bluuebunny/crossref_metadata_2025 huggingface dataset:
Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription
Authors: Teng Zhen , Yang Lu , Zhang Qian , Chen Yujue , Wang Xianfeng , Zheng Yiran , Tian Aiguo , Tian Di , Lin Zhen , Deng Wu-Min , Liu Hong
Published: May 2024

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 andDrosophilaS2 cells and inDrosophilalarval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.
Differences in size and number of embryonic type-II neuroblast lineages correlate with divergent timing of central complex development between beetle and fly
Authors: Rethemeier Simon , Fritzsche Sonja , Mühlen Dominik , Bucher Gregor , Hunnekuhl Vera S.
Published: May 2024

Despite its conserved basic structure, the morphology of the insect brain and the timing of its development underwent evolutionary adaptations. However, little is known about the developmental processes that create this diversity. The central complex is a brain centre required for multimodal information processing and an excellent model to understand neural development and divergence. It is produced in large parts by type-II neuroblasts, which produce intermediate progenitors, another type of cycling precursor, to increase their neural progeny. These neural stem cells are believed to be conserved among insects, but little is known on their molecular characteristics in insects other than flies.Tribolium castaneumhas emerged as a valuable new insect model for brain development and evolution. However, type-II neuroblast lineages and their role in central complex development have so far not been studied in this beetle.

Using CRISPR-Cas9 we created a fluorescent enhancer trap marking expression ofTribolium fez/earmuff, a key marker for type-II neuroblast derived intermediate progenitors. Using combinatorial labelling of further markers includingTc-pointed,Tc-deadpan,Tc-asenseandTc-prosperowe characterized the type-II neuroblast lineages present in theTriboliumembryo and their sub-cell-types. Intriguingly, we found 9 type-II neuroblast lineages per hemisphere in theTriboliumembryo whileDrosophilaproduces only 8 per brain hemisphere. In addition, these lineages are significantly larger at the embryonic stage ofTriboliumthan they are inDrosophilaand contain more intermediate progenitors. Finally, we mapped these lineages to the domains of early expressed head patterning genes. Notably,Tc-otdis absent from all type-II neuroblasts and intermediate progenitors, whereasTc-six3marks an anterior subset of the type-II-lineages. The placodal markerTc-six4specifically marks the territory where anterior medial type-II neuroblasts differentiate.

In conclusion, we identified a conserved pattern of gene expression in holometabolan central complex forming type-II neuroblast lineages, and conserved head patterning genes emerged as new candidates for conferring spatial identity to individual lineages. The higher number and greater lineage size of the embryonic type-II neuroblasts in the beetle correlate with a previously described embryonic phase of central complex formation which is not found in the fly. These findings stipulate further research on the causal link between timing of stem cell activity and temporal and structural differences in central complex development.
A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24
Authors: Nyame Perpetual , Togami Akihiro , Yoshida Tomofumi , Masunaga Takuya , Monira Begum MST , Terasawa Hiromi , Monde Nami , Tahara Yurika , Tanaka Reiko , Tanaka Yuestu , Appiah-Kubi Joyce , Amesimeku Wright Ofotsu , Hossain Md Jakir , Otsuka Masami , Yoshimura Kazuhisa , Ikeda Terumasa , Sawa Tomohiro , Satou Yorifumi , Fujita Mikako , Maeda Yosuke , Tateishi Hiroshi , Monde Kazuaki
Published: May 2024

The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7.

Importance

A collection of scientific strategies has been revealed to find long-term cure for HIV-1 infection. One of these techniques, the therapeutic approach, involves harnessing late events that are not targeted by current medication. The regulator of HIV-1 assembly and release, the HIV-1 Gag protein, has emerged as a prospective inhibitor. We set up a high-efficiency, economically viable, and facile screening system for the identification of late-stage inhibitors. Herein, we discovered a heterocyclic compound that inhibits HIV-1 release. This newly high- performance testing technique can be employed in virological research for investigating HIV- 1 late-stage processes.
Growth ofStaphylococcus aureusin the presence of oleic acid shifts the glycolipid fatty acid profile and increases resistance to antimicrobial peptides
Authors: Raskovic Djuro , Alvarado Gloria , Hines Kelly M. , Xu Libin , Gatto Craig , Wilkinson Brian J. , Pokorny Antje
Published: May 2024

