bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-session intervention with and without video support to prevent the worsening of emotional distress among healthcare workers during the SARS-CoV-2 pandemic: a randomized clinical trial
Authors: Salum Giovanni Abrahão , Spanemberg Lucas , Costa Marianna de Abreu , Simioni André Rafael , Gosmann Natan Pereira , de Souza Lívia Hartmann , Cuijpers Pim , Pine Daniel Samuel , Brunoni André Russowsky , Katz Natan , Umpierre Roberto Nunes , Kristensen Christian Haag , Manfro Gisele Gus , Fleck Marcelo Pio de Almeida , Dreher Carolina Blaya
Published: September 2024

BACKGROUND

The SARS-CoV-2 pandemic was a major stressful event that significantly affected healthcare providers. This study aimed to compare the efficacy of a single-session intervention (SSI) with and without weekly personalized pre-recorded videos to prevent the worsening of emotional distress.

METHODS

Nationwide randomized clinical trial conducted in Brazil from May 19, 2020 to December 31, 2021. We included healthcare professionals with levels of anxiety, depression, or irritability below a T-score of 70, defined by the Patient-Reported Outcomes Measurement Information System. The exclusion criterion was suicide risk. Participants were randomized to SSI or SSI plus weekly personalized pre-recorded videos for four weeks (SSI-ET). The primary outcome was the proportion of participants with a significant escalation of symptoms (i.e., T-score above 70). The trial was registered withClinicalTrials.gov(NCT04632082).

FINDINGS

Of the 3328 volunteers assessed for eligibility, 1112 participants were allocated to either SSI (n=549) or SSI-ET (n=563). The cumulative proportion of incident cases at six months was 17.5% (95% CI 13.1% to 21.6%) for SSI and 15% (95% CI 10.9% to 18.8%) for SSI-ET, with no difference between groups (HR=0.81, 95% CI 0.83 to 1.79). Both groups presented significant symptom reduction in the one-month assessment and maintained over three and six-month follow-ups (Cohen’s d range = 0.68 - 1.08).

CONCLUSIONS

We found no benefit of adding asynchronous videos to SSIs; however, we found strong effects for the synchronous component for preventing symptom worsening. This component emphasizes core elements of mental health support, such as active listening, validation, and empathic care. Due to its simplicity and scalability, this intervention shows promise as a public health measure to be widely implemented.

FUNDING

Ministry of Health of Brazil, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundo de Incentivo à Pesquisa/Hospital de Clínicas de Porto Alegre.
Properties of Alzheimer’s disease brain-derived tau aggregates define tau processing by human astrocytes
Authors: Reid Matthew J. , Salazar Melissa Leija , Troakes Claire , Lynham Steven , Srivastava Deepak P. , Perez-Nievas Beatriz Gomez , Noble Wendy
Published: September 2024

The templated misfolding of tau proteins accounts for tau pathology spread in Alzheimer’s disease (AD). Post-translational modifications, including phosphorylation at specific residues, are closely linked with tau seeding ability and clinical disease progression. Increasing evidence supports a contributing role for astrocytes in tau spread. This study demonstrates that tau aggregates from postmortem AD brain are internalized and processed by human astrocytes. Differences in the efficiency of tau internalization, clearance and/or seeding were noted, which may reflect molecular properties of tau. Notably, we observed a direct relationship between alterations in tau handling by astrocytes and astrocyte responses, which were evident in transcriptomic data. Dysregulated genes include several previously identified as upregulated in reactive astrocytes in AD brain, as well as being implicated in pathological tau clearance by autophagy and other pathways. The study provides new insights into the complex interplay between tau molecular diversity and astrocyte responses in AD.
Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms
Authors: Wenz Brandon M. , He Yuan , Chen Nae-Chyun , Pickrell Joseph K. , Li Jeremiah H. , Dudek Max F. , Li Taibo , Keener Rebecca , Voight Benjamin F. , Brown Christopher D. , Battle Alexis
Published: September 2024

Background

Understanding the genetic causes for variability in chromatin accessibility can shed light on the molecular mechanisms through which genetic variants may affect complex traits. Thousands of ATAC-seq samples have been collected that hold information about chromatin accessibility across diverse cell types and contexts, but most of these are not paired with genetic information and come from diverse distinct projects and laboratories.

Results

We report here joint genotyping, chromatin accessibility peak calling, and discovery of quantitative trait loci which influence chromatin accessibility (caQTLs), demonstrating the capability of performing caQTL analysis on a large scale in a diverse sample set without pre-existing genotype information. Using 10,293 profiling samples representing 1,454 unique donor individuals across 653 studies from public databases, we catalog 23,381 caQTLs in total. After joint discovery analysis, we cluster samples based on accessible chromatin profiles to identify context-specific caQTLs. We find that caQTLs are strongly enriched for annotations of gene regulatory elements across diverse cell types and tissues and are often strongly linked with genetic variation associated with changes in expression (eQTLs), indicating that caQTLs can mediate genetic effects on gene expression. We demonstrate sharing of causal variants for chromatin accessibility and diverse complex human traits, enabling a more complete picture of the genetic mechanisms underlying complex human phenotypes.

