bluuebunny/crossref_metadata_2025 huggingface dataset:
Global plate model choice impacts reconstructions of the latitudinal biodiversity gradient
Authors: Jones Lewis A , Gearty William , Buffan Lucas , Allen Bethany J
Published: January 2025

The latitudinal gradient of declining species richness from the Equator towards the poles is one of the most pervasive macroecological patterns on Earth today. However, the ubiquity of this trend over geological timescales remains unclear. One reason for this uncertainty is that palaeobiologists need Global Plate Models (GPMs) to estimate the latitudinal position of organisms' remains at time of deposition. However, as GPMs constitute hypotheses for how tectonic plates have moved over Earth's history, reconstructions of the latitudinal biodiversity gradient (LBG) might also vary based on the GPM used. Here, using the fossil record of five major marine invertebrate groups, we evaluate the impact of GPM choice on reconstructions of the LBG over the Phanerozoic. Our results show that GPM choice can lead to different conclusions about the shape and strength of LBGs in deep time, even at a coarse spatial scale. These findings suggest additional caution is needed when reconstructing deep-time biogeographic patterns and macroevolutionary events, such as the origin of the present-day LBG. We therefore advocate for future palaeobiogeographic studies to conduct sensitivity analyses investigating the impact of GPM choice on their conclusions, and for greater interdisciplinary collaboration between palaeobiologists and palaeogeographic modellers to avoid common issues in the use of GPMs.
Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice
Authors: Mackowiak Bryan , Haggerty David L. , Lehner Taylor , Lin Yu-Hong , Fu Yaojie , Lu Hongkun , Pawlosky Robert J. , Ren Tianyi , Seo Wonhyo , Feng Dechun , Zhang Li , Lovinger David M. , Gao Bin
Published: January 2025

Background

Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. Ethanol is mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde and further to acetate via aldehyde dehydrogenases (ALDHs). Understanding how ethanol and its metabolites work together to initiate and drive continued ethanol consumption is crucial for identifying interventions for alcohol use disorder (AUD). Therefore, the goal of our study was to determine how ADH1, which is mainly peripherally-expressed and metabolizes >90% of ingested ethanol, modulates ethanol metabolite distribution and downstream behaviors.

Methods

Ethanol consumption in drinking-in-the-dark (DID) and two-bottle choice (2BC) drinking paradigms, ethanol metabolite concentrations, and lickometry were assessed after ADH1 inhibition and/or inAdh1-knockout (Adh1KO) mice.

Results

We found thatAdh1KO mice of both sexes exhibited decreased ethanol consumption and preference compared to wild-type (WT) mice in DID and 2BC. ADH1 inhibitor fomepizole (4-MP) also significantly decreased normal and sweetened ethanol consumption in DID studies. Measurement of ethanol and its metabolites revealed that ethanol was increased at 1h but not 15 min, peripheral acetaldehyde was slightly decreased at both time points, and ethanol-induced increases in acetate were abolished after ethanol administration inAdh1KO mice compared to controls. Similarly, ethanol accumulation as a function of consumption was 2-fold higher inAdh1KO or 4-MP treated mice compared to controls. We then used lickometry to determine how this perturbation in ethanol metabolism affects drinking microstructure.Adh1KO mice consume most of their ethanol in the first 30 min like WT mice but display altered temporal shifts in drinking behaviors and do not form normal bout structures, resulting in lower ethanol consumption.

Conclusions

Our study demonstrates that ADH1-mediated ethanol metabolism is a key determinant of ethanol consumption, highlighting a fundamental knowledge gap around how ethanol and its metabolites drive ethanol consumption.
Fine-Tuning of Material Properties via Catch Bonds
Authors: Rabbi Md Foysal , Koenderink Gijsje H. , Mulla Yuval , Kim Taeyoon
Published: January 2025

Semiflexible polymer networks are ubiquitous in biological systems, including a scaffolding structure within cells called the actin cytoskeleton. The polymers in these networks are often interconnected by transient bonds. For example, actin filaments in the cytoskeleton are physically connected via cross-linkers. The mechanical and kinetic properties of the cross-linkers significantly affect the rheological properties of the actin cytoskeleton. Here, we employed an agent-based model to elucidate how the force-dependent behaviors of the cross-linkers determine the material properties of passive networks without molecular motors and the force generation of active networks with molecular motors. The cross-linkers are assumed to behave as a slip bond whose dissociation rate is proportional to forces or as a catch-slip bond whose dissociation rate is inversely proportional to forces at low force level but proportional to forces at high force level. We found that catch-slip-bond cross-linkers can increase both stress and strain at a yield point by forming force-bearing elements that turn over continuously, which is impossible to achieve without the catch-slip bonds. In addition, we demonstrated that the catch-slip-bond cross-linkers help myosin motors generate greater internal contractile forces by reinforcing the force-bearing parts of the active network.
Assessing Generative Model Coverage of Protein Structures with SHAPES
Authors: Lu Tianyu , Liu Melissa , Chen Yilin , Kim Jinho , Huang Po-Ssu
Published: January 2025

