bluuebunny/crossref_metadata_2025_split huggingface dataset:
The energy metabolic footprint of predictive processing in the human brain
Authors: Hechler André , de Lange Floris P. , Riedl Valentin 
Published: December 2023

AbstractNeural activity is a highly energy-intensive process. In the human brain, signaling consumes up to 75% of the available energy resources with postsynaptic potentials as the largest factor. Visual processing is especially costly, with increases in energy consumption of up to 20% in the visual cortex. In recent years, vision has been cast as a constructive process, harnessing prior knowledge in a constant feedback loop of top-down prediction and bottom-up sensory input. Interestingly, sensory input that is in line with our predictions might be processed at lower energy metabolic cost. However, there is no evidence for this claim yet, possibly due to the scarcity of measures that quantify energy consumption in the human brain.Here, we used a novel MR method measuring the cerebral metabolic rate of oxygen during sensory stimulation of visual sequences that varied in their predictability. Since predictive processing is driven by estimates of uncertainty, we assessed how confident subjects were in their knowledge of the underlying patterns. We found that processing predictable sequences steeply decreased in energetic cost with increasing confidence. Strikingly, these energetic effects were not limited to visual areas, summing up to a cortical difference of 13% between high and low levels of confidence. Furthermore, sequences deviating from expectations were energetically cheaper than predictable ones for low confidence levels, but costlier for high levels. These results speak for a major role of predictive processing in balancing the brain’s energy budget and emphasize the impact of interindividual differences when learning predictive patterns.
Ffp1, an ancestralPorphyromonasspp. fimbrillin
Authors: Acuña-Amador Luis , Barloy-Hubler Frédérique 
Published: December 2023

AbstractBackgroundLittle is known about fimbriae in thePorphyromonasgenus. Besidesfimandmfa, a thirdPorphyromonas gingivalisadhesin called Ffp1 has been described, and seems to be capital for outer membrane vesicle (OMV) production.ObjectiveWe aimed to investigate the distribution and diversity of type V fibrillin, particularly Ffp1, in thePorphyromonasgenus.MethodsA bioinformatic phylogenomic analysis was conducted using all accessiblePorphyromonasgenomes in order to generate a domain search for fimbriae, using HMM profiles.ResultsFfp1 was found as the sole fimbrillin in all the analyzed genomes. After manual biocuration and 3D modeling, this protein was determined to be a type V fimbrillin, with a closer structural resemblance to aBacteroides ovatusfimbrillin than to FimA or Mfa1 fromP. gingivalis.ConclusionIt appears that Ffp1 represents ancestral fimbriae present in allPorphyromonasspecies. Additional investigations are necessary to elucidate the biogenesis of Ffp1 fimbriae and his potential role in OMV production and niche adaptation.
APE1 associates with 60S ribosomes and tRNAs and regulates the expression of IGF2BP1
Authors: Li Wai Ming , Tafech Belal , Lee Chow H. 
Published: December 2023

AbstractApurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional protein known for its DNA repair function and redox regulation, is often found overexpressed in cancers. APE1 can be found in the nucleus, cytoplasm and secreted extracellularly. APE1 subcellular distribution in the cytoplasm is frequently reported in various types of cancer but the biological significance remains unknown. In this study, APE1 in the cytoplasm of HepG2 cells was investigated using various techniques including microscopy, differential centrifugation, sucrose gradient fractionation and CL-IP. APE1 was found to associate with 60S ribosomes and tRNAs under native conditions, suggesting it may have a specific function in the translational machinery. Knockdown of APE1 in HepG2 cells led to increased protein expression of IGF2BP1 as well as enhanced HepG2 cell migration, suggesting that APE1 can act as a tumor suppressor in this cell line model of hepatocellular carcinoma. When APE1 was depleted, the translation of a reporter construct containing the 3’UTR of IGF2BP1 was enhanced. This study provides evidence in support of the role of cytoplasmic APE1 in the control of IGF2BP1 protein translation and sheds light on the potential novel function of cytoplasmic APE1.
The ULK1 effector BAG2 regulates autophagy initiation by modulating AMBRA1 localization
Authors: Siva Sankar Devanarayanan , Kaeser-Pebernard Stephanie , Vionnet Christine , Favre Sebastian , Oliveira De Marchioro Lais , Pillet Benjamin , Zhou Jianwen , Kovacs Werner Josef , Kressler Dieter , Antonioli Manuela , Fimia Gian Maria , Dengjel Jӧrn 
Published: December 2023

