bluuebunny/crossref_metadata_2025 huggingface dataset:
Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells
Authors: Kowar Alexander , Becker Jonas P. , Del Pizzo Rossella , Tang Zhiwei , Champagne Julien , Körner Pierre-René , Navarro Jasmine Montenegro , Tilghman Fiona Megan , Sakeer Hanan , Riemer Angelika B. , Agami Reuven , Loayza-Puch Fabricio
Published: January 2025

Mitosis is a critical phase of the cell cycle and a vulnerable point where cancer cells can be effectively disrupted, leading to cell death and inhibition of tumor growth. However, challenges such as drug resistance remain significant in clinical applications. During mitosis, mRNA translation is generally downregulated, while non-canonical translation of specific transcripts proceeds. Here, we demonstrate that mitotic cancer cells redistribute ribosomes toward the 5’ untranslated region (5’ UTR) and the start of the coding sequence (CDS), enhancing the translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). This mitotic induction of uORF/uoORF enriches the presentation of immunopeptides at the surface of cancer cells following treatment with mitotic inhibitors. Functional assays indicate the potential of such neoepitopes to provoke cancer-cell killing by T cells. Altogether, our findings highlight the therapeutic potential of targeting uORF/uoORF-derived neoepitopes in combination with mitotic inhibitors to enhance immune recognition and tumor cell elimination.
SLFN11-mediated tRNA regulation induces cell death by disrupting proteostasis in response to DNA-damaging agents
Authors: Iimori Yuki , Morita Teppei , Masuda Takeshi , Kitajima Shojiro , Kono Nobuaki , Kageyama Shun , Galipon Josephine , Sasaki Atsuo T. , Kanai Akio
Published: January 2025

DNA-damaging agents (DDAs) have long been used in cancer therapy. However, the precise mechanisms by which DDAs induce cell death are not fully understood and drug resistance remains a major clinical challenge. Schlafen 11 (SLFN11) was identified as the gene most strongly correlated with the sensitivity to DDAs based on mRNA expression levels. SLFN11 sensitizes cancer cells to DDAs by cleaving and downregulating tRNALeu(TAA). Elucidating the detailed mechanism by which SLFN11 induces cell death is expected to provide insights into overcoming drug resistance. Here, we show that, upon administration of DDAs, SLFN11 cleaves tRNALeu(TAA), leading to ER stress and subsequent cell death regulated by inositol-requiring enzyme 1 alpha (IRE1α). These responses were significantly alleviated by SLFN11 knockout or transfection of tRNALeu(TAA). Our proteomic analysis suggests that tRNALeu(TAA) influences proteins essential for maintaining proteostasis, especially those involved in ubiquitin-dependent proteolysis. Additionally, we identified the cleavage sites of tRNALeu(TAA) generated by SLFN11 in cells, and revealed that tRNA fragments contribute to ER stress and cell death. These findings suggest that SLFN11 plays a crucial role in proteostasis by regulating tRNAs, and thus determines cell fate under DDA treatment. Consequently, targeting SLFN11-mediated tRNA regulation could offer a novel approach to improve cancer therapy.

GRAPHICAL ABSTRACT
Unveiling Hidden Threats: Introduction of a Routine Workflow for Label-Free and Non-destructive Detection of Microplastics in Human FFPE Tissue Sections
Authors: Gruber Elisabeth S. , Karl Verena , Duswald Kristina , Bhamidipalli Mukund S. , Schlederer Michaela , Limberger Tanja , Teleky Béla , Kenner Lukas , Brandstetter Markus
Published: January 2025

Microplastic (MP) pollution has emerged as a significant environmental and health concern. This study aimed at developing a novel method for detecting MP particles in deparaffinized formalin-fixed paraffin-embedded (FFPE) routine tissue sections of human colon samples. By utilizing mid-infrared photothermal (MIP) microscopy, also known as optical photothermal infrared (OPTIR) spectroscopy, we here aimed to establish a work-flow representing a non-destructive infrared spectroscopic approach for distinct identification and localization of polymers in FFPE colon tissue sections by respecting standardized protocols well integrated into clinical routine. After OPTIR analysis, samples were processed to H&E staining for histopathological analysis at defined regions of interest. By using OPTIR spectroscopy, we succeeded in localizing polyethylene (PE), polystyrene (PS), and polyethylene terephthalate (PET) MPs in distinct regions of interest (21 PE particles, 1 PS particle, 1 PET fiber) and clearly identifying the embedded polymers in the respective colon tissue sections. Subsequent H&E analysis confirmed characteristic histopathological features of inflammation spatially associated with the respective MP polymers. We present here for the first time a diagnostic workflow that has the potential to enhance our understanding of MP accumulation in routine organ tissue slides and allows for exploration of its implications for human health. The observed morphological H&E features in proximity to the identified MPs could possibly indicate a link between MP exposure and colon inflammation.
AI in ECG-Based Electrolyte Imbalance Prediction: A Systematic Review and Meta Analysis
Authors: Dasdelen Muhammed Furkan , Almas Furkan , Dasdelen Zehra Betul , Balci Yapalak Ayse Nur , Marr Carsten
Published: January 2025

Background

Electrolyte imbalances significantly affect heart function, making electrocardiography (ECG) a crucial non-invasive tool. This study systematically reviewed and meta-analyzed AI models’ diagnostic accuracy for detecting these imbalances from ECG, aiming to enhance early detection and improve cardiac care.

