bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Utility of Neurophysiologic Classification (and Declassification) of Myoclonus
Authors: Callister Marcus N. , Klanderman Molly C. , Stockard Alyssa , Van Der Walt Charles , Pena Ashley B. , Caviness John N.
Published: June 2024

Background

Movement clinical neurophysiology studies can distinguish myoclonus, tremor, and other jerky movements, however there has been limited demonstration of their real-world clinical impact.

Objective

Investigate movement study utility in clarifying movement classification and guiding patient management.

Methods

Retrospective study of myoclonus-related movement studies.

Results

Of 262 patients referred for consideration of myoclonus, 105 (40%) had myoclonus, 156 (59%) had no myoclonus (the commonest alternative classifications were functional jerks and tremor), and 1 was uncertain. An additional 29 studies identified myoclonus without prior clinical suspicion. 119/134 (89%) myoclonus cases had a specific neurophysiologic subtype identified, most commonly cortical (64, 54%). Diagnostic differential narrowed in 60% of cases, and a new diagnosis was made in 42 (14%) patients. Medication changes were made in 151 patients (52%), with improvement in 35/51 (67%) with follow-up.

Conclusions

Movement studies effectively clarified movement classification and identified unsuspected myoclonus, leading to changes in diagnosis and management.
Reproductive Tract Microbial Transitions from Late Gestation to Early Postpartum Using 16S rRNA Metagenetic Profiling in First-Pregnancy Heifers
Authors: Druker Shaked , Sicsic Ron , Ravid Shachar , Scheinin Shani , Raz Tal
Published: June 2024

Studies in recent years indicate that reproductive tract microbial communities are crucial for shaping mammals’ health and reproductive outcomes. Following parturition, uterine bacterial contamination often occurs due to the open cervix, which may lead to postpartum uterine inflammatory diseases, especially in primiparous individuals. However, investigations into spatio-temporal microbial transitions in the reproductive tract of primigravid females remain limited. Our objective was to describe and compare the microbial community compositions in the vagina at late gestation and in the vagina and uterus at early postpartum in first-pregnancy heifers. Three swab samples were collected from 33 first-pregnancy Holstein-Friesian heifers: one vaginal sample at gestation day 258±4, and vaginal and uterine samples at postpartum day 7±2. Each sample underwent 16S rRNA V4 region metagenetic analysis via Illumina MiSeq, with bioinformatics following Mothur MiSeq SOP. The reproductive tract bacterial communities were assigned to 1,255 genus-level OTUs across 30 phyla. Dominant phyla, accounting for approximately 90% of the communities, included Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria. However, the results revealed distinct shifts in microbial composition between the prepartum vagina (Vag-pre), postpartum vagina (Vag-post), and postpartum uterus (Utr-post). The Vag-pre and Utr-post microbial profiles were the most distinct. The Utr-post group had lower relative abundances of Proteobacteria but higher abundances of Bacteroidetes, Fusobacteria, and Tenericutes compared to Vag-pre, while Vag-post displayed intermediate values for these phyla, suggesting a transitional profile. Additionally, the Utr-post group exhibited lower bacterial richness and diversity compared to both Vag-pre and Vag-post. The unsupervised probabilistic Dirichlet Multinomial Mixtures model identified two distinct community types: most Vag-pre samples clustered into one type and Utr-post samples into another, while Vag-post samples were distributed evenly between the two. LEfSe analysis revealed distinct microbial profiles at the genus level. Overall, specific microbial markers were associated with anatomical and temporal transitions, revealing a dynamic microbial landscape during the first pregnancy and parturition. These differences highlight the complexity of these ecosystems and open new avenues for research in reproductive biology and microbial ecology.
The urban physical exposome and leisure-time physical activity in early midlife: a FinnTwin12 study
Authors: Wang Zhiyang , Aaltonen Sari , Teeuwen Roos , Milias Vasileios , Peuters Carmen , Raimbault Bruno , Palviainen Teemu , Lumpe Erin , Dick Danielle , Salvatore Jessica E. , Foraster Maria , Dadvand Payam , Júlvez Jordi , Psyllidis Achilleas , van Kamp Irene , Kaprio Jaakko
Published: June 2024