Conclusions

Our work provides a proof of principle for caQTL calling from previously ungenotyped samples, and represents one of the largest, most diverse caQTL resources currently available, informing mechanisms of genetic regulation of gene expression and contribution to disease.
RTN4IP1 is essential for the final stages of mitochondrial complex I assembly and coenzyme Q biosynthesis
Authors: Oláhová Monika , Guerra Rachel M. , Collier Jack J. , Heidler Juliana , Thompson Kyle , White Chelsea R. , Castañeda-Tamez Paulina , Cabrera-Orefice Alfredo , Lightowlers Robert N. , Chrzanowska-Lightowlers Zofia M. A. , Wittig Ilka , Pagliarini David J. , Taylor Robert W.
Published: September 2024

A biochemical deficiency of mitochondrial complex I (CI) underlies ∼30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants inRTN4IP1,encoding a mitochondrial NAD(P)H oxidoreductase. Here, we demonstrate that RTN4IP1 deficiency causes a CI assembly defect in both patient fibroblasts and knockout cells, and report that RTN4IP1 is abona fideCI assembly factor. Complexome profiling revealed accumulation of unincorporated ND5-module and impaired N-module production. RTN4IP1 patient fibroblasts also exhibited defective coenzyme Q biosynthesis, substantiating this emerging function of RTN4IP1. Thus, our data reveal RTN4IP1 plays an essential role in both the terminal stages of CI assembly and in coenzyme Q metabolism, and that pathogenicRTN4IP1variants impair both functions in patients with mitochondrial disease.
Right Caudate Volume and Executive Functions in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)
Authors: Hai Tasmia , Swansburg Rose , Kahl Cynthia K. , Mrazik Martin , Lemay Jean-François , MacMaster Frank P.
Published: September 2024

Background

The caudate and putamen have previously been implicated in Attention-Deficit/Hyperactivity Disorder (ADHD). However, previous studies have not investigated the relationship between the caudate and putamen with executive function (EF). The current study investigated the clinical relevance of the caudate and putamen with respect to EF.

Method

We studied 49 children (24 ADHD/25 typically developing children (TDC)). All participants in the ADHD group had to undergo a 48-hour stimulant medication washout period. Participants completed cognitive tasks related to working memory/inhibition and underwent a T1-weighted MRI sequence. All parents completed behaviour rating scales using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2). Data were analyzed using multivariate analysis of covariance, Pearson correlations, and linear regressions.

Results

Children with ADHD demonstrated a higher frequency of perseverative errors compared to TDC (p <.05), and their parents reported significantly more EF challenges(p<.001). No difference was observed in the working memory tasks. No significant volumetric differences were seen in the caudate or the putamen. A linear regression model suggested that the right caudate volume accounted for 10.3% of the variance in emotion regulation as reported by parents on the BRIEF-2 in the overall sample.

Discussion

We observed significant EF challenges without volumetric differences. However, the right caudate was correlated to parent ratings of emotional regulation, highlighting the need to consider emotional regulation difficulties in ADHD.
Brain-wide circuitry underlying altered auditory habituation in zebrafish models of autism
Authors: Wilde Maya , Ghanbari Anahita , Mancienne Tessa , Moran Ailís , Poulsen Rebecca E. , Constantin Lena , Lee Conrad , Scholz Leandro Aluisio , Arnold Joshua , Qin Wei , Karle Timothy J. , Petrou Steven , Favre-Bulle Itia , Hoffman Ellen J. , Scott Ethan K.
Published: September 2024

Auditory processing is widely understood to occur differently in autism, though the patterns of brain activity underlying these differences are not well understood. The diversity of autism also means brain-wide networks may change in various ways to produce similar behavioral outputs. We used larval zebrafish to investigate auditory habituation in four genetic lines relevant to autism:fmr1,mecp2,scn1labandcntnap2. In free-swimming behavioral tests, we found each line had a unique profile of auditory hypersensitivity and/or delayed habituation. Combining the optical transparency of larval zebrafish with genetically encoded calcium indicators and light-sheet microscopy, we then observed brain-wide activity at cellular resolution during auditory habituation. As with behavior, each line showed unique alterations in brain-wide spontaneous activity, auditory processing, and adaptation in response to repetitive acoustic stimuli. We also observed commonalities in activity across our genetic lines that indicate shared circuit changes underlying certain aspects of their behavioral phenotypes. These were predominantly in regions involved in sensory integration and sensorimotor gating rather than primary auditory areas. Overlapping phenotypes include differences in the activity and functional connectivity of the telencephalon, thalamus, dopaminergic regions, and the locus coeruleus, and excitatory/inhibitory imbalance in the cerebellum. Unique phenotypes include loss of activity in the habenula inscn1lab, increased activity in auditory regions infmr1,and differences in network activity over time inmecp2andcntnap2. Comparing these distinct but overlapping brain-wide auditory networks furthers our understanding of how diverse genetic factors can produce similar behavioral effects through a range of circuit- and network-scale mechanisms.
E. coliassociated with Crohn’s disease exhibit distinct strategies to colonize macrophages
Authors: Bruder Emma , Nedjar Hosni , Quenech’Du Nicole , Chevarin Caroline , Vazeille Emilie , Granotier Marie , Singh Parul , Buisson Anthony , Barnich Nicolas , Espéli Olivier
Published: September 2024

