bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Ratiometric Catalog of Protein Isoform Shifts in the Cardiac Fetal Gene Program
Authors: Han Yu , Wennersten Sara A. , Pandi Boomathi P. , Ng Dominic C. M. , Lau Edward , Lam Maggie P. Y. 
Published: April 2024

AbstractThe fetal genetic program orchestrates cardiac development and the re-expression of fetal genes is thought to underlie cardiac disease and adaptation. Here, a proteomics ratio test using mass spectrometry is applied to find protein isoforms with statistically significant usage differences in the fetal vs. postnatal mouse heart. Changes in isoform usage ratios are pervasive at the protein level, with 104 significant events observed, including 88 paralog-derived isoform switching events and 16 splicing-derived isoform switching events between fetal and postnatal hearts. The ratiometric proteomic comparisons rediscovered hallmark fetal gene signatures including a postnatal switch from fetal β (MYH7) toward α (MYH6) myosin heavy chains and from slow skeletal muscle (TNNI1) toward cardiac (TNNI3) troponin I. Altered usages in metabolic proteins are prominent, including a platelet to muscle phosphofructokinase (PFKP - PFKM), enolase 1 to 3 (ENO1 - ENO3), and alternative splicing of pyruvate kinase M2 toward M1 (PKM2 - PKM1) isoforms in glycolysis. The data also revealed a parallel change in mitochondrial proteins in cardiac development, suggesting the shift toward aerobic respiration involves also a remodeling of the mitochondrial protein isoform proportion. Finally, a number of glycolytic protein isoforms revert toward their fetal forms in adult hearts under pathological cardiac hypertrophy, suggesting their functional roles in adaptive or maladaptive response, but this reversal is partial. In summary, this work presents a catalog of ratiometric protein markers of the fetal genetic program of the mouse heart, including previously unreported splice isoform markers.
Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy
Authors: Ouyang Minhui , Detre John A. , Hyland Jessica L. , Sindabizera Kay L. , Kuschner Emily S , Edgar J. Christopher , Peng Yun , Huang Hao 
Published: April 2024

AbstractInfant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we found the emergence of the cortical hierarchy revealed by highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increased in a biphasic pattern with initial rapid and sequentially slower rate, with break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices were associated with enhanced language and motor skills, and frontoparietal association cortices for cognitive skills. The study discovered emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy, and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.
Modulation of biphasic pattern of cortical reorganization in spinal cord transected rats by external magnetic fields
Authors: Kaur Sajeev , Kochhar Kanwal Preet , Jain Suman 
Published: April 2024

AbstractMagnetic field induces electric field in the brain and has the potential to modulate cortical plasticity giving rise to sustained excitability as well as behavioral modifications. The present study demonstrates the effect of extremely low frequency magnetic field (ELF-MF) on cortical reorganization after SCI in complete transection rat model. The spinal cord of male albino Wistar rats was completed transected at T-13 spinal level and ELF-MF (50 Hz, 17.96 µT) exposure given either for 5 or 12 or 32 days for temporal observations. A significant functional recovery was evident in locomotor, sensorimotor and motor behavioral tests after 32 days of magnetic field exposure. This was associated with an amelioration in cortical electrical activity, decrease in the lesion area and volume and modulation of plasticity associated proteins like Nogo-A and BDNF in a biphasic pattern. The results suggest improvement of functional, electrical and morphological parameters along with upregulation of plasticity associated proteins in an in-vivo SCI rat model following ELF-MF exposure for 32 days but not after 5, 12 days exposure
How fast are viruses spreading in the wild?
Authors: Dellicour Simon , Bastide Paul , Rocu Pauline , Fargette Denis , Hardy Olivier J. , Suchard Marc A. , Guindon Stéphane , Lemey Philippe 
Published: April 2024

AbstractGenomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics allowing to unveil the dispersal dynamics and evaluate the capacity to spread among hosts. Heterogeneous sampling intensity of genomic sequences can however impact the accuracy of dispersal insights gained through phylogeographic inference. In our study, we implement a simulation framework to evaluate the robustness of three dispersal metrics — a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance signal metric — to the sampling effort. Our results reveal that both the diffusion coefficient and isolation-by-distance signal metrics appear to be robust to the number of samples considered for the phylogeographic reconstruction. We then use these two dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of isolation-by-distance patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.
Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes
Authors: Pastor Florentin , Charles Emilie , Belmudes Lucid , Chabrolles Hélène , Cescato Marion , Rivoire Michel , Burger Thomas , Passot Guillaume , Durantel David , Lucifora Julie , Couté Yohann , Salvetti Anna 
Published: April 2024

