bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritable viral symbionts in the familyIflaviridaeare widespread among aphids
Authors: Rozo-Lopez Paula , Torres Vanesa , Torres Joseph , Käfer Simon , Parker Benjamin J.
Published: February 2025

Abstract

Heritable microbes shape host phenotypes and are important drivers of evolution. While interactions between insects and bacterial symbionts have been extensively studied, the prevalence and consequences of insect-viral symbiosis are an open question. We show that viral symbionts in the familyIflaviridaeare widespread among aphids, an important model for research on bacterial symbiosis. We discovered multiple new species of iflaviruses that are maintained in asexual lines without apparent fitness costs and are transmitted vertically from mothers to offspring. Using field data and phylogenetic evidence, we further show that aphid iflaviruses likely move horizontally across species, but through laboratory experiments, we demonstrated that horizontal transfer among species infesting the same host plants does not persist throughout clonal lineages. Using quantitative PCR and immunohistochemistry, we discovered that viral infections localize in the host fat bodies and developing embryos. Surprisingly, we also found viral infections inside bacteria-housing cells called bacteriocytes, with a positive correlation between viral and bacterial symbiont density, indicating a mechanism for vertical transmission. Together, our work suggests that iflaviruses are an important but previously unrecognized piece of aphid symbiosis and sets the stage to use this model to answer new questions about host-microbe associations.

Importance

In recent years, the rise of metatranscriptome sequencing has led to the rapid discovery of novel viral sequences in insects. However, few studies have carefully investigated the dynamics of insect-virus interactions to produce a general understanding of viral symbiosis. Aphids are a significant agricultural pest but also an important model for understanding the evolution of host-microbe interactions and the molecular basis of bacterial symbiosis. We show that heritable iflaviruses are an important but previously unrecognized part of the aphid heritable microbiome, with viral symbionts transmitted alongside bacteria from mothers to offspring, potentially via specialized bacteriocytes that house symbiotic microbes. Our findings have important implications for furthering the understanding of insect-microbe symbiosis and the potential for biocontrol of agriculturally relevant pest species.
“Nobody has ever spoken to me about PCD and fertility issues”: Fertility experiences of people with primary ciliary dyskinesia and their family caregivers
Authors: Schreck Leonie D , Meyer Sophie , Pedersen Eva SL , Lam Yin Ting , Silberschmidt Hansruedi , Bellu Sara ,   Living with PCD patient advisory group, Zambrano Sofía C , Kuehni Claudia E , Goutaki Myrofora
Published: February 2025

Background

Primary ciliary dyskinesia (PCD) affects fertility in both women and men. To understand the impact and concerns among people with PCD and parents of affected children (family caregivers), we explored how they report their experiences with fertility.

Methods

We used qualitative data from a questionnaire on fertility fromLiving with PCD, an international participatory study. In optional open-ended comment fields, participants shared their thoughts and experiences related to fertility. We adopted conventional content analysis and analysed the data inductively.

Results

We identified five categories illustrating participants’ experiences with fertility: Challenging experiences of fertility care, PCD-related reproductive concerns, non-PCD-related factors complicating fertility, psychological impact of infertility, and family caregivers as gatekeepers of fertility information.

Conclusion

We need enhanced support and standardised reproductive counselling and health care for people with PCD to enable informed decisions on fertility, and to reduce the fertility related concerns and psychological impact faced by many.

Highlights

– People with primary ciliary dyskinesia (PCD) had challenging fertility experiences

– Impact of PCD on pregnancy and disease heritability were causes for concern

– Other reasons not related to PCD but affecting fertility complicated the journey

– Infertility as an emotionally difficult topic strongly impacted participants’ lives

– Family caregivers acted as gatekeepers for fertility information of their children
Characterization of isolated human astrocytes from aging brain
Authors: Serrano Geidy E. , Aslam Sidra , Walker Jessica E. , Piras Ignazio S. , Huentelman Matthew J. , Arce Richard A. , Glass Michael J. , Intorcia Anthony J. , Suszczewicz Katsuko E. , Borja Claryssa I. , Cline Madison P. , Qiji Sanaria H , Lorenzini Ileana , Beh Suet Theng , Mariner Monica , Krupp Addison , McHattie Rylee , Shull Anissa , Wermager Zekiel R , Beach Thomas G.
Published: February 2025

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance and responding to injury and repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading to imbalances in the brain’s internal milieu that eventually impact neuronal function and leads to neurodegeneration. Until now most of the evidence of astrocytic dysfunction in aging has come from experiments done with whole tissue homogenates, astrocytes collected by laser capture or cell cultures derived from animal models or cell lines. In this study we used postmortem-derived whole cells sorted with anti-GFAP antibodies to compare the unbiased, whole-transcriptomes of human astrocytes from control, older non-impaired individuals and subjects with different neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (ADD) and progressive supranuclear palsy (PSP). We found hundreds of dysregulated genes between disease and control astrocytes. In addition, we identified numerous genes shared between these common neurodegenerative disorders that are similarly dysregulated; in particular, UBC a gene for ubiquitin, which is a protein integral to cellular homeostasis and critically important in regulating function and outcomes of proteins under cellular stress, was upregulated in PSP, PD, and ADD when compared to control.
BarQC: Quality Control and Preprocessing for SPLiT-Seq Data
Authors: Rossello Maria , Tandonnet Sophie , Almudi Isabel
Published: February 2025

