bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ABCF proteins inEscherichia coliindividually alleviate nascent peptide-induced noncanonical translations
Authors: Chadani Yuhei , Uemura Eri , Yamazaki Kohei , Kurihara Miku , Taguchi Hideki 
Published: October 2023

AbstractOrganisms possess a wide variety of proteins with a diverse repertoire of amino acid sequences, and their synthesis relies on the ribosome. Empirical observations have led to the misconception that ribosomes are robust protein factories, but in reality, they have several weaknesses. For instance, ribosomes stall during the translation of the proline-rich sequences, but the translation elongation factor EF-P assists in synthesizing proteins containing the poly-proline sequences. Thus, living organisms have evolved to expand the translation capability of ribosomes through the acquisition of translation elongation factors, enabling the synthesis of diverse proteins.In this study, we have revealed thatEscherichia coliATP-Binding Cassette family-F (ABCF) proteins, YheS, YbiT, EttA and Uup, individually cope with various noncanonical translations induced by nascent peptide sequences within the exit tunnel of the ribosome. The correspondence between noncanonical translations and ABCFs was YheS for the translational arrest by nascent SecM, YbiT for poly-basic sequence-dependent ribosome stalling and poly-acidic sequence-dependent intrinsic ribosome destabilization (IRD), EttA for IRD at the early stage of elongation, and Uup for poly-proline-dependent stalling. Our results suggest that the ATP hydrolysis-coupled structural rearrangement and interdomain linker sequence between the two nucleotide-binding domains play crucial roles in alleviating the noncanonical translations. Our study highlights a new aspect of ABCF proteins to reduce the potential risks that are encoded within the nascent peptide sequences.Significance statementProteins, that constitute living organisms, exhibit a diverse range of amino acid sequences. However, it has become evident that ribosomes have difficulties in synthesizing certain amino acid sequences, including the poly-basic, poly-acidic, and poly-proline sequences. The mechanisms underlying the expression of proteins with such challenging sequences remain largely elusive. In this study, we have unveiled that translation factor ABCF proteins inEscherichia colipromote various kinds of problematic amino acid sequences that inhibit efficient translation. Through the actions of translation elongation factors including the ABCF proteins, the translation system acquires robustness in synthesizing a vast repertoire of amino acid sequences.
7,8-Dihydroxyflavone is a direct inhibitor of pyridoxal phosphatase
Authors: Brenner Marian , Zink Christoph , Witzinger Linda , Keller Angelika , Hadamek Kerstin , Bothe Sebastian , Neuenschwander Martin , Villmann Carmen , von Kries Jens Peter , Schindelin Hermann , Jeanclos Elisabeth , Gohla Antje 
Published: October 2023

ABSTRACTVitamin B6 deficiency has been linked to cognitive impairment in human brain disorders for decades. Still, the molecular mechanisms linking vitamin B6 to these pathologies remain poorly understood, and whether vitamin B6 supplementation improves cognition is unclear as well. Pyridoxal phosphatase (PDXP), an enzyme that controls levels of pyridoxal 5’-phosphate (PLP), the co-enzymatically active form of vitamin B6, may represent an alternative therapeutic entry point into vitamin B6-associated pathologies. However, pharmacological PDXP inhibitors to test this concept are lacking. We now identify a PDXP and age-dependent decline of PLP levels in the murine hippocampus that provides a rationale for the development of PDXP inhibitors. Using a combination of small molecule screening, protein crystallography and biolayer interferometry, we discover, visualize and analyze 7,8-dihydroxyflavone (7,8-DHF) as a direct and potent PDXP inhibitor. 7,8-DHF binds and reversibly inhibits PDXP with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons, 7,8-DHF increases PLP in a PDXP-dependent manner. These findings validate PDXP as a druggable target. Of note, 7,8-DHF is a well-studied molecule in brain disorder models, although its mechanism of action is actively debated. Our discovery of 7,8-DHF as a PDXP inhibitor offers novel mechanistic insights into the controversy surrounding 7,8-DHF-mediated effects in the brain.
Investigations on Antarctic fish IgM drives the generation of an engineered mAb by CRISPR/Cas9
Authors: Ametrano Alessia , Miranda Bruno , Moretta Rosalba , Dardano Principia , De Stefano Luca , Oreste Umberto , Coscia Maria Rosaria 
Published: October 2023

