bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of ZNRF3/RNF43 Unleashes EGFR in Cancer
Authors: Yue Fei , Ku Amy T. , Stevens Payton D. , Michalski Megan N. , Jiang Weiyu , Tu Jianghua , Shi Zhongcheng , Dou Yongchao , Wang Yi , Feng Xin-Hua , Hostetter Galen , Wu Xiangwei , Huang Shixia , Shroyer Noah F. , Zhang Bing , Williams Bart O. , Liu Qingyun , Lin Xia , Li Yi
Published: January 2024

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated withZNRF3/RNF43mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression ofZNRF3reduces EGFR levels and suppresses cancer cell growthin vitroandin vivo, whereas knockout ofZNRF3/RNF43stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data highlight ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptors, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.
TCR-engineered T-cells directed against Ropporin-1 constitute a safe and effective treatment for triple-negative breast cancer in near-clinical models
Authors: Kortleve Dian , Hammerl Dora , Brakel Mandy v , Wijers Rebecca , Roelofs Daphne , Kroese Kim , Timmermans Mieke , Liao Chen-Yi , Trapman-Jansen Anita , Foekens Renée , Michaux Justine , de Beijer Monique , Buschow Sonja I. , Demmers Jeroen A.A. , Kok Marleen , Danen Erik H.J. , Bassani-Sternberg Michal , Martens John W. , Abbott Rachel J.M. , Debets Reno
Published: January 2024

Triple-negative breast cancer (TNBC) shows an urgent need for new therapies. We discovered Ropporin-1 (ROPN1) as a target to treat TNBC with T-cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues. HLA-A2-binding peptides were detected via immunopeptidomics and predictions and used to retrieve T-cell receptors (TCRs) from naïve repertoires. Following gene introduction into T-cells and stringent selection, we retrieved a highly specific TCR directed against the epitope FLYTYIAKV that did not recognize non-cognate epitopes from alternative source proteins. Notably, this TCR mediated killing of three-dimensional tumoroidsin vitroand tumor cellsin vivoand outperformed standard-of-care drugs. Finally, the T-cell product expressing this TCR and manufactured using a clinical protocol fulfilled standard safety and efficacy assays. Collectively, we have identified and preclinically validated ROPN1 as a target and anti-ROPN1 TCR T-cells as a treatment for the vast majority of TNBC patients.
Unraveling Glioblastoma Heterogeneity: Introducing SP2G Method for Identifying Invasive Sub-Populations
Authors: Crestani Michele , Kakogiannos Nikolaos , Iannelli Fabio , Dini Tania , Maderna Claudio , Giannotta Monica , Pelicci Giuliana , Maiuri Paolo , Monzo Pascale , Gauthier Nils C.
Published: January 2024

Glioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, we linked glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry. We now introduce SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient-derived glioblastoma cells and rapidly pinpoint the most invasive sub-populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by our semi-automated, open-source, Fiji macro suite that characterizes migration modes accurately. With SP2G, we could reveal intra-patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. Thus, our system presents a versatile and potentially pan-cancer workflow to detect diverse invasive tumor sub-populations in patient-derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level.

Teaser

Cracking the inter and intra-patient diversity in Glioblastoma migration profiles
Analysis of a diverse wheat germplasm panel reveals a highly diverse introgression landscape and provides evidence for inter-homoeolog chromosomal recombination
Authors: Heuberger Matthias , Bernasconi Zoe , Jung Esther , Herren Gerhard , Widrig Victoria , Keller Beat , Sánchez-Martín Javier , Wicker Thomas
Published: January 2024

Agriculturally important genes are often introgressed into crops from closely related donor species or landraces. The gene pool of hexaploid bread wheat (Triticum aestivum)is known to contain numerous such “alien” introgressions. Recently established high-quality reference genome sequences allow prediction of the size, frequency, and identity of introgressed chromosome regions. Here, we characterise chromosomal introgressions in bread wheat using exome capture data from the WHEALBI collection. We identified 26,664 putative introgression segments of at least 2 Mb across 434 wheat accessions. Detailed study of the most frequent introgressions identifiedT. timopheviior its close relatives as a frequent donor species. Importantly, 118 introgressions of at least 10 Mb were exclusive to single wheat accessions, revealing that large populations need to be studied to assess the total diversity of the wheat pangenome. In one case, a 14 Mb introgression in chromosome 7D, exclusive to cultivar Pamukale, was shown by QTL mapping to harbor a recessive powdery mildew resistance gene. We identified multiple events where distal chromosomal segments of one subgenome were duplicated in the genome and replaced the homoeologous segment in another subgenome. We propose that these examples are the results of inter-homoeolog recombination. Our study produced an extensive catalogue of the wheat introgression landscape, providing a resource for wheat breeding. Of note, the finding that the wheat gene pool contains numerous rare, but potentially important introgressions and chromosomal rearrangements has implications for future breeding.

