bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC1 controls the generation and maintenance of effector-like CD8+T cells during chronic viral infection
Authors: Rica Ramona , Waldherr Monika , Schülein Marlene , Miyakoda Emi , Sandner Lisa , Stolz Valentina , Waltenberger Darina , Krausgruber Thomas , Bock Christoph , Boucheron Nicole , Ellmeier Wilfried , Sakaguchi Shinya
Published: March 2024

CD8+T cell exhaustion is a complex process that involves the differentiation of persistently activated CD8+T cells into functionally distinct cell subsets. Here, we investigated the role of the key epigenetic regulator histone deacetylase 1 (HDAC1) in the differentiation of exhausted T (Tex) cells during chronic viral infection. We uncovered that HDAC1 controls the generation and maintenance of effector-like CX3CR1+Tex cells in a CD8+T cell-intrinsic manner. Deletion of HDAC1 led to expansion of an alternative Tex cell subset characterized by high expression of T cell exhaustion markers, and this was accompanied by elevated viremia. HDAC1 knockout altered the chromatin landscape in progenitor Tex cells, abrogated the expression of effector-like signature genes and interfered with cell fate specification toward the CX3CR1+Tex cell subset. We conclude that HDAC1 is functionally required for controlling viral load during chronic infection by ensuring adequate CX3CR1+Tex cell subset differentiation.

Highlights

HDAC1 promotes the generation of CX3CR1+effector-like Tex cell subsets in chronic viral infection in a CD8+T cell-intrinsic manner.

Deletion of HDAC1 leads to an increase of a cell subset enriched in exhaustion markers and is accompanied with elevated viremia.

HDAC1 is required for the maintenance of the CX3CR1+Tex cell pool.

HDAC1 deletion alters the chromatin landscape at effector-like signature gene loci in progenitor Tex cells.
Proteomic Characterization of Intrahepatic Cholangiocarcinoma Identifies Distinct Subgroups and Proteins Associated with Time-To-Recurrence
Authors: Werner Tilman , Budau Klara-Luisa , Cosenza-Contreras Miguel , Hause Frank , Kurowski Konrad , Pinter Niko , Schüler Julia , Werner Martin , Sigel Carlie , Tang Laura H. , Bronsert Peter , Schilling Oliver
Published: March 2024

Background & Aims

Intrahepatic cholangiocarcinoma (ICC) is a poorly understood cancer with dismal survival and high recurrence rates. ICCs are often detected in advanced stages. Surgical resection is the most important first-line treatment but limited to non-advanced cases, whereas chemotherapy provides only a moderate benefit. The proteome biology of ICC has only been scarcely studied and the prognostic value of initial ICC’s proteomic features for the time-to-recurrence (TTR) remains unclear.

Methods

We dissected formalin-fixed, paraffin-embedded samples from 80 tumor– and 77 matching adjacent non-malignant (TANM) tissues. All samples were measured via liquid-chromatography mass-spectrometry (LC-MS/MS) in data independent acquisition mode (DIA).

Results

Tumor– and TANM tissue showed strongly different biologies and DNA-repair, translation, and matrisomal processes were upregulated in ICC. In a hierarchical clustering analysis, we determined two proteomic subgroups of ICC, which showed significantly diverging TTRs. Cluster 1, which is associated with a beneficial prognosis, was enriched for matrisomal processes and proteolytic processing, while cluster 2 showed increased RNA and protein turnover. In a second, independent Cox’ proportional hazards model analysis, we identified individual proteins whose expression correlates with TTR distribution. Proteins with a positive hazard ratio were mainly involved in carbon/glucose metabolism and protein turnover. Conversely, proteins associated with a low hazard ratio were mostly linked to the extracellular matrix. Additional proteome profiling of patient-derived xenograft tumor models of ICC successfully distinguished tumor and stromal proteins and provided insights into cell-matrix interactions.

Conclusions

We successfully determine the proteome biology of ICC and present two proteome clusters in ICC patients with significantly different TTR rates and distinct biological motifs. A xenograft model confirmed the importance of tumor-stroma interactions for this cancer.
Three-dimensional modeling of flow through microvascular beds and surrounding interstitial spaces
Authors: Rajeeva Pandian Navaneeth Krishna , Farell Alanna , Davis Emily , Sundaram Subramanian , van Steen Abraham Christoffel Ignatius , Chang Teo Jessica Li , Eyckmans Jeroen , Chen Christopher S
Published: March 2024

The health and function of microvascular beds are dramatically impacted by the mechanical forces that they experience due to fluid flow. These fluid flow-generated forces are challenging to measure directly and are typically calculated from experimental flow data. However, current computational fluid dynamics (CFD) models either employ truncated 2D models or overlook the presence of extraluminal flows within the interstitial space between vessels that result from the permeability of the endothelium lining the vessels, which are crucial components affecting flow dynamics. To address this, we present a bottom-up modeling approach that assesses fluid flow in 3D-engineered vessel networks featuring an endothelial lining and interstitial space. Using image processing algorithms to segment 3D confocal image stacks from engineered capillary networks, we reconstructed a 3D computational model of the networks. We incorporated vascular permeability and matrix porosity values to model the contributions of the endothelial lining and interstitial spaces to the flow dynamics in the networks. Simulations suggest that including the endothelial monolayer and the interstitium significantly affects the predicted flow magnitude in the vessels and flow profiles in the interstitium. To demonstrate the importance of these factors, we showed experimentally and computationally that while cytokine (IL-1β) treatment did not affect the network architecture, it significantly increased vessel permeability and resulted in a dramatic decrease in wall shear stresses and flow velocities intraluminally within the networks. In conclusion, this framework offers a robust methodology for studying flow dynamics in 3D in vitro vessel networks, enhancing our understanding of vascular physiology and pathology.

