bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitotic exchange in female germline stem cells is the major source of Sex Ratio chromosome recombination in Drosophila pseudoobscura
Authors: Koury Spencer 
Published: June 2022

ABSTRACTSex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with three non-overlapping inversions. In the male germline, Sex Ratio chromosomes distort segregation of X and Y chromosomes (99:1), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (50:50), but non-overlapping inversions strongly suppress recombination establishing a 26 Megabase haplotype (constituting ~20% of the haploid genome). Rare crossover events located between non-overlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals these recombination events were 6.5-fold more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, recombination-induced viability defects consistent with unequal exchange caused asymmetric recovery rates of complementary recombinant classes. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26 Megabase Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally-occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.
Fully Transient CRISPR/Cas12f system in plants capable of broad-spectrum resistance against Begomovirus
Authors: Haider Sibtain , Faiq Ali , Khan Muhammad Zuhaib , Mansoor Shahid , Amin Imran 
Published: June 2022

AbstractCRISPR/Cas system has emerged as the most efficient genome editing technology for both eukaryotic and prokaryotic cells. Recently, biologist have started using CRISPR/Cas9 as a defence machinery in plants against DNA viruses by targeting conserve regions of their genome. Considerable resistance requires formation of stable transgenic lines with multiple gRNAs, targeting specific viruses. Development of such transgenic plants is not only time consuming but also there will always be some uncertainty of their efficiency and off targets in plant genome. Newly discovered miniature CRISPR/Cas12f (Cas14a) system has unique ability to chop down every ssDNA fragment once activated through targeted cleavage. Here we report first fully functional transient CRISPR/Cas12f system in plants. We also show that Cas12f with just one gRNA is enough for substantial broad-spectrum resistance against Gemini viruses. Plant phenotype showed nearly complete recovery and qPCR results showed multifold decrease infection of CLCuV in CRISPR/Cas12f treated plants compare to the infected plants (infected with CLCuMuV and CLCuKV). Smaller size, broad range and more efficiency make Cas12f a superior alternative of Cas9 against diverse group of ssDNA viruses.
Histone malonylation is regulated by SIRT5 and KAT2A
Authors: Zhang Ran , Bons Joanna , Bielska Olga , Carrico Chris , Rose Jacob , Heckenbach Indra , Scheibye-Knudsen Morten , Schilling Birgit , Verdin Eric 
Published: June 2022

AbstractThe posttranslational modification lysine malonylation is found in many proteins, including histones. However, it remains unclear whether histone malonylation is regulated or functionally relevant. Here, we report that availability of malonyl-co-enzyme A (malonyl-CoA), an endogenous provider of malonyl groups, affects lysine malonylation, and that the deacylase SIRT5 selectively reduces malonylation of histones. To determine if histone malonylation is enzymatically catalyzed, we knocked down each of the 22 lysine acetyltransferases (KATs) to test their malonyltransferase potential. KAT2A knockdown in particular reduced histone malonylation levels. By mass spectrometry, H2B_K5 was highly malonylated and significantly regulated by SIRT5 in mouse brain and liver. Acetyl-CoA carboxylase (ACC), the malonyl-CoA producing enzyme, was partly localized in the nucleolus, and histone malonylation increased nucleolar area and ribosomal RNA expression. Levels of global lysine malonylation and ACC expression were higher in older mouse brains than younger mice. These experiments highlight the role of histone malonylation in ribosomal gene expression.
Abasic site ring opening and DNA-protein crosslink reversal by the SRAP protein YedK
Authors: Paulin Katherine A. , Cortez David , Eichman Brandt F. 
Published: June 2022

