bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrophosphoproteomics: extensive protein pyrophosphorylation revealed in human cell lines
Authors: Morgan Jeremy A. M. , Singh Arpita , Kurz Leonie , Nadler-Holly Michal , Penkert Martin , Krause Eberhard , Liu Fan , Bhandari Rashna , Fiedler Dorothea 
Published: November 2022

AbstractReversible protein phosphorylation is a central signaling mechanism in eukaryotic cells. While the identification of canonical phosphorylation sites using mass-spectrometry (MS) based proteomics has become routine, annotation of non-canonical phosphorylation has remained a challenge. Here, we report a tailored pyrophosphoproteomics workflow to detect and reliably assign protein pyrophosphorylation in two human cell lines, providing the first direct evidence of endogenous protein pyrophosphorylation. Detection of protein pyrophosphorylation was reproducible, specific and consistent with previous biochemical evidence relating the installation of the modification to inositol pyrophosphates (PP-InsPs). We manually validated 148 pyrophosphosites across 71 human proteins, the most heavily pyrophosphorylated of which were the nucleolar proteins NOLC1 and TCOF1. A predictive workflow based on the MS data set was established to recognize putative pyrophosphorylation sequences, and UBF1, a nucleolar protein incompatible with the proteomics method, was biochemically shown to undergo pyrophosphorylation. When the biosynthesis of PP-InsPs was perturbed in a model cell line, proteins expressed in this background exhibited lower levels of pyrophosphorylation. Disruption of PP-InsP biosynthesis also significantly reduced rDNA transcription, potentially by lowering pyrophosphorylation on regulatory proteins NOLC1, TCOF1, and UBF1. Overall, protein pyrophosphorylation emerges as an archetype of non-canonical phosphorylation, and should be considered in future phosphoproteomic analyses.
PRRC2 proteins regulate translation initiation by promoting leaky scanning
Authors: Bohlen Jonathan , Roiuk Mykola , Teleman Aurelio A. 
Published: November 2022

ABSTRACTRoughly half of animal mRNAs contain upstream Open Reading Frames (uORFs). These uORFs represent an impediment to translation of the main ORF since ribosomes usually bind the mRNA cap at the 5’ end and then scan for ORFs in a 5’-to-3’ fashion. One way for ribosomes to bypass uORFs is via leaky scanning, whereby the ribosome disregards the uORF start codon. Hence leaky scanning is an important instance of post-transcriptional regulation that affects gene expression. Few molecular factors regulating or facilitating this process are known. Here we show that the PRRC2 proteins PRRC2A, PRRC2B and PRRC2C regulate translation initiation. We find that they bind eukaryotic translation initiation factors and preinitiation complexes, and are enriched on ribosomes translating mRNAs with uORFs. We find that PRRC2 proteins promote leaky scanning past translation start codons, thereby promoting translation of mRNAs containing uORFs. Since PRRC2 proteins have been associated with cancer, this provides a mechanistic starting point for understanding their physiological and pathophysiological roles.
Trans-eQTL mapping in gene sets identifies network effects of genetic variants
Authors: Wang Lili , Babushkin Nikita , Liu Zhonghua , Liu Xuanyao 
Published: November 2022