TRANSLATIONAL IMPACT STATEMENT

This study introduces a new approach to modeling and flow assessment in 3D microvascular beds and surrounding interstitial spaces. Modeling interstitial space and endothelial monolayer thickness is essential for capturing fluid leakage from the microvascular network into the interstitial space and vice versa when the endothelial monolayer permeability is significantly affected in pathological conditions. Our approach to modeling 3D vascular networks can be used in vivo and in clinical settings to understand flow in tissue microvasculature and its surroundings under disease and healthy conditions.
Chromosome-scale pearl millet genomes reveal aCARLACTONOIC ACID METHYL TRANSFERASEas key determinant of strigolactone pattern and Striga susceptibility
Authors: Kuijer Hendrik NJ , Wang Jian You , Bougouffa Salim , Abrouk Michael , Jamil Muhammad , Incitti Roberto , Alam Intikhab , Balakrishna Aparna , Alvarez Derry , Votta Cristina , Chen Guan-Ting Erica , Martínez Claudio , Zuccolo Andrea , Berqdar Lamis , Sioud Salim , Fiorilli Valentina , de Lera Angel R , Lanfranco Luisa , Gojobori Takashi , Wing Rod A , Krattinger Simon G , Gao Xin , Al-Babili Salim
Published: March 2024

The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weedStriga hermonthica,which requires host-released strigolactones (SLs) for seed germination. Herein, we identified four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10), but absent in the resistant 29Aw (Aw). We generated chromosome-scale genome assemblies including four gapless chromosomes for each line. We found the Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putativeCARLACTONOIC ACID METHYL TRANSFERASE1(CLAMT1) genes. Upon transient expression, P10CLAMT1b produced methyl carlactonoate (MeCLA), an intermediate in SL biosynthesis. Feeding Aw with MeCLA resulted in the production of two P10-specific SLs. Screening a diverse pearl millet panel confirmed the pivotal role of theCLAMT1section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.
The dependence of shugoshin on Bub1-kinase activity is dispensable for the maintenance of spindle assembly checkpoint response inCryptococcus neoformans
Authors: Polisetty Satya Dev , Bhat Krishna , Das Kuladeep , Clark Ivan , Hardwick Kevin G. , Sanyal Kaustuv
Published: March 2024

During chromosome segregation, the spindle assembly checkpoint (SAC) detects errors in kinetochore-microtubule attachments. Timely activation and maintenance of the SAC until defects are corrected is essential for genome stability. Here, we show that shugoshin (Sgo1), a conserved tension-sensing protein, ensures the maintenance of SAC signals in response to unattached kinetochores during mitosis in a basidiomycete budding yeastCryptococcus neoformans. Sgo1 maintains optimum levels of Aurora B kinaseIpl1and protein phosphatase 1 (PP1) at kinetochores. The absence of Sgo1 results in the loss of Aurora BIpl1with a concomitant increase in PP1 levels at kinetochores. This leads to a premature reduction in the kinetochore-bound Bub1 levels and early termination of the SAC signals. Intriguingly, the kinase function of Bub1 is dispensable for shugoshin's subcellular localization. Sgo1 is predominantly localized to spindle pole bodies (SPBs) and along the mitotic spindle with a minor pool at kinetochores. In the absence of proper kinetochore-microtubule attachments, Sgo1 reinforces the Aurora B kinaseIpl1-PP1 phosphatase balance, which is critical for prolonged maintenance of the SAC response.
Phosphate-binding pocket on cyclin B governs CDK substrate phosphorylation and mitotic timing
Authors: Ng Henry Y. , Adly Armin N. , Whelpley Devon H. , Suhandynata Raymond T. , Zhou Huilin , Morgan David O.
Published: March 2024

Cell cycle progression is governed by complexes of the cyclin-dependent kinases (CDKs) and their regulatory subunits cyclin and Cks1. CDKs phosphorylate hundreds of substrates, often at multiple sites. Multisite phosphorylation depends on Cks1, which binds initial priming phosphorylation sites to promote secondary phosphorylation at other sites. Here, we describe a similar role for a recently discovered phosphate-binding pocket (PP) on B-type cyclins. Mutation of the PP in Clb2, the major mitotic cyclin of budding yeast, alters bud morphology and delays the onset of anaphase. Using phosphoproteomicsin vivoand kinase reactionsin vitro, we find that mutation of the PP reduces phosphorylation of several CDK substrates, including the Bud6 subunit of the polarisome and the Cdc16 and Cdc27 subunits of the anaphase-promoting complex/cyclosome. We conclude that the cyclin PP, like Cks1, controls the timing of multisite phosphorylation on CDK substrates, thereby helping to establish the robust timing of cell-cycle events.
Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number maintenance
Authors: Nelson Jonathan O , Slicko Alyssa , Raz Amelie A , Yamashita Yukiko M
Published: March 2024