Staphylococcus aureusreadily adapts to various environments and quickly develops antibiotic resistance, which has led to an increase in multidrug-resistant infections. Hence,S. aureuspresents a significant global health issue and its adaptations to the host environment are crucial for understanding pathogenesis and antibiotic susceptibility. WhenS. aureusis grown conventionally, its membrane lipids contain a mix of branched-chain and straight-chain saturated fatty acids. However, when unsaturated fatty acids are present in the growth medium, they become a major part of the total fatty acid composition. This study explores the biophysical effects of incorporating straight-chain unsaturated fatty acids intoS. aureusmembrane lipids. Membrane preparations from cultures supplemented with oleic acid showed more complex differential scanning calorimetry scans than those grown in tryptic soy broth alone. When grown in the presence of oleic acid, the cultures exhibited a transition significantly above the growth temperature, attributed to the presence of glycolipids with long-chain fatty acids causing acyl chain packing frustration within the bilayer. Functional aspects of the membrane were assessed by studying the kinetics of dye release from unilamellar vesicles induced by the antimicrobial peptide mastoparan X. Dye release was slower from liposomes prepared from cells grown in oleic acid-supplemented cultures, suggesting that changes in membrane lipid composition and biophysics protect the cell membrane against peptide-induced lysis. These findings underscore the intricate relationship between the growth environment, membrane lipid composition, and the physical properties of the bacterial membrane, which should be considered when developing new strategies against S. aureus infections.
The tricellular junction protein ILDR2 in glomerulopathies: insights and implications
Authors: Siegerist Florian , Kliewe Felix , Hammer Elke , Schakau Paul , Chi Soh Joanne Ern , Weber Claudia , Puelles Victor , Lindemeyer Maja , Reichelt-Wurm Simone , Drenic Vedran , Chatziantoniou Christos , Chadjichristos Christos E. , Zhang Yiying , Banas Miriam C. , Nauck Matthias , Völker Uwe , Endlich Nicole
Published: May 2024

The tricellular tight junctions are crucial for the regulation of paracellular flux at tricellular junctions, where tricellulin (MARVELD2) and angulins (ILDR1, ILDR2 or LSR) are localized. The role of ILDR2 in podocytes, specialized epithelial cells in the kidney, is still unknown. We investigated the role of ILDR2 in glomeruli and its influence on blood filtration. Western blots, scRNA-seq and superresolution microscopy showed a strong expression of MARVELD2 and ILDR2 in podocytes that colocalizes with the podocyte-specific claudin CLDN5. Co-immunoprecipitation revealed that ILDR2 directly binds CLDN5. In glomerulopathies, induced by nephrotoxic serum and by DOCA-salt heminephrectomy, ILDR2 was strongly upregulated. Furthermore,Ildr2knockout mice exhibited glomerular hypertrophy and decreased podocyte density, however, did not develop effacement of podocyte foot processes or proteinuria. LC-MS/MS proteomic analysis of isolated glomeruli showed an increase in matrix proteins such as fibronectin and agrin. This suggests a protective role of ILDR2 in glomerulopathies.
Transient interdomain interactions modulate the monomeric structural ensemble and self-assembly of Huntingtin Exon 1
Authors: Mohanty Priyesh , Phan Tien Minh , Mittal Jeetain
Published: May 2024

Polyglutamine expansion (≥ 36 residues) within the N-terminal exon-1 of Huntingtin (Httex1) leads to Huntington’s disease, a neurodegenerative condition marked by the presence of intranuclear Htt inclusions. Notably, the polyglutamine tract in Httex1 is flanked by an N-terminal coiled-coil domain - N17 (17 amino acids), which undergoes self-association to promote the formation of soluble Httex1 oligomers and brings the aggregation-prone polyQ tracts in close spatial proximity. However, the mechanisms underlying the subsequent conversion of soluble oligomers into insoluble β-rich aggregates with increasing polyQ length, remain unclear. Current knowledge suggests that expansion of the polyQ tract increases its helicity, and this favors its oligomerization and aggregation. In addition, studies utilizing photocrosslinking, conformation-specific antibodies and a stable coiled-coil heterotetrametric system fused to polyQ indicate that domain “cross-talk” (i.e., interdomain interactions) may play a role in the emergence of toxic conformations and the conversion of Httex1 oligomers into fibrillar aggregates. Here, we performed extensive atomistic molecular dynamics (MD) simulations (aggregate time ∼ 0.7 ms) to uncover the interplay between structural transformation and domain “cross-talk” on the conformational ensemble and oligomerization landscape of Httex1. Notably, our MD-derived ensembles of N17-polyQ monomers validated against13C NMR chemical shifts indicated that in addition to elevated α- helicity, polyQ expansion also favors transient, interdomain (N17-polyQ) interactions which result in the emergence of β-sheet conformations. Further, interdomain interactions competed with increased polyQ tract α-helicity to modulate the stability of N17-mediated dimers and thereby promoted a heterogenous dimerization landscape. Finally, we observed that the C-terminal proline-rich domain (PRD) promoted condensation of Httex1 through self-interactions involving its P10/P11tracts while also interacting with N17 to suppress its α-helicity. In summary, our study demonstrates a significant role for domain “cross-talk” in modulating the monomeric structural ensemble and self-assembly of Httex1.
Global biogeography of N2-fixing microbes:nifHamplicon database and analytics workflow
Authors: Morando Michael , Magasin Jonathan , Cheung Shunyan , Mills Matthew M. , Zehr Jonathan P. , Turk-Kubo Kendra A.
Published: May 2024