Methods

We searched 9 databases and reference lists. Two reviewers assessed bias via the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Test performance data were extracted into 2×2 tables and pooled estimates of specificity, sensitivity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model, presented in forest plots and summary receiver operating characteristic curves. We explored heterogeneity by meta-regression, examining internal/external datasets and the number of leads.

Results

21 studies addressing potassium, calcium, and sodium were included. A meta-analysis was conducted only on potassium imbalances (10 studies), covering over 600,000 ECGs from five countries, mostly 12-lead. Among eight studies focused on hyperkalemia, pooled sensitivity, specificity, and DOR were 0.856 (95% CI: 0.829–0.879), 0.788 (0.744–0.826), and 21.8 (17.8–26.7). For hypokalemia (six studies), pooled sensitivity, specificity, and DOR were 0.824 (0.785– 0.856), 0.724 (0.668–0.774), and 12.27 (9.15–16.47). QUADAS-2 assessment showed a 52% high risk of bias in patient selection, mainly due to inadequate sampling details and case-control approaches.

Conclusion

AI models can detect ECG-based electrolyte abnormalities, particularly hyperkalemia, and valuable in ICU settings requiring frequent electrolyte assessments and in home monitoring for patients with end-stage renal disease. However, larger retrospective and prospective studies across diverse clinical settings, hospitals, ethnic groups, countries, and regions are warranted.
Deciphering the zebrafish hepatic duct heterogeneity and cell plasticity using lineage tracing and single-cell transcriptomics
Authors: Mi Jiarui , Ren Lipeng , Liu Ka-Cheuk , Buttò Lorenzo , Colquhoun Daniel , Andersson Olov
Published: January 2025

Despite the liver’s recognized regenerative potential, the role of the hepatic ductal cells (a.k.a. biliary epithelial cells), its heterogeneity, and functionality remain incompletely understood in this process. This study provides a comprehensive examination of the molecular and cellular mechanisms underpinning liver ductal development and liver regeneration in zebrafish, with a spotlight on the functional roles ofherfamily genes in these processes. Using state-of-the-art knock-in zebrafish models and single-cell transcriptomics we reveal the differential expression patterns of the differenthergenes, of whichher2,her6, andher9, were identified as specific molecular signatures for distinguishing different ductal cell types with unique morphology and spatial distribution. Particularly,her9serves as a pan-ductal marker and shows responsiveness to the synergistic effect of Notch and BMP signaling. By analyzing multiple single-cell RNA-seq datasets, we identify numerous ductal markers which are functional proteins for ductal integrity, and most notably CRISPR mutagenesis demonstrates thather9is essential for hepatocyte recovery. Using multiple transgenic and knock-in zebrafish lines and genetic fate mapping, we provide a detailed characterization of the ductal remodeling process under development and extreme loss of intra-hepatic duct, highlighting the remarkable ductal cell plasticity. Single-cell transcriptomics of lineage-tracedher9-expressing liver ducts in static and regenerative states uncover distinct cell clusters with unique molecular signatures and morphology, reflecting the liver’s regenerative dynamics and highlight relevant key biological processes that could be leveraged to expedite liver regeneration.
Metatranscriptomics sheds light on “who is doing what” in the coralPorites lutea
Authors: Tandon Kshitij , Hu Juntong , Ricci Francesco , Blackall Linda Louise , Medina Mónica , Kühl Michael , Verbruggen Heroen
Published: January 2025

Global decline of coral reefs due to climate change calls for effective, nature-based strategies to protect these crucial ecosystems. Developing such strategies requires a thorough understanding of the complex roles and interactions of key inhabitants within coral holobionts. Using a metatranscriptomics approach, we investigated the transcriptionally active microbiome of the healthy stony coralPorites lutea, focusing on the coral tissue, the green endolithic algal layer (Ostreobium layer), and the deeper coral skeleton. We show distinct, metabolically active communities within these compartments and highlight substantial metabolic redundancy across carbon, nitrogen, and sulphur pathways. Our study provides the first transcriptomic evidence of the ability ofOstreobiumto transfer fixed carbon to other members of the holobiont and the coral host. Additionally, we identified critical roles of diverse coral holobiont members in nutrient cycling and maintaining homeostasis through scavenging of reactive oxygen and nitrogen species. This study provides novel molecular-level understanding of the functional roles played by diverse coral holobiont members in their respective compartments and underscores that corals harbour several distinct microbiomes with a wide array of functions.
Comprehensive Infectome Analysis Reveals Diverse Infectious Agents with Zoonotic Potential in Wildlife
Authors: Hou Xin , Wang Jing , Wang Da-Xi , Chen Ye , Li Xin-Xin , Wu Wei-Chen , Le Shi-Jia , Mei Shi-Qiang , Liu Han-Lin , Feng Yun , Yang Li-Fen , Shi Pei-Bo , Ren Zi-Rui , Yang Lin , He Hai-Jian , Song Wan-Jie , Chen Jie , Zhu Meng-Meng , Jiang Zhi-Wen , Li Xing-Mei , Li Mei-Rong , Guo Deyin , Holmes Edward C. , Deng Zi-Qing , Shi Mang
Published: January 2025