Leisure-time physical activity is beneficial for health and is associated with various urban characteristics. Using the exposome framework, the totality of the environment, this study investigated how urban physical environments were associated with leisure-time physical activity during early midlife. A total of 394 participants (mean age: 37, range 34-40) were included from the FinnTwin12 cohort residing in five major Finnish cities in 2020. We comprehensively curated 145 urban physical exposures at residential addresses of participants and measured three leisure-time physical activity measures: (1) total leisure-time physical activity (total LTPA) and its sub-domains (2) leisure-time physical activity without commuting activity (LTPA) and (3) commuting activity. Using K-prototypes cluster analysis, we identified three urban clusters: “original city center,” “new city center,” and “suburban”. Results from adjusted linear regression models showed that participants in the “suburban” cluster had lower levels of total LTPA (beta: -0.13, 95% CI: -0.23, -0.03) and LTPA (beta: -0.17, 95% CI: -0.28, -0.05), compared to those in the “original city center” cluster. The eXtreme Gradient Boosting models ranked exposures related to greenspaces, pocket parks, and road junctions as the top important factors influencing outcomes, and their relationships with outcomes were largely non-linear. More road junctions and more pocket parks correlated with higher total LTPA and LTPA. When the all-year normalized difference vegetation index within a 500 m buffer fell below 0.4, it correlated with higher levels of total LTPA, whereas above 0.4, it correlated with lower levels. To conclude, our findings revealed a positive correlation between urbanicity and physical activity in Finnish cities and decomposed this complexity into crucial determinants. Importance rankings and nonlinear patterns offer valuable insights for future policies and projects targeting physical inactivity.
Co-developing a novel intervention to promote wellbeing of family caregivers of individuals with spinal cord injury: Research protocol
Authors: Mohammadi Somayyeh , Erlander Beth , Cathcart Heather , Robillard Julie M. , Whitehurst David GT , Pauly Elena , Pagé Brooke , Sauvageau Sophia , Miller William C.
Published: June 2024

Family caregivers of individuals with spinal cord injury (fcSCI) are responsible for providing assistance with activities of daily living for individuals with spinal cord injury (SCI), which can include emotional support and physical assistance. Over time, providing daily support can put fcSCI at risk of experiencing caregiver burden. Burden and distress can have a substantial impact on fcSCI’s wellbeing as well as their ability to respond to the needs of the individual with SCI. A direct predictor of fcSCI burden is their appraisal of their ability to cope with the individual with SCI’s illness. Therefore, supporting fcSCI’s access to education relevant to their role and the health and wellbeing of the individual with SCI can help decrease levels of burden. The purpose of this study is to evaluate the fidelity of the intervention named COMPANION and the study protocol for an eHealth approach designed to improve outcomes for fcSCI. COMPANION, co-created with caregiver partners, is an online education program designed to provide accessible education and support for fcSCI. A concurrent mixed methods study including a feasibility randomized controlled trial will be conducted to (i) assess the process, resource, management and treatment indicators; (ii) estimate the parameters needed for a full-scale, multi-site randomized controlled trial and (iii) evaluate the effect that COMPANION has on caregiver clinical outcomes compared to a control group. The primary outcome measured will be fcSCI’s burden in addition to secondary outcomes measuring depression, anxiety, relationship satisfaction, and quality of life. The fcSCI in the intervention group will be given access to COMPANION (at T1) and data will be collected again after three months (T2) and six months (T3) to capture the impact of COMPANION on fcSCI’s psychological wellbeing. Study results will evaluate whether the full study can and should be conducted and will lead to refinement of COMPANION.
Inter-individual differences in cerebrovascular reactivity are synchronized within functional networks and tissue layers: evidence from healthy older adults and patients with hypertension
Authors: Nanayakkara Nuwan D. , Meusel Liesel-Ann , Anderson Nicole D. , Chen J. Jean
Published: June 2024

Functional-connectivity mapping has primarily relied resting-state functional MRI (rs-fMRI), and resting-state functional networks (RSNs) have been used widely to represent interactions within brain circuits. However, recent work demonstrated that resting-state functional networks (RSNs) may co-exist with vascular networks. In this work, we clarify the nature of these vascular networks by assessing the spatial covariation structure in breath-holding-based CVR amplitude and lag in a group of healthy older adults. We demonstrate a spatial synchrony in CVR amplitude and lag co-variations across participants confined to RSNs. Such a network structure is not seen when looking at the time-variate BOLD signal response to the breathhold. a network structure is also maintained in older adults with clinical hypertension, demonstrating its robustness against vascular pathologies. CVR amplitude is also found to vary with tissue layer in the grey matter and white matter, being most variable in deep WM and least variable in superficial cortex. Conversely, CVR lag appears to be organized by fibre tracts. This work demonstrates the use of cross-participant covariation patterns in CVR as an informative way of mapping the vascular routes in the GM and WM, and also raises questions about the nature and interpretation of RSNs.
Genome analysis of the esca-associated Basidiomycetes Fomitiporia mediterranea, Fomitiporia polymorpha, Inonotus vitis, and Tropicoporus texanus reveals virulence factor repertoires characteristic of white-rot fungi
Authors: Garcia Jadran F , Balderas Rosa Figueroa , Comont Gwenaelle , Delmas Chloe , Baumgartner Kendra , Cantu Dario
Published: June 2024

Some Basidiomycete fungi are important plant pathogens, and certain species have been associated with the grapevine trunk disease esca. We present the genomes of four species associated with esca: Fomitiporia mediterranea, Fomitiporia polymorpha, Tropicoporus texanus, and Inonotus vitis. We generated high-quality phased genome assemblies using long-read sequencing. The genomic and functional comparisons identified potential virulence factors, suggesting their roles in disease development. Similar to other white-rot fungi known for their ability to degrade lignocellulosic substrates, these four genomes encoded a variety of lignin peroxidases and carbohydrate-active enzymes (CAZymes) such as CBM1, AA9, and AA2. The analysis of gene family expansion and contraction revealed dynamic evolutionary patterns, particularly in genes related to secondary metabolite production, plant cell wall decomposition, and xenobiotic degradation. The availability of these genomes will serve as a reference for further studies of diversity and evolution of virulence factors and their roles in Esca symptoms and host resistance.
Deep Geometric Framework to Predict Antibody-Antigen Binding Affinity
Authors: Bandara Nuwan , Premathilaka Dasun , Chandanayake Sachini , Hettiarachchi Sahan , Varenthirarajah Vithurshan , Munasinghe Aravinda , Madhawa Kaushalya , Charles Subodha
Published: June 2024