Recent advances in generative modeling enable efficient sampling of protein structures, but their tendency to optimize for designability imposes a bias toward idealized structures at the expense of loops and other complex structural motifs critical for function. We introduce SHAPES (Structural and Hierarchical Assessment of Proteins with Embedding Similarity) to evaluate five state-of-the-art generative models of protein structures. Using structural embeddings across multiple structural hierarchies, ranging from local geometries to global protein architectures, we reveal substantial undersampling of the observed protein structure space by these models. We use Fréchet Protein Distance (FPD) to quantify distributional coverage. Different models are distinct in their coverage behavior across different sampling noise scales and temperatures; the frequency of TERtiary Motifs (TERMs) further supports the observations. More robust sequence design and structure prediction methods are likely crucial in guiding the development of models with improved coverage of the designable protein space.
Long-Read Low-Pass Sequencing for High-Resolution Trait Mapping
Authors: Lee Kendall C. , Korani Walid , Bentz Philip C. , Pokhrel Sameer , Ozias-Akins Peggy , Harkess Alex , Vaughn Justin , Clevenger Josh
Published: January 2025

Accelerating crop improvement is critical to meeting food security demands in a changing climate. Long-read sequencing offers advantages over short-reads in resolving structural variations (SVs) and aligning to complex genomes, but its high cost has limited adoption in breeding programs. Here, we develop a high-throughput, scalable approach for long-read low-pass (LRLP) sequencing and variant analysis with PacBio HiFi reads, and apply it to trait mapping in a complex tetraploid peanut (Arachis hypogaea) genome multi-parent advanced generation intercross. We analyze LRLP using both a single reference genome and a pangraph, using both proprietary and open-source tools to analyze SVs and coverage. An increased number of variants are consistently called for LRLP data compared to short-read data. At 1.63x average depth, LRLP sequencing covered 55% of the genome and 58% of gene space, outperforming 1.68x depth short-read low-pass sequencing, which achieved only 17% and 11%, respectively. Enhanced data retention after filtering for probabilistic misalignment and an ~8.5x decrease in cost per value further demonstrated LRLPs efficacy. Our results highlight LRLP sequencing as a scalable, cost-effective tool for high-resolution trait mapping, with transformative potential for plant breeding and broader genomic applications.
RNA sequencing reveals key factors modulating TNFα-stimulated odontoblast-like differentiation of dental pulp stem cells
Authors: Irfan Muhammad , Kim Ji Hyun , Sreekumar Sreelekshmi , Chung Seung
Published: January 2025

Inflammation is a complex host response to harmful infections or injuries, playing both beneficial and detrimental roles in tissue regeneration. Notably, clinical dentinogenesis associated with caries development occurs within an inflammatory environment. Reparative dentinogenesis is closely linked to intense inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs) into the dentin lineage. Understanding how inflammatory responses influence DPSCs is essential for elucidating the mechanisms underlying dentin and pulp regeneration. Given the limited data on this process, a broad approach is employed here to gain a deeper understanding of the complex mechanisms involved and to identify downstream signaling targets. This study aims to investigate the role of inflammation and the complement receptor C5L2 in the odontoblastic differentiation of DPSCs and the associated transcriptomic changes using poly-A RNA sequencing (RNA-seq). RNA-seq techniques provide insight into the transcriptome of a cell, offering higher coverage and greater resolution of its dynamic nature. Following inflammatory stimulation, DPSCs exhibit significantly altered gene profiles, including marked upregulation of key odontogenic genes, highlighting the critical role of inflammation in dentinogenesis. We demonstrate that TNFα-treated odontoblast-like differentiating DPSCs, under C5L2 modulation, exhibit significant differential gene expression and transcriptomic changes. The data presented may provide new avenues for experimental approaches to uncover pathways in dentinogenesis by identifying specific transcription factors and gene profiles.
A genetically based computational drug repurposing framework for rapid identification of candidate compounds: application to COVID-19
Authors: Voloudakis Georgios , Lee Kyung Min , Vicari James M. , Zhang Wen , Hoagland Daisy , Venkatesh Sanan , Bian Jiantao , Anyfantakis Marios , Wu Zhenyi , Rahman Samir , Gao Lina , Cho Kelly , Lee Jennifer S. , Iyengar Sudha K. , Luoh Shiuh-Wen , Assimes Themistocles L. , Hoffman Gabriel E. , tenOever Benjamin R. , Fullard John F. , Lynch Julie A. , Roussos Panos
Published: January 2025

Background

The development and approval of novel drugs are typically time-intensive and expensive. Leveraging a computational drug repurposing framework that integrates disease-relevant genetically regulated gene expression (GReX) and large longitudinal electronic medical record (EMR) databases can expedite the repositioning of existing medications. However, validating computational predictions of the drug repurposing framework remains a challenge.