Patients with Crohn’s disease exhibit abnormal colonization of the intestine by Proteobacteria, particularly the adherent-invasiveEscherichia coli(AIEC) group. These bacteria are predominant in the mucus, adhere to epithelial cells, colonize them, and survive inside macrophages. We recently demonstrated that the acclimation of strain LF82 to phagolysosomal stress occurs in two distinct steps: first, a replication halt producing stress- tolerant persisters, and second, a replication phase that leads to the formation of Intracellular Bacterial Communities (IBC) organized with a biofilm-like matrix. Given the significant genomic diversity among strains with the AIEC phenotype, we conducted a comparative analysis of the genomes and macrophage colonization characteristics of 13 AIEC strains collected from patients during a clinical study conducts by the CHU of Clermont-Ferrand. Our results demonstrate that IBCs serve as replicative niches for all AIEC strains within macrophages. However, these strains form IBCs using different strategies, including varying levels of phagosome detoxification, distinct biofilm characteristics, and diverse macrophage responses. Our study reveals a strong positive correlation between vacuole acidification and persister induction that explains intracellular survival of the different strains. In addition, we revealed distinct AIEC dissemination strategies outside macrophages, which may contribute to the propagation of inflammation in the human host. These findings highlight that research on pathogens and pathobionts with plastic genomes should not rely solely on a few laboratory models.
The Hox Gene,abdominal Acontrols timely mitotic entry of neural stem cell and their growth during CNS development inDrosophila
Authors: Das Papri , Murthy Smrithi , Abbas Eshan , White Kristin , Arya Richa
Published: September 2024

The size of a cell is important for its function and physiology. Interestingly, size variation can be easily observed in clonally derived embryonic and hematopoietic stem cells. Here, we investigated the regulation of stem cell growth and its association with cell fate. We observed heterogeneous sizes of neuroblasts or neural stem cells (NSCs) in theDrosophilaventral nerve cord (VNC). Specifically, thoracic NSCs were larger than those in the abdominal region of the VNC. Our research uncovered a significant role of the Hox geneabdominal A(abdA) in the regulation of abdominal NSC growth. Developmental expression of AbdA retards their growth and delays mitotic entry compared to thoracic NSCs. The targeted loss ofabdAenhanced their growth and caused an earlier entry into mitosis with a faster cycling rate. Furthermore, ectopic expression ofabdAreduced the size of thoracic NSCs and delayed their entry into mitosis. We suggest thatabdAplays an instructive role in regulating NSC size and exit from quiescence. This study demonstrates for the first time the involvement ofabdAin NSC fate determination by regulating their growth, entry into mitosis and proliferation rate, and thus their potential to make appropriate number of progeny for CNS patterning.

Significance statement

Understanding the upstream regulation of various aspects of the cell cycle is very important, how cell growth influences the process is largely unknown.

We found an instructive role of the Hox geneabdominal Ain maintaining the small size of neural stem cells (NSCs) and limiting their ability to undergo mitosis.

This mechanism is crucial, as it helps NSCs generate the necessary number of neurons at the appropriate developmental stage, thereby contributing to proper central nervous system patterning.
Crystal structure and catalytic mechanism of PL35 family glycosaminoglycan lyases with an ultrabroad substrate spectrum
Authors: Wei Lin , Cao Hai-Yan , Zou Ruyi , Du Min , Zhang Qingdong , Lu Danrong , Xu Xiangyu , Xu Yingying , Wang Wenshuang , Chen Xiu-Lan , Zhang Yu-Zhong , Li Fuchuan
Published: September 2024

Recently, a new class of glycosaminoglycan (GAG) lyases (GAGases) belonging to PL35 family has been discovered with an ultrabroad substrate spectrum that can degrade three types of uronic acid-containing GAGs (hyaluronic acid, chondroitin sulfate and heparan sulfate) or even alginate. In this study, the structures of GAGase II fromSpirosoma fluvialeand GAGase VII fromBacteroides intestinalisDSM 17393 were determined at 1.9 and 2.4 Å resolution, respectively, and their catalytic mechanism was investigated by the site-directed mutant of their crucial residues and molecular docking assay. Structural analysis showed that GAGase II and GAGase VII consist of an N-terminal (α/α)6toroid multidomain and a C-terminal two-layered β-sheet domain with Mn2+. Notably, although GAGases share similar folds and catalytic mechanisms with some GAG lyases and alginate lyases, they exhibit higher structural similarity with alginate lyases than GAG lyases, which may present a crucial structural evidence for the speculation that GAG lyases with (α/α)ntoroid and antiparallel β-sheet structures arrived by a divergent evolution from alginate lyases with the same folds. Overall, this study not only solved the structure of PL35 GAG lyases for the first time and investigated their catalytic mechanism, especially the reason why GAGase III can additionally degrade alginate, but also provided a key clue in the divergent evolution of GAG lyases that originated from alginate lyases.
RNase III inSalmonellaEnteritidis enhances bacterial virulence by reducing host immune responses
Authors: Chan Bill Kwan-wai , Li Yingxue , Ni Hongyuhang , Chan Edward Wai-chi , Deng Xin , Huang Linfeng , Chen Sheng
Published: September 2024