In drug development, the efficacy of an antibody depends on how the antibody interacts with the target antigen. The strength of these interactions gives an indication of how successful an antibody is in neutralizing an antigen. Therefore, the strength, measured by “binding affinity”, is a critical aspect of antibody engineering. In theory, the higher the binding affinity, the higher the chances are that the antibody is successful against the target antigen. Currently, techniques such as molecular docking and molecular dynamics are utilized in quantifying the binding affinity. However, owing to the computational complexity of the aforementioned techniques, running simulations for large antibodies/antigens remains a daunting task. Despite the commendable improvements in deep learning-based binding affinity prediction, such approaches are highly dependent on the quality of the antibody-antigen structures and they tend to overlook the importance of capturing the evolutionary details of proteins upon mutation. Further, most of the existing datasets for the task only include antibody-antigen pairs related to one antigen variant and, thus, are not suitable for developing comprehensive data-driven approaches. To circumvent the said complexities, we first curate the largest and most generalized datasets for antibody-antigen binding affinity prediction, consisting of both protein sequences and structures. Subsequently, we propose a deep geometric neural network comprising a structure-based model and a sequence-based model that considers both atomistic and evolutionary details when predicting the binding affinity. The proposed framework exhibited a 10% improvement in mean absolute error compared to the state-of-the-art models while showing a strong correlation between the predictions and target values. We release the datasets and code publicly (https://drug-discovery-entc.github.io/p2pxml/) to support the development of antibody-antigen binding affinity prediction frameworks for the benefit of science and society.
Axon length-dependent synapse loss is mediated by neuronal cytokine-induced glial phagocytosis
Authors: Tenedini Federico , Yin Chang , Huang Jessica , Dhiman Neena , Soba Peter , Parrish Jay Z.
Published: June 2024

Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors, but our understanding of this specific vulnerability is limited. UsingDrosophilalarval class IV dendrite arborization (C4da) neurons, we found that neuronal activation of the integrated stress response (ISR) induces axon length-dependent degeneration (LDD). We identified the Interleukin-6 homologue unpaired 3 (upd3) as both necessary and sufficient for LDD in C4da neurons. Upd3 recruits glial cells to phagocytose presynapses preferentially on neurons with long axons, revealing an intrinsic axon length-dependent vulnerability to glia-mediated presynapse removal. Finally, we found that axon length-dependent presynapse loss in fly models of human NDDs utilized this pathway. Altogether, our studies identify inflammatory cytokine signaling from neurons to glia as a key determinant in axon length-dependent vulnerability.

One-Sentence Summary

Sensory neurons exhibit intrinsic length-dependent vulnerability to presynapse removal driven by cytokine activation of glia.
Improving the reliability of T2measurement in magnetic resonance imaging
Authors: Yang Xiuli
Published: June 2024

Magnetic resonance imaging (MRI) is a versatile technique broadly utilized in research and clinic. Among the information available from MRI measurements, transversal relaxation time (T2) is a basic but critical one to reflect the microstructure and microenvironment at the molecular level. A popular method to estimate T2is employing a series of evolution time (TE) values and, thereafter, fitting with the exponential model (termed as T2fitting). Despite of the popularity in using T2fitting, there is a lack of knowledge how related experimental parameters, such as signal-to-noise (SNR), number of TE utilized, dynamic range of TE, and repetition number of each TE, affect the measurement reproducibility. In this study, we performed Monte Carlo simulations to investigate how SNR, TE number, TE range, and repetition number influence the reliability of T2measurement, which was indexed by coefficient of variations. Good reliability with ≤5.0% variation can be achieved when the normalized noise level is below 2.2%. Optimal TE range for measuring T2is related to the T2under evaluation. TE number and repetition number can be increased to reduce measurement variations.
Intragenomic conflict underlies extreme phenotypic plasticity in queen-worker caste determination in honey bees (Apis mellifera)
Authors: Bresnahan Sean T. , Mahony Shaun , Anton Kate , Harpur Brock , Grozinger Christina M.
Published: June 2024