Key message

This study highlights the potential of rare introgressions, as demonstrated by a major QTL for powdery mildew resistance on chromosome 7D. It further shows evidence for inter-homoeolog recombination in wheat.
Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation
Authors: Miao Yue , Du Yongtao , Wang Baolei , Liang Jingjing , Liang Yu , Dang Song , Liu Jiahao , Li Dong , He Kangmin , Ding Mei
Published: January 2024

The spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5. The recruitment of USP8 dissociates Rabex5 from early endosomes (EEs) and meanwhile promotes the recruitment of the Rab7 GEF SAND-1/Mon1. In USP8-deficient cells, the level of active Rab5 is increased, while the Rab7 signal is decreased. As a result, enlarged EEs with abundant intraluminal vesicles accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation.
Ability of mycobacterial pathogens to establish a persistent infection is lost by deletion of a single gene,rel, regulator of the stringent response
Authors: Mahmoud Asmaa H. , Abdellrazeq Gaber S. , Fry Lindsay M. , Schneider David A. , Attreed Sarah , Burton Leeanna , Sangewar Neha , Mwangi Waithaka , deSouza Cleverson , Hulubei Victoria , Davis William C. , Park Kun Taek
Published: January 2024

Studies in a mouse model revealedMycobacterium tuberculosis(Mtb) with a deletion ofrel, regulator of the stringent response, could not establish a persistent infection. Studies in cattle with aMycobacterium. a. paratuberculosis reldeletion mutant revealed inability to establish a persistent infection was associated with development of CD8 cytotoxic T cells (CTL) that kill intracellular bacteria. Further comparative studies ex vivo withMbvCalmette-Guérin (BCG) and a BCGreldeletion mutant revealed no clear difference in development of CTL in vitro. As reported, a study of the recall response was conducted with cattle vaccinated with either BCG or with BCGrel,to determine if information could be obtained that would show how gene products under control ofrelinterfere with the CTL response to mycobacterial pathogens in vivo. The study revealed the CTL response elicited by vaccination with BCG was impaired, in comparison with the response elicited by BCGrel. Comparative analysis of the recall response ex vivo revealed the functional impairment was not associated with the timing of appearance of the recall response, expression of IFN-γ, TNF-α, IL-17, or IL-22, or molecules that mediate intracellular killing. Further studies are needed to determine how CD8 CTL functional activity is modulated in vivo by gene products regulated byrel.
DNA microbeads for spatio-temporally controlled morphogen release within organoids
Authors: Afting Cassian , Walther Tobias , Wittbrodt Joachim , Göpfrich Kerstin
Published: January 2024

Organoids have proven to be powerfulin vitromodel systems that mimic features of the corresponding tissuein vivo. However, across tissue types and species, organoids still often fail to reach full maturity and function, because biochemical cues cannot be provided from within the organoid to guide their development. The establishment of such tools has been identified as a major goal of the field. Here, we introduce DNA microbeads as a novel tool for implementing spatio-temporally controlled morphogen gradients inside of organoids at any point in their life cycle. The DNA microbeads are formed in a simple one-pot process, they can be stored for a year and their viscoelastic behavior and surface modification is tunable to mimic the corresponding tissue. Employing medaka retinal organoids and early embryos, we show that DNA microbeads can be integrated into embryos and organoids by microinjection and erased in a non-invasive manner with light. Coupling a recombinant surrogate Wnt to the DNA microbeads we demonstrate the spatio-temporally controlled release of the morphogen from the microinjection site, which leads to the formation of retinal pigmented epithelium while maintaining neuroretinal ganglion cells. We were thus able to bioengineer retinal organoids to more closely mirror the cell type diversity ofin vivoretinas. The DNA microbead technology can easily be adapted to other organoid applications for improved tissue mimicry.
Characterization of the growth promotion and defense enhancement of soybean plants driven by seed treatment of multiple soybean-associated beneficial bacteria
Authors: Calderon Rosalie B. , Ontoy John Christian , Barpharga Inderjit , Ham Jong Hyun
Published: January 2024

We screened soybean-associated bacterial strains from soybean fields in Louisiana, USA, based on various biological activities beneficial for soybean growth and health. Furthermore, we constructed sets of synthetic bacterial community (SBC) containing multiple strains of soybean-associated beneficial bacteria (SABB) having different types of beneficial activities and tested their effects of seed treatment on soybean growth and disease resistance. We found that all three sets of SBC (i.e., Set-1, Set-2, and Set-3) tested promoted soybean growth and yield significantly through seed treatment, showing better performance than the most effective SABB strainPseudomonas putidaSABB7 alone and the commercial seed-treating product included for comparison. Our analysis of soybean microbiomes in the root endosphere and rhizosphere based on 16S rDNA sequence profiles revealed thatBradyrhizobium elkanii, a symbiotic bacterium of soybean, was enriched in both compartments by seed treatment with Set-2 or Set-m4, which were the best-performing bacterial mixture among the three SABB sets and the most effective subset of Set-2, respectively. In addition, the soybean gene expression profile determined by RNA-seq revealed that seed treatment with Set-2 or Set-m4 made soybean plants grown from the treated-seeds induce a higher level of defense-related genes upon infection by the fungal pathogenRhizoctonia solanicompared to those from untreated seeds. These experimental results strongly suggest that the beneficial effects of the bacterial mixtures on plant growth and defense through seed treatment are largely mediated by the change of soybean-associated microbiomes that enriches beneficial components such asB. elkaniiand the defense-priming effect that induces robust defense responses upon pathogen infection. This study provides a valuable insight into the development of innovative and sustainable management strategies through seed treatment of beneficial microbes in a form of SBC for soybean and further other major crops.