SPLiT-seq is a cost-effective single-cell RNA-sequencing method, easy to implement in most laboratories. However, the data preprocessing is not straightforward, and no solution currently exists to perform a basic quality control of the data. Here, we present BarQC, a quality control tool, which identifies and corrects barcodes in SPLiT-seq data and provides a report on the distribution of each barcode and UMI as well as an estimation of the number of cells present in the data. Additionally, BarQC can be incorporated in the preprocessing pipeline by constructing a sorted BAM file tagged with each barcode sequence.

Availability of Implementation

BarQC was implemented in Python3, and its source code is freely available on GitHub athttps://github.com/mayflylab/barQC/under the MIT Licence. BarQC has been tested on a Linux server.
A wireless, 60-channel, AI-enabled neurostimulation platform
Authors: Rizzuto Daniel S. , Hu Zhe , Utin Daniel , Kahn Joshua , Ho Chris , Smiles Andrew , Gross Robert E. , Lega Bradley C. , Das Sandhitsu R. , Kahana Michael J.
Published: February 2025

Electrical stimulation of the human brain has emerged as a powerful therapeutic modality, enabling the alteration of neural circuits underlying cognition and behavior. Recent evidence indicates that stimulation’s effects on physiology and behavior depend on endogenous variation in brain state, as measured by field-potential recordings. Here, we describe a 60-channel brain-computer interface – the Smart Neurostimulation System (SNS) – that combines closed-loop analysis of spectral features of the field potential with multi-channel stimulation capabilities. We demonstrate system functionality via bench tests and from anin vivoovine study exercising a subset of the device’s functionality. Our ovine study shows that the SNS can reliably measure neural correlates of behavior (motion) and the physiological effects of stimulation. We demonstrate the safety of stimulation via histology following a 120-day stimulation study.
A single low-dimensional neural component of motor unit activity explains force generation across repetitive isometric tasks
Authors: Cabral Hélio V. , Inglis J. Greig , Pourreza Elmira , Dos Santos Milena A. , Cosentino Caterina , O’Reilly David , Delis Ioannis , Negro Francesco
Published: February 2025

Previous studies suggest that low-dimensional control underlies motor unit activity, with low-frequency oscillations in common synaptic inputs serving as the primary determinant of muscle force production. In this study, we used principal component analysis (PCA) and factor analysis (FA) to investigate the relationship between low-dimensional motor unit components and force oscillations during repetitive isometric tasks with similar force profiles. We assessed the consistency of these components across trials in both individual (tibialis anterior; first dorsal interosseous) and synergistic muscles (vastus medialis, VM; vastus lateralis, VL). Participants performed 15 trials of a force-matching learning task. Three post-skill acquisition trials were selected for analysis to ensure high similarity in force profiles. Motor units were decomposed from high-density surface electromyograms, tracked across trials, and their smoothed discharge rates were decomposed into low-dimensional components using PCA and FA. Parallel analysis indicated that a single component could explain the smoothed discharge rates for the individual muscles and two components for VM-VL. Importantly, the first component explained most of the variance (∼70%) in smoothed discharge rates across all muscles. The first motor unit component also showed significantly higher correlations with force oscillations than the second component and remained highly consistent across trials. These findings were further supported by a non-linear framework combining network- and information-theoretic tools, which revealed high motor unit network density in the first component of all muscles. Collectively, these results suggest that, during isometric contractions, motor unit activity is primarily controlled by a single dominant shared synaptic input that closely mirrors force oscillations.
Protocol of the study for Setting up of a system for “Medical Certification of Cause of Death” for non-institutional deaths in a selected area of a Taluk of Kolar district, Karnataka, India: feasibility and validity
Authors: Madhusudan M , Sukanya R , Vaitheeswaran K
Published: February 2025

Rationale

The current coverage of “Medical Certification of Cause of Death” in India is only 22.5%. This is largely due to significant proportion of deaths occurring outside the hospitals (non-institutional deaths). The “cause of death” in such cases is unlikely to be certified by any doctor. The present study attempts to address this gap by developing a system of MCCD for “non-institutional deaths” in the country.

Novelty

This is a first of its kind study attempting to address the gap of coverage as well as reliability of MCCD for “non-institutional deaths”.

Objectives

To assess the feasibility of “Physician derived Cause of death” approach for deducing “cause of death” in “non-institutional deaths” in a selected area of Kolar Taluk, Karnataka and to validate this approach

Methods

Doctors of selected major hospitals in Kolar taluk and PHC medical officers and private practitioners of 2 selected PHC areas of the taluk would be trained in arriving at “Cause of Death” in “non-institutional deaths” using the “PhyCoD” tool. The “cause of death” deduced by this approach would be validated against the ‘gold standard’ autopsy wherever possible. The approach will also be tested for “inter-rater reliability”.

