bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Dementia Among Medicare Beneficiaries With and Without Urinary Incontinence
Authors: High Rachel A. , Ford Cassie B. , Handa Victoria L. , Anger Jennifer
Published: September 2024

Importance

Dementia and urinary incontinence (UI) have been associated in cross-sectional studies. The temporal relationship between these 2 conditions is not well understood.

Objective

The aim of the study was to investigate the risk of incident dementia in female adults with and without UI using the Medicare 5% Limited Data Set.

Study Design

This retrospective cohort study matched females with UI to continent controls by index year, age, and dual Medicare/Medicaid eligibility. A 2-year look back period was used to exclude prevalent dementia and neurologic disorders. The 5-year cumulative incidence of dementia was estimated for women with UI and controls. Cox proportional hazard models assessed the association of variables with dementia, adjusting for age, dual Medicare/Medicaid eligibility, race, and comorbidities.

Results

A total of 8,651 female beneficiaries with UI (n = 8,651) were more likely than matched controls (n = 8,651) to report White race and several medical comorbidities. The 5-year cumulative incidence of dementia diagnosis was lower in the UI versus controls (8.8% vs 10.6%, P < 0.001). In multivariable analysis with adjustment for covariates, UI diagnosis was associated with a lower hazard of dementia diagnosis (hazard ratio 0.82 [0.74, 0.91], P < 0.001).

Conclusions

Among female Medicare beneficiaries without baseline neurologic disorders, having any UI diagnosis was associated with a lower risk of dementia diagnosis. Further studies assessing UI symptoms and dementia diagnosis with rigorous and valid assessment tools are needed to confirm this finding.
Scale at the interface of spatial and social ecology
Authors: Picardi Simona , Abrahms Briana L. , Merkle Jerod A.
Published: September 2024

Animals simultaneously navigate spatial and social environments, and their decision-making with respect to those environments constitutes their spatial (e.g. habitat selection) and social (e.g. conspecific associations) phenotypes. The spatial–social interface is a recently introduced conceptual framework linking these components of spatial and social ecology. The spatial–social interface is inherently scale-dependent, yet it has not been integrated with the rich body of literature on ecological scale. Here, we develop a conceptual connection between the spatial–social interface and ecological scale. We propose three key innovations that incrementally build upon each other. First, the use–availability framework that underpins a large body of literature in behavioural ecology can be used in analogy to the phenotype–environment nomenclature and is transferable across the spatial and social realms. Second, both spatial and social phenotypes are hierarchical, with nested components that are linked via constraints—from the top down—or emergent properties—from the bottom up. Finally, in both the spatial and social realms, the definitions of environment and phenotype depend on the focal scale of inquiry. These conceptual innovations cast our understanding of the relationships between social and spatial dimensions of animal ecology in a new light, allowing a more holistic understanding and clearer hypothesis development for animal behaviour.

This article is part of the theme issue ‘The spatial–social interface: a theoretical and empirical integration’.
Faithful pals and familiar locales: differentiating social and spatial site fidelity during reproduction
Authors: Hendrix J. G. , Robitaille A. L. , Kusch J. M. , Webber Q. M. R. , Vander Wal E.
Published: September 2024

Site fidelity—the tendency to reuse familiar spaces—is expected to improve fitness. Familiarity with the local environment is particularly crucial when resource demands or predation risk are high. Consequently, site fidelity often peaks during reproduction when energetic costs are high and offspring are vulnerable. For many species, the environment they experience is not solely a function of geography but also of the social environment. Social fidelity, the selection for familiar social environments, could constitute an independent or parallel strategy to spatial fidelity when considering behaviour at the spatial–social interface. Using global positioning system locations from caribou across Newfoundland, we tested whether females selected calving sites based on proximity to familiar conspecifics, in addition to geographical (spatial) fidelity. These strategies were synergistic, not alternative, and correlated across the population but more variable within individuals. We also tested whether either form of fidelity affected reproductive success. We failed to detect an effect of spatial or social fidelity on reproductive success in this population. Nevertheless, given the association between social and spatial fidelity and the demonstrated fitness consequences of site fidelity in other systems, familiar conspecifics and the potential benefits these social partners provide may be an underappreciated component driving site fidelity.

This article is part of the theme issue ‘The spatial–social interface: a theoretical and empirical integration’.
Spatial memory obviates following behaviour in an information centre of wild fruit bats
Authors: Lourie Emmanuel , Shamay Tomer , Toledo Sivan , Nathan Ran
Published: September 2024

According to the information centre hypothesis (ICH), colonial species use social information in roosts to locate ephemeral resources. Validating the ICH necessitates showing that uninformed individuals follow informed ones to the new resource. However, following behaviour may not be essential when individuals have a good memory of the resources’ locations. For instance, Egyptian fruit bats forage on spatially predictable trees, but some bear fruit at unpredictable times. These circumstances suggest an alternative ICH pathway in which bats learn when fruits emerge from social cues in the roost but then use spatial memory to locate them without following conspecifics. Here, using an unique field manipulation and high-frequency tracking data, we test for this alternative pathway: we introduced bats smeared with the fruit odour of the unpredictably fruiting
Ficus sycomorus
trees to the roost, when they bore no fruits, and then tracked the movement of conspecifics exposed to the manipulated social cue. As predicted, bats visited the
F. sycomorus
trees with significantly higher probabilities than during routine foraging trips (of >200 bats). Our results show how the integration of spatial memory and social cues leads to efficient resource tracking and highlight the value of using large movement datasets and field experiments in behavioural ecology.