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus – Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.
AMPylation regulates PLD3 processing
Authors: Hoffmann Laura , Eckl Eva-Maria , Bérouti Marleen , Pries Michael , Koller Aron , Guhl Charlotte , Hellmich Ute A. , Hornung Veit , Xiang Wei , Jae Lucas T. , Kielkowski Pavel
Published: January 2025

The 5’-3’ exonuclease phospholipase D3 (PLD3) is a single-pass transmembrane protein undergoing sequential post-translational modifications (PTM) byN-glycosylation, AMPylation and proteolytic cleavage. The substrates of PLD3 5’-3’ exonuclease activity are single-stranded DNAs and RNAs, which act as ligands for Toll-like receptors (TLRs) and trigger a downstream pro-inflammatory response. Although PLD3 has primarily been studied in immune cells, recent findings indicate its enrichment in neurons, where it plays a role in regulating axonal fitness in Alzheimer’s disease (AD). However, the regulatory mechanisms governing the proteolytic processing of PLD3 into its catalytically active soluble form and its functional roles in both immune and neuronal cells remain unclear. Here, we describe the functional implications of PLD3 AMPylation, its direct interaction with the protein adenylyltransferase FICD, and changes in PLD3 processing in Parkinson’s disease (PD) patient-derived neurons. We identified PLD3 AMPylation sites within the proteins’ soluble region and show that mutation of these sites lead to loss of PLD3 exonuclease catalytic activity. FICD AMP-transferase accelerates PLD3 degradation and induces cellular stress response. Furthermore, depletion of the two human AMP-transferases FICD and SelO point towards a complex regulatory network governing PLD3 AMPylation. Together, our findings demonstrate a critical role of AMPylation in PLD3 processing and regulation of its catalytic activity and provide new insights into the protein’s transport and localization to lysosomes. The observation that PLD3 regulation in PD-derived neurons is altered compared to healthy neurons further highlights its role in neurodegenerative diseases.
Age-dependent alterations in the head-direction signal in a rat model of Fragile X Syndrome
Authors: Moore Noah , Duszkiewicz Adrian J. , Asiminas Antonis , Dudchenko Paul A. , Peyrache Adrien , Wood Emma R.
Published: January 2025

Fragile X Syndrome (FXS) is a common monogenic cause of autism spectrum disorder and intellectual disability (ASD/ID), but the neural mechanisms underlying its symptoms remain unclear. Here, we investigate the development of the head-direction (HD) system in a rat model of FXS (Fmr1-/yrats). Using high-density silicon probes, we recorded neuronal activity in the postsubiculum (PoSub), a cortical hub of the HD system, during exploration and sleep in juvenile and adultFmr1-/yand wild-type (WT) rats. JuvenileFmr1-/yrats exhibited enhanced HD tuning characterized by sharper directional tuning curves and improved stability of the HD signal in relation to the external environment. This enhancement was intrinsic to the HD circuit and persisted across behavioral and sleep states. However, by adulthood, HD tuning inFmr1-/yrats became unstable, with increased drift in the allocentric reference frame despite intact intrinsic HD dynamics. These findings reveal a transient enhancement of spatial coding in the HD system of juvenileFmr1-/yrats, followed by a degradation in adulthood, providing insights into network-level dysfunctions in FXS and their developmental trajectories. Overall, our work establishes the HD system as a valuable and tractable model for studying neurodevelopmental disorders.
Transfer learning applied in predicting small molecule bioactivity
Authors: Tian Li , Huang Hugh Hongkai , Martin Eric , Wei Judy Ying , Xu Shaoyong , Huang Junzhou
Published: January 2025

Despite over a half-century of effort by computational chemists, developing accurate empirical QSAR (Quantitative Structure-Activity Relationships) models for predicting bioactivity directly from chemical structure has remained elusive. The difficulties have been especially pronounced for virtual screening, finding new active compounds substantially different from the known chemical matter used to train the models. Recent breakthroughs have been achieved by employing transfer of learning across huge numbers of bioactivity assays, greatly increasing the amount and diversity of chemical and biological information that informs each model. An early example was Profile-QSAR (pQSAR), a 2-level stacked model, where level-2 PLS (Partial Least Squares) models characterize compounds by their profile of bioactivity predictions from individual level-1 random forest regression QSAR models built on up to 10,000+ other assays. This study introduces metaNN, a meta-learner that trains deep neural networks (DNN) for each individual assay initialised from a well-generalized consensus DNN optimized across all assays. Comparison of the results suggested that while Profile-QSAR and metaNN perform similarly overall, metaNN works slightly better for smaller assays which were well-predicted by the consensus DNN; whereas pQSAR struggled more with smaller assays, due to the large number of level-1 models but was less sensitive to similarity to an overall consensus. An ensemble average of both methods combined the strengths of each, working better than either alone. The similar performance of the 2 largely orthogonal algorithms raises questions about whether we are approaching a limit of prediction accuracy in transfer learning, for this application scenario.
Involvement of PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 in COPII assembly by interacting with SAR1 GTPase
Authors: Lung (龍惠方) Hui-Fang , Chu Jia-Dong , Liu Tzu-Yin
Published: January 2025

