bluuebunny/crossref_metadata_2025 huggingface dataset:
NeoPhAR: Next-generation Phage Therapy for Antimicrobial Resistance
Authors: Rivera-Orellana Sebastián , Yeager Justin , Tejera Eduardo , López-Cortés Andrés
Published: December 2024

Growing antimicrobial resistance (AMR) infections are among the top contemporary concerns in public healthcare systems which can place considerable burdens on healthcare systems. Phage therapy has long been considered a viable option to help combat AMR infections, including on broad geographic scales. One bottleneck in the application of phage therapy is the accurate matching of host-specific phages to bacterial strains, which is traditionally done using molecular techniques. Here we present an open-access deep learning-based model that shows incredible potential to accurately predict phages for therapeutic use. Our goal is to attenuate the matching process so that specific phages, or a cocktail of phages can be prepared for patients with a high probability of therapeutic success, helping to democratize phage therapy treatments even in low to middle-income countries where genomic resources can be limited, costly, or time prohibitive. We feel this is an important first step towards incorporating and applying bioinformatic practices in promising fields such as phage therapy.
The Arp2/3 complex maintains genome integrity and survival of epidermal Langerhans cells
Authors: Delgado Maria-Graciela , Burkhart Ann-Kathrin , Villar Javiera , Amadio Roberto , Racz Vanessa S. , Sanséau Doriane , De Silva Nilushi , Mariano Livia Lacerda , Shmakova Anna , Chipont Anna , San Roman Mabel , Bracchetti Giulia , Calmettes Vincent , Alraies Zahraa , Maurin Mathieu , Dauphin Aurelien , Guerin Coralie , Ginhoux Florent , Manel Nicolas , Fachinetti Daniele , Benvenuti Federica , Iden Sandra , Lennon-Duménil Ana-Maria
Published: December 2024

Myeloid cells use intracellular actin networks for key cellular processes, including cell migration and chemotaxis, phagocytosis or macropinocytosis, as well as immune synapse formation. However, whether these networks play any role in the development and/or survival of myeloid cells in tissues remains open. Here, we found that the Arp2/3 complex, which is responsible for the nucleation of branched actin networks, is needed for thein vivomaintenance of epidermal Langerhans cells (LCs) throughout life. Mice harboring a genetic deletion of the Arpc4 subunit of the complex form LC networks at birth, but these cells decline in numbers following a process reminiscent of premature cellular aging. By combiningin vivoanalyses of LCs within vitroexperiments on bone-marrow-derived dendritic cells, we found that Arpc4-deficient cells manage to progress through the cell cycle but accumulate DNA damage associated with aberrant nuclear shapes and events of nuclear envelope rupture. These results provide the first evidence for a physiological role of Arp2/3 in maintenance of genome integrity and survival of immune cells in tissues.
Auxin fluctuation and PIN polarization in moss leaf cell reprogramming
Authors: Tang Han , Chen Li-Hang , Friml Jiří
Published: December 2024

Auxin and its PIN-FORMED (PIN) exporters are essential for tissue repair and regeneration in flowering plants. To gain insight into the evolution of this mechanism, we investigated their roles in leaves excised fromPhyscomitrium patens, a bryophyte known for its remarkable cell reprogramming capacity. We used various approaches to manipulate auxin levels, including exogenous application, pharmacological manipulations, and auxin biosynthesis mutants. We observed no significant effect on the rate of cell reprogramming. Rather, our analysis of auxin dynamics revealed a decrease in auxin levels upon excision, which was followed by a local increase before the reprogramming process began. Mutant analysis revealed that PpPINs are required for effective cell reprogramming, and endogenously expressed PpPINA-GFP accumulates polarly at sites that will develop into future filamentous stem cells. In addition, hyperpolarized PpPINA variants carrying mutated phosphorylation sites showed a marked delay in reprogramming, whereas endogenous or non-polar versions do not have this effect. These results underscore that both, the levels and the polarity of PpPINA are important for efficient cell reprogramming. Overall, these findings highlight the pivotal role of PIN polarity in plant regeneration. Furthermore, they suggest that understanding polarity mechanisms could have broader implications for improving regenerative processes across various plant species.
JMJD6 and YBX1 physically interact and regulate HOTAIR proximal promoter
Authors: Gupta Aritra , Bhardwaj Siddharth , Desai Kartiki V.
Published: December 2024

