bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription factors operate on a limited vocabulary of binding motifs inArabidopsis thaliana
Authors: Zenker Sanja , Wulf Donat , Meierhenrich Anja , Becker Sarah , Eisenhut Marion , Stracke Ralf , Weisshaar Bernd , Bräutigam Andrea
Published: August 2023

Predicting gene expression from promoter sequence requires understanding of the different signal integration points within a promoter. Sequence-specific transcription factors (TFs) binding to their cognate TF binding motifs control gene expression in eukaryotes by activating and repressing transcription. Their interplay generates complex expression patterns in reaction to environmental conditions and developmental cues.

We hypothesized that signals are not only integrated by different TFs binding various positions in a promoter, but also by single TF binding motifs onto which multiple TFs can bind. Analyzing 2,190 binding motifs, we identified only 76 core TF binding motifs in plants. Twenty-one TF protein families act highly specific and bind a single conserved motif. Four TF families are classified as semi-conserved as they bind up to four motifs within a family, with divisions along phylogenetic groups. Five TF families bind diverse motifs. Expression analyses revealed high competition within TF families for the same binding motif. The results show that singular binding motifs act as signal integrators in plants where a combination of binding affinity and TF abundance likely determine the output.
Intermodal consistency of whole-brain connectivity and signal propagation delays
Authors: Jedynak Maciej , Lopez Emahnuel Troisi , Romano Antonella , Jirsa Viktor , David Olivier , Sorrentino Pierpaolo
Published: August 2023

Measuring the propagation of perturbations across the human brain and their transmission delays is critical for network neuroscience, but it is a challenging problem that still requires cross-validation approaches. Here, we compare results from a recently introduced, non-invasive technique of functional delays estimation from source-reconstructed electro/magnetoencephalography, to the corresponding findings from a large dataset of cortico-cortical evoked potentials estimated from intracerebral stimulations of epileptic pharmaco-resistant patients. The two methods yield significantly similar probabilistic connectivity maps and signal propagation delays. This similarity suggests a correspondence between the mechanisms underpinning the propagation of spontaneously generated scale-free perturbations (i.e. neuronal avalanches observed in resting state activity studied using magnetoencephalography) and the spreading of cortico-cortical evoked potentials. This manuscript provides evidence for the accuracy of a subject-specific estimate of functional delays obtained non-invasively from reconstructed sources. Conversely, our findings show that estimates obtained from externally-induced perturbations capture physiological activities. In conclusion, this manuscript constitutes a cross-validation between two different modalities. Importantly, the capability to measure delays non-invasively (as per MEG) paves the way for the inclusion of functional delays in personalized large-scale brain models as well as in diagnostic and prognostic algorithms.
Lesion aware automated processing pipeline for multimodal neuroimaging stroke data and The Virtual Brain (TVB)
Authors: Bey Patrik , Dhindsa Kiret , Kashyap Amrit , Schirner Michael , Feldheim Jan , Bönstrup Marlene , Schulz Robert , Cheng Bastian , Thomalla Götz , Gerloff Christian , Ritter Petra
Published: August 2023

Background

Processing stroke magnetic resonance imaging (MRI) brain data can be susceptible to lesion-based abnormalities. In this study we developed and validated the Lesion Aware automated Processing Pipeline (LeAPP) that incorporates mitigation measures, improving volumetric and connectomics outputs compared to current standards in automated MRI processing pipelines.

Methods

Building upon the Human Connectome Project (HCP) minimal processing pipeline, we introduced correction measures, such as cost-function masking and virtual brain transplant, and extended functional and diffusion processing to match acquisition protocols often found in a clinical context. A total of 51 participants (36 stroke patients (65.7±12.96 years, 18 female) and 15 healthy controls (69.2±7.4 years, 7 female)) were processed across four time points for patients (3-5, 30-40, 85-95, 340-380 days after stroke onset) and one time point for controls. Artificially lesioned brains (N=82), derived from healthy brains and informed by real stroke lesions were created, thus generating ground-truth data for validation. The processing pipeline and validation framework are available as containerized open-source software. Reconstruction quality has been quantified on whole brain level and for lesion affected and unaffected regions-of-interest (ROIs) using metrics like dice score, volume difference and center-of-gravity distance. Global and local level connectome reconstruction was assessed using node strength, node centrality and clustering coefficient.

Results

The new pipeline LeAPP provides close reconstructions of the ground truth. Deviations in reconstructed averaged whole brain node strength and all ROI based volume and connectome metrics were significantly reduced compared to the HCP pipeline without stroke specific mitigation measures.

Conclusions

LeAPP improves reconstruction quality of multimodal MRI processing for brain parcellation and structural connectome estimation significantly over the non-adapted HCP in the presence of lesions and provides a robust framework for diffusion and functional image processing of clinical stroke data. This novel open-source automated processing pipeline contributes to a development towards reproducible research.