Abstract Figure
Taxonomy and phylogeny of the family Suberitidae (Porifera: Demospongiae) in California
Authors: Turner Thomas L. , Rouse Greg W. , Weigel Brooke L. , Janusson Carly , Lemay Matthew A. , Thacker Robert W.
Published: January 2024

This study presents a comprehensive taxonomic revision of the family Suberitidae (Porifera: Demospongiae) for California, USA. We include the three species previously known from the region, document two additional species previously known from other regions, and formally describe four new species asPseudosuberites latkesp. nov.,Suberites californianasp. nov.,Suberites kumeyaaysp. nov., andSuberites agaricussp. nov. Multi-locus DNA sequence data is presented for seven of the nine species, and was combined with all publicly available data to produce the most comprehensive global phylogeny for the family to date. By integrating morphological and genetic data, we show that morphological characters may be sufficient for regional species identification but are likely inadequate for global classification into genera that reflect the evolutionary history of the family. We therefore propose that DNA sequencing is a critical component to support future taxonomic revisions.
A highly contiguous genome assembly for the Yellow Warbler (Setophaga petechia)
Authors: Tsai Whitney L. E. , Escalona Merly , Garrett Kimball L. , Terrill Ryan S. , Sahasrabudhe Ruta , Nguyen Oanh , Beraut Eric , Seligmann William , Fairbairn Colin W. , Harrigan Ryan J. , McCormack John E. , Alfaro Michael E. , Smith Thomas B. , Bay Rachael A.
Published: January 2024

The Yellow Warbler (Setophaga petechia) is a small songbird in the New World Warbler family (Parulidae) that exhibits phenotypic and ecological differences across a widespread distribution and is important to California’s riparian habitat conservation. Here, we present a high-qualityde novogenome assembly of a vouchered female Yellow Warbler from southern California. Using HiFi long-read and Omni-C proximity sequencing technologies, we generated a 1.22 Gb assembly including 687 scaffolds with a contig N50 of 6.80 Mb, scaffold N50 of 21.18 Mb, and a BUSCO completeness score of 96.0%. This highly contiguous genome assembly provides an essential resource for understanding the history of gene flow, divergence, and local adaptation and can inform conservation management of this charismatic bird species.
Impacts of increasing isolation and environmental variation on Florida Scrub-Jay demography
Authors: Summers Jeremy , Cosgrove Elissa J. , Bowman Reed , Fitzpatrick John W. , Chen Nancy
Published: January 2024

Isolation caused by anthropogenic habitat fragmentation can destabilize populations. Populations relying on the inflow of immigrants can face reduced fitness due to inbreeding depression as fewer new individuals arrive. Empirical studies of the demographic consequences of isolation are critical to understand how populations persist through changing conditions. We used a 34-year demographic and environmental dataset from a population of cooperatively-breeding Florida Scrub-Jays (Aphelocoma coerulescens) to create mechanistic models linking environmental and demographic factors to population growth rates. We found that the population has not declined despite both declining immigration and increasing inbreeding, owing to a coinciding response in breeder survival. We find evidence of density-dependent immigration, breeder survival, and fecundity, indicating that interactions between vital rates and local density play a role in buffering the population against change. Our study elucidates the impacts of isolation on demography and how long-term stability is maintained via demographic responses.
Disruption inCYLC1leads to acrosome detachment, sperm head deformity, and male in/subfertility in humans and mice
Authors: Jin Hui-Juan , Fan Yong , Yang Xiao-Yu , Dong Yue , Zhang Xiao-Zhen , Geng Xin-Yan , Yan Zheng , Wu Ling , Ma Meng , Li Bin , Lyu Qi-Feng , Pan Yun , Liu Ming-Xi , Kuang Yan-Ping , Chen Su-Ren
Published: January 2024