In a previous study, we showed JMJD6 interacted with HOTAIR promoter (−123 to -103 bp upstream of TSS, JIR) and augmented its transcription. Maximal JMJD6 mediated induction required (−216 to -123 bp) region.In silicoprediction and ENCODE data suggested that YBX1 could be that potential candidate and in this study the region is designated as YBX1 interacting region (YIR). In breast cancer cell lines, we show that JMJD6 and YBX1 regulate each other’s expression and physically interact with each other when recombinantly expressed, as endogenous proteins and when synthesizedin vitro.Domain mapping indicated that A/P domain of YBX1 interacted with JMJC domain of JMJD6. Luciferase activity of HOTAIR promoter constructs, pHP216 and pHP123, increased in presence of YBX1 in MCF7, Vec and JMJD6 overexpressing JOE cells but was lost in the presence of JMJD6 and YBX1 siRNAs. Interestingly, activity of pHP123 that lacks YIR also decreased upon YBX1 knock out (YKO). Next, by individual JMJD6, YBX1 and ChIP-re-ChIP assays we demonstrate that both proteins co-occupy this promoter region. Further, electrophoretic mobility shift assays showed that YIR probes retarded two complexes, which lost intensity in YKO cells. Interestingly, JIR-protein complex disappeared in YKO cells. Together these data imply that YBX1 not only enhanced promoter activity but may also be involved in JMJD6 recruitment. Taken together, our data proposes that the interaction and positive feed forward loop perpetuated by JMJD6 and YBX1 may culminate in HOTAIR induction, which in turn is known to drive tumor progression.
Type 1 lymphocytes and interferon-γ accumulate in the thalamus and restrict seizure susceptibility after traumatic brain injury
Authors: Mroz Nicholas M. , Ciesielska Agnieszka , Ewing-Crystal Nathan A. , Dorman Leah C. , Han Rafael T. , Barron Jerika J. , Silva Nicholas J. , Molofsky Anna V. , Molofsky Ari B. , Paz Jeanne T.
Published: December 2024

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide and can lead to secondary sequelae such as increased seizure susceptibility. Emerging work suggests that the thalamus, the relay center of the brain that undergoes secondary damage after cortical TBI, is involved with heightened seizure risks after TBI. TBI also induces the recruitment of peripheral immune cells, including T cells, to the site(s) of injury, but it is unclear how these cells impact neurological sequelae post-TBI. Here, we characterize the identities and kinetics of lymphocytic infiltrates into the cortex and thalamus using a mouse model of cortical TBI. We identify a population of IFNγ-producing type 1 lymphocytes that infiltrate specific thalamic subregions over weeks following injury, where they elicit a local IFNγ response in microglia and neuronal subset(s). Depletion of CD4+T cells protects mice from TBI-induced seizure susceptibility by de-repressing other non-CD4+type 1 lymphocytes and disease-associated microglia (DAMs) in the thalamus. Strikingly, we find that a single dose of IFNγ prior to challenge with a proconvulsant agent was sufficient to reduce TBI-induced seizure incidence, severity, and mortality. This work identifies IFNγ as a direct modulator of TBI-associated seizure susceptibility, which could have therapeutic implications for the treatment of TBI patients.
Negative feedback equalizes polarity sites in a multi-budding yeast
Authors: Crocker Alex W. , Petrucco Claudia A. , Guan Kaiyun , Wirshing Alison C.E. , Ekena Joanne L. , Lew Daniel J. , Elston Timothy C. , Gladfelter Amy S.
Published: December 2024

Morphogenesis in fungi and animals is directed by polarization of small GTPases Cdc42 and Rac. In the budding yeastSaccharomyces cerevisiaecompetition between polarity patches results in one polarized patch and the growth of a single bud. Here, we describe cell polarity in the yeastAureobasidium pullulans, which establishes multiple coexisting polarity sites yielding multiple buds during a single cell division cycle. Polarity machinery components oscillate in their abundance in these coexisting sites but do so independently of one another, pointing to a lack of global coupling between sites. Previous theoretical work has demonstrated that negative feedback in a polarity circuit could promote coexistence of multiple polarity sites, and time-delayed negative feedback is known to cause oscillations. We show that both these features of negative feedback depend on a protein we identified as Pak1, and that Pak1 requires Rac1 but not Cdc42 for its localization. This work shows how conserved signaling networks can be modulated for distinct morphogenic programs even within the constraints of fungal budding.
Unraveling genetic mysteries: phenotype-shaping profiles in chronic sarcoidosis
Authors: Kullberg Susanna , Darlington Pernilla , Ellinghaus David , Prasse Antje , Iseda Tomoko , Chuquimia Olga , Eklund Anders , Schreiber Stefan , Müller-Quernheim Joachim , Kockum Ingrid , Wheelock Åsa , Padyukov Leonid , Mirsaeidi Mehdi S. , Spagnolo Paolo , Rivera Natalia V.
Published: December 2024

Background

Sarcoidosis represents a complex inflammatory condition of unknown origin, characterized by diverse clinical profiles, particularly identifiable as Löfgren’s syndrome (LS) and non-LS cases. Delving into the genetic underpinnings of chronic sarcoidosis phenotypes is essential for advancing our understanding and treatment of this disease.

Methods

To classify chronicity, pulmonologists evaluated sarcoidosis phenotypes over a follow-up period of two years, distinguishing between chronic and nonchronic classifications. We assessed the genetics of these chronicity phenotypes in a Swedish cohort of 1,515 sarcoidosis cases (679 nonchronic and 836 chronic) alongside 3,085 controls using the Immunochip array. To confirm our findings, replication analysis was conducted in a German cohort of 1,216 sarcoidosis cases (485 nonchronic and 731 chronic) and 3,042 controls. A comprehensive meta-analysis of significant SNPs (p < 5e-8) was carried out using inverse variance weighting. Additionally, we employed gene-based analysis, enrichment mapping, and pathway analysis to gain deeper functional insights.