Graphical abstract
Expansion Strategy-Driven Micron-Level Resolution Mass Spectrometry Imaging of Lipids in Mouse Brain Tissue
Authors: Winnie Hung Yik Ling , Xie Chengyi , Wang Jianing , Diao Xin , Li Ruxin , Wang Xiaoxiao , Qiu Shulan , Fang Jiacheng , Cai Zongwei
Published: August 2023

A novel method for enhanced resolution, termed expansion mass spectrometry imaging (Ex-MSI), has been developed for lipid mass spectrometry imaging, utilizing existing commercially available mass spectrometers without necessitating modifications. This approach involves embedding tissue sections in a swellable polyelectrolyte gel, with the target biomolecules indirectly anchored to the gel network. By employing matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), the method has realized an enhancement in spatial resolution that surpasses the conventional resolution limits of commercial instruments by approximately 4.5 folds. This enhancement permits the detailed visualization of intricate structures within the mouse brain at a subcellular level, with a lateral resolution nearing 1 μm. As a physical technique for achieving resolution beyond standard capabilities, this approach is readily adaptable and presents a powerful tool for high-definition imaging in biological research.
PP2A and GSK3 act as modifiers of FUS-ALS by modulating mitochondrial transport
Authors: Tziortzouda Paraskevi , Steyaert Jolien , Scheveneels Wendy , Sicart Adria , Stoklund Dittlau Katarina , Barbosa Correia Adriana Margarida , Pal Arun , Hermann Andreas , Van Damme Philip , Moens Thomas , Van Den Bosch Ludo
Published: August 2023

ALS is a fatal neurodegenerative disease which currently lacks effective treatments. Mutations in the RNA-binding protein FUS are a common cause of familial ALS, accounting for around 4% of fALS cases. Studying the mechanisms by which mutant FUS is toxic to neurons may provide insight into the pathogenesis of both familial and sporadic forms of ALS. Here we identify Protein Phosphatase 2A (PP2A) and Glycogen Synthase Kinase 3 (GSK3) as novel modifiers of FUS-ALSin vivo, looking from fly to human. PP2A-C and GSK3β inhibition rescued FUS-induced toxicity inDrosophilaand disease-relevant phenotypes in human iPSC-derived spinal motor neurons (sMNs). In bothDrosophilaand human iPSC-sMNs, we observed reduced GSK3β inhibitory phosphorylation, suggesting that FUS dysfunction results in GSK3β hyperactivity. We found that PP2A acts upstream of GSK3, affecting its inhibitory phosphorylation, and in synergy they modulate mitochondrial transport through the motor protein kinesin. Our data providein vivoevidence that PP2A and GSK3 are disease modifiers, and reveal an unexplored mechanistic link between PP2A, GSK3 and kinesin in FUS-associated ALS.
Social network structure scales with group size in a multi-species analysis
Authors: Gagliardi Brenna Marie , St-Amant Nader , Dakin Roslyn
Published: August 2023

Social networks can shape the evolution and transmission of behaviours. Recent studies have characterized social networks within species, but we know relatively little about the drivers of variation in the structure of social networks across species. Here, we analyze a database of 631 social networks from more than 30 animal species to test how social network properties scale with group size. We examine three properties of social network topology: the uniformity of edge weights within the group, the selectivity of individuals for particular social partners, and the amount of heterogeneity among individuals in social behaviour. We show that most of the variation in these three network properties is due to differences between focal species and/or study methodologies, with only negligible differences between the three animal classes in our analysis (birds, mammals, and insects). Our analysis also indicates that group size is the key factor that determines the topology of animal social networks. In smaller groups, edge weights are distributed more uniformly, and individuals show greater selectivity regarding their social partners. These results suggest that there are general scaling rules governing the social networks of diverse animal species. In small groups, individuals form strong connections to a selective set of partners, whereas in large groups, weaker ties are common, and individuals are less likely to limit their interactions to specific partners.

Significance Statement

Sociality is observed throughout the animal kingdom. Animal societies also vary widely in group size, from a few individuals to groups with millions on individuals. How do animal social networks vary across this spectrum? We investigated this question using data compiled from recent bird, mammal, and insect studies. Surprisingly, we found broad overlap in the social network structures of these three distinct animal classes. We tested the effect of group size on social network structure, and found that in small groups, individuals form stronger social ties with preferred social partners; by contrast, animals in large groups have weaker and less selective social ties. These results suggest that diverse animal groups are governed by similar processes that determine the structure of their social networks.
The genomic landscape, causes, and consequences of extensive phylogenomic discordance in Old World mice and rats
Authors: Thomas Gregg W. C. , Hughes Jonathan J. , Kumon Tomohiro , Berv Jacob S. , Erik Nordgren C. , Lampson Michael , Levine Mia , Searle Jeremy B. , Good Jeffrey M.
Published: August 2023