Preserving a large number of essential yet highly unstable ribosomal DNA (rDNA) repeats is critical for the germline to perpetuate the genome through generations. Spontaneous rDNA loss must be countered by rDNA copy number (CN) expansion. Germline rDNA CN expansion is best understood inDrosophila melanogaster, which relies on unequal sister chromatid exchange (USCE) initiated by DNA breaks at rDNA. The rDNA-specific retrotransposon R2 responsible for USCE-inducing DNA breaks is typically expressed only when rDNA CN is low to minimize the danger of DNA breaks; however, the underlying mechanism of R2 regulation remains unclear. Here we identify the insulin receptor (InR) as a major repressor of R2 expression, limiting unnecessary R2 activity. Through single-cell RNA sequencing we find that male germline stem cells (GSCs), the major cell type that undergoes rDNA CN expansion, have reduced InR expression when rDNA CN is low. Reduced InR activity in turn leads to R2 expression and CN expansion. We further find that dietary manipulation alters R2 expression and rDNA CN expansion activity. This work reveals that the insulin pathway integrates rDNA CN surveying with environmental sensing, revealing a potential mechanism by which diet exerts heritable changes to genomic content.
Health-related quality of life in children and adolescents born very preterm and its correlates: a cross-sectional study
Authors: Haile Sarah R , Peralta Gabriela P , Adams Mark , Bharadwaj Ajay N , Bassler Dirk , Moeller Alexander , Natalucci Giancarlo , Radtke Thomas , Kriemler Susi
Published: March 2024

Objective

We aimed to assess health-related quality of life (HRQOL) in a cohort of very preterm born children and adolescents (aged 5-16), and to compare it with their fullterm born siblings and the general population. We also explored correlates of HRQOL among the very preterm born.

Design

Cross-sectional survey

Patients

Children born <32 weeks gestation (N = 442) as well as their fullterm born siblings (N = 145)

Main outcome measures

Primary outcome was KINDL total score (0 worst - 100 best), a validated multidimensional measure of HRQOL in children and adolescents.

Methods

Linear mixed models accounted for family unit. Secondary analysis compared very preterm born children to another cohort of healthy children from the same time period. A classification tree analysis explored potential correlates of HRQOL.

Results

On average, preterm children, both <28 and 28-31 weeks gestational age, had similar KINDL total score to fullterm sibling controls (-2.3, 95% CI -3.6 to -0.6), and to population controls (+1.4, 95% CI 0.2 to 2.5). Chronic non-respiratory health conditions (such as attention deficit hyperactivity disorder (ADHD) or heart conditions, but not including cerebral palsy), age, and respiratory symptoms affecting daily life were key correlates of HRQOL among very preterm born children.

Conclusions

Very preterm birth in children and adolescents was not associated with a relevant reduction in HRQOL compared to their fullterm born peers. However, lower HRQOL was explained by other factors, such as older age, and the presence of chronic non-respiratory health conditions, but also by possibly modifiable current respiratory symptoms. The influence of respiratory symptom amelioration and its potential influence on HRQOL needs to be investigated further.

What is already known on this topic

As infants born very preterm become more likely to survive, the importance of health-related quality of life (HRQOL) increases. Research on HRQOL in very preterm born children and adolescents often focuses on non-modifiable risk factors without potential interventions.

What this study adds

HRQOL in very preterm born children and adolescents is similar to that of their siblings and to the general population. Age, respiratory symptoms, and chronic health conditions were associated with HRQOL. Better control of respiratory symptoms could improve HRQOL in very preterm born children and adolescents.

How this study might affect research, practice or policy

A better understanding of the complex picture of pulmonary disease following prematurity throughout life and interventions to treat respiratory symptoms may be leveraged to improve HRQOL as very preterm born children and adolescents grow.
Generalizability of trial criteria on amyloid-lowering therapy against Alzheimer’s disease to individuals with MCI or early AD in the general population
Authors: Claus Jacqueline J. , vom Hofe Ilse , van Ijlzinga Veenstra Annekee , Licher Silvan , Seelaar Harro , de Jong Frank J. , Neitzel Julia , Vernooij Meike W. , Ikram M. Arfan , Wolters Frank J.
Published: March 2024

Background

Treatment with monoclonal antibodies against amyloid-β slowed cognitive decline in recent randomized clinical trials in patients with mild cognitive impairment (MCI) and early dementia due to Alzheimer’s disease (AD). However, stringent trial eligibility criteria may affect generalizability of these findings to clinical practice.

Methods

We extracted eligibility criteria for trials of aducanumab, lecanemab and donanemab from published reports, and applied these to participants with MCI or early clinical AD dementia from the population-based Rotterdam Study. Participants underwent questionnaires, genotyping, brain MRI, cognitive testing, and cardiovascular assessment. We had continuous linkage with medical records and pharmacy dispensary data. We determined amyloid status using an established and validated prediction model based on age andAPOEgenotype. We assessed progression to dementia within 5 years among participants with MCI, stratified for eligibility.

