bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Neural Correlates of Novelty and Variability in Human Decision-Making under an Active Inference Framework
Authors: Zhang Shuo , Tian Yan , Liu Quanying , Wu Haiyan 
Published: September 2023

ABSTRACTActive inference integrates perception, decision-making, and learning into a united theoretical frame-work, providing an efficient way to trade off exploration and exploitation by minimizing (expected) free energy. In this study, we asked how the brain represents values and uncertainties (novelty and variability), and resolves these uncertainties under the active inference framework in the exploration-exploitation trade-off. 25 participants performed a contextual two-armed bandit task, with electroen-cephalogram (EEG) recordings. By comparing the model evidence for active inference and rein-forcement learning models of choice behavior, we show that active inference better explains human decision-making under novelty and variability, which entails exploration or information seeking. The EEG sensor-level results show that the activity in the frontal, central, and parietal regions is associated with novelty, while activity in the frontal and central brain regions is associated with variability. The EEG source-level results indicate that the expected free energy is encoded in the frontal pole and middle frontal gyrus and uncertainties are encoded in different brain regions but with overlap. Our study dissociates the expected free energy and uncertainties in active inference theory and their neural correlates, speaking to the construct validity of active inference in characterizing cognitive processes of human decisions. It provides behavioral and neural evidence of active inference in decision processes and insights into the neural mechanism of human decisions under uncertainties.
Adaptive HD-sEMG decomposition: Towards robust real-time decoding of neural drive
Authors: Yeung Dennis , Negro Francesco , Vujaklija Ivan 
Published: September 2023

AbstractNeural interfacing via decomposition of high-density surface electromyography (HD-sEMG) should be robust to signal non-stationarities incurred by changes in joint pose and contraction intensity. We present an adaptive real-time motor unit (MU) decoding algorithm and test it on HD-sEMG collected from the extensor carpi radialis brevis during isometric contractions over a range of wrist angles and contraction intensities. The performance of the algorithm was verified using high-confidence benchmark decompositions derived from concurrently recorded intramuscular electromyography (iEMG). In trials where contraction conditions between the initialization and testing data differed, the adaptive decoding algorithm maintained significantly higher decoding accuracies when compared to static decoding methods. Using ‘gold standard’ verification techniques, we demonstrate the limitations of filter re-use decoding methods and show the necessity of parameter adaptation to achieve robust neural decoding.
Mobile barrier mechanisms for Na+-coupled symport in an MFS sugar transporter
Authors: Hariharan Parameswaran , Shi Yuqi , Katsube Satoshi , Willibal Katleen , Burrows Nathan D. , Mitchell Patrick , Bakhtiiari Amirhossein , Stanfield Samantha , Pardon Els , Kaback H. Ronald , Liang Ruibin , Steyaert Jan , Viner Rosa , Guan Lan 
Published: September 2023

AbstractWhile many 3D structures of cation-coupled transporters have been determined, the mechanistic details governing the obligatory coupling and functional regulations still remain elusive. The bacterial melibiose transporter (MelB) is a prototype of the Na+-coupled major facilitator superfamily transporters. With a conformational nanobody (Nb), we determined a low-sugar affinity inward-facing Na+-bound cryoEM structure. Collectively with the available outward-facing sugar-bound structures, both the outer and inner barriers were localized. The N-and C-terminal residues of the inner barrier contribute to the sugar selectivity pocket. When the inner barrier is broken as shown in the inward-open conformation, the sugar selectivity pocket is also broken. The binding assays by isothermal titration calorimetry revealed that this inward-facing conformation trapped by the conformation-selective Nb exhibited a greatly decreased sugar-binding affinity, suggesting the mechanisms for the substrate intracellular release and accumulation. While the inner/outer barrier shift directly regulates the sugar-binding affinity, it has little or no effect on the cation binding, which is also supported by molecular dynamics simulations. Furthermore, the use of this Nb in combination with the hydron/deuterium exchange mass spectrometry allowed us to identify dynamic regions; some regions are involved in the functionally important inner barrier-specific salt-bridge network, which indicates their critical roles in the barrier switching mechanisms for transport. These complementary results provided structural and dynamic insights into the mobile barrier mechanism for cation-coupled symport.
Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness
Authors: Mortaheb Sepehr , Fort Larry D. , Mason Natasha L. , Mallaroni Pablo , Ramaekers Johannes G. , Demertzi Athena 
Published: September 2023

