterrence related to stalking.Design/methodology/approachThe authors have combined recent mixed method research findings and existing general deterrence literature with their practitioner experiences of working with this population, to provide a novel viewpoint paper intending to influence advancements in knowledge in this area.FindingsRecent qualitative research investigating the function of stalking in a small sample (see Wheatleyet al., 2020a) noted the participants’ focus on the lack of deterrence. For example, participants described feeling emotionally stuck in their pursuits, experiencing poor access to help and support, being ignorant of the potential custodial consequences of their offending and even stating that imprisonment provided a harsh yet necessary moment of reality.Originality/valueThis novel discussion paper reviews these findings in relation to both the available research based on deterrence generally and deterrence related to stalking and the experience of working with stalking cases in clinical practice. This paper explores what we know about the motivations that underlie stalking behaviour and how that relates to the effectiveness of deterrence, including the role of traditional criminal justice approaches to this type of offending.
A framework of open government data (OGD) e-service quality dimensions with future research agenda
Authors: Alexopoulos Charalampos , Saxena Stuti , Rizun Nina , Shao Deo 
Published: February 2023

Purpose
This research paper aims to present a framework of open government data (OGD) relating to e-service quality dimensions. In addition, it provides a research agenda for the e-service delivery of OGD.

Design/methodology/approach
A literature review pertaining to e-service quality with special reference to e-government was delivered to deduce the key dimensions of e-service quality for OGD.

Findings
Five e-service quality dimensions of OGD are identified in the study; website design, fulfilment, service provision to the user while interfacing with the OGD Web portal, service provision to the user during and after the value-creation and innovation period and security/privacy. To further OGD re-use for value creation and innovation, it is important that the e-service quality dimensions are built into all OGD programmes by public authorities.

Originality/value
Hitherto, extant research has focused on the data quality dimensions of OGD, but the dimensions linked with e-service have not been explored. This study seeks to fill this gap and, in addition, suggests further research requirements in this field.
Linkages between natural gas, fertiliser and cereal prices: A note
Authors: Vatsa Puneet , Miljkovic Dragan , Baek Jungho 
Published: February 2023

AbstractWe use structural vector autoregressions to analyse the dynamic effects of shocks to natural gas and nitrogenous fertiliser prices on three major cereal crops: maize, rice and wheat. We find that the response of cereal prices to natural gas and fertiliser price shocks has been relatively small, instantaneous and transitory. These findings suggest that crop prices may change rapidly in response to energy and fertiliser prices, even when there are no shifts in the underlying fundamentals in crop markets. Furthermore, because the effects of the shocks dissipate rather quickly, short‐term measures to address swings in food prices may suffice.
Application of chickpea‐based edible coating with chickpea husk polyphenols on the preservation of sunflower seeds
Authors: Camiletti Ornella F. , Bergesse Antonella E. , Aleman Rebeca , Riveros Cecilia G. , Grosso Nelson R. 
Published: February 2023

AbstractThe objective of this study was to evaluate the protective effect of a chickpea‐based edible coating with the addition of polyphenols on the chemical, microbiological, and sensory quality of roasted sunflower seeds throughout storage. Four different samples were prepared: roasted sunflower seeds (control sample, SF‐C), roasted sunflower seeds with BHT (SF‐BHT), roasted sunflower seeds with chickpea‐based coating (SF‐CCs), and roasted sunflower seeds with chickpea‐based coating with chickpea polyphenolic extract (SF‐CCPE). The samples were stored for 60 days at room temperature, and their chemical, microbiological, and sensory parameters were analyzed. The acceptability of fresh samples was also studied. The use of chickpea‐based coatings retarded the lipid oxidation process efficiently, but the inclusion of chickpea polyphenols in the coating enhanced the protective effect. At 60th day of storage, no statistically significant differences were found between SF‐CCPE and SF‐BHT in relation to peroxides and conjugated dienes values, saturated/unsaturated ratio, and hexanal content. Linoleic acid content was reduced significantly more in SF‐CCs than SF‐CCPE. The addition of chickpea coating with chickpea antioxidants did not modify the flavor of the sunflower seeds and was the most accepted treatment by the consumer. The formation of undesirable flavors (cardboard and oxidized) was less in SF‐CC, SF‐CCPE, and SF‐BHT without finding significant differences between these treatments. None of the samples presented microbiological contamination or an increase in bacteria, yeast, and molds during storage. The chickpea‐based coating was able to retard lipid oxidation in roasted sunflower seeds, proving to be a good alternative as a natural method to preserve foods with high lipid content.Practical ApplicationDiscarded chickpeas and chickpea husks constitute byproducts from the chickpea industry. The grain husks are currently discarded or marketed at a very low cost, constituting a novel residue with antioxidant properties. Considering the growing interest in sustainability and the circular economy, this investigation proposes the utilization of nutritional materials to prepare edible coatings. The chickpea‐based coatings loaded with polyphenol extract (obtained from the husk of chickpea) demonstrated to have a protective effect against lipid oxidation process in sunflower seeds, which represent a good alternative to be used for the food industry to increase the shelf life of lipid foods.