This article is part of the theme issue ‘The spatial–social interface: a theoretical and empirical integration’.
The CONSIDER Intervention Fidelity Framework for Complex Interventions in Healthcare: A “Best-Fit” Framework Synthesis
Authors: Páez Arsenio , Nunan David , McCulloch Peter , Beard David
Published: September 2024

Background

The focus of clinical trials is typically interventions’ efficacy, or whether they attain their desired outcomes. Comparatively less attention is focused on understanding how or why interventions succeed, or fail to attain, those outcomes. This may be particularly important in trials of complex interventions such as surgery or physiotherapy, which are multifaceted and often tailored to individual participants, providers, or settings, increasing the potential for variations in intervention delivery and effects. The correspondence between the intervention that was planned and what was actually delivered in a trial is the intervention’s fidelity. Several benefits for high levels of intervention fidelity have been proposed. However, a lack of a uniform definition for fidelity and its key components may hinder intervention delivery in clinical trials and the translation of evidence-based interventions to clinical practice.

Methods

In this study, we undertook systematic review, and “Best-fit” framework synthesis to develop an empirically-based intervention fidelity framework for complex interventions in rehabilitation.

Results

The resultingCONSIDER (Complex iNterventionS Design dElivery Recepit) frameworkis first integrated fidelity framework developed specifically for clinical trials of for complex interventions rehabiliation. CONSIDER consists of three main components, Design, Delivery and Receipt and the factors moderating them. Design encompasses the core elements of the intervention and the protocol for the clinical trial to evaluate its effectiveness. Delivery encompasses the actual implementation of the protocol and treatment integrity. It is focused primarily on the actions of the intervention providers. Receipt addresses the exposure of the trial participants to the intervention and their response to it.

Conclusions

This fidelity framework is the first designed suit the unique complexities and challenges presented by physical complex interventions. It can help promote transparency and reproducibility and helps researchers design clinical trials that reduce waste, enable uptake into clinical practice, and benefit the practice and evidencing of physiotherapy, surgery and other physical complex interventions.
Enhancing Interventional Cardiology Training: A Porcine Heart-Based Coronary Intervention Simulator
Authors: Reifart Joerg , Iaizzo Paul Anthony
Published: September 2024

Introduction

Access to simulators for interventional cardiology is currently limited. High acuity, low occurrence procedures (HALO), such as coronary perforation or iatrogenic dissection, are not trained in currently available simulators. We developed a cost-effective coronary intervention simulator designed to enhance the training of both novice and experienced interventionalists.

Methods

Porcine hearts from 6-month-old Yorkshire pigs (heart weight: 300-500g) were obtained from a large animal research laboratory. Guide catheters were inserted into the coronary artery ostia and secured with superglue. To maintain shape and rigidity, commercially available polyurethane insulation foam was injected into the ventricles. The guide catheter was then connected to a Tuohy valve linked to a 3-way stopcock. One connection led to a pressure infusion bag filled with tap water (inflated at > 300 mmHg); the other was used for contrast injection. The heart was set on a radiolucent box with a fluid collector underneath. Clinical scenarios were simulated using 3D-printed stenoses and occlusions, blood clots for occlusive myocardial infarction, balloon oversizing for dissections, and needle trauma for perforations.

Results

The simulator was used to practice coronary angiography, managing perforations, bifurcations, dissections, and acute coronary occlusions.

Assembly, set-up, and simulation time until refilling the perfusion bag was required were 50, 25, and 30 minutes, respectively. Intravascular imaging with Optical Coherence Tomography was successfully used to guide interventions. The simulator was frozen and reused more than three times without notable deterioration.

Conclusion

A wide range of clinical scenarios can be trained with our model. Its preparatory flexibility, including the ability to be frozen for on-demand training, enhances its utility. Limitations include the absence of pulsatile flow, heart movement, and the inability to train guide catheter intubation.
FACILITATORS AND BARRIERS TO UPTAKE OF CHILD-FRIENDLY 3 MONTHS OF ISONIAZID AND RIFAMPICIN (3HR) FIXED DRUG COMBINATION (FDC) FOR TUBERCULOSIS PREVENTIVE THERAPY (TPT) IN NIGERIA
Authors: Eneogu Rupert , Ihesie Austin , Daniel Olugbenga , Chukwuogo Ogoamaka , Nongo Debby , Agbaje Aderonke , Odume Bethrand , Kuye Joseph , Oyelaran Omosalewa , Egbule Daniel , Gemert Wayne Van , Mupfumi Lucy , D’auvergne Cleophas , Chijioke-Akaniro Obioma , Anyaike Chukwuma , Olarewaju Sunday
Published: September 2024

The uptake of TB preventive therapy (TPT) for child and adult contacts of index TB patients in Nigeria has been suboptimal. Nigeria introduced the 3-month isoniazid-rifampicin (3HR) shorter regimen TPT for all eligible contacts through the USAID-funded Stop TB Partnership introducing New Tools Project (iNTP). This study assesses the facilitators and barriers to the uptake of the newly introduced child-friendly 3HR TPT for child contacts of TB patients in Nigeria.