AbstractApuirinic/apyrimidinic (AP, or abasic) sites in DNA are one of the most common forms of DNA damage. AP sites are reactive and form crosslinks to both proteins and DNA, are prone to strand breakage, and inhibit DNA replication and transcription. The protein HMCES protects cells from strand breaks, inhibits mutagenic translesion synthesis, and participates in repair of interstrand DNA crosslinks derived from AP sites by forming a stable thiazolidine DNA-protein crosslink (DPC) to AP sites in single-stranded DNA (ssDNA). Despite the importance of HMCES to genome maintenance and the evolutionary conservation of its catalytic SRAP (SOS Response Associated Peptidase) domain, the enzymatic mechanisms of DPC formation and resolution are unknown. Using the bacterial homolog YedK, we show that the SRAP domain catalyzes conversion of the AP site to its reactive, ring-opened aldehyde form, and provide structural evidence for the Schiff base intermediate that forms prior to the more stable thiazolidine. We also report two new activities, whereby SRAP reacts with polyunsaturated aldehydes at DNA 3’-ends generated by bifunctional DNA glycosylases and catalyzes direct reversal of the DPC to regenerate the AP site, which provide insight into possible mechanisms by which HMCES DPCs are resolved in cells.
Single-cell Multi-omics Integration for Unpaired Data by a Siamese Network with Graph-based Contrastive Loss
Authors: Liu Chaozhong , Wang Linhua , Liu Zhandong 
Published: June 2022

AbstractSingle-cell omics technology is being rapidly developed to measure the epigenome, genome, and transcriptome across a range of cell types. However, integrating omics data from different modalities is still challenging. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by utilizing graph-based contrastive loss. By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitopes data. Further evaluation demonstrated our model’s unique capacity in removing the batch effect, which is a common problem in actual practice. To show how the integration impacts downstream analysis, we established model-based smoothing and cis-regulatory element inferring method and validated it with external pcHi-C evidence. Finally, the framework was applied to a COVID-19 dataset to compensate the original work with integration-based analysis, showing its necessity in single-cell multi-omics research.
The Genetic Architecture of Morphological Scaling
Authors: Wilcox Austin S. , Vea Isabelle M. , Frankino W. Anthony , Shingleton Alexander W. 
Published: June 2022

AbstractMorphological scaling relationships between the sizes of individual traits and the body captures the characteristic shape of a species, and the evolution of scaling is the primary mechanism of morphological diversification. However, we have almost no knowledge of the genetic architecture of scaling, critical if we are to understand how scaling evolves. Here we explore the genetic architecture of population-level morphological scaling relationships – the scaling relationship fit to multiple genetically-distinct individuals in a population – by describing the distribution of individual scaling relationships – genotype-specific scaling relationships that are unseen or cryptic. These individual scaling relationships harbor the genetic variation that determines relative trait growth within individuals, and theoretical studies suggest that their distribution dictates how the population scaling relationship will respond to selection. Using variation in nutrition to generate size variation within 197 isogenic lineages of Drosophila melanogaster, we reveal extensive variation in the slopes of the wing-body and leg-body scaling relationships among individual genotypes. This genetic variation reflects variation in the nutritionally-induced size plasticity of the wing, leg and body. Surprisingly, we find that variation in the slope of individual scaling relationships primarily results from variation in nutritionally-induced plasticity of body size, not leg or wing size. These data allow us to predict how different selection regimes alter scaling in Drosophila and is the first step in identifying the genetic targets of such selection. More generally, our approach provides a framework for understanding the genetic architecture of scaling, an important prerequisite to explaining how selection changes scaling and morphology.
A cell-permeant nanobody-based degrader that induces fetal hemoglobin
Authors: Shen Fangfang , Zheng Ge , Setegne Mekedlawit , Tenglin Karin , Izada Manizheh , Xie Henry , Zhai Liting , Orkin Stuart H. , Dassama Laura M. K. 
Published: June 2022