Results

Our meta-analysis uncovered significant genetic associations with chronic sarcoidosis phenotypes, including LS nonchronic (rs3135356; OR = 3.13, 95% CI: 2.38 - 4.12), non-LS nonchronic (rs2395162; OR = 2.34, 95% CI: 1.96 - 2.85), and non-LS chronic cases (rs1049550; OR = 0.68, 95% CI: 0.59 - 0.76). Specifically, gene-based analysis revealed thatCLIC1is associated with nonchronic forms, whileANXA11is linked to the chronic phenotype. Our enrichment analysis highlighted the expression of quantitative trait loci (eQTLs) in immune cells, whole blood, and lung tissues. The pathway analysis pinpointed the antigen presentation pathway as vital to understanding chronicity phenotypes.

Conclusions

This study illuminates the distinct genomic features that differentiate chronic sarcoidosis phenotypes, underscoring the critical involvement of immune-related genes and regulatory networks. By advancing the knowledge of sarcoidosis chronicity, these findings pave the way for targeted therapeutic interventions and personalized treatment strategies that can significantly improve patient outcomes.
Coancestry superposed on admixed populations yields measures of relatedness at individual-level resolution
Authors: Chen Danfeng , Storey John D.
Published: December 2024

The admixture model is widely applied to estimate and interpret population structure among individuals. Here we consider a “standard admixture” model that assumes the admixed populations are unrelated and also a generalized model, where the admixed populations themselves are related via coancestry (or covariance) of allele frequencies. The generalized model yields a potentially more realistic and substantially more flexible model that we call “super admixture”. This super admixture model provides a one-to-one mapping in terms of probability moments with the population-level kinship model, the latter of which is a general model of genome-wide relatedness and structure based on identity-by-descent. We introduce a method to estimate the super admixture model that is based on method of moments, does not rely on likelihoods, is computationally efficient, and scales to massive sample sizes. We apply the method to several human data sets and show that the admixed populations are indeed substantially related, implying the proposed method captures a new and important component of evolutionary history and structure in the admixture model. We show that the fitted super admixture model estimates relatedness between all pairs of individuals at a resolution similar to the kinship model. The super admixture model therefore provides a tractable, forward generating probabilistic model of complex structure and relatedness that should be useful in a variety of scenarios.
Induction of Senescence During Postpartum Mammary Gland Involution supports tissue remodeling and promotes postpartum tumorigenesis
Authors: Chiche Aurelie , Charifou Elsa , Djoual Lamia , Wang Shuoyang , Temime Laurianne , Saclier Marielle , Wang Shaoxiang , Chantrel Jeremy , Li Han
Published: December 2024

Cellular senescence is an evolutionarily conserved stress response1, yet its roles during physiological processes remain underexplored2,3. Senescent cells are known to promote tissue repair4,5and suppress tumorigenesis6, but their accumulation contributes to various pathological and physiological processes, including cancer and ageing7–9. However, it is currently unknown whether physiological senescence can be co-opted by oncogenic events to promote tumorigenesis. Postpartum mammary gland involution is a major tissue remodelling event in adulthood10,11, resembling the wound healing process, and is closely linked to postpartum breast cancer (PPBC)12providing a compelling context to investigate this question. Here, we show that senescence is induced in alveolar luminal cells during involution in a p16-dependent manner. Reducing senescent cells hinders tissue remodeling and delays involution, underscoring their physiological importance. However, using a PPBC mouse model where the oncogenic event coincides with involution, we demonstrate that eliminating involution-associated senescent cells markedly extended the cancer latency. Mechanistically, we reveal that senescent cells enhance tumor-initiating cell plasticity in a paracrine manner, promoting tumor invasion and metastasis. Collectively, our findings uncover a dual role of senescence in mediating postpartum tissue remodeling and promoting tumorigenesis, highlighting a scenario where physiological senescence is hijacked to drive cancer progression. This work underscores that senescence might be a unifying mechanism linking tissue repair to tumorigenesis.
Can we infer excitation-inhibition balance from the spectrum of population activity?
Authors: Chakravarty Kingshuk , Roy Sangheeta , Sinha Aniruddha , Kumar Arvind
Published: December 2024

Networks in the brain operate in an excitation-inhibition (EI) balanced state. Altered EI balance underlies aberrant dynamics and impaired information processing. Given its importance, it is crucial to establish non-invasive measures of the EI balances. Previous studies have suggested that relative EI balance can be inferred from the spectrum of the population signals such as Local Field Potentials, Electroencephalogram and Magnetoencephalography. This idea exploits the fact that in most cases excitatory and inhibitory synapses have quite different time constants. However, it is not clear to what extent spectral slope of population activity is related to the network parameters that define the EI balance e.g. excitatory and inhibitory conductance. To address this question we simulated two different types of recurrent networks and measured spectral slope for a wide range of parameters. Our results show that the slope of the spectrum cannot predict the ratio of excitatory and inhibitory synaptic conductance. Only in a small set of simulations a change in the spectral slope was consistent with the corresponding change in the synaptic weights or inputs to the network. Thus, our results show that we should be careful in interpreting the change in the slope of the population activity spectrum.

