bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts
Authors: Glauninger Hendrik , Bard Jared A.M. , Wong Hickernell Caitlin J. , Airoldi Edo M. , Li Weihan , Singer Robert H. , Paul Sneha , Fei Jingyi , Sosnick Tobin R. , Wallace Edward W. J. , Drummond D. Allan 
Published: April 2024

AbstractStress-induced condensation of mRNA and proteins into stress granules is conserved across eukaryotes, yet the function, formation mechanisms, and relation to well-studied conserved transcriptional responses remain largely unresolved. Stress-induced exposure of ribosome-free mRNA following translational shutoff is thought to cause condensation by allowing new multivalent RNA-dependent interactions, with RNA length and associated interaction capacity driving increased condensation. Here we show that, in striking contrast, virtually all mRNA species condense in response to multiple unrelated stresses in budding yeast, length plays a minor role, and instead, stress-induced transcripts are preferentially excluded from condensates, enabling their selective translation. Using both endogenous genes and reporter constructs, we show that translation initiation blockade, rather than resulting ribosome-free RNA, causes condensation. These translation initiation-inhibited condensates (TIICs) are biochemically detectable even when stress granules, defined as microscopically visible foci, are absent or blocked. TIICs occur in unstressed yeast cells, and, during stress, grow before the appearance of visible stress granules. Stress-induced transcripts are excluded from TIICs primarily due to the timing of their expression, rather than their sequence features. Together, our results reveal a simple system by which cells redirect translational activity to newly synthesized transcripts during stress, with broad implications for cellular regulation in changing conditions.
Dissecting Schizophrenia Biology Using Pleiotropy with Cognitive Genomics
Authors: Bhattacharyya Upasana , John Jibin , Lencz Todd , Lam Max 
Published: April 2024

AbstractGiven the increasingly large number of loci discovered by psychiatric GWAS, specification of the key biological pathways underlying these loci has become a priority for the field. We have previously leveraged the pleiotropic genetic relationships between schizophrenia and two cognitive phenotypes (educational attainment and cognitive task performance) to differentiate two subsets of illness-relevant SNPs: (1) those with “concordant” alleles, which are associated with reduced cognitive ability/education and increased schizophrenia risk; and (2) those with “discordant” alleles linked to reduced educational and/or cognitive levels but lower schizophrenia susceptibility. In the present study, we extend our prior work, utilizing larger input GWAS datasets and a more powerful statistical approach to pleiotropic meta-analysis, the Pleiotropic Locus Exploration and Interpretation using Optimal test (PLEIO). Our pleiotropic meta-analysis of schizophrenia and the two cognitive phenotypes revealed 768 significant loci (159 novel). Among these, 347 loci harbored concordant SNPs, 270 encompassed discordant SNPs, and 151 “dual” loci contained concordant and discordant SNPs. Competitive gene-set analysis using MAGMA related concordant SNP loci with neurodevelopmental pathways (e.g., neurogenesis), whereas discordant loci were associated with mature neuronal synaptic functions. These distinctions were also observed in BrainSpan analysis of temporal enrichment patterns across developmental periods, with concordant loci containing more prenatally expressed genes than discordant loci. Dual loci were enriched for genes related to mRNA translation initiation, representing a novel finding in the schizophrenia literature.
Abdominal aortic aneurysms’ histomorphology differs on the individual patient level and is not associated with classic risk factors – the HistAAA study
Authors: Nackenhorst Maja Carina , Menges Felix , Bohmann Bianca , Zschäpitz David , Bollwein Christine , Flemming Sven , Sachs Nadja , Eilenberg Wolf , Brostjan Christine , Neumayer Christoph , Trenner Matthias , Ibing Wiebke , Schelzig Hubert , Reeps Christian , Maegdefessel Lars , Regele Heinz , Wagenhäuser Markus Udo , Scholz Claus Jürgen , Gasser Thomas Christian , Busch Albert 
Published: April 2024