A species tree is a central concept in evolutionary biology whereby a single branching phylogeny reflects relationships among species. However, the phylogenies of different genomic regions often differ from the species tree. Although tree discordance is often widespread in phylogenomic studies, we still lack a clear understanding of how variation in phylogenetic patterns is shaped by genome biology or the extent to which discordance may compromise comparative studies. We characterized patterns of phylogenomic discordance across the murine rodents (Old World mice and rats) – a large and ecologically diverse group that gave rise to the mouse and rat model systems. Combining new linked-read genome assemblies for seven murine species with eleven published rodent genomes, we first used ultra-conserved elements (UCEs) to infer a robust species tree. We then used whole genomes to examine finer-scale patterns of discordance and found that phylogenies built from proximate chromosomal regions had similar phylogenies. However, there was no relationship between tree similarity and local recombination rates in house mice, suggesting that genetic linkage influences phylogenetic patterns over deeper timescales. This signal may be independent of contemporary recombination landscapes. We also detected a strong influence of linked selection whereby purifying selection at UCEs led to less discordance, while genes experiencing positive selection showed more discordant and variable phylogenetic signals. Finally, we show that assuming a single species tree can result in high error rates when testing for positive selection under different models. Collectively, our results highlight the complex relationship between phylogenetic inference and genome biology and underscore how failure to account for this complexity can mislead comparative genomic studies.
Ribose lowers RpoS translation through RbsD mRNA
Authors: Badaoui Andrew , Smith Isabel , Balla Melisa , Cavanaugh Mikayla , Lockart Julia , Parsons Dylan , Martes Esteban , Dorean Shaina , Diop Cheik , Tran Thomas , Peterson Celeste N.
Published: August 2023

TheEscherichia colisigma factor RpoS accumulates during starvation, activates transcription of the general stress response, and then rapidly returns to low levels upon nutrient replenishment. Sugar levels modulate RpoS levels by signaling though central metabolism, ATP and the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) transport system, which favors glucose. However, there have been few examples of dedicated control pathways for specific sugars regulating RpoS. We screened an overexpression library with a RpoS’-‘LacZ reporter and found that overexpressing the ribose metabolismrbsDgene reduced RpoS levels. A functional RbsD ribose pyranase protein was not necessary for the effect, suggesting that the RbsD mRNA was responsible for the effect. We used a series of LacZ fusions and RT-qPCR to determine how RbsD mRNA affects RpoS and found that regulation of RpoS occurred at the level of translation. Furthermore, the effect ofrbsDoverexpression was diminished in strain that did not have the RpoS untranslated hairpin loop or the small RNA chaperone Hfq. RbsD mRNA has previously been shown to bind to the sRNA DsrA. We demonstrated that the effect of RbsD on RpoS was dependent on the sRNAs DsrA and ArcZ and Hfq. Finally, we showed that the sugar ribose lowers RpoS levels in a manner that requires RbsD. In summary, our results demonstrate that RpoS levels respond specifically to ribose though a component of the ribose metabolism pathway and the main player, RbsD, acts as dual function mRNA that has a regulatory role by interacting with the sRNAs that control RpoS.
A systems vaccinology resource to develop and test computational models of immunity
Authors: Shinde Pramod , Soldevila Ferran , Reyna Joaquin , Aoki Minori , Rasmussen Mikkel , Willemsen Lisa , Kojima Mari , Ha Brendan , Greenbaum Jason A , Overton James A , Guzman-Orozco Hector , Nili Somayeh , Orfield Shelby , Gygi Jeremy P. , da Silva Antunes Ricardo , Sette Alessandro , Grant Barry , Olsen Lars Rønn , Konstorum Anna , Guan Leying , Ay Ferhat , Kleinstein Steven H. , Peters Bjoern
Published: August 2023

Computational models that predict an individual’s response to a vaccine offer the potential for mechanistic insights and personalized vaccination strategies. These models are increasingly derived from systems vaccinology studies that generate immune profiles from human cohorts pre- and post-vaccination. Most of these studies involve relatively small cohorts and profile the response to a single vaccine. The ability to assess the performance of the resulting models would be improved by comparing their performance on independent datasets, as has been done with great success in other areas of biology such as protein structure predictions. To transfer this approach to system vaccinology studies, we established a prototype platform that focuses on the evaluation of Computational Models of Immunity to Pertussis Booster vaccinations (CMI-PB). A community resource, CMI-PB generates experimental data for the explicit purpose of model evaluation, which is performed through a series of annual data releases and associated contests. We here report on our experience with the first such ‘dry run’ for a contest where the goal was to predict individual immune responses based on pre-vaccination multi-omic profiles. Over 30 models adopted from the literature were tested, but only one was predictive, and was based on age alone. The performance of new models built using CMI-PB training data was much better, but varied significantly based on the choice of pre-vaccination features used and the model building strategy. This suggests that previously published models developed for other vaccines do not generalize well to Pertussis Booster vaccination. Overall, these results reinforced the need for comparative analysis across models and datasets that CMI-PB aims to achieve. We are seeking wider community engagement for our first public prediction contest, which will open in early 2024.
Novel hepatocellular carcinomas (HCC) Subtype-Specific Biomarkers
Authors: Croft Jacob , Quintanar Odalys , Gao Liyuan , Sheng Victor , Zhang Jun
Published: August 2023

Introduction

Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a global health concern and a leading cause of cancer-related deaths. HCC accounts for a significant portion of liver cancers and has low survival rates of 5% to 30%, especially for HCC patients with a survival rate of 15%. Early detection is challenging due to the absence of symptoms in the early stages. The complexity and molecular diversity of HCC contribute to its poor prognosis. Understanding its molecular subtypes and mechanisms is crucial for improved management.