Caste determination of honey bees (Apis mellifera) is a prime example of developmental plasticity, where differences in larval diet will result in identical genotypes yielding either long-lived, reproductive queens or short-lived, facultatively sterile workers. Beyond environmental factors, intragenomic conflict between genes inherited from the mother (matrigenes) versus the father (patrigenes) is also hypothesized to generate this plasticity. In honey bees, the Kinship Theory of Intragenomic Conflict predicts selection on patrigenes to enhance traits that result in fitness gained through reproduction, and thus patrigenes should favor the queen caste fate. Here, we conducted allele-specific transcriptome analyses on queen-destined larvae (QL) and worker-destined larvae (WL) at 192 hours post-fertilization (hpf), a critical stage for caste determination. Our findings reveal hundreds of genes with parent-of-origin effects (POEs), with significant patrigene-biased transcription in QL. Genes with POEs in honey bees resemble imprinted genes in other taxa in terms of genomic clustering, recombination rate, intron length and CpG density, and a subset are maintained from 24hpf eggs. Previous studies demonstrated that DNA methylation, the canonical regulatory mechanism underlying transcriptional POEs in placental mammals, angiosperms, and some insects, is not operating in honey bees or other social insects. We use allele-specific ChIP-seq analyses to demonstrate that POEs on caste-specific histone post-translational modification (HPTM) profiles of H3K27me3, H3K4me3 and H3K27ac are associated with POEs on transcription. Together, these findings suggest that parent-of-origin intragenomic conflicts may contribute broadly to phenotypic plasticity and may be associated with HPTMs, suggesting a “non-canonical” genomic imprinting-like system in social insects.
Olfactory facilitation of visual categorization in the 4-month-old brain depends on visual demand
Authors: Kiseleva Anna , Rekow Diane , Schaal Benoist , Leleu Arnaud
Published: June 2024

To navigate their environment, infants rely on intersensory facilitation when unisensory perceptual demand is high, a principle known as inverse effectiveness. Given that this principle was mainly documented in the context of audiovisual stimulations, here we aim to determine whether it applies to olfactory-to-visual facilitation. We build on previous evidence that the mother’s body odor facilitates face categorization in the 4-month-old brain, and investigate whether this effect depends on visual demand. Scalp electroencephalogram (EEG) was recorded in 2 groups of 4-month-old infants while they watched 6-Hz streams of visual stimuli with faces displayed every 6thstimulus to tag a face-selective response at 1 Hz. We used variable natural stimuli in one group (NatGroup), while stimuli were simplified in the other group (SimpGroup) to reduce perceptual categorization demand. During visual stimulation, infants were alternatively exposed to their mother’svs. a baseline odor. For both groups, we found an occipito-temporal face-selective response, but with a larger amplitude for the simplified stimuli, reflecting less demanding visual categorization. Importantly, the mother’s body odor enhances the response to natural, but not to simplified, face stimuli, indicating that maternal odor improves face categorization when it is most demanding for the 4-month-old brain. Overall, this study demonstrates that the inverse effectiveness of intersensory facilitation applies to the sense of smell during early perceptual development.

Highlights

- Intersensory facilitation is a function of unisensory perceptual demand in infants (inverse effectiveness).

- This inverse relation between multisensory and unisensory perception has been mainly documented using audiovisual stimulations.

- Here we show that olfactory-to-visual facilitation depends on visual demand in 4-month-old infants.

- The inverse effectiveness of intersensory facilitation during early perceptual development applies to the sense of smell.
ATP Citrate Lyase Supports Cardiac Function and NAD+/NADH Balance And Is Depressed in Human Heart Failure
Authors: Meddeb Mariam , Koleini Navid , Jun Seungho , Keykhaei Mohammad , Farshidfar Farnaz , Zhao Liang , Kwon Seoyoung , Lin Brian , Keceli Gizem , Paolocci Nazareno , Hahn Virginia , Sharma Kavita , Pearce Erika L. , Kass David A.
Published: June 2024

Background

ATP-citrate lyase (ACLY) converts citrate into acetyl-CoA and oxaloacetate in the cytosol. It plays a prominent role in lipogenesis and fat accumulation coupled to excess glucose, and its inhibition is approved for treating hyperlipidemia. In RNAseq analysis of human failing myocardium, we foundACLYgene expression is reduced; however the impact this might have on cardiac function and/or metabolism has not been previously studied. As new ACLY inhibitors are in development for cancer and other disorders, such understanding has added importance.

Methods

Cardiomyocytes,ex-vivobeating hearts, andin vivohearts with ACLY inhibited by selective pharmacologic (BMS303141, ACLYi) or genetic suppression, were studied. Regulation of ACLY gene/protein expression, and effects of ACLYi on function, cytotoxicity, tricarboxylic acid (TCA)-cycle metabolism, and redox and NAD+/NADH balance were assessed. Mice with cardiac ACLY knockdown induced by AAV9-acly-shRNA or cardiomyocyte tamoxifen-inducibleAclyknockdown were studied.

Results

Aclygene expression was reduced more in obese patients with heart failure and preserved EF (HFpEF) than HF with reduced EF.In vivopressure-overload andin vitrohormonal stress increased ACLY protein expression, whereas it declined upon fatty-acid exposure. Acute ACLYi (1-hr) dose-dependently induced cytotoxicity in adult and neonatal cardiomyocytes, and caused substantial reduction of systolic and diastolic function in myocytes andex-vivobeating hearts. In the latter, ATP/ADP ratio also fell and lactate increased. U13C-glucose tracing revealed an ACLY-dependent TCA-bypass circuit in myocytes, where citrate generated in mitochondria is transported to the cytosol, metabolized by ACLY and then converted to malate to re-enter mitochondria, bypassing several NADH-generating steps. ACLYi lowered NAD+/NADH ratio and restoring this balance ameliorated cardiomyocyte toxicity. Oxidative stress was undetected with ACLYi. Adult hearts following 8-weeks of reduced cardiac and/or cardiomyocyte ACLY downregulation exhibited ventricular dilation and reduced function that was prevented by NAD augmentation. Cardiac dysfunction from ACLY knockdown was worse in hearts subjected to sustained pressure-overload, supporting a role in stress responses.