AbstractObjectiveAbdominal aortic aneurysm (AAA) treatment is upon a diameter threshold by open (OAR) or endovascular aortic repair. So far, attempts for medical growth abrogation have failed. This study aims to elucidate the heterogeneity of AAA based on histomorphology in correlation to individual patient data and aneurysm metrics.Patients and MethodsAneurysm samples from the left anterior wall from four university center biobanks underwent histologic analysis including angiogenesis, calcification, fibrosis, type and grade of inflammation in adventitia and media. Clinical information included age, comorbidities, etc., type of aneurysm (intact, symptomatic, ruptured, inflammatory) and growth. Aneurysm morphology included diameter and semi-automated geometric analysis using Endosize©(Therenva) and finite element methods (A4Clinics©Research Edition, Vacops GmbH).Results364 patients’ samples (85.4% male, median age 69 years) were evaluated and scored for acute (mixed/granulocytes) or chronic (mononuclear/plasma cells) inflammation, which was not associated with rupture (52x), symptomatic (37x; p = 0.51) or diameter (57 [52–69] mm; p = 0.87). The degree of fibrosis and the presence of angiogenesis were significantly higher (both p < 0.001) with increasing inflammation, which in turn significantly decreased with patient age (est = −0.015/year, p = 0.017). No significant differences in were seen for ruptured (vs. intact), acute (vs. elective), male (vs. female) or diabetic patients. Current smoking was associated with chronic inflammation (p = 0.007) and a higher degree of fibrosis (p = 0.03). Aneurysm geometric morphology (n=252) or annual growth rate (n=142) were not associated with histologic characteristics. Yet, local luminal thrombus formation was significantly higher with increasing inflammation (p = 0.04).ConclusionType and degree of inflammation are the most distinguishable histologic characteristics in the AAA wall between individual patients, yet not associated with diameter or rupture. Local luminal thrombus formation is associated with inflammatory features and suggests a vivid bio-physical compartment with intra-individual differences.
Characterization ofBrettanomyces bruxellensisphenolic acid decarboxylase enzyme expressed inE. coli
Authors: Lentz Michael 
Published: April 2024

AbstractBrettanomycesyeasts are considered spoilage organisms in commercial fermentation settings, but some historical beer styles and several modern specialty beer styles rely onBrettanomycesfor unique aroma and flavor contributions. The organoleptic properties of beer utilizing intentionalBrettanomycesfermentations can be unpredictable and inconsistent. This study investigates the contributions ofBrettanomycesfermentations to volatile phenolic character by expression of phenolic acid decarboxylase enzyme cloned from B.bruxellensis. Protein was expressed and isolated fromE. colicells. The enzyme has broad temperature and pH ranges, and showed variable activity against the most common potential hydroxycinnamic acid substrates.
Analysis of antibiotic response in Clinical WoundPseudomonas aeruginosaisolates: Unveiling Proteome Dynamics of tobramycin tolerant phenotype
Authors: Buchholtz Kasandra , Jersie-Christensen Rosa , Krogfelt Karen Angeliki , Mojsoska Biljana 
Published: April 2024

AbstractPseudomonas aeruginosa(P. aeruginosa) is an opportunistic human pathogen, causing serious chronic infections.P. aeruginosacan adapt efficiently to antibiotic stressors via different genotypic or phenotypic strategies such as resistance and tolerance. The adaptation regulatory system is not always very well understood. In this study, we use shotgun proteomics to investigate the system-level response to tobramycin in two clinical woundP. aeruginosaisolates and PAO1. We profiled each strain for its antibiotic drug-tolerant phenotype using supra-minimum inhibitory concentrations (supra-MIC) of tobramycin and applied proteomics to investigate the protein expression profiles. The MIC revealed that all isolates were susceptible to tobramycin but at supra-MIC concentrations at stationary growth, a degree of tolerance was observed for the isolates. We identified around 40 % of the total proteins encoded by theP. aeruginosagenome and highlighted shared and unique protein signatures for all isolates. Comparative proteome profiling in the absence of antibiotic treatment showed divergent fingerprints, despite similarities in the growth behavior of the isolates. In the presence of tobramycin, the isolates shared a common response in the downregulation of proteins involved in the two-component system, whereas stress response proteins were present at higher levels. Our findings provide insight into the use of proteomic tools to dissect the system-level response in clinical isolates in the absence and presence of antibiotic stress.
“Comprehensive Analysis of Nascent Transcriptome Reveals Diverse Transcriptional Profiles Across the Trypanosoma cruzi Genome Underlining the Regulatory Role of Genome Organization, Chromatin Status, and Cis-Acting Elements”
Authors: Carvalho de Lima Pedro Leonardo , de Sousa Lopes Leticia , Nunes Rosón Juliana , Borges Alyssa , Karla Bellini Natalia , Tahira Ana , Santos da Silva Marcelo , Pires David , Elias Maria Carolina , da Cunha Julia Pinheiro Chagas 
Published: April 2024