This was a cross-sectional descriptive study using mixed methods. In-depth interviews were conducted among 36 purposely selected Healthcare Workers (HCWs) and 36 caregivers of child contacts. Records of TPT-eligible child contacts (0–14 years) from April to September 2022 were retrospectively extracted. Study data were analyzed using appropriate statistical tools for qualitative and quantitative techniques.

There were 7,906 child contacts identified, of which 7,902 (99.9%) contacts were screened for TB, 1,704 (21.5%) were presumptive, 264 (15.5%) diagnosed with TB, and 6,994 were eligible for TB Preventive Therapy. Additionally, out of 6,994 eligible child contacts, 3984 (57%) were initiated on TPT with 2,982 (74,8%) enrolled on 3HR and 1,002 (25%) on 6H. Of the clients placed on 3HR, 2,499 (85%) completed treatment, 309 (10.5%) lost to follow-up, 27(0.92%) developed Tuberculosis while 48 (1.6%) interrupted treatment.

The key drivers of 3HR TPT uptake among child contacts were TPT-related health education and counseling. Access barriers to 3HR TPT elicited included stigma, poverty, transportation cost, stock out, ineffective monitoring and management of side effects issues of 3HR TPT, subpar Government funding and commitment to addressing TPT implementation challenges and inadequate knowledge among HCWs and caregivers.

In conclusion, 3HR-TPT uptake among child contacts of index TB patients was high. Enhanced provider training and intensive community health education should be sustained while identified individual, structural, and institutional barriers should be addressed to improve implementation.
CRISPR-CAS9 MEDIATED EDITING OF THELACZGENE FOR OPTIMIZING LIPASE PRODUCTION AND CHARACTERIZATION IN ENGINEEREDESCHERICHIA COLIUSING POTATO PEEL AS A GLUCOSE SOURCE
Authors: Minari Joseph Bamidele , Dada Idowu Samuel , Abdulazeez Dhikrullah Oluwatope , Nwosu Gift E.
Published: September 2024

Improper disposal of potato peels harms the environment, wasting nutrient-rich resources that could be used for beneficial enzyme production like lipase. This study aimed to edit thelacZ geneinEscherichiacoli using utilizing the CRISPR Cas9 technology. Both edited and uneditedE. coliwere used for submerged fermentation of potato peels to produce and characterize lipase. ThelacZgene was edited using the CRISPR Cas9 technology, and the efficiency was measured using multiplex PCR and gel electrophoresis. To measure lipolytic activity, olive oil screening was performed. The temperature and pH of the lipase were used to characterize it after partial purification and submerged fermentation at 10°C, 30°C, and 45°C. Blue colonies indicated thelacZ genewas unedited,lacZgene editing and repair was demonstrated by white colonies, and no colonies demonstrated the editing but not repair of thelacZgene. Bands at 1,100 bp indicated uneditedlacZ gene, while 650 bp showed editedlacZ gene. Increased cell mass was observed at 10°C. CRISPR Cas9 editedE. colishowed a clearer zone than the unedited in the lipase medium. The highest lipase activity from both edited and uneditedE. coliwas at 35°C, and the lowest at 65°C. Optimal pH was 7, with lowest activity at pH 4. The CRISPR Cas9 editedE. colidemonstrated significantly higher enzyme activities (p<0.05). This study concluded that CRISPR Cas9-mediatedlacZ geneediting inE. colienhances its ability to utilize potato peels, increasing lipase production.
Cis-regulatory elements driving motor neuron-restricted viral payload expression within the mammalian spinal cord
Authors: Nagy M Aurel , Price Spencer , Wang Kristina , Gill Stanley P , Ren Erika , McElrath Lorna , Pajak Victoria , Deighan Sarah , Liu Bin , Liu Xiaodong , Diallo Aissatou , Lo Shih-Ching , Kleiman Robin , Henderson Christopher , Suh Junghae , Griffith Eric C , Greenberg Michael E , Hrvatin Sinisa
Published: September 2024

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression. Subsequent testing of these candidates identified two CREs that confer MN-selective gene expression in the spinal cord as well as reduced off-target expression in dorsal root ganglia. Within one of these candidate elements, we identified a compact core transcription factor (TF)-binding region that drives MN-selective gene expression. Finally, we demonstrate that selective spinal cord expression of this mouse CRE is preserved in non-human primates. These findings suggest that the generation of cell-type-selective viral reagents, in which cell-type-selective CREs drive restricted gene expression, will be valuable research tools in mice and other mammalian species, with potentially significant therapeutic value in humans.
Development of a national osteopathic practice-based research network: the NCOR Research Network
Authors: Draper-Rodi Jerry , Fawkes Carol , Bailey Daniel
Published: September 2024

Objectives

To describe the development of the NCOR Research Network, the first osteopathic Practice-Based Research Network (PBRN) in the UK, and provide data on its members’ characteristics, clinical practices, and patient demographics.