Methods

The study utilized publicly available data to investigate the potential diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC) based on their transcript per million (TPM) expression levels. A dataset of 407 HCC patient profiles was analyzed for survival trends and gene expression patterns.

Results

Through a comprehensive approach, over 900 potential prognostic candidates were identified. Further analysis narrowed down 647 prognostic and diagnostic candidate biomarkers. The study also explored the role of the CmPn signaling network in HCC, reaffirming that its components could act as prognostic markers. Additionally, the study-utilized machine learning to discover 102 transcription factors (TFs) associated with HCC, from candidate biomarkers.

Conclusions

The findings provide insights into the molecular basis of HCC and offer potential avenues for improved diagnosis, treatment, and patient outcomes. The expanded prognostic biomarker pool aids in pinpointing HCC-specific grading and staging biomarkers, facilitating targeted therapies for improved patient outcomes and survival rates
Working memory-related activity in catecholaminergic nuclei in schizophrenia
Authors: Amekran Nada , Mäki-Marttunen Verónica
Published: August 2023

Schizophrenia is a complex psychiatric condition in which cortical, subcortical and neuromodulatory alterations have been implicated in its symptom expression. Long standing views of schizophrenia symptoms have posed that alterations in catecholaminergic systems, which explain psychotic symptoms, may be also associated with the cognitive impairments commonly observed in this condition. However, evidence on the involvement of catecholaminergic regions on cognitive functions in schizophrenia remains scarce. Working memory is one cognitive domain where schizophrenia patients present more impairments at higher levels of cognitive load. Here we explored the activation of catecholaminergic regions during a working memory task in schizophrenia. We reanalyzed an openly available functional magnetic resonance imaging dataset where schizophrenia patients and healthy controls were scanned while performing the N-back task. We compared activation of two dopaminergic areas, ventral tegmental area and substantia nigra, and of a noradrenergic nucleus, locus coeruleus, to the presentation of targets, and compared three different levels of cognitive load (0-, 1– and 2-back). We found that across nuclei, higher load was related to lower activation. Furthermore, schizophrenia patients showed reduced activation at the highest load level when compared to healthy controls. These findings point to catecholaminergic systems as mediators of the deficits in effort processing in schizophrenia. Our study lends further support for the importance of including catecholaminergic systems in the mechanisms of cognitive deficits in schizophrenia.
Social contact patterns following the COVID-19 pandemic: a snapshot of post-pandemic behaviour from the CoMix study
Authors: Jarvis Christopher I , Coletti Pietro , Backer Jantien A , Munday James D , Faes Christel , Beutels Philippe , Althaus Christian L. , Low Nicola , Wallinga Jacco , Hens Niel , Edmunds W John
Published: August 2023

Background

The COVID-19 pandemic led to unprecedented changes in behaviour. To estimate if these persisted a final new round of the CoMix survey was conducted in four countries at a time when all societal restrictions had been lifted for several months.

Methods

We conducted a survey on a nationally representative sample in the UK, Netherlands (NL), Belgium (BE), and Switzerland (CH). Participants were asked about their contacts and behaviours on the previous day. We calculated contact matrices and compared the contact levels to a pre-pandemic baseline to estimate R0.

Results

Data collection occurred from 17 November to 7 December 2022. 7,477 participants were recruited. Some were asked to undertake the survey on behalf of their children. Only 14.4% of all participants reported wearing a facemask on the previous day, varying between 6.7% in NL to 17.8% in CH. Self-reported vaccination rates in adults were similar for each country at around 86%. Trimmed mean recorded contacts were highest in NL with 9.9 (95% confidence interval [CI] 9.0 to 10.8) contacts per person per day and lowest in CH at 6.0 (95% CI 5.4 to 6.6). The number of contacts at home were similar between the countries. Contacts at work were lowest in the UK (1.4 contacts per person per day) and highest in NL at 2.8 contacts per person per day. Other contacts were also lower in the UK at 1.6 per person per day (95% CI 1.4 to 1.9) and highest in NL at 3.4 recorded per person per day (95% CI 4.0 to 4.0). Using the next-generation approach suggests that R0for a close-contact disease would be roughly half pre-pandemic levels in the UK, 80% in NL and intermediate in the other two countries.