AbstractIgM is the major circulating Ig isotype in teleost fish, showing in Antarctic fish unique features such as an extraordinary long hinge region, which plays a crucial role in antibody structure and function. In this work, we describe the replacement of the hinge region of a murine monoclonal antibody (mAb) with the peculiar hinge from Antarctic fish IgM. We use the CRISPR/Cas9 system as a powerful tool for generating the engineered mAb. Then, we assessed its functionality by using an innovative plasmonic substrate based on bimetallic nanoislands (AgAuNIs). The affinity constant of the modified mAb was 2.5-fold higher than the one obtained from wild-type mAb against the specific antigen. Here, we show the suitability of the CRISPR/Cas9 method for modifying a precise region in immunoglobulin gene loci. The overall results could open a frontier in further structural modifications of mAbs for biomedical and diagnostic purposes.
Fyn-mediated phosphorylation of Menin disrupts telomere maintenance in stem cells
Authors: Paul Souren , McCourt Preston M. , Le Le Thi My , Ryu Joohyun , Czaja Wioletta , Bode Ann M. , Contreras-Galindo Rafael , Dong Zigang 
Published: October 2023

AbstractTelomeres protect chromosome ends and determine the replication potential of dividing cells. The canonical telomere sequence TTAGGG is synthesized by telomerase holoenzyme, which maintains telomere length in proliferative stem cells. Although the core components of telomerase are well-defined, mechanisms of telomerase regulation are still under investigation. We report a novel role for the Src family kinase Fyn, which disrupts telomere maintenance in stem cells by phosphorylating the scaffold protein Menin. We found that Fyn knockdown prevented telomere erosion in human and mouse stem cells, validating the results with four telomere measurement techniques. We show that Fyn phosphorylates Menin at tyrosine 603 (Y603), which increases Menin’s SUMO1 modification, C-terminal stability, and importantly, its association with the telomerase RNA component (TR). Using mass spectrometry, immunoprecipitation, and immunofluorescence experiments we found that SUMO1-Menin decreases TR’s association with telomerase subunit Dyskerin, suggesting that Fyn’s phosphorylation of Menin induces telomerase subunit mislocalization and may compromise telomerase function at telomeres. Importantly, we find that Fyn inhibition reduces accelerated telomere shortening in human iPSCs harboring mutations for dyskeratosis congenita.
PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs
Authors: Contreras Xavier , Depierre David , Akkawi Charbel , Srbic Marina , Helsmoortel Marion , Cuvier Olivier , Kiernan Rosemary 
Published: October 2023

AbstractPervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or PAXT. By proteomic analysis, we have identified additional subunits of PAXT, including many orthologs of MTREC found inS. pombe. In particular, we show that polyA polymerase gamma (PAPγ) was associated with PAXT. Genome-wide mapping of the binding sites of ZFC3H1, RBM27 and PAPγ, showed that PAXT is recruited to the TSS of hundreds of genes. Loss of ZFC3H1 abolished recruitment of PAXT subunits including PAPγ to TSSs and concomitantly increased the abundance of PROMPTs at the same sites. Moreover, PAPγ, as well as MTR4 and ZFC3H1, was implicated in the polyadenylation of PROMPTs. Our results thus provide key insights into the direct targeting of PROMPT ncRNAs by PAXT at their genomic sites.
A human-specific microRNA controls the timing of excitatory synaptogenesis
Authors: Soutschek Michael , Bianco Alessandra Lo , Galkin Simon , Wüst Tatjana , Colameo David , Germade Tomas , Gross Fridolin , von Ziegler Lukas , Bohacek Johannes , Germain Pierre-Luc , Winterer Jochen , Kleele Tatjana , Schratt Gerhard 
Published: October 2023