ABSTRACTPhosphorylation is a major post-translation modification (PTM) of proteins which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either promote or counteract viral replication. Among more than 500 kinases constituting the human kinome only few have been described as important for the Hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core protein (HBc) protein. In addition, little is known on the consequences of HBV infection on the activity of cellular kinases.The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape early after infection. For this, primary human hepatocytes (PHHs) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phosphoproteomic analysis was conducted two- and seven-days post-infection. The results indicated that while, as expected, HBV infection only minimally modified the cell proteome, significant changes were observed in the phosphorylation state of several host proteins at both times points. Gene enrichment and ontology analyses of up- and down-phosphorylated proteins revealed common and distinct signatures induced by infection. In particular, HBV infection resulted in up-phosphorylation of proteins involved in DNA damage signaling and repair, RNA metabolism, in particular splicing, and cytoplasmic cell-signaling. Down-phosphorylated proteins were mostly involved in cell signaling and communication. Validation studies carried out on selected up-phosphorylated proteins, revealed that HBV infection induced a DNA damage response characterized by the appearance of 53BP1 foci, the inactivation of which by siRNA increased cccDNA levels. In addition, among up-phosphorylated RNA binding proteins (RBPs), SRRM2, a major scaffold of nuclear speckles behaved as an antiviral factor. In accordance with these findings, kinase prediction analysis indicated that HBV infection upregulates the activity of major kinases involved in DNA repair. These results strongly suggest that HBV infection triggers an intrinsic anti-viral response involving DNA repair factors and RBPs that contribute to reduce HBV replication in cell culture models.
p53-induced GDF-15 expression promotes a pro-regenerative response in human chondrocytes upon cartilage injury
Authors: Marques Sara Sofi , Liebaug Alexandra , Maurer Svenja , Rothenbacher Dietrich , Brenner Rolf E , Riegger Jana 
Published: April 2024

AbstractPosttraumatic osteoarthritis (PTOA) is a special form of OA, developing after joint injuries. Except for some minor differences between the clinical characteristics of patients suffering from idiopathic OA (IOA) and PTOA, no biologic marker has yet been identified to distinguish IOA from PTOA. In this study, we investigated the expression of the stress-responsive cytokine growth differentiation factor 15 (GDF-15) in clinical samples from the Ulm OA study cohort (PTOA: n =12; IOA: n=54) and in a human ex vivo cartilage trauma model.We found significantly higher GDF-15 levels in synovial fluid of end-stage PTOA patients as compared to IOA patients. Further, we confirmed that fibroblast-like synoviocytes secreted increased levels of GDF-15 after stimulation with medium ofex vivo-traumatized cartilage. GDF-15 and its receptor, GFRAL, were significantly elevated in highly degenerated OA cartilage. By means of a human cartilage trauma model, we discovered that chondrocytes produced GDF-15 upon tissue injury, while antioxidative treatment attenuated GDF-15 secretion. We confirmed that oxidative stress and subsequent activation of p53 resulted in GDF-15 expression. As a transcriptional target of p53, GDF-15 was associated with chondrosenescence. Although the cytokine might therefore represent a senescence-associated secretory phenotype (SASP) factor, stimulation with exogenous GDF-15 did not cause detrimental effects but induced a pro-regenerative response in chondrocytes, characterized by enhanced proliferation as well as chondro- and cell protection after cartilage trauma. Overall, this study first describes GDF-15 as a stress-responsive and potentially pro-regenerative cytokine in the context of human PTOA.
The host GTPase Dynamin 2 modulates apical junction structure to control cell-to-cell spread ofListeria monocytogenes
Authors: Tijoriwalla Serena , Liyanage Thiloma , Herath Thilina U.B. , Lee Nicole , Rehman Attika , Gianfelice Antonella , Ireton Keith 
Published: April 2024

SUMMARYThe food-borne pathogenListeria monocytogenesuses actin-based motility to generate plasma membrane protrusions that mediate the spread of bacteria between host cells. In polarized epithelial cells, efficient protrusion formation byListeriarequires the secreted bacterial protein InlC, which binds to a carboxyl-terminal Src Homology 3 (SH3) domain in the human scaffolding protein Tuba. This interaction antagonizes Tuba, thereby diminishing cortical tension at the apical junctional complex and enhancingL. monocytogenesprotrusion formation and spread. Tuba contains five SH3 domains apart from the domain that interacts with InlC. Here we show that the human GTPase Dynamin 2 associates with two SH3 domains in the amino terminus of Tuba and acts together with this scaffolding protein to control spread ofL. monocytogenes. Genetic or pharmacological inhibition of Dynamin 2 or knockdown of Tuba each restored normal protrusion formation and spread to a bacterial strain deleted for theinlCgene (ΔinlC). Dynamin 2 localized to apical junctions in uninfected human cells and to protrusions in cells infected withListeria. Localization of Dynamin 2 to junctions and protrusions depended on Tuba. Knockdown of Dynamin 2 or Tuba diminished junctional linearity, indicating a role for these proteins in controlling cortical tension. Collectively, our results show that Dynamin 2 cooperates with Tuba to promote intercellular tension that restricts spread of ΔinlC Listeria. By expressing InlC, wild-typeL. monocytogenesovercomes this restriction.
Assembly of the Bacterial Ribosome with Circularly Permuted rRNA
Authors: Dong Xiyu , Sheng Kai , Gebert Luca F.R. , Aiyer Sriram , MacRae Ian J. , Lyumkis Dmitry , Williamson James R. 
Published: April 2024