Marine nitrogen (N) fixation is a globally significant biogeochemical process carried out by a specialized group of prokaryotes (diazotrophs), yet our understanding of their ecology is constantly evolving. Although marine dinitrogen (N2)-fixation is often ascribed to cyanobacterial diazotrophs, indirect evidence suggests that non-cyanobacterial diazotrophs (NCDs) might also be important. One widely used approach for understanding diazotroph diversity and biogeography is polymerase chain reaction (PCR)-amplification of a portion of thenifHgene, which encodes a structural component of the N2-fixing enzyme complex, nitrogenase. An array of bioinformatic tools exists to processnifHamplicon data, however, the lack of standardized practices has hindered cross-study comparisons. This has led to a missed opportunity to more thoroughly assess diazotroph biogeography, diversity, and their potential contributions to the marine N cycle. To address these knowledge gaps a bioinformatic workflow was designed that standardizes the processing ofnifHamplicon datasets originating from high-throughput sequencing (HTS). Multiple datasets are efficiently and consistently processed with a specialized DADA2 pipeline to identify amplicon sequence variants (ASVs). A series of customizable post-pipeline stages then detect and discard spuriousnifHsequences and annotate the subsequent quality-filterednifHASVs using multiple reference databases and classification approaches. This newly developed workflow was used to reprocess nearly all publicly availablenifHamplicon HTS datasets from marine studies, and to generate a comprehensivenifHASV database containing 7909 ASVs aggregated from 21 studies that represent the diazotrophic populations in the global ocean. For each sample, the database includes physical and chemical metadata obtained from the Simons Collaborative Marine Atlas Project (CMAP). Here we demonstrate the utility of this database for revealing global biogeographical patterns of prominent diazotroph groups and highlight the influence of sea surface temperature. The workflow andnifHASV database provide a robust framework for studying marine N2fixation and diazotrophic diversity captured bynifHamplicon HTS. Future datasets that target understudied ocean regions can be added easily, and users can tune parameters and studies included for their specific focus. The workflow and database are available, respectively, in GitHub (https://github.com/jdmagasin/nifH-ASV-workflow) and Figshare (https://doi.org/10.6084/m9.figshare.23795943.v1).
Psilocybin facilitates fear extinction: importance of dose, context, and serotonin receptors
Authors: Woodburn Samuel C. , Levitt Caleb M. , Koester Allison M. , Kwan Alex C.
Published: May 2024

A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for posttraumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin’s potential effect in fear learning paradigms. More specifically, the extents to which dose, timing of administration, and serotonin receptors may influence psilocybin’s effect on fear extinction are not understood. In this study, we used an auditory delay fear conditioning paradigm to determine the effects of psilocybin on fear extinction, extinction retention, and fear renewal in male and female mice. Psilocybin robustly enhances fear extinction when given acutely prior to testing for all doses tested. Psilocybin exerts long-term effects to elevate extinction retention and suppress fear renewal in a novel context, though these changes were sensitive to dose. Administration of psilocybin prior to fear learning or immediately after extinction yielded no change in behavior, indicating that concurrent extinction experience is necessary for the drug’s effects. Co-treatment with a 5-HT2Areceptor antagonist blocked psilocybin’s effects for extinction, extinction retention and fear renewal, whereas 5-HT1Areceptor antagonism attenuated only the effect on fear renewal. Collectively, these results highlight dose, context, and serotonin receptors as crucial factors in psilocybin’s ability to facilitate fear extinction. The study provides preclinical evidence to support investigating psilocybin as a pharmacological adjunct for extinction-based therapy for PTSD.
Functional dissection of complex and molecular trait variants at single nucleotide resolution
Authors: Siraj Layla , Castro Rodrigo I , Dewey Hannah , Kales Susan , Nguyen Thanh Thanh L , Kanai Masahiro , Berenzy Daniel , Mouri Kousuke , Wang Qingbo , McCaw Zachary R , Gosai Sager J , Aguet François , Cui Ran , Vockley Christopher M , Lareau Caleb A , Okada Yukinori , Gusev Alexander , Jones Thouis R , Lander Eric S , Sabeti Pardis C , Finucane Hilary K , Reilly Steven K , Ulirsch Jacob C , Tewhey Ryan
Published: May 2024

Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics. The majority of these variants have individually weak effects and lie in non-coding gene-regulatory elements where we lack a complete understanding of how single nucleotide alterations modulate transcriptional processes to affect human phenotypes. To address this, we measured the activity of 221,412 trait-associated variants that had been statistically fine-mapped using a Massively Parallel Reporter Assay (MPRA) in 5 diverse cell-types. We show that MPRA is able to discriminate between likely causal variants and controls, identifying 12,025 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% can plausibly be explained by the disruption of a known transcription factor (TF) binding motif. We dissect the mechanisms of 136 variants using saturation mutagenesis and assign impacted TFs for 91% of variants without a clear canonical mechanism. Finally, we provide evidence that epistasis is prevalent for variants in close proximity and identify multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants underlying complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.
HEPN-AbiV is an RNase in the antiphage system AbiV
Authors: Zhu Xiaojun , Morency Carlee , Picard Marie-Ève , Mosterd Cas , McAlister Jason A. , Perrault-Jolicoeur Alice , Geddes-McAlister Jennifer , Shi Rong , Moineau Sylvain
Published: May 2024

Prokaryotes and eukaryotes possess defense systems, which can be either innate or acquired, to protect against viral infections. At the bacterial population level, abortive infection (Abi) serves as an innate immune defense mechanism against phage invasion. The AbiV antiviral system is prevalent in several bacterial genomes and exhibits diverse characteristics in terms of gene composition and evolution. Our investigation into theLactococcusAbiV system revealed a novel two-component system,abiV1andabiV2, both of which are essential for its function as a type III toxin-antitoxin system. The toxin component AbiV (product ofabiV1) is an RNase belonging to the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) superfamily as it carries the consensus Rx4-6H motif.In vivoassays coupled with mass spectrometry showed that the lactococcal AbiV was expressed in the presence or absence of phages whilein vitroexperiments demonstrated that AbiV1 degraded ribosomal RNA but not mRNA. On the other hand, the antitoxin component (abiV2) was found to function as an RNA molecule that inhibited the nuclease activity of the AbiV1 toxin. The structural characterization of AbiV revealed that this RNase utilizes a large patch of positively charged area across the dimer to anchor RNA molecules. In addition, we showed that the AbiV N-terminal region (amino acids 1 to 23) is crucial for its RNase activity as a truncated AbiV lacking this segment adopted distinct conformational states incompatible with RNA binding. This study provided novel insights into the mode of action of the antiviral system AbiV.
PI3 kinase-unrelated effects of LY294002 and LY303511 on serotonin-induced Ca2+and cAMP signaling
Authors: Kotova Polina D. , Dymova Ekaterina A. , Rogachevskaja Olga A. , Kolesnikov Stanislav S.
Published: May 2024

The phosphoinositide 3-kinase (PI3K) is involved in regulation of multiple intracellular processes. Although the inhibitory analysis is generally employed for validating a physiological role of PI3K, increasing body of evidence suggests that PI3K inhibitors can exhibit PI3K-unrelated activity as well. Here we studied effects of PI3K inhibitor LY294002 and its inactive analogue LY303511 on Ca2+and cAMP signals initiated by serotonin. In the present study several monoclonal HEK293 cell lines were used, in particular, monitoring of Ca2+signals were carried out on Fura-2 loaded cells expressed recombinant serotonin 5-HT2Creceptors, cAMP signals were studied on cells expressed the genetically encoded cAMP sensor Pink Flamindo and recombinant 5-HT4receptors, for monitoring PI3K activity cells stably expressed the genetically encoded PIP3sensor PH(Akt)-Venus were used. It turned out that LY294002 suppressed Ca2+signals initiated by activation 5-HT2Creceptors irrespectively of PI3K inhibition, but did not affect cAMP responses initiated by 5-HT4receptors. In turn LY303511 suppressed cAMP signals initiated by 5-HT4receptors, and elicited Ca2+transients exclusively in cells expressed 5-HT2Creceptors. Based on these facts and the results of the inhibitory analysis, we hypothesize that the described effects may be due to the activity of LY294002 and LY303511 on the serotonin 5-HT2Cand 5-HT4receptors.
Elucidating Molecular Mechanism and Chemical Space of Chalcones through Knowledge Graph and Machine Learning: A Combined Bio-Cheminformatic Pipeline
Authors: Manaithiya Ajay , Bhowmik Ratul , Acharjee Satarupa , Sharma Sameer , Kumar Sunil , Imran Mohd. , Mathew Bijo , Parkkila Seppo , Aspatwar Ashok
Published: May 2024

