bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of lamins B1 and B2 alters chromatin mobility and induces differential gene expression by a mesoscale-motion dependent mechanism
Authors: Pujadas Emily M. , Wei Xiaolong , Acosta Nicolas , Carter Lucas , Yang Jiekun , Almassalha Luay , Daneshkhah Ali , Rao Suhas S.P. , Agrawal Vasundhara , Seker-Polat Fidan , Aiden Erez Lieberman , Kanemaki Masato T. , Backman Vadim , Adli Mazhar 
Published: June 2023

ABSTRACTBACKGROUNDB-type lamins are critical nuclear envelope proteins that interact with the 3D genomic architecture. However, identifying the direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous B-type lamins using Auxin-inducible degron (AID) technology.RESULTSPaired with a suite of novel technologies, live-cell Dual Partial Wave Spectroscopic (Dual-PWS) microscopy,in situHi-C, and CRISPR-Sirius, we demonstrate that lamin B1 and lamin B2 depletion transforms chromatin mobility, heterochromatin positioning, gene expression, and loci-positioning with minimal disruption to mesoscale chromatin folding. Using the AID system, we show that the disruption of B-lamins alters gene expression both within and outside lamin associated domains, with distinct mechanistic patterns depending on their localization. Critically, we demonstrate that chromatin dynamics, positioning of constitutive and facultative heterochromatic markers, and chromosome positioning near the nuclear periphery are significantly altered, indicating that the mechanism of action of B-type lamins is derived from their role in maintaining chromatin dynamics and spatial positioning.CONCLUSIONSOur findings suggest that the mechanistic role of B-type lamins is stabilization of heterochromatin and chromosomal positioning along the nuclear periphery. We conclude that degrading lamin B1 and lamin B2 has several functional consequences related to both structural disease and cancer.
Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB
Authors: Zhou Ling-Yun , Jin Chen-Xi , Wang Wen-Xiao , Song Lei , Shin Jung-Bum , Du Ting-Ting , Wu Hao 
Published: June 2023

AbstractThe MRTF-SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various cell types. However, the specific contribution of MRTF-SRF in hair cells remains unknown. In this study, we showed that hair cell-specific deletion ofSrforMrtfb, but notMrtfa, leads to similar defects in the development of stereocilia dimensions and the maintenance of cuticular plate integrity. We used FACS-based hair cell RNA-seq analysis to investigate the mechanistic underpinnings of the changes observed inSrfandMrtfbmutants, respectively. Interestingly, the transcriptome analysis revealed distinct profiles of genes regulated bySrfandMrtfb, suggesting different transcriptional regulation mechanisms of actin cytoskeleton activities mediated bySrfandMrtfb. Exogenous delivery of calponin 2 using Adeno-associated virus transduction inSrfmutants partially rescued the impairments of stereocilia dimensions and the F-actin intensity of cuticular plate, suggesting the involvement ofCnn2, as anSrfdownstream target, in regulating the hair bundle morphology and cuticular plate actin cytoskeleton organization. Our study uncovers, for the first time, the unexpected differential transcriptional regulation of actin cytoskeleton mediated bySrfandMrtfbin hair cells, and also demonstrates the critical role of SRF-CNN2 in modulating actin dynamics of the stereocilia and cuticular plate, providing new insights into the molecular mechanism underlying hair cell development and maintenance.
Optimizer’s dilemma: optimization strongly influences model selection in transcriptomic prediction
Authors: Crawford Jake , Chikina Maria , Greene Casey S. 
Published: June 2023

AbstractMotivationMost models can be fit to data using various optimization approaches. While model choice is frequently reported in machine-learning-based research, optimizers are not often noted. We applied two different implementations of LASSO logistic regression implemented in Python’s scikit-learn package, using two different optimization approaches (coordinate descent and stochastic gradient descent), to predict driver mutation presence or absence from gene expression across 84 pan-cancer driver genes. Across varying levels of regularization, we compared performance and model sparsity between optimizers.ResultsAfter model selection and tuning, we found that coordinate descent (implemented in theliblinearlibrary) and SGD tended to perform comparably.liblinearmodels required more extensive tuning of regularization strength, performing best for high model sparsities (more nonzero coefficients), but did not require selection of a learning rate parameter. SGD models required tuning of the learning rate to perform well, but generally performed more robustly across different model sparsities as regularization strength decreased. Given these tradeoffs, we believe that the choice of optimizers should be clearly reported as a part of the model selection and validation process, to allow readers and reviewers to better understand the context in which results have been generated.Availability and implementationThe code used to carry out the analyses in this study is available athttps://github.com/greenelab/pancancer-evaluation/tree/master/01_stratified_classification. Performance/regularization strength curves for all genes in the Vogelstein et al. 2013 dataset are available athttps://doi.org/10.6084/m9.figshare.22728644.
Target-directed microRNA degradation regulates developmental microRNA expression and embryonic growth in mammals
Authors: Jones Benjamin T , Han Jaeil , Zhang He , Hammer Robert E. , Evers Bret M. , Rakheja Dinesh , Acharya Asha , Mendell Joshua T. 
Published: June 2023

AbstractMicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in development and disease. Target-directed miRNA degradation (TDMD), a pathway in which miRNAs that bind to specialized targets with extensive complementarity are rapidly decayed, has emerged as a potent mechanism of controlling miRNA levels. Nevertheless, the biological role and scope of miRNA regulation by TDMD in mammals remains poorly understood. To address these questions, we generated mice with constitutive or conditional deletion ofZswim8, which encodes an essential TDMD factor. Loss ofZswim8resulted in developmental defects in heart and lung, growth restriction, and perinatal lethality. Small RNA sequencing of embryonic tissues revealed widespread miRNA regulation by TDMD and greatly expanded the known catalog of miRNAs regulated by this pathway. These experiments also uncovered novel features of TDMD-regulated miRNAs, including their enrichment in co-transcribed clusters and examples in which TDMD underlies ‘arm switching’, a phenomenon wherein the dominant strand of a miRNA precursor changes in different tissues or conditions. Importantly, deletion of two miRNAs, miR-322 and miR-503, rescued growth ofZswim8null embryos, directly implicating the TDMD pathway as a regulator of mammalian body size. These data illuminate the broad landscape and developmental role of TDMD in mammals.
Gradient organisation of functional connectivity within resting state networks is present from 25 weeks gestation in the human fetal brain
Authors: Moore Jucha Willers , Wilson Siân , Oldehinkel Marianne , Cordero-Grande Lucilio , Uus Alena , Kyriakopoulou Vanessa , Duff Eugene P , O’Muircheartaigh Jonathan , Rutherford Mary A , Andreae Laura C , Hajnal Joseph V , Edwards A David , Beckmann Christian F , Arichi Tomoki , Karolis Vyacheslav R 
Published: June 2023

ABSTRACTDuring the third trimester of human gestation, the structure and function of the fetal brain is developing rapidly, laying the foundation for its connectivity framework across the lifespan. During this juncture, resting state functional MRI can be used to identify resting state networks (RSNs) which mature across gestation to resemble canonical RSNs at full term. However, the emergence of finer grain organisation of connectivity within these RSNs in the fetal brain is unknown. Using in-utero resting state fMRI, we performed connectopic mapping analysis to explore the presence of gradients in functional connectivity organisation of 11 cortical RSNs, known as connectopic maps in fetuses aged 25-37 weeks gestation (GW). We hypothesised that, if present, development of connectopic maps would be network specific in the third trimester of gestation, such that this property would be present within the earlier maturing primary sensory and motor networks before those associated with higher association function. In keeping with this, we found smooth connectopic maps in all of the studied RSNs from 25 GW, with the most spatially consistency across gestational age in the primary sensory and motor networks. Voxel-wise permutation testing of the connectopic maps identified local clusters of voxels within networks that significantly covaried with age, specifically in multisensory processing areas, suggesting multisensory processing may be developing during this period. Our analysis shows that functional gradient organisation is already established in the fetal brain and develops throughout gestation, which has strong implications for understanding how cortical organisation subserves the emergence of behaviour in the ensuing period.
Cytoplasmic redox imbalance in the thioredoxin system activates Hsf1 and results in hyperaccumulation of the sequestrase Hsp42 with misfolded proteins
Authors: Gonçalves Davi , Peffer Sara , Morano Kevin A. 
Published: June 2023