The plant-specific endoplasmic reticulum (ER)-resident PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (PHF1) is structurally related to SEC12, which initiates the coat protein complex II (COPII) assembly as a guanine nucleotide exchange factor (GEF) by activating the small GTPase SAR1. In contrast, PHF1 loses the conserved catalytic residues critical for GEF activity and instead specifically assists the ER exit of the plant PHOSPHATE TRANSPORTER1 (PHT1) family. However, the underlying molecular mechanism remains to be elucidated. In this study, we showed that the overexpression ofArabidopsis thalianaPHT1;1 (AtPHT1;1) but not of SUGAR TRANSPORTER 1 (AtSTP1) caused a portion ofAtPHF1 distribution intoAtSAR1b-,AtSAR1c- andAtSEC24a-labeled ER exit sites in the tobacco transient expression system. Based on thein-plantatripartite split-GFP association,AtPHF1 interacted withAtSAR1b andAtSAR1c but not with other COPII-related proteins. By performing the miniTurbo-based proximity labeling in agro-infiltrated tobacco leaves, we verified the interaction ofAtPHF1 andAtSAR1b and demonstrated its physiological relevance by co-immunoprecipitation of the endogenousAtPHF1 andAtPHT1;1/2/3 proteins withAtSAR1c-GFP usingArabidopsistransgenic lines. Furthermore, while both the cytosolic and transmembrane domains ofAtPHF1 contribute to the interaction withAtSAR1b andAtSAR1c,AtPHF1 preferentially interacted with the GDP-locked inactive form ofAtSAR1b. On the basis of these findings, we propose that by interacting with SAR1 GTPase, PHF1 participates in the early step of COPII recruitment for the ER export of PHT1 proteins.
Re-visiting the potential impact of doxycycline post-exposure prophylaxis (doxy-PEP) on the selection of doxycycline resistance inNeisseriacommensals
Authors: Robinson Leah R. , McDevitt Caroline J. , Regan Molly R. , Quail Sophie L. , Swartz Makenna , Wadsworth Crista B.
Published: January 2025

Doxycycline post-exposure prophylaxis (doxy-PEP) is a preventative strategy demonstrated to reduce bacterial sexually transmitted infections in high-risk populations. However, the impact of doxy-PEP on antibiotic resistance acquisition in key members of our microbiomes, is as of yet unclear. For example, commensalNeisseriaare known reservoirs of resistance for gonococci through horizontal gene transfer (HGT), and are more likely to experience bystander selection due to doxy-PEP as they are universally carried. Thus, the consequences of doxycycline selection on commensalNeisseriawill be critical to investigate to understand possible resistance mechanisms that may be transferred to an important human pathogen. Here, we usein vitroantibiotic gradients to evolve fourNeisseriacommensals (N. cinerea, N. canis, N. elongata, and N. subflava,n=4 per species) across a 20-day time course; and use whole genome sequencing to nominate derived mutations. After selection, 12 of 16 replicates evolved doxycycline resistance (> 1 μg/mL). Across resistant lineages: An A46T substitution in the repressor of the Mtr efflux pump (MtrR) and a V57M substitution in the 30 ribosomal protein S10 were clearly associated with elevated MICs. Additional mutations in ribosomal components also emerged in strains with high MICs (i.e.,16S rRNA G1057C, RplX A14T). We find the MtrR 46T, RpsJ 57M, and RplX 14T circulating in natural commensal populations. Furthermore,in vitroco-evolution ofN. gonorrhoeaewithNeisseriacommensals demonstrated rapid transfer of the pConj plasmid toN. subflavaandN. cinerea, and pblatoN. cinerea. Finally, collection of novel commensals from human hosts reveals 46% of isolates carrying doxycycline resistance; and doxycycline resistance was significantly greater in participants self-reporting doxycycline use in the past 6 months. High-level doxycycline resistance (> 8 μg/mL) was always associated with carriage of the ribosomal protection protein (tetM)and pConj. Ultimately, characterizing the contemporary prevalence of doxycycline resistance, and underlying resistance mechanisms, in commensal communities may help us to predict the long-term impact of doxy-PEP onNeisseria, and the likelihood of transferring particular genotypes across species’ boundaries.
Source of dietary protein alters the abundance of proteases, intestinal epithelial and immune proteins both directly and via interactions with the gut microbiota
Authors: Awan Ayesha , Bartlett Alexandria , Blakeley-Ruiz J. Alfredo , Richie Tanner , Ziegler Amanda , Kleiner Manuel
Published: January 2025