Design

Cross-sectional survey study.

Setting

Online survey of osteopaths practising in the United Kingdom.

Participants

570 osteopaths registered with the General Osteopathic Council who consented to participate in the NCOR Research Network.

Primary and secondary outcome measures

Demographic characteristics of osteopaths, details of their clinical practice, patient demographics, common presenting complaints, treatment approaches, and attitudes towards evidence-based practice.

Results

The median age bracket of participants was 50-59 years, with 55% identifying as women. Participants had a median of 17 years of clinical experience. Most worked in private practice (71% as principals, 32% as associates), seeing 20-39 hours of patients per week. The majority (87%) regularly treated adults aged 65 or older. Low back pain was the most common complaint seen daily (56%). Spinal articulation/mobilization (79%) and soft tissue massage (78%) were the most frequently used techniques. Participants reported positive views towards evidence-based practice but cited lack of research skills and time as barriers to engagement.

Conclusions

The NCOR Research Network provides a foundation for future osteopathic research in the UK. While the sample was not fully representative of UK osteopaths, it offers insights into current osteopathic practice. The network aims to foster collaboration between clinicians and academics, potentially bridging the gap between research and practice in osteopathy.

Protocol registration

https://doi.org/10.17605/OSF.IO/HPWG4

Article summary

Strengths and limitations of this study:

This study establishes the first osteopathic Practice-Based Research Network (PBRN) in the UK, providing a novel infrastructure for collaborative research in osteopathy.

The survey was developed based on previous PBRN studies and existing UK osteopathic datasets, allowing for comparability of data across different research initiatives.

A diverse recruitment strategy was employed, including various channels such as the regulatory body, professional organisations, and both face-to-face and online presentations, to reach a wide range of osteopaths.

The sample in this study is not fully representative of the UK osteopathic profession when compared to the General Osteopathic Council registrant data, which may limit the generalisability of the findings.

As the survey data were self-reported by osteopaths, the findings may be subject to recall or social desirability biases.
One-Sided Matching Portal (OSMP): a tool to facilitate rare disease patient matchmaking
Authors: Osmond Matthew , Price E. Magda , Buske Orion J , Frew Mackenzie , Couse Madeline , Hartley Taila , Klamann Conor , Le Hannah G. B. H. , Xu Jenny , So Delvin , Jain Anjali , Lu Kevin , Mo Kevin , Wyllie Hannah , Wall Erika , Driver Hannah G , Cheung Warren , Cohen Ana S.A. , Farrow Emily G. , Thiffault Isabelle ,   Care4Rare Canada Consortium, Turinsky Andrei , Pastinen Tomi , Brudno Michael , Boycott Kym M
Published: September 2024

Background: Genomic matchmaking - the process of identifying multiple individuals with overlapping phenotypes and rare variants in the same gene - is an important tool facilitating gene discoveries for unsolved rare genetic disease (RGD) patients. Current approaches are two-sided, meaning both patients being matched must have the same candidate gene flagged. This limits the number of unsolved RGD patients eligible for matchmaking. A one-sided approach to matchmaking, in which a gene of interest is queried directly in the genome-wide sequencing data of RGD patients, would make matchmaking possible for previously undiscoverable individuals. However, platforms and workflows for this approach have not been well established. Results: We released a beta version of the One-Sided Matching Portal (OSMP), a platform capable of performing one-sided matchmaking queries across thousands of participants stored in genomic databases. The OSMP returns variant-level and participant-level information on each variant occurrence (VO) identified in a queried gene and displays this information through a customizable data table. A workflow for one-sided matchmaking was developed so that researchers could effectively prioritize the many VOs returned from a given query. This workflow was then tested through pilot studies where two sets of genes were queried in over 2,500 individuals: 130 genes that were newly associated with disease in OMIM, and 178 candidate genes that were not yet associated with a described disease-gene association in OMIM. These pilots both returned a large number of initial VOs (12,872 and 20,308, respectively), however the workflow successfully filtered out over 99.8% of these VOs before they were sent for review by a patient′s clinician. Filters on participant-level information, such as variant zygosity, participant phenotype, and whether a variant was also present in unaffected participants were especially effective in this workflow at reducing the number of false positive matches. Conclusions: As demonstrated through the two pilot studies, one-sided matchmaking queries can be efficiently performed using the OSMP. The availability of variant-level and participant-level data is key to ensuring this approach is practical for researchers. In the future, the OSMP will be connected to additional RD databases to increase the accessibility of matchmaking to unsolved RGD patients.
Feasibility study of the application of Magnetic Resonance Elastography (MRE) to diagnose adenomyosis
Authors: Jain V , Hojo E , McKillop G , Oniscu A , Le Y , Chen J , Ehman R , Roberts N , Critchley HOD
Published: September 2024

Structured Abstract

Introduction

Adenomyosis is an under-recognised condition in which definitive diagnosis is only possible via histology after hysterectomy, an unacceptable option for those wishing to preserve fertility. Recent cellular/molecular studies indicate adenomyotic lesions may be fibrotic leading to increased uterine tissue stiffness. 3D Magnetic Resonance Elastography (MRE) is a novel imaging technique that allows in vivo measurement of tissue stiffness (via elastograms). 3D MRE has not been reported to study adenomyosis. The feasibility study aimed to utilise a novel 3D MRE protocol to measure global uterine stiffness and to investigate its potential application for non-invasive in vivo diagnosis of adenomyosis.