Significant statement

Non-invasive signals such as electroencephalogram (EEG) and magneto-encephalogram (MEG) are routine acquired from human subjects in different functional and dysfunctional states. It is of great interest to relate properties of EEG/MEG to the underlying physiology and network properties. In this regard, recently it was proposed that the slope of the EEG/MEG spectrum can be related to excitation-inhibition balance: steeper slopes indicate higher inhibition. Here we show that such an explanation holds only for a small set of conditions. In most cases spectral slope is not informative of underlying excitation-inhibition balance. Thus, we argue that while spectral slope may be a good biomarker of brain state, it is not informative about the underlying excitation-inhibition balance or network parameters.
Evaluation of Immunopharmacological Efficacy of LiveLeishmania donovaniOverexpressing Ld_ζ1domainfor Protection Against Experimental Human Visceral Leishmaniasis
Authors: Bansal Ruby , Shafi Sadat , Garg Prachi , Srivastava Aakriti , Garg Swati , Jha Neha , Singhal Jhalak , Deethamvali Ghouse Peer Gajala , Pati Pandey Ramendra , Basu Subhajit , Singh Shailja
Published: December 2024

Objective

To evaluate the efficacy and immunogenicity of the zeta domain over-expressingLeishmania donovani(Ld_ζ1domain) as a vaccination candidate against visceral leishmaniasis (VL).

Methods

In this study,Leishmaniaoverexpressor Ld_ζ1domain(OE) were transformed by electroporation using a GFP-tagged Ld_ζ1domainrecombinant plasmid. The resulting overexpressing cells were analysedin vitroto assess their growth dynamics and infectivity. We also investigated the immune-protective potential of these overexpressor in a mouse model challenged withLeishmania donovani. The immune response, including Th1 and Th2 pathways, was thoroughly characterized using RT-PCR and ELISA assays. In addition, the study conducted a thorough evaluation of the mouse’s spleen and liver parasites, as well as quantitative evaluation of tissue pathological changes.

Results

Ld_ζ1domain(OE) parasites exhibited significantly lower viability and replication rates than WT parasites, andin vivostudies showed that mice immunized with the Ld_ζ1(OE)domainhad lower parasite numbers than mice infected with LdWT. Spleen and liver showed significant histological changes suggestive of protection. Parasite burden in the spleen and liver of vaccinated mice were significantly reduced. The immune response showed increased IFN-γ levels and lower IL-10 production, resulting in a greater IFN-γ/IL-10 ratio, indicating parasite elimination. The vaccination also caused a significant IgG humoral response and increased nitric oxide production in immunized mice.

Conclusion

Our findings demonstrated that overexpressing the zeta toxin resulted in controlled parasite attenuation, lowering pathogenicity while retaining immunogenic features. Our work established the zeta over-expressor’s protective efficacy, immunogenicity, and proliferation in response to aLeishmaniachallengein vitroandin vivo. This preliminary prototype study suggested that Ld_ζ1domain(OE) parasites may be suitable for developing an attenuated vaccine against leishmaniasis.

Graphical representation

A schematic representation on the protective effectiveness, immunogenicity, and proliferation of the zeta over-expressor in response toLeishmaniachallengein vitroandin vivomodel.
Development of a monoclonal antibody against duck IFN-γ protein and the application for Intracellular Cytokine Staining
Authors: Chen Yingyi , Song Wei , Chen Junqiang , Jin Chenyang , Lin Jiewei , Liao Ming , Dai Manman
Published: December 2024

ABSTRACT

Interferon-γ (IFN-γ), a member of the type II IFN family, is a crucial cytokine in the immune system and serves as an important indicator of immune response. Intracellular Cytokine Staining (ICS) is a technique used to analyze the production of cytokines within individual cells, and it has a wide range of applications in the fields of immunological monitoring, vaccine trials, and the study of infectious diseases. This study aimed to prepare monoclonal antibodies against duck IFN-γ protein and to establish an ICS protocol for detecting the duck IFN-γ protein. The duIFN-γ-His or duIFN-γ-Fc gene was cloned into the pEE12.4 expression vector and expressed as a recombinant protein of size 20.2 KDa or 54.9 KDa in 293F cells. The purified recombinant proteins were inoculated into BALB/c mice to generate splenic lymphocytes capable of secreting anti-duIFN-γ antibodies, and hybridoma cells were obtained after fusion with SP2/0 cells. A new hybridoma cell line named 24H4, which stably secreted IgG3 κ subtype antibody against duck IFN-γ. This monoclonal antibody (mAb) was identified by Western Blot to recognize duck IFN-γ antibodies, and the indirect ELISA results showed that its ability to recognize IFN-γ protein reached 0.001 μg/ml. The established ICS method was used to stain PBMCs after ConA stimulation, and duck IFN-γ protein was successfully detected by flow cytometry, indicating that the ICS method was successfully established. This study we use the monoclonal antibody, 24H4, provides a crucial tool for subsequent research on duck cellular immune responses.
Diversity of set-related neuronal activity in the dorsal premotor cortex of monkeys during a path-planning task
Authors: Sakamoto Kazuhiro , Saito Naohiro , Mushiake Hajime
Published: December 2024

Actions involve multiple levels. The dorsal premotor area (PMd) of the primate cerebral cortex is involved in the preparation of actions based on perceptual information. In this study, we recorded neuronal activity from the PMd of monkeys while they performed a path-finding task. In the task, the animals were required to move a cursor step by step to a goal in a maze-like display, and the arm movement and the direction of the cursor operation were dissociated. We observed neurons involved in the preparation of a single arm movement and neurons involved in the preparation of a single cursor operation. Cursor operation-related neurons were also obtained from the lateral prefrontal cortex (lPFC), but the PMd neurons showed more preparatory properties during the execution period than the lPFC neurons. Furthermore, we found neurons involved in the preparation of a specific sequence of cursor movements. The PMd included not only all types of single-shot preparatory neurons but also preparatory neurons for a variety of complex sequences for arm movements and cursor manipulation. These results suggest that the PMd contains diverse neurons involved in different levels of action preparation. Such diversity is one of the critical neural bases for robust goal-directed behavior in complex environments.