ABSTRACTCo-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate duringin vitroribosome synthesis using a set of circularly permuted (CiPer) rRNAs. The observed ensemble of twenty-three resolved ribosome large subunit intermediates reveals conserved assembly routes with an underlying hierarchy among cooperative assembly blocks. There are intricate interdependencies for the formation of key structural rRNA helices revealed from the circular permutation of rRNA. While the order of domain synthesis is not obligatory, the order of domain association does appear to proceed with a particular order, likely due to the strong evolutionary pressure on efficient ribosome synthesis. This work reinforces the robustness of the known assembly hierarchy of the bacterial large ribosomal subunit, and offers a coherent view of how efficient assembly of CiPer rRNAs can be understood in that context.
Ribosome-binding protein 1, RRBP1, maintains peroxisomal biogenesis
Authors: Fatima Kaneez , Vihinen Helena , Akpinar Bala Ani , Somborac Tamara , Jokitalo Eija , Katajisto Pekka , Konovalova Svetlana 
Published: April 2024

ABSTRACTPeroxisomes are single membrane-bound organelles essential for human health, yet the mechanism of peroxisomal biogenesis remains poorly described. Here using a systematic double screening approach, we identified ribosome-binding protein 1, RRBP1, as a novel peroxisomal biogenesis factor in human cells. We showed that the number of peroxisomes and the levels of peroxisomal proteins are reduced by RRBP1 KO in HEK293T cells. In addition, the processing of peroxisomal matrix proteins, such as ACOX1 and thiolase was affected in RRBP1 KO HEK293T cells. Using electron microscopy, we showed that RRBP1, an ER membrane protein, is involved in the maintaining of the long-distance contact sites between ER and peroxisomal membranes, suggesting that the role of RRBP1 in peroxisomal biogenesis is mediated through inter-organellar contact sites. Altogether our results showed that RRBP1 promotes peroxisomal biogenesis in human cells highlighting the power of systematic approaches in discovering novel factors of organellar biogenesis.
Self-incompatibility phenotypes of SRK mutants can be predicted with high accuracy
Authors: Yamamoto Masaya , Ohtake Shotaro , Shinosawa Akihisa , Shirota Matsuyuki , Mitsui Yuki , Kitashiba Hiroyasu 
Published: April 2024

ABSTRACTOnly very limited information is available on why some non-synonymous variants severely alter gene function while others have no effect. To identify the characteristic features of mutations that strongly influence gene function, this study focused onS-locus receptor kinase,SRK, which encodes a highly polymorphic receptor kinase expressed in stigma papillary cells that underlies a female determinant of self-incompatibility in Brassicaceae. A set of 299Arabidopsis thalianatransformants expressing mutatedSRKbfromA. lyratawas constructed and analyzed to determine the genotype and self-incompatibility phenotype of each transformant. Almost all the transformants showing the self-incompatibility defect contained mutations in AlSRKb that altered localization to the plasma membrane. The observed mutations occurred in amino acid residues that were highly conserved acrossShaplotypes and whose predicted locations were in the interior of the protein. These mutations were likely to underlie the self-incompatibility defect as they caused significant changes to amino acid properties. Such findings suggested that mutations causing the self-incompatibility defect were more likely to result from changes to AlSRKb biosynthesis than from loss of function. In addition, this study showed the RandomForest and Extreme Gradient Boosting methods could predict self-incompatibility phenotypes of SRK mutants with high accuracy.
Lung megakaryocytes are long-lived, arise from Flt3-negative bone marrow cells, and contribute to platelet recovery in thrombocytopenia
Authors: Livada Alison C. , McGrath Kathleen E. , Malloy Michael , Li Chen , Ture Sara K. , Kingsley Paul D. , Koniski Anne D. , Vit Leah A. , Nolan Katherine E. , Mickelsen Deanne , Monette Grace E. , Maurya Preeti , Palis James , Morrell Craig N. 
Published: April 2024