Expected outcome

Development of a tool for physicians for deducing “Cause of Death” in “non-institutional deaths”

Increased coverage of MCCD for “non-institutional deaths”

Improved accuracy in the reporting of “cause of death” for “non-institutional deaths”

Reduced delay in the reporting of “cause of death” for “non-institutional deaths”
Assessment of trends and determinants of under-five mortality among children born to older women: Evidence from Ethiopian Demographic and Health Surveys
Authors: Temesegen Tamerat Denekew , Demissie Tariku Dejene , Damtew Solomon Abrha
Published: February 2025

Introduction

Mortality has long been used as an indicator of the level of socio-economic development of a country. Global attention has been drawn to under-five mortality through the Sustainable Development Goals (SDGs). The burden of under-five mortality of children is still not fairly divided. Two regions account for around 80% of under-five deaths among children: sub-Saharan Africa and South Asia. Ethiopia is one of six nations that account for half of the world’s under-five mortality.

Methods

The Ethiopia Demographic and Health Survey (EDHS) from the years 2000, 2005, 2011, and 2016 provided nationally representative cross-sectional data. Six thousand one hundred nighty nine (6,199) children born to older women within the five years prior to the study formed the data. Home interviews were used to gather demographic data, such as mother and child characteristics, socioeconomic factors, and environmental variables. Frequencies were computed to characterize the study participants Multiple-level binary regression analysis was utilized to get the Adjusted Odds Ratio (AOR) and its 95% confidence interval (CI).

Result

The absolute number of under five deaths is 128/1000 live births in the year 2000 which reduce to 56/1000 live births in 2016. This study identified factors contributing for under-five mortality among children of women aged 35 to 49 years old. Sex of the child (female_ 0.65 (0.53, 0.79)), late age at first birth, 31 to 4o years at first birth 0.34 (0.11, 0.98), family size, having a family size of 6 to 10 0.18 (0.14, 0.24), longer birth interval, greater than 3 years 0.35 (0.26, 0.47) and ANC visits 1 to 3 ANC vests 0.65 (0.5, 0.84) lowered the odds of under-five mortality among children of relatively elders. On the other hand, Women aged 35 to 49 years who gave a twin Birth 6.15 (3.94, 9.6)), those with number of births in the last five years having 4 children (2.64 (1.15, 6.06)), those with number of children ever born, having 9 or above children 3.79 (2.1, 6.84), those who gave birth at late age the index child, mother gave birth of the index child at late age (45 to 49) 2.13 (1.55, 2.93) had higher odds for their children experiencing child death before they celebrated their fifth birthday.

Conclusion

The absolute number of under five deaths of older women is 128/1000 live births in the year 2000 which reduce to 56/1000 live births in 2016.Female children, children born from first from elder mothers, those children residing am family with large size, children born with longer birth interval and children for whom their mothers received ANC visits were found to Have lower odds of mortality.
ISME - Incoherent Sampling of Multi-Echo data to minimize cardiac-induced noise in brain maps of R2* and magnetic susceptibility
Authors: Raynaud Quentin , Oliveira Rita , Corbin Nadège , Balbastre Yaël , van Heeswijk Ruud B. , Lutti Antoine
Published: February 2025

Purpose

Brain maps of the MRI parameters R2* and magnetic susceptibility (χ) enable the investigation of microscopic tissue changes associated with brain disease in patient populations. However, maps of R2* andχare computed from gradient-echo data acquired at multiple echo times and are affected by cardiac-induced physiological noise. In this study, we introduce ISME – a sampling strategy that minimizes the level of cardiac-induced noise in brain maps of R2* andχ.

Methods

Cardiac-induced noise causes exponential-like effects on the decay of the signal magnitude that vary across the cardiac cycle, increasing the variability of R2* andχestimates. ISME uses phase-encoding gradients to shift the k-space frequency of the acquired data between consecutive readouts of a multi-echo train. As a result, the multi-echo data at a given k-space index is acquired at different phases of the cardiac cycle. We compare the variability of R2* andχmaps acquired with ISME and with standard multi-echo trajectories in N=10 healthy volunteers. We also investigate the effect of both sampling strategies on the spatial aliasing of pulsating MR signals in R2* andχmaps and propose a weighted-least square (NWLS) approach for the estimation of R2* that accounts for the increase in cardiac-induced noise with echo time.

Results

Compared to standard multi-echo trajectories, ISME reduces the variability of R2* andχacross repetitions by 25/26/21% and 24/32/23% in the cerebellum/brainstem/whole brain, respectively. With ISME, the spatial aliasing of pulsating MR signals is incoherent between raw echo images, leading to visually sharper R2* maps. The proposed NWLS approach for the estimation of R2* removes the dependence of the fitting residuals on echo time and brings an additional 3/2/1% reduction of the R2* variability in the cerebellum/brainstem/whole brain.