Results

Of 968 participants (mean age: 75 years, 56% women), 779 had MCI and 189 early clinical AD dementia. Across the three drug trials, around 40% of participants would be ineligible because of predicted amyloid negativity. At least one clinical exclusion criterion was present in 76.3% (95% CI; 73.3-79.3) of participants for aducanumab, 75.8% (73.0-78.7) for lecanemab, and 59.8% (56.4–63.3) for donanemab. Criteria that most often led to exclusion were a history of cardiovascular disease (35.2%), use of anticoagulant (31.2%), use of psychotropic or immunological medications (20.4%), history of anxiety or depression (15.9%), or lack of social support (15.6%). One-third of participants were ineligible based on brain MRI findings alone, which was similar across trials and due predominantly to various manifestations of cerebral small-vessel disease. Combining amyloid, clinical, and imaging criteria, eligibility ranged from 9% (7.0-11.1) for aducanumab, 8% (6.2-9.9) lecanemab to 15% (12.4-17.5) for donanemab. Risk of progression to dementia tended to be higher for ineligible than for eligible participants for lecanemab (hazard ratio [95%CI]: 1.64 [0.92-2.91]), aducanumab (HR: 1.17 [0.65-2.12]), and only marginally for donanemab (HR: 1.03 [0.67-1.59]).

Conclusions

Findings from recent RCTs reporting protective effects of monoclonal antibodies against amyloid-β are applicable to less than 15% of community-dwelling individuals with MCI or early AD. These findings underline that evidence for drug efficacy and safety is lacking for the vast majority of patients with MCI/AD in routine clinical practice.
Assessing methylation detection for primary human tissue using Nanopore sequencing
Authors: Genner Rylee , Akeson Stuart , Meredith Melissa , Jerez Pilar Alvarez , Malik Laksh , Baker Breeana , Miano-Burkhardt Abigail ,   CARD-long-read Team, Paten Benedict , Billingsley Kimberley J , Blauwendraat Cornelis , Jain Miten
Published: March 2024

DNA methylation most commonly occurs as 5-methylcytosine (5-mC) in the human genome and has been associated with human diseases. Recent developments in single-molecule sequencing technologies (Oxford Nanopore Technologies (ONT) and Pacific Biosciences) have enabled readouts of long, native DNA molecules, including cytosine methylation. ONT recently upgraded their Nanopore sequencing chemistry and kits from R9 to the R10 version, which yielded increased accuracy and sequencing throughput. However the effects on methylation detection have not yet been documented.

Here we performed a series of computational analyses to characterize differences in Nanopore-based 5mC detection between the ONT R9 and R10 chemistries. We compared 5mC calls in R9 and R10 for three human genome datasets: a cell line, a frontal cortex brain sample, and a blood sample. We performed an in-depth analysis on CpG islands and homopolymer regions, and documented high concordance for methylation detection among sequencing technologies. The strongest correlation was observed between Nanopore R10 and Illumina bisulfite technologies for cell line-derived datasets. Subtle differences in methylation datasets between technologies can impact analysis tools such as differential methylation calling software. Our findings show that comparisons can be drawn between methylation data from different Nanopore chemistries using guided hypotheses. This work will facilitate comparison among Nanopore data cohorts derived using different chemistries from large scale sequencing efforts, such as the NIH CARD Long Read Initiative.
A novel LysinB from an F2 sub-cluster mycobacteriophageRitSun
Authors: Arora Ritu , Nadar Kanika , Bajpai Urmi
Published: March 2024

With the growing antibiotic resistance in mycobacterial species posing a significant threat globally, there is an urgent need to find alternative solutions. Bacteriophage-derived endolysins aid in releasing phage progeny from the host bacteria by attacking the cell wall at the end of their life cycle. Endolysins are attractive antibacterial candidates due to their rapid lytic action, specificity and low risk of resistance development. In mycobacteria, owing to the complex, hydrophobic cell wall, mycobacteriophages usually synthesize two endolysins: LysinA, which hydrolyzes peptidoglycan; LysinB, which delinks mycolylarabinogalactan from peptidoglycan and releases mycolic acid. In this study, we conducted domain analysis and functional characterization of a recombinant LysinB fromRitSun, an F2 sub-cluster mycobacteriophage. Several properties ofRitSunLysinB are important as an antimycobacterial agent: its ability to lyseMycobacterium smegmatis‘from without’, a specific activity of 1.36 U/mg, higher than the reported ones and its inhibitory effect on biofilm formation. Given the impervious nature of the mycobacterial cell envelope, native endolysins’ ability to damage cells on exogenous applications warrants further investigation. A molecular dissection ofRitSunLysinB to identify its cell wall destabilizing sequence could be utilized to engineer other native lysins as fusion proteins and expand their activity profile.
Common modes of ERK induction resolve into context specific signalling via a combination of signal duration and cell type specific transcriptional repression
Authors: Perera Marta , Brickman Joshua M
Published: March 2024