Dietary protein has been shown to impact long-term health outcomes differentially depending on its amount and source. It has been suggested that interactions of the gut microbiota with dietary proteins mediate some of the effects of dietary protein on health outcomes. However, it remains unclear what specific host responses drive the health effects of dietary proteins from different plant and animal sources. Additionally, which specific host responses are mediated by interactions of dietary protein source with the gut microbiota and which host responses are caused by dietary proteins directly is not well understood. We used metaproteomics to quantify dietary, host, and microbial proteins in fecal samples of conventional and germ-free mice fed purified dietary protein from six different plant and animal sources, including casein, egg-white, soy, brown rice, pea, and yeast. We characterized differences in the host fecal proteome across the six dietary protein sources as well as between the conventional and germ-free mice for each source to determine how the host responds to the different dietary protein sources and the role of the gut microbiota in mediating these responses. We found that both the source of dietary protein and the presence or absence of the gut microbiota drive the host response to dietary protein source in the fecal host proteome. Host proteins pertaining to immune response, digestion, and barrier function were differentially abundant in different protein sources with and without the gut microbiota. These changes in the host response correlated with changes in microbial composition and differences in protein digestibility. Our results show how dietary protein sources, through their interactions with the gut microbiota, impact several aspects of host physiology.
Canaries differentially modulate solo and overlapping singing during the transition to the breeding season
Authors: Totiger Santhosh , Alcami Pepe
Published: January 2025

Songbirds sing different song types depending on the social context. Songs can be categorized into two types based on their timing relative to other birds’ songs: solo and temporally-over-lapping songs. Overlapping songs have been typically characterized in the breeding season, in which they are associated with an aggressive social context. However, whether both song types occur year long, and whether they show differential modulation of their frequency and properties during the transition between the non-breeding and the breeding season has been rarely studied. Here we investigate, in a group of domesticated canaries(Serinus canaria), the variation of singing in both song types at the transition between the nonbreeding and the breeding season. We found that both song types were present outside the breeding season. Whereas for solo songs, duration and its variability, fraction of time singing and number of songs increased as the breeding season approached, overlapping songs showed opposite trends. Furthermore, both song types were distributed more homogeneously as the daylength increased. Overall, the differential changes of both song types at the seasonal time scale suggest differential underlying mechanisms and functions of these two song types found in a social setting.
Structural insights into mechanisms of zinc scavenging by theCandida albicanszincophore Pra1
Authors: Syrjanen Johanna L , Nore Alexandre , Roselletti Elena , Chakraborty Tanmoy , Perera Rajika L , Wilson Duncan
Published: January 2025

Candida albicanscauses more than 400,000 life-threatening, and half a billion mucosal infections annually. In response to infection, the host limits availability of essential micronutrients, including zinc, to restrict growth of the invading pathogen. As assimilation of zinc is essential forC. albicanspathogenicity, its limitation induces the secretion of the zincophore protein Pra1 to scavenge zinc from the host. Pra1 also plays a number of important roles in host-pathogen interactions and is conserved in most fungi. However, the structure of fungal zincophores is not known. Here, we present the first cryogenic electron microscopy structures ofC. albicansPra1 in its apo- and zinc- bound states, at 2.8 and 2.5 Å resolution respectively. Our work reveals a hexameric ring-like assembly with multiple zinc binding sites. Through genetic studies, we show that one of these zinc binding sites is essential forC. albicansgrowth under zinc restriction but does not affect the inflammatory properties of Pra1. These data provide a foundation for future work to explore the structural basis of Pra1-mediated host-pathogen interactions,C. albicanszinc uptake, as well therapeutics development.
The complete λ-carrageenan depolymerization cascade from a marine Pseudoalteromonad revealed by structural analysis of the enzymes
Authors: Vickers Chelsea J. , Hettle Andrew G. , Hobbs Joanne K. , Shapiro-Ward Sarah , Pluvinage Benjamin , Medley Brendon J. , McGuire Bailey E. , Mihalynuk Liam , Nitin  , Zandberg Wesley F. , Boraston Alisdair B.
Published: January 2025

Carrageenans are a complex group of polysaccharides derived from the cell walls of red macroalgae. They are an abundant, yet recalcitrant nutrient source for most marine heterotrophic bacteria. Some member species of thePseudoalteromonasgenus are effective at metabolizing carrageenan. However, the enzymatic pathway for λ-carrageenan, one of the most sulfated naturally occurring polysaccharides, remains unknown. Using detailed structural analysis by X-ray crystallography we reveal the sophisticated and cyclic enzymatic cascade deployed byPseudoalteromonas distincta(strain U2A) to utilize λ-carrageenan. The cascade incorporates ten glycoside hydrolases and five sulfatases that are specific for λ-carrageenan and cooperate to completely deconstruct this polysaccharide, thus yielding galactose monosaccharides for subsequent energy production. The detailed molecular understanding of λ-carrageenan depolymerisation provided includes structural evidence for a lesser described sulfatase catalytic mechanism and elucidation of a distinct catabolic cascade that is unique from previously described carrageenan metabolic pathways. This insight also holds potential for the application of enzymatic logic in the generation of high value products from abundant natural biopolymers, such as carrageenans.
A neural signature of touch aversion and interpersonal problems in Borderline Personality Disorder
Authors: Voelter Jella , Postin Danilo , Croy Ilona , Hurlemann René , Scheele Dirk
Published: January 2025

Introduction

Patients with borderline personality disorder (BPD) suffer from severe social impairments and interpersonal problems. Social touch can provide comfort and facilitate the maintenance of social bonds, and preliminary evidence indicates a negative evaluation of social touch in patients with BPD. However, the neural mechanisms underlying aberrant touch processing in BPD and its role for social impairments are still unclear.