Significance

There are different levels in actions. The dorsal premotor cortex (PMd) is involved in the preparation of actions based on perceptual information. Here, we recorded neuronal activity from the PM d of monkeys while performing a path-finding task, i.e., moving a cursor step by step to a goal in a maze-like display. In addition to neurons involved in the preparation of a single arm movement and neurons involved in the preparation of a single cursor operation, cells involved in the preparation of a specific sequence of cursor movements were observed. These results suggest that the PMd contains diverse neurons involved in different levels of action preparation. Such diversity is one of the critical neural bases for robust goal-directed behavior in complex environments.
Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity
Authors: Mancl Jordan M. , Liang Wenguang G. , Bayhi Nicholas L. , Wei Hui , Carragher Bridget , Potter Clinton S. , Tang Wei-Jen
Published: December 2024

Insulin degrading enzyme (IDE) is a dimeric 110 kDa M16A zinc metalloprotease that degrades amyloidogenic peptides diverse in shape and sequence, including insulin, amylin, and amyloid-β, to prevent toxic amyloid fibril formation. IDE has a hollow catalytic chamber formed by four homologous subdomains organized into two ∼55 kDa N- and C-domains (IDE-N and IDE-C, respectively), in which peptides bind, unfold, and are repositioned for proteolysis. IDE is known to transition between a closed state, poised for catalysis, and an open state, able to release cleavage products and bind new substrate. Here, we present five cryoEM structures of the IDE dimer at 3.0-4.1 Å resolution, obtained in the presence of a sub-saturating concentration of insulin. Analysis of the heterogeneity within the particle populations comprising these structures combined with all-atom molecular dynamics (MD) simulations permitted a comprehensive characterization of IDE conformational dynamics. Our analysis identified the structural basis and key residues for these dynamics that were not revealed by IDE static structures. Notably arginine-668 serves as a molecular latch mediating the open-close transition and facilitates key protein motions through charge-swapping interactions at the IDE-N/C interface. Our size-exclusion chromatography-coupled small-angle X-ray scattering and enzymatic assays of an arginine-668 to alanine mutant indicate a profound alteration of conformational dynamics and catalytic activity. Taken together, this work highlights the power of integrating experimental and computational methodologies to understand protein dynamics, offers the molecular basis of unfoldase activity of IDE, and provides a new path forward towards the development of substrate-specific modulators of IDE activity.
Exploring the Boundaries of Medulloblastoma Subgroups with Synthetic Data Generation
Authors: Prol-Castelo Guillermo , Tejada-Lapuerta Alejandro , Urda-García Beatriz , Núñez-Carpintero Iker , Valencia Alfonso , Cirillo Davide
Published: December 2024

Medulloblastoma is a childhood brain tumor traditionally classified into four molecular subgroups. Recent evidence suggests that Groups 3 and 4 represent a biological continuum rather than distinct entities, a paradigm shift with significant implications for understanding disease biology and treatment strategies. Nevertheless, assessing this hypothesis is challenging mainly due to data scarcity. In this study, we utilize transcriptomics data to provide evidence supporting the existence of an intermediate subgroup between Groups 3 and 4 with distinct molecular features. Leveraging synthetic data generation with a Variational Autoencoder, we address data scarcity limitations effectively. Our findings are corroborated by prior studies employing different methodologies and datasets, further reinforcing the robustness of our results. Additionally, we apply explainability techniques to the VAE, uncovering key relationships between gene expression and disease subgroups. This study demonstrates the potential of synthetic data generation to refine rare disease subtyping and advance our understanding of the underlying biological mechanisms.
E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells
Authors: Oguh Alexis U. , Haemmerle Matthew W. , Sen Sabyasachi , Rozo Andrea V. , Shrestha Shristi , Cartailler Jean-Philippe , Fazelinia Hossein , Ding Hua , Preza Sam , Yang Juxiang , Yang Xiaodun , Sussel Lori , Alvarez-Dominguez Juan R. , Doliba Nicolai , Spruce Lynn A. , Arrojo e Drigo Rafael , Stoffers Doris A.
Published: December 2024

The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specificSpopdeletion mouse strain (SpopβKO) and found thatSpopis necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux. Integration of proteomic, TF-regulatory gene network, and biochemical analyses identified XBP1 as a functionally important SPOP substrate in pancreatic β cells. Furthermore, loss of SPOP strengthened the IRE1α–XBP1 axis of unfolded protein response (UPR) signaling. ER stress promoted proteasomal degradation of SPOP, supporting a model whereby SPOP fine-tunes XBP1 activation during the UPR. These results position SPOP as a regulator of β-cell function and proper UPR activation.
Interpretation of the horizontal beam response near the third integer resonance
Authors: Cortés García E. C. , Niedermayer P. , Singh R. , Taylor R. , Feldmeier E. , Hun M. , Benedetto E. , Haberer T.
Published: December 2024

The beam response to an external periodic excitation delivers relevant information about the optics, tune distribution, and stability of a circulating beam in a storage ring. In this contribution, the horizontal beam response to the excitation (transfer function) under conditions typical for slow extraction is presented for a coasting beam. The resulting spectrum exhibits a splitting behavior. The single particle dynamics is discussed and an interpretation based on the simulation results is presented.