AbstractNearly all trait-associated variants identified in GWAS are non-coding. Thecisregulatory effects of these variants have been extensively characterized, but how they impact gene regulation intranshas been the subject of much fewer studies. Mappingtransgenetic effects is very challenging because their effect sizes tend to be small and a large multiple testing burden reduces the power to detect them. In addition, read mapping biases can lead to many false positives. To reduce mapping biases and substantially improve power to maptrans-eQTLs, we developed a pipeline called trans-PCO, which combines careful read and gene filters with a principal component (PC)-based multivariate association test. Our simulations demonstrate that trans-PCO substantially outperforms existingtrans-eQTL mapping methods, including univariate and primary PC-based methods. We applied trans-PCO to two gene expression datasets from whole blood, DGN (N= 913) and eQTLGen (N= 31,684), to identifytrans-eQTLs associated with gene co-expression networks and hallmark gene sets representing well-defined biological processes. In total, we identified 14,985 high-qualitytrans-eSNPs–module pairs associated with 197 co-expression gene modules and biological processes. To better understand the effects of trait-associated variants on gene regulatory networks, we performed colocalization analyses between GWAS loci of 46 complex traits andtrans-eQTLs identified in DGN. We highlight several examples where our map oftranseffects helps us understand how trait-associated variants impact gene regulatory networks and biological pathways. For example, we found that a locus associated with platelet traits nearARHGEF3 trans-regulates a set of co-expressed genes significantly enriched in the platelet activation pathway. Additionally, six red blood cell trait-associated locitrans-regulate a gene set representing heme metabolism, a crucial process in erythropoiesis. In conclusion, trans-PCO is a powerful and reliable tool that detectstransregulators of cellular pathways and networks, which opens up new opportunities to learn the impact of trait-associated loci on gene regulatory networks.
Escherichia colicells are primed for survival before lethal antibiotic stress
Authors: Hossain Tahmina , Singh Abhyudai , Butzin Nicholas C. 
Published: November 2022

AbstractNon-genetic factors can cause significant fluctuations in gene expression levels. Regardless of growing in a stable environment, this fluctuation leads to cell-to-cell variability in an isogenic population. This phenotypic heterogeneity allows a tiny subset of bacterial cells in a population, referred to as persister cells, to tolerate long-term lethal antibiotic effects by entering into a non-dividing, metabolically altered state. One fundamental question is whether this heterogeneous persister population is due to a pre-existing genetic mutation or a result of a transiently-primed reversible cell state. To explore this, we tested clonal populations starting from a single cell using a modified Luria–Delbrück fluctuation test. Through we kept the conditions the same, the diversity in persistence level among clones was relatively consistent: varying from ∼60-100 and ∼40-70 fold for ampicillin (Amp) and apramycin (Apr), respectively. Then we divided and diluted each clone to observe whether the same clone had comparable persister levels for more than one generation. Replicates had similar persister levels even when clones were divided, diluted by 1:20, and allowed to grow for ∼5 generations. This result explicitly shows a cellular memory passed on for generations and eventually lost when cells are diluted to 1:100 and regrown (>7 generations). Our result demonstrates 1) the existence of a small population prepared for stress (“primed cells”) resulting in higher persister numbers, 2) the primed memory state is reproducible and transient, passed down for generations but eventually lost, and 3) a heterogeneous persister population is a result of a transiently-primed reversible cell state and not due to a pre-existing genetic mutation.
Circuit dissection and functional validation of a cross-species emotional biomarker
Authors: Jackson Adam , Cohen Joshua , Phensy Aarron , Chang Edward , Dawes Heather , Sohal Vikaas S. 
Published: November 2022

ABSTRACTEmotional responses arise from limbic circuits including the hippocampus and amygdala. In the human brain, beta-frequency communication between these structures correlates with self-reported mood and anxiety. However, both the mechanism and significance of this biomarker as a readout vs. driver of emotional state remain unknown. Here we show that beta-frequency communication between the ventral hippocampus and basolateral amygdala also predicts anxiety-related behavior in mice on both long timescales (∼30 min) and immediately preceding behavioral choices. Genetically encoded voltage indicators reveal that this biomarker reflects synchronization between somatostatin interneurons across both structures. Indeed, synchrony between these neurons dynamically predicts approach vs. avoidance, and optogenetically shifting this synchronization by just 25 msec is sufficient to bidirectionally modulate anxiety-related behaviors. Thus, back-translation establishes a human biomarker as a causal determinant (not just predictor) of emotional state, revealing a novel mechanism whereby interregional synchronization that is frequency-, phase- and cell type-specific controls anxiety processing.
Comparisons of healthcare resource utilisation and costs between Brugada syndrome and congenital long QT syndrome: a territory-wide study
Authors: Lee Sharen , Chung Cheuk To , Radford Danny , Chou Oscar Hou In , Lee Teddy Tai Loy , Leung Keith Sai Kit , Roever Leonardo , Rajan Rajesh , Bazoukis George , Letsas Konstantinos P , Zeng Shaoying , Liu Fang Zhou , Wong Wing Tak , Liu Tong , Tse Gary 
Published: November 2022