We developed a bio-cheminformatics method, exploring disease inhibition mechanisms using machine learning-enhanced quantitative structure-activity relationship (ML-QSAR) models and knowledge-driven neural networks. ML-QSAR models were developed using molecular fingerprint descriptors and the Random Forest algorithm to explore the chemical spaces of Chalcones inhibitors against diverse disease properties, including antifungal, anti-inflammatory, anticancer, antimicrobial, and antiviral effects. We generated and validated robust machine learning-based bioactivity prediction models ((https://ashspred.streamlit.app/) for the top genes. These models underwent ROC and applicability domain analysis, followed by molecular docking studies to elucidate the molecular mechanisms of the molecules. Through comprehensive neural network analysis, crucial genes such as AKT1, HSP90A1, SRC, and STAT3 were identified. The PubChem fingerprint-based model revealed key descriptors: PubchemFP521 for AKT1, PubchemFP180 for SRC, PubchemFP633 for HSP90, and PubchemFP145 and PubchemFP338 for STAT3, consistently contributing to bioactivity across targets. Notably, chalcone derivatives demonstrated significant bioactivity against target genes, with compound RA1 displaying a predictive pIC50value of 5.76 against HSP90A and strong binding affinities across other targets. Compounds RA5 to RA7 also exhibited high binding affinity scores comparable to or exceeding existing drugs. These findings emphasize the importance of knowledge-based neural network-based research for developing effective drugs against diverse disease properties. These interactions warrant furtherin vitroandin vivoinvestigations to elucidate their potential in rational drug design. The presented models provide valuable insights for inhibitor design and hold promise for drug development. Future research will prioritize investigating these molecules formycobacterium tuberculosis, enhancing the comprehension of effectiveness in addressing infectious diseases.
Genomic epidemiology of ESBL-producingEscherichia colifrom humans and an Aotearoa New Zealand river
Authors: Gray Holly A , Biggs Patrick J , Midwinter Anne C , Rogers Lynn E , Fayaz Ahmed , Akhter Rukhshana N , Burgess Sara A
Published: May 2024

In Aotearoa New Zealand, urinary tract infections in humans are commonly caused by extended-spectrum beta-lactamase (ESBL)-producingEscherichia coli. This group of antimicrobial resistant bacteria are often multidrug resistant. However, there is limited information on ESBL-producingE. colifound in the environment and their link with human clinical isolates. In this study, we examined the genetic relationship of environmental and human clinical ESBL-producingE. coliand isolates collected in parallel within the same area over 14 months. Environmental samples were collected from treated effluent, stormwater and multiple locations along an Aotearoa New Zealand river. Treated effluent, stormwater and river water sourced downstream of the treated outflow point were the main sources of ESBL-producingE. coli(7/14 samples, 50.0%; 3/6 samples, 50%; and 15/28 samples, 54% respectively). Whole genome sequence comparison was carried out on 307 human clinical and 45 environmental ESBL-producingE. coliisolates. Sequence type 131 was dominant for both clinical (147/307, 47.9%) and environmental isolates (11/45, 24.4%). The most prevalent ESBL genes were bothblaCTX-M-27andblaCTX-M-15for the clinical isolates (134/307, 43.6%) andblaCTX-M-15for the environmental isolates (28/45, 62.2%). A core single nucleotide polymorphism analysis of these isolates suggested that some strains were shared between humans and the local river. These results highlight the importance of understanding different transmission pathways for the spread of ESBL-producingE. coli.

2. Impact statement

Extended spectrum beta lactamase (ESBL)-producingE. colifrequently cause urinary tract infections that exhibit multidrug resistance. Surveillance studies have identified the predominant strains and resistance genes associated with urinary tract infections. However, there is limited information on the extent of spread beyond the patient. We describe the genetic relatedness of ESBL-producing environmental and clinicalE. coliisolated during the same temporal-spatial period in Aotearoa New Zealand. Comparative genomic analyses of these bacteria provide evidence of clonal spread between humans and the environment, highlighting the need to integrate environmental surveillance into antimicrobial resistance monitoring.

3. Data summary

All Illumina sequence reads for this study have been deposited in GenBank under BioProject PRJNA1032159, except for strain SB0283h1, whose data can be found under BioProject PRJNA715472. The sequence read accessions for each genome are provided in the supplementary material.

The code used for the genomic and statistical analyses is available from the GitHub repositoryhttps://github.com/sburgess1/Manawat-_ESBL.

The authors confirm all supporting data and protocols have been provided within the article or through supplementary data files.
O-glycosylation of intrinsically disordered regions regulates homeostasis of membrane proteins in streptococci
Authors: Rahman Mohammad M. , Zamakhaeva Svetlana , Rush Jeffrey S. , Chaton Catherine T. , Kenner Cameron W. , Hla Yin Mon , Tsui Ho-Ching Tiffany , Uversky Vladimir N. , Winkler Malcolm E. , Korotkov Konstantin V. , Korotkova Natalia
Published: May 2024