Methods

To benchmark the drug repurposing framework, we first performed a 5-method-rank-based computational drug prioritization pipeline by integrating multi-tissue GReX associated with COVID-19-related hospitalization, with drug transcriptional signature libraries from the Library of Integrated Network-Based Cellular Signatures. We prioritized FDA-approved medications from the 10 top-ranked compounds, and assessed their association with COVID-19 incidence within the Veterans Health Administration (VHA) cohort (~9 million individuals). In parallel, we evaluatedin vitroSARS-CoV-2 replication inhibition in human lung epithelial cells for the selected candidates.

Results

Ourin silicopipeline identified seven FDA-approved drugs among the top ten candidates. Six (imiquimod, nelfinavir and saquinavir, everolimus, azathioprine, and retinol) had sufficient prescribing rates or feasibility for further testing. In the VHA cohort, azathioprine (odds ratio [OR]=0.69, 95% CI 0.62–0.77) and retinol (OR=0.81, 95% CI 0.72–0.92) were significantly associated with reduced COVID-19 incidence. Conversely, nelfinavir and saquinavir demonstrated potent SARS-CoV-2 inhibitionin vitro(~95% and ~65% viral load reduction, respectively). No single compound showed robust protection in bothin vivoandin vitrosettings.

Conclusions

These findings underscore the power of GReX-based drug repurposing in rapidly identifying existing therapies with potential clinical relevance; four out of six compounds showed a protective effect in one of the two validation approaches. Crucially, our results highlight how a complementary evaluation—combining epidemiological data andin vitroassays—helps refine the most promising candidates for subsequent mechanistic studies and clinical trials. This integrated validation approach may prove vital for accelerating therapeutic development against current and future health challenges.
Automated characterisation of cerebral microbleeds using their size and spatial distribution on brain MR images
Authors: Sundaresan Vaanathi , Zamboni Giovanna , Dineen Robert A , Auer Dorothee P , Sotiropoulos Stamatios N , Sprigg Nikola , Jenkinson Mark , Griffanti Ludovica
Published: January 2025

Cerebral microbleeds (CMBs) are small, hypointense hemosiderin deposits in the brain measuring around 2-10 mm in diameter. As one of the important biomarkers of small vessel disease, they have been associated with various neurodegenerative and cerebrovascular diseases. Hence, automated detection, and subsequent extraction of clinically useful metrics (e.g., size and spatial distribution) from CMBs are essential for investigating their clinical impact, especially in large-scale studies. While some work has been done for CMB segmentation, extraction of clinically relevant information is not yet explored. Herein, we propose the first automated method to characterise CMBs using their size and spatial distribution i.e., CMB count in three regions (and their sub-structures) used in microbleed anatomical rating scale (MARS): infratentorial, deep and lobar. Our method uses structural atlases of the brain for determining individual regions. On an intracerebral haemorrhage study dataset, we achieve a mean absolute error of 2mm for size estimation and an overall accuracy>90% for automated rating. The code and the atlas of MARS regions in MNI space are publicly available.

Key points

We present a method to automatically characterise cerebral microbleeds (size and location).

The method achieved a mean absolute error of 2 mm for size estimation.

Automated rating for infratentorial, deep and lobar regions achieved overall accuracy >90%

We made the code and atlas of MARS regions publicly available.
Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response
Authors: Thorel L. , Dolivet E. , Morice P-M. , Florent R. , Divoux J. , Perréard M. , Lecouflet L. , Desmartin G. , Marde Alagama C. , Giffard F. , Leconte A. , Lequesne J. , Clarisse B. , Briand M. , Traore A. , Villenet C. , Meneboo JP. , Babin G. , Gaichies L. , Martin-Françoise S. , Le Brun JF. , Rouzier R. , Brotin E. , Denoyelle C. , Vigneron N. , Leman R. , Vaur D. , Castera L. , Blanc-Fournier C. , Elie N. , Plancoulaine B. , Joly F. , Meryet-Figuière M. , Figeac M. , Weiswald L-B. , Poulain L.
Published: January 2025

There is an urgent need of precision medicine for ovarian cancer patients to identify patients who respond to chemotherapy and PARP inhibitors, a therapy targeting homologous recombination deficiency (HRD). Here we established a panel of 37 long-term patient-derived tumor organoids (PDTO) models of various histological subtypes from 224 patients and demonstrated that they mimic the histological and molecular characteristics of original tumors. Screening of chemotherapeutic drugs showed that PDTO exhibit heterogeneous responses, and that response of PDTO from high-grade serous ovarian carcinoma to carboplatin recapitulated patient response to first-line treatment. Additionally, the detection of HRD phenotype of PDTO using functional assay was associated with the results of the HRD test Genomic Instability Scar (GIScar). Although larger-scale investigations are needed to confirm the predictive potential of PDTO, these results provide further evidence of the potential interest of ovarian PDTO for functional precision medicine even if many challenges remain to be addressed.
CD2 expression is co-regulated with stemness- and exhaustion-associated factors in human T cells
Authors: Demetriou Philippos , Iakovou Maria , Gregoriou Gregoria , Vrachnos Dimitris , Chi Jianxiang , Tamamouna Vasilia , Constantinou Stavros , Papanastasiou Vakis , Antoniades Athos , Costeas Paul
Published: January 2025