Conclusion

ISME allows the mitigation of cardiac-induced noise in brain maps of R2* andχ, improving reproducibility.
Age-related differences in the association between REM sleep and the polygenic risk for Parkinson’s disease
Authors: Talwar Puneet , Mortazavi N. , Koshmanova Ekaterina , Muto Vincenzo , Degueldre Christian , Berthomier Christian , Collette Fabienne , Bastin Christine , Phillips Christophe , Maquet Pierre , Mikhail Zubkov , Vandewalle Gilles
Published: February 2025

Objective

Parkinson’s disease (PD) is one of the rare diseases for which sleep alteration is a true marker of disease outcome. Yet, how the association between sleep and PD emerges over the healthy lifetime is not established. We examined association between polygenic risk score (PRS) for PD and the variability in the electrophysiology of Rapid Eye Movement (REM) sleep in 345 younger (18-31y) and 85 older (50-69y) healthy individuals.

Methods

In this prospective cross-sectional study, in-lab EEG recordings of sleep were recorded to extract REM sleep metrics. PRS was computed using SBayesR approach.

Results

Generalized Additive Model for Location, Scale and Shape (GAMLSS) analysis showed significant association of REM duration (pcorr=0.002)and theta energy in REM (pcorr=0.0002) with PRS for PD in interaction with age group. In the younger sub-sample, REM duration and theta energy were positively associated with PD PRS. In contrast, in the older sub-sample, the same associations were negative (though only qualitatively for REM theta energy) and may differ between men and women.

Interpretation

REM sleep is associated with the PRS for PD in early adulthood, 2 to 5 decades prior to typical symptoms onset. The association switches from positive in younger individuals, presumably free of alpha-synuclein, to negative in older individuals, possibly because of the progressive presence of alpha-synuclein aggregates or of the repeated increased oxidative metabolism imposed by REM sleep. Our findings may unravel core associations between PD and sleep and may contribute to novel intervention targets to prevent or delay PD.
A Mean-Field Approach to Criticality in Spiking Neural Networks for Reservoir Computing
Authors: Freddi Ruggero , Cicala Francesco , Marzetti Laura , Basti Alessio
Published: February 2025

Reservoir computing is a neural network paradigm for processing temporal data by exploiting the dynamics of a fixed, high-dimensional system, enabling efficient computation with reduced complexity compared to fully trainable recurrent networks. This work presents an analytical framework for configuring in the critical regime a reservoir based on spiking neural networks with a highly general topology. Specifically, we derive and solve a mean-field equation that governs the evolution of the average membrane potential in leaky integrate-and-fire neurons, and provide an approximation for the critical point. This framework reduces the need for an extensive online fine-tuning, offering a streamlined path to near-optimal network performance from the outset. Through extensive simulations, we validate the theoretical predictions by analyzing the network’s spiking dynamics and quantifying its computational capacity using the information-based Lempel-Ziv-Welch complexity near criticality. Finally, we explore self-organized quasi-criticality by implementing a local learning rule for synaptic weights, demonstrating that the network’s dynamics remain close to the theoretical critical point. Beyond AI, our approach and findings also have significant implications for computational neuroscience, providing a principled framework for quantitatively understanding how biological networks leverage criticality for efficient information processing.
Neural responses in early, but not late, visual cortex are well predicted by random-weight CNNs with sufficient model complexity
Authors: Farahat Amr , Vinck Martin
Published: February 2025

Convolutional neural networks (CNNs) were inspired by the organization of the primate visual system, and in turn have become effective models of the visual cortex, allowing for accurate predictions of neural stimulus responses. While training CNNs on brain-relevant object-recognition tasks may be an important pre-requisite to predict brain activity, the CNN’s brain-like architecture alone may already allow for accurate prediction of neural activity. Here, we evaluated the performance of both task-optimized and brain-optimized convolutional neural networks (CNNs) in predicting neural responses across visual cortex, and performed systematic architectural manipulations and comparisons between trained and untrained feature extractors to reveal key structural components influencing model performance. For human and monkey area V1, random-weight CNNs employing the ReLU activation function, combined with either average or max pooling, significantly outperformed other activation functions. Random-weight CNNs matched their trained counterparts in predicting V1 responses. The extent to which V1 responses can be predicted correlated strongly with the neural network’s complexity, which reflects the non-linearity of neural activation functions and pooling operations. However, this correlation between encoding performance and complexity was significantly weaker for higher visual areas that are classically associated with object recognition, such as monkey IT. To test whether this difference between visual areas reflects functional differences, we trained neural network models on both texture discrimination and object recognition tasks. Consistent with our hypothesis, model complexity correlated more strongly with performance on texture discrimination than object recognition. Our findings indicate that random-weight CNNs with sufficient model complexity allow for comparable prediction of V1 activity as trained CNNs, while higher visual areas require precise weight configurations acquired through training via gradient descent.
Generation ofC9orf72h370mice, an intron 1 humanisedC9orf72repeat-expansion knock-in model
Authors: Nair Remya R , Carcolé Mireia , Thompson David , Tibbit Charlotte , McLeod Ross , Cammack Alexander , Jakubcova Tatiana , Biggs Daniel , Wyles Matthew , Parker Matthew , Caulder Adam , Teboul Lydia , Fisher-Ward Chloe L , Awan Ali R , Flower Michael , Davies Benjamin , Isaacs Adrian M , Fisher Elizabeth MC , Cunningham Thomas J
Published: February 2025