Proteins harboring intrinsically disordered regions (IDRs) lacking stable secondary or tertiary structures are abundant across the three domains of life. These regions have not been systematically studied in prokaryotes. Our genome-wide analysis identifies extracytoplasmic serine/threonine-rich IDRs in several biologically important membrane proteins in streptococci. We demonstrate that these IDRs areO-glycosylated with glucose by glycosyltransferases GtrB and PgtC2 inStreptococcus pyogenesandStreptococcus pneumoniae, and with N-acetylgalactosamine by a Pgf-dependent mechanism inStreptococcus mutans. Absence of glycosylation leads to a defect in biofilm formation under ethanol-stressed conditions inS. mutans. We link this phenotype to the C-terminal IDR of a post-translocation secretion chaperone PrsA.O-glycosylation of the IDR protects this region from proteolytic degradation. The IDR length attenuates the efficiency of glycosylation and, consequently, the expression level of PrsA. Taken together, our data reveal thatO-glycosylation of IDRs functions as a dynamic switch of protein homeostasis in streptococci.
Structural basis for Rab6 activation by the Ric1-Rgp1 complex
Authors: Feathers J. Ryan , Vignogna Ryan C. , Fromme J. Christopher
Published: May 2024

Rab GTPases act as molecular switches to regulate organelle homeostasis and membrane trafficking. Rab6 plays a central role in regulating cargo flux through the Golgi and is activated via nucleotide exchange by the Ric1-Rgp1 protein complex. Ric1-Rgp1 is conserved throughout eukaryotes but the structural and mechanistic basis for its function has not been established. Here we report the cryoEM structure of a Ric1-Rgp1-Rab6 complex representing a key intermediate of the nucleotide exchange reaction. This structure reveals the overall architecture of the complex and enabled us to identify interactions critical for proper recognition and activation of Rab6 on the Golgi membrane surface. Ric1-Rgp1 interacts with the nucleotide-binding domain of Rab6 using an uncharacterized helical domain, which we establish as a novel RabGEF domain by identifying residues required for Rab6 nucleotide exchange. Unexpectedly, the complex uses an arrestin fold to interact with the Rab6 hypervariable domain, indicating that interactions with the unstructured C-terminal regions of Rab GTPases may be a common specificity mechanism used by their activators. Collectively, our findings provide a detailed mechanistic understanding of regulated Rab6 activation at the Golgi.
Hyperbolic enhancement of a quantum battery
Authors: Downing Charles Andrew , Ukhtary Muhammad Shoufie
Published: May 2024

A quantum system which can store energy, and from which one can extract useful work, is known as a quantum battery. Such a device raises interesting issues surrounding how quantum physics can provide certain advantages in the charging, energy storage, or discharging of the quantum battery as compared to their classical equivalents. However, the pernicious effect of dissipation degrades the performance of any realistic battery. Here, we show how one can circumvent this problem of energy loss by proposing a quantum battery model which benefits from quantum squeezing. Namely, charging the battery quadratically with a short temporal pulse induces a hyperbolic enhancement in the stored energy, such that the dissipation present becomes essentially negligible in comparison. Furthermore, we show that when the driving is strong enough, the useful work which can be extracted from the quantum battery, that is the ergotropy, is exactly equal to the stored energy. These impressive properties imply a highly efficient quantum energetic device with abundant amounts of ergotropy. Our theoretical results suggest a possible route to realizing high-performance quantum batteries, which could be realized in a variety of platforms exploiting quantum continuous variables.

Published by the American Physical Society
2024
Transverse emittance growth due to rf noise in crab cavities: Theory, measurements, cure, and high luminosity LHC estimates
Authors: Baudrenghien P. , Mastoridis T.
Published: May 2024

The High-Luminosity LHC (HL-LHC) upgrade with planned operation from 2029 onward has a goal of achieving a tenfold increase in the integrated number of recorded collisions thanks to a doubling of the intensity per bunch (2.2×1011 protons) and a reduction of β* (the β value in the two high luminosity detectors, namely ATLAS and CMS) to 15 cm. Such an increase in recorded collisions would significantly expedite new discoveries and exploration. Crab cavities are an important component of the HL-LHC upgrade and will contribute strongly to achieving an increase in the number of recorded collisions. However, noise injected through the crab cavity radio frequency (rf) system could cause significant transverse emittance growth and limit luminosity lifetime. We presented a theoretical formalism relating transverse emittance growth to rf noise in an earlier work. In this follow-up paper, we summarize measurements in the super-proton synchrotron (SPS) at CERN that validate the theory, we present estimates of the emittance growth rates using state-of-the-art rf and low-level rf (LLRF) technologies, and we set the rf noise specifications to achieve acceptable performance. A novel dedicated feedback system acting through the crab cavities to mitigate emittance growth will be required. In this work, we develop a theoretical formalism to evaluate the performance of such a feedback system in any collider, identify limiting components, present simulation results to validate these studies, and derive key design parameters for an HL-LHC implementation of such a feedback system.