AbstractProximity-based strategies to degrade proteins have enormous therapeutic potential in medicine, but the technologies are limited to proteins for which small molecule ligands exist. The identification of such ligands for therapeutically relevant but “undruggable” proteins remains challenging. Herein, we employed yeast surface display of synthetic nanobodies to identify a protein ligand selective for BCL11A, a critical repressor of fetal globin gene transcription. Fusion of the nanobody to a cell-permeant miniature protein and an E3 adaptor creates a degrader that depletes cellular BCL11A in erythroid precursor cells, thereby inducing the expression of fetal hemoglobin, a modifier of clinical severity of sickle cell disease and β-thalassemia. This work establishes a new paradigm for the targeted degradation of previously intractable proteins using cell-permeant nanobody-based degraders.One sentence summaryA cell-permeant, protein-based degrader is used for the induction of fetal hemoglobin.
Electrophysiological indices of individual differences in adult language learning
Authors: Nalaye Halima , Cross Zachariah R. , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina 
Published: June 2022

AbstractIndividual differences in second language (L2) learning can offer insights into the neurobiological bases of learning aptitude. One neurophysiological marker of inter-individual differences in cognition is the individual alpha frequency (IAF), a trait-like measure correlated with cognition. Further, the N400 is an electrophysiological marker indexing stimulus irregularity and has been used to study L2 learning; however, its relationship with IAF and L2 learning remains unknown. To examine the relation between IAF and L2 learning (indexed by N400 amplitude), we report data from a modified miniature language learning study. After a vocabulary learning period, participants (N = 38, Mage = 25.3, SD = 7.13) judged the grammaticality of classifier-noun pairs, with mixed-effects modelling revealing lower IAF individuals were better than higher IAF individuals at grammaticality judgements. N400 amplitude also reduced across the experiment in low relative to high IAF individuals, indicating the relationship between IAF and language learning is more complex than initially postulated.
Mutations in NBEAL2 do not impact Weibel-Palade body biogenesis and Von Willebrand factor secretion in Gray Platelet Syndrome Endothelial Colony Forming Cells
Authors: Kat Marije , van Moort Iris , Bürgisser Petra E. , Kuijpers Taco W. , Hofman Menno , Favier Marie , Favier Rémi , Margadant Coert , Voorberg Jan , Bierings Ruben 
Published: June 2022

AbstractBackgroundGray Platelet Syndrome (GPS) patients with Neurobeachin-like 2 (NBEAL2) deficiency produce platelets lacking alpha-granules (AGs) and present with lifelong bleeding symptoms. AGs are lysosome-related organelles (LROs) and store the hemostatic protein Von Willebrand factor (VWF) and the transmembrane protein P-selectin. Weibel-Palade bodies (WPBs) are LROs of endothelial cells and also store VWF and P-selectin. In megakaryocytes, NBEAL2 links P-selectin on AGs to the SNARE protein SEC22B on the endoplasmic reticulum (ER), thereby preventing premature release of cargo from AG precursors. In endothelial cells, SEC22B drives VWF trafficking from ER to Golgi and promotes the formation of elongated WPBs, but it is unclear if this requires NBEAL2.ObjectivesTo investigate a potential role for NBEAL2 in WPB biogenesis and VWF secretion using NBEAL2 deficient endothelial cells.MethodsInteraction of SEC22B with NBEAL2 in endothelial cells was investigated by interactomic mass spectrometry and pull down analysis. Endothelial Colony Forming Cells (ECFCs) were isolated from healthy controls and 3 unrelated GPS patients with mutations inNBEAL2.ResultsWe show that SEC22B binds to NBEAL2 in ECs. GPS patient-derived ECFCs are deficient of NBEAL2, but reveal normal formation and maturation of WPBs and normal WPB cargo recruitment. Neither basal nor histamine-induced VWF secretion are altered in the absence of NBEAL2.ConclusionsWhile NBEAL2 deficiency causes absence of AGs in GPS patients, it has no impact on WPB functionality in ECs. Our data highlight the difference in regulatory mechanisms between these two hemostatic storage compartments.EssentialsWe characterized Gray Platelet Syndrome patient-derived endothelial cells with biallelic NBEAL2 mutationsex vivo.NBEAL2 is not essential for Weibel-Palade body biogenesis, maturation, and Von Willebrand factor secretion from endothelial cells.
Single-cell metabolic profiling reveals subgroups of primary human hepatocytes showing heterogeneous responses to drug challenge
Authors: Sanchez-Quant E. , Richter M. L. , Colomé-Tatché M. , Martinez-Jimenez C.P. 
Published: June 2022

