bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Diagnostic Stewardship on Ordering Trends and Pathogen Yield from mNGS Studies
Authors: Shean Ryan C. , Garrett Elizabeth , Malleis James , Lieberman Joshua A. , Bradley Benjamin T.
Published: April 2024

Background

Given the cost and unclear clinical impact of metagenomic next-generation sequencing (mNGS), laboratory stewardship may improve utilization. This study examines mNGS results from two academic medical centers employing different stewardship approaches.

Methods

80 mNGS orders (54 CSF and 26 plasma) were identified from 2019 to 2021 at the University of Washington (UW), which requires director-level approval for mNGS orders, and the University of Utah (Utah), which does not restrict ordering. The impact of mNGS results and the relationship to traditional microbiology orders were retrospectively evaluated.

Results

19% (10/54) CSF and 65% (17/26) plasma studies detected at least one organism. Compared to CSF results, plasma results were more frequently clinically significant (23% vs 7%) and led to more novel diagnoses (15% vs 0%). Results affecting antibiotic management were more common for plasma than CSF (32% vs. 2%). Stewardship practices were not associated with statistically significant differences in results or antimicrobial management. The number and cost of traditional microbiology tests at UW was greater than Utah for CSF mNGS testing (UW: 46 tests, $6237; Utah: 26 tests, $2812; p<0.05) but similar for plasma mNGS (UW: 31 tests, $3975; Utah: 21 tests, $2715; p=0.14). mNGS testing accounted for 30-50% of the total microbiology costs.

Conclusions

Improving the diagnostic performance of mNGS by stewardship remains challenging due to low positivity rates and difficulties assessing clinical impact. From a fiscal perspective, stewardship efforts should focus on reducing testing in low-yield populations given the high costs of mNGS relative to overall microbiology testing expenditures.
Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure toP. falciparuminfected mosquito bites
Authors: Lapidus Sarah , Goheen Morgan M. , Sy Mouhamad , Deme Awa B. , Ndiaye Ibrahima Mbaye , Diedhiou Younous , Mbaye Amadou Moctar , Hagadorn Kelly A. , Sene Seynabou Diouf , Pouye Mariama Nicole , Thiam Laty Gaye , Ba Aboubacar , Guerra Noemi , Mbengue Alassane , Raduwan Hamidah , Vigan-Womas Inés , Parikh Sunil , Ko Albert I. , Ndiaye Daouda , Fikrig Erol , Chuang Yu-Min , Bei Amy K.
Published: April 2024

Background

Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure toAnophelesmosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected withP. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO.

Methods

We tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with knownP. falciparuminfection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay.

Results

AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinicalP. falciparuminfection and declined 3 months after infection.

Discussion

Reactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes inP. falciparum-infected mosquito exposure.
A Natural History ofNAA15-related Neurodevelopmental Disorder Through Adolescence
Authors: Makwana Rikhil , Christ Carolina , Patel Rahi , Marchi Elaine , Harpell Randie , Lyon Gholson J.
Published: April 2024

NAA15 is a member of the NatA N-terminal acetyltransferase complex, which also includes the NAA10 enzymatic sub-unit. Individuals with variants in theNAA15coding region developNAA15-related neurodevelopmental syndrome, which presents with a wide array of manifestations that affect the heart, brain, musculoskeletal system, and behavioral and cognitive development. We tracked a cohort of 27 participants (9 females and 18 males) over time, each with a pathogenicNAA15variant, and administered the Vineland-3 assessment to assess their adaptive functioning. We found that the cohort performed significantly worse compared to the normalized Vineland values. On average, females performed better than males, and they performed significantly better on the Motor Domain and Fine Motor Sub-Domain portions of the assessment. Over time, females showed a decrease in adaptive functioning, with the decline being especially correlated at the Coping, Domestic, and Fine motor sub-domains. Males (after excluding one outlier) showed a moderate positive correlation between age and ABC standard score. Ultimately, additional longitudinal data should be collected to determine the validity of the between sex-differences and to better understand the change in adaptive behavioral outcomes of individuals withNAA15-neurodevelopmental disorder as they age.
Nausea and Gastric Myoelectrical Activity are Influenced by Hormonal Contraception in Chronic Gastroduodenal Disorders
Authors: Lim Alexandria H , Varghese Chris , Sebaratnam Gabrielle , Schamberg Gabriel , Calder Stefan , Gharibans Armen , Andrews Christopher N , Daker Charlotte , Foong Daphne , Ho Vincent , Wise Michelle R , O’Grady Greg
Published: April 2024

Background

Chronic gastroduodenal disorders such as chronic nausea and vomiting syndrome (CNVS), functional dyspepsia (FD) and gastroparesis, are more prevalent among young women, many of whom are hormonal contraception users. We aimed to evaluate the effects of hormonal contraception on symptom severity and gastric myoelectrical activity in people with chronic gastroduodenal disorders.

Methods

This analysis was conducted on a large international cohort of patients who met Rome IV criteria for CNVS or FD and had undergone body surface gastric mapping using Gastric Alimetry (Alimetry, New Zealand). Symptoms were continuously reported on 0-10 Likert scales using a validated symptom logging app.