Published by the American Physical Society
2024
N3LL
resummation of one-jettiness for
Z
-boson plus jet production at hadron colliders
Authors: Alioli Simone , Bell Guido , Billis Georgios , Broggio Alessandro , Dehnadi Bahman , Lim Matthew A. , Marinelli Giulia , Nagar Riccardo , Napoletano Davide , Rahn Rudi
Published: May 2024

We present the resummation of one-jettiness for the color-singlet plus jet production process pp→(γ*/Z→ℓ+ℓ−)+jet at hadron colliders up to the fourth logarithmic order (N3LL). This is the first resummation at this order for processes involving three colored partons at the Born level. We match our resummation formula to the corresponding fixed-order predictions, extending the validity of our results to regions of the phase space where further hard emissions are present. This result paves the way for the construction of next-to-next-to-leading order simulations for color-singlet plus jet production matched to parton showers in the framework.

Published by the American Physical Society
2024
Transverse energy-energy correlators in the color-glass condensate at the electron-ion collider
Authors: Kang Zhong-Bo , Penttala Jani , Zhao Fanyi , Zhou Yiyu
Published: May 2024

We investigate the transverse energy-energy correlators (TEEC) in the small-x regime at the upcoming Electron-Ion Collider (EIC). Focusing on the back-to-back production of electron-hadron pairs in both ep and eA collisions, we establish a factorization formula given in terms of the hard function, quark distributions, soft functions, and TEEC jet functions, where the gluon saturation effect is incorporated. Numerical results for TEEC in both ep and eA collisions are presented, together with the nuclear modification factor RA. Our analysis reveals that TEEC observables in deep inelastic scattering provide a valuable approach for probing gluon saturation phenomena. Our findings underscore the significance of measuring TEEC at the EIC, emphasizing its efficacy in advancing our understanding of gluon saturation and nuclear modifications in high-energy collisions.

Published by the American Physical Society
2024
Neutron star cooling with lepton-flavor-violating axions
Authors: Zhang Hong-Yi , Hagimoto Ray , Long Andrew J.
Published: May 2024

The cores of dense stars are a powerful laboratory for studying feebly coupled particles such as axions. Some of the strongest constraints on axionlike particles and their couplings to ordinary matter derive from considerations of stellar axion emission. In this work we study the radiation of axionlike particles from degenerate neutron star matter via a lepton-flavor-violating coupling that leads to muon-electron conversion when an axion is emitted. We calculate the axion emission rate per unit volume (emissivity) and by comparing with the rate of neutrino emission, we infer upper limits on the lepton-flavor-violating coupling that are at the level of |gaeμ|≲10−6. For the hotter environment of a supernova, such as SN 1987A, the axion emission rate is enhanced and the limit is stronger, at the level of |gaeμ|≲10−11, competitive with laboratory limits. Interestingly, our derivation of the axion emissivity reveals that axion emission via the lepton-flavor-violating coupling is suppressed relative to the familiar lepton-flavor-preserving channels by the square of the plasma temperature to muon mass ratio, which is responsible for the relatively weaker limits.

Published by the American Physical Society
2024
EFT corrections to scalar and vector quasinormal modes of rapidly rotating black holes
Authors: Miguel Filipe S.
Published: May 2024

Quasinormal modes characterize the final stage of a black hole merger. In this regime, spacetime curvature is high, making these modes effective tools to probe potential corrections to general relativity. In this paper, we utilize the effective field theory framework to compute the leading-order correction to massless scalar and electromagnetic quasinormal modes. Proceeding perturbatively in the size of the effective field theory length scale, we describe a general method to compute the frequencies for Kerr black holes of any spin. In the electromagnetic case, we study both parity even and parity odd effective field theory corrections, and, surprisingly, prove that the two have the same spectrum. Furthermore, we find that, the corrected frequencies separate into two families, corresponding to the two polarizations of light. The corrections pertaining to each family are equal and opposite. Our results are validated through several consistency checks.

Published by the American Physical Society
2024
Investigating peer recognition across an introductory physics sequence: Do first impressions last?
Authors: Sundstrom Meagan , Kageorge Logan
Published: May 2024

Students’ beliefs about the extent to which meaningful others, including their peers, recognize them as a strong science student are correlated with their persistence in science courses and careers. Yet, prior work has found a gender bias in peer recognition, in which student nominations of strong peers disproportionately favor men over women, in some instructional science contexts. Researchers have hypothesized that such a gender bias diminishes over time, as determined by students’ academic year: studies have found a gender bias in peer recognition in science courses aimed at first-year students, but not in science courses aimed at beyond first-year students. This hypothesis that patterns of peer recognition change over time, however, has yet to be tested with longitudinal data—previous studies only examine snapshots of different students in different science courses. In this study, we isolate the effect of time on peer recognition by analyzing student nominations of strong peers across a two-semester introductory physics course sequence, containing the same set of students and the same instructor in both semesters, at a mostly women institution. Using a combination of social network analysis and qualitative methods, we find that while many students receive similar levels of peer recognition over time, the four most highly nominated students—the recognition celebrities—exhibit some change between semesters even in this highly controlled setting. Furthermore, we observe that these changes in the celebrities track closely with changes in student outspokenness and that being outspoken is likely more important for gaining recognition than earning a high grade in the class. These findings lend support to prior work’s hypothesis that peer recognition changes over time, but also challenge the generalizability of previous results (i.e., that patterns of recognition are related to students’ academic year). Instead, peer recognition seems highly sensitive to variables such as individual students’ participation and, therefore, may be course specific. We provide recommendations for both when and how instructors may intervene on peer recognition based on our results.