Conclusions

The pandemic appears to have resulted in lasting changes in contact patterns that would be expected to have an impact on the epidemiology of many different pathogens. Further post-pandemic surveys are necessary to confirm this finding.
CRISPR-Hybrid: A CRISPR-Mediated Intracellular Directed Evolution Platform for RNA Aptamers
Authors: Su-Tobon Qiwen , Fan Jiayi , Feeney Kevin , Ren Hongyuan , Autissier Patrick , Wang Peiyi , Huang Yingzi , Niu Jia
Published: August 2023

Recent advances in gene editing and precise regulation of gene expression based on CRISPR technologies have provided powerful tools for the understanding and manipulation of gene functions. Fusing RNA aptamers to the sgRNA of CRISPR can recruit cognate RNA-binding protein (RBP) effectors to target genomic sites, and the expression of sgRNA containing different RNA aptamers permit simultaneous multiplexed and multifunctional gene regulations. Here, we report an intracellular directed evolution platform for RNA aptamers against intracellularly expressed RBPs. We optimized a bacterial CRISPR-hybrid system coupled with FACS, and identified novel high affinity RNA aptamers orthogonal to existing aptamer-RBP pairs. Application of orthogonal aptamer-RBP pairs in multiplexed CRISPR allowed effective simultaneous transcriptional activation and repression of endogenous genes in mammalian cells.
Pangenome evaluation of gene essentiality inStreptococcus pyogenes
Authors: Jespersen Magnus G. , Hayes Andrew J. , Tong Steven Y. C. , Davies Mark R.
Published: August 2023

Populations of bacterial pathogens are made of strains that often have variable gene content, termed the pangenome. Variations in the genetic makeup of a single strain can alter bacterial physiology and fitness in response to different environmental stimuli. To define biologically relevant genes within a genome, genome-wide knockout transposon mutant libraries have been used to identify genes essential for survival or virulence in a particular strain. Such phenotypic studies have been applied in four different genotypes of the major human pathogenStreptococcus pyogenes, yet challenges exist in comparing results across studies conducted in different genetic backgrounds and conditions. To advance genotype-phenotype inferences within a population genomic framework of 250S. pyogenesreference genomes, we systematically re-analysed publicly available transposon sequencing datasets fromS. pyogenesusing a transposon sequencing specific analysis pipeline, Transit. Across 4 genetic backgrounds and 9 phenotypic conditions, 311 genes were highly essential for survival, corresponding to ∼22% of the core genome. Among the 311 genes, functions related to information storage, and processing were overrepresented. Genes associated with cellular processing and signalling were of significantly higher essentiality underin vivoconditions (animal models with differing disease manifestation and site of colonisation) compared toin vitro(varying types of culture media). Finally, essential operons acrossS. pyogenesgenotypes were defined, with an increased number of essential operons detected underin vivoconditions. This study provides an extendible database to which new studies can be added, and a searchable html-based resource to direct future investigations intoS. pyogenespopulation biology.

Importance

Streptococcus pyogenesis a human adapted pathogen occupying restricted ecological niches. Understanding essentiality of genes across different strains and experimental conditions is important to direct research questions and efforts to prevent the large burden of disease caused byS. pyogenes. To this end we systematically reanalysed transposon sequencing studies inS. pyogenesusing transposon sequencing specific methods, integrating them into an extendible meta-analysis framework. This provides a repository of gene essentiality inS. pyogenesfor the community to guide future phenotypic studies.
Escherichia coliMicrocin B17 as a chassis for the development of novel antimicrobial peptides
Authors: Withanage Shamal , Masschelein Joleen , Pinheiro Vitor B.
Published: August 2023

Antimicrobial resistance remains an urgent and growing global health problem. Peptides with antimicrobial activity are widespread in nature but are rarely harnessed for application, making them an underexplored and untapped resource. Many harbor post-translational modifications, which are essential for function and have evolved alongside specialized export and immunity machineries – leading to the current paradigm that natural sequences cannot be changed, and curtailing their development as antimicrobial agents. Nonetheless, we found sufficient ambiguity in literature to question if that remained true forE. coliMccB17. We demonstrate that its natural machinery for synthesis, export and immunity, can be co-opted as a platform for novel azole-modified antimicrobial peptide discovery. We show that the sequence space available for exploration is large and densely populated with functional sequences.

One-Sentence Summary

E. colican be harnessed as anin vivoplatform for the isolation of novel antimicrobial azole-modified peptides.
Common as well as unique methylation-sensitive DNA regulatory elements in three mammalian SLC9C1 genes
Authors: Gardner Cameron C. , Abele Jason A. , Winkler Thomas J. , Reckers Caroline N. , Anas Sydney A. , James Paul F.
Published: August 2023