Fibroblast Growth Factor (FGF) signalling via ERK exerts diverse roles in development and disease. In mammalian preimplantation embryos and naïve pluripotent stem cells ERK promotes differentiation, whereas in primed pluripotent states closer to somatic differentiation ERK sustains self-renewal. How can the same pathway produce different outcomes in two related cell types? To explore context-dependent ERK signalling in embryonic development and differentiation we generated cell and mouse lines that allow for tissue- and time-specific cell intrinsic ERK activation. Using these tools, we find variations in response to ERK are mostly mediated by repression of transcriptional targets that occur in tandem with reductions in chromatin accessibility at regulatory regions. Furthermore, immediate early ERK responses are largely shared by different cell types, but become refined producing cell-specific programs as increasing durations of signalling interface with cell specific gene regulatory networks. Induction in naïve pluripotency is accompanied by chromatin changes, whereas in later stages it is not, suggesting that chromatin context doesn’t shape signalling response. Altogether, our data suggest that cell-type specific responses to ERK signalling exploit the same immediate early response, but then sculpt it to specific lineages via repression of distinct cellular programs and downstream indirect stimulation of available enhancer networks.
Steroidal glycoalkaloid biosynthesis and fungal tolerance are regulated by ELONGATED HYPOCOTYL 5, SlHY5, in tomato
Authors: Sinha Hiteshwari , Kumar Ravi Shankar , Datta Tapasya , Singh Deeksha , Srivastava Suchi , Trivedi Prabodh Kumar
Published: March 2024

Tomato (Solanum lycopersicumL.) is one of the highest consumable fruit crops, rich in nutrients, and has been an important target for enhancing the accumulation of various metabolites. Tomato also contains cholesterol-derived molecules, steroidal glycoalkaloids (SGAs), which contribute to pathogen defence but are toxic to humans and considered anti-nutritional compounds. Previous studies suggest the role of various transcription factors in SGA biosynthesis; however, the role of light and associated regulatory factors has not been studied in tomatoes. Here, we demonstrated that SGA biosynthesis is regulated by light through the ELONGATED HYPOCOTYL 5 homolog, SlHY5, by binding to light-responsive G-boxes present in the promoters of the structural and regulatory genes. Our analysis suggests that SlHY5 could complement theArabidopsis thalianaandNicotiana tabacum, hy5mutants at molecular, morphological, and biochemical levels. We report the development of CRISPR/Cas9-based knockout mutant plants of tomato,slhy5CR, and show down-regulation of the SGA and phenylpropanoid pathway genes leading to a significant reduction in SGA (α-tomatine and dehydrotomatine) and flavonol contents, whereas SlHY5 overexpression (SlHY5OX) plants show opposite effect. An enhanced SGA and flavonol levels in SlHY5OX lines provided tolerance againstAlternaria solanifungus, whileSlHY5CRwas susceptible to the pathogen. This study advances our understanding of the HY5-dependent light-regulated biosynthesis of SGAs and flavonoids and their role in biotic stress in tomatoes.

One Sentence Summary

Light-associated transcription factor, ELONGATED HYPOCOTYL 5, regulates biosynthesis of anti-nutrient molecules, steroidal glycoalkaloids, and fungal tolerance in tomato
SUMO Promotes DNA Repair Protein Collaboration to Support Alterative Telomere Lengthening in the Absence of PML
Authors: Zhao Rongwei , Xu Meng , Wondisford Anne R. , Lackner Rachel M. , Salsman Jayme , Dellaire Graham , Chenoweth David M. , O’Sullivan Roderick J. , Zhao Xiaolan , Zhang Huaiying
Published: March 2024

Alternative lengthening of telomeres (ALT) pathway maintains telomeres in a significant fraction of cancers associated with poor clinical outcomes. A better understanding of ALT mechanisms can provide a basis for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins plays a critical role in the formation of ALT telomere-associated PML bodies (APBs), where telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, whether and how SUMO contributes to ALT beyond APB formation remains elusive. Here, we report that SUMO promotes collaboration among DNA repair proteins to achieve APB-independent telomere maintenance. By using ALT cancer cells with PML protein knocked out and thus devoid of APBs, we show that sumoylation is required for manifesting ALT features, including telomere clustering and telomeric DNA synthesis, independent of PML and APBs. Further, small molecule-induced telomere targeting of SUMO produces signatures of phase separation and ALT features in PML null cells in a manner depending on both sumoylation and SUMO interaction with SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are linked to the enrichment of DNA repair proteins, including Rad52, Rad51AP1, and BLM, to the SUMO-containing telomere foci. Finally, we find that Rad52 can undergo phase separation, enrich SUMO on telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that, in addition to forming APBs, SUMO also promotes collaboration among DNA repair proteins to support telomere maintenance in ALT cells. Given the promising effects of sumoylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.
Chromatin Accessibility Profiling and Data Analysis Using ATAC-seq inNothobranchius furzeri
Authors: Reeves G. Adam , Singh Param Priya , Brunet Anne
Published: March 2024

The state of genome-wide chromatin accessibility in cells, tissues, or organisms can be investigated with a technique called assay for transposase-accessible chromatin using sequencing (ATAC-seq). ATAC-seq is a powerful approach for profiling the epigenomic landscape of cells using very low input materials. Analysis of chromatin accessibility data allows for prediction of gene expression and identification of regulatory elements such as potential enhancers and specific transcription-factor binding sites. Here, we describe an optimized ATAC-seq protocol for the preparation of isolated nuclei and subsequent next-generation sequencing from whole embryos and tissues of the African turquoise killifish (Nothobranchius furzeri). Importantly, we provide an overview of a pipeline for processing and analyzing ATAC-seq data from killifish.
Optimized optical tomography of quantum states of a room-temperature alkali-metal vapor
Authors: Kopciuch Marek , Smolis Magdalena , Miranowicz Adam , Pustelny Szymon
Published: March 2024