AbstractWe previously characterized lung megakaryocytes (Mks) as largely extravascular cells with an immune modulatory phenotype (Pariser et al., 2021). Because bone marrow (BM) Mks are relatively short lived, it is assumed that extravascular lung Mks are constantly ‘seeded’ from the BM, but there are no experimental data to validate this concept. To investigate lung Mk origin and how their origin may impact lung Mk functions, we developed novel models using CFSE dye delivered oropharyngeal (OP) and biotin labeling to specifically label lung Mks and identify lung Mk derived platelets. Labeled lung Mks were present for up to four months, while BM Mks had a less than 1 week lifespan. In a parabiosis model, lung Mks were only partially replaced by a circulating source over a 1-month time period. Unlike tissue resident lung macrophages, we determined using MDS1-Cre-ERT2TdTomato mice that lung Mks arise from a hematopoietic stem cell (HSC) source. However, studies with FlkSwitch mTmG mice showed that lung Mks originate from a Flt3-negative cell lineage, that does not go through a multipotent progenitor stage. CFSE labeling of lung cells enabled us to track lung Mk-derived platelets and we found that about 10% of circulating platelets at steady-state are lung resident Mk-derived, but in the context of sterile thrombocytopenia there was a doubling of lung Mk derived platelets (about 20%). Lung-derived platelets were similarly increased in a murine malaria infection model (Plasmodium yoelii) typified by chronic thrombocytopenia. Taken together, our studies indicate that lung Mks arise from a Flt3-negative, HSC-dependent pathway and contribute relatively more platelets during thrombocytopenia.
How to reduce construction risks in rural areas: an evolutionary game analysis
Authors: Chen Wei , Yang Zhuzhang , Yan Hang , Zhao Ying 
Published: April 2024

PurposeThe construction industry is widely recognized as one of the most hazardous sectors in the world. Despite extensive research on safety management, a critical issue remains that insufficient attention is devoted to safety practices in rural areas. Notably, accidents frequently occur during the construction of rural self-built houses (RSH) in China. Safety management tends to be overlooked due to the perceived simplicity of the construction process. Furthermore, it is essential to acknowledge that China currently lacks comprehensive laws and regulations governing safety management in RSH construction. This paper aims to analyze the behavior of key stakeholders (including households, workmen, rural village committee and the government) and propose recommendations to mitigate safety risks associated with RSH construction.Design/methodology/approachThis paper applies evolutionary game theory to analyze the symbiotic evolution among households, workmen and rural village committee, in situations with or without government participation. Additionally, numerical simulation is utilized to examine the outcomes of various strategies implemented by the government.FindingsWithout government participation, households, workmen, and rural village committee tend to prioritize maximizing apparent benefits, often overlooking the potential safety risks. Numerical simulations reveal that while government involvement can guide these parties towards safer decisions, achieving the desired outcomes necessitates the adoption of reasonable and effective strategies. Thus, the government needs to offer targeted subsidies to these stakeholders.Originality/valueConsidering that during the construction phase, stakeholders are the main administrators accountable for safety management. However, there exists insufficient research examining the impact of stakeholder behavior on RSH construction safety. This study aims to analyze the behavior of stakeholders about how to reduce the safety risks in building RSH. Thus, the authors intend to contribute to knowledge in this area by establishing evolutionary game model. Firstly, this study carried out a theoretical by using tripartite evolutionary game to reveal the reasons for the high safety risk during building RSH. Practically, this research points out the important role of households, workmen and rural village committee in improving safety management in rural areas. Besides, some suggestions are proposed to the government about how to reduce construction safety risks in rural areas.
The influence of dark triad on knowledge hiding behavior with workplace spirituality as a moderator in higher education institutions
Authors: Joshi Parikshit , Singh Anshu , Joshi Garima , Singh Preeti 
Published: April 2024

PurposeIn the knowledge management (KM) literature, there are umpteen discussions on knowledge sharing; however, the scholarly community still faces a dearth of literature on knowledge hiding behavior (KHB) and its determinants. The current study aims to examine the direct effect of dark triad (DT) personality dimensions (machiavellianism, narcissism and psychopathy) on KHB dimensions (rationalized hiding, evasive hiding and playing dumb). Drawing on social control theory, this study also explores the moderating effect of workplace spirituality (WS) on the direct relationship between DT and KHB.Design/methodology/approachUsing purposive sampling, 281 matched-pair datasets from faculty members working with higher education institutions (HEI) in India have been obtained. The direct relationship has been tested through regression analysis and moderation analysis has been performed using the PROCESS macro for SPSS.FindingsThe study has successfully mapped DT dimensions with KHB dimensions, and it is observed that machiavellians mostly use evasive hiding, narcissists believe in rationalized hiding and paying dumb is mostly used by psychopaths. Workplace spirituality (WS) weakens the direct relationship between DT and KHB.Practical implicationsHEIs are advised to foster a climate conducive to WS by getting faculty to realize that their job is something larger than themselves through developing a sense of community among faculty members.Originality/valueThis empirical study extends the KM literature and expands the scope of bridging the gaps on KHB. It is one of the few studies to examine the impact of DT on KHB with WS as a moderator in HEIs.