Published by the American Physical Society
2024
Enhancing peer instruction in physics: Understanding cognitive processes and refining rules
Authors: Gjerde Vegard , Hagane Sivert
Published: May 2024

Peer Instruction gives practice in the abstract language of physics, addresses common misconceptions among students, and is more effective than traditional lecturing. However, it is not clear what makes Peer Instruction effective nor how we might improve the method. An emerging perspective is that what makes Peer Instruction effective is how it stimulates certain cognitive processes. Research also indicates that providing rules for discussion may improve the effect of peer instruction. Hence, we wanted to answer two research questions in this study: (i) What cognitive learning processes occur during peer discussions? (ii) How do students follow discussion rules? To answer our research questions, we recorded and thematically analyzed peer discussions during Peer Instruction in an introductory physics course. The most prevalent cognitive process during peer discussions was decoding the problem. The most prevalent type of explanation was explanations with physics concepts, which usually led the students to an incorrect answer. The next most prevalent type of explanation was explanation with physics models, which usually led the students to the correct answer. The students also explained with reference to their experience or examples—intuitive or analogical explanations—and it usually added little to the conversation, was wrong, or created confusion. Some discussion rules had limited impact, prompting suggestions for rule improvements to optimize Peer Instruction. Our work contributes to the literature on Peer Instruction with a cognitively based description of the learning processes and how we might further improve and ensure the effectiveness of Peer Instruction.

Published by the American Physical Society
2024
Entanglement negativity between separated regions in quantum critical systems
Authors: Parez Gilles , Witczak-Krempa William
Published: May 2024

We study the entanglement between disjoint subregions in quantum critical systems through the lens of the logarithmic negativity. We work with systems in arbitrary dimensions, including conformal field theories and their corresponding lattice Hamiltonians, as well as resonating valence-bond states. At small separations, the logarithmic negativity is big and displays universal behavior, but we show nonperturbatively that it decays faster than any power at large separations. This can already be seen in the minimal setting of single-spin subregions. The corresponding absence of distillable entanglement at large separations generalizes the one-dimensional result, and indicates that quantum critical ground states do not possess long-range bipartite entanglement, at least for bosons. For systems with fermions, a more suitable definition of the logarithmic negativity exists that takes into account fermion parity, and we show that it decays algebraically. Along the way we obtain general results for the moments of the partially transposed density matrix.

Published by the American Physical Society
2024
Quantum catalysis in cavity quantum electrodynamics
Authors: Junior A. de Oliveira , Perarnau-Llobet Martí , Brunner Nicolas , Lipka-Bartosik Patryk
Published: May 2024

Catalysis plays a key role in many scientific areas, most notably in chemistry and biology. Here we present a catalytic process in a paradigmatic quantum optics setup, namely the Jaynes-Cummings model, where an atom interacts with an optical cavity. The atom plays the role of the catalyst, and it allows for the deterministic generation of nonclassical light in the cavity. Considering a cavity prepared in a “classical” coherent state, and choosing appropriately the atomic state and the interaction time, we obtain an evolution with the following properties. First, the state of the cavity has been modified, and it now features nonclassicality, as witnessed by sub-Poissonian statistics or Wigner negativity. Second, the process is catalytic in the sense that the atom is deterministically returned to its initial state exactly, and it can be reused multiple times. What is more, we also show that our findings are robust under dissipation and can be applied to scenarios featuring cavity loss and atomic decay. Finally, we investigate the mechanism of this catalytic process, in particular highlighting the key role of correlations and quantum coherence.

Published by the American Physical Society
2024
Protection of correlation-induced phase instabilities by exceptional susceptibilities
Authors: Reitner M. , Crippa L. , Fus D. R. , Budich J. C. , Toschi A. , Sangiovanni G.
Published: May 2024

At thermal equilibrium, we find that generalized susceptibilities encoding the static physical response properties of Hermitian many-electron systems possess inherent non-Hermitian (NH) matrix symmetries. This leads to the generic occurrence of exceptional points (EPs), i.e., NH spectral degeneracies, in the generalized susceptibilities of prototypical Fermi-Hubbard models, as a function of a single parameter such as chemical potential. We demonstrate that these EPs are necessary to promote correlation-induced thermodynamic instabilities, such as phase separation occurring in the proximity of a Mott transition, to a topologically stable phenomenon.

Published by the American Physical Society
2024