AbstractCells employ multiple systems to maintain homeostasis when experiencing environmental stress. For example, the folding of nascent polypeptides is exquisitely sensitive to proteotoxic stressors including heat, pH and oxidative stress, and is safeguarded by a network of protein chaperones that concentrate potentially toxic misfolded proteins into transient assemblies to promote folding or degradation. The redox environment itself is buffered by both cytosolic and organellar thioredoxin and glutathione pathways. How these systems are linked is poorly understood. Here, we determine that specific disruption of the cytosolic thioredoxin system resulted in constitutive activation of the heat shock response inSaccharomyces cerevisiaeand accumulation of the sequestrase Hsp42 into an exaggerated and persistent juxtanuclear quality control (JUNQ) compartment. Terminally misfolded proteins also accumulated in this compartment in thioredoxin reductase (TRR1)-deficient cells, despite apparently normal formation and dissolution of transient cytoplasmic quality control (CytoQ) bodies during heat shock. Notably, cells lackingTRR1andHSP42exhibited severe synthetic slow growth exacerbated by oxidative stress, signifying a critical role for Hsp42 under redox challenged conditions. Finally, we demonstrated that Hsp42 localization patterns intrr1Δcells mimic those observed in chronically aging and glucose-starved cells, linking nutrient depletion and redox imbalance with management of misfolded proteins via a mechanism of long-term sequestration.
Cell type and condition specific functional annotation of schizophrenia associated non-coding genetic variants
Authors: Rummel Christine K. , Gagliardi Miriam , Herholt Alexander , Ahmad Ruhel , Murek Vanessa , Weigert Liesa , Hausruckinger Anna , Maidl Susanne , Jimenez-Barron Laura , Trastulla Lucia , Eder Mathias , Rossner Moritz , Ziller Michael J. 
Published: June 2023

AbstractSchizophrenia (SCZ) is a highly polygenic disease and genome wide association studies have identified thousands of genetic variants that are statistically associated with this psychiatric disorder. However, our ability to translate these associations into insights on the disease mechanisms has been challenging since the causal genetic variants, their molecular function and their target genes remain largely unknown. In order to address these questions, we established a functional genomics pipeline in combination with induced pluripotent stem cell technology to functionally characterize ~35,000 non-coding genetic variants associated with schizophrenia along with their target genes. This analysis identified a set of 620 (1.7%) single nucleotide polymorphisms as functional on a molecular level in a highly cell type and condition specific fashion. These results provide a high-resolution map of functional variant-gene combinations and offer comprehensive biological insights into the developmental context and stimulation dependent molecular processes modulated by SCZ associated genetic variation.
Extracellular vesicle-mediated trafficking of developmental cues is altered during human brain disease
Authors: Pipicelli Fabrizia , Forero Andrea , Moser Sylvain , Matteo Francesco Di , Baumann Natalia , Grätz Christian , Pisfil Mariano Gonzalez , Bekjarova Zagorka , Pfaffl Michael W. , Canafoglia Laura , Pütz Benno , Kielkowski Pavel , Cernilogar Filippo M. , Maccarrone Giuseppina , Jabaudon Denis , Giaimo Rossella Di , Cappello Silvia 
Published: June 2023

AbstractCellular crosstalk is an essential process influenced by numerous factors including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neuron-to-neuron communication, but the role of EVs in progenitor-to-neuron and -astrocyte communication and whether EVs display cell-type-specific features for cellular crosstalk during neurogenesis is unknown. Here, using human-derived cerebral organoids, neural progenitors, neurons, and astrocytes, we found that many proteins coded by genes associated with neurodevelopmental disorders are transported via EVs. Thus, we characterized the protein content of EVs and showed their cell type-specific dynamics and function during brain development. Changes in the physiological crosstalk between cells can lead to neurodevelopmental disorders. EVs from patients with epilepsy were found altered in composition and function. Alterations in the intracellular and extracellular compartments highlighted a clear dysregulation of protein trafficking. This study sheds new light on the biology of EVs during brain development and neurodevelopmental disorders.Abstract FigureGraphical abstract(left) EV uptake mechanism varies depending on the receiving cell type; NPCs transport neuron EVs (nEVs) and astrocyte EVs (aEVs) to the nucleus, astrocytes localize progenitor EVs (pEVs) to the cytoplasm, and neurons retain pEVs and aEVs along the plasma membrane. (right) Cerebral organoids (COs) from progressive Myoclonus Epilepsy Type I (EPM1) patients release EVs lacking key proteins in neurodevelopment and proteins necessary for EV biogenesis and release. Illustration created using BioRender.
A fuzzy synthetic evaluation approach for climate for innovation measurement in construction firms
Authors: Nguyen Minh Van , Nguyen Tu Thanh 
Published: June 2023