ABSTRACTXenobiotics are primarily metabolized by hepatocytes in the liver, and primary human hepatocytes (PHHs) are the gold standard model for the assessment of drug efficacy, safety and toxicity in the early phases of drug development. Recent advances in single-cell genomics have shown liver zonation and ploidy as main drivers of cellular heterogeneity. However, little is known about the impact of hepatocyte specialization on liver function upon metabolic challenge, including hepatic metabolism, detoxification, and protein synthesis. Here, we investigate the metabolic capacity of individual human hepatocytesin vitro, and assess how chronic accumulation of lipids enhances cellular heterogeneity and impairs the metabolisms of drugs. A phenotyping five-probe cocktail was used to identify four functional subgroups of hepatocytes that respond differently to drug challenge and fatty acid accumulation. These four subgroups display differential gene expression profiles upon cocktail treatment and xenobiotic metabolism-related specialization. Notably, intracellular fat accumulation leads to increased transcriptional variability and diminished the drug-related metabolic capacity of hepatocytes. Our results demonstrate that, upon a metabolic challenge such as exposure to drugs or intracellular fat accumulation, hepatocyte subgroups lead to different and heterogeneous transcriptional responses.
Effect of reinforcement of mixed metal oxide nanoparticles in polyurethane resin for barrier and dynamic mechanical properties of steel structures
Authors: Xavier Joseph Raj 
Published: June 2022

Purpose
This study aims to study the effect of the reinforcement of mixed CeO2-ZrO2 nanoparticles in the polyurethane (PU) for protection properties of steel structures.

Design/methodology/approach
Electrochemical techniques were used to study the anticorrosion properties of the generated PU/CeO2-ZrO2 nanocomposite coated steel. Dynamic mechanical testing was done to investigate the mechanical properties.

Findings
In natural seawater, Electrochemical impedance spectroscopy experiments indicated outstanding protective behaviour for the PU/CeO2-ZrO2-coated steel. The coating resistance of the PU/CeO2-ZrO2 nanocomposite coating was found to be roughly 30% greater than that of the PU coating. Scanning electron microscopy with energy dispersive X-ray spectroscopy and X-ray diffraction analyses of the coated steel surface revealed that the CeO2-ZrO2 was accumulated at the corrosion products, preventing the corrosion. Dynamic mechanical analysis revealed that when the nanoparticle concentration was 3 Wt.%, the PU/CeO2-ZrO2 nanocomposite coating had improved dynamic mechanical parameters.

Originality/value
The coating resistance of the PU/CeO2-ZrO2 nanocomposite was determined to be 2999.17 kΩ.cm2. The perceived current by scanning electrochemical microscopy analysis across the PU/CeO2-ZrO2 coating was 1.7 nA. The PU/CeO2-ZrO2 nanocomposite had a good hydrophobic behaviour (WCA: 101o). The newly synthesised PU/CeO2-ZrO2 composite offered great barrier and mechanical properties, preventing material degradation and increase the lifespan of the coated steel. Hence, this form of coating could be used as a viable coating material for industrial purposes.
Development and validation of scale to measure responsible consumption
Authors: Jain Vijay Kumar , Dahiya Aditi , Tyagi Vikas , Sharma Preeti 
Published: June 2022