AbstractNeural circuit development in the human cortex is considerably prolonged in comparison to non-human primates, a trait that contributes to the remarkable cognitive capacity of modern humans. Here, we explore the regulatory role of non-coding RNAs, which dramatically expanded during brain evolution, in synapse development of human-induced pluripotent stem-cell derived neurons. Inhibition of a human-specific microRNA, miR-1229-3p, results in accelerated formation of excitatory synapses and enhanced synaptic transmission. Mechanistically, miR-1229-3p controls mitochondrial homeostasis by targeting important regulators of mitochondrial autophagy and fission, such as Pink1. Stimulation of mitochondrial metabolism rescues decreased calcium buffering in miR-1229-3p depleted neurons. Our findings reveal an important function of human-specific miR-1229-3p in developmental timing of human synaptogenesis and generally implicate non-coding RNAs in the control of human connectivity and cognition.One-Sentence SummaryA human-specific microRNA slows down the formation and maturation of neuronal synapses by reducing mitochondrial metabolism and renewal.
Targeted Protein Relocalization via Protein Transport Coupling
Authors: Ng Christine S. C. , Liu Aofei , Cui Bianxiao , Banik Steven M. 
Published: October 2023

AbstractSubcellular protein localization regulates protein function and can be corrupted in cancers1and neurodegenerative diseases2–4. The localization of numerous proteins has been annotated5–7, and pharmacologically relevant approaches for precise rewiring of localization to address disease-driving phenotypes would be an attractive targeted therapeutic approach. Molecules which harness the trafficking of a shuttle protein to control the subcellular localization of a target protein could provide an avenue for targeted protein relocalization for interactome-rewiring therapeutics. To realize this concept, we deploy a quantitative approach to identify features which govern the ability to hijack protein trafficking, develop a collection of shuttle proteins and ligands, and demonstrate relocalization of proteins bearing endogenous localization signals. Using a custom imaging analysis pipeline, we show that endogenous localization signals can be overcome through molecular coupling of target proteins to shuttle proteins containing sufficiently strong native localization sequences expressed in the necessary abundance. We develop nuclear hormone receptors as viable shuttles which can be harnessed with Targeted Relocalization Activating Molecules (TRAMs) to redistribute disease-driving mutant proteins such as SMARCB1Q318X, TDP43ΔNLS, and FUSR495X. Small molecule-mediated relocalization of FUSR495Xto the nucleus from the cytoplasm reduced the number of cellular stress granules in a model of cellular stress. Using Cas9-mediated knock-in tagging, we demonstrate nuclear enrichment of both low abundance (FOXO3a) and high abundance (FKBP12) endogenous proteins via molecular coupling to nuclear hormone receptor trafficking. Finally, small molecule-mediated redistribution of NMNAT1 from nuclei to axons in primary neurons was able to slow axonal degeneration and pharmacologically mimic the WldS gain-of-function phenotype from mice resistant to certain types of neurodegeneration8. The concept of targeted protein relocalization could therefore nucleate approaches for treating disease through interactome rewiring.
OptoProfilin: A Single Component Biosensor of Applied Cellular Stress
Authors: Mann Noah , Hill Jahiem , Wang Kenneth , Hughes Robert M. 
Published: October 2023

ABSTRACTThe actin cytoskeleton is a biosensor of cellular stress and a potential prognosticator of human disease. In particular, aberrant cytoskeletal structures such as cofilin-actin rods and stress granules formed in response to energetic and oxidative stress are closely linked to neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and ALS. Whether these cytoskeletal phenomena can be harnessed for the development of biosensors for cytoskeletal dysfunction and, by extension, neurodegenerative disease progression, remains an open question. In this work, we describe the design and development of an optogenetic iteration of profilin, an actin monomer binding protein with critical functions in cytoskeletal dynamics. We demonstrate that this optically activated profilin (‘OptoProfilin’) can act as an optically triggered biosensor of applied cellular stress in select immortalized cell lines. Notably, OptoProfilin is a single component biosensor, likely increasing its utility for experimentalists. While a large body of preexisting work closely links profilin activity with cellular stress and neurodegenerative disease, this, to our knowledge, is the first example of profilin as an optogenetic biosensor of stress-induced changes in the cytoskeleton.
Powder shampoo formulation with antioxidant activity: in vitro perspectives
Authors: Madhavan Aishwariya , Unnati Meher , Rachana K. , Jain Prateek , Bhashasaraswathi K. , Joshi Apurva Kumar 
Published: October 2023