Results

127 people were included: 43 females using hormonal contraception, 30 premenopausal females not using hormonal contraception, 30 postmenopausal females, and 24 males. Premenopausal females who used hormonal contraception had higher nausea scores than non-users (3.80 [IQR 2.00-5.42] vs 2.25 [0.20-4.43]; p<0.05), particularly when using the combined oral contraceptive pill (COCP) with hormone-free intervals compared to continuous use (5.20 [4.30-6.00] vs. 2.40 [1.70-3.80], p=0.02). Premenopausal women were more symptomatic than postmenopausal women and men (p<0.001). The Principal Gastric Frequency was higher in hormonal contraception users (median 3.1 cpm [IQR 3.00-3.30] vs. 3.00 cpm [2.90-3.10], p<0.001), and highest in users of progestogen-only formulations (p<0.02).

Conclusion

Women with gastrointestinal disorders on hormonal contraception experience increased nausea in comparison to non-users of hormonal contraception, with substantial variation in nausea severity dependent on contraceptive type. Hormonal contraception users also demonstrated modified gastric electrophysiology. Women with chronic gastroduodenal symptoms should be asked about their use of hormonal contraception and non-hormonal contraceptive alternatives trialled as a means to reduce symptoms.
Herbivory can increase plant fitness via reduced interspecific competition – evidence from models and mesocosms
Authors: Böttner Laura , Dudenhausen Fabio , Nouere Sara , Malacrinò Antonino , Schäfer Martin , Koene Joris M. , Huber Meret , Xu Shuqing
Published: April 2024

Herbivores are generally considered to reduce plant fitness. However, as in natural communities herbivores often feed on several competing plant species, herbivores can also increase plant fitness by reducing interspecific competition among plants. In this study, we developed a testable model to predict plant fitness in the presence of an interspecific competitor and an herbivore that feeds on both plant species. Our model allows to predict at which herbivore and competitor densities the focal species will benefit from herbivory. This can be estimated by quantifying the effects of the herbivore on the fitness of the focal plant and on its competitor, and by estimating the levels of intra- and interspecific competition in a pair-wise fashion, respectively. We subsequently validated the model in indoor microcosms using three interacting species: an aquatic macrophyte (the giant duckweedSpirodela polyrhiza), its native competitors (green algae), and its native herbivore (the pond snailLymnaea stagnalis). Additional outdoor mesocosm experiments supported our model under natural conditions. Together, this study provides a conceptual framework to understand how herbivores shape plant fitness in a community context.
Alternative oxidase alleviates mitochondrial oxidative stress during limited nitrate reduction inArabidopsis thaliana
Authors: Otomaru Daisuke , Ooi Natsumi , Monden Kota , Suzuki Takamasa , Noguchi Ko , Nakagawa Tsuyoshi , Hachiya Takushi
Published: April 2024

The conversion of nitrate to ammonium, i.e., nitrate reduction, is a major consumer of reductants in plants. Previous studies have reported that the mitochondrial alternative oxidase (AOX) is upregulated under limited nitrate reduction conditions, including no/low nitrate or when ammonium is the sole nitrogen (N) source. Electron transfer from ubiquinone to AOX bypasses the proton-pumping complexes III and IV, thereby consuming reductants efficiently. Thus, upregulated AOX under limited nitrate reduction may dissipate excessive reductants and thereby attenuate oxidative stress. Nevertheless, so far there is no firm evidence for this hypothesis due to the lack of experimental systems to analyze the direct relationship between nitrate reduction and AOX. We therefore developed a novel culturing system forA. thalianathat manipulates activities of nitrate reduction and AOX separately without causing N starvation, ammonium toxicity, and lack of nitrate signal. Using this system we examined genome-wide gene expression and plant growth to better understand the relationship between AOX and nitrate reduction. Here we show that AOX alleviates mitochondrial oxidative stress and sustains plant growth under limited nitrate reduction.
Fmp40 ampylase regulates cell survival upon oxidative stress by controlling Prx1 and Trx3 oxidation
Authors: Masanta Suchismita , Wiesyk Aneta , Panja Chiranjit , Pilch Sylwia , Ciesla Jaroslaw , Sipko Marta , De Abhipshita , Enkhbaatar Tuguldur , Maslanka Roman , Skoneczna Adrianna , Kucharczyk Roza
Published: April 2024

Reactive oxygen species (ROS), play important roles in cellular signaling, nonetheless are toxic at higher concentrations. Cells have many interconnected, overlapped or backup systems to neutralize ROS, but their regulatory mechanisms remain poorly understood. Here, we reveal an essential role for mitochondrial AMPylase Fmp40 from budding yeast in regulating the redox states of mitochondrial 1-Cys peroxiredoxin, Prx1, which is the only protein shown to neutralize H2O2with the oxidation of the mitochondrial glutathione and Trx3, thioredoxin, directly involved in the reduction of Prx1. Deletion ofFMP40impacts a cellular response to H2O2treatment that leads to programmed cell death (PCD) induction and an adaptive response involving up or down regulation of genes encoding, among others the catalase Cta1, PCD inducing factor Aif1, and mitochondrial redoxins Trx3 and Grx2. This ultimately perturbs the reduced glutathione and NADPH cellular pools. We further demonstrated that Fmp40 AMPylates Prx1, Trx3, and Grx2in vitroand interacts with Trx3in vivo. AMPylation of the threonine residue 66 in Trx3 is essential for this protein’s proper endogenous level of and its precursor forms’ maturation under oxidative stress conditions. Additionally, we showed the Grx2 involvement in the reduction of Trx3in vivo. Taken together, Fmp40, through control of the reduction of mitochondrial redoxins, regulates the hydrogen peroxide, GSH and NADPH signaling influencing the programmed cell death execution.