AbstractTrypanosomatids are eukaryotic parasites exhibiting polycistronic transcription and trans-splicing. Post-transcriptional mechanisms are acknowledged as pivotal in gene expression regulation of their protein-coding genes. To comprehensively investigate the impact of transcription on gene expression inTrypanosoma cruziand the association with the epigenetic landscape, we conducted a genome-wide nascent transcriptomic analysis. Our findings reveal significant asymmetrical transcriptional abundance across the genome, notably between polycistronic transcription units (PTUs) enriched in conserved genes (core PTUs) and those containing virulence genes (disruptive PTUs). We found that trypanosomes exploit linear genome organization to regulate transcription abundance by embedding virulence genes into highly transcribed core-enriched PTUs, by positioning PTUs near non-coding regions of small non-coding RNAs (e.g., tRNAs, snoRNAs), and by placing core CDSs in PTUs of various sizes. Additionally, we found correlations between open chromatin status and nascent transcript levels, both globally and particularly at transcription starting regions (divergent strand switch regions - dSSRs), indicating a crucial role for chromatin architecture in transcriptional regulation. While both core and disruptive dSSRs exhibit similar levels of some epigenetic marks (H2B.V deposition and 5mC), disruptive dSSRs display significantly higher 5hmC content and nucleosome occupancy compared to core dSSRs. Furthermore, we identified distinct conserved motifs within dSSRs of core and disruptive PTUs. These findings challenge the notion of constitutive and uniform transcription inT. cruzi, underscoring the paramount importance of linear genome organization, cis-acting motifs, and chromatin landscape in transcriptional regulation.
Geranylgeranylated-SCFFBXO10Regulates Selective Outer Mitochondrial Membrane Proteostasis and Function
Authors: Bhat Sameer Ahmed , Vasi Zahra , Jiang Liping , Selvaraj Shruthi , Ferguson Rachel , Gudur Anish , Ismail Hagar , Adhikari Ritika , Dhabaria Avantika , Ueberheide Beatrix , Kuchay Shafi 
Published: April 2024

AbstractE3-ubiquitin ligases (E3s) are main components of the ubiquitin-proteasome system (UPS), as they determine substrate specificity in response to internal and external cues to regulate protein homeostasis. However, the regulation of membrane protein ubiquitination by E3s within distinct cell membrane compartments or organelles is not well understood. We show that FBXO10, the interchangeable component of the SKP1/CUL1/F-box ubiquitin ligase complex (SCF-E3), undergoes lipid-modification with geranylgeranyl isoprenoid at Cysteine953 (C953), facilitating its dynamic trafficking to the outer mitochondrial membrane (OMM). FBXO10 polypeptide does not contain a canonical mitochondrial targeting sequence (MTS); instead, its geranylgeranylation at C953 and the interaction with two cytosolic factors, PDE6δ (a prenyl group-binding protein), and HSP90 (a mitochondrial chaperone) orchestrate specific OMM targeting of prenyl-FBXO10 across diverse membrane compartments. The geranylgeranylation-deficient FBXO10(C953S) mutant redistributes away from the OMM, leading to impaired mitochondrial ATP production, decreased mitochondrial membrane potential, and increased mitochondrial fragmentation. Phosphoglycerate mutase 5 (PGAM5) was identified as a potential substrate of FBXO10 at the OMM using comparative quantitative mass spectrometry analyses of enriched mitochondria (LFQ-MS/MS), leveraging the redistribution of FBXO10(C953S). FBXO10, but not FBXO10(C953S), promoted polyubiquitylation and degradation of PGAM5. Examination of the role of this pathway in a physiological context revealed that the loss of FBXO10 or expression of prenylation-deficient-FBXO10(C953S) inhibited PGAM5 degradation, disrupted mitochondrial homeostasis, and impaired myogenic differentiation of human iPSCs and murine myoblasts. Our studies identify a mechanism for selective E3-ligase mediated regulation of mitochondrial membrane proteostasis and metabolic health, potentially amenable to therapeutic intervention.
Aldehydic load as an objective imaging biomarker of mild traumatic brain injury
Authors: Kirby Alexia , Ward Cian , Calvert Nicholas D. , Daniel Ryan , Leung Joseph Wai-Hin , Sharma Ashwin , Suchý Mojmír , Donatelli Cassandra , Wang Jing , Standen Emily , Shuhendler Adam J. 
Published: April 2024