We demonstrate an experimental technique for the quantum-state tomography of the collective qutrit states of a room-temperature alkali-metal vapor. It is based on the measurements of the polarization of light traversing the vapor subjected to a magnetic field. To assess the technique's robustness against errors, experimental investigations are supported with numerical simulations. This not only allows us to determine the fidelity of the reconstructed states, but also to analyze the quality of the reconstruction for specific experimental parameters, such as light tuning and the number of measurements. By utilizing the conditional number, we demonstrate that the reconstruction robustness can be optimized by a proper adjustment of experimental parameters, and further improvement is possible with the repetition of specific measurements. Our results demonstrate the potential of this high-fidelity reconstruction method of quantum states of room-temperature atomic vapors.

Published by the American Physical Society
2024
Experimental characterization of the optical klystron effect to measure the intrinsic energy spread of high-brightness electron beams
Authors: Prat Eduard , Kittel Christoph , Calvi Marco , Craievich Paolo , Dijkstal Philipp , Reiche Sven , Schietinger Thomas , Wang Guanglei
Published: March 2024

The intrinsic energy spread of electron beams needs to be measured to characterize and optimize high-brightness electron beam sources such as those driving x-ray free-electron lasers (FELs). We demonstrate the use of the optical klystron effect as a precise and high-resolution method to measure the electron beam energy spread. The optical klystron setup consists of undulator modules and magnetic chicanes placed between them. The energy spread is found by measuring the radiation power produced in the undulators as a function of the chicanes’ strengths. High resolution and simplicity are the advantages of this approach, in contrast to the standard method, which measures the longitudinal phase space of the electron beam with a transverse deflector. The demonstration was performed at Athos, the soft x-ray FEL beamline of SwissFEL, for which we measured energy spreads below 1 MeV at a central beam energy of 3.4 GeV. We have verified the consistency of the method for different parameters (radiation wavelengths, undulator polarization configurations, and electron bunch durations) and we have benchmarked it against the standard measurement approach using a transverse deflector. Our results confirm the optical klystron as a valid approach to measure the electron beam energy spread. The method can be especially useful to reconstruct low energy spread values, where the conventional approach may be resolution limited, such as in ultra high-brightness radiofrequency photoinjectors or plasma sources, or when transverse deflectors are not available.

Published by the American Physical Society
2024
Correlation functions for the
N*(1535)
and the inverse problem
Authors: Molina Raquel , Xiao Chu-Wen , Liang Wei-Hong , Oset Eulogio
Published: March 2024

The N*(1535) can be dynamically generated in the chiral unitary approach with the coupled channels, K0Σ+,K+Σ0,K+Λ, and ηp. In this work, we evaluate the correlation functions for every channel and face the inverse problem. Assuming the correlation functions to correspond to real measurements, we conduct a fit to the data within a general framework in order to extract the information contained in these correlation functions. The bootstrap method is used to determine the uncertainties of the different observables, and we find that, assuming errors of the same order than in present measurements of correlation functions, one can determine the scattering length and effective range of all channels with a very good accuracy. Most remarkable is the fact that the method predicts the existence of a bound state of isospin 12 nature around the mass of the N*(1535) with an accuracy of 6 MeV. These results should encourage the actual measurement of these correlation functions (only the K+Λ one is measured so far), which can shed valuable light on the relationship of the N*(1535) state to these coupled channels, a subject of continuous debate.

Published by the American Physical Society
2024
Searches for axionlike particles via
γγ
fusion at future
e+e−
colliders
Authors: Teles Patricia Rebello , d’Enterria David , Gonçalves Victor P. , Martins Daniel E.
Published: March 2024

Opportunities for searches for axionlike particles (ALPs) coupling to photons in e+e− collisions at the Future Circular Collider (FCC-ee) and International Linear Collider (ILC) are investigated. We perform a study of the photon-fusion production of ALPs decaying into two photons, e+e−→γγe+a(γγ)e−, over the light-by-light continuum background, for the planned FCC-ee and ILC center-of-mass energies and integrated luminosities. An analysis of the feasibility measurements is presented using parametrized simulations for two types of detectors. Upper limits at 95% confidence level (C.L.) on the cross section for ALP production, σ(γγ→a→γγ), and on the ALP-photon coupling are obtained over the ma≈0.1–1000  GeV ALP mass range, and compared to current and future collider searches. Production cross sections down to σ(γγ→a→γγ)≈1  fb (1 ab) will be probed at ma≈1 (300) GeV, corresponding to constraints on the axion-photon coupling as low as gaγγ≈2×10−3  TeV−1.