PurposeThis research aims to identify the climate for innovation variables and to propose an innovative tool to quantitatively assess the degree of climate for innovation of construction firms.Design/methodology/approach14 climate-for-innovation variables were identified from a literature review and discussion with experienced practitioners. After that, a questionnaire survey was developed to collect data. Factor analysis was used to analyze data gathered from 157 completed responses. Then, fuzzy synthetic evaluation (FSE) was employed to assess the degree of climate for innovation in Vietnamese construction firms.FindingsClimate-for-innovation variables were categorized into four factors by factor analysis. The FSE analysis shows leadership is the most critical category of four factors, followed by working culture, organization and employee commitment. The calculation also illustrates that the climate for innovation in Vietnamese construction firms is at a moderate level.Originality/valueThis research is one of the first integrated climate for innovation of construction firms in a comprehensive formulation. The formulation provides the decision-makers with a reliable tool to evaluate the degree of climate for innovation, thus having appropriate strategies to develop sustainable innovation performance within their organizations.
A domain model for geometric modeling in support of the automated BIM modeling
Authors: Yang Lin , Li Qiming , Pan Wei 
Published: June 2023

PurposeThis research aims to argue that manual geometric modeling is blocking the building information modeling (BIM) promotion to small-size companies. Therefore, it is necessary to study a manner of automated modeling to reduce the dependence of BIM implementation on manpower. This paper aims to make a study into such a system to propose both its theory and prototype.Design/methodology/approachThis research took a prototyping as the methodology, which consists of three steps: (1) proposing a theoretical framework supporting automated geometric modeling process; (2) developing a prototype system based on the framework; (3) conducting a testing for the prototype system on its performance.FindingsPrevious researches into automated geometric modeling only respectively focused on a specific procedure for a particular engineering domain. No general model was abstracted to support generic geometric modeling. This paper, taking higher level of abstraction, proposed such a model that can describe general geometric modeling process to serve generic automated geometric modeling systems.Research limitations/implicationsThis paper focused on only geometric modeling, skipping non-geometric information of BIM. A complete BIM model consists of geometric and non-geometric data. Therefore, the method of combination of them is on the research agenda.Originality/valueThe model proposed by this paper provide a mechanism to translate engineering geometric objects into textual representations, being able to act as the kernel of generic automated geometric modeling systems, which are expected to boost BIM promotion in industry.
Trust recovery tactics in financial services: the moderating role of service failure severity
Authors: Raza Ali , Tsiotsou Rodoula , Sarfraz Muhammad , Ishaq Muhammad Ishtiaq 
Published: June 2023

PurposeGiven the fierce competition in financial services, service failure management and trust restoration tactics are becoming strategic priorities. Studies investigating trust restoration have increased over the years due to the significance of trust in services and the frequency of trust violations. Drawing on the sense-making and defensive approaches of attribution theory, this study aims to explore the effectiveness of various trust recovery tactics (e.g. apology, explanation, and investigation) in financial services considering the prevalence of service failure severity.Design/methodology/approachBased on a scenario-based survey, this study gathered data from 402 consumers of different banks in Pakistan. The study analyzed the data using ordinary least square regressions and structural equation modeling.FindingsThe study indicated that explanation is more effective in repairing character-competence and commitment-based trust, while investigation remained highly effective for inducing congruence-based trust. Interestingly, an apology was more effective for communication-based trust repairing, while context-based trust recovery was unaffected against all recovery tactics. Despite the prevalence of severe service failure, recovery actions proved fully effective for character-competence and commitment-based trust while partially effective for congruence-based trust recovery. This study also found that severe service failure undermines the effectiveness of recovery actions in repairing communication and context-based trust.Originality/valueThe study extends the literature on trust recovery by integrating sense-making and defensive attribution theory. The sense-making approach contributes to the existing knowledge on trust recovery by elucidating how consumers and service providers develop a shared understanding to facilitate the recovery mechanism of multidimensional trust in financial services.
Natural resource abundance and income inequality: a case study of Algeria
Authors: Chekouri Sidi Mohammed 
Published: June 2023

Purpose
This study aims to present an empirical investigation on the effect of natural resource rent on income inequality in Algeria over the period 1980–2020.

Design/methodology/approach
The analysis is carried out by using the novel developed method dynamic autoregressive distributed lag (ARDL) simulation technique alongside the Kernel-based regularized least squares.

Findings
The bounds test revealed a long-run relationship between natural resource rent and income inequality. Our estimation results suggest that natural resource rent, GDP per capita and government expenditures are all associated with lower income inequality in the short and long term. Moreover, the author found that better institutional quality is more likely to reduce income inequality in Algeria. This empirical finding is further validated by the counterfactual shocks from the dynamic ARDL simulation, which reveal a significant decrease in predicted income inequality following a positive change in resource rents and a gradual, significant increase in inequality after a negative change in resource rents.

Originality/value
The present study is the first to use the dynamic ARDL model to investigate the impact of positive and negative changes in natural resource rent on income inequality in Algeria.