AbstractConcussion is a mild traumatic brain injury (mTBI) defined as complex neurological impairment induced by biomechanical forces without structural brain damage. There does not yet exist an objective diagnostic tool for concussion. Downstream injury from mTBI stems from oxidative damage leading to the production of neurotoxic aldehydes. A collagen-based 3D corticomimetic scaffold was developed affording anin vitromodel of concussion, which confirmed increased aldehyde production in live neurons following impact. To evaluate total aldehyde levelsin vivofollowing mTBI, a novel CEST-MRI contrast agent, ProxyNA3, has been implemented in a new model of closed-head, awake, single-impact concussion developed in aged and young mice with aldehyde dehydrogenase 2 (ALDH2) deficiency. Behavioural tests confirm deficits immediately after injury. ProxyNA3-MRI was performed before impact, and on days two- and seven- post-impact. MRI signal enhancement significantly increased at two days post-injury and decreased to baseline seven days post-injury in all mice. An increase in astrocyte activation at seven days post-injury confirms the onset of a neuroinflammatory response following aldehyde production in the brain. The data suggest that advanced age and ALDH2 deficiency contribute to increased aldehydic load following mTBI. Overall, ProxyNA3was capable of mapping concussion-associated aldehydes, supporting its application as an objective diagnostic tool for concussion.
Getting seniors back on their bicycle; a pretest-posttest case-control study on the improvement of bicycle balance control
Authors: Maris Eric 
Published: April 2024

AbstractObjectiveQuantify the effectiveness and generalizability of an intervention that aims at restoring bicycle balance control skills in seniors that have quit cycling.MethodsThe intervention was designed such that the difficulty of the bicycle balance control task could be increased in a stepwise fashion, gradually approaching the difficulty of bicycle balance control on the public roads. The intervention lasted 11 weeks and involved three components: (1) training on an exercise bicycle, (2) balance control training on a bicycle simulator, and (3) cycling on the public roads with a safe start-and-stop technique that was practiced on the bicycle simulator. The intervention was administered to a group of community-dwelling senior citizens (N=23) that had quit cycling (N=19) or that were on the verge of doing so (N=4). The effectiveness of the intervention was evaluated by comparing balance control skill and confidence between a post- and a pre-intervention measurement. As a check for possible spontaneous recovery, the same comparison was also performed in a matched control group that did not participate in the intervention.ResultsThis intervention produced a very large improvement (Cohen’s d = 1.5, t(16)=6.0, p<.001) in balance control skills and confidence on the public roads.ConclusionBicycle balance control skills and confidence can be restored over a short period of time, but this does not rule out the importance of the slower process of acquiring a sufficient lower body strength.Impact StatementIncreasing balance control skills and confidence is a realistic short-term target for rehabilitation interventions.
Characterizing the critical success factors influencing blockchain technology adoption in Indian public distribution system: an exploratory approach
Authors: Vishnu C.R. , Chatterjee Proshayan , Maddali Sai Pradyumna , Akenroye Temidayo O. 
Published: April 2024

PurposeThe public distribution system (PDS) is an Indian food security system established to manage the distribution of food grains at affordable prices. As a result of the population explosion, the long-established PDS system finds it challenging to maintain operational efficiency, quality, trust and transparency. This paper explores the possibility of leveraging blockchain technology to overcome these operational hurdles.Design/methodology/approachThrough a literature review and expert interactions, the present research identifies critical success factors in terms of enablers and barriers that influence the adoption of blockchain technology in PDS. Furthermore, we propose two independent interpretive structural models (ISM) and MICMAC to characterize these attributes.FindingsThe research identifies 15 distinct enablers and ten barriers that influence the diffusion of the latest technology in the sector at focus. The analyses disclose the interrelationships/dependencies among these enablers and between barriers, along with their individual driving power and dependence power.Practical implicationsThe research showcases the importance of automating the system and illustrates how the features of blockchain technology can assist in augmenting stakeholder satisfaction levels. However, poor or nonexistent government regulations and patronage are found to be the major impediments to adoption. The research also delineates the cost implications of this barrier through its interrelationships with other barriers.Originality/valueInteresting inferences are drawn from the models that offer actionable insights for the industry, government and technologists for improving PDS performance. Such interventions will ensure national food security through enhanced trust and transparency, which can further improve efficiency and effectiveness.
Consumer responses to CEO activism: an impression management approach
Authors: Cabano Frank Gregory , Li Mengge , Jiménez Fernando R. 
Published: April 2024