The perinuclear theca (PT) is a dense cytoplasmic web encapsulating the sperm nucleus. The physiological roles of PT in sperm biology and the clinical relevance of variants of PT proteins to male infertility are still largely unknown. We reveal that cylicin-1, a major constituent of the PT, is vital for male fertility in both mice and humans. Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus. Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an ‘IAM-cylicins-NE’ sandwich structure, anchoring the acrosome to the nucleus. WES of more than 500 Chinese infertile men with sperm head deformities was performed and aCYLC1variant was identified in 19 patients.Cylc1-mutant mice carrying this variant also exhibited sperm acrosome/head deformities and reduced fertility, indicating that thisCYLC1variant most likely affects human male reproduction. Furthermore, the outcomes of assisted reproduction were reported for patients harbouring theCYLC1variant. Our findings demonstrate a critical role of cylicin-1 in the sperm acrosome-nucleus connection and suggestCYLC1variants as potential risk factors for human male fertility.
Germline HLA-DQ genotype influences response to CAR T-cell therapy in patients with large B-cell lymphoma
Authors: Le Mene Melchior , Allain Vincent , Villemonteix Juliette , Cuffel Alexis , Taupin Jean-Luc , di Blasi Roberta , Thieblemont Catherine , Caillat-Zucman Sophie
Published: January 2024

CD19-directed chimeric antigen receptor (CAR) T cells have greatly improved the prognosis of relapsed/refractory large B-cell lymphoma (rrLBCL), yet treatment failure occurs in more than half of patients, usually in the first 3 months after treatment. While they primarily act through CAR-dependent, HLA-independent recognition of tumor targets, CAR-T cells may also indirectly contribute to long-term tumor immunosurveillance by stimulating endogenous immunity. We hypothesized that HLA diversity, measured by the HLA evolutionary divergence (HED) metric which reflects the breadth of the immunopeptidome presented to host T cells, could influence antitumor response after CAR T-cell therapy, as seen after immune chekpoint inhibitor treatment. We studied 127 rrLBCL patients treated with commercial CAR-T cells in our center, of whom 50 % achieved durable response. We observed no impact of diversity at any HLA locus, except for HED-DQA1 that was surprisingly negatively associated with response. Analysis of the distribution of HLA-DQ alleles according to clustering of HED values pointed to the DQ1/DQ1 genotype as an independent predictor of durable response and lower incidence of relapse/progression. These findings highlight the unsuspected role of germline HLA-DQ molecules in the response to CAR-T cells and suggest an important contribution of cross-talk between CAR-T cells and endogenous immune cells.

Key Points

Germline HLA-DQ genotype is an independent predictor of durable response and lower incidence of relapse/progression after CAR T-cell therapy in rrLBCL

HLA-DQ1/DQ1 genotype could influence the host immune response after CAR T-cell therapy and increase the chances of a durable response
Development and validation of a realistic type III esophageal atresia simulator for the training of pediatric surgeons
Authors: Montero Javier Arredondo , Pérez Riveros Blanca Paola , Bueso Asfura Oscar Emilio , Martín-Calvo Nerea , Pueyo Francisco Javier , López de Aguileta Castaño Nicolás
Published: January 2024

Background

The technical complexity and limited casuistry of neonatal surgical pathology limit the possibilities of developing the necessary technical competencies by specialists in training. Esophageal atresia constitutes the paradigm of this problem. The use of 3D models for training is a promising line of research, although the literature is limited.

Methods

We conceptualized, designed, and produced an anatomically realistic model for the open correction of type III oesophageal atresia. We validated it with two groups of participants (experts and non-experts) through face, construct, and content validity questionnaires.

Results

The model was validated by 9 experts and 9 non-experts. The mean procedure time for the experts and non-experts groups was 34.0 and 38.4 minutes respectively. Two non-experts did not complete the procedure at the designed time (45 minutes). Regarding the face validity questionnaire, the mean rating of the model was 3.2 out of 4. Regarding the construct validity, we found statistically significant differences between groups for the equidistance between sutures, 100% correct in the expert group vs. 42.9% correct in the non-expert group (p=0.02), and for the item “Confirms that tracheoesophageal fistula closure is watertight before continuing the procedure”, correctly assessed by 66.7% of the experts vs. by 11.1% of non-experts (p=0.05). Concerning content validity, the mean score was 3.3 out of 4 for the experts and 3.3 out of 4 for the non-experts (p=0.32).

Conclusions

The present model is a cost-effective, simple to produce, and validated option for the training of open correction of type III oesophageal atresia. Future studies with larger sample sizes and blinded validators are needed before drawing definitive conclusions.

Funding

None
COVID-19 inequalities in England: a mathematical modelling study of transmission risk and clinical vulnerability by socioeconomic status
Authors: Goodfellow Lucy , van Leeuwen Edwin , Eggo Rosalind M
Published: January 2024

Background

The COVID-19 pandemic resulted in major inequalities in infection burden between areas of varying socioeconomic deprivation in many countries, including England. Areas of higher deprivation tend to have a different population structure - generally younger - which can increase viral transmission due to higher contact rates in school-going children and working-age adults. Higher deprivation is also associated with higher presence of chronic comorbidities, which were convincingly demonstrated to be risk factors for severe COVID-19 disease. These two major factors need to be combined to better understand and quantify their relative importance in the observed COVID-19 inequalities.