Graphical abstract
Systematic genome-wide discovery of host factors governing bacteriophage infectivity
Authors: Chitboonthavisuk Chutikarn , Martin Cody , Huss Phil , Peters Jason M. , Anantharaman Karthik , Raman Srivatsan
Published: April 2024

Bacterial host factors regulate the infection cycle of bacteriophages. Except for some well-studied host factors (e.g., receptors or restriction-modification systems), the contribution of the rest of the host genome on phage infection remains poorly understood. We developed ‘PHAGEPACK’, a pooled assay that systematically and comprehensively measures each host gene’s impact on phage fitness. PHAGEPACK combines CRISPR interference with phage packaging to link host perturbation to phage fitness during active infection. Using PHAGEPACK, we constructed a genome-wide map of genes impacting T7 phage fitness in permissiveE. coli, revealing pathways previously unknown to affect phage packaging. When applied to the non-permissiveE. coliO121, PHAGEPACK identified pathways leading to host resistance; their removal increased phage susceptibility up to a billion-fold. Bioinformatic analysis indicates phage genomes carry homologs or truncations of key host factors, potentially for fitness advantage. In summary, PHAGEPACK offers valuable insights into phage-host interactions, phage evolution, and bacterial resistance.
Adverse Event Comparison between Glucagon-like Peptide-1 Receptor Agonists and Other Anti-Obesity Medications Following Bariatric Surgery
Authors: Samuels Jason M , Niswender Kevin , Roumie Christianne L. , Self Wesley , Holzman Michael , Spann Matthew , Flynn C. Robb , Ye Fei , Irlmeier Rebecca , Funk Luke M. , Patel Mayur
Published: April 2024

Introduction

The safety of Glucagon-like Peptide 1 Receptor Agonists (GLP1RAs) following bariatric surgery remains largely unknown. This study aims to compare the incidence of adverse events (AEs) with GLP1RAs and other anti-obesity medications (AOMs) after bariatric surgery.

Methods

This single-center retrospective cohort included patients (ages 16-65) if they met the following criteria: underwent laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Subjects were categorized as users of ‘FDA-approved’ or ‘off label’ AOMs or GLP1RAs AOMs if documented as receiving the medication on the cohort entry date or after. Non-GLP1RA AOMs were Phentermine, Orlistat, Topiramate, Canagliflozin, Dapagliflozin, Empagliflozin, Naltrexone, Bupropion/Naltrexone, and Phentermine/Topiramate. GLP1RAs AOMs included: Semaglutide, Dulaglutide, Exenatide, Liraglutide. Primary outcome was AEs incidence. Logistic regression was used to determine the association of AOM exposure with AEs.

Results

We identified 599 patients meeting inclusion criteria (83% female, median 47.8 years old (IQR 40.9 – 55.4). Median surgery to AOM duration was 30 months (IQR 0 – 62). GLP1RAs were not associated with higher odds of AEs (adjusted Odds Ratio, (aOR) 1.1, [95% CI 0.5 – 2.6] and 1.1 [95% CI 0.6 – 2.3] for GLP1RA versus FDA-approved and ‘Off-Label’ AOMs, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01. [95% CI 0.0 – 0.01], p<0.001).

Conclusion

GLP1RAs were not associated with an increased risk of AEs compared to non-GLP1RA AOMs in patients who previously underwent bariatric surgery. Prospective studies are needed to identify the optimal timeframe for initiation of GLP1RA.
The SPFH complex HflK-HflC regulates aerobic respiration in bacteria
Authors: Perez-Lopez Maria Isabel , Lubrano Paul , Angelidou Georgia , Glatter Timo , Paczia Nicole , Link Hannes , Sourjik Victor
Published: April 2024

The bacterial HflK-HflC membrane complex is a member of the highly conserved SPFH protein family, which is found throughout all domains of life and includes eukaryotic stomatins, flotillins, and prohibitins. These proteins organize cell membranes and are involved in various processes. However, the exact physiological functions of most bacterial SPFH proteins remain unclear. Here, we report that the HflK-HflC complex inEscherichia coliis required for growth under high aeration. The absence of this complex causes an aerobic growth defect due to a reduced abundance of IspG, a crucial enzyme in the isoprenoid biosynthetic pathway. This reduction leads to lower levels of ubiquinone, reduced respiration, lower ATP levels, and misregulated expression of respiratory genes. The regulation of aerobic respiration by the HflK-HflC complex resembles the mitochondrial respiratory defects caused by prohibitin mutations in mammalian and yeast cells, suggesting a functional commonality between these bacterial and eukaryotic SPFH proteins.
Accelerating antimalarial drug discovery with a new high-throughput screen for fast-killing compounds
Authors: Sakura Takaya , Ishii Ryuta , Yoshida Eri , Kita Kiyoshi , Kato Teruhisa , Inaoka Daniel Ken
Published: April 2024