The SLC9C1 gene (which encodes the NHE10 protein) is essential for male fertility in both mice and humans, however the epigenetic mechanisms regulating its testis/sperm-specific gene expression have yet to be studied. Here we identify and characterize DNA regulatory elements of the SLC9C1 gene across three mammalian species: mouse, rat, and human. First,in silicoanalysis of these mammalian SLC9C1 genes identified a CpG island located upstream of the transcription start site in the same relative position in all three genes. Further analysis reveals that this CpG island behaves differently, with respect to gene regulatory activity, in the mouse SLC9C1 gene than it does in the rat and human SLC9C1 gene. The mouse SLC9C1 CpG island displays strong promoter activity by itself and seems to have a stronger gene regulatory effect than either the rat or human SLC9C1 CpG islands. While the function of the upstream SLC9C1 CpG island may be divergent across the three studied species, it appears that the promoters of these three mammalian SLC9C1 genes share similar DNA methylation-sensitive regulatory mechanisms. All three SLC9C1 promoter regions are differentially methylated in lung and testis, being more hypermethylated in lung relative to the testis, and DNA sequence alignments provide strong evidence of primary sequence conservation. Luciferase assays reveal thatin vitromethylation of constructs containing different elements of the three SLC9C1 genes largely exhibit methylation-sensitive promoter activity (reduced promoter activity when methylated) in both HEK 293 and GC-1spg cells. In total, our data suggest that the DNA methylation-sensitive elements of the mouse, rat, and human SLC9C1 promoters are largely conserved, while the upstream SLC9C1 CpG island common to all three species seems to perform a different function in mouse than it does in rat and human. This work provides evidence that while homologous genes can all be regulated by DNA methylation-dependent epigenetic mechanisms, the location of the specific cis-regulatory elements responsible for this regulation can differ across species.
SCP Viz – A universal graphical user interface for single protein analysis in single cell proteomics datasets
Authors: Warshanna Ahmed , Orsburn Benjamin C.
Published: August 2023

Single cell proteomics (SCP) requires the analysis of dozens to thousands of single human cells to draw biological conclusions. However, assessing of the abundance of single proteins in output data presents a considerable challenge, and no simple universal solutions currently exist. To address this, we developed SCP Viz, a statistical package with a graphical user interface that can handle small and large scale SCP output from any instrument or data processing software. In this software, the abundance of individual proteins can be plotted in a variety of ways, using either unadjusted or normalized outputs. These outputs can also be transformed or imputed within the software. SCP Viz offers a variety of plotting options which can help identify significantly altered proteins between groups, both before and after quantitative transformations. Upon the discovery of subpopulations of single cells, users can easily regroup the cells of interest using straightforward text-based filters. When used in this way, SCP Viz allows users to visualize proteomic heterogeneity at the level of individual proteins, cells, or identified subcellular populations. SCP Viz is compatible with output files from MaxQuant, FragPipe, SpectroNaut, and Proteome Discoverer, and should work equally well with other formats. SCP Viz is publicly available athttps://github.com/orsburn/SCPViz. For demonstrations, users can download our test data from GitHub and use an online version that accepts user input for analysis athttps://orsburnlab.shinyapps.io/SCPViz/.

Abstract graphic
PTPN2 copper-sensing rapidly relays copper level fluctuations into EGFR/CREB activation and associatedCTR1transcriptional repression
Authors: Ross Matthew O. , Xie Yuan , Owyang Ryan C. , Ye Chang , Zbihley Olivia N.P. , Lyu Ruitu , Wu Tong , Wang Pingluan , Karginova Olga , Olopade Olufunmilayo I. , Zhao Minglei , He Chuan
Published: August 2023

Fluxes in human intra- and extracellular copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate (cAMP). We herein applied an unbiased temporal evaluation of the whole-genome transcriptional activities modulated by fluctuations in copper levels to identify the copper sensor proteins responsible for driving these activities. We found that fluctuations in physiologically-relevant copper levels rapidly modulate EGFR/MAPK/ERK signal transduction and activation of the transcription factor cAMP response element-binding protein (CREB). Both intracellular and extracellular assays support Cu1+inhibition of the EGFR-phosphatase PTPN2 (and potentially the homologous PTPN1)–via direct ligation to the PTPN2 active site cysteine side chain–as the underlying mechanism of copper-stimulated EGFR signal transduction activation. Depletion of copper represses this signaling pathway. We additionally showi) copper supplementation drives transcriptional repression of the copper importerCTR1andii) CREB activity is inversely correlated withCTR1expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper-stimulated MAPK/ERK/CREB-signaling andCTR1expression, thereby uncovering a previously unrecognized link between copper levels and cellular signal transduction.
Mutation in SLC45A2 leads to loss of melanin in parrot feathers
Authors: Roy Shatadru Ghosh , Bakhrat Anna , Abdu Moty , Afonso Sandra , Pereira Paulo , Carneiro Miguel , Abdu Uri
Published: August 2023

Bird plumage coloration is a complex and multi-factorial process that involves both genetic and environmental factors. Diverse pigment groups contribute to plumage variation in different birds. In parrots, the predominant green color results from the combination of two different primary colors-yellow and blue. Psittacofulvin, a pigment uniquely found in parrots, is responsible for the yellow coloration, while blue is suggested to be the result of light scattering by feather nanostructures and melanin granules. So far, genetic control of melanin-mediated blue coloration has been elusive. In this study, we demonstrated that feather from theyellowmutant rose-ringed parakeet displays loss of melanosome granules in spongy layer of feather barb. Using whole genome sequencing, we found that mutation in SLC45A2, an important solute carrier protein in melanin synthetic pathway, is responsible for the sex-linkedyellowphenotype in rose-ringed parakeet. Intriguingly, one of the mutations, P53L found in yellowP. krameriis already reported as P58A/S in the human albinism database, known to be associated with human OCA4. We further showed that mutations inSLC45A2gene affect melanin production also in other members of Psittaculidae family such as alexandrine, and plum-headed parakeets. Additionally, we demonstrate that the mutations associated with the sex-linkedyellowphenotype, localized within the transmembrane domains of the SLC45A2 protein, affect the protein localization pattern. This is the first evidence of plumage color variation involvingSLC45A2in parrots and confirmation of associated mutations in the transmembrane domains of the protein that affect its localization.