Salmonellais an important foodborne pathogen which comprises strains that exhibit varied virulence phenotypes and the capability of causing invasive human infection. In this study, the gene expression profile of foodborne and clinicalSalmonellastrains that exhibit high- and low-level virulence was investigated, with results showing that the expression level of a number of genes, including therncgene which encodes the RNase III ribonuclease, were exceptionally high in the high virulence strains. Investigation of the role ofrncin mediating expression of virulence phenotypes inSalmonellashowed that the product of this gene could enhance expression of the superoxide dismutase SodA, which is an essential determinant of survival fitness ofSalmonellaunder the oxidative stress elicited by the host immunity. On the other hand, we also discovered that the double-stranded RNA (dsRNA) released fromSalmonellacould trigger immune response of the host, and that the high-level expression of therncgene enabledSalmonellato evade the host immunity by reducing the amount of dsRNA accumulated in the bacterial cell. These findings provide insightful understanding of the regulation ofSalmonellavirulence and facilitate development of novel antimicrobial treatments through suppression of virulence expression and survival fitness of this important pathogen.
Developmental changes in diffusion markers of neurite vary across the hippocampus and covary with the cellular composition of hippocampal tissue
Authors: Kember J. , Gracia-Tabuenca Z. , Patel R. , Chakravarty M. , Chai X.J.
Published: September 2024

The hippocampus is a critical brain structure supporting memory encoding and retrieval, yet the development of its microstructure in humans remains unknown. Understanding this development may provide insight into the mechanisms underlying memory and their disruption in disease. To address this, we non-invasively estimated the density and branching complexity of neurite (dendrites, axons, glial processes) using diffusion-weighted MRI in 364 participants aged 8–21. With development, we observed large increases in neurite density and branching complexity that persisted until approximately 15 years of age before stabilizing at adult-like values. Increases in neurite density were relatively homogenous across hippocampal axes, whereas increases in branching complexity were heterogeneous; increasing primarily in CA1, SRLM, subiculum, and anterior hippocampus. To assess whether this development may be attributable to specific cell-types, we tested for spatial overlap between age-related change in neurite and the cell-type composition of hippocampal tissue via cross-reference with an out-of-sample gene-expression atlas. We found age-related changes in neurite density spatially overlapped with a granule cell component; whereas age-related changes in neurite branching complexity overlapped with a pyramidal neuron component. These results provide the first glimpse at the nonlinear maturation of hippocampal microstructure and the cell-type composition of hippocampal tissue underlying these changes.
Dynamics in thePhytophthora capsicieffector AVR3a11 confirm the core WY domain fold
Authors: Tolchard James , Chambers Vicki S. , Boutemy Laurence S. , Banfield Mark J. , Blumenschein Tharin M. A.
Published: September 2024

Oomycete pathogens cause large economic losses in agriculture through diseases such as late blight (Phytophthora infestans), and stem and root rot of soybean (Phytophthora sojae). The effector protein AVR3a, fromP. infestans, and its homologue AVR3a11 fromP. capsici, are examples of host-translocated effectors that interact with plant proteins to evade defence mechanisms and enable infection. Both proteins belong to the family of RXLR effectors and contain an N-terminal secretion signal, an RXLR motif for translocation into the host cell, and a C-terminal effector domain. Within this family, a large number of proteins have been predicted to contain one or more WY domains as their effector domain, and this domain is proposed to encompass a conserved minimal core fold containing three helices, further stabilised by additional helices or dimerization. In AVR3a11, a helical N-terminal extension to the core fold forms a four-helix bundle, as determined by X-ray crystallography. For a complete picture of the dynamics of AVR3a11, we have determined the solution structure of AVR3a11, and studied its dynamics in the fast timescale (ns-ps, from NMR relaxation parameters) and in the slow timescale (seconds to minutes, from hydrogen/deuterium exchange experiments). Hydrogen/deuterium exchange showed that the N-terminal helix is less stable than the other three helices, confirming the core fold originally proposed. Relaxation measurements confirm that AVR3a11 undergoes extensive conformational exchange, despite the uniform presence of fast motions in the spectral density function throughout most of its sequence. As functional residues are located in the more mobile regions, this flexibility in the slow/intermediate timescale may be functionally important.

Lay Summary

The effector protein AVR3a11, from the plant pathogenPhytophthora capsici, shows conformational flexibility in solution, particularly in the N-terminal helix, and in an intermediate timescale (ms-s). This confirms the core fold originally proposed and suggests that flexibility may be functionally important.
Copper resistance inLegionella pneumophila: role of genetic factors and host cells
Authors: Cameron Gillian , Faucher Sebastien P.
Published: September 2024

Copper is frequently found in drinking water due to its presence in the natural environment and the widespread usage of copper pipes. This toxic metal has a well-known antimicrobial activity, an activity harnessed in copper-silver ionization (CSI) to eliminate the opportunistic pathogenLegionella pneumophilafrom engineered water systems. Despite utilizing the antimicrobial properties of copper inLegionellacontrol, little is known about how copper containing environments affectL. pneumophilapopulations. The goal of this study is to understand howL. pneumophilaresponds to copper within a hot water distribution system (HWDS) environment. To answer this question, different sequence types and regulatory mutants were exposed to copper to compare their survival.L. pneumophilaisolates of 4 sequence types from 3 different HWDSs exhibited a wide diversity of phenotypes after copper stress. The ΔletAand ΔletSmutants were sensitive to copper, indicating that the LetAS two component system is important for copper resistance. Additionaly, transmissive phase cultures were more resistant to copper than replicative phase cultures. Therefore, the regulation of entry into transmissive phase by the LetAS system is essential forL. pneumophila’s ability to survive copper stress. In a water system,L. pneumophilareplicates within eukaryotic hosts. When cocultured with the host ciliateTetrahymena pyriformis,L. pneumophilawas more resistant to copper than when the bacteria were in a monoculture. No difference inL. pneumophilareplication inside of hosts in cocultures with or without copper was observed. This result confirms that the presence of host cells protectsL. pneumophilafrom copper stress. Therefore, presence of host cells in water system may limit the efficacy of copper-based control strategies.
Sweet science: Exploring the impact of fructose and glucose on brown adipocyte differentiation using optical diffraction tomography
Authors: Anantha Pooja , Wu Xiangdong , Elsaid Salaheldeen , Raj Piyush , Barman Ishan , Tee Sui Seng
Published: September 2024