An autosomal dominant GGGGCC repeat expansion in intron 1 of theC9orf72gene is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we set out to engineer a gene targeted mouse model harbouring a pathogenic length humanisedC9orf72repeat expansion allele, in order to model pathological mechanisms in a physiological context. In human disease, pathogenic repeats typically range from the hundreds to thousands of units in length, representing a considerable challenge for cellular and in vivo model generation given the instability of GC rich and repetitive DNA sequences during molecular cloning. To overcome this challenge, we developed new methodology to synthetically and iteratively build pure GGGGCC repeats within a linear vector system, which we then seamlessly and scarlessly embedded within the native human genomic sequence. This created a gene targeting DNA vector for homologous recombination of the human sequence in mouse embryonic stem cells. We used this novel targeting vector to generate a new gene targeted mouse allele,C9orf72h370, that for the first time has mouseC9orf72intron 1 scarlessly replaced with human intron 1 including a pure (GGGGCC)370hexanucleotide repeat expansion. We confirm that the mouse model expresses human intron 1-derived RNA and produces dipeptide repeat proteins derived from the GGGGCC repeat expansion. We now provide this model as a new freely available resource for the field. In addition, we demonstrate the utility of our cloning method for engineering diverse repeat expansion sequences for modelling other disorders, such as Fragile X Syndrome.
Verapamil and its metabolite norverapamil inhibit theMycobacterium tuberculosisMmpS5L5 efflux pump to potentiate the activity bedaquiline and other antitubercular drugs
Authors: Fountain Adam J , Waller Natalie JE , Cheung Chen-Yi , Jowsey William , Chrisp Michael T , Troll Mark , Edelstein Paul H , Cook Gregory M , McNeil Matthew B , Ramakrishnan Lalita
Published: February 2025

Bedaquiline is the cornerstone of a new regimen for the treatment of drug-resistant tuberculosis. However, its clinical use is threatened by the emergence of bedaquiline-resistant strains ofMycobacterium tuberculosis. Bedaquiline targets mycobacterial ATP synthase but the predominant route to clinical bedaquiline resistance is via upregulation of the MmpS5L5 efflux pump due to mutations that inactivate the transcriptional repressor Rv0678. Here, we show that the MmpS5L5 efflux pump reduces susceptibility to bedaquiline as well as its new, more potent derivative TBAJ-876 and other antimicrobial substrates, including clofazimine and the DprE1 inhibitors PBTZ-169 and OPC-167832. Furthermore, the increased resistance of Rv0678 mutants stems entirely from increased MmpS5L5 activity. These results highlight the potential of a pharmacological MmpS5L5 inhibitor to increase drug efficacy. Verapamil, primarily used as a calcium channel inhibitor, is known to inhibit diverse efflux pumps and to potentiate bedaquiline and clofazimine activity inM. tuberculosis. Here, we show that verapamil potentiates the activity of multiple diverse MmpS5L5 substrates. Using biochemical approaches, we demonstrate that verapamil does not exert this effect by acting as a disruptor of the protonmotive force used to power MmpS5L5, as previously proposed, suggesting that verapamil inhibits the function of the MmpS5L5 pump. Finally, norverapamil, the major verapamil metabolite, which has greatly reduced calcium channel activity, has equal potency in reducing resistance to MmpS5L5 substrates. Our findings highlight verapamil’s potential for enhancing bedaquiline TB treatment, for preventing acquired resistance to bedaquiline and other MmpS5L5 substrates, while also providing the impetus to identify additional MmpS5L5 inhibitors.

Significance Statement

Bedaquiline, an antitubercular drug targeting ATP synthase, forms the backbone of highly efficacious treatment regimens for drug-resistant tuberculosis. Bedaquiline resistance is emerging as a significant problem and is most commonly caused by mutations in Rv0678 that result in upregulation of the MmpS5L5 efflux pump. Here we define the contribution of the MmpS5L5 efflux pump to drug resistance in wild-type and Rv0678 mutant strains and show that the commonly used drug verapamil can inhibit MmpS5L5 activity. This suggests that this safe and inexpensive drug may be useful in enhancing bedaquiline treatment of TB and to help prevent bedaquiline acquired resistance.
Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity
Authors: Dalton Casey , Mojsilovic-Petrovic Jelena , Safren Nathaniel , Snoznik Carley , Gebis Kamil K , Wang Yi-Zhi , Lamitina Todd , Savas Jeffrey , Kalb Robert
Published: February 2025