Methods

We used UK Census data on health status and demography stratified by decile of the Index of Multiple Deprivation (IMD), which is a measure of socioeconomic deprivation. We calculated epidemiological impact using an age-stratified COVID-19 transmission model, which incorporated different contact patterns and clinical health profile by decile. To separate the contribution of each factor, we also considered a scenario where the clinical health profile of all deciles was at the level of the least deprived. We also considered the effectiveness of school closures in each decile.

Results

In the modelled epidemics in urban areas, the most deprived decile experienced 9% more infections, 13% more clinical cases, and a 97% larger peak clinical size than the least deprived; we found similar inequalities in rural areas. 21% of clinical cases and 16% of deaths in England observed under the model assumptions would not occur if all deciles experienced the clinical health profile of the least deprived decile. We found that more deaths were prevented in more affluent areas during school closures.

Conclusions

This study demonstrates that both clinical and demographic factors synergise to generate health inequalities in COVID-19, that improving the clinical health profile of populations would increase health equity, and that some interventions can increase health inequalities.
Quantifying morphological changes in middle trapezius with ultrasound scanning and a novel histogram-matching algorithm for adults with and without Facioscapulohumeral dystrophy (FSHD)
Authors: Philp Fraser , Meilak Erik , Seyres Martin , Willis Tracey , Winn Naomi , Pandyan Anand
Published: January 2024

Background and Objectives

Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease causing changes in muscle structure that can negatively affect upper-limb function. Echogenicity, measured using quantified muscle ultrasound, is a potential biomarker that could be used for informing decision making. Histogram-matching allows for image normalisation, which could enable comparison of echogenicity between different machine capture settings which is a current limitation. This study aimed to investigate if ultrasonography and histogram-matching can measure trapezius muscle echogenicity and morphology for differentiating between people with and without FSHD, and different levels of arm function.

Methods

Single measurement timepoint case control study of adults with FSHD and age- and sex-matched controls. Main outcomes were trapezius echogenicity and muscle thickness measured using 2D-ultrasound, and maximum thoracohumeral elevation angle, measured using 3D-movement analysis. A sensitivity analysis evaluating the effect of histogram-matching and different reference images was conducted. Between group differences for echogenicity were evaluated using an unpaired student t-test. Echogenicity, muscle thickness and range of movement were plotted to evaluate the explained variance between variables.

Results

Data was collected for 14 participants (10M:4F), seven with FSHD and seven controls with a mean (SD) age of 41.6 (15.7). Normalisation was necessary and echogenicity values for the FSHD group were higher than the controls (118.2 (34.0) vs 42.3 (14.0) respectively, with statistically significant differences (p=0.002). An overall variance of 6.2 (LLOA −2.9 to ULOA 15.4) was identified between reference images. Echogenicity accounted for the largest explained variance in muscle thickness (R2=0.81) and range of movement (R2=0.74), whilst muscle thickness and range of movement was the lowest (R2=0.61).

Discussion

People with FSHD demonstrated higher echogenicity, smaller muscle thicknesses and less range of movement. Histogram-matching for comparison of echogenicity values is necessary and can provide quantifiable differences. Different reference images affect echogenicity values but the variability is less than between group differences. Further work is needed to evaluate the longitudinal variability associated with this method on a larger sample of people with varying levels of arm function. Ultrasound scanning and post-histogram matching may be used to quantify and compare differences in muscle structure and function people with and without FSHD.
Aspergillus-mediated allergic airway inflammation is triggered by dendritic cell recognition of a defined spore morphotype, a process that can be targeted via antifungal therapeutics
Authors: Houlder EL , Gago S , Vere G , Conn D , Khan S , Thomson D , Shepherd MW , Lebedinec R , Brown GD , Bromley M , MacDonald AS , Cook PC
Published: January 2024

Background

Exposure to fungi, especiallyAspergillus fumigatus (A.f.), can elicit potent allergic inflammation that triggers and worsens asthmatic disease. Dendritic cells (DCs), initiate allergic inflammatory responses to allergic stimuli. However, it is unclear ifA.f.spores during isotropic growth (early spore swelling) can activate DCs to initiate allergic responses or if germination is required. This lack of basic understanding of howA.f.causes disease is a barrier to the development of new treatments.

Objective

To show that a preciseA.f. morphotype stage during spore swelling can trigger DCs to mediate allergic inflammatory responses and ascertain if antifungal therapeutics can be effective at suppressing this process.

Methods

We employed anA.f.strain deficient in pyrimidine biosynthesis (ΔpyrG) to generate populations ofA.f.spores arrested at different stages of isotropic growth (swelling) via temporal removal of uracil and uridine from growth media. These arrested spore stages were cultured with bone marrow derived DCs (BMDCs), and their activation measured via flow cytometry and ELISA to interrogate which growth stage was able to activate BMDCs. These BMDCs were then adoptively transferred into the airways, to assess if they were able to mediate allergic inflammation in naive recipient mice. Allergic airway inflammationin vivowas determined via flow cytometry, ELISA and qPCR. This system was also used to determine if antifungal drug (itraconazole) treatment could alter early stages of spore swelling and therefore BMDC activation andin vivoallergic inflammation upon adoptive transfer.