The CD2-CD58 pathway has been highlighted as a major player in anti-tumour T cell immunity. Our study reveals that CD2 costimulation strength significantly correlates with T cell activation, the average number of cell divisions, fold expansion, and IFN-γ production. Our findings suggest that the correlation of CD2 strength with the level of CD25 expression is a potential regulatory mechanism by which CD2 strength enhances above proliferation parameters. We find that human brain cancer tumour-infiltrating CD8+ and CD4+ T cells exhibit reduced levels of CD2, suggestive of a compromised CD2 strength upon CD2 engagement. Through a genome-wide CRISPR-Cas9 knockout screen, we identified two epigenetic regulators, SUZ12 and BAP1, as positive modulators of CD2 expression. We demonstrate that BAP1 is crucial for the upregulation and sustained high expression of CD2 following T cell activation. We reveal that CD2 is co-regulated with other co-stimulatory/inhibitory receptors, and factors associated with T cell stemness and exhaustion, in a dose-dependent manner. Importantly, we rescue the loss of CD2 due to BAP1 knockout by pharmacological inhibition of histone deacetylases making this a harnessable regulatory pathway. The insight from our study enhance our understanding of CD2-mediated T cell regulation and identify essential regulators of this pathway.
Fine root endophytes forming winter mycorrhiza
Authors: Sentoku Takeshi , Komatsuda Yuki , Shimada Hayato , Arai Michio , Kobae Yoshihiro
Published: January 2025

Arbuscular mycorrhizal fungi, classified in the subphylum Glomeromycotina, are obligate symbionts that depend on photosynthetic products from plants. There is substantial evidence that AMF support plant and crop growth in natural and agricultural ecosystems. Fine root endophytes (FRE) also co-occur in plant roots with AMF in all but tropical environments. However, their presence remains poorly recognised, and their lifestyle and functionality remain largely unknown. Our analysis demonstrates that, in contrast to AMF, FRE colonise plants during the winter season, when photosynthesis is more challenging. It is also noteworthy that FRE was unable to colonise the roots of spring-sown crops. The results of our laboratory pot experiments demonstrated that low temperatures are not sufficient for FRE colonisation. Furthermore, we observed that FRE, in contrast to AMF, exhibited increased colonisation in soils containing metabolically inactive plants. Our results suggest that FRE does not contribute to the increase of ecosystem biomass through direct photosynthesis in summer, but may play an overlooked role in the formation of mycorrhiza-based soil ecosystems in winter. However, this winter ecosystem can be disrupted by conventional bare fallow management of the field, interrupting the annual cycle.
Phenological turnover matters when making trait-based predictions of plant-pollinator interactions
Authors: Cantwell-Jones Aoife R , Everson Juliet , Bates Olivia , Al-Hayali Abdullah , Allen George , Berard Lucas , Celiebe Frauke , Egleston Suzannah , Hudson Lucia , James Jacqui , Jung Lena , Kattan Moganavalli , Lejeune Renee , Svedin Johan , van Brakel Silas , van Unen Manon , Tylianakis Jason M , Larson Keith , Gill Richard J
Published: January 2025

1. Understanding the processes determining species interactions is key to predicting and safeguarding ecological networks under rapid environmental change. One approach to estimating interactions is to use morphologies of taxa interacting across trophic levels to reveal suites of traits they are more likely to interact with (i.e. a trait niche). 2. Previous work studying these morphological trait niches has typically used interactions between species that are pooled in space and time. However, species assemblages, and the traits of individuals within species, can change across even small landscapes over a season, leading to morphological trait space being dynamically reshaped. Therefore, it is unclear how morphological trait turnover affects our inferences of trait niches, and our ability to answer this is in part limited by a lack of individual-level trait data. 3. Here, we directly address this by studying a montane Arctic plant-pollinator community over five growing seasons (>1,300 hours of fieldwork). Specifically, we linked every recorded plant-bumblebee interaction with the traits of the bee individual involved (n = 1,150), to investigate 1) whether plant taxa (n = 10) exhibited bee trait niches by interacting with specific regions of multidimensional trait space of visiting bumblebees, and 2) how our inference of these trait niches was affected by considering bumblebee trait turnover and plant taxon turnover. 4. When not considering turnover (interactions in space and time are pooled), plant taxa demonstrated bee trait niches. However, next we considered how bee trait space is reshaped over the elevational and seasonal gradient (especially with the emergence of different castes), and how this reshaping co-occurs with different spatiotemporal ranges of the plant taxa. From this we found the degree to which plant taxa exhibited trait niches declined significantly, and that seasonal reshaping of bee trait space was the primary driver of this trend. 5. Overall, in highly dynamic systems, like the Arctic, overlooking community turnover could mask and even overestimate the ability of morphology to explain interactions. Hence, determining how morphological traits of individual interaction partners are in phenological synchrony at localised scales will be fundamental to understanding the role morphology plays in underpinning plant-pollinator interactions.
Consistent covariation of dispersal, life history and thermal niches across terrestrial arthropods
Authors: Logghe Garben , Batsleer Femke , Fandos Guillermo , Maes Dirk , Bonte Dries
Published: January 2025