The urgent need for rapidly acting compounds in the development of antimalarial drugs underscores the significance of such compounds in overcoming resistance issues and improving patient adherence to antimalarial treatments. The present study introduces a high-throughput screening (HTS) approach using 1536-well plates, employingPlasmodium falciparumlactate dehydrogenase (PfLDH) combined with nitroreductase (NTR) and fluorescent probes to evaluate inhibition of the growth of the asexual blood stage of malaria parasites. This method was adapted to efficiently measure the parasite reduction ratio (PRR) in a 384-well plate format, streamlining the traditionally time-consuming screening process. By successfully screening numerous compounds, this approach identified fast-killing hits early in the screening process, addressing challenges associated with artemisinin-based combination therapies. The high-throughput PRR method is expected to be of value in continuously monitoring fast-killing properties during structure-activity relationship studies, expediting the identification and development of novel, rapidly acting antimalarial drugs within phenotypic drug discovery campaigns.
Border quarantine, vaccination and public health measures to mitigate the impact of COVID-19 importations: a modelling study
Authors: Lydeamore Michael J , Zachreson Cameron , Conway Eamon , Shearer Freya M , Baker Christopher M , Ross Joshua V , Miller Joel C , McCaw James M , Geard Nicholas , McVernon Jodie , Price David J
Published: April 2024

We developed a flexible infectious disease model framework that combines a detailed individual-based model of arrival pathways (quarantine model) and an individual-based model of the arrivals environment (community model) to inform border risk assessments. The work was motivated by Australia’s desire to safely increase international arrival volumes, which had been heavily constrained since early 2020 as a result of the COVID-19 pandemic. These analyses supported decisions on quarantine and border policy in the context of the Australian government’s national reopening plan in late 2021.

The quarantine model provides a detailed representation of transmission within quarantine and time-varying infectiousness and test sensitivity within individuals, to characterise the likelihood and infectiousness of breaches from quarantine. The community model subsequently captures the impact these infectious individuals have in the presence of varying vaccination coverage, arrival volumes, public health and social measures (PHSMs) and test-trace-isolate-quarantine system effectiveness in the Australian context.

Our results showed that high vaccination coverage would be required to safely reopen with support from ongoing PHSMs, and quarantine pathways have minimal impact on infection dynamics in the presence of existing local transmission. The modelling pipeline we present can be flexibly adapted to a range of scenarios and thus provides a useful framework for generating timely risk assessments in the event of future pandemics.
Eye care practitioners and falls prevention: protocol for a scoping review
Authors: Chen Jingyi , Alam Khyber , Lee Si Ye , Hill Anne-Marie
Published: April 2024

Introduction

Falls are the leading cause of injury in older adults and can lead to substantial costs for the individual and society. Eye care practitioners in the community provide services for a large proportion of the older adult population and can play a key role in falls prevention, however it is unclear whether they are implementing evidence-based recommendations in practice. The aim of this scoping review is to map and synthesise the current evidence for community-based eye care practitioners translating falls prevention evidence into clinical practice.

Methods and analysis

The study will use the framework by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Studies that have been published in English from 1990 to current on the topic of eye care practitioners and falls prevention in older adults will be searched on MEDLINE, Embase, and CINAHLPlus databases. Grey literature will be searched using Web of Science and OpenMD. The titles and abstracts of results will be screened against the inclusion criteria and full texts will be analysed. Data from final included articles will be extracted by two independent reviewers using a tool created according to the Joanna Briggs Institute guidelines. The World Falls Guidelines will be used as a framework for data mapping. Results will be charted, collated, and summarised narratively.

Ethics and dissemination

It is anticipated that the results from this scoping review will highlight any gaps in the literature regarding eye care practitioner awareness and implementation of falls prevention guidelines and inform future research and clinical recommendations. Ethics approval is not required. Findings will be submitted to a peer-reviewed journal for publication.
A new targeting motif for endoplasmic reticulum surface proteins
Authors: Arad Sivan , Suseendran Parkesh , Ravid Shani , Peleg Yoav , Ben-Dor Shifra , Fidel Elena , Olender Tsviya , Wang Xiaofeng , Schuldiner Maya , Fenech Emma J
Published: April 2024

The Endoplasmic Reticulum (ER) is the entry site to the secretory pathway, serving as the targeting destination for ∼30% of the proteome. The mechanisms for targeting soluble or integral membrane secretory pathway proteins are well-studied. However, it is currently unknown how the tens of ER surface proteins (SuPs), central for organelle function, reach the outer leaflet of the membrane. It was previously shown that an amphipathic helix (AH) from the Brome mosaic virus protein 1a, is both necessary and sufficient for targeting to the ER surface in baker’s yeast. We therefore utilized this helix as a model substrate and performed a high-content screen to uncover factors that affect SuP targeting. Our results suggest a role for membrane lipid composition in targeting specificity. To see if the presence of an AH is a more general mechanism for SuP targeting, we searched for their presence within SuPs of both yeast and humans. Five endogenous yeast SuPs contained AHs, and of these four were sufficient for ER localization. Moreover, the presence of an AH was conserved to human SuP orthologs. By altering helix features we determine the parameters that affect this new targeting motif. Hence our work demonstrates how specific properties of AHs encode affinity for the ER membrane. More globally, understanding how SuPs are targeted correctly takes us a step forward in determining the underlying mechanisms of cellular localization and secretory pathway functions.