Results

We found thatA.f. isotropic growth is essential to trigger BMDC activation and mediate allergic airway inflammation. Furthermore, using time arrestedA.f.stages, we found that least 3h in growth media enabled spores to swell sufficiently to activate BMDCs to elicit allergic airway inflammationin vivo. Incubation of germinatingA.f.with itraconazole reduced spore swelling and partially reduced their ability to activate BMDCs to elicitin vivoallergic airway inflammation.

Conclusion

In summary, our results have pinpointed the precise stage ofA.f. development when germinating spores are able to activate DCs to mediate downstream allergic airway inflammation. Furthermore, we have identified that antifungal therapeutics can be effective in reducing the potential ofA.f.spores to stimulate allergic responses, highlighting a potential mechanism by which antifungal treatment might help to prevent the development of fungal allergy.
Epigenetic priming of embryonic lineages in the mammalian epiblast
Authors: Sendra Miquel , McDole Katie , Jimenez-Carretero Daniel , Hourcade Juan de Dios , Temiño Susana , Raiola Morena , Guignard Léo , Keller Philipp J , Sánchez-Cabo Fátima , Domínguez Jorge N. , Torres Miguel
Published: January 2024

Understanding the diversification of mammalian cell lineages is an essential to embryonic development, organ regeneration and tissue engineering. Shortly after implantation in the uterus, the pluripotent cells of the mammalian epiblast generate the three germ layers: ectoderm, mesoderm and endoderm1. Although clonal analyses suggest early specification of epiblast cells towards particular cell lineages2–4, single-cell transcriptomes do not identify lineage-specific markers in the epiblast5–11and thus, the molecular regulation of such specification remains unknow. Here, we studied the epigenetic landscape of single epiblast cells, which revealed lineage priming towards endoderm, ectoderm or mesoderm. Unexpectedly, epiblast cells with mesodermal priming show a strong signature for the endothelial/endocardial fate, suggesting early specification of this lineage aside from other mesoderm. Through clonal analysis and live imaging, we show that endothelial precursors show early lineage divergence from the rest of mesodermal derivatives. In particular, cardiomyocytes and endocardial cells show limited lineage relationship, despite being temporally and spatially co-recruited during gastrulation. Furthermore, analysing the live tracks of single cells through unsupervised classification of cell migratory activity, we found early behavioral divergence of endothelial precursors shortly after the onset of mesoderm migration towards the cardiogenic area. These results provide a new model for the phenotypically silent specification of mammalian cell lineages in pluripotent cells of the epiblast and modify current knowledge on the sequence and timing of cardiovascular lineages diversification12,13.
SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension
Authors: Cebul Elizabeth R. , Marivin Arthur , Wexler Leland R. , Perrat Paola N. , Bénard Claire Y. , Garcia-Marcos Mikel , Heiman Maxwell G.
Published: January 2024

Adherens junctions (AJs) are a fundamental organizing structure for multicellular life. Although AJs are studied mainly in epithelia, their core function – stabilizing cell contacts by coupling adhesion molecules to the cytoskeleton – is important in diverse tissues. We find that twoC. eleganssensory neurons, URX and BAG, require conserved AJ proteins for dendrite morphogenesis. We previously showed that URX and BAG dendrites attach to the embryonic nose via the adhesion molecule SAX-7/L1CAM, acting both in neurons and glia, and then extend by stretch during embryo elongation. Here, we find that a PDZ-binding motif (PB) in the SAX-7 cytoplasmic tail acts with other interaction motifs to promote dendrite extension. Using pull-down assays, we find that the SAX-7 PB binds the multi-PDZ scaffolding protein MAGI-1, which bridges it to the cadherin-catenin complex protein HMP-2/β-catenin. Using cell-specific rescue and depletion, we find that both MAGI-1 and HMR-1/Cadherin act in glia to non-autonomously promote dendrite extension. Double mutant analysis indicates that each protein can act independently of SAX-7, suggesting a multivalent adhesion complex. The SAX-7 PB motif also binds AFD-1/Afadin, loss of which further enhancessax-7BAG dendrite defects. As MAGI-1, HMR-1, and AFD-1 are all found in epithelial AJs, we propose that an AJ-like complex in glia promotes dendrite extension.
Quantum oscillations revealing topological band in kagome metal
ScV6Sn6
Authors: Yi Changjiang , Feng Xiaolong , Mao Ning , Yanda Premakumar , Roychowdhury Subhajit , Zhang Yang , Felser Claudia , Shekhar Chandra
Published: January 2024

Compounds with kagome lattice structure are known to exhibit Dirac cones, flatbands, and van Hove singularities, which host numerous versatile quantum phenomena. Inspired by these intriguing properties, we investigate the temperature and magnetic field-dependent electrical transports along with the theoretical calculations of ScV6Sn6, a nonmagnetic charge-density wave (CDW) compound. At low temperatures, the compound exhibits Shubnikov–de Haas quantum oscillations, which help to design the Fermi-surface (FS) topology. This analysis reveals the existence of several small FSs in the Brillouin zone, combined with a large FS. Among them, the FS-possessing Dirac band is nontrivial and generates a nonzero Berry phase. In addition, the compound also shows the anomalous Hall-like behavior up to the CDW phase transition, and they might be correlated. Combining these interesting physical properties with the CDW phase, ScV6Sn6 presents a unique material example of the versatile HfFe6Ge6 family and provides various promising opportunities to explore the series further.