Published by the American Physical Society
2024
Quantum Monte Carlo study of the phase diagram of the two-dimensional uniform electron liquid
Authors: Azadi Sam , Drummond N. D. , Vinko Sam M.
Published: December 2024

We present a study of spin-unpolarized and spin-polarized two-dimensional uniform electron liquids using variational and diffusion quantum Monte Carlo (VMC and DMC) methods with Slater-Jastrow-backflow trial wave functions. Ground-state VMC and DMC energies are obtained in the density range 1≤rs≤40. Single-particle and many-body finite-size errors are corrected using canonical-ensemble twist-averaged boundary conditions and extrapolation of twist-averaged energies to the thermodynamic limit of infinite system size. System-size-dependent errors in Slater-Jastrow-backflow DMC energies caused by partially converged VMC energy minimization calculations are discussed. We find that, for 1≤rs≤5, optimizing the backflow function at each twist lowers the twist-averaged DMC energy at finite system size. However, nonsystematic system-size-dependent effects remain in the DMC energies, which can be partially removed by extrapolation from multiple finite system sizes to infinite system size. The DMC energies in the thermodynamic limit are used to parametrize a local spin density approximation correlation functional for inhomogeneous electron systems. Our zero-temperature phase diagram shows a single transition from a paramagnetic fluid to a hexagonal Wigner crystal at rs=35(1), with no region of stability for a ferromagnetic fluid.

Published by the American Physical Society
2024
Light-controlled terahertz plasmonic time-varying media: Momentum gaps, entangled plasmon pairs, and pulse-induced time reversal
Authors: Kiselev Egor I. , Pan Yiming , Lindner Netanel H.
Published: December 2024

This Letter establishes a Floquet engineering framework in which coherent high frequency light with a time dependent amplitude can be used to parametrically excite and amplify THz plasmons, mirror plasmonic wave packets in time, and generate momentum-gapped plasmonic band structures, entangled plasmon pairs, and THz radiation in two dimensional Dirac systems. Our results show how low frequency plasmons can be coherently excited and manipulated without the need for THz light.

Published by the American Physical Society
2024
Gravitational tensor-monopole moment of the hydrogen atom to order
O(α)
Authors: Ji Xiangdong , Yang Jinghong , Liu Yizhuang
Published: December 2024

We calculate the gravitational tensor-monopole moment of the momentum-current density Tij in the ground state of the hydrogen atom to order O(α) in quantum electrodynamics (QED). The result is τH/τ0−1=4α3π(lnα2−0.028)=−3.06×10−2 where τ0=ℏ2/4me is the leading-order moment. The physics of the next-to-leading-order correction is similar to that of the famous Lamb shift for energy levels.

Published by the American Physical Society
2024
Neutral pion to two-photons transition form factor revisited
Authors: Sultan M. Atif , Kang Jiayin , Bashir Adnan , Chang Lei
Published: December 2024

Based upon a combined formalism of Schwinger-Dyson and Bethe-Salpeter equations in quantum chromodynamics (QCD), we propose a QCD-kindred algebraic model for the dressed quark propagator, for the Bethe-Salpeter amplitude of the pion and the electromagnetic quark-photon interaction vertex. We then compute the γ*π0γ transition form factor Gγ*π0γ(Q2) for a wide range of photon momentum transfer squared Q2. The quark propagator is expanded out in its perturbative functional form but with dynamically generated dressed quark mass. It has complex conjugate pole singularities in the complex-momentum plane, which is motivated by the solution of the quark gap equation with rainbow-ladder truncation of the infinite set of Schwinger-Dyson equations. This complex pole singularity structure of the quark propagator can be associated with a signal of confinement, which prevents quarks from becoming stable asymptotic states. The Bethe-Salpeter amplitude is expressed without a spectral density function, which encapsulates its low- and large-momentum behavior. The QCD evolution of the distribution amplitude is also incorporated into our model through the direct implementation of Efremov-Radyushkin-Brodsky-Lepage evolution equations. We include the effects of the quark anomalous magnetic moment in the description of the quark-photon vertex, whose infrared enhancement is known to dictate hadronic properties. Once the QCD-kindred model is constructed, we calculate the form factor Gγ*π0γ(Q2) and find it consistent with direct QCD-based studies, as well as most available experimental data. It slightly exceeds the conformal limit for large Q2, which might be attributed to the scaling violations in QCD. The associated interaction radius and neutral pion decay width turn out to be compatible with experimental data.