Article Summary

The vibrant green tone of parrot plumage emerges from a blend of yellow and blue. While yellow comes from a unique pigment psittacofulvin, the genetics of blue structural color has puzzled scientists. Through novel genetic study, here we identified mutations inSLC45A2gene, causing loss of melanin in feathers that contributes to the blue structural color. This insight opens a new chapter in understanding avian coloration and the complex interplay of feather microstructure and genetics in nature’s palette.
Crystal structure and Hirshfeld surface analysis of (2E)-1-(4-bromophenyl)-3-(2-methylphenyl)prop-2-en-1-one
Authors: Akkurt Mehmet , Naghiyev Farid N. , Khrustalev Victor N. , Asadov Khammed A. , Khalilov Ali N. , Bhattarai Ajaya , Mamedov İbrahim G.
Published: August 2023

In the title compound, C16H13BrO, the planes of the aromatic rings are inclined at an angle of 23.49 (15)°, and the configuration about the C=C bond is E. In the crystal, the molecules are linked into chains by weak C—H...O interactions along the b axis. Successive chains form a zigzag structure along the c axis, and these chains are connected to each other by face-to-face π–π stacking interactions along the a axis. These layers, parallel to the (001) plane, are linked by van der Waals interactions, thus consolidating the crystal structure. Hirshfeld surface analysis showed that the most significant contacts in the structure are H...H (43.1%), C...H/H...C (17.4%), Br...H/H...Br (14.9%), C...C (11.9%) and O...H/H...O (9.8%).
Synthesis, structure and Hirshfeld surface analysis of a coordination compound of cadmium acetate with 2-aminobenzoxazole
Authors: Razzoqova Surayyo , Ibragimov Aziz , Torambetov Batirbay , Kadirova Shakhnoza , Holczbauer Tamas , Ashurov Jamshid , Ibragimov Bakhtiyar
Published: August 2023

A first coordination compound of 2-aminobenzoxazole (2AB), namely, bis(2-aminobenzoxazole-κN
3)bis(acetato-κ2
O,O′)cadmium(II), [Cd(CH3COO)2(2AB)2], has been synthesized from ethanol solutions of Cd(CH3(COO)2 and 2AB. In the monoclinic crystals with the space group C21/c, the cadmium ions coordinate two neutral 2AB molecules in a monodentate fashion through the oxazole N atom, while two acetate ligands are coordinated through the O atoms in a bidentate manner. The coordination polyhedron of the central ion is substantially distorted octahedral. There are two relatively strong intramolecular hydrogen bonds in the complex molecule. Additionally, two intermolecular hydrogen bonds associate complex molecules into columns running in the [1\overline{1}0] and [110] directions. The Hirshfeld surface analysis shows that 45.7% of the intermolecular interactions are from H...H contacts, 24.7% are from O...H/H...O contacts and 18.8% are from C...H/H...C contacts, while other contributions are from N...H/H...N and O...O contacts.
CA-CD: context-aware clickbait detection using new Chinese clickbait dataset with transfer learning method
Authors: Wang Hei-Chia , Maslim Martinus , Liu Hung-Yu
Published: August 2023

Purpose

A clickbait is a deceptive headline designed to boost ad revenue without presenting closely relevant content. There are numerous negative repercussions of clickbait, such as causing viewers to feel tricked and unhappy, causing long-term confusion, and even attracting cyber criminals. Automatic detection algorithms for clickbait have been developed to address this issue. The fact that there is only one semantic representation for the same term and a limited dataset in Chinese is a need for the existing technologies for detecting clickbait. This study aims to solve the limitations of automated clickbait detection in the Chinese dataset.

Design/methodology/approach

This study combines both to train the model to capture the probable relationship between clickbait news headlines and news content. In addition, part-of-speech elements are used to generate the most appropriate semantic representation for clickbait detection, improving clickbait detection performance.

Findings

This research successfully compiled a dataset containing up to 20,896 Chinese clickbait news articles. This collection contains news headlines, articles, categories and supplementary metadata. The suggested context-aware clickbait detection (CA-CD) model outperforms existing clickbait detection approaches on many criteria, demonstrating the proposed strategy's efficacy.

Originality/value

The originality of this study resides in the newly compiled Chinese clickbait dataset and contextual semantic representation-based clickbait detection approach employing transfer learning. This method can modify the semantic representation of each word based on context and assist the model in more precisely interpreting the original meaning of news articles.
Enhancing the adoption of building information modeling in the Iranian AEC sector: insights from a Delphi study
Authors: Hatami Nazanin , Rashidi Ali
Published: August 2023

Purpose

Architecture, engineering and construction (AEC) is an important industry worldwide and one of the largest economic sectors in several developing countries, particularly in Iran. The Iranian AEC sector suffers from low productivity and needs to adopt building information modeling (BIM) to reduce inefficiencies. Therefore, this paper was conducted to identify the BIM barriers and propose practical solutions to overcome them in Iran.