Published by the American Physical Society
2024
Renormalization group functions in two-dimensional massive Dirac-like systems near an interface
Authors: Braga Alessandra N. , Pires Wagner P. , Silva Jeferson Danilo L. , Alves Danilo T. , Alves Van Sérgio
Published: January 2024

In a recent paper [], pseudo quantum electrodynamics was used to simulate the Coulomb interaction between electrons and determine the mass renormalization in a two-dimensional Dirac-like system. In the present paper, we expand upon these findings by examining this system in a certain distance from a planar interface separating two dielectrics. Using the random-phase approximation, we calculate the renormalization group functions and show how the behaviors of the mass, Fermi velocity, and the anomalous dimension of the fermion field are affected by the presence of this interface. To exemplify an application of our formulas, we calculate the influence of this interface on the renormalized energy band gap in a two-dimensional material. In the appropriate limits, our results recover the corresponding ones reported in the aforementioned publication, as well as in others.

Published by the American Physical Society
2024
Gauge violation spectroscopy of synthetic gauge theories
Authors: Qi Hao-Yue , Zheng Wei
Published: January 2024

Recently synthetic gauge fields have been implemented on quantum simulators. Unlike the gauge fields in the real world, in synthetic gauge fields, the gauge charge can fluctuate and gauge invariance can be violated, which leads to rich physics unexplored before. In this work, we first propose the gauge violation spectroscopy as a powerful experimentally accessible measurement of synthetic gauge theories. We show that the gauge violation spectroscopy exhibits no dispersion. Using three models as examples, two of which can be exactly solved by bosonization, and one that has been realized in experiment, we further demonstrate the gauge violation spectroscopy can be used to detect the confinement and deconfinement phases. In the confinement phase, it shows a δ-function behavior, while in the deconfinement phase, it has a finite width.

Published by the American Physical Society
2024
Photogalvanic response in multi-Weyl semimetals
Authors: Raj Arpit , Chaudhary Swati , Fiete Gregory A.
Published: January 2024

We investigate the dependence of the photogalvanic response of a twofold degenerate multi-Weyl semimetal on its topological charge, tilt, and chemical potential. We derive analytical expressions for the shift and injection conductivities for tilted charge-n Weyl points using a low-energy two-band effective Hamiltonian. We compute the response for more realistic tight-binding models of a double-Weyl semimetal with broken time-reversal symmetry to find significant deviations from the effective low-energy continuum model predictions. We analyze several different limits of these models, describe the nature of these deviations, and provide estimates of their dependence on the frequency and other model parameters. Our analysis provides a simple explanation for the first-principle calculation based frequency dependence of the injection current in SrSi2. We also obtain analytical results for the charge-4 Weyl semimetal using a new approach, providing all relevant information about the nature of its second-order dc response and the precise condition for observing quantized circular photogalvanic effect. This approach can easily be extended to a systematic study of second harmonic generation and first-order optical conductivity in charge-4 Weyl semimetals.

Published by the American Physical Society
2024
Robustness of interdependent hypergraphs: A bipartite network framework
Authors: Pan Xingyu , Zhou Jie , Zhou Yinzuo , Boccaletti Stefano , Bonamassa Ivan
Published: January 2024

In this paper, we develop a bipartite network framework to study the robustness of interdependent hypergraphs. From such a perspective, nodes and hyperedges of a hypergraph are equivalent to each other, a property that largely simplifies their mathematical treatment. We develop a general percolation theory based on this representation and apply it to study the robustness of interdependent hypergraphs against random damage, which we verify with numerical simulations. We analyze a variety of interacting patterns, from heterogeneous to correlated hyperstructures, and from full- to partial-dependency couplings between an arbitrary number of hypergraphs, and characterize their structural stability via their phase diagrams. Given its generality, we expect that our framework will provide useful insights for the development of more realistic venues to characterize cascading failures in interdependent higher-order systems.