The thermogenic capacity of brown adipose tissue (BAT) has garnered much attention for its potential to regulate systemic energy balance. BAT depot size and function need to be tightly to prevent loss of metabolic homeostasis due to energy dissipation via non-shivering thermogenesis. While adipocyte-intrinsic mechanisms controlling thermogenesis are critical, an increasing appreciation for the role of the BAT microenvironment is emerging. For example, changes in circulating hexoses due to dietary intake have shown to impact BAT function. Here, we show that murine BAT preadipocytes metabolism is impacted when fructose is used as the sole carbon source. Similarly differentiation medium containing only fructose yield mature adipocytes with fewer lipid droplets, with a concomitant decrease in adipogenic genes. These deficiencies are also observed in human BAT preadipocytes, where cutting-edge optical imaging modalities show a decrease in total cell mass and lipid mass in fructose-only medium. Taken together, the metabolic microenvironment significantly impacts BAT growth and function, with implications for the role of diets potentially mitigating the efficacy of BAT-targeted therapies.
Characterization and bioinformatic filtering of ambient gRNAs in single-cell CRISPR screens using CLEANSER
Authors: Liu Siyan , Hamilton Marisa C. , Cowart Thomas , Barrera Alejandro , Bounds Lexi R. , Nelson Alexander C. , Doty Richard W. , Allen Andrew S. , Crawford Gregory E. , Majoros William H. , Gersbach Charles A.
Published: September 2024

Recent technological developments in single-cell RNA-seq CRISPR screens enable high-throughput investigation of the genome. Through transduction of a gRNA library to a cell population followed by transcriptomic profiling by scRNA-seq, it is possible to characterize the effects of thousands of genomic perturbations on global gene expression. A major source of noise in scRNA-seq CRISPR screens are ambient gRNAs, which are contaminating gRNAs that likely originate from other cells. If not properly filtered, ambient gRNAs can result in an excess of false positive gRNA assignments. Here, we utilize CRISPR barnyard assays to characterize ambient gRNA noise in single-cell CRISPR screens. We use these datasets to develop and train CLEANSER, a mixture model that identifies and filters ambient gRNA noise. This model takes advantage of the bimodal distribution between native and ambient gRNAs and includes both gRNA and cell-specific normalization parameters, correcting for confounding technical factors that affect individual gRNAs and cells. The output of CLEANSER is the probability that a gRNA-cell assignment is in the native distribution over the ambient distribution. We find that ambient gRNA filtering methods impact differential gene expression analysis outcomes and that CLEANSER outperforms alternate approaches by increasing gRNA-cell assignment accuracy.

Graphical Abstract
Extracellular vesicle bioactivity and potential clinical utility is determined by mesenchymal stromal cell clonal subtype
Authors: Ioannou Savvas , Kay Alasdair G. , Stone Andrew P. , Rand Emma , Elberfeld Samuel , Bolton William , Larson Tony , Crossland Rachel E. , Kehoe Oksana , Mentlak David A. , Wang Xiao-Nong , MacDonald Chris , Genever Paul G.
Published: September 2024

Mesenchymal stromal cells (MSCs) are a promising source of therapeutic extracellular vesicles (EVs), however it is not clear how heterogeneity within a non-clonal MSC population will affect the collective EV pool. Here we used immortalised clonal MSC lines, termed Y201 and Y202, to examine how MSC phenotype influences EV character and function.

Although morphologically similar, Y201 EVs were more abundant in EV biomarkers versus Y202 EVs, with an enhanced miRNA and proteomic content, predicted to contribute to an elaborate EV corona particularly abundant in RGD-containing proteins fibronectin and MFG-E8. We demonstrated that Y201 EVs, but not Y202 EVs, significantly increased the proliferation of articular chondrocytes and that the proliferative effect was mediated at least in part via an RGD (integrin)-FAK-ERK1/2 axis. Both Y201 and Y202 EV subsets significantly reduced proliferative index scores of activated T cells. However, only Y201 EVs, not Y202 EVs, suppressed disease activity compared to controls in differentin vivomodels of inflammatory peritonitis and arthritis.