AbstractCanonical autophagy is regulated by ULK1, the most proximal protein kinase specifically regulating autophagy initiation. To gain new insights into functions of the ULK1 holo-complex in autophagy regulation, we generated a deep ULK1 complex interactome by combining affinity purification- and proximity labelling-mass spectrometry of all four ULK1 complex members: ULK1, ATG13, ATG101 and RB1CC1/FIP200. Under starvation conditions, the ULK1 complex interacts with several protein and lipid kinases and phosphatases implying the formation of a signalosome. Interestingly, also several selective autophagy receptors interact with ULK1 indicating the activation of selective autophagy pathways by nutrient starvation. One effector of the ULK1 complex is the HSC/HSP70 co-chaperone BAG2, which regulates the subcellular localization of the VPS34 lipid kinase complex member AMBRA1. Depending on the nutritional status, BAG2 has opposing roles. In growth promoting conditions, the unphosphorylated form of BAG2 sequesters AMBRA1, attenuating autophagy induction. In starvation conditions, ULK1 phosphorylates BAG2 on Ser31, supporting its recruitment to the ER membrane and positively affecting autophagy flux.
Evidence for a Compensatory Relationship between Left- and Right-Lateralized Brain Networks
Authors: Peterson Madeline , Braga Rodrigo M. , Floris Dorothea L. , Nielsen Jared A. 
Published: December 2023

AbstractThe two hemispheres of the human brain are functionally asymmetric. At the network level, the language network exhibits left-hemisphere lateralization. While this asymmetry is widely replicated, the extent to which other functional networks demonstrate lateralization remains a subject of investigation. Additionally, it is unknown how the lateralization of one functional network may affect the lateralization of other networks within individuals. We quantified lateralization for each of 17 networks by computing the relative surface area on the left and right cerebral hemispheres. After examining the ecological, convergent, and external validity and test-retest reliability of this surface area-based measure of lateralization, we addressed two hypotheses across multiple datasets (Human Connectome Project = 553, Human Connectome Project-Development = 343, Natural Scenes Dataset = 8). First, we hypothesized that networks associated with language, visuospatial attention, and executive control would show the greatest lateralization. Second, we hypothesized that relationships between lateralized networks would follow a dependent relationship such that greater left-lateralization of a network would be associated with greater right-lateralization of a different network within individuals, and that this pattern would be systematic across individuals. A language network was among the three networks identified as being significantly left-lateralized, and attention and executive control networks were among the five networks identified as being significantly right-lateralized. Next, correlation matrices, an exploratory factor analysis, and confirmatory factor analyses were used to test the second hypothesis and examine the organization of lateralized networks. We found general support for a dependent relationship between highly left-and right-lateralized networks, meaning that across subjects, greater left lateralization of a given network (such as a language network) was linked to greater right lateralization of another network (such as a ventral attention/salience network) and vice versa. These results further our understanding of brain organization at the macro-scale network level in individuals, carrying specific relevance for neurodevelopmental conditions characterized by disruptions in lateralization such as autism and schizophrenia.
Host autophagy is exploited by the intracellular parasiteToxoplasma gondiito enhance amino acids levels
Authors: White Matthew D. , Angara Rajendra K. , Dias Leticia Torres , Shinde Dhananjay D. , Thomas Vinai C. , Augusto Leonardo 
Published: December 2023