AbstractIntroductionHealthcare resource utilisation and costs are important metrics of healthcare burden, but they have rarely been explored in the setting of cardiac ion channelopathies.PurposeThe aim of this study is to compare HCRUs and costs between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS) in a single city of China.MethodsThis was a territory-wide retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for accident and emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analysed over a 19-year period (2001-2019) at the cohort level. Comparisons were made between BrS and LQTS cohorts using incidence rate ratios (IRRs [95% confidence intervals]).ResultsOver the 19-year study period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38-61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9-44] years, 32% male) patients were included. BrS patients had lower total costs compared to LQTS patients (2,008,126 [2,007,622-2,008,629] vs. 2,343,864 [2,342,828-2,344,900]; IRR: 0.857 [0.855-0.858]). For specific attendance types, BrS patients had higher costs for A&E attendances (83,113 [83,048-83,177] vs. 70,604 [70,487-70,721]; IRR: 1.177 [1.165-1.189]) and general outpatient services (2,176 [2,166-2,187] vs. 921 [908-935]; IRR: 2.363 [2.187-2.552]). However, they had lower costs for inpatient stay (1,391,624 [1,391,359-1,391,889] vs. 1,713,742 [1,713,166-1,714,319]; IRR: 0.812 [0.810-0.814]) and to a smaller extent, lower costs for specialist outpatient services (531213 [531049-531376] vs. 558597 [558268-558926]; IRR: 0.951 [0.947-0.9550]) compared to LQTS patients.ConclusionOverall, BrS patients consume 14% less healthcare resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients. Further studies are needed to examine patient-based attendances and costs to identify subgroups of high HCRU users for both cohorts.
Toxin-mediated downregulation of absorptive ion transporters NHE3, DRA, and SGLT1 in the colon contributes to diarrhea associated withClostridioides difficileinfection
Authors: Peritore-Galve F. Christopher , Kaji Izumi , Smith Anna , Walker Lauren M. , Shupe John A. , Dudeja Pradeep K. , Goldenring James R. , Lacy D. Borden 
Published: November 2022

ABSTRACTBackground & AimClostridioides difficileinfection (CDI) is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis. Two protein toxins, TcdA and TcdB, produced byC. difficileare the major determinants of disease. However, the physiological cause of diarrhea associated with CDI is not well understood. We investigated the effects of CDI on paracellular permeability and apical ion transporters.MethodsWe studied intestinal permeability and apical membrane transporters in female C57BL/6J mice. Üssing chambers were used to measure regional differences in paracellular permeability and ion transporter function in intestinal mucosa. Intestinal tissues were collected from mice and analyzed by immunofluorescence microscopy and RNA-sequencing.ResultsCDI increased intestinal permeability through the size-selective leak pathwayin vivo, but permeability was not increased at the sites of pathological damage. Chloride secretion was reduced in the cecum during infection by decreased CaCC function. Infected mice had decreased SGLT1 (also called SLC5A1) activity in the cecum and colon along with diminished apical abundance and an increase in luminal glucose. SGLT1 and DRA (also called SLC26A3) expression was ablated by either TcdA or TcdB, but NHE3 (also called SLC9A3) was decreased in a TcdB-dependent manner. Finally, expression of these three ion transporters was drastically reduced at the transcriptional level.ConclusionsCDI increases intestinal permeability and decreases apical abundance of NHE3, SGLT1, and DRA. This combination may cause a dysfunction in water and solute absorption in the lower gastrointestinal tract, leading to osmotic diarrhea. These findings may open novel pathways for attenuating CDI-associated diarrhea.GRAPHICAL ABSTRACT
High-Contrast PET imaging with [18F]-NT160, a Class-IIa Histone Deacetylase (Class-IIa HDAC) Probe for In Vivo Imaging of Epigenetic Machinery in the Central Nervous System
Authors: Turkman Nashaat , Xu Sulan , Huang Chun-Han , Eyermann Christopher , Salino Julia , Khan Palwasha 
Published: November 2022