The authors declare that they have no conflict of interest.
Osmotic stress in roots drives lipoxygenase-dependent plastid remodeling through singlet oxygen production
Authors: Cohen-Hoch Dekel , Chen Tomer , Sharabi Lior , Dezorella Nili , Itkin Maxim , Feiguelman Gil , Malitsky Sergey , Fluhr Robert
Published: April 2024

Osmotic stress, caused by the lack of water or by high salinity, is a common environmental problem in roots. Osmotic stress can be reproducibly simulated with the application of solutions of the high-molecular-weight and impermeable polyethylene glycol. Different reactive oxygen species such as singlet oxygen, superoxide and hydrogen peroxide accompany this stress. Among them, singlet oxygen, produced as a byproduct of lipoxygenase activity, was shown to be associated with limiting root growth. To better understand the source and effect of singlet oxygen, its production was followed at the cellular level. Osmotic stress initiated profound changes in plastid morphology and vacuole structure. By confocal and electron microscopy the plastids were shown to be a source of singlet oxygen accompanied by the appearance of multiple small extraplastidic bodies that were also an intense source of singlet oxygen. A marker protein, CRUMPLED LEAF, indicated that these small bodies originated from the plastid outer membrane. Remarkably a type 9 lipoxygenase, LOX5, was shown to change its distribution from uniformly cytoplasmic to a more clumped distribution together with plastids and the small bodies. In addition, oxylipin products of type 9 lipoxygenase increased while products of type 13 lipoxygenases decreased. Inhibition of lipoxygenase by SHAM inhibitor or in down-regulated lipoxygenase lines prevented cells from initiating the cellular responses leading to cell death. In contrast, singlet oxygen scavenging halted terminal cell death. These findings underscore the reversible nature of osmotic stress-induced changes, emphasizing the pivotal roles of lipoxygenases and singlet oxygen in root stress physiology.
VRN2-PRC2 facilitates light-triggered repression of PIF signaling to coordinate growth in Arabidopsis
Authors: Osborne Rory , Labandera Anne-Marie , Ryder Alex J. , Kanali Anastasia , Akintewe Oluwatunmise , Schwarze Maximillian A. , Morgan Christian D. , Xu Tianyuan , Hartman Sjon , Kaiserli Eirini , Gibbs Daniel J.
Published: April 2024

The polycomb protein VERNALIZATION2 (VRN2) is a plant-specific subunit of the polycomb repressive complex 2 (PRC2), a conserved eukaryotic holoenzyme that represses gene expression by depositing the histone H3K27me3 mark in chromatin. Previous work established VRN2 as an oxygen-regulated target of the N-degron pathway that may function as a sensor subunit connecting PRC2 activity to the perception of positional and environmental cues. Here we show that VRN2 is enriched in hypoxic meristematic regions and emerging leaves ofArabidopsisunder non-stressed conditions, and thatvrn2 mutants are larger than wild type, indicating that VRN2-PRC2 negatively regulates growth and development. This growth phenotype is caused by ectopic expression of genes that promote cell expansion, including manySAURgenes and other direct PIF transcription factor targets. Analysis ofSAUR19promoter activity and expression dynamics revealed that VRN2 is required to specifically repress these genes in the light. Moreover, we show that VRN2 is epistatic to PIF4, and directly binds and methylates histones of key loci in the PIF4 transcriptional network to provide robust light-responsive control of gene expression and growth. We propose that hypoxia-stabilised VRN2-PRC2 sets a conditionally repressed chromatin state at PIF-regulated hub genes early in leaf ontogeny coinciding with the cell division phase, and that this is required for enhancing their subsequent repression via a light-responsive signalling cascade as cells enter the expansion phase. Thus, we have identified VRN2-PRC2 as core component of a spatially regulated and developmentally encoded epigenetic mechanism that co-ordinates environment-responsive growth by facilitating light-triggered suppression of PIF signalling.
Design of highly functional genome editors by modeling the universe of CRISPR-Cas sequences
Authors: Ruffolo Jeffrey A. , Nayfach Stephen , Gallagher Joseph , Bhatnagar Aadyot , Beazer Joel , Hussain Riffat , Russ Jordan , Yip Jennifer , Hill Emily , Pacesa Martin , Meeske Alexander J. , Cameron Peter , Madani Ali
Published: April 2024