AbstractToxoplasma gondii,a widespread parasite, has the ability to infect nearly any nucleated cell in warm-blooded vertebrates. It is estimated that around 2 billion people globally have been infected by this pathogen. Although most healthy individuals can effectively control parasite replication, certain parasites may evade the immune response, establishing cysts in the brain that are refractory to the immune system and resistance to available drugs. For its chronic persistence in the brain, the parasite relies on host cells’ nutrients, particularly amino acids and lipids. Therefore, understanding how latent parasites persist in the brain is crucial for identifying potential drug targets against chronic forms. While shielded within parasitophorous vacuoles (PVs) or cysts,Toxoplasmaexploits the host endoplasmic reticulum (ER) metabolism to sustains its persistence in the brain, resulting in host neurological alterations. In this study, we demonstrate thatT. gondiidisrupts the host ER homeostasis, resulting in accumulation of unfolded protein with the host ER. The host counters this stress by initiating an autophagic pathway known as ER-phagy, which breaks down unfolded proteins into amino acids, promoting their recycling. Remarkably, the persistence of latent forms in cell culture as well as behavioral changes in mice caused by the latent infection could be successfully reversed by restricting the availability of various amino acids duringT. gondiinfection. Our findings unveil the underlying mechanisms employed byT. gondiito exploit host ER and lysosomal pathways, enhancing nutrient levels during infection. These insights provide new strategies for the treatment of toxoplasmosis.ImportanceIntracellular parasites employ several mechanisms to manipulate the cellular environment, enabling them to persist in the host.Toxoplasma gondii, a single-celled parasite, possesses the ability to infect virtually any nucleated cell of warm-blooded vertebrates, including nearly 2 billion people worldwide. Unfortunately, existing treatments and immune responses are not entirely effective in eliminating the chronic persisting forms of the parasite. This study reveals thatT. gondiiinduces the host’s autophagic pathway to boost amino acid levels in infected cells. The depletion of amino acids, in turn, influences the persistence of the parasite’s chronic forms, resulting in a reduction of neurological alterations caused by chronic infection in mice. Significantly, our investigation establishes the crucial role of host ER-phagy in the parasite’s persistence within the host during latent infection.
The Hippo kinases control inflammatory Hippo signaling and restrict bacterial infection in eukaryotic phagocytes
Authors: St. Louis Brendyn M. , Quagliato Sydney M. , Su Yu-Ting , Dyson Gregory , Lee Pei-Chung 
Published: December 2023

AbstractThe Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the Hippo pathway that limits organ size and tumor formation in animals. Intriguingly, pathogens hijack this host pathway during infection, but the role of MST1/2 in innate immune cells against pathogens is unclear. In this study, we generatedMst1/2knockout macrophages to investigate the regulatory activities of the Hippo kinases in immunity. Transcriptomic analyses identified differentially expressed genes (DEGs) that are enriched in biological pathways, such as systemic lupus erythematosus, tuberculosis, and apoptosis. Surprisingly, pharmacological inhibition of the downstream components LATS1/2 in the canonical Hippo pathway did not affect expression of a set of immune DEGs, suggesting that MST1/2 control these genes via alternative inflammatory Hippo signaling. Moreover, MST1/2 may affect immune communication by influencing the release of cytokines, such as TNFα, CXCL10, and IL-1ra. Comparative analyses of the single- and double-knockout macrophages revealed that MST1 and MST2 differentially regulate TNFα release and expression of the immune transcription factor, MAF, demonstrating that the two homologous Hippo kinases individually play a unique role in innate immunity. Notably, MST1 and MST2 are both required for macrophages to activate apoptosis. Lastly, we demonstrated that the Hippo kinases are critical factors in mammalian macrophages and single-cell amoebae to restrict infection byLegionella pneumophila,Escherichia coli, andPseudomonas aeruginosa. Together, these results uncover non-canonical inflammatory Hippo signaling in macrophages and the evolutionarily conserved role of the Hippo kinases in anti-microbial defense of eukaryotic hosts.
Transient Zn2+deficiency induces replication stress and compromises daughter cell proliferation
Authors: Holtzen Samuel E. , Navid Elnaz , Kainov Joseph D. , Palmer Amy E. 
Published: December 2023