At autopsy, >95% of ALS cases display a redistribution of the essential RNA binding protein TDP-43 from the nucleus into cytoplasmic aggregates. The mislocalization and aggregation of TDP-43 is believed to be a key pathological driver in ALS. Due to its vital role in basic cellular mechanisms, direct depletion of TDP-43 is unlikely to lead to a promising therapy. Therefore, we have explored the utility of identifying modifier genes that modify its mislocalization or aggregation. We have previously shown that loss of rad-23 improves locomotor deficits in TDP-43 C. elegans models of disease and increases the degradation rate of TDP-43 in cellular models. To understand the mechanism through which these protective effects occur, we generated an inducible mutant TDP-43 HEK293 cell line. We find that knockdown of RAD23A reduces insoluble TDP-43 levels in this model and primary rat cortical neurons expressing human TDP-43A315T. Utilizing a discovery-based proteomics approach, we then explored how loss of RAD23A remodels the proteome. Through this proteomic screen, we identified USP13, a deubiquitinase, as a new potent modifier of TDP-43 induced aggregation and cytotoxicity. We find that knockdown of USP13 reduces the abundance of sarkosyl insoluble mTDP-43 in both our HEK293 model and primary rat neurons, reduces cell death in primary rat motor neurons, and improves locomotor deficits in C. elegans ALS models.
Particle-in-cell simulation of laser wakefield accelerators with oblique lasers in quasicylindrical geometry
Authors: Ma Minghao , Zeng Ming , Wang Jia , Lu Guangwei , Yan Wenchao , Chen Liming , Li Dazhang
Published: February 2025

In the studies of optical injections in laser or beam-driven wakefield accelerators, there is a frequent demand for using obliquely propagating assistant lasers in particle-in-cell simulations. In conventional methods, this is only possible in either two- or three-dimensional Cartesian geometries, which have the drawbacks of either lack of fidelity for the actual situation or requiring a huge amount of computational resources. In this work, we develop a new method that uses an expression-defined oblique laser field to simulate such situations in quasicylindrical geometry particle-in-cell simulations, having the advantages of both maintaining good fidelity and saving computational resources. As an example, we use this method in the scissor-cross ionization injection scheme for the optimization of the injected beam quality. This method is widely applicable to particle injections with assistant lasers in wakefield accelerators, as long as the assistant lasers only influence the injected particles during the injection process.

Published by the American Physical Society
2025
Berry phase effects on the transverse conductivity of Fermi surfaces and their detection via spin qubit noise magnetometry
Authors: Morgenthaler Mark , Villadiego Inti Sodemann
Published: February 2025

The quasistatic transverse conductivity of clean Fermi liquids at long wavelengths displays a remarkably universal behavior: it is determined solely by the radius of curvature of the Fermi surface and does not depend on details such as the quasiparticle mass or their interactions. Here we demonstrate that Berry phases do not alter such universality by directly computing the transverse conductivity of two-dimensional electronic systems with Dirac dispersions, such as those appearing in graphene and its chiral multilayer variants. Interestingly, however, such universality ceases to hold at wave vectors comparable to the Fermi radius, where Dirac fermions display a vividly distinct transverse conductivity relative to parabolic Fermions, with a rich wave vector dependence that includes divergences, oscillations, and zeros. We discuss how this can be probed by measuring the T1 relaxation time of spin qubits, such as NV centers or nuclear spins, placed near such 2D systems.

Published by the American Physical Society
2025
Photonuclear reactions on stable isotopes of molybdenum at bremsstrahlung endpoint energies of 10–23 MeV
Authors: Rasulova F. A. , Aksenov N. V. , Alekseev S. I. , Belyshev S. S. , Chuprakov I. , Fursova N. Yu. , Madumarov A. S. , Khushvaktov J. H. , Kuznetsov A. A.
Published: February 2025

In this study experiments were performed at bremsstrahlung end-point energies of 10–23 MeV with the beam from the MT-25 microtron (Joint Institute for Nuclear Research, Dubna) using the γ-activation technique. The experimental values of relative yields, cross sections per equivalent quantum and flux-averaged cross sections were compared with theoretical results obtained on the basis of TALYS-2.0 code with the standard parameters and the combined model of photonucleon reactions. Including isospin splitting in the combined model of photonucleon reactions allows describing experimental data on reactions with proton escape in the energy range from 15 to 23 MeV. Therefore, taking into account isospin splitting is necessary for a correct description of the decay of the giant dipole resonance.

Published by the American Physical Society
2025
Enhancing charge ratio sensitivity to hadronization effects via jet selections on resolved SoftDrop splitting
Authors: Apolinário Liliana , Madureira Nuno Olavo , Elayavalli Raghav Kunnawalkam
Published: February 2025

The study of quantum chromodynamics (QCD) at ultrarelativistic energies can be performed in a controlled environment through lepton-hadron deep inelastic scatterings. In such collisions, the high-energy partonic emissions that follow from the ejected hard partons are accurately described by perturbative QCD. However, the lower energy scales at which quarks and gluons experience color confinement, i.e., hadronization mechanism, fall outside the validity regions for perturbative calculations, requiring phenomenological models tuned to data to describe it. As such, hadronization physics cannot be currently derived from first principles alone. Monte Carlo event generators are useful tools to describe these processes as they simulate both the perturbative and the nonperturbative interactions, with model-dependent energy scales that control parton dynamics. This work employs jets—experimental reconstructions of final-state particles likely to have a common partonic origin—to inspect this transition further. Although originally proposed to circumvent hadronization effects, we show that jets can be utilized as probes of nonperturbative phenomena via their substructure. The charge correlation ratio was recently shown to be sensitive to hadronization effects. Our work further improves this sensitivity to nonperturbative scales by introducing a new selection based on the relative placement of the within the clustering tree, defined as the unclustering that resolves the jet’s leading charged particles.