Purpose
This paper aims to examine how and why consumers respond to chief executive officer (CEO) activism on social media. The authors developed a conceptual model that proposes impression management as a mechanism for consumer response to CEO activism.

Design/methodology/approach
In Study 1a, the authors examined 83,259 tweets from 90 CEOs and compared consumer responses between controversial and noncontroversial tweets. In Study 1b, the authors replicated the analysis, using a machine-learning topic modeling approach. In Studies 2 and 3, the authors used experimental designs to test the theoretical mechanism.

Findings
On average, consumers tend to respond more to CEO posts dealing with noncontroversial issues. Consumers’ relative reluctance to like and share controversial posts is motivated by fear of rejection. However, CEO fame reverses this effect. Consumers are more likely to engage in controversial activist threads by popular CEOs. This effect holds for consumers high (vs low) in public self-consciousness. CEO fame serves as a “shield” behind which consumers protect their online image.

Research limitations/implications
The study focused on Twitter (aka “X”) in the USA. Future research may replicate the study in other social media platforms and countries. The authors introduce “shielding” – liking and sharing content authored by a recognizable source – as a tactic for impression management on social media.

Practical implications
Famous CEOs should speak up about controversial issues on social media because their voice helps consumers engage more in such conversations.

Originality/value
This paper offers a theoretical framework to understand consumer reactions to CEO activism.
The role of foreign aid in the nexus between capital flight and unemployment in sub-Saharan Africa
Authors: Asongu Simplice , Odhiambo Nicholas M. 
Published: April 2024

PurposeThis study assesses the relevance of foreign aid to the incidence of capital flight and unemployment in 20 countries in sub-Saharan Africa.Design/methodology/approachThe study is for the period 1996–2018, and the empirical evidence is based on interactive quantile regressions in order to assess the nexuses throughout the conditional distribution of the unemployment outcome variable.FindingsFrom the findings, capital flight has a positive unconditional incidence on unemployment, while foreign aid dampens the underlying positive unconditional nexus. Moreover, in order for the positive incidence of capital flight to be completely dampened, foreign aid thresholds of 2.230 and 3.964 (% of GDP) are needed at the 10th and 25th quantiles, respectively, of the conditional distribution of unemployment. It follows that the relevance of foreign aid in crowding out the unfavourable incidence of capital flight on unemployment is significantly apparent only in the lowest quantiles or countries with below-median levels of unemployment. The policy implications are discussed.Originality/valueThe study complements the extant literature by assessing the importance of development assistance in how capital flight affects unemployment in sub-Saharan Africa.
TOURQUAL scale: psychometric properties and internal structure validation
Authors: Mondo Tiago Savi , Medeiros Sandro , Sthapit Erose , Freitas Almeida Freitas Lara Brunelle Almeida , Björk Peter 
Published: April 2024

Purpose
This study aims to focus on assessing the psychometric properties necessary to validate the internal structure of the TOURQUAL scale.

Design/methodology/approach
A quantitative research study was conducted in collaboration with the Brazilian Network of Tourism Observatories, comprising 927 respondents surveyed between October 2021 and May 2022. The data analysis involved the application of descriptive statistics and exploratory factor analysis, in alignment with the principles outlined in the Standards for Educational and Psychological Testing 2014 to validate the scale.

Findings
The findings of this study validate the TOURQUAL scale as a robust tool for assessing the perceived quality of tourist services, with results demonstrating one-dimensionality and replicability.

Originality/value
To the best of the authors’ knowledge, this study is the first to assess the psychometric properties for validating the internal structure of the TOURQUAL scale.