Methods

We recruited 55 BPD patients and 31 healthy controls and used functional magnetic resonance imaging to probe neural responses to slow (i.e. C-tactile (CT)-optimal; affective) and fast (i.e. CT-suboptimal; discriminative) touch before and after four weeks of a residential dialectical behavior therapy (DBT) program. In addition to assessing BPD symptoms and interpersonal problems, we evaluated touch allowance maps and the attitude towards social touch.

Results

BPD patients showed a comprehensive negative bias towards social touch before the DBT, evident in a significantly more negative attitude towards and reduced comfort zones of social touch compared to healthy controls. Moreover, reduced comfort zones of social touch were associated with more interpersonal problems. Activation in the posterior insular cortex in response to CT-optimal touch was significantly reduced and correlated with the severity of interpersonal problems in BPD patients. Despite significant improvements in overall BPD symptom load, dysfunctional social touch processing persisted after four weeks of DBT, indicating trait-like disturbances in BPD.

Conclusions

An impaired insula-mediated integration of affective and sensory components of touch may constitute a clinically relevant biological signature of the complex interpersonal problems in BPD.
Sex Differences in the Comorbidity between Attention Deficit-Hyperactivity Disorder and Posttraumatic Stress Disorder: A Systematic Literature Review and Meta-Analysis
Authors: Wilson Julia , Fida Doruntina , Maurer Rie , Wiley Aleta , Rajasekera Therese , Spagnolo Primavera
Published: January 2025

Objective

Attention Deficit-Hyperactivity Disorder (ADHD) and Posttraumatic Stress Disorder (PTSD) are often comorbid and share a common core of symptoms. However, sex and gender-related factors significantly influence their prevalence, clinical presentation, and diagnosis. Here, we conducted a systematic literature review and meta-analysis to examine sex differences in ADHD/PTSD comorbidity during childhood and adulthood.

Methods

A scoping review of PsycINFO and PubMed yielded 13 eligible studies with complete outcome data. We conducted fixed-effects meta-analyses of the sex-stratified prevalence of ADHD/PTSD using pooled odds ratios (OR) with a 95% confidence interval (CI). Fixed-effects subgroup analyses were performed using age as a subgroup. Effect size heterogeneity was assessed using the I2index and Cochran’s Q test.

Results

In the whole sample (N= 13,585; F= 7005, M= 6580), the diagnosis of ADHD/PTSD was significantly higher in females than in males (OR = 1.32,p= 0.02). Between-study heterogeneity was low-to-moderate and not significant (I2= 41%;p= 0.06), validating the fixed-effects model. Age-stratified subgroup analyses revealed higher ADHD/PTSD odds in females compared to males only in adult populations (OR=1.41;p =0.01). Additionally, females were more likely to be diagnosed with both disorders in studies where ADHD was the primary diagnosis (OR = 1.60;p =0.002), and in studies employing structured clinical interviews as diagnostic tools (OR = 1.46;p =0.009).

Conclusions

Our study is the first to show that the association between ADHD and PTSD is stronger in females, suggesting that ADHD may increase risk for PTSD in a sex-specific manner.
Dynamic global acetylation remodeling during the yeast heat shock response
Authors: Hardman-Kavanaugh Rebecca E. , Storey Aaron J. , Stuecker Tara N. , Hood Stephanie E. , Barrett-Wilt Gregory A. , Krishnamurthi Venkata R. , Wang Yong , Byrum Stephanie D. , Mackintosh Samuel G. , Edmondson Rick D. , Wahls Wayne P. , Tackett Alan J. , Lewis Jeffrey A.
Published: January 2025

All organisms experience stress and must rapidly respond to changing conditions. Thus, cells have evolved sophisticated rapid-response mechanisms such as post-translational protein modification to rapidly and reversibly modulate protein activity. One such post-translational modification is reversible lysine acetylation, where proteomic studies have identified thousands of acetylated proteins across diverse organisms. While the sheer size of the ‘acetylome’ is striking, the function of acetylation for the vast majority of proteins remains largely obscure. Here, we show that global acetylation plays a previously unappreciated role in the heat shock response ofSaccharomyces cerevisiae.We find that dysregulated acetylation renders cells heat sensitive, and moreover, that the acetylome is globally remodeled during heat shock over time. Using quantitative acetyl-proteomics, we identified ∼400 high-confidence acetyl marks across ∼200 proteins that significantly change in acetylation when cells are shifted to elevated temperature. Proteins with significant changes in lysine acetylation during heat shock strongly overlap with genes induced or repressed by stress. Thus, we hypothesize that protein acetylation augments the heat shock response by activating induced proteins and inactivating repressed proteins. Intriguingly, we find nearly 40 proteins with at least two acetyl marks that significantly change in the opposite directions. These proteins are strongly enriched for chaperones and ribosomal proteins, suggesting that these two key processes are coordinately regulated by protein acetylation during heat shock. Moreover, we hypothesize that the same type of activating and inactivating marks that exist on histones may be a general feature of proteins regulated by acetylation. Overall, this work has identified a new layer of post-translational regulation that likely augments the classic heat shock response.
Proxy panels enable privacy-aware outsourcing of genotype imputation
Authors: Zhi Degui , Jiang Xiaoqian , Harmanci Arif
Published: January 2025