Materials and Methods

3D MRE protocol was conducted on one healthy volunteer (control) and four patients with suspected adenomyosis and heavy menstrual bleeding (HMB), diagnosed via transvaginal ultrasound and clinical history (REC:20/SS/0123 and 19/SS/0102). Two patients underwent hysterectomy, and representative uterine tissue samples were assessed for (i) histological presence of adenomyosis via H&E staining; (ii) cellular/molecular measures of tissue stiffness (collagen [picrosirius red], α-smooth muscle actin, e-cadherin); (iii) relationship between in vivo assessment of the uterus via MRI images and 3D MRE findings with in vitro uterine tissue histology from the same individuals.

Results

3D MRE was successfully used to acquire elastograms for four patients with adenomyosis (diffuse n=3, focal n=1) and one healthy volunteer. Calculated global uterine stiffness was higher in women with adenomyosis (2.93kPa; range 2.34 – 3.39kPa) compared to a healthy volunteer (2.04kPa). Areas of stiffness on 3D elastograms reflected adenomyotic changes visualised via conventional MRI, with the added benefit of also correlating with histology/immunohistochemical assessment for markers of tissue stiffness.

Discussion

A novel 3D MRE protocol has been applied to obtain the global uterine stiffness in four women with HMB and suspected adenomyosis, and one healthy volunteer. 3D MRE has the potential to provide superior non-invasive tissue characterisation in vivo when compared to conventional MRI in the assessment of adenomyosis due to the correlation of imaging and tissue findings. Further studies are now needed to confirm the above exploratory findings, prior to performing a potential clinical trial.
Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development
Authors: de la Porte Alexandra , Schröder Julia , Thomas Moritz , Geuder Johanna , Sterr Michael , Pastor Xavier , Sanderson Leslie E. , Barakat Tahsin Stefan , Enard Wolfgang , Marr Carsten , Schröter Christian , Drukker Micha
Published: September 2024

Embryos from different mammalian species develop at characteristic timescales. These timescales are recapitulated during the differentiation of pluripotent stem cellsin vitro. Specific genes and molecular pathways that modulate cell differentiation speed between mammalian species remain to be determined. Here we use single-cell multi-omic analysis of neural differentiation of mouse, cynomolgus and human pluripotent cells to identify regulators for differentiation speed. We demonstrate that species-specific transcriptome dynamics are mirrored at the chromatin level, but that the speed of neural differentiation is insensitive to manipulations of cell growth and cycling. Exploiting the single-cell resolution of our data, we identify glycogen storage levels regulated by UDP-glucose pyrophosphorylase 2 (UGP2) as a species-dependent trait of pluripotent cells, and show that lowered glycogen storage in UGP2 mutant cells is associated with accelerated neural differentiation. The control of energy storage could be a general strategy for the regulation of cell differentiation speed.
Phonetic underpinnings of sound symbolism across multiple domains of meaning
Authors: Lacey Simon , Matthews Kaitlyn L. , Sathian K. , Nygaard Lynne C.
Published: September 2024

Sound symbolism occurs when the sound of a word alone can convey its meaning, e.g. ‘balloon’ and ‘spike’ sound rounded and pointed, respectively. Sound-symbolic correspondences are widespread in natural languages, but it is unclear how they are instantiated across different domains of meaning. Here, participants rated auditory pseudowords on opposing scales of seven different sound-symbolic domains: shape (rounded-pointed), texture (hard-soft), weight (light-heavy), size (small-big), brightness (bright-dark), arousal (calming-exciting), and valence (good-bad). Ratings showed cross-domain relationships, some mirroring those between corresponding physical domains, e.g. size and weight ratings were associated, reflecting a physical size-weight relationship, while others involved metaphorical mappings, e.g., bright/dark mapped onto good/bad, respectively. The phonetic features of the pseudowords formed unique sets with characteristic feature weightings for each domain and tended to follow the cross-domain ratings relationships. These results suggest that sound-symbolic correspondences rely on domain-specific patterns of phonetic features, with cross-domain correspondences reflecting physical or metaphorical relationships.
USP37 protects mammalian cells during DNA replication stress by counteracting CUL2LRR1and TRAIP
Authors: Villa Fabrizio , Ainsworth Johanna , Labib Karim P.M.
Published: September 2024

The USP37 deubiquitylase is important for mammalian cells to survive DNA replication stress but the underlying mechanisms are unknown. Here we demonstrate that USP37 binds the CDC45-MCM-GINS (CMG) helicase, which forms the stable core of the replisome and is regulated by ubiquitylation. The Pleckstrin-Homology Domain of USP37 binds CDC45 and structure-guided mutations that displace USP37 from CMG are sufficient to phenocopy loss of USP37 catalytic activity. Importantly, USP37 counteracts CMG helicase ubiquitylation by the CUL2LRR1ligase, which induces helicase disassembly during termination. We show that depletion of CUL2LRR1suppresses the sensitivity of Usp37 mutants to DNA synthesis defects and to ATR checkpoint kinase inhibitors. In contrast, mutation of the TRAIP ubiquitin ligase specifically suppresses the sensitivity of Usp37 mutants to topological stress during chromosome replication. We propose that USP37 evolved to reverse the untimely action of the two ubiquitin ligases that regulate the CMG helicase during chromosome replication in metazoa.
Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
Authors: Umans Benjamin D. , Gilad Yoav
Published: September 2024