AbstractTo provide insights into neurophenomenological richness after psilocybin intake, we investigated the link between dynamical brain patterns and the ensuing phenomenological pattern after psilocybin intake. Healthy participants received either psilocybin (n=22) or placebo (n=27) while in ultra-high field 7T MRI scanning. Changes in the phenomenological patterns were quantified using the 5-Dimensional Altered States of Consciousness (5D-ASC) Rating Scale, revealing alterations across all dimensions under psilocybin. Changes in the neurobiological patterns displayed that psilocybin induced widespread increases in averaged functional connectivity. Time-varying connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low BOLD signal amplitude, suggesting heightened cortical arousal. In terms of neurophenomenology, canonical correlation analysis primarily linked the transition probabilities of the hyperconnected pattern with feelings of oceanic boundlessness (OBN), and secondly with visionary restructuralization. We suggest that the brain’s tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. For the first time, these findings link brain dynamics with phenomenological alterations, providing new insights into the neurophenomenology and neurophysiology of the psychedelic state.
The circadian clock regulates PIF3 protein stability in parallel to red light
Authors: Liu Wei , Lowrey Harper , Leung Chun Chung , Adamchek Christopher , Du Juan , He Jiangman , Chen Meng , Gendron Joshua M. 
Published: September 2023

AbstractThe circadian clock is an endogenous oscillator, but its importance lies in its ability to impart rhythmicity on downstream biological processes or outputs. Focus has been placed on understanding the core transcription factors of the circadian clock and how they connect to outputs through regulated gene transcription. However, far less is known about posttranslational mechanisms that tether clocks to output processes through protein regulation. Here, we identify a protein degradation mechanism that tethers the clock to photomorphogenic growth. By performing a reverse genetic screen, we identify a clock-regulated F-box type E3 ubiquitin ligase,CLOCK-REGULATED F-BOX WITH A LONG HYPOCOTYL 1(CFH1), that controls hypocotyl length. We then show that CFH1 functions in parallel to red light signaling to target the transcription factor PIF3 for degradation. This work demonstrates that the circadian clock is tethered to photomorphogenesis through the ubiquitin proteasome system and that PIF3 protein stability acts as a hub to integrate information from multiple environmental signals.
Single-cell Herpes Simplex Virus type-1 infection of neurons using drop-based microfluidics reveals heterogeneous replication kinetics
Authors: Fredrikson Jacob P. , Domanico Luke F. , Pratt Shawna L. , Loveday Emma K. , Taylor Matthew P. , Chang Connie B. 
Published: September 2023

AbstractSingle-cell analyses of viral infections often reveal heterogeneity that is not detected by traditional population-level studies. This study applies drop-based microfluidics to investigate the dynamics of HSV-1 infection of neurons at the single-cell level. We used micron-scale Matrigel beads, termed microgels, to culture individual murine Superior Cervical ganglia (SCG) neurons or epithelial cells. Microgel-cultured cells are subsequently enclosed in individual media-in-oil droplets with a dual fluorescent-reporter HSV-1, enabling real-time observation of viral gene expression and replication. Infection within drops revealed that the kinetics of initial viral gene expression and replication were dependent on the inoculating dose. Notably, increasing inoculating doses led to earlier onset of viral gene expression and more frequent productive viral replication. These observations provide crucial insights into the complexity of HSV-1 infection in neurons and emphasize the importance of studying single-cell outcomes of viral infection. The innovative techniques presented here for cell culture and infection in drops provide a foundation for future virology and neurobiology investigations.
Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons
Authors: Sleigh James N. , Mattedi Francesca , Richter Sandy , Annuario Emily , Ng Kristal , Emilie Steinmark I. , Ivanova Iveta , Darabán István L. , Joshi Parth P. , Rhymes Elena R. , Awale Shirwa , Yahioglu Gokhan , Mitchell Jacqueline C. , Suhling Klaus , Schiavo Giampietro , Vagnoni Alessio 
Published: September 2023

ABSTRACTMitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intra-mitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.
Higher-order combinatorial chromatin perturbations by engineered CRISPR-Cas12a for functional genomics
Authors: Hsiung CC , Wilson CM , Sambold NA , Dai R , Chen Q , Misiukiewicz S , Arab A , Teyssier N , O’Loughlin T , Cofsky JC , Shi J , Gilbert LA 
Published: September 2023

AbstractMultiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting 1-3 genomic sites per cell. To develop a tool for higher-order (>3) combinatorial targeting of genomic sites with CRISPRi in functional genomics screens, we engineered anAcidaminococcusCas12a variant -- referred to asmultiplexed transcriptional interference AsCas12a (multiAsCas12a). multiAsCas12a incorporates a key mutation, R1226A, motivated by the hypothesis of nicking-induced stabilization of the ribonucleoprotein:DNA complex for improving CRISPRi activity. multiAsCas12a significantly outperforms prior state-of-the-art Cas12a variants in combinatorial CRISPRi targeting using high-order multiplexed arrays of lentivirally transduced CRISPR RNAs (crRNA), including in high-throughput pooled screens using 6-plex crRNA array libraries. Using multiAsCas12a CRISPRi, we discover new enhancer elements and dissect the combinatorial function of cis-regulatory elements. These results instantiate a group testing framework for efficiently surveying potentially numerous combinations of chromatin perturbations for biological discovery and engineering.
Sociodemographic and regional differences in neonatal and infant mortality in Switzerland: The Swiss National Cohort
Authors: Skrivankova Veronika W , Schreck Leonie D , Berlin Claudia , Panczak Radoslaw , Staub Kaspar , Zwahlen Marcel , Schulzke Sven M , Egger Matthias , Kuehni Claudia E 
Published: September 2023

SummaryBackgroundDespite a well-funded healthcare system with universal insurance coverage, Switzerland has one of the highest neonatal and infant mortality rates among high-income countries. Identifying avoidable risk factors targeted by evidence-based policies is a public health priority. We describe neonatal and infant mortality in Switzerland from 2011–2018 and explore associations with neonatal and pregnancy-related variables, parental sociodemographic information, regional factors, and socioeconomic position (SEP) using data from a long-term nation-wide cohort study.MethodsWe included 680,077 live births—representing 99.3% of all infants born in Switzerland between January 2011 and December 2018. We deterministically linked the national live birth register with the mortality register and with census and survey data to create a longitudinal dataset of neonatal and pregnancy-related variables; parental sociodemographic information, such as civil status, age, religion, education, nationality; regional factors, such as urbanity, language region; and the Swiss neighbourhood index of SEP (Swiss-SEP index). Information on maternal education was available for a random subset of 242,949 infants. We investigated associations with neonatal and infant mortality by fitting multivariable Poisson regression models with robust standard errors. Several sensitivity analyses assessed the robustness of our findings.ResultsOverall, neonatal mortality rates between 2011 and 2018 were 3.0 per 1000 live births, varying regionally from 3.2 in German-speaking to 2.4 in French-speaking and 2.1 in Italian-speaking Switzerland. For infant mortality, respective rates were 3.7 per 1000 live births overall, varying from 3.9 to 3.3 and 2.9. Adjusting for sex, maternal age, multiple birth and birth rank, neonatal mortality remained significantly associated with language region [rate ratio (RR) 0.72, 95% confidence interval (CI): 0.64–0.80 for French-speaking and RR 0.66, 95% CI: 0.51–0.87 for Italian-speaking region], with marital status (RR 1.55, 95% CI: 1.40–1.71 for unmarried), nationality (RR 1.40, 95% CI: 1.21–1.62 for non-European Economic Area vs. Swiss), and the Swiss-SEP index (RR 1.17, 95% CI: 1.00–1.36 for lowest vs. highest SEP quintile). In the subset, we showed a possible association of neonatal mortality with maternal education (RR 1.24, 95% CI: 0.95–1.61 for compulsory vs tertiary education).ConclusionWe provide detailed evidence about the social patterning of neonatal and infant mortality in Switzerland and reveal important regional differences with about 30% lower risks in French-and Italian-speaking compared with German-speaking regions. Underlying causes for such regional differences, such as cultural, lifestyle, or healthcare-related factors, warrant further exploration to inform and provide an evidence base for public health policies.
The use of cultured human alveolar basal cells to mimic honeycomb formation in idiopathic pulmonary fibrosis
Authors: Blumer Sabrina , Khan Petra , Artysh Nataliia , Plappert Linda , Savic Spasenija , Knudsen Lars , Jonigk Danny , Kuehnel Mark P. , Prasse Antje , Hostettler Katrin E. 
Published: September 2023