Published by the American Physical Society
2024
Roles of the scalar
f0(500)
and
f0(980)
in the process
D0→π0π0K¯0
Authors: Zhang Xiao-Hui , Zhang Han , Ke Bai-Cian , Liu Li-Juan , Li De-Min , Wang En
Published: December 2024

Motivated by the near-threshold enhancement and the dip structure around 1 GeV in the π0π0 invariant mass distribution of the process D0→π0π0K¯0 observed by the CLEO Collaboration, we have investigated this process by taking into account the contribution from the S-wave pseudoscalar meson–pseudoscalar meson interactions within the chiral unitary approach, and also the one from the intermediate resonance K¯*(892). Our results are in good agreement with the CLEO measurements, which implies that the near-threshold enhancement near the

π

0

π

0

threshold is mainly due to the contributions from the scalar meson f0(500) and the intermediate K¯*, and the cusp structure around 1 GeV in the π0π0 invariant mass distribution should be associated with the scalar meson f0(980).

Published by the American Physical Society
2024
Femtoscopy correlation functions and mass distributions from production experiments
Authors: Albaladejo M. , Feijoo A. , Nieves J. , Oset E. , Vidaña I.
Published: December 2024

We discuss the relation between the Koonin-Pratt femtoscopic correlation function (CF) and invariant mass distributions from production experiments. We show that the equivalence is total for a zero source-size and that a Gaussian finite-size source provides a form-factor for the virtual production of the particles. Motivated by this remarkable relationship, we study an alternative method to the Koonin-Pratt formula, which connects the evaluation of the CF directly with the production mechanisms. The differences arise mostly from the T–matrix quadratic terms and increase with the source size. We study the case of the D0D*+ and D+D*0 correlation functions of interest to unravel the dynamics of the exotic Tcc(3875)+, and find that these differences become quite sizable already for 1 fm sources. We nevertheless conclude that the lack of coherence in high-multiplicity-event reactions and in the creation of the fire-ball source that emits the hadrons certainly make much more realistic the formalism based on the Koonin-Pratt equation. We finally derive an improved Lednicky-Lyuboshits (LL) approach, which implements a Lorentz ultraviolet regulator that corrects the pathological behavior of the LL CF in the punctual source-size limit.

Published by the American Physical Society
2024
Double pion photoproduction off nucleons in covariant chiral perturbation theory
Authors: Kang Kai-Ge , Cao Xiong-Hui , Yao De-Liang , Zheng Han-Qing
Published: December 2024

The double pion photoproduction off nucleons near threshold is analyzed in a covariant baryon chiral perturbation theory up to next to leading order, where the Δ(1232), N*(1400), and ρ(770) resonances are included as explicit degrees of freedom. For the process γp→π+π0n, the chiral results of total cross sections, invariant-mass distributions, and beam-helicity asymmetry are in good agreement with the experimental data within uncertainties. For the process γp→π0π0p, the prediction of total cross section deviates from the existing experimental data. Once the final-state interaction of ππ in the isoscalar S-wave channel is taken into account, a good description of the cross section is achieved. The effect of the Roper resonance always turns out be negligible, and hence can be thrown away in future study of this process.

Published by the American Physical Society
2024
Exploring observable effects of scalar operators beyond SMEFT in the angular distribution of
B→K*0τ+τ−
Authors: Karmakar Siddhartha , Dighe Amol
Published: December 2024

The SU(2)L×U(1)Y invariance of the Standard Model effective field theory (SMEFT) imposes relations among different low-energy effective field theory Wilson coefficients (WCs), any deviations from which would signal the presence of physics beyond SMEFT. In this work, we investigate two such relations (CS=−CP, CS′=CP′) among the scalar and the pseudoscalar new physics WCs that can contribute to b→sττ processes. We show that, even when new physics violating these relations would not be measurable in the branching ratios of Bs→τ+τ− and B→K(*)τ+τ− at HL-LHC and FCC-ee, it can still manifest itself in the angular distribution of B→K*0τ+τ−. We identify the combinations of angular observables in this decay channel that are sensitive to scenarios beyond SMEFT. We find that the two observables S6c and A7, and their combination, have the potential to identify physics beyond SMEFT.

Published by the American Physical Society
2024
High-energy neutrino signals from supernova explosions: A new window into dark photon parameter space
Authors: Syvolap Vsevolod , Ruchayskiy Oleg
Published: December 2024

Dark photons, hypothetical feebly interacting massive vector bosons, appear in many extensions of the Standard Model. This study investigates their production and subsequent decay during supernova explosions. We demonstrate that the decay of dark photons, with masses ranging from 200 to 400 MeV, can lead to the emission of neutrinos with energies surpassing those emitted by supernovae. These neutrinos therefore serve as a distinct signal of new physics, allowing for the exploration of previously uncharted regions of the dark photon parameter space and complementing both accelerator-based searches and other astrophysical constraints. The signal is largely unaffected by the specifics of the supernova’s temperature and density radial profiles outside the SN core. Our results indicate that searching for high-energy neutrinos accompanying supernova explosions provides a novel approach to probe physics beyond the Standard Model, including dark photons, heavy neutral leptons, and other feebly interacting particles with masses in the hundreds of MeV range.