PurposeThe purpose of the study was to develop a powder shampoo with antioxidant attributes.Design/methodology/approachDry shampoo compositions were formulated containing alpha olefin sulfonate (AOS), sodium cocoyl isethionate (SCI), microcrystalline cellulose, mannitol, carboxymethyl cellulose, maltodextrin and sodium benzoate with or without extract of Cinnamomum zeylanicum bark. Cinnamon extract was chosen for this study owing to its ubiquitously known antioxidant attributes. The formulations were tested for detergency action and antioxidant potential in vitro.FindingsCinnamomum zeylanicum extract exhibited noticeable antioxidant activity in vitro. The authors observed that addition of the bark extract to the shampoo formulation was associated with remarkable increase in total phenolic content, total antioxidant activity and radical scavenging activity without any effect on detergency action.Research limitations/implicationsThis preliminary study provides a powder shampoo formulation which exhibits antioxidant attributes as a result of incorporation of cinnamon bark extract. Clinical efficacy of the formulation remains to be tested.Practical implicationsOwing to the powder format of the shampoo, the formulation can be manufactured with ease and economically. Functionalizing the formulation with enhancement of antioxidant activity by incorporation of cinnamon bark extract may be associated with beneficial clinical outcomes, which remains to be tested.Social implicationsThe proposed formulation may be stored and sold in eco-friendly packing material, thus could pave the way for reducing the burden of plastic consumption by the shampoo industry.Originality/valueThe present work demonstrates that incorporation of cinnamon bark extract to a powder shampoo formulation, containing AOS and SCI as principle surfactants, significantly enhances its antioxidant attributes.
All by myself: examining social media’s effect on social withdrawal and the mediating roles of moral disengagement and cyberaggression
Authors: Tan Caroline S.L. 
Published: October 2023

Purpose
The purpose of this study is to examine how the constructs of false self, preference for online social interaction (POSI), compulsive internet use (CIU), and online disinhibition affect social withdrawal in a social media context. The mediating effects of moral disengagement and cyber aggression are also tested.

Design/methodology/approach
Data were collected using an online survey (n = 533) from consumers in Japan. This study used structural equation modeling and PROCESS to examine the proposed relationships.

Findings
The study revealed that false self positively affects moral disengagement while online disinhibition positively affects cyber aggression and moral disengagement. Preference for online social interaction and compulsive internet use both positively impacts social withdrawal. Cyber aggression and moral disengagement were established mediators between false self/ Preference for online social interaction/ compulsive internet use/ online disinhibition and social withdrawal.

Research limitations/implications
Although restricted to cyberaggression, owing to the reciprocal relationship between cyber victimization and cyberaggression, cyber victimization can be included for further study. This study expands the understanding of social withdrawal within the context of social media.

Practical implications
Based on the findings, policies and programs that address mental health that build self-esteem, self-confidence and reduce anxiety ought to be undertaken. Managing and formulating guidelines on anonymity should also be taken into consideration.

Originality/value
This research demonstrates the crucial constructs that affect social media users negatively from the aspects of cyberaggression, moral disengagement and social withdrawal. It also establishes the importance of mental health in reducing adverse effects from social media.
The lip motion trajectory of eccentric oil seal considering material viscoelasticity
Authors: Zhai Fugang , Li Shengnan , Xing Yangtao 
Published: October 2023

Purpose
This paper aims to study the motion trajectory of the oil seal for shaft in eccentric state and derive equation of lip motion trajectory.

Design/methodology/approach
This paper analyzes the force during the motion of the eccentric lip by considering the material viscoelasticity, and a cam-plate mechanism is established as an equivalent model for the motion between the shaft and the lip; according to this, the equation of lip motion trajectory is derived.

Findings
The trajectory of the lip lags that of the shaft in the eccentric state because the viscoelasticity-affected lip recovery velocity is lower than the shaft recovery speed. The lip trajectory enters the lag phase earlier and the lag phase’s duration is longer with the increase of the eccentricity and rotational speed, because the deviation of the recovery velocities between the lip and the shaft will be exacerbated.