EVs released by closely related MSC subtypes within the same heterogeneous population differ significantly in terms of cargo abundance, bioactivity, and pre-clinicalin vivoefficacy. Analysis of defined EV subsets will aid mechanistic understanding and prioritisation for EV therapeutics.
The partitioning of fatty acids between membrane and storage lipids controls ER membrane expansion.
Authors: Lysyganicz Pawel K , Barbosa Antonio D , Khondker Shoily , Stewart Nicholas A , Carman George M , Stansfeld Phillip J , Dymond Marcus K , Siniossoglou Symeon
Published: September 2024

The biogenesis of membrane-bound organelles involves the synthesis, remodelling and degradation of their constituent phospholipids. How these pathways regulate organelle size, remains still poorly understood. Here we demonstrate that a lipid degradation pathway inhibits the expansion of the endoplasmic reticulum (ER) membrane. Phospholipid diacylglycerol acyltransferases (PDATs) use endogenous phospholipids as fatty acyl donors to generate triglyceride stored in lipid droplets. The significance of this non-canonical triglyceride biosynthetic pathway has remained elusive. We find that the activity of the yeast PDAT Lro1 is regulated by a membrane- proximal domain facing the luminal side of the ER bilayer. To reveal the biological roles of PDATs, we engineered an Lro1 variant with derepressed activity. We show that active Lro1 mediates the retraction of ER membrane expansion driven by phospholipid synthesis. Furthermore, the subcellular distribution and membrane turnover activity of Lro1 are controlled by diacylglycerol, produced by the activity of Pah1, a conserved member of the lipin family. Collectively, our findings reveal a lipid metabolic network that regulates endoplasmic reticulum biogenesis by converting phospholipids into storage lipids.
Protein domain embeddings for fast and accurate similarity search
Authors: Iovino Benjamin Giovanni , Tang Haixu , Ye Yuzhen
Published: September 2024

Recently developed protein language models have enabled a variety of applications with the protein contextual embeddings they produce. Per-protein representations (each protein is represented as a vector of fixed dimension) can be derived via averaging the embeddings of individual residues, or applying matrix transformation techniques such as the discrete cosine transformation (DCT) to matrices of residue embeddings. Such protein-level embeddings have been applied to enable fast searches of similar proteins; however, limitations have been found; for example, PROST is good at detecting global homologs but not local homologs, and knnProtT5 excels for proteins with single domains but not multidomain proteins. Here, we propose a novel approach that first segments proteins into domains (or subdomains) and then applies the DCT to the vectorized embeddings of residues in each domain to infer domain-level contextual vectors. Our approach, called DCTdomain, uses predicted contact maps from ESM-2 for domain segmentation, which is formulated as adomain segmentationproblem and can be solved using arecursive cutalgorithm (RecCut in short) in quadratic time to the protein length; for comparison, an existing approach for domain segmentation uses a cubic-time algorithm. We show such domain-level contextual vectors (termed asDCT fingerprints) enable fast and accurate detection of similarity between proteins that share global similarities but with undefined extended regions between shared domains, and those that only share local similarities. In addition, tests on a database search benchmark show that the DCTdomain is able to detect distant homologs by leveraging the structural information in the contextual embeddings.
Stout smearing and Wilson flow in lattice perturbation theory
Authors: Ammer Maximilian , Dürr Stephan
Published: September 2024

We present the expansion of stout smearing and the Wilson flow in lattice perturbation theory to order g03, which is suitable for one-loop calculations. As the Wilson flow is generated by infinitesimal stout smearing steps, the results are related to each other by taking the appropriate limits. We show how to apply perturbative stout smearing or Wilson flow to the Feynman rules of any lattice fermion action and illustrate them by calculating the self-energy of the clover-improved Wilson fermion.

Published by the American Physical Society
2024
Probing
χcJ(J=0,1,2)
decay into baryon and antibaryon with SU(3) flavor analysis
Authors: Lan Bo , Fan Xiu-Ping , Wang Ru-Min
Published: September 2024

With the available experimental results on χcJ(J=0,1,2) decays, we explore the decays of χcJ→B8B¯8 and χcJ→B10B¯10 based on the SU(3) flavor symmetry. In addition, we give an extensive discussion on the possible contributions from the SU(3) breaking effect and Σ0−Λ mixing. With the decay amplitude determined from an effective Hamiltonian, we also present the expected branching fractions for those unobserved decay modes, e.g., χcJ→nn¯ and χcJ→ΛΣ¯0+Λ¯Σ0, which are expected to be observed at the BESIII experiment and the future planned Super Tau-Charm facilities. Our results provide valuable insights that will aid in advancing our understanding of the mechanisms and characteristics of χcJ decays.

Published by the American Physical Society
2024
Scalar spectral functions from the spectral functional renormalization group
Authors: Horak Jan , Ihssen Friederike , Pawlowski Jan M. , Wessely Jonas , Wink Nicolas
Published: September 2024

We compute spectral functions in a scalar ϕ4-theory in three spacetime dimensions via the spectral functional renormalization group. This approach allows for the direct, manifestly Lorentz covariant computation of correlation functions in Minkowski spacetime, including a physical on-shell renormalization. We present numerical results for the spectral functions of the two- and four-point correlation functions for different values of the coupling parameter. These results agree very well with those obtained from another functional real-time approach, the spectral Dyson-Schwinger equation.

Published by the American Physical Society
2024
Waiting for inflation: A new initial state for the Universe
Authors: Melcher Brandon , Pradhan Arnab , Watson Scott
Published: September 2024

We propose a cosmological lingering phase for the initial state prior to inflation which would help address the singularity problem of inflation. The Universe begins with a constant (Hagedorn) temperature and then transitions into an inflationary universe while preserving the null energy condition (NEC). We first consider the phase space of positive spatial curvature models within general relativity and with matter sources that respect the NEC. Depending on the duration of the postlingering inflation, these models can produce a small amount of observable spatial curvature in the cosmic microwave background. We also discuss how lingering can arise with or without spatial curvature in theories of quantum gravity when considering the thermodynamic scaling of particles and its impact on the early Universe. The string theory dilaton is essential to the dynamics. There are many open questions that remain.