Published by the American Physical Society
2025
Matching current observational constraints with nonminimally coupled dark energy
Authors: Wolf William J. , Ferreira Pedro G. , García-García Carlos
Published: February 2025

We show that a Universe with a nonminimally coupled scalar field can fit current measurements of the expansion rate of the Universe better than the standard Λ-cold dark matter model or other minimally coupled dark energy models. In particular, the nonminimal coupling in this model allows for the dark energy model to exhibit stable phantom crossing behavior, which seems to be suggested by the constraints on the dark energy equation of state coming from the most recent data. While we find a clear improvement in the goodness of fit for this dark energy model with respect to others that have been considered in the recent literature, using information theoretic criteria, we show that the evidence for it is still inconclusive.

Published by the American Physical Society
2025
Discrete generative diffusion models without stochastic differential equations: A tensor network approach
Authors: Causer Luke , Rotskoff Grant M. , Garrahan Juan P.
Published: February 2025

Diffusion models (DMs) are a class of generative machine learning methods that sample a target distribution by transforming samples of a trivial (often Gaussian) distribution using a learned stochastic differential equation. In standard DMs, this is done by learning a “score function” that reverses the effect of adding diffusive noise to the distribution of interest. Here we consider the generalisation of DMs to lattice systems with discrete degrees of freedom, and where noise is added via Markov chain jump dynamics. We show how to use tensor networks (TNs) to efficiently define and sample such “discrete diffusion models” (DDMs) without explicitly having to solve a stochastic differential equation. We show the following: (i) by parametrising the data and evolution operators as TNs, the denoising dynamics can be represented exactly; (ii) the auto-regressive nature of TNs allows to generate samples efficiently and without bias; (iii) for sampling Boltzmann-like distributions, TNs allow to construct an efficient learning scheme that integrates well with Monte Carlo. We illustrate this approach to study the equilibrium of two models with non-trivial thermodynamics, the d=1 constrained Fredkin chain and the d=2 Ising model.

Published by the American Physical Society
2025
Controlling multistimuli elastic response by bistable micromodules
Authors: Pattloch Sven , Dzubiella Joachim
Published: February 2025

Controlling the elastic response of materials to multiple stimuli is a key prerequisite for the design of adaptive soft matter, e.g., for applications in medicine or soft robotics. Here, we discuss a statistical mechanics model in which the nonlinear elastic response is governed by mechanically coupled bistable micromodules which can be switched by external stimuli. Exact analytical solutions show complex stimuli-mediated, nonlinear stiffening/softening responses tuneable by the microscopic switching parameters. Importantly, we report up to two maxima in the softness (compliance) originating from cooperative transitions and show how to control their existence and properties. We demonstrate the usefulness of the model by fitting it to experimental extension-force data on various scales. We further illustrate how to explore the entire nonlinear response map as a function of multiple stimuli, utilizing distinct pathways to either cancel/reset or amplify the elastic responses through a combination of these stimuli. Our analysis should be useful for the design of nonlinear elasticity, e.g., in bistable microgel networks or mechanical metamaterials.

Published by the American Physical Society
2025
Unconventional and robust light-matter interactions based on the non-Hermitian skin effect
Authors: Du Lei , Kockum Anton Frisk
Published: February 2025

Lattice models featuring the non-Hermitian skin effect have attracted rapidly growing interest due to their nontrivial spectral topology and the exotic field dynamics they enable. Such non-Hermitian lattices provide a promising paradigm for engineering exotic light-matter interactions which benefit from the intrinsic chirality and unconventional (non-Bloch) band theory. Here we study a series of unconventional light-matter interactions between quantum emitters and the prototypical Hatano-Nelson model, and briefly discuss the case with an extended lattice model dubbed the bosonic Kitaev chain. We focus on the robustness of the dynamics against various imperfections and elucidate the underlying mechanisms. We consider both small emitters, which interact with the lattice at single sites, and giant emitters, coupling at multiple sites. The latter exhibit an exclusive amplification mechanism, which we find enables decoherence-free dynamics even in the presence of extra dissipation in the system. The protection from dissipation arises from the cooperation of the non-Hermiticity and the self-interference effect, and is therefore lacking for small emitters. These results not only provide deeper insights into the interplay of non-Hermiticity and various interference effects, but also have potential applications in engineering exotic spin Hamiltonians and quantum networks.