Conclusions

ACLY supports normal cardiac function through maintenance of the NAD+/NADH balance and is upregulated by hemodynamic and hormonal stress, but depressed by lipid excess. ACLY levels are most reduced in human HFpEF with obesity potentially worsening cardio-metabolic reserve.
Ratios in Disguise, Truths Arise: Glycomics Meets Compositional Data Analysis
Authors: Bennett Alexander R. , Lundstrøm Jon , Chatterjee Sayantani , Thaysen-Andersen Morten , Bojar Daniel
Published: June 2024

Comparative glycomics data are an instance of compositional data defined by the Aitchison simplex, where measured glycans are parts of a whole, indicated by relative abundances, which are then compared between conditions. Applying traditional statistical analyses to this type of data often results in misleading conclusions, such as spurious “decreases” of glycans between conditions when other structures sharply increase in abundance, or routine false-positive rates of >25% for differential abundance. Our work introduces a compositional data analysis framework, specifically tailored to comparative glycomics, to account for these data dependencies. We employ center log-ratio (CLR) and additive log-ratio (ALR) transformations, augmented with a model incorporating scale uncertainty/information, to introduce the most robust and sensitive glycomics data analysis pipeline. Applied to many publicly available comparative glycomics datasets, we show that this model controls false-positive rates and results in new biological findings. Additionally, we present new modalities to analyze comparative glycomics data with this framework. Alpha- and beta-diversity enable exploration of glycan distributions within and between biological samples, while cross-class glycan correlations shed light on complex and previously undetected interdependencies. These new approaches have revealed deeper insights into glycome variations that are critical to understanding the roles of glycans in health and disease.
A Second Drug Binding Site in P2X3
Authors: Thach Trung , Dhanabalan KanagaVijayan , Nandekar Prajwal Prabhakarrao , Stauffer Seth , Heisler Iring , Alvarado Sarah , Snyder Jonathan , Subramanian Ramaswamy
Published: June 2024

Purinergic P2X3 receptors form trimeric cation-gated channels, which are activated by extracellular ATP. P2X3 plays a crucial role in chronic cough and affects over 10% of the population. Despite considerable efforts to develop drugs targeting P2X3, the highly conserved structure within the P2X receptor family presents obstacles for achieving selectivity. Camlipixant, a potent and selective P2X3 antagonist, is currently in phase III clinical trials. However, the mechanisms underlying receptor desensitization, ion permeation, principles governing antagonism, and the structure of P2X3 when bound to camlipixant remain elusive. In this study, we established a stable cell line expressing homotrimeric P2X3 and utilized a peptide scaffold to purify the complex and determine its structure using cryo-electron microscopy (cryo-EM). P2X3 binds to camlipixant at a previously unidentified drug-binding site and functions as an allosteric inhibitor. Structure-activity studies combined with modeling and simulations have shed light on the mechanisms underlying the selective targeting and inhibition of P2X3 by camlipixant, distinguishing it from other members of the P2X receptor family.
Molecular tension authenticates apoptotic cells being phagocytosed
Authors: Min Chanhyuk , Cho Hyeokjin , Yu Jeongmin , Moon Byeongjin , Jeon Jaeseon , Shahdab Nafeesa , Moon Hyunji , Yang Susumin , Lee Juyeon , Jin Jaeseong , Hong Mingi , Chung Won-jin , Park Jihwan , Lee Gwangrog , Park Daeho
Published: June 2024

Profound cytoskeletal reorganization and plasma membrane deformation in phagocytes is indispensable for phagocytosis of massive apoptotic cells, but whether these dynamics accompany a mechanical signal modulating signaling during efferocytosis remains largely unexplored. Here, we report that tension between phosphatidylserine (PS) and PS receptors (PSR) generated at the phagocytic synapse serves as a signal to determine whether PS-exposing cells should be phagocytosed. Mechanistically, increased membrane tension of phagocytes via Rac1-dependent actin polymerization and membrane stiffness of apoptotic cells caused tension between PS and PSRs, leading to phosphoinositide 3-kinase recruitment to PSRs, which resulted in Rac1 inactivation and myosin II phosphorylation required for phagocytic cup closure. Our observations imply that tension between PS and PSRs acts as a mechanical fail-safe to prevent removal of all PS-exposing cells for the integrity of efferocytosis.