AbstractCells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+is required at the G1/S transition and during S-phase for timely completion of S-phase. A short pulse of Zn2+deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+is removed during the mother cell’s S-phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+deficiency in S-phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.SignificanceZinc is an essential micronutrient required for cells to grow and proliferate. However, the mechanism of how zinc influences proliferation is unknown. We show that short exposure to mild zinc deficiency in S-phase impairs DNA synthesis and induces replication stress, leading to pauses in daughter cell proliferation. However, pulses of low zinc during other phases of the cell cycle don’t affect mother cell cycle progression or daughter cell proliferation. These results indicate that while zinc is important for many proteins, during the cell cycle short pulses of mild zinc deficiency have the biggest impact on a cell’s ability to synthesize DNA, suggesting that DNA polymerase complex acts as a gate keeper, sensing zinc status in the cell.
pIGLET: Safe harbor landing sites for reproducible and efficient transgenesis in zebrafish
Authors: Lalonde Robert L. , Wells Harrison H. , Kemmler Cassie L. , Nieuwenhuize Susan , Lerma Raymundo , Burger Alexa , Mosimann Christian 
Published: December 2023

ABSTRACTStandard methods for transgenesis in zebrafish depend on random transgene integration into the genome followed by resource-intensive screening and validation. Targeted vector integration into validated genomic loci using phiC31 integrase-basedattP/attBrecombination has transformed mouse andDrosophilatransgenesis. However, while the phiC31 system functions in zebrafish, validated loci carryingattP-based landing or safe harbor sites suitable for universal transgenesis applications in zebrafish have not been established. Here, using CRISPR-Cas9, we converted two well-validated single insertionTol2-based zebrafish transgenes with long-standing genetic stability into twoattPlanding sites, calledphiC31 Integrase Genomic Loci Engineered for Transgenesis(pIGLET). Generating fluorescent reporters,loxP-based Switch lines, CreERT2 drivers, and gene-regulatory variant reporters in thepIGLET14aandpIGLET24blanding site alleles, we document their suitability for transgenesis applications across cell types and developmental stages. For both landing sites, we routinely achieve 25-50% germline transmission of targeted transgene integrations, drastically reducing the number of required animals and necessary resources to generate individual transgenic lines. We document that phiC31 integrase-based transgenesis intopIGLET14aandpIGLET24breproducibly results in representative reporter expression patterns in injected F0 zebrafish embryos suitable for enhancer discovery and qualitative and quantitative comparison of gene-regulatory element variants. Taken together, our new phiC31 integrase-based transgene landing sites establish reproducible, targeted zebrafish transgenesis for numerous applications while greatly reducing the workload of generating new transgenic zebrafish lines.SHORT ABSTRACTTargeted transgenesis into pre-established, “safe harbor,” landing sites remains a missing technique in zebrafish. Here, we establishedphiC31 Integrase Genomic Loci Engineered for Transgenesis (pIGLET) by CRISPR-Cas9-based conversion of two previously validatedTol2transgenes intoattPsites. phiC31-mediated transgenesis into ourpIGLET14aandpIGLET24b attPlanding sites results in 25-50% germline transmission efficiency and quantifiable transgene activity. Our landing sites are suitable for reproducible, routine zebrafish transgenesis for diverse applications.
Reprogramming the cells secretory machinery: A cystic fibrosis rescue
Authors: Cho Won Jin , Jena Bhanu P. 
Published: December 2023