Published by the American Physical Society
2024
Optical spin readout of single rubidium atoms trapped in solid neon
Authors: Lancaster David M. , Dargyte Ugne , Weinstein Jonathan D.
Published: March 2024

In this work, we optically resolve and detect individual rubidium atoms trapped in solid neon. Additionally, we optically pump the rubidium's spin state using polarized light and measure the spin state via laser-induced fluorescence. When combined with the previously demonstrated magnetic field sensing capabilities of matrix-isolated rubidium atoms, these results are very promising for nanoscale sensing and for performing nuclear magnetic resonance (NMR) spectroscopy of individual molecules cotrapped in the matrix.

Published by the American Physical Society
2024
Opposite Effects of the Rotational and Translational Energy on the Rates of Ion-Molecule Reactions near 0 K: The
D2++NH3
and
D2++ND3
Reactions
Authors: Hahn Raphaël , Schlander David , Zhelyazkova Valentina , Merkt Frédéric
Published: March 2024

The ion-molecule reactions D2++NH3 and D2++ND3 are studied at low collision energies (Ecoll from zero to approximately kB×50  K), with the D2+ ions in the ground rovibrational state and for different rotational temperatures of the ammonia molecules, using the Rydberg-Stark merged-beam approach. Two different rotational temperatures (approximately 15 K and approximately 40 K), measured by (2+1) resonance-enhanced multiphoton-ionization spectroscopy, are obtained by using a seeded supersonic expansion in He and a pure ammonia expansion, respectively. The experimental data reveal a strong enhancement of the rate coefficients at the lowest collision energies caused by the charge-dipole interaction. Calculations based on a rotationally adiabatic capture model accurately reproduce the observed kinetic-energy dependence of the rate coefficients. The rate coefficients increase with increasing rotational temperature of the ammonia molecules, which contradicts the expectation that rotational excitation should average the dipoles out. Moreover, these reactions exhibit a pronounced inverse kinetic isotope effect. The difference is caused by nuclear-spin-statistical factors and the smaller rotational constants and tunneling splittings in ND3.

Published by the American Physical Society
2024
Twitter as a counter-storytelling site for students of Color working to abolish the police
Authors: Farrington Re'Nyqua
Published: March 2024

Purpose

Given the historical legacy of policing Black bodies, this research focuses on the structures of anti-Blackness within school policing and the strategies students of Color activists use as they work to defund or abolish police departments in the Los Angeles Unified School District (LAUSD).

Design/methodology/approach

Specifically, this article looks to Twitter as a counter-storytelling space for students of Color activists to organize and build movements to end anti-Black school policing. Through the frameworks of critical race theory (CRT) and Black critical theory (BlackCrit), this research applies inductive coding to analyze 42 Twitter posts from three students of Color-led organizations based in Los Angeles.

Findings

This document analysis presents four themes, which describe four dominant strategies students of Color activists use in their campaigns to defund or abolish school police in the LAUSD: (1) centering Blackness and Black student experiences, (2) making demands for the elimination of funding and support for school police, (3) calling for a shift in funding to support Black students and (4) employing multiple tactics concurrently.

Research limitations/implications

These findings demonstrate the importance of developing and centering a critical understanding of anti-Blackness to achieve racial and educational justice within social movements.

Originality/value

Moreover, the demands of students of Color activists reflect visions of public schools free from anti-Black school policing.
Piston-like particle jamming for enhanced stiffness adjustment of soft robotic arm
Authors: Wang Tianlei , Ding Fei , Sun Zhenxing
Published: March 2024

Purpose

Stiffness adjusting ability is essential for soft robotic arms to perform complex tasks. A soft state enables dexterous operation and safe interaction, while a rigid state enables large force output or heavy weight carrying. However, making a compact integration of soft actuators with powerful stiffness adjusting mechanisms is challenging. This study aims to develop a piston-like particle jamming mechanism for enhanced stiffness adjustment of a soft robotic arm.

Design/methodology/approach

The arm has two pairs of differential tendons for spatial bending, and a jamming core consists of four jamming units with particles sealed inside braided tubes for stiffness adjustment. The jamming core is pushed and pulled smoothly along the tendons by a piston, which is then driven by a motor and a ball screw mechanism.

Findings

The tip displacement of the arm under 150 N jamming force and no more than 0.3 kg load is minimal. The maximum stiffening ratio measured in the experiment under 150 N jamming force is up to 6–25 depends on the bending direction and added load of the arm, which is superior to most of the vacuum powered jamming method.

Originality/value

The proposed robotic arm makes an innovative compact integration of tendon-driven robotic arm and motor-driven piston-like particle jamming mechanism. The jamming force is much larger compared to conventional vacuum-powered systems and results in a superior stiffening ability.
Do institutional pillars support or harm entrepreneurship and economic growth? A systematic review
Authors: Raimi Lukman , Bamiro Nurudeen Babatunde , Haini Hazwan
Published: March 2024

Purpose

The relationships among institutions, entrepreneurship, and economic growth are hotly contested topics. The objective of this present study is to conduct a systematic literature review aimed at comprehensively assessing the relationships between institutional pillars, entrepreneurship and economic growth.

Design/methodology/approach

Specifically, a comprehensive analysis of 141 empirical publications was carried out using the PRISMA protocol. The reviewed publications were taken from the Web of Science, Scopus and Google Scholar databases. Thirty-three articles that met the eligibility criteria of quality, relevance and timeliness of the publications were included in the the study.