One of the major challenges in genomic data sharing is protecting participants’ privacy in collaborative studies and in cases when genomic data are outsourced to perform analysis tasks, for example, genotype imputation services and federated collaborations genomic analysis. Although numerous cryptographic methods have been developed, these methods may not yet be practical for population-scale tasks in terms of computational requirements, rely on high-level expertise in security, and require each algorithm to be implemented from scratch. In this study, we focus on outsourcing of genotype imputation, a fundamental task that utilizes population-level reference panels, and develop protocols that rely on using “proxy panels” to protect genotype panels, whereas the imputation task is being outsourced at servers. The proxy panels are generated through a series of protection mechanisms such as haplotype sampling, allele hashing, and coordinate anonymization to protect the underlying sensitive panel's genetic variant coordinates, genetic maps, and chromosome-wide haplotypes. Although the resulting proxy panels are almost distinct from the sensitive panels, they are valid panels that can be used as input to imputation methods such as Beagle. We demonstrate that proxy-based imputation protects against well-known attacks with a minor decrease in imputation accuracy for variants in a wide range of allele frequencies.
Massless fermions in uniform flux background on
T2×R
: Vacuum quantum numbers from single-particle filled modes using lattice regulator
Authors: Karthik Nikhil , Narayanan Rajamani , Romero Ray
Published: January 2025

The quantum numbers of monopoles in R3 in the presence of massless fermions have been analyzed using a uniform flux background in S2×R coupled to fermions. An analogous study in T2×R is performed by studying the discrete symmetries of the Dirac Hamiltonian in the presence of a static uniform field on T2 with a total flux of Q in the continuum. The degenerate ground states are classified based on their transformation properties under π2 rotations of T2 that leave the background field invariant. We find that the lattice analysis with overlap fermions exactly reproduces the transformation properties of the single-particle zero modes in the continuum. Whereas the transformation properties of the single-particle negative energy states can be studied in the continuum and the lattice, we are also able to study the transformation properties and the particle number (charge) of the many-body ground state on a finite lattice, and we show that the contributions from the fully filled single-particle states cannot be ignored.

Published by the American Physical Society
2025
Classical features, Anderson-Higgs mechanism, and unitarity in Lee-Wick pseudo-electrodynamics
Authors: Neves M. J.
Published: January 2025

In this paper, the dimensional reduction is applied to the Lee-Wick electrodynamics in which the classical sources are confined on a spatial plane. As result, the Lee-Wick pseudoelectrodynamics is achieved as a nonlocal electromagnetism defined in 1+2 dimensions. The Abelian Anderson-Higgs mechanism is so introduced in the Lee-Wick pseudo-electrodynamics through a complex scalar sector in 1+2 dimensions, breaking spontaneously the U(1)-gauge symmetry of the nonlocal theory. As consequence, the pseudo-Lee-Wick field acquires a light mass, beyond the usual heavy Lee-Wick mass, that is a natural mass parameter of the theory. After the spontaneous symmetry breaking takes place, classical features of the theory are discussed, as the pseudo-Proca-Lee-Wick electrodynamics, with the field equations and conservation laws. The introduction of Lee-Wick fermions also is proposed, in which it opens the discussion of a viable pseudo-Proca-Lee-Wick quantum electrodynamics in 1+2 dimensions. The unitarity at the tree level of the Lee-Wick pseudo-electrodynamics is discussed through the optical theorem.

Published by the American Physical Society
2025
Role of the curvaton after the last Planck dataset
Authors: Choi Gongjun , Ke Wenqi , Olive Keith A.
Published: January 2025

The expected improvements in the precision of inflationary physics observables including the scalar spectral index ns and the tensor-to-scalar ratio r will reveal more than just the viability of a particular model of inflation. In the presence of a curvaton field χ, supposedly dead models of inflation can be resurrected, as these observables are affected by curvaton perturbations. For currently successful models, improved constraints will enable us to constrain the properties of extra decaying scalar degrees of freedom produced during inflation. In this work, we demonstrate these diverse uses of a curvaton field with the most recent constraints on (ns,r) and two exemplary inflation models, a Starobinsky-like model and a model of new inflation. The specific models used as examples can be derived in the context of supergravity. Our analysis invokes three free parameters: the curvaton mass mχ, its decay rate Γχ, and the reheating temperature TRH produced by inflaton decays. We systematically analyze possible postinflationary era scenarios of a curvaton field. By projecting the most recent cosmic microwave background (CMB) data on (

n

s

,

r

) into this parameter space, we can either set constraints on the curvaton parameters from successful models of inflation (so that the success is not spoiled) or determine the parameters that are able to save a model for which ns is predicted to be below the experimental data. We emphasize that the initial value of ⟨χ2⟩∝H4/mχ2 produced during inflation is determined from a stochastic approach and thus not a free parameter in our analysis. We also investigate the production of local non-Gaussianity fNL(loc) and apply current CMB constraints to the parameter space. Intriguingly, we find that a large value of fNL(loc) of O(1) can be produced for both of the two representative inflation models.