The interaction between genetic variants and environmental stressors is key to understanding the mechanisms underlying neurological diseases. In this study, we used human brain organoids to explore how varying oxygen levels expose context-dependent gene regulatory effects. By subjecting a genetically diverse panel of 21 brain organoids to hypoxic and hyperoxic conditions, we identified thousands of gene regulatory changes that are undetectable under baseline conditions, with 1,745 trait-associated genes showing regulatory effects only in response to oxygen stress. To capture more nuanced transcriptional patterns, we employed topic modeling, which revealed context-specific gene regulation linked to dynamic cellular processes and environmental responses, offering a deeper understanding of how gene regulation is modulated in the brain. These findings underscore the importance of genotype-environment interactions in genetic studies of neurological disorders and provide new insights into the hidden regulatory mechanisms influenced by environmental factors in the brain.
BRD4 phosphorylation regulates the structure of chromatin nanodomains
Authors: Seitz Clayton , Fu Donghong , Liu Mengyuan , Ma Hailan , Liu Jing
Published: September 2024

The interplay between chromatin structure and phase-separating proteins is an emerging topic in cell biology with implications for understanding disease states. Here, we investigate the functional relationship between bromodomain protein 4 (BRD4) and chromatin architecture. By combining molecular dynamics simulations with live-cell imaging, we demonstrate that BRD4, when mutated at specific N-terminus sites, significantly impacts nucleosome nanodomain (NN) organization and dynamics. Our findings reveal that enhanced chromatin binding activity of BRD4 condenses NNs, while both loss or gain of BRD4 chromatin binding reduced diffusion of single nucleosomes, suggesting a role for BRD4 in the regulation of nanoscale chromatin architecture and the chromatin microenvironment. These observations shed light on the nuanced regulation of chromatin structure by BRD4, offering insights into its role in maintaining the nuclear architecture and transcriptional activity.
Latent infection of an active giant endogenous virus in a unicellular green alga
Authors: Erazo-Garcia Maria P. , Sheyn Uri , Barth Zachary K. , Craig Rory J. , Wessman Petronella , Jivaji Abdeali M. , Ray W. Keith , Svensson-Coelho Maria , Cornwallis Charlie K. , Rengefors Karin , Brussaard Corina P. D. , Moniruzzaman Mohammad , Aylward Frank O.
Published: September 2024

Latency is a common strategy in a wide range of viral lineages, but its prevalence in giant viruses remains unknown. Here we describe the activity and viral production from a 617 kbp integrated giant viral element in the model green algaChlamydomonas reinhardtii. We resolve the integrated viral region using long-read sequencing and show that viral particles are produced and released in otherwise healthy cultures. A diverse array of viral-encoded selfish genetic elements are expressed during GEVE reactivation and produce proteins that are packaged in virions. In addition, we show that field isolates ofChlamydomonassp. harbor latent giant viruses related to theC. reinhardtiiGEVE that exhibit similar infection dynamics, demonstrating that giant virus latency is prevalent in natural host communities. Our work reports the largest temperate virus documented to date and the first active GEVE identified in a unicellular eukaryote, substantially expanding the known limits of viral latency.
Climate History and Metabolic Trade-offs shape the Bacterial Response to Drought
Authors: Bouskill Nick , Chacon Stephany , Cusack Daniela , Dietterich Lee , Chen Liang , Khurram Aizah , Voriskova Jana , Holman Hoi-Ying
Published: September 2024

Soil drying challenges microbial viability and survival, with bacteria employing various mechanisms to respond to shifts in osmolarity, including dormancy or metabolic upregulation of osmoprotectants. However, the extent to which these responses are shaped by an organisms phylogeny or the climate history of a given environment is poorly understood. This study examines the responses of phylogenetically similar bacteria from semi-arid and humid tropical forest soils to osmotic and matric stress using synchrotron radiation-based Fourier Transform Infrared spectromicroscopy. This non-destructive approach depicts the biochemical phenotype for whole cells under control and stress conditions. We observed that, under osmotic stress, bacteria upregulated cell-signaling pathways, rapidly turned over lipid-storage compounds, and increased osmolyte production. In contrast, matric stress induced a more muted response, typically elevating the production of carbohydrate stress compounds, such as glycine betaine and trehalose. While phylogenetically similar bacteria showed comparable biochemistry under control conditions, climate history played an important role in regulating responses to stress, whereby a stronger metabolic response was observed from semi-arid relative to tropical forest isolates. We conclude that bacterial stress response to drought can be more diverse than previously observed, and regulated by both phylogeny and climate history.
Spatial Cellular Networks from omics data with SpaCeNet
Authors: Schrod Stefan , Lück Niklas , Lohmayer Robert , Solbrig Stefan , Völkl Dennis , Wipfler Tina , Shutta Katherine H. , Ben Guebila Marouen , Schäfer Andreas , Beißbarth Tim , Zacharias Helena U. , Oefner Peter J. , Quackenbush John , Altenbuchinger Michael
Published: September 2024