One-Sentence Summary

Tension between phosphatidylserine and its receptors acts as a final decision-maker determining phagocytosis of apoptotic cells.
Signal Antagonists SuppressPseudomonas syringaePathogenicity
Authors: Mas-Roselló Josep , Mathew Anugraha , Avramenko Veronika , Ren Jiajun , Steiner Till , Sieber Simon , Eberl Leo , Gademann Karl
Published: June 2024

The bacterial plant pathogenPseudomonas syringaecauses significant damage to economically important crops worldwide. These bacteria coordinate their behavior and virulence through specific signaling compounds, such as the diazeniumdiolate leudiazen. Conventional antibacterial treatments enable the development of resistant strains. A more attractive treatment strategy would involve antagonists that suppress the expression of virulence factors without killing the pathogen, potentially reducing the risk of resistance development. Herein, we present the design and synthesis of analogs of leudiazen, which positively regulates the production of mangotoxin inP. syringaepv.syringae(Pss). Several compounds display inhibitory activity towards mangotoxin production, and a lead compound abolishes necrosis in infected tomato leaves, without significantly affecting bacterial growth. Thus, this study represents a promising advance towards developing effective and sustainable methods for bacterial disease control.
A proteome-wide yeast degron collection for the dynamic study of protein function
Authors: Valenti Rosario , David Yotam , Edilbi Dunya , Dubreuil Benjamin , Asraf Yeynit , Meir-Salame Tomer , Sass Ehud , Schuldiner Maya
Published: June 2024

Genome-wide collections of yeast strains, known as libraries, revolutionized the way systematic studies are carried out. Specifically, libraries that involve a cellular perturbation, such as the deletion collection, have facilitated key biological discoveries. However, short-term rewiring and long-term accumulation of suppressor mutations often obscure the functional consequences of such perturbations. We present the AID library which supplies “on demand” protein depletion to overcome these limitations. Here, each protein is tagged with a Green Fluorescent Protein (GFP) and an Auxin inducible degron (AID), enabling rapid protein depletion that can be quantified systematically using the GFP element. We characterized the degradation response of all strains and demonstrated its utility by revisiting seminal yeast screens for genes involved in cell cycle progression as well as mitochondrial distribution and morphology. In addition to recapitulating known phenotypes, we also uncovered proteins with previously unrecognized roles in these central processes. Hence, our tool expands our knowledge of cellular biology and physiology by enabling access to phenotypes that are central to cellular physiology and therefore rapidly equilibrated.
Morphometric Analysis of Actin Networks
Authors: Akenuwa Oghosa H. , Gu Jinmo , Nebenführ Andreas , Abel Steven M.
Published: June 2024

The organization of cytoskeletal elements is pivotal for coordinating intracellular transport in eukaryotic cells. Several quantitative measures based on image analysis have been proposed to characterize morphometric features of fluorescently labeled actin networks. While helpful in detecting differences in actin organization between treatments or genotypes, the accuracy of these measures could not be rigorously assessed due to a lack of ground-truth data to which they could be compared. To overcome this limitation, we utilized coarse-grained computer simulations of actin filaments and crosslinkers to generate synthetic actin networks with varying levels of bundling. We converted the simulated networks into pseudo-fluorescence images similar to images obtained using confocal microscopy. Using both published and novel analysis procedures, we extracted a series of morphometric parameters and benchmarked them against analogous measures based on the ground-truth actin configurations. Our analysis revealed a set of parameters that reliably reports on actin network density, orientation, ordering, and bundling. Application of these morphometric parameters to root epidermal cells ofArabidopsis thalianarevealed subtle changes in network organization between wild-type and mutant cells. This work provides robust measures that can be used to quantify features of actin networks and characterize changes in actin organization for different experimental conditions.
Second-order phase transitions and divergent linear response in dynamical mean-field theory
Authors: van Loon Erik G. C. P.
Published: June 2024

Second-order phase transitions appear as a divergence in one of the linear response functions. For a system of correlated electrons, the relevant divergent response can and does involve many-particle observables, most famously the double occupancy. Generally, evaluating the linear response function of many-particle observables requires a many-particle generalization of the Bethe-Salpeter equation. However, here I show that the divergence of linear response functions in dynamical mean-field theory is governed by a -particle Bethe-Salpeter equation, even for many-particle observables. The reason for this is that the divergence at the second-order phase transition is produced by the self-consistent feedback of the dynamical mean field.

Published by the American Physical Society
2024
H→bs¯
decay and its implication for the vectorlike singlet fermion model
Authors: Zhang Jin , Jin Hong-Ying , Steele T. G.
Published: June 2024

The vectorlike quark model is one of the extensions of the standard model (SM) of particle physics. The simplest version of this model introduces a vectorlike singlet quark which can mix with SM quarks and give rise to new contributions to the flavor-changing decays of the Higgs boson. In this work we first present a systematic analysis of the branching ratios of the decays H→bs¯,bd¯ at leading order in the standard model. Our results show that it is challenging to observe these two modes because of their small branching ratios. Then augmenting the SM with a vectorlike singlet top quark, assuming the top partner only mixes with the top quark, complete one-loop contributions are taken into account in the amplitudes. Further results indicate that the branching ratios of the decays H→bs¯,bd¯ are sensitive to the mass of the top partner MT and the mixing effects characterized by sinθL. By tuning the values of MT and sinθL, the branching ratios may rise to a level accessible to LHC experiments. Combined with the branching ratios obtained from a probabilistic model, the allowed areas in the MT−sinθL plane are displayed. Tagging efficiencies and feasibility for detecting H→bs¯ are specifically discussed and we conclude that with large statistics it is promising to discover the H→bs¯ decay at the LHC.