Findings

Three key lessons emerged from the review. First, it was discovered that entrepreneurship and economic growth are influenced by three institutional pillars at various levels, including the regulatory, cognitive and normative pillars. Second, according to the type of institutional quality, the institutional pillars in a causal framework have a good or negative impact on entrepreneurship. Third, novel enterprise creation, self-employment, citizen employment, poverty alleviation, radical innovation, formalization of the informal sector, promotion of competition in existing and new markets, Gross Domestic Product (GDP) growth and the emergence of new business models that significantly improve quality of life.

Originality/value

The study proposes a conceptual framework for further exploring this important relationship based on solid empirical evidence. By providing a theoretically grounded framework, the paper fills the gaps in the literature and helps to clarify the relationship between institutional foundations, entrepreneurship and economic progress.
Functional traits are more strongly correlated with biomass than diameter growth
Authors: Bin Yue , Russo Sabrina E. , Zhang Jiantan , Li Yanpeng , Cao Honglin , Ye Wanhui , Lian Juyu
Published: March 2024

The functional basis of tree growth is often evaluated based on trunk diameter even though diameter is only one dimension of growth that may not be an integrative measure of resource allocation.

We tested the hypothesis that growth—functional trait relationships are stronger when key sources of variation in tree growth are also accounted for, namely tree height and DBH, as well as size‐related variation in wood density and seed production using data from 3881 trees of 24 species in a subtropical forest using ordinary least square regression and standard major axis regression.

Wood density varied with tree size for 14 of 24 species, generally increasing with size. For 18 of 24 species, the correlations of leaf mass per area and an index of photosynthetic investment (PI) with biomass growth was stronger than with diameter growth rate. Juveniles did not show stronger relationships than adults but biomass growth adding up with seed production showed stronger relationships with PI than biomass growth alone for three of eight species.

Synthesis. Thus, our study helps resolve a paradox of trait‐based ecology, that is, weak growth—trait relationships, as stronger relationships emerged when accounting for more sources of intraspecific, among‐tree variation in resource allocation.
Investigating Crowdfunding Campaign Value Capture Strategy from the Consumer‐based Perspective
Authors: Zhao Liang , Sun Zhe , Hajli Nick
Published: March 2024

Knowledge about whether entrepreneurs’ backer‐oriented actions help facilitate successful fundraising, and the mechanism behind it, is still limited. This study aims to mitigate this gap by exploring reward‐based crowdfunding success through the consumer‐based perspective (CBP). Using the elaboration likelihood model (ELM), we investigate how entrepreneurs’ backer‐oriented behaviour influences potential backers’ information processing and changes their attitude towards campaigns. By analysing a unique dataset collected from China's largest reward‐based crowdfunding platform, our empirical results demonstrate that an entrepreneur's backer‐oriented behaviour and strength are positively associated with reward‐based crowdfunding success. This paper provides a new angle to investigate reward‐based crowdfunding success, emphasizing the importance of CBP during the fundraising stage. In addition to high‐quality campaign content, entrepreneurs’ backer‐oriented actions, such as answering questions and providing elaborate answers, are crucial in facilitating fundraising. The implications for future theory development, empirical research and crowdfunding practitioners are discussed.
Vicarious Liability and Conferred Authority: Trustees of the Barry Congregation of Jehovah's Witnesses v BXB
Authors: Beuermann Christine
Published: March 2024

In Trustees of the Barry Congregation of Jehovah's Witnesses v BXB, the Supreme Court held that there was a single approach to determining all cases of vicarious liability. No ‘tailoring’ of that approach was required either because the defendant was a religious organisation or because the tort in question was sexual abuse. It followed that the Court of Appeal had erred in placing significance on the authority conferred by the defendant on the tortfeasor to guide the behaviour of the claimant when determining vicarious liability. This note explores whether there is any role for conferred authority after Barry. To accommodate distinctions in the existing cases and contain further unwarranted expansion, it is argued that it is necessary to recognise a discrete form of strict liability for the tort of another, distinct from vicarious liability, that responds to the potential for conferred authority to be abused.
Female school leadership in the United Arab Emirates: Validation of a ‘heuristic’ inclusive education leadership model
Authors: Alnuaimi Aysha , Opoku Maxwell Peprah
Published: March 2024

Inclusive education has been widely accepted as a useful policy to offer equal access to education to all children. However, practices have stalled in many countries, including the United Arab Emirates (UAE), necessitating support for system strengthening to enhance the existing practices in schools. While leadership is at the heart of effective practices, there is little discussion on the leadership required to leverage inclusive practices. In the UAE, little information is available regarding inclusive education leadership at early school levels, which is dominated by female teachers. This study examined the structural validity of the heuristic leadership framework, which focuses on leadership tenets (transaction, transformation and instruction) controlled by school leaders, to explain female leadership practices in the implementation of inclusive education in early education schools in the UAE. A scale based on the study framework (heuristics leadership framework) was used to collect data from 151 school leaders, including principals, vice principals, faculty heads and lead teachers, working at early school levels across the UAE. The results of this study provide theoretical support for the heuristic leadership framework and some demographics, providing valuable insights into leadership practices among female education leaders in the UAE.