Published by the American Physical Society
2024
Search for Cosmic-Ray Boosted Sub-MeV Dark-Matter–Electron Scattering in PandaX-4T
Authors: Shang Xiaofeng , Abdukerim Abdusalam , Bo Zihao , Chen Wei , Chen Xun , Chen Yunhua , Cheng Chen , Cheng Zhaokan , Cui Xiangyi , Fan Yingjie , Fang Deqing , Geng Lisheng , Giboni Karl , Guo Xuyuan , Han Chencheng , Han Ke , He Changda , He Jinrong , Huang Di , Huang Junting , Huang Zhou , Hou Ruquan , Hou Yu , Ji Xiangdong , Ji Xiangpan , Ju Yonglin , Li Chenxiang , Li Jiafu , Li Mingchuan , Li Shuaijie , Li Tao , Lin Qing , Liu Jianglai , Lu Congcong , Lu Xiaoying , Luo Lingyin , Luo Yunyang , Ma Wenbo , Ma Yugang , Mao Yajun , Meng Yue , Ning Xuyang , Pang Binyu , Qi Ningchun , Qian Zhicheng , Ren Xiangxiang , Shaheed Nasir , Shao Xiyuan , Shen Guofang , Shen Manbin , Si Lin , Sun Wenliang , Tao Yi , Wang Anqing , Wang Meng , Wang Qiuhong , Wang Shaobo , Wang Siguang , Wang Wei , Wang Xiuli , Wang Xu , Wang Zhou , Wei Yuehuan , Wu Mengmeng , Wu Weihao , Wu Yuan , Xiao Mengjiao , Xiao Xiang , Xiong Kaizhi , Yan Binbin , Yan Xiyu , Yang Yong , Yu Chunxu , Yuan Ying , Yuan Zhe , Yun Youhui , Zeng Xinning , Zhang Minzhen , Zhang Peng , Zhang Shibo , Zhang Shu , Zhang Tao , Zhang Wei , Zhang Yang , Zhang Yingxin , Zhang Yuanyuan , Zhao Li , Zhou Jifang , Zhou Ning , Zhou Xiaopeng , Zhou Yubo , Zhou Zhizhen , Ge Shao-Feng , Xia Chen ,   PandaX Collaboration
Published: September 2024

We report the first search for the elastic scatterings between cosmic-ray boosted sub-MeV dark matter (DM) and electrons in the PandaX-4T liquid xenon experiment. Sub-MeV DM particles can be accelerated by scattering with electrons in the cosmic rays and produce detectable electron recoil signals in the detector. Using the commissioning data from PandaX-4T of 0.63  tonne·year exposure, we set new constraints on DM-electron scattering cross sections for DM masses ranging from 10  eV/c2 to 3  keV/c2.

Published by the American Physical Society
2024
Interplay between Point and Extended Defects and Their Effects on Jerky Domain-Wall Motion in Ferroelectric Thin Films
Authors: Bulanadi Ralph , Cordero-Edwards Kumara , Tückmantel Philippe , Saremi Sahar , Morpurgo Giacomo , Zhang Qi , Martin Lane W. , Nagarajan Valanoor , Paruch Patrycja
Published: September 2024

Defects have a significant influence on the polarization and electromechanical properties of ferroelectric materials. Statistically, they can be seen as random pinning centers acting on an elastic manifold, slowing domain-wall propagation and raising the energy required to switch polarization. Here we show that the “dressing” of defects can lead to unprecedented control of domain-wall dynamics. We engineer defects of two different dimensionalities in ferroelectric oxide thin films—point defects externally induced via He2+ bombardment, and extended quasi-one-dimensional a domains formed in response to internal strains. The a domains act as extended strong pinning sites (as expected) imposing highly localized directional constraints. Surprisingly, the induced point defects in the He2+ bombarded samples orient and align to impose further directional pinning, screening the effect of a domains. This defect interplay produces more uniform and predictable domain-wall dynamics. Such engineered interactions between defects are crucial for advancements in ferroelectric devices.

Published by the American Physical Society
2024
Ballistic deposition with memory: A new universality class of surface growth with a new scaling law
Authors: Roman Ahmed , Zhu Ruomin , Nemenman Ilya
Published: September 2024

Motivated by recent experimental studies in microbiology, we suggest modifying the classic ballistic deposition model of surface growth, where the memory of a deposition at a site induces more depositions at that site or its neighbors. By studying the statistics of surfaces in this model, we obtain three independent critical exponents: the growth exponent β=5/4, the roughening exponent α=2, and the new (size) exponent γ=1/2. The model requires modifying the Family-Vicsek scaling, resulting in the dynamical exponent z=α+γβ=2. This modified scaling collapses the surface width vs time curves for various lattice sizes. This previously unobserved universality class of surface growth could describe the surface properties of a wide range of natural systems.