Gene editing has the potential to solve fundamental challenges in agriculture, biotechnology, and human health. CRISPR-based gene editors derived from microbes, while powerful, often show significant functional tradeoffs when ported into non-native environments, such as human cells. Artificial intelligence (AI) enabled design provides a powerful alternative with potential to bypass evolutionary constraints and generate editors with optimal properties. Here, using large language models (LLMs) trained on biological diversity at scale, we demonstrate the first successful precision editing of the human genome with a programmable gene editor designed with AI. To achieve this goal, we curated a dataset of over one million CRISPR operons through systematic mining of 26 terabases of assembled genomes and meta-genomes. We demonstrate the capacity of our models by generating 4.8x the number of protein clusters across CRISPR-Cas families found in nature and tailoring single-guide RNA sequences for Cas9-like effector proteins. Several of the generated gene editors show comparable or improved activity and specificity relative to SpCas9, the prototypical gene editing effector, while being 400 mutations away in sequence. Finally, we demonstrate an AI-generated gene editor, denoted as OpenCRISPR-1, exhibits compatibility with base editing. We release OpenCRISPR-1 publicly to facilitate broad, ethical usage across research and commercial applications.
Hidden-flavor four-quark states in the charm and bottom region
Authors: Hoffer Joshua , Eichmann Gernot , Fischer Christian S.
Published: April 2024

We discuss the spectrum and the internal composition of ground and excited four-quark states in the charm and bottom energy region. To this end we extend previous calculations within the framework of the relativistic four-body Faddeev-Yakubovsky equation to include quantum numbers with JPC=0++,0−+,1−−,1+− and 1++ and study their internal composition in terms of heavy-light meson pairs, hadroquarkonia and diquark-antidiquark clusters. We observe similar patterns in the charm and bottom energy region with different compositions of the four-quark states depending on JPC quantum numbers. Most notably, we find that all states with C·P=+1 are dominated by heavy-light meson contributions, whereas for axial-vector states with JPC=1+− including the Zc(3900) we find a much more complicated picture depending on the flavor content. We systematically compare our results for the spectrum with existing experimental results and provide predictions for future analyses.

Published by the American Physical Society
2024
Electromagnetic fields in compact binaries: Post-Newtonian wave generation and application to double white dwarfs systems
Authors: Henry Quentin , Larrouturou François , Le Poncin-Lafitte Christophe
Published: April 2024

The aim of this work is twofold: (i) to properly define a wave-generation formalism for compact-supported sources embedded in Einstein-Maxwell theory, relying on matched post-Newtonian and multipolar-post-Minkowskian expansions; (ii) to apply this formalism (which is valid for any type of post-Newtonian sources) to the case of two stars with constant and aligned magnetic dipoles, by computing the fluxes of energy and angular momentum to the next-to-leading order, as well as the gravitational amplitude modes. Assuming eccentric orbits, we derive the evolution of orbital parameters, as well as the observables of the system, notably the gravitational phase for quasicircular orbits. Finally, we give some numerical estimates for the contribution of the magnetic dipoles for some realistic systems.

Published by the American Physical Society
2024
Bethe Ansatz for the superconformal index with unequal angular momenta
Authors: Aharony Ofer , Mamroud Ohad , Nowik Shimon , Weissman Meir
Published: April 2024

A few years ago it was shown that the superconformal index of the N=4 supersymmetric SU(N) Yang-Mills theory in the large N limit matches with the entropy of 1/16-supersymmetric black holes in type IIB string theory on AdS5×S5. In some cases, an even more detailed match between the two sides is possible. When the two angular momentum chemical potentials in the index are equal, the superconformal index can be written as a discrete sum of Bethe ansatz solutions, and it was shown that specific terms in this sum are in a one-to-one correspondence to stable black hole solutions, and that the matching can be extended to nonperturbative contributions from wrapped D3-branes. A Bethe ansatz approach to computing the superconformal index exists also when the ratio of the angular momentum chemical potentials is any rational number, but in those cases it involves a sum over a very large number of terms (growing exponentially with N). Benini showed that a specific one of these terms matches with the black hole, but the role of the other terms is not clear. In this paper we analyze some of the additional contributions to the index in the Bethe ansatz approach, and we find that their matching to the gravity side is much more complicated than in the case of equal chemical potentials. In particular, we find some contributions that are larger than the one that was found to match the black holes, in which case they must cancel with other large contributions. We give some evidence that cancellations of this type are possible, but we leave a full understanding of how they work to the future.

Published by the American Physical Society
2024
Magnetic-order-mediated carrier and phonon dynamics in
MnBi2Te4
Authors: Cheng L. , Xiang T. , Qi J.
Published: April 2024

We investigate the quasiparticle dynamics in MnBi2Te4 single crystals using ultrafast optical spectroscopy. Our results show that there exist anomalous dynamical optical responses below the antiferromagnetic (AFM) ordering temperature TN. In specific, we reveal that both the initial carrier decay and recombination processes can be modulated via introducing the AFM order in subpicosecond and picosecond timescales, respectively. We also discover a long relaxation process emerging below TN with a timescale approaching the nanosecond regime, and can be attributed to the T-dependent spin-lattice interaction. There also emerges an unusual phonon energy renormalization below TN, which is found to arise from its coupling to the spin degree via the exchange interaction and magnetic anisotropy. Our findings provide key information for understanding the dynamical properties of nonequilibrium carrier, spin, and lattice in MnBi2Te4.