Arthropods, as ectotherms, are experiencing global declines, with many species facing the need to either acclimate or disperse in response to climate change. To generate general insights into such responses, a framework integrating traits on life history, dispersal and thermal niche is currently lacking. In light of this, understanding to which degree these traits covary and are organised into syndromes are key to improve distribution forecasting under climate change. We quantified life history, dispersal and thermal range covariation among 4000 Western European arthropod species spanning eight orders, considering phylogenetic relationships to account for shared ancestry. We demonstrate the existence of two independent axes of life history variation: the fast-slow continuum and the reproductive strategy axis. Notably, species at the fast end of the continuum tend to have higher dispersal capacities and broader thermal niches than slower species. The resulting syndromes were surprisingly consistent across orders, indicating a relatively uniform pattern of trait covariations across arthropod groups. These trait combinations, which generally enhance range-shifting potential, point to the emergence of two distinct groups of arthropods: those well-suited and those less equipped to mitigate the effects of future climate change.
Age- and estrous-dependent effects of psilocybin in rats
Authors: Zylko AL , Rakoczy RJ , Roberts BF , Wilson M , Powell A , Page A , Heitkamp M , Fiest D , Jones JA , McMurray MS
Published: January 2025

Psilocybin, a psychedelic compound in “magic” mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intraoral psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Head twitch responses are thought to be mediated by 5-HT2Areceptors, but no age-or estrous-related differences in 5-HT2Areceptor expression were observed in the medial prefrontal cortex. Collectively, these results highlight the existence of age-and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.
Real-time diagnostics and personalized wound therapy powered by AI and bioelectronics
Authors: Li Houpu , Yang Hsin-ya , Lu Fan , Hee Wan Shen , Asefifeyzabadi Narges , Baniya Prabhat , Gallegos Anthony , Schorger Kaelan , Zhu Kan , Recendez Cynthia , Tebyani Maryam , Kesapragada Manasa , Keller Gordon , Kim Sujung , Luka George , Zlobina Ksenia , Nguyen Tiffany , Figuerres Sydnie , Franco Celeste , Devarajan Koushik , Barbee Alexie , Lin Kylie , Clayton Shannon M. , Eaton Annabelle , Aslankoohi Elham , Soulika Athena M. , Zhao Min , Teodorescu Mircea , Gomez Marcella , Isseroff Roslyn Rivkah , Rolandi Marco
Published: January 2025

Impaired wound healing affects millions worldwide, especially those without timely healthcare access. TheraHeal provides a portable, wireless platform for real-time, continuous, and personalized wound care. The platform integrates a wearable device for wound imaging and delivery of therapy with an AI Physician. The AI Physician analyzes wound images, diagnoses the wound stage, and prescribes therapies to guide optimal healing. Bioelectronic actuators in the wearable device deliver therapies, including electric fields or drugs, dynamically in a closed-loop system. TheraHeal evaluates wound progress, adjusts therapy as needed, and sends updates to human physicians through a graphical user interface, which also supports manual intervention. In a large animal model, TheraHeal enhanced tissue regeneration, reduced inflammation, and accelerated healing, showcasing its potential to transform personalized wound care.
Biological, experimental and analytical determinants influencing bile acids concentrations in human blood: a review and meta-analysis
Authors: Joseph Sebastian , de Buyl Sophie , Leclercq Isabelle A. , Clerbaux Laure-Alix
Published: January 2025

Background

Despite over three decades of research, the use of peripheral bile acid concentrations or proportions as biomarkers for human liver injury remain inconclusive due to variable and inconsistent findings.

Objective

The aim of this systematic review and meta-analysis was to identify factors contributing to the variability in published bile acid research and propose recommendations to enhance the robustness and reproducibility of future studies.

Methods

A search of the PubMed database and a systematic manual screening of references until May 2024 for studies reporting peripheral bile acid concentrations in humans was conducted. English-language studies reporting mean or median concentrations of at least one of 15 predetermined circulating bile acids in human cohorts were included. The exclusion criteria were editorials, commentaries, letters to the editor, conference proceedings, abstracts, and monographs. Raw bile acid concentrations, subject demographics (number, average age, sex distribution, health status, fasted/fed status), the blood matrix analysed, the matrix volume analysed, the bile acid extraction process, and analytical technique when available were extracted by a single observer.

Results

65 studies involving 215 cohorts were selected. Bile acid concentrations in normal cohorts exhibit large intervariability. The analytical technique used to measure bile acid concentrations, the fasted/fed status of patients at the time of sampling, the choice of blood collection matrix, the starting volume of this matrix, and the choice of protein precipitation solvent are found to be determinants of this variability.

Limitations

Only mean or median bile acid concentrations in study cohorts were extracted from studies and compared since bile acid concentrations are rarely reported in individual subjects. Analysing mean or median bile acid concentrations in study cohorts may not give a true sense of bile acid concentrations and therefore their determinants.