Published by the American Physical Society
2024
Collective coordinate fix in the path integral
Authors: Bhattacharya Arindam , Cotler Jordan , Dersy Aurélien , Schwartz Matthew D.
Published: December 2024

Collective coordinates are frequently employed in path integrals to manage divergences caused by fluctuations around saddle points that align with classical symmetries. These coordinates parametrize a manifold of zero modes and more broadly provide judicious coordinates on the space of fields. However, changing from local coordinates around a saddle point to more global collective coordinates is remarkably subtle. The main complication is that the mapping from local coordinates to collective coordinates is generically multivalued. Consequently one is forced to either restrict the domain of path integral in a delicate way, or otherwise correct for the multivaluedness by dividing the path integral by certain intersection numbers. We provide a careful treatment of how to fix collective coordinates while accounting for these intersection numbers, and then demonstrate the importance of the fix for free theories. We also provide a detailed study of the fix for interacting theories and show that the contributions of higher intersections to the path integral can be nonperturbatively suppressed. Using a variety of examples ranging from single-particle quantum mechanics to quantum field theory, we explain and resolve various pitfalls in the implementation of collective coordinates.

Published by the American Physical Society
2024
Consistency of Lorentz-violating Yang-Mills theories: Gauge invariance and nonperturbative effects
Authors: Pereira Antonio D.
Published: December 2024

Previous investigations on the renormalizability properties of Lorentz-violating Yang-Mills (LVYM) theories in the Landau gauge have pointed out the necessity of the inclusion of a masslike term for the gauge fields. If one aims at generalizing the theory to a more complicated gauge, such a masslike term can bring severe issues regarding gauge dependence of correlation functions of observables. We propose a Lorentz-violating Yang-Mills theory supplemented by a gauge-invariant mass term which generalizes the model in the Landau gauge. We discuss the foundational aspects of the model and highlight how it simplifies in the Landau gauge. Following the recent literature in pure Yang-Mills theories, we remark how the proposed massive extension of LVYM theories can be used as an effective model to access infrared properties within perturbation theory. Finally, we present a Becchi-Rouet-Stora-Tyutin-invariant formulation of the so-called refined Gribov-Zwanziger action in the presence of Lorentz-violating terms in linear covariant gauges and the underlying tree-level gauge-field propagator which is enriched by the nonperturbative information carried by the elimination of Gribov copies.

Published by the American Physical Society
2024
Categorical symmetry of the standard model from gravitational anomaly
Authors: Putrov Pavel , Wang Juven
Published: December 2024

In the Standard Model, some combination of the baryon B and lepton L number symmetry is free of mixed anomalies with strong and electroweak su(3)×su(2)×u(1)Y˜ gauge forces. However, it can still suffer from a mixed gravitational anomaly, hypothetically pertinent to leptogenesis in the very early Universe. This happens when the total “sterile right-handed” neutrino number nνR is not equal to the family number Nf. Thus, the invertible B−L symmetry current conservation can be violated quantum mechanically by gravitational backgrounds such as gravitational instantons. Specifically, we show that a noninvertible categorical B−L generalized symmetry still survives in gravitational backgrounds. In general, we propose a construction of noninvertible symmetry charge operators as topological defects derived from invertible anomalous symmetries that suffer from mixed gravitational anomalies. Examples include the perturbative local and nonperturbative global anomalies classified by Z and Z16, respectively. For this construction, we utilize the anomaly inflow bulk-boundary correspondence, the 4D Pontryagin class and the gravitational Chern-Simons 3-form, the 3D Witten-Reshetikhin-Turaev-type topological quantum field theory with a framing anomaly corresponding to a 2D rational conformal field theory with an appropriate rational chiral central charge, and the 4D Z4TF-time-reversal symmetric topological superconductor with 3D boundary topological order.

Published by the American Physical Society
2024
Finite-temperature instantons from first principles
Authors: Steingasser Thomas , König Morgane , Kaiser David I.
Published: December 2024

We derive the finite-temperature quantum-tunneling rate from first principles. The tunneling rate depends on both temperature and time. We demonstrate that the relevant instantons should, therefore, be defined on a Keldysh-Schwinger contour, and we discuss how the familiar Euclidean time result arises from the limit of large physical times. We identify distinct behavior in the high- and low-temperature limits, incorporating effects from background fields. We construct a consistent perturbative scheme that incorporates large finite-temperature effects.

Published by the American Physical Society
2024
Critical fluctuations at a finite-time dynamical phase transition
Authors: Vadakkayil Nalina , Esposito Massimiliano , Meibohm Jan
Published: December 2024

We explore the critical properties of the recently discovered finite-time dynamical phase transition in the nonequilibrium relaxation of Ising magnets after a temperature quench. The transition is characterized by a sudden switch in the relaxation dynamics and it occurs at a sharp critical time. While previous works have focused either on mean-field interactions or on investigating the critical time, we analyze the critical fluctuations at the phase transition in the nearest-neighbor Ising model on a square lattice using Monte Carlo simulations. By means of a finite-size scaling analysis, we extract the critical exponents for the transition. In two spatial dimensions, we find that the exponents are consistent with those of the two-dimensional Ising universality class when the system is initially in the vicinity of the critical point. For initial temperatures below the critical one, however, the critical exponents differ from the Ising-exponents, indicating a distinct dynamical critical phenomenon.

Published by the American Physical Society
2024