Originality/value
Innovatively, by considering the viscoelasticity of the material, the cam-plate mechanism is used to equivalent the motion of the shaft-lip to derive the equation for the radial motion trajectory of the eccentric lip. The regularity of lip motion is the key to determining the performance of oil seals, and the eccentric lip trajectory research method revealed in this paper provides a research basis for the performance research and optimization of eccentric oil seals.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-06-2023-0161/
Earnings management: a three-decade analysis and future prospects
Authors: Bansal Manish 
Published: October 2023

PurposeThis paper undertakes an extensive and systematic review of the literature on earnings management (EM) over the past three decades (1992–2022). Furthermore, the study identifies emerging research themes and proposes future avenues for further investigation in the realm of EM.Design/methodology/approachFor this study, a comprehensive collection of 2,775 articles on EM published between 1992 and 2022 was extracted from the Scopus database. The author employed various tools, including Microsoft Excel, R studio, Gephi and visualization of similarities viewer, to conduct bibliometric, content, thematic and cluster analyses. Additionally, the study examined the literature across three distinct periods: prior to the enactment of the Sarbanes-Oxley Act (1992–2001), subsequent to the implementation of the Sarbanes-Oxley Act (2002–2012), and after the adoption of International Financial Reporting Standards (2013–2022) to draw more inferences and insights on EM research.FindingsThe study identifies three major themes, namely the operationalization of EM constructs, the trade-off between EM tools (accrual EM, real EM and classification shifting) and the role of corporate governance in mitigating EM in emerging markets. Existing literature in these areas presents mixed and inconclusive findings, suggesting the need for further theoretical development. Further, the study findings observe a shift in research focus over time: initially, understanding manipulation techniques, then evaluating regulatory measures, and more recently, investigating the impact of global accounting standards. Several emerging research themes (technology advancements, cross-cultural and cross-national studies, sustainability, behavioral aspects and non-financial indicators of EM) have been identified. This study subsequent analysis reveals an evolving EM landscape, with researchers from disciplines like data science, computer science and engineering applying their analytical expertise to detect EM anomalies. Furthermore, this study offers significant insights into sophisticated EM techniques such as neural networks, machine learning techniques and hidden Markov models, among others, as well as relevant theories including dynamic capabilities theory, learning curve theory, psychological contract theory and normative institutional theory. These techniques and theories demonstrate the need for further advancement in the field of EM. Lastly, the findings shed light on prominent EM journals, authors and countries.Originality/valueThis study conducts quantitative bibliometric and thematic analyses of the existing literature on EM while identifying areas that require further development to advance EM research.
Prediction of traditional Chinese medicine prescriptions based on multi-label resampling
Authors: Jiang Xiaomei , Wang Shuo , Liu Wenjian , Yang Yun 
Published: October 2023

PurposeTraditional Chinese medicine (TCM) prescriptions have always relied on the experience of TCM doctors, and machine learning(ML) provides a technical means for learning these experiences and intelligently assists in prescribing. However, in TCM prescription, there are the main (Jun) herb and the auxiliary (Chen, Zuo and Shi) herb collocations. In a prescription, the types of auxiliary herbs are often more than the main herb and the auxiliary herbs often appear in other prescriptions. This leads to different frequencies of different herbs in prescriptions, namely, imbalanced labels (herbs). As a result, the existing ML algorithms are biased, and it is difficult to predict the main herb with less frequency in the actual prediction and poor performance. In order to solve the impact of this problem, this paper proposes a framework for multi-label traditional Chinese medicine (ML-TCM) based on multi-label resampling.Design/methodology/approachIn this work, a multi-label learning framework is proposed that adopts and compares the multi-label random resampling (MLROS), multi-label synthesized resampling (MLSMOTE) and multi-label synthesized resampling based on local label imbalance (MLSOL), three multi-label oversampling techniques to rebalance the TCM data.FindingsThe experimental results show that after resampling, the less frequent but important herbs can be predicted more accurately. The MLSOL method is shown to be the best with over 10% improvements on average because it balances the data by considering both features and labels when resampling.Originality/valueThe authors first systematically analyzed the label imbalance problem of different sampling methods in the field of TCM and provide a solution. And through the experimental results analysis, the authors proved the feasibility of this method, which can improve the performance by 10%−30% compared with the state-of-the-art methods.