ABSTRACTCystic fibrosis (CF) is a genetic disorder resulting in the secretion of highly viscous mucus in the airways, leading to lung infection, respiratory failure, morbidity and mortality. CF is attributed to mutation in the CF Transmembrane Conductance Regulator (CFTR) gene that codes for a chloride transporting channel at the cell plasma membrane. More than 2,000 mutations in the CF gene have been identified; however, the ΔF508 CFTR is the most common, accounting for approximately 70% of all CFTR mutations. Our earlier studies demonstrate the CFTR protein to be among the nearly 30 proteins constituting the porosome secretory machinery at the plasma membrane in human airway epithelial mucous-secreting cells. Additionally, our recent studies show that stimulated human airway epithelial cells pre-exposed to CFTR inhibitors result in loss of mucus secretion, suggesting the involvement of CFTR in porosome-mediated mucus secretion. To further test the hypothesis that CFTR is involved in porosome-mediated mucus secretion in the human airways, and to develop a therapeutic approach to overcome this defect in ΔF508 CFTR human bronchial epithelial cells, the current study was undertaken. Mass spectrometry and Western Blot analysis of porosomes isolated from WT-CFTR Human Bronchial Epithelial (HBE) Cells and ΔF508-CFTR CF HBE cells, demonstrate a varying loss or gain of several porosome proteins, including a decrease in the t-SNARE protein SNAP-23 and undetectable levels of the Ras GTPase activating like-protein IQGAP1 in the ΔF508-CFTR CF cells. This suggested that mutation in porosome-associated CFTR protein additionally affects other proteins within the porosome secretory machinery, negatively impacting mucus secretion. Hence, to ameliorate defects in mucus secretion in CF, the reconstitution of functional porosomes obtained from WT-CFTR HBE cells into the plasma membrane of ΔF508-CFTR mutant cells was performed. Results from the study demonstrate that porosome reconstitution rescues mucus secretion approximately four-fold more effectively than the currently available CF drugs Tezacaftor and Ivacaftor.
Employee stock ownership plans and within-firm income inequality: evidence from China
Authors: Ning Peng , Geng Lixiao , Jia Liangding 
Published: December 2023

Purpose
Drawing on bargaining power and the inequality aversion perspective, this study aims to probe employees’ influence on addressing income inequality between top executives and nonexecutive employees. Meanwhile, it examines the moderating role of employee-related factors and plan attributes.

Design/methodology/approach
This study uses a staggered difference-in-differences design with a propensity scoring match approach and verification of the parallel trend assumption to test the hypotheses.

Findings
The results support the hypothesis that employee stock ownership plans (ESOPs) significantly reduce within-firm income inequality. The negative effect is amplified by both the presence of trade unions and the unemployment rate at the regional level, as well as the duration of the lock-in period and the scale of participants within the stock ownership plan.

Practical implications
This study has implications for income inequality research and ESOP design and provides theoretical support for policymakers and corporate governance.

Originality/value
This study contributes to the literature on income inequality by examining the implementation of ESOPs from the employee perspective. Furthermore, it extends the current literature by investigating the strengthening effects of regional factors and ESOP attributes on the relationship between ESOPs and income inequality. The conclusions provide new empirical evidence to promote the effective implementation of ESOPs by combining internal and external factors.
Investigating the impact of indoor environmental quality and internal design on students' satisfaction in Tehran and North Cyprus dormitories
Authors: Karimi Hirou , Adibhesami Mohammad Anvar , Ghasemi Maryam , Sepehri Borhan , Mahdavi Estalkhsar Bonin 
Published: December 2023

PurposeThis study was conducted to investigate the impact of indoor environmental quality (IEQ) and internal design on the performance of students in university dormitories in Tehran and North Cyprus.Design/methodology/approachUsing a survey questionnaire, 298 students living in student dormitories in Tehran and North Cyprus were surveyed for data collection.FindingsResearch has shown that the academic performance and well-being of students are heavily impacted by factors related to IEQ and internal design. The study conducted in Tehran and North Cyprus has identified the most effective components of IEQ and internal design for student dormitories. The study suggests that proper ventilation, furniture design, temperature control and lighting design are key factors that significantly affect IEQ and internal design. Control and lighting design are key factors that significantly affect IEQ and internal design.Originality/valueOriginality: The study utilizes a comparative study designed to analyze the differences and similarities between the two locations.