Published by the American Physical Society
2024
Effect of the crystallographic orientation of the surface of single-crystal Si wafers on the endotaxial growth of NiSi2 nanoplates
Authors: Schuitek Thiago Paulino , da Silva Costa Daniel , Pereira Mattoso Filho Ney , Kellermann Guinther
Published: September 2024

A multi-technique analysis was used to investigate how the orientation of single-crystal Si wafer surfaces affects the size, shape and orientation of NiSi2 nanocrystals grown within the wafers through the thermal diffusion of Ni atoms from a nickel-doped thin film deposited on the surface. Nickel-doped thin films were prepared on silicon wafers with three distinct crystallographic orientations, [001], [110] and [111]. Three sets of samples were then annealed at 500, 600 and 700°C for 2 h. Regardless of crystallographic orientation or annealing temperature, NiSi2 nanoplates with a nearly hexagonal shape grew close to the external surface of the wafers, aligning their larger surfaces parallel to one of the planes of the Si{111} crystallographic form. The crystallographic orientation and annealing temperature in the 500–700°C range did not significantly affect the final values of the average diameter and thickness of the nanoplates. However, significant differences were noted in the number of nanoplates formed in Si wafers with different crystallographic orientations. The results indicate that these observed differences are correlated with the number of pre-existing defects in the wafers that influence the heterogeneous nucleation process. In addition, the average size and size dispersion were determined for pores at the surface of the Si wafers formed due to the etching process used for native oxide removal.
The dark side of work-life policies: the influence of co-workers taking childcare leave on work anxiety
Authors: Osso Katia , Halinski Michael
Published: September 2024

Purpose

While work-life policies (WLPs) are tools that employees may draw on to better manage and balance their work and life demands, there is growing evidence that suggests the usage of WLPs may negatively impact other employees. Drawing from the theory of role dynamics and social role theory, we examine the indirect effect of co-workers taking childcare leave (CTCL) on work anxiety via work-role overload, as well as the impact of gender on this indirect relationship.

Design/methodology/approach

We used Prolific Academic to recruit 236 employees to participate in a three-wave study. These data were analyzed as a hypothesized structural equation modelling (SEM) using SPSS AMOS.

Findings

Findings reveal: (1) CTCL positively relates to work anxiety via work-role overload, and (2) gender moderates this indirect effect such that this positive relationship is stronger for men than women.

Practical implications

Work-life policy makers should take note of the “hidden costs” associated with work-life policy usage on other employees. Managers should work with policy users to mitigate the negative effects of policy usage on others.

Originality/value

In contrast to broader WLP research, which focuses on the benefits of policy usage on the policy user, this research shows the negative implications of work-life policies on others’ work anxiety via work-role overload. In doing so, it becomes the first study to showcase a crossover effect of CTCL on employees’ work anxiety.
The augmenting role of digital banking in reconstructing women's economic empowerment
Authors: Rohatgi Swati , Gera Navneet
Published: September 2024

Purpose

The purpose of this study is to identify and assess the role of predictors to women’s economic empowerment (WEE). Moreover, the mediating role of digital banking usage (DBU) between financial literacy (FL) and WEE is empirically tested. The study also examines the moderation effect of educational level (EL) and employment sector (ES) on WEE.

Design/methodology/approach

Using a mixed-method approach, a comprehensive questionnaire was used to collect data of 482 women working in the formal ESs of Delhi-NCR. Partial least square structural equation modeling using SmartPLS-4 was used to test the explanatory and predictive power of the proposed model. This was followed by semi-structured interviews to collect qualitative data from 14 respondents.

Findings

The results present the following important findings: first, DBU, FL, women’s agency (WA) and workplace human resource policies (HR) significantly impact WEE, whereas government support (GS) and FL significantly impact DBU; second, DBU significantly mediates the relationship between FL and WEE; and third, ES significantly moderates the relationship between DBU and WEE.

Practical implications

This research also shares significant findings for practitioners and organizations by holistically identifying factors affecting WEE. These findings apply to both the human resource department of the employment sectors and the management of the banking sector.

Originality/value

The present study adds value to the scarce literature on the impact of DBU on WEE and highlights the mediating role of DBU along with the moderation effect of EL and ES. The study model incorporates novel constructs that impact WEE and offers new insights to various stakeholders in enhancing WEE. In addition, qualitative method was used to complement the quantitative findings.
Ethical mindset and the efficacy of tax ethical awareness initiatives
Authors: Danysh Hashemi Shannon , Daneshfar Alireza
Published: September 2024

Purpose

This study delves into the impact of an ethical mindset on the efficacy of ethical awareness within the tax profession and aims to ascertain whether the presence of an ethical mindset can account for the discrepancies in the literature and enhance the effectiveness of ethical awareness initiatives.

Design/methodology/approach

The research used a tax experiment involving both treatment and control groups. Both groups were presented with a tax-related scenario, with the treatment group subjected to a specific ethical awareness intervention. To gauge the participants’ ethical mindsets, they were divided into strong self-interest and mild self-interest mindset groups based on their Machiavellian scores. The analysis was conducted utilizing ANOVA to scrutinize the results.

Findings

The key findings shed light on the fact that while ethical awareness endeavors can enhance the likelihood of individuals making ethical choices in tax decisions, their effectiveness varies significantly depending on the individual’s ethical mindset. Furthermore, results show that gender affected the relationship between ethical mindset and ethical awareness effectiveness, and males with mild self-interest score reacted more to the ethical awareness intervention. Results support that individuals’ ethical mindset, measured as strong self-interest and mild self-interest, is pivotal in determining the effectiveness of ethical awareness efforts.

Originality/value

This study is unique because it evaluates the effect of ethical mindsets to provide a novel way to improve tax ethical awareness initiatives.