AbstractWe utilized positron emission tomography (PET) imagingin vivoto map the spatiotemporal biodistribution/expression (protein density) of class-IIa histone deacetylases (class-IIa HDACs) in the brain. Herein, we report an improved radiosynthesis of [18F]-NT160 using 4-hydroxy-TEMPO which led to a significant improvement in radiochemical yield and molar activity. PET imaging with [18F]-NT160, a highly potent class-IIa HDAC inhibitor with sub-nM affinity for HDAC4 and 5 isoforms, led to high-quality and high-contrast images among various brain regions. [18F]-NT160 displayed excellent pharmacokinetic and imaging characteristics: brain uptake is high in gray matter regions, leading to high-quality PET images; tissue kinetics are appropriate for an18F tracer and specific binding for class-IIa HDACs is demonstrated by self-blockade. Higher uptake with [18F]-NT160 was observed in the hippocampus, thalamus, and cortex while there was relatively lower uptake in the cerebellum and striatum. Overall, our current studies with [18F]-NT160 will likely facilitate the development and clinical translation of class-IIa HDACs of the next generation of PET tracers for imaging and targeted therapy of cancer and the diseases of the central nervous system (CNS).
CORRELATION BETWEEN AGE-RELATED CHANGES IN SKIN MORPHOLOGY AND TROPHIC FUNCTION OF THE TRIGEMINAL NERVE
Authors: Kolomiytsev A. K. , Bazilevich A. V. , Peshkov M.V. 
Published: November 2022

AbstractHuge advancements in the field of cosmetology and numerous methods of skin restoration have kept the studies of skin aging continually relevant and up-to-date. Age-related changes in the physiological parameters of skin cover might be related to a trophic innervation disorder, which, in its turn, is caused by aging manifesting itself in the corresponding structures of the vegetative nervous system. The present article aims at describing this particular skin aging mechanism. Reduction of the amount of cells inn. sensorius superiorof the trigeminal nerve has been proven to be connected with a decrease in the amount of cells in the innervated areas of skin. This process may be considered one of the mechanisms of aging realized as a systemic phenomenon.
A call for impact! Launch of the new impact article
Authors: Keeling Debbie Isobel , Marshall Greg W. 
Published: November 2022

Purpose
The research landscape is rapidly changing and people need to evolve the way in which they think about publishing their work. The purpose of this paper is to introduce the new article type – the impact article – which is specifically designed to allow collaborators to showcase their impact work and also share learning about how impact is (or is not) achieved.

Design/methodology/approach
This introductory paper outlines the rationale for the impact article and explains its new structure, using examples from the very first set of five impact articles to be published in the journal.

Findings
There is a clear appetite for sharing and learning more about the reality of impact. Providing a facilitating structure to enable sharing, this study identifies five core building blocks to bringing about valuable impact: problem generation and identifying the impact to be achieved; working with stakeholders; the (co-)creation and learning process; impact outcomes; and the ethics of impact.

Research limitations/implications
The new impact article type encourages authors to explore the impact process from start to finish, and to share learning about the process, including dealing with the unexpected and often changing nature of impact. These important learnings will inform future impact work, especially learning about what can (and cannot) be achieved and in what timeframes.

Practical implications
Collaboration is key to achieving impact. The new impact article aims to give voice to all stakeholders, through co-authorship opportunities and exploring the differences in perspectives on impact between stakeholders, including differing understanding of the ethics of impact. And to encourage multi-stakeholder co-creative working by enabling the sharing of best practice models and methods of collaborative working.