Published by the American Physical Society
2025
Particle production from phase transition bubbles
Authors: Mansour Henda , Shakya Bibhushan
Published: January 2025

While first order phase transitions (FOPTs) have been extensively studied as promising cosmological sources of gravitational waves, the phenomenon of particle production from the dynamics of the background field during FOPTs has received relatively little attention in the literature, where it has only been studied with semianalytic estimates in some simplified settings. This paper provides improved numerical studies of this effect in more realistic frameworks, revealing important qualitative details that have been missed in the literature. We also provide easy to use analytic formulas that can be used to calculate particle production in generic FOPT setups.

Published by the American Physical Society
2025
Beyond the Quantum Cramér-Rao Bound
Authors: Hervas J. R. , Goldberg A. Z. , Sanz A. S. , Hradil Z. , Řeháček J. , Sánchez-Soto L. L.
Published: January 2025

The quantum Cramér-Rao bound (QCRB) stands as a cornerstone of quantum metrology. Yet, akin to its classical counterpart, it provides only local information and overlooks higher-order details. We leverage the theory of higher-order asymptotics to circumvent these issues, providing corrections to the performance of estimators beyond the QCRB. While the QCRB often yields a whole family of optimal states and several optimal measurements, our approach allows us to identify optimal states and measurements within the family that are otherwise equivalent according to the QCRB alone; these are requisite for optimal metrology before reaching the asymptotic limit. These results are especially pertinent when dealing with unitary processes.

Published by the American Physical Society
2025
Rheology of the vertex model of tissues: Simple shear and oscillatory geometries
Authors: Grossman Doron , Joanny Jean-Francois
Published: January 2025

Most tissue properties and biological processes in tissues are dependent on or are regulated by the local mechanical stresses: Examples are cell division and differentiation, or, at larger scales, tissue morphogensis. In this paper, we theoretically study the rheology of two-dimensional epithelial tissues described by a discrete vertexlike model of actively dividing cells. We use a general analytical coarse-grained continuum formulation, which allows for explicit calculation of the mechanical stresses and the cell size and shape in various geometries. We discuss two different scenarios, a tissue under an applied simple shear and a supported tissue on an oscillating substrate. We show that this model predicts most often a shear-thinning behavior under a constant shear rate and, in certain circumstances, a crossover from shear thickening at low shear rates to shear thinning at high shear rates. We give an analytical expression for the tissue response in an oscillating strain experiment in the linear regime and calculate it numerically in the nonlinear regime. When the tissue is supported by an oscillating substrate, it reorients depending on frequency and the Poisson ratio of the substrate. Reorientation can be gradual or sharp, depending on the tissue's reference perimeter and the substrate Poisson ratio and on frequency. We also show the existence of a tricritical point in the orientation phase space.

Published by the American Physical Society
2025
All product eigenstates in Heisenberg models from a graphical construction
Authors: Gerken Felix , Runkel Ingo , Schweigert Christoph , Posske Thore
Published: January 2025

Recently, large degeneracy based on product eigenstates has been found in spin ladders, kagome-like lattices, and motif magnetism, connected to spin liquids, anyonic phases, and quantum scars. We unify these systems by a complete classification of product eigenstates of Heisenberg XXZ Hamiltonians with Dzyaloshinskii-Moriya interaction on general graphs in the form of Kirchhoff rules for spin supercurrents. By this, we construct spin systems with extensive degree of degeneracy linked to exotic condensates which could be studied in atomic gases and quantum spin lattices.

Published by the American Physical Society
2025
Acetyl α-D-2,3,4-triacetyllyxopyranoside
Authors: Culver Shawn , Rhoad Jonathan S.
Published: January 2025

The structure of the title compound, C13H18O9, has monoclinic (P21) symmetry. It is of interest with respect to stereochemistry and the anomeric effect. Two acetyl subsituents adopt equatorial orientations and two are axial. The extended structure displays C—H...O hydrogen bonding.
Workplace practices and work-life balance in Europe: the role of gender and home and family care
Authors: Ferreira Pedro , Gomes Sofia , Lopes João M.
Published: January 2025

Purpose

The purpose of this study is to explore the ways in which work practices promote work-life balance when family time is available (as a spillover effect from work to personal life) and how differently they affect men and women.

Design/methodology/approach

A quantitative and longitudinal approach is taken based on data from a large database made up of 71,758 workers from 36 European countries, collected in 2021 by the European Working Conditions Survey. After preliminary analysis (including exploratory and confirmatory factorial analysis), the partial least square method was used to test the hypothesis of the conceptual model.

Findings

The results of this study reveal that some work practices (autonomy and confidence at work) positively affect work-life balance. The time available for family and domestic care positively affects work-life balance, and this effect is more relevant for women than for men.

Practical implications

These results are important for organizations that wish to promote not only family-friendly work practices but also above all gender-friendly work practices.

Originality/value

Based on a large sample of European workers, this study makes an important contribution by filling the gap on the understanding and importance of mechanisms outside the organizational context for promoting work-life balance through work practices, thus extending the notion of spillover effects while considering gender differences.