Discussion

Experimental, analytical and biological sources of mean peripheral bile acid concentration variability were identified. These must be standardised across future studies to clarify the potential of peripheral bile acids as biomarkers.
Geometry effects on protein mobility in a synapse
Authors: Dannenberg Simon , Reshetniak Sofiia , Mohammadinejad Sarah , Rizzoli Silvio O. , Klumpp Stefan
Published: January 2025

It is generally assumed that synaptic function requires a tight regulation of the mobility and localisation of synaptic proteins. Evidence for this hypothesis has been difficult to gather. Protein mobility can be measured via fluorescence recovery after photobleaching (FRAP), but the inter- pretation of the results remains challenging. In this study, we performin silicoFRAP experiments to study the effects of the synaptic geometry and/or protein binding to synaptic vesicles on protein mobility. We matched simulations with published FRAP data for 40 different synaptic proteins, to obtain diffusion coefficients, vesicle binding rates, and binding times. Importantly, we identify two mechanisms that govern the obtained recovery times: redistribution of material inside the synaptic bouton and inflow through the axon. We show that their dissection is crucial for the correct interpretation of FRAP experiments, especially for proteins binding to synaptic vesicles.
Integrating explicit reliability for optimal choices: effect of trustworthiness on decisions and metadecisions
Authors: Ota Keiji , Gajdos Thibault , Ciston Anthony , Haggard Patrick , Charles Lucie
Published: January 2025

In everyday life, decision-makers need to integrate information from various sources which differ in how reliable the correct information is provided. The present study addressed whether people can optimally use explicit information about the trustworthiness of the information source and whether people know how information sources affect their decisions. In each trial, we presented a sequence of six information sources which indicated a correct colour (red or blue) each with a different level of reliability. Each source was explicitly labelled the reliability percentage, i.e., the likelihood that a source provides correct information. Participants were asked to decide which colour was more likely to be correct. In the first series of three experiments, we found that participants failed to make use of explicit reliability cues optimally. In particular, participants were less able to use reliably wrong information sources (reliability below 50%) than reliably correct information sources (reliability above 50%), even though these two types of information sources were equally informative. In addition, participants failed to ignore the colour displayed by unreliable sources (50% reliability), although these sources gave just random information for a binary decision. In the second series of two experiments, we asked participants, after each choice, to report their subjective feelings of whether they followed or opposed a colour suggested by sources with a specific reliability percentage. We found that the ratings of the participants’ influence report tracked the amount of evidence which supported the choice they just made. Further, participants were able to introspect their own choice bias guided by unreliable information sources. These findings suggest that human choice behaviour deviates from Bayesian integration. However, people have a good metacognitive monitoring of how their decisions are driven by external stimuli.
Ceratopteris richardiiU6 promoters and plants expressing Cas9 endonuclease as tools for efficient genome editing in a fern
Authors: Schulz Robin , Theißen Günter
Published: January 2025

Ferns and their allies (monilophytes) represent the second most species-rich group of land plants and are of considerable ecological importance. As a sister group of seed plants (including flowering plants) they are also of great evolutionary interest. Compared to flowering plants, however, much less is known about the developmental and molecular biology of ferns. Among the most important reasons have been the huge genome sizes of ferns and technical obstacles such as the lack of an efficient transformation system. In recent years the situation has improved considerably, however. For the fern model systemCeratopteris richardiia whole genome sequence has been published, and an efficient transformation system has been developed. To further facilitate studies on fern biology we aim at simplifying genome engineering ofC. richardiiwith the CRISPR-Cas9 system. We reportC. richardiiplants that express Cas9 nuclease under control of the strong CaMV 35S promoter. For efficient expression of single guide RNA (sgRNA) by RNA polymerase III we identifiedC. richardiiU6 promoters. These technical improvements may foster many fields of fern physiology, development and evolution.
Acoustic features of and behavioral responses to emotionally intense mouse vocalizations
Authors: Ghasemahmad Zahra , Perumal Karthic Drishna , Sharma Bhavya , Panditi Rishita , Wenstrup Jeffrey J.
Published: January 2025

Social vocalizations contain cues that reflect the motivational state of a vocalizing animal. Once perceived, these cues may in turn affect the internal state and behavioral responses of listening animals. Using the CBA/CAJ mouse model of acoustic communication, this study examined acoustic cues that signal intensity in male-female interactions, then compared behavioral responses to intense mating vocal sequences with those from another intense behavioral context, restraint. Experiment I in this study examined behaviors and vocalizations associated with male-female social interactions. Based on several behaviors, we distinguished more general, courtship-type interactions from mating interactions involving mounting or attempted mounting behaviors. We then compared vocalizations between courtship and mating. The increase in behavioral intensity from courtship to mating was associated with altered syllable composition, more harmonic structure, lower minimum frequency, longer duration, reduced inter-syllable interval, and increased sound intensity. We then used these features to construct highly salient playback stimuli associated with mating. In Experiment II, we compared behavioral responses to playback of these mating sequences with responses to playback of aversive vocal sequences produced by restrained mice, described in previous studies. Subjects were females in estrus and males. We observed a range of behavioral responses. Some (e.g., Attending and Stretch-Attend) showed similar responses across playback type and sex, while others were context dependent (e.g., Flinching, Locomotion). Still other behaviors showed either an effect of sex (e.g., Self-Grooming, Still-and-Alert) or an interaction between playback type and sex (Escape). These results demonstrate both state-dependent features of mouse vocalizations and their effectiveness in evoking a range of behavioral responses, independent of contextual cues provided by other sensory stimuli or behavioral interactions.
Post menopausal women with Musculoskeletal disorder (MSKDs) and its relationship with regular dietary habit
Authors: Islam Md Faruqul , Faruque Md. Omar , Alauddin Md. , Kabir Md Feroz , Moula Golam , Hossian Akter , Bin Sultan Zahid , Afridi Shahid , Islam Md Waliul
Published: January 2025