Originality/value
This new type of article aims to celebrate and make explicit the impact of research and so complements existing types of articles that might be separately published on the research itself. The impact article is designed to facilitate knowledge exchange about impact, not underlying research conceptualization and methodologies, but the challenge of designing, developing, tracking and demonstrating impact.
Making sense of internal social media and participatory communication: exploring the employee perspective in a change process in a public sector organization
Authors: Madsen Vibeke Thøis 
Published: November 2022

PurposeThis article explores how employees in a public sector organization (PSO) make sense of the introduction of a social intranet and new employee communication roles. The aim is to understand employee sensemaking and how sensemaking influences the change process within the organization.Design/methodology/approachThe article is based on a case study in a Danish PSO with 30,000 employees. The empirical material includes strategic documents, online observations and seven focus groups with employees conducted before, during and after the introduction of a new social intranet.FindingsThe employees found that making sense of the purpose with the social intranet is difficult. A managerial approach to change communication could easily result in employees' frustrations and concerns being dismissed as signs of resistance to change. From a communication perspective, the findings reveal that the employees engaged in seven different sensemaking enactments.Research limitations/implicationsChange cannot be understood simply as something that employees are for or against. Instead, a change process should be perceived as a set of communication processes or sensemaking enactments happening in interactions between employees that can act in favor of, against or neutrally toward change.Practical implicationsManagers and communication professionals can interact with the seven sensemaking enactments, and some tentative initiatives are suggested in the article.Originality/valueThe article explores the employee perspective in a change process in a PSO and identifies seven employee sensemaking enactments highlighting that change happens in communication processes.
Comparative study of drinking water management in Mexico City and Singapore
Authors: Silva Jorge Alejandro , Martínez Omaña María Concepción 
Published: November 2022

PurposeThe aim of this research is to analyse the literature on drinking water management in Mexico City and Singapore, considering water supply, institutional organisation and management, and rates so as to propose recommendations for improvement in the water management of the Mexico City.Design/methodology/approachThe preferred reporting items for systematic reviews and meta-analysis (PRISMA) methodology is used to review the literature on drinking water management in Mexico City and Singapore in time periods from 1325 to 2021 and from 1819 to 2021, respectively, emphasising the contemporary part. The information search was realised through different prestigious databases and official documents from the governments of Mexico and Singapore, as well as international organisations. After analysing, 40 documents were included to discuss the results.FindingsThere is a contrast between water management in Singapore and Mexico City because Singapore has strong institutions coordinated with each other along with the private and social sectors and has efficient fundraising and infrastructure investment systems. Although they are cities that developed in different circumstances, a comparison between them allowed to glimpse some aspects that may be useful to replicate in Mexico City.Originality/valueThis research is novel because there is no comparative analysis like the one presented in the literature, so it is suggested to continue delving into the topics covered in future research to have more elements that allow improving drinking water management in Mexico City.
Virtual-point-based geometric error compensation model for additive manufacturing machines
Authors: Zapico Pablo , Peña Fernando , Valiño Gonzalo , Rico José Carlos , Meana Víctor , Mateos Sabino 
Published: November 2022

Purpose
The lack of geometric and dimensional accuracy of parts produced by additive manufacturing (AM) is directly related to the machine, material and process used. This paper aims to propose a method for the analysis and compensation of machine-related geometric errors applicable to any AM machine, regardless of the manufacturing process and technology used.

Design/methodology/approach
For this purpose, an error calculation model inspired by those used in computerized numerical control machines and coordinate measuring machines was developed. The error functions of the model were determined from the position deviations of a set of virtual points that are not sensitive to material and process errors. These points were obtained from the measurement of an ad hoc designed and manufactured master artefact. To validate the model, off-line compensation was applied to both the original designed artefact and an example part.

Findings
The geometric deviations in both cases were significantly smaller than those found before applying the geometric compensation. Dimensional enhancements were also achieved on the example part by using a correction parameter available in the three-dimensional printing software, whose value was adjusted from the measurement of the geometrically compensated master artefact.

Research limitations/implications
The errors that persist in the part derive from both material and process. Compensation for these type of errors requires a detailed analysis of the influencing parameters, which will be the subject of future research.

Originality/value
The use of the virtual-point-based error model increases the quality of additively manufactured parts and can be used in any AM system.