Design/methodology/approach

A comprehensive literature review, two rounds of the Delphi technique and semi-structured interviews with 12 Iranian experts in the AEC sector were conducted. The data were analyzed using the mean score, standard deviation and nonparametric tests.

Findings

The present study identified 26 BIM barriers in the Iranian AEC community and provided practical strategies for improving BIM adoption. The identified barriers were categorized into six main groups including source barriers, financial barriers, unawareness barriers, organizational barriers, regulatory barriers and market-demand barriers. The main three BIM barriers in Iran were the lack of government intervention, change-resistant and the gap between industry and academia. Kruskal–Wallis tests revealed that there are no statistically significant differences in perceptions of BIM barriers between respondents. The Mann–Whitney test indicated that there is no statistically significant difference in perceptions between engineers and architects except for one.

Originality/value

There are few studies on BIM adoption across developing countries, particularly in Iran. Moreover, the results can also be used in other developing nations with similar conditions.
Consumer avoidance toward message stream advertising on mobile social media: a stimulus-organism-response perspective
Authors: Li Xiaodong , Liu Zibing , Chen Yuan , Ren Ai
Published: August 2023

Purpose

Message stream advertising (MSA) has become an increasingly popular option for advertising on mobile social media. However, MSA is often avoided by consumers, and this avoidance deserves more research attention. The purpose of this study is therefore to identify the underlying mechanism and key variables that affect consumer avoidance of MSA in the context of mobile social media.

Design/methodology/approach

A face-to-face survey was administered to current mobile users of WeChat (N = 438). Structural equation modeling was conducted to test the relationships in the research model.

Findings

Results revealed that mobile consumers employ mechanical avoidance methods (i.e. zipping, muting and zapping) against MSA. The findings also demonstrated that advertising intrusiveness (stimulus) is directly linked to negative emotions, perceived entertainment and sense of control (organism), which, in turn, relate to MSA avoidance (response).

Originality/value

The study contributes to the MSA avoidance literature by using the stimulus-organism-response model to deepen the understanding of consumers' MSA avoidance on mobile social media, and it suggests important managerial implications for advertising practitioners and platform operators.
Futuristic portfolio optimization problem: wavelet based long short-term memory
Authors: Abolmakarem Shaghayegh , Abdi Farshid , Khalili-Damghani Kaveh , Didehkhani Hosein
Published: August 2023

Purpose

This paper aims to propose an improved version of portfolio optimization model through the prediction of the future behavior of stock returns using a combined wavelet-based long short-term memory (LSTM).

Design/methodology/approach

First, data are gathered and divided into two parts, namely, “past data” and “real data.” In the second stage, the wavelet transform is proposed to decompose the stock closing price time series into a set of coefficients. The derived coefficients are taken as an input to the LSTM model to predict the stock closing price time series and the “future data” is created. In the third stage, the mean-variance portfolio optimization problem (MVPOP) has iteratively been run using the “past,” “future” and “real” data sets. The epsilon-constraint method is adapted to generate the Pareto front for all three runes of MVPOP.

Findings

The real daily stock closing price time series of six stocks from the FTSE 100 between January 1, 2000, and December 30, 2020, is used to check the applicability and efficacy of the proposed approach. The comparisons of “future,” “past” and “real” Pareto fronts showed that the “future” Pareto front is closer to the “real” Pareto front. This demonstrates the efficacy and applicability of proposed approach.

Originality/value

Most of the classic Markowitz-based portfolio optimization models used past information to estimate the associated parameters of the stocks. This study revealed that the prediction of the future behavior of stock returns using a combined wavelet-based LSTM improved the performance of the portfolio.
Dispersion and persistence in the competitive balance of North American major leagues 1960–2019
Authors: Gerrard Bill , Kringstad Morten
Published: August 2023

Purpose

This paper focuses on the proliferation of empirical measures of competitive balance arising from its multi-dimensionality (i.e. win dispersion versus performance persistence), and the increasing complexity and specificity of league structures. This has led to significant inconsistencies in the assessments of competitive balance, rendering it difficult to derive policy recommendations.

Design/methodology/approach

The authors extend previous empirical studies of the four North American major leagues (i.e. MLB, NFL, NBA and NHL) using six competitive balance measures to (1) compare changes in competitive balance over the period 1960–2019; (2) to investigate the degree to which win dispersion and performance persistence move in the same direction; and (3) to explore the extent to which competitive balance has changed across facility construction eras and regulatory regimes.

Findings

The authors find that the assessment of competitive balance is both metric-dependent and time-dependent, reinforcing the importance of using a portfolio of measures rather than a single metric. The findings also highlight the importance of understanding the dispersion-persistence relationship.

Originality/value

The authors stress that leagues must be aware of a potential dispersion-persistence trade-off when intervening to improve competitive balance.