Published by the American Physical Society
2024
Dark matter and spacetime symmetry restoration
Authors: Magueijo João
Published: June 2024

We examine local physics in the presence of variables: variables associated with the whole of the spacelike surfaces of a foliation. These could be the (pseudo)constants of nature and their conjugate times, but our statements are more general. Interactions between the local and the global (for example, dependence of the local action on global times dual to constants) degrades full space-time diffeomorphism invariance down to spatial diffeomorphism invariance, and so an extra degree of freedom appears. When these presumably primordial global interactions switch off, the local action recovers full invariance and so the usual two gravitons, but a legacy matter component is left over, bearing the extra degree of freedom. Under the assumption that the preferred foliation is geodesic, this component behaves like dark matter, except that 3 of its 4 local degrees of freedom are frozen, forcing its rest frame to coincide with the preferred foliation. The nonfrozen degree of freedom (the number density of the effective fluid) is the survivor of the extra “graviton” present in the initial theory and keeps memory of all the past global interactions that took place in a given location in the preferred foliation. Such “painted-on” dark matter is best distinguished from the conventional one in situations where the preferred frame would be preposterous if all 4 degrees of freedom of dark matter were available. We provide one example: an outflowing halo of legacy matter with exact escape speed at each point and a very specific profile, surrounding a condensed structure made of normal matter.

Published by the American Physical Society
2024
Poissonian Cellular Potts Models Reveal Nonequilibrium Kinetics of Cell Sorting
Authors: Belousov R. , Savino S. , Moghe P. , Hiiragi T. , Rondoni L. , Erzberger A.
Published: June 2024

Cellular Potts models are broadly applied across developmental biology and cancer research. We overcome limitations of the traditional approach, which reinterprets a modified Metropolis sampling as dynamics, by introducing a physical timescale through Poissonian kinetics and by applying principles of stochastic thermodynamics to separate thermal and relaxation effects from athermal noise and nonconservative forces. Our method accurately describes cell-sorting dynamics in mouse-embryo development and identifies the distinct contributions of nonequilibrium processes, e.g., cell growth and active fluctuations.

Published by the American Physical Society
2024
Effect of the atomic structure of complexions on the active disconnection mode during shear-coupled grain boundary motion
Authors: Pemma Swetha , Janisch Rebecca , Dehm Gerhard , Brink Tobias
Published: June 2024

The migration of grain boundaries leads to grain growth in polycrystals and is one mechanism of grain-boundary-mediated plasticity, especially in nanocrystalline metals. This migration is due to the movement of dislocationlike defects, called disconnections, which couple to externally applied shear stresses. While this has been studied in detail in recent years, the active disconnection mode was typically associated with specific macroscopic grain boundary parameters. We know, however, that varying microscopic degrees of freedom can lead to different atomic structures without changing the macroscopic parameters. These structures can transition into each other and are called complexions. Here, we investigate [111¯] symmetric tilt boundaries in fcc metals, where two complexions—dubbed domino and pearl—were observed before. We compare these two complexions for two different misorientations: In Σ19b[111¯](178) boundaries, both complexions exhibit the same disconnection mode. The critical stress for nucleation and propagation of disconnections is nevertheless different for domino and pearl. At low temperatures, the Peierls-like barrier for disconnection propagation dominates, while at higher temperatures the nucleation is the limiting factor. For Σ7[111¯](145) boundaries, we observed a larger difference. The domino and pearl complexions migrate in different directions under the same boundary conditions. While both migration directions are possible crystallographically, an analysis of the complexions' structural motifs and the disconnection core structures reveals that the choice of disconnection mode and therefore migration direction is directly due to the atomic structure of the grain boundary.

Published by the American Physical Society
2024
Epitaxial superlattices as a framework for stabilizing different
LaNiO3
structures
Authors: Misják F. , Ortiz R. A. , Geiger D. , Kinyanjui M. K. , Schierle E. , Fürsich K. , Christiani G. , Logvenov G. , Keimer B. , Kaiser U. , Benckiser E.
Published: June 2024

Targeted material design is at the center of research efforts on epitaxial, complex oxide heterostructures. Due to the strong electron-lattice coupling, small structural modifications are often decisive for the resulting macroscopic, physical properties of artificially layered materials. Here we report on a detailed structural analysis of a set of differently stacked LaNiO3−LaGaO3 superlattices by transmission electron microscopy. We find that the relative thickness ratio of the two superlattice sublayers affects the structural network, resulting in different Ni–O bond lengths and Ni–O–Ni angles under the same epitaxial strain conditions. Whereas the bond length values depend mainly on the LaNiO3 layer thickness, bond angles are mainly influenced by the LaGaO3 layer thickness. The orbital polarization determined from x-ray absorption spectroscopy measurements shows that the superlattice with the smallest deviation of both values compared to bulk shows the highest orbital polarization. Therefore, the thickness ratio of the two superlattice components can be regarded as an additional effective tool to tune the functional properties of nickelates.