Objectives

to examine the association between consistent dietary patterns and musculoskeletal diseases (MSKDs) in postmenopausal women.

Methods

A descriptive cross-sectional study recruited 576 women aged 42 to 70 years who received treatment at the Centre for the Rehabilitation of the Paralyzed (CRP), specifically the Musculo-Skeletal Department, located in Savar, CRP-Dhaka Mirpur Centre, and Unique Pain and Paralysis Centre (UPPC), Dhaka Mirpur, Bangladesh during the period from December 2022 to December 2023. The musculoskeletal disorders (MSKDs) were determined by Nordic MSK Questionnaire (NMQ) and regular dietary habit was determined by the 24-hour Dietary consumption Questionnaire. Data were collected by face-to-face interviews on demographic factors, medical history, menopausal state, and symptoms. Correlation models were used to identify factors associated between MSKDs and dietary habit.

Results

Among all participants, the age was categorized in several years and no one experiencing menstrual cycle in last 3 month. The mean overweight and obese BMI were 38.50% and 9.20%. All most all participants were feeling chronic pain on various part of body last 12 months and mean pain rating were 6.111.321. As well as dietary intake were calculation of each individual throughout a 24-hour period. The chronic MSKDs and protein was associated with upper back(p=0.046), carbohydrate was associated with LBP (p=0.005), hip pain (0.008) and knee pain (0.002) while fat was associated with shoulder pain (p=0.007*), wrist pain (p=0.002*), hip pain (p=0.044*), knee pain (p=0.002*), and ankle pain (p=0.010*) but acute pain was only associated with carbohydrate (p=0.012) which had significant.

Conclusion

Post menopausal women with acute MSKDs had suchlike no relation with regular dietary habit but a substantial association was seen with some chronic MSKDs.
Genetic contributions to premenstrual symptoms: revisiting the role of theESR1gene
Authors: Lahnsteiner Angelika , Hidalgo-Lopez Esmeralda , Noachtar Isabel , Hausinger Tobias , Gnaiger Anna , Griesbach Katrin , Scutelnic Diana , Risch Angela , Pletzer Belinda Angela
Published: January 2025

Premenstrual dysphoric disorder (PMDD) and its subclinical form categorized as premenstrual syndrome (PMS), are severe mood disorders characterized by cyclical depressive symptoms, anxiety, irritability, and other functional impairments, impacting a broad range of women during the late luteal phase. The estrogen receptor 1 (ESR1)gene encodes the estrogen receptor alpha (ERα) which plays a critical role in mediating estrogen signaling and regulates various physiological and psychological processes. In this study, we investigated the relationship between six single nucleotide polymorphisms (SNPs) in intron 4 of theESR1gene and premenstrual symptom severity, emphasizing symptom- genotype associations and SNP interactions. Results demonstrated that specific SNPs were linked to distinct symptom profiles, such as anxiety, difficulty concentrating, and sleep disturbances. Interactions between SNPs revealed both risk-enhancing and protective effects. These findings suggest that premenstrual symptoms may stem from a genotype-linked reduced sensitivity to ovarian hormones, providing a foundation for future research.
Sex Differences in Endocannabinoid and Inflammatory Markers Associated with Posttraumatic Stress Disorder
Authors: Rajasekera Therese A. , Joseph Anna , Pan Hui , Dreyfuss Jonathan M. , Fida Doruntina , Wilson Julie , Behee Madeline , Fichorova Raina N , Cinar Resat , Spagnolo Primavera A.
Published: January 2025

Background

Posttraumatic stress disorder (PTSD) is one of the most sex-polarized psychiatric disorders, with women exhibiting twice the prevalence of men. The biological mechanisms underlying this sex disparity are not fully understood. Growing evidence suggests that alterations of the stress-buffering endocannabinoid (eCB) system and heightened inflammation are central to PTSD pathophysiology and may contribute to sex-biases in PTSD risk and severity. Here, we examined sex-differences in levels of circulating eCBs and peripheral pro-inflammatory markers in a cohort of men and women with PTSD and non-psychiatric controls.