Published by the American Physical Society
2024
Improving transmon qudit measurement on IBM Quantum hardware
Authors: Kehrer Tobias , Nadolny Tobias , Bruder Christoph
Published: January 2024

The Hilbert space of a physical qubit typically features more than two energy levels. Using states outside the qubit subspace can provide advantages in quantum computation. To benefit from these advantages, individual states of the d-dimensional qudit Hilbert space have to be discriminated during readout. We propose and analyze two measurement strategies that improve the distinguishability of transmon qudit states. Based on a model describing the readout of a transmon qudit coupled to a resonator, we identify the regime in hardware parameter space where each strategy is optimal. We discuss these strategies in the context of a practical implementation of the default measurement of a ququart on IBM Quantum hardware whose states are prepared by employing higher-order X gates that make use of two-photon transitions.

Published by the American Physical Society
2024
Recursive quantum eigenvalue and singular-value transformation: Analytic construction of matrix sign function by Newton iteration
Authors: Mizuta Kaoru , Fujii Keisuke
Published: January 2024

Quantum eigenvalue transformation (QET) and its generalization, quantum singular value transformation (QSVT), are versatile quantum algorithms that allow us to apply broad matrix functions to quantum states, which cover many significant quantum algorithms such as Hamiltonian simulation. However, finding a parameter set which realizes preferable matrix functions in these techniques is difficult for large-scale quantum systems: there is no analytical result other than trivial cases as far as we know and we often suffer also from numerical instability. In this Letter, we propose recursive QET or QSVT (R-QET or R-QSVT) in which we can execute complicated matrix functions by recursively organizing block-encoding by low-degree QET or QSVT. Owing to the simplicity of recursive relations, it works only with a few parameters with exactly determining the parameters, while its iteration results in complicated matrix functions. In particular, by exploiting the recursive relation of Newton iteration, we construct the matrix sign function, which can be applied for eigenstate filtering for example, in a tractable way. We show that an analytically obtained parameter set composed of only eight different values is sufficient for executing QET of the matrix sign function with an arbitrarily small error ɛ. Our protocol will serve as an alternative protocol for constructing QET or QSVT for some useful matrix functions without numerical instability.

Published by the American Physical Society
2024
Population-Density Bounds for 100% Domestic Renewable Energy Generation
Authors: Madsen Dorte Nørgaard , Hansen Jan Petter , Emblemsvåg Jan
Published: January 2024

The long-running discussion on the global theoretical and practical potential of renewable energy is strongly affected by the size and connectivity of power networks. Small regional and national networks driven predominantly by intermittent and variable energy sources will require significantly more back-up power than continental networks containing a variety of weather zones. Thus, large networks will require less back-up but this comes with the drawback that some nations or regions rely on import from others. For example, in Europe in 2022, energy dependence on gas imports from Russia led to energy shortages and escalating prices. In this work, we estimate the limits of primary energy supply based on renewables, mainly solar photovoltaic (PV) sources and wind, in this setting. Taking as a starting point an average of 14 European countries, we find the mean energy consumption per unit time in what we argue is sufficient and necessary power per capita to maintain a sustainable life. The required energy generation is then translated into an area of energy production that, together with estimated area requirements for biological diversity, food, and infrastructure, constitutes a given fraction of the land area. When compared with typical human population densities, we find that before reaching one person per hectare, the area requirements exceed what is available. The results support the part of the scientific community that claims that a 100% renewable global power supply is unrealistic, especially as the world population steadily grows toward 10×109 people.

Published by the American Physical Society
2024
Blockchain technology roles to overcome accounting, accountability and assurance barriers in supply chain finance
Authors: Rijanto Arief
Published: January 2024

Purpose

Know your customer (KYC), accounting standards, issuance, clearing, and trade settlement became the major barrier to implement accounting, accountability and assurance process in supply chain finance (SCF). Blockchain technology features have the potential to solve accounting problems. This research focuses on exploring how blockchain technology provides solutions to overcome the barriers of accounting process in SCF. The benefits, opportunities, costs and risks related to blockchain adoption are also explored.

Design/methodology/approach

Multi-case study and qualitative methods are used with a framework based on blockchain role to overcome the accounting process barriers. Ten blockchain projects in SCF and 29 interviews of participants as a unit of analysis are considered.

Findings

The findings indicate that blockchain technology offers solutions to solve accounting, accountability and assurance problems in SCF. Validity, verification, smart contracts, automation and enduring data on trade transactions potentially solve those barriers. However, it is also necessary to consider costs such as implementation, technology, education and integration costs. Then there are possible risks such as regulatory compliance, operational, code development and scalability risk. This finding reflects the current status of blockchain technology roles in SCF.

Research limitations/implications

This study unveils blockchain's SCF accounting potential, emphasizing multi-case method limitations and future research prospects. Diverse contexts challenge findings' applicability, warranting cross-industry studies for deeper insights. Addressing selection bias and integrating quantitative measures can enhance understanding of blockchain's accounting impact.

Practical implications

Accounting professionals can get an idea of the future direction and impact of blockchain technology on accounting, accountability and assurance processes.

Originality/value

This study provides initial findings on the potential, costs and risks of blockchain that is beneficial for parties involved in SCF, especially for banks and insurance underwriters. In addition, the findings also provide direction for the contribution of blockchain technology to accounting theory in the future.