Published by the American Physical Society
2024
Error correlations in photonic qudit-mediated entanglement generation
Authors: Liu Xiaoyu , Bharos Niv , Markovich Liubov , Borregaard Johannes
Published: April 2024

Generating entanglement between distributed network nodes is a prerequisite for the quantum internet. Entanglement distribution protocols based on high-dimensional photonic qudits enable the simultaneous generation of multiple entangled pairs, which can significantly reduce the required coherence time of the qubit registers. However, current schemes require fast optical switching, which is experimentally challenging. In addition, the higher degree of error correlation between the generated entangled pairs in qudit protocols compared to qubit protocols has not been widely studied in detail. We propose a qudit-mediated entangling protocol that completely circumvents the need for optical switches at the expense of a lower success probability of the scheme. Furthermore, we quantify the amount of error correlation between the simultaneously generated entangled pairs and analyze the effect on entanglement purification algorithms and teleportation-based quantum error correction. We find that optimized purification schemes can efficiently correct the correlated errors, while the quantum error correction codes studied here perform worse than for uncorrelated error models.

Published by the American Physical Society
2024
Visualizing entanglement in multiqubit systems
Authors: Bley Jonas , Rexigel Eva , Arias Alda , Longen Nikolas , Krupp Lars , Kiefer-Emmanouilidis Maximilian , Lukowicz Paul , Donhauser Anna , Küchemann Stefan , Kuhn Jochen , Widera Artur
Published: April 2024

In the field of quantum information science and technology, the representation and visualization of quantum states and related processes are essential for both research and education. In this context, a focus lies especially on ensembles of few qubits. There exist many powerful representations for single-qubit and multiqubit systems, such as the famous Bloch sphere and generalizations. Here, we utilize the dimensional circle notation as a representation of such ensembles, adapting the so-called circle notation of qubits and the idea of representing the n-particle system in an n-dimensional space. We show that the mathematical conditions for separability lead to symmetry conditions of the quantum state visualized, offering a new perspective on entanglement in few-qubit systems and therefore on various quantum algorithms. In this way, dimensional notations promise significant potential for conveying nontrivial quantum entanglement properties and processes in few-qubit systems to a broader audience, and could enhance understanding of these concepts as a bridge between intuitive quantum insight and formal mathematical descriptions.

Published by the American Physical Society
2024
Temperature dependence of charge conversion during NV-center relaxometry in nanodiamond
Authors: Cardoso Barbosa Isabel , Gutsche Jonas , Lönard Dennis , Dix Stefan , Widera Artur
Published: April 2024

Temperature-dependent nitrogen-vacancy (NV)-center relaxometry is an established tool to characterize paramagnetic molecules near a sensing diamond, gaining momentum in different fields of science. However, recent results indicate that conversion between NV-center charge states impedes these measurements and influences the results for the T1 time. While the temperature dependence of NV centers' T1 time is well studied, additional contributions from temperature-dependent charge conversion during the dark time may further affect the measurement results. We combine temperature-dependent relaxometry and fluorescence spectroscopy at varying laser powers to unravel the temperature dependence of charge conversion in nanodiamond for biologically relevant temperatures. While we observe a decrease of the T1 time with increasing temperatures, charge conversion remains unaffected by the temperature change. These results allow the temperature-dependent performance of T1 relaxometry without further consideration of temperature dependence of charge conversion.

Published by the American Physical Society
2024
Optical dipolar chiral sorting forces and their manifestation in evanescent waves and nanofibers
Authors: Golat Sebastian , Kingsley-Smith Jack J. , Diez Iago , Martinez-Romeu Josep , Martínez Alejandro , Rodríguez-Fortuño Francisco J.
Published: April 2024

Optical fields can exert forces of chiral nature on molecules and nanoparticles, which would prove extremely valuable in the separation of enantiomers with pharmaceutical applications, yet it is inherently complex, and the varied frameworks used in the literature further complicate the theoretical understanding. This paper unifies existing approaches used to describe dipolar optical forces and introduces a symmetry-based “force basis” consisting of twelve vector fields, each weighted by particle-specific coefficients, for a streamlined description of force patterns. The approach is rigorously applied to evanescent waves and dielectric nanofibers, yielding concise analytical expressions for optical forces. Through this, we identify optimal strategies for enantiomer separation, offering invaluable guidance for future experiments.

Published by the American Physical Society
2024
Effects of nucleation at a first-order transition between two superconducting phases: Application to
CeRh2As2
Authors: Szabó András L. , Fischer Mark H. , Sigrist Manfred
Published: April 2024

Recent experiments observed a phase transition within the superconducting regime of the heavy-fermion system CeRh2As2 when subjected to a c-axis magnetic field. This phase transition has been interpreted as a parity switching from even to odd parity as the field is increased, and is believed to be of first order. If correct, this scenario provides a unique opportunity to study the phenomenon of local nucleation around inhomogeneities in a superconducting context. Here, we study such nucleation in the form of sharp domain walls emerging on a background of spatially varying material properties and hence, critical magnetic field. To this end, we construct a spatially inhomogeneous Ginzburg-Landau functional and apply numerical minimization to demonstrate the existence of localized domain-wall solutions and study their physical properties. Furthermore, we propose ultrasound attenuation as an experimental bulk probe of domain-wall physics in the system. In particular, we predict the appearance of an absorption peak due to domain-wall percolation upon tuning the magnetic field across the first-order transition line. We argue that the temperature dependence of this peak could help identify the nature of the phase transition.