Published by the American Physical Society
2024
In Situ
Magnetometry of Iron in Human Dopaminergic Neurons Using Superresolution MRI and Ion-Beam Microscopy
Authors: Brammerloh Malte , Sibgatulin Renat , Herrmann Karl-Heinz , Morawski Markus , Reinert Tilo , Jäger Carsten , Müller Roland , Falkenberg Gerald , Brückner Dennis , Pine Kerrin J. , Deistung Andreas , Kiselev Valerij G. , Reichenbach Jürgen R. , Weiskopf Nikolaus , Kirilina Evgeniya
Published: June 2024

Paramagnetic transition metals play a crucial role as cofactors in various cellular catalytic processes. However, their high concentrations in reactive oxidation states can induce oxidative stress, resulting in cell dysfunction or death. Hence, it is vital to have methods to monitor metal concentrations and paramagnetic properties in cells for medicine and cell biology. Here we present a novel multimodal method for in-cell magnetometry enabling direct measurement of metal magnetic properties within individual cells in tissue, without prior isolation and at room temperature. Individual cell magnetic moments are measured using superresolution magnetic resonance imaging (MRI) microscopy at 9.4 T by detecting microscopic magnetic-field perturbations around the cells. The cellular metal content is quantified using ion-beam microscopy or synchrotron micro-x-ray fluorescence for the same cells. The metal magnetic susceptibility at 9.4 T is then obtained from the slope of the cell magnetic moments’ dependence on cell metal content. To estimate the susceptibility at lower fields, multifield MR relaxometry and biophysical modeling are employed, extrapolating the 9.4-T susceptibility values to fields as low as 3 T. We apply the new method to determine the susceptibility of iron accumulated in human dopaminergic neurons inside neuromelanin, the by-product of dopamine synthesis. The susceptibility of iron in neuromelanin is measured to be χρ=(2.98±0.19)×10−6  m3/kg providing unique insights into the biochemistry of iron inside dopaminergic neurons. The obtained value reveals a predominant monoatomic low-affinity iron-binding site within neuromelanin, indicating a higher neurotoxicity of iron than previously suggested. Furthermore, the measured susceptibility value establishes a quantitative relationship between cellular iron concentration and iron-sensitive MRI parameters, which can be noninvasively measured . This breakthrough paves the way for the detection of dopaminergic neuron density and iron load, requiring a standard clinical MRI scanner only. It promises to facilitate early diagnosis of Parkinson’s disease. In conclusion, our presented novel method enables the direct measurements of magnetic properties of paramagnetic metals within single cells with high sensitivity and across large cell groups within a macroscopic volume, providing invaluable information about the cellular biology of metals.

Published by the American Physical Society
2024
Lost in translation: is Taiwan’s bilingual policy in graduate school a myth?
Authors: Feng Kuo-Zheng
Published: June 2024

Purpose

This study intended to bridge this gap by investigating the perspectives of international students regarding Taiwan’s bilingual education policy and its impact on their willingness to enroll in graduate programs in Taiwan. Additionally, the comparisons among international students from diverse backgrounds were examined.

Design/methodology/approach

Employing a qualitative research design, the study included nine participants from three countries, with each country contributing three students. Three sessions of semi-structured interviews were conducted, supplemented by the analysis of 15 documents from 8 organizations and universities.

Findings

Results indicated predominantly negative views toward Taiwan’s bilingual education policy, with little impact reported by two participants and none by others. Furthermore, themes derived from document analysis deviated from participants' viewpoints.

Originality/value

A focus on students from southern Asia, which was the major source of international students in Taiwan, becomes critical. In the same vein, little literature has been found concerning graduate students' perceptions toward bilingual education policy, which should be thoroughly explored as well.
Processing and analysis of friction vibration signal of diamond-like carbon film microtextured dry gas seal rings
Authors: Chen Delin , Chen Yan , Chen Jinxin
Published: June 2024

Purpose

This paper aims to analyze the characteristics of friction vibration signals and identify the vibration excitation source at the start and stop stage of microtextured end face of dry gas seals.

Design/methodology/approach

The friction pair consists of a diamond-like carbon (DLC) film microtextured seal ring and a spiral groove seal ring. Friction vibration signal feature extraction method based on harmonic wavelet packet and spectrum analysis was proposed. Signals were collected using acceleration sensor, acquisition card and LabVIEW software. Vibration acceleration signal was decomposed into 32 frequency bands using MATLAB wavelet packet transformation. The 32nd band coefficient was extracted for reconstruction, time-domain and spectral waveforms were obtained and spectra before/after denoising were compared.

Findings

The end face of the DLC film microtextured seal ring generates a good dynamic pressure effect, and the friction and vibration reduction effects are obvious. The harmonic wavelet packet can decompose the vibration signal conveniently and precisely. In the case of this experiment, the frequency of vibration of the seal ring is 7500 HZ.

Originality/value

The results show that the method is effective for the processing of friction vibration signal and the identification of vibration excitation source. The findings will provide ideas for the frictional vibration signal processing and basis for further research in the field of tribology of dry gas seal ring.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-03-2024-0084/