Methods

88 individuals with PTSD and 85 sex- and age-matched controls (HC) were retrospectively selected from the Mass General Brigham Biobank. Serum was assayed to measure circulating eCBs [anandamide (AEA), 2-arachidonyl glycerol (2-AG), oleoylethanolamide (OEA), and arachidonic acid (AA] and inflammatory markers [interleukin-1β (IL-1β), IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNFα), and C-reactive Protein (CRP)]. Linear regression was used to predict differential abundance of each analyte by disease state (PTSD/HC) within the male and female subgroups. Two-sided t-tests with Benjamini-Hochberg correction were used to examine differences across subgroups. Analyses were repeated in those with comorbid major depressive disorder.

Results

Male PTSD patients showed a significant decrease in AEA, AA and OEA levels compared to male controls (p’s < .001) and to female subgroups (PTSD and HCs) (p< .001). In contrast, among females, PTSD patients showed elevated levels of IL-6 (p<.05) and IL-8 (p<.05). Both male and female PTSD patients exhibited an increase in TNFα concentrations (p<.05), compared to HCs. Similar results were obtained in the subgroup of individuals with comorbid MDD and after controlling for theFAAH385A genotype.

Conclusions

Our findings show for the first time that decrease in eCB levels is absent in women with PTSD, who in turn exhibit a broader increase in inflammatory markers, thus suggesting that biological perturbations underlying PTSD may vary by sex.
Incidence and predictors of pulmonary exacerbations in primary ciliary dyskinesia: an international prospective cohort study
Authors: Schreck Leonie D , Goutaki Myrofora , Pedersen Eva SL , Copeland Fiona , Fernández Trini López ,   Living with PCD patient advisory group, Lucas Jane S , Kuehni Claudia E
Published: January 2025

Introduction

Pulmonary exacerbations contribute to disease progression in chronic lung diseases. In a large prospective cohort study, we studied the incidence and predictors of pulmonary exacerbations among persons with primary ciliary dyskinesia (PCD), which can inform follow-up care. We also assessed healthcare use, changes in management, and pathogens during exacerbations.

Methods

Participants in theLiving with PCDstudy reported increased respiratory symptoms in the past seven days, indicating a pulmonary exacerbation, from June 2020 through May 2022 via online questionnaires. We derived incidence rates and studied predictors of pulmonary exacerbation incidence by fitting multivariable negative binomial regression models.

Results

We obtained data from 660 persons (408 adults, 57 adolescents, 195 children) who completed 17,853 follow-up questionnaires (median 17, range 1-84). The 1026 reported exacerbations indicate an incidence rate of 3.1 pulmonary exacerbations per person per year, with minor variation across age groups, but changes over time. Incidence was higher among adult females [incidence rate ratio (IRR) 2.0, 95% confidence interval (CI) 1.4-2.7] and those in whomPseudomonas aeruginosawas isolated (children IRR 1.9, 95% CI 1.1-3.6; adults IRR 1.4, 95% CI 1.0-1.9). Participants saw a health professional during only 185 of 1404 exacerbation weeks (13%).Pseudomonas aeruginosawas the pathogen most frequently observed during exacerbations in children (18 of 118 samples, 15%) and adults (132 of 303 samples, 44%).

Conclusion

Pulmonary exacerbations are frequent in PCD and heighten the disease burden. Patients for whom targeted management is particularly important include adult females and those who carryPseudomonas aeruginosa.
A Mitochondrial Supplement Improves Function and Mitochondrial Activity in Autism: A double-blind placebo-controlled cross-over trial
Authors: Hill Zoë , McCarty Patrick J , Boles Richard G. , Frye Richard E.
Published: January 2025

Autism spectrum disorder (ASD) is associated with mitochondrial dysfunction but studies demonstrating the efficacy of treatments are scarce. We sought to determine whether a mitochondrial-targeted dietary supplement designed for children with ASD improved mitochondrial function and ASD symptomatology using a double-blind placebo-controlled cross-over design. Sixteen children [Mean Age 9y 4m; 88% male] with non-syndromic ASD and mitochondrial enzyme abnormalities, as measured by MitoSwab (Religen, Plymouth Meeting, PA), received weight-adjusted SpectrumNeeds®(NeuroNeeds, Old Lyme, CT) and QNeeds®(NeuroNeeds) and placebos matched on taste, texture and appearance during two separate 12-week blocks. Which product received first was randomized. The treatment significantly normalized citrate synthase and complex IV activity as measured by the MitoSwab. Mitochondrial respiration of peripheral blood mononuclear cell respiration, as measured by the Seahorse XFe96 (Agilent, Santa Clara, CA) with the mitochondrial oxidative stress test, became more resilient to oxidative stress after the treatment, particularly in children with poor neurodevelopment. The mitochondrial supplement demonstrated significant improvement in standardized parent-rated scales in neurodevelopment, social withdrawal, and hyperactivity with large effect sizes (Cohen’s d’ = 0.77-1.25), while changes measured by the clinical and psychometric instruments were not significantly different. Adverse effects were minimal. This small study on children with ASD and mitochondrial abnormalities demonstrates that a simple, well-tolerated mitochondrial-targeted dietary supplement can improve mitochondrial physiology, ASD symptoms. Further larger controlled studies need to verify and extend these findings. These findings are significant as children with ASD have few other effective treatments.