Advances in omics technologies have allowed spatially resolved molecular profiling of single cells, providing a window not only into the diversity and distribution of cell types within a tissue, but also into the effects of interactions between cells in shaping the transcriptional landscape. Cells send chemical and mechanical signals which are received by other cells, where they can subsequently initiate context-specific gene regulatory responses. These interactions and their responses shape the individual molecular phenotype of a cell in a given microenvironment. RNAs or proteins measured in individual cells, together with the cells' spatial distribution, provide invaluable information about these mechanisms and the regulation of genes beyond processes occurring independently in each individual cell. “SpaCeNet” is a method designed to elucidate both the intracellular molecular networks (how molecular variables affect each other within the cell) and the intercellular molecular networks (how cells affect molecular variables in their neighbors). This is achieved by estimating conditional independence (CI) relations between captured variables within individual cells and by disentangling these from CI relations between variables of different cells.
Coherent interaction-free detection of noise
Authors: McCord John J. , Dogra Shruti , Paraoanu Gheorghe Sorin
Published: September 2024

The measurement and characterization of noise is a flourishing area of research in mesoscopic physics. In this work, we propose interaction-free measurements as a noise-detection technique, exploring two conceptually different schemes: the coherent and the projective realizations. These detectors consist of a qutrit whose second transition is resonantly coupled to an oscillatory field that may have noise in amplitude or phase. For comparison, we consider a more standard detector previously discussed in this context: a qubit coupled in a similar way to the noise source. We find that the qutrit scheme offers clear advantages, allowing precise detection and characterization of the noise, while the qubit does not. Finally, we study the signature of noise correlations in the detector's signal.

Published by the American Physical Society
2024
Axion cogenesis without isocurvature perturbations
Authors: Co Raymond T. , Yamada Masaki
Published: September 2024

Axion rotations can simultaneously explain the dark matter abundance and the baryon asymmetry of the Universe by kinetic misalignment and axiogenesis. We consider a scenario in which the Peccei-Quinn symmetry breaking field is as large as the Planck scale during inflation and the axion rotation is initiated by the inflaton-induced potential immediately after the end of inflation. This is a realization of the cogenesis scenario that is free of problems with domain walls and isocurvature perturbations thanks to large explicit Peccei-Quinn symmetry breaking at the Planck scale during inflation. The baryon asymmetry can be more efficiently produced by leptoaxiogenesis, in which case the axion mass is predicted to be larger than O(0.1)  meV. We also discuss a UV complete model in supersymmetric theories.

Published by the American Physical Society
2024
Promoting counter-hedonic entertainment in China: assessing the effectiveness of the free trial market strategy
Authors: Zhang Ziqiong , Sun Peiliang , Wang Le , Zhang Zili
Published: September 2024

Purpose

Counter-hedonic entertainment, characterized by evoking negative emotions in consumers, has emerged as one of the most popular and profitable forms of entertainment in Western countries. However, this entertainment type is not as popular in China as in Western countries. This study examines whether the free trial of counter-hedonic entertainment can promote the consumption of such entertainment and explores the moderating effect of contextual factors on this relationship.

Design/methodology/approach

This study investigates the promotional effectiveness of the free trial strategy on counter-hedonic entertainment through a quasi-experiment involving the broadcasting of a large-scale free counter-hedonic program. This study has analyzed the counter-hedonic consumption data from 31 major cities in China and employed econometric modeling to test the hypotheses.

Findings

Results show that the free trial of counter-hedonic entertainment can promote the sales of entertainment with similar categories. The follow-up moderation analyses show that the positive effect is amplified on days with less sunlight and for consumers with abundant (vs scarce) financial resources, thereby providing evidence to support the underlying drivers of the positive effect – the need for arousal and confidence frame. Meanwhile, the free trial of counter-hedonic entertainment also has a long-term effect after airing.

Originality/value

Based on existing research on consumers’ counter-hedonic consumption motivation, this study confirms the effectiveness and boundary conditions of the free trial strategy in promoting counter-hedonic entertainment consumption for the first time. The results also offer actionable insights for counter-hedonic entertainment marketers and practitioners.
Third actor introductions to interaction episodes aiming at fast-forwarding new firm relationship development
Authors: Hassel John-Erik
Published: September 2024

Purpose

This paper aims to address third actor introductions to interaction episodes aiming at fast-forwarding the continuous development of business relationships of new firms.

Design/methodology/approach

The study is qualitative, collecting data from 30 interviews from 28 informants associated with creation of new ventures and business network development in the context of a novel type of third actor called venture builder. Venture builders are privately owned organizations devoted to new firm creation in a factory-like mode, collaborating with individual entrepreneurs.