Published by the American Physical Society
2024
Entanglement phase transitions in non-Hermitian Floquet systems
Authors: Zhou Longwen
Published: April 2024

The competition between unitary time evolution and quantum measurements could induce phase transitions in the entanglement characteristics of quantum many-body dynamics. In this work, we reveal such entanglement transitions in the context of non-Hermitian Floquet systems. Focusing on noninteracting fermions in a representative bipartite lattice with balanced gain/loss and under time-periodic quenches, we uncover rich patterns of entanglement transitions due to the interplay between driving and non-Hermitian effects. Specially, we find that the monotonic increase of quenched hopping amplitude could flip the system between volume-law and area-law entangled Floquet phases, yielding alternated entanglement transitions. Meanwhile, the increase of gain/loss strength could trigger area-law to volume-law reentrant transitions in the scaling behavior of steady-state entanglement entropy, which are abnormal and highly unexpected in nondriven systems. Connections between entanglement transitions and parity-time-reversal (PT) transitions in Floquet spectra are further established. Our findings not only build a foundation for exploring entanglement phase transitions in Floquet non-Hermitian setups, but also provide efficient means to engineer and control such transitions by driving fields.

Published by the American Physical Society
2024
Wells Fargo Circles the Wagons: Communicating during a Crisis
Authors: Craddock Jenny , West June
Published: April 2024

In October 2016, Timothy Sloan, the newly appointed CEO of American banking giant Wells Fargo, faced a massive public-relations crisis. A few weeks earlier, a United States government agency had announced the results of its regulatory review of the bank and exposed a shocking practice common in the retail division, in which aggressive community bankers had created more than a million fraudulent accounts and credit card applications on behalf of unaware customers for the past several years. Over the next few weeks, the bank—and Sloan's predecessor, John Stumpf, in particular—suffered from harsh criticism from politicians, journalists, and former employees alike, ultimately forcing Stumpf's resignation. As Sloan sought to minimize the public-image backlash and restore general trust in Wells Fargo, he struggled to construct the best communication strategy for the bank's next chapter.
The Astroworld tragedy as an argument for proactive crisis management
Authors: Murray Margaret Anne , Marvin April
Published: April 2024

Purpose

The Astroworld concert tragedy is used as an example of crisis (mis)management and the potential utility of the 4R model. Although the 4R model has been implemented in high-risk emergency management situations, it is useful in the PR field because of its actionable approach, creating a way for practitioners to prepare for and manage crisis situations.

Design/methodology/approach

This is an analysis of the crisis that occurred at Astroworld, spanning preparation, day-of events, casualties and enduring reputational impact. The paper applies the 4R method to the Astroworld tragedy to show how it could have lessened or even prevented the tragedy. Finally, the SCCT model is used to explain why the official post-crisis statements were ineffective.

Findings

Social media has heightened the importance of a quick and effective organizational response to risk and crisis situations because poor responses can go viral quickly. However, social media also provides intelligence and crowd sourced information that can inform PR practitioners of emerging crisis scenarios. It is also an underutilized tool for two-way communication during crises.

Practical implications

The 4R approach is beneficial to general practitioners as it simplifies crisis best-practices, something essential for quick action. As our world changes and becomes less predictable, practitioners must have a clear plan to protect their organizations and the public surrounding them. This approach includes reduction, readiness, response and recovery, which are all essential in crisis communication.

Originality/value

The 4R method has not been explored or applied in the PR field. This paper highlights how the model has been utilized in the emergency management field and illustrates the way 4R can serve the PR field.
Racial discrimination in entrepreneurship: a synthesis and conceptual framework
Authors: Basu Madhurima , Sinha Rai Siddhant , Nandakumar M.K. , Hota Pradeep Kumar , Battisti Martina
Published: April 2024

Purpose

This study aims to synthesize and conceptualize the highly fragmented yet important literature on racial discrimination in entrepreneurship.

Design/methodology/approach

A bibliometric analysis and literature review were performed that involved 523 articles containing 26,926 references.

Findings

The bibliometric analysis identified three dominant research themes that comprehensively illustrate the state of research in this domain: strategic, sociocultural and individual-level perspectives. The synthesis of extant literature helped in formulating a holistic conceptual model that portrays the genuineness of racial discrimination in entrepreneurship. The sources, factors and impact of racial discrimination faced by entrepreneurs were identified. Based on the review and analysis of keywords, certain fruitful future research directions were formulated that will take the field forward.

Originality/value

This work is the first attempt to review the literature that narrows down the focus to racial discrimination in entrepreneurship (from other discriminations such as gender, cultural and religious discrimination) as one form of discrimination due to its unique origins and consequences.