PurposeThe objective of this paper is to identify dimensions of responsible consumption from consumer perspective and develop a reliable and valid measurement scale.Design/methodology/approachThis paper has employed mixed methodology to develop items for responsible consumption. In first phase, experts' interviews were carried out to unearth the dimensions of responsible consumption. In second phase, quantitative survey was carried out to among consumers to measure their response. This was done using five-point Likert scale. The reliability and validity were ensured through empirical data online. Structural equation modeling was used to test the structural model.FindingsThe result showed that consumer perception of responsible consumption consists of five dimensions (Rationality, Sustainable Consumption, Local Consumption, Ethical Consumption and Minimalism). The result also showed strong relationship among satisfaction and responsible consumption dimensions.Practical implicationsIt will help policymakers to measure and promote responsible consumption thereby improving environmental performance and reducing carbon footprint.Originality/valueThis is the first study to develop valid and reliable instrument for responsible consumption. The findings will have several implications both theoretical and practical for policymakers and society.
CEO power and CSR: the moderating role of CEO characteristics
Authors: Chu Hsuan-Lien , Liu Nai-Yng , Chiu She-Chih 
Published: June 2022

PurposeThe purpose of this study is to examine the moderating role of the characteristics of the chief executive officer (CEO) on the association between CEO power and corporate social responsibility (CSR) performance.Design/methodology/approachThis paper conducts multiple regression analyses to empirically test the proposed hypotheses based on a sample of US-based publicly held companies. The sample period extends from 2000 to 2018. Firm-level CSR ratings are obtained from the Kinder, Lydenberg and Domini (KLD) database (currently known as MSCI ESG STATS). Financial data and CEO data are retrieved from Compustat and ExecuComp databases, respectively. Additional test and robustness analysis are performed.FindingsThis paper shows that firms with more powerful CEOs are less likely to engage in CSR activities. The negative association between CEO power and CSR is found to be exacerbated by CEOs who are younger, more competent and overconfident; however, this negative association is mitigated by CEOs who are female. This paper also finds that gender plays a more important role among CEO characteristics. Collectively, the findings highlight the potential opportunities to better understand the role of various CEO characteristics that jointly affect CSR.Originality/valueFirst, this is the first study providing a comprehensive empirical analysis of how various CEO characteristics jointly affect CSR. Prior studies that focus on standalone CEO characteristics offer an incomplete picture of the relation between a single CEO characteristic and a firm's CSR performance. The current study thus extends the research field by examining the association between seemingly unrelated CEO characteristics and CSR performance. The results also highlight that gender is the critical factor moderating the relationship between CEO power and CSR performance when it is compared with CEO age, ability and overconfidence. Second, the authors add to the literature on employee selection by showing that female CEOs mitigate the negative effect of managerial power on CSR performance. Although the currently available empirical research in management control systems focuses on ex-post analyses of moral hazard mitigation for incumbent employees, both the economics and management literature acknowledge ex ante evidence suggesting that employee selection is even more important. Our findings may provide insight into the selection of CEOs.
Understanding the (lack of) utilization of work-family practices: a multilevel perspective
Authors: Lee Yin , Kramer Amit 
Published: June 2022

PurposeMany employees do not use work-family practices to their full extent, even when they are in need of them. Drawing on the concept of psychological safety the authors propose a new construct: psychological accessibility– employees' sense of embracing the benefits of work-family practices without experiencing a fear of using them. The authors argue that the psychological accessibility of work-family practices could explain the variations in the utilization of work-family practices among employees with similar levels of family needs. Furthermore, the authors propose multilevel contextual factors that could affect the psychological accessibility of work-family practices.Design/methodology/approachThe authors develop a theoretical multilevel framework for work-family practices that places psychological accessibility at its core and addresses accessibility of work-family practices from a macro level that includes institutions and the different attributes of the national culture, a meso level that includes work time norms in organizations, and a micro level, that includes the social context at the team level in organizations.FindingsAs part of the conceptual development the authors offer 10 propositions.Originality/valueThe authors' multilevel model of psychological accessibility could explain the variations in the utilization of work-family practices across different national, organizational and group contexts. This paper refocuses scholarly attention to the psychological antecedents of the utilization of work-family practices. The authors offer some practical recommendations to make the utilization of work-family practices a psychologically safe activity.