Findings

The findings suggest that interaction episodes, central to the development of new relationships, may be triggered by introductions managed by third actors using different types of involvement depending on the location and focus of the potential relationship. A framework is presented including four types of introductions to interaction episodes, aiming at saving time by removing the perceived distance between new firms and their counterparts in the initiation of business relationships. The framework describes four types of introductions of interaction episodes: Managed, Advised, Facilitated and Monitored.

Originality/value

Triggers and introductions of interaction episodes for new firms has previously been sparsely addressed. This paper presents how third actor involvement, by the introductions of interaction episodes with internal and external counterparts is managed with an aim of fast-forwarding relationship development.
Stablecoins and inflation in Latin America: the case of Argentina
Authors: Garita Mauricio , Cerezo Bregni Celso Fernando , Asturias Rodrigo
Published: September 2024

Purpose

The purpose of this academic paper is to analyze Argentina’s inflationary situation through an understanding of its monetary policy over the years, and to identify its effect on the country’s poverty, explaining the relationship between fiat currencies and stable currencies.

Design/methodology/approach

By analyzing the case of Argentina through descriptive methodology, the authors provide information on the use of stable currencies in Argentina and the reasons behind their use.

Findings

Through descriptive research, the authors were able to find out the situation regarding the use of stable currencies in Argentina. We identified how the country’s monetary policy has affected inflation and thus purchasing power parity.

Research limitations/implications

Given that cryptocurrency information is based on privacy, there are certain arguments that must be referred through qualitative aspects.

Practical implications

The importance of stablecoins in high inflation countries.

Social implications

The understanding on how cryptocurrencies are able to maintain purchasing power and help avoid inflation related poverty.

Originality/value

Discussion of cryptocurrency items, specifically stablecoins, has been limited due to their recent emergence and the existing discussion about their legality. The study presents an argument on the use of stablecoins by presenting a case that has not yet been studied.
The role of endospore appendages in spore–spore interactions in the pathogenic Bacillus cereus group
Authors: Jonsmoen Unni Lise , Malyshev Dmitry , Sleutel Mike , Kristensen Elise Egeli , Zegeye Ephrem Debebe , Remaut Han , Andersson Magnus , Aspholm Marina Elisabeth
Published: September 2024

Species within the Bacillus cereus sensu lato group, known for their spore‐forming ability, are recognized for their significant role in food spoilage and food poisoning. The spores of B. cereus are adorned with numerous pilus‐like appendages, referred to as S‐ENAs and L‐ENAs. These appendages are thought to play vital roles in self‐aggregation, adhesion, and biofilm formation. Our study investigates the role of S‐ENAs and L‐ENAs, as well as the impact of various environmental factors on spore‐to‐spore contacts and the interaction between spores and vegetative cells, using both bulk and single‐cell approaches. Our findings indicate that ENAs, especially their tip fibrillae, play a crucial role in spore self‐aggregation, but not in the adhesion of spores to vegetative cells. The absence of L‐BclA, which forms the L‐ENA tip fibrillum, reduced spore aggregation mediated by both S‐ENAs and L‐ENAs, highlighting the interconnected roles of S‐ENAs and L‐ENAs. We also found that increased salt concentrations in the liquid environment significantly reduced spore aggregation, suggesting a charge dependency of spore‐spore interactions. By shedding light on these complex interactions, our study offers valuable insights into spore dynamics. This knowledge can inform future studies on spore behaviour in environmental settings and assist in developing strategies to manage bacterial aggregation for beneficial purposes, such as controlling biofilms in food production equipment.
Political incentives and corporate income tax: Evidence from China
Authors: Zhao Chunxiang , Yang Yang , Huang Yong
Published: September 2024

We investigate how local politicians in China exploit their discretion in enforcing tax laws to enhance their prospects of promotion to higher offices. We find that non‐state‐owned enterprises (non‐SOEs) tend to pay less income tax in the initial years after a new city leader assumes office, but this tax payment increases over the leader's tenure. Throughout city leaders' tenure, the income tax paid by non‐SOEs shows an upward trend. This political turnover effect is more pronounced among non‐SOEs incorporated in the administrative region of city leaders facing intensified peer competition and/or having a stronger incentive for promotion. By manipulating the intensity of tax enforcement over their tenure, city leaders create an upward trend in tax revenue to showcase their ability to generate sustainable fiscal revenue. Further analysis indicates that growing tax revenue over the tenure significantly increases the promotion prospects of city leaders. Overall, our findings suggest that local leaders strategically manipulate tax enforcement and revenue to enhance their prospects for promotion in contemporary China.
Collective procrastination and protest cycles
Authors: Gieczewski Germán , Kocak Korhan
Published: September 2024

This paper studies a model of “pivotal protesting,” in which citizens act in order to change the outcome rather than to collect private benefits. We show that, when citizens face repeated opportunities to protest against a regime, pivotal protesting entails complex dynamic considerations: The continuation value of the status quo influences the citizens' willingness to protest today. Thus, a mere change in expectations about the future may trigger a revolt. The same logic often induces a pattern of protest cycles, driven by a novel source of inefficiency: An expectation that a protest will take place tomorrow can excessively sap incentives to coordinate on protesting today. Thus, potential protests crowd each other out. This can lead to a form of collective procrastination: Access to more opportunities to protest can lower the citizens' welfare, as collective action becomes inefficiently delayed.