Published by the American Physical Society
2025
Wave packet dynamics in parabolic optical lattices: From Bloch oscillations to long-range dynamical tunneling
Authors: Ali Usman , Holthaus Martin , Meier Torsten
Published: February 2025

We investigate the dynamics of wave packets in a parabolic optical lattice formed by combining an optical lattice with a global parabolic trap. Our study examines the phase space representation of the system's eigenstates by comparing them to the classical phase space of a pendulum, to which the system effectively maps. The analysis reveals that quantum states can exhibit mixed dynamics by straddling the separatrix. A key finding is that the dynamics around the separatrix enables the controlled creation of highly nonclassical states, distinguishing them from the classical oscillatory or rotational dynamics of the pendulum. By considering a finite momentum of the initial wave packet, we demonstrate various dynamical regimes. Furthermore, a slight energy mismatch between nearly degenerate states localized at opposite turning points of the trap potential results in controlled long-range dynamical tunneling. These results can be interpreted as quantum beating between a clockwise rotating and a counterclockwise rotating pendulum.

Published by the American Physical Society
2025
Observation of Pattern Stabilization in a Driven Superfluid
Authors: Liebster Nikolas , Sparn Marius , Kath Elinor , Duchene Jelte , Fujii Keisuke , Görlitz Sarah L. , Enss Tilman , Strobel Helmut , Oberthaler Markus K.
Published: February 2025

The formation of patterns in driven systems has been studied extensively, and their emergence can be connected to a fine balance of instabilities and stabilization mechanisms. While the early phase of pattern formation can be understood on the basis of linear stability analyses, the longtime dynamics can only be described by accounting for the interactions between the excitations generated by the drive. Here, we observe the stabilization of square patterns in an interaction-driven, two-dimensional Bose-Einstein condensate. These patterns emerge due to inherent high-order processes that become relevant in the regime of large phonon occupations. Theoretically, this can be understood as the emergence of a stable fixed point of coupled nonlinear amplitude equations, which include phonon-phonon interactions. We experimentally probe the predicted flows toward such a stable fixed point, as well as repulsion from a saddle fixed point, using the experimental control unique to quantum gases.

Published by the American Physical Society
2025
Necklacelike Pattern of Vortex Bound States
Authors: Hou Zhiyong , Chen Kailun , Hong Wenshan , Wang Da , Duan Wen , Yang Huan , Li Shiliang , Luo Huiqian , Wang Qiang-Hua , Xiang Tao , Wen Hai-Hu
Published: February 2025

A vortex is a topological defect in the superconducting condensate when a magnetic field is applied to a type-II superconductor, as elucidated by the Ginzburg-Landau theory. Because of the confinement of the quasiparticles by a vortex, it exhibits a circular-shaped pattern of bound states with discrete energy levels, as predicted by the Caroli–de Gennes–Matricon theory in 1964. Here, however, we report a completely new type of vortex pattern which is necklacelike in an iron-based superconductor KCa2Fe4As4F2. Our theoretical analysis shows that this necklacelike vortex pattern arises primarily from selective off-shell interference between vortex bound states of opposite angular momenta in the presence of rotational symmetry breaking due to disorders. This fascinating effect can be observed in a system with a small Fermi energy and wave vector, conditions fortuitously met in our samples. Our results not only disclose a novel vortex structure, but also unravel a completely new quantum phenomenon in the superconducting condensate.

Published by the American Physical Society
2025
Transformative impacts of technological developments on architectural education: a holistic scientometric analysis
Authors: Kose Irem , Gumusburun Ayalp Gulden
Published: February 2025

Purpose

This study aims to outline the transformative impacts of technological developments (TD) on architectural education (AE). The focus is on studying the dynamics of convergence and erosion, aiming to understand the impact of current digital transformations such as the COVID-19 pandemic, sustainability considerations and technology integration on AE.

Design/methodology/approach

A scientometric analysis and bibliometric search were performed to understand the current knowledge in the field. The Web of Science (WoS) was selected for its comprehensive collection of significant research articles and integrated analytical tools for generating representative data. The study involved an extensive bibliometric analysis of 131 journal articles on TD in AE from 2000 to 2023. Subsequently, the VOSviewer software was employed to illuminate the transformative impacts of technological advancements on AE. Robust methodologies, including citation analysis and co-citation networks, unravel quantitative dimensions such as publication trends, influential authors, prolific journals, geographic distribution and prevalent themes or technological domains within the discourse.

Findings

The findings reveal significant evolution in AE due to TD, with notable shifts influenced by factors such as the COVID-19 pandemic, sustainability concerns and the integration of modern technologies. Key findings include the increasing adoption of online platforms and technologies like Building Information Modeling (BIM), the crucial role of design thinking methodologies and the recognition of innovative modules such as architectural photogrammetry and augmented reality (AR) applications. Furthermore, keyword clusters were classified into six groups: “AE pedagogy and curriculum development,” “Development of architectural design process and studio,” “Educational approaches and digitalization in architectural design,” “Transition to online AE,” “Development/emergence of photogrammetry at architectural education” and “use of AR.”

Originality/value

Although several studies have addressed TD in AE from various perspectives and methods, they have yet to investigate the subject using scientometric analysis from a holistic perspective. A holistic exploration of TD in AE still needs to be improved in the existing literature. In contrast to previous investigations, this study is the first to leverage the quantitative analytical capabilities of VOSviewer. The originality lies in uncovering quantitative dimensions such as publication trends, influential authors and prevalent themes, providing a comprehensive understanding of the nuanced dimensions of this evolving intersection.