SummaryHoneycomb cysts (HC) within the alveolar region are distinct histopathological features in the lungs of idiopathic pulmonary fibrosis (IPF) patients. HC are lined with basal cells (BC), or with a bronchiolar-like epithelium composed of basal-, ciliated- and secretory epithelial cells. By using cultured IPF patient-derived alveolar BC, we aimed to establishin vitro- andin vivomodels to mimic HC formation in IPF. In order to do so, we cultured the cells (1) on an air liquid interface (ALI) or (2) in a three dimensional (3D) organoid modelin vitro, and (3) investigated the cells’ behavior after instillation into bleomycin-challenged micein vivo. Under the here testedin vitro- andin vivoconditions, alveolar BC differentiate and formed HC-like structures, which closely resemble HC within the IPF lung. These models therefore represent powerful tools to study HC formation, and its potential therapeutic inhibition in IPF.
Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity
Authors: Krivec Nuša , Couvreu de Deckersberg Edouard , Lei Yingnan , Al Delbany Diana , Regin Marius , Verhulst Stefaan , van Grunsven Leo A. , Sermon Karen , Spits Claudia 
Published: September 2023

SUMMARYGains of 1q are a highly recurrent chromosomal abnormality in human pluripotent stem cells. In this work, we show that gains of 1q impact the differentiation capacity to derivates of the three germ layers, leading to miss-specification to cranial placode and non-neural ectoderm during neuroectoderm differentiation and by poorer expression of lineage specific markers in hepatoblasts and cardiac progenitors. Competition assays show that the cells retain their selective advantage during differentiation, which is mediated by a higher expression ofMDM4, a gene located in the common region of gain.MDM4drives the winner phenotype of the mutant cells in both the undifferentiated and differentiating state by reducing the cells’ sensitivity to DNA-damage through decreased p53-mediated apoptosis. Finally, we find that cell density in culture plays a key role in promoting the competitive advantage of the cells by increasing DNA damage.
Mapping the substrate landscape of protein phosphatase 2A catalytic subunit PPP2CA
Authors: Brewer Abigail , Sathe Gajanan , Pflug Billie E. , Macartney Thomas J. , Sapkota Gopal P. 
Published: September 2023

SummaryProtein phosphatase 2A (PP2A) is an essential Ser/Thr phosphatase that regulates a plethora of cellular processes. PP2A operates as a holoenzyme complex, comprising one each of the scaffolding (A), regulatory (B) and catalytic (C) subunits. PPP2CA is the principal catalytic subunit of the PP2A holoenzyme complex. Although previous studies have reported many substrates of specific PP2A holoenzyme complexes, the full scope of PP2A substrates in cells remains to be defined. To address this, we generated HEK293 cells in which PPP2CA was homozygously knocked in with a dTAG, allowing for efficient and selective degradation of dTAG-PPP2CA with proteolysis-targeting chimeras (PROTACs) targeting the dTAG. By employing an unbiased global phospho-proteomic analysis, we identified 6,280 phospho-peptides corresponding to 2,204 proteins that showed a significant increase in abundance upon dTAG-PPP2CA degradation, implicating them as potential PPP2CA substrates. Among these, some were established PP2A substrates, while most were novel. Bioinformatic analyses revealed the involvement of the identified potential PPP2CA substrates in many cellular processes, including spliceosome function, the cell cycle, RNA transport and ubiquitin-mediated proteolysis. We show that a pSP/pTP motif is a predominant target for PPP2CA. We confirmed some of our phospho-proteomic data with immunoblotting, by utilising commercially available phospho-specific antibodies. We provide an in-depth atlas of potential PPP2CA substrates and establish targeted degradation as a robust tool to unveil phosphatase substrates in cells.
Islamic banks’ Sharia compliance disclosure: an international evidence
Authors: Benamraoui Abdelhafid , Moussa Tantawy , Hussien Alsohagy Mostafa 
Published: September 2023

Purpose
This paper aims to investigate the disparity and compliance of information disclosures in Islamic banks (IBs). Specifically, the research examines IBs’ compliance with Sharia disclosure requirements.

Design/methodology/approach
To determine the extent of disclosures and compliance with Islamic business principles, content analysis is applied to the annual reports of a sample of IBs from 11 countries. A comprehensive reporting framework has also been developed to assess the transparency and compliance of IBs with Islamic business principles. Institutional theory and core Islamic principles are used to inform the study and its findings.

Findings
The results reveal that IBs demonstrate limited transparency on the key Sharia compliance issues, and there is a wide variation in the level of reporting across the countries studied. Moreover, the authors find that IBs located in the single integrated regulatory framework (RF) countries disclose more information, followed by those located in dual RF countries and then those located in Islamic RF countries.

Originality/value
This study presents a unique and comprehensive framework to assess the areas of Sharia disclosure by IBs and provides a conceptual rationing for the actual level of IBs’ Sharia reporting. This study also fills a significant gap in the literature, as most studies in this field are based on a single-country study. The results are deemed of direct relevance to IBs’ managers, investors, policymakers, regulators and the wider public, particularly in the Muslim world.