bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIPP3 and TIPP3-fast: Improved Abundance Profiling in Metagenomics
Authors: Shen Chengze , Wedell Eleanor , Pop Mihai , Warnow Tandy 
Published: October 2024

AbstractWe present TIPP3 and TIPP3-fast, new tools for abundance profiling in metagenomic datasets. Like its predecessor, TIPP2, the TIPP3 pipeline uses a maximum likelihood approach to place reads into labeled taxonomies using marker genes, but it achieves superior accuracy to TIPP2 by enabling the use of much larger taxonomies through improved algorithmic techniques. We show that TIPP3 outperforms leading methods for abundance profiling in two important contexts: when reads come from genomes not already in a public database (i.e., novel genomes) and when reads contain sequencing errors. We also show that TIPP3-fast has slightly lower accuracy than TIPP3, but is still more accurate than other leading methods and uses a small fraction of TIPP3’s runtime. Additionally, we highlight the potential benefits of restricting abundance profiling methods to those reads that map to marker genes (i.e., using a filtered marker-gene based analysis), which we show typically improves accuracy. TIPP3 is freely available athttps://github.com/c5shen/TIPP3.Author summaryTIPP3 is a new marker gene-based abundance profiling tool that builds on TIPP and TIPP2 with significant enhancements. TIPP3 supports larger reference packages (∼ 55,000 sequences per marker gene) and achieves higher accuracy in abundance profiling, especially with challenging input reads containing sequencing errors or novel genomes. TIPP3 outperforms TIPP2 and other leading methods in profiling accuracy, and its fast version TIPP3-fast is competitive in runtime with the competing methods while being more accurate under challenging conditions. TIPP3 is open-source and available athttps://github.com/c5shen/TIPP3.
Machine Learning Approach to Single Cell Transcriptomic Analysis of Sjogren’s Disease Reveals Altered Activation States of B and T Lymphocytes
Authors: McDermott Maxwell , Li Wenyi , Wang Yin-Hu , Lacruz Rodrigo , Nadorp Bettina , Feske Stefan 
Published: October 2024

ABSTRACTSjogren’s Disease (SjD) is an autoimmune disorder characterized by salivary and lacrimal gland dysfunction and immune cell infiltration leading to gland inflammation and destruction. Although SjD is a common disease, its pathogenesis is not fully understood. In this study, we conducted a single-cell transcriptome analysis of peripheral blood mononuclear cells (PBMC) from patients with SjD and symptomatic non-SjD controls to identify cell types and functional changes involved in SjD pathogenesis. All PBMC populations showed marked differences in gene expression between SjD patients and controls, particularly an increase in interferon (IFN) signaling gene signatures. T and B cells of SjD patients displayed a depletion of ribosomal gene expression and pathways linked to protein translation. SjD patients had increased frequencies of naive B cells, which featured a unique gene expression profile (GEP) distinct from controls and had hallmarks of B cell hyperactivation. Non-negative matrix factorization (NMF) also identified several non-overlapping GEPs in CD4+and CD8+T cells with differential usage in SjD patients and controls. Of these, only theTh1 activationGEP was enriched in T cells of SjD patients whereas the other two GEPs were depleted in T cells, emphasizing the important role of Th1 cells in SjD. Our study provides evidence for aberrant and unique gene expression patterns in both B and T lymphocytes of SjD patients that point to their altered activation states and may provide new insights into the pathogenesis of SjD.
Highly porous granular hydrogels reinforced by electrospun hydrogel fibers for long-term stability
Authors: Whitewolf Jack , Riley Lindsay , Brady Brooke , Grewal Greg , Segura Tatiana , Highley Chris 
Published: October 2024

AbstractGranular hydrogels (GHs) formed from hydrogel microparticles (HMPs) possess inherent, microscale porosity. In GHs including microporous annealed particle (MAP) hydrogels as well as unannealed GHs, increases in pore size and total porosity correlate with enhanced cellular infiltration and growth. However, increased porosity or pore size are typically achieved by decreasing HMP density, reducing interparticle contacts and weakening hydrogel structure. Here, to achieve a highly porous GH without compromising stability, we developed an approach using sacrificial HMPs to achieve high, mesoscale porosity and high-aspect ratio hydrogel fibers to reinforce the scaffold. The use of sacrificial HMPs circumvented the need to decrease packing density, creating GHs with up to 60% porosity. The hydrogel fibers span particles in the porous space, stabilizing the porous structure by enhancing interactions among GH components. Upon 5-10% v/v fiber incorporation, highly porous GHs retained their structure over 28 days ofin vivoculture, compared to 4 days in GHs without fibers. These scaffolds supported and promoted endothelial cell growth as porosity increased. Overall, this study presents a stable, highly porous granular scaffold system with high processability and cytocompatibility.
Effects of organic and inorganic contaminants and their mixtures on metabolic health and gene expression in developmentally exposed zebrafish
Authors: Bérubé Roxanne , LeFauve Matthew K. , Khalaf Aicha , Aminioroomi Darya , Kassotis Christopher D. 
Published: October 2024

AbstractOrganic and inorganic chemicals co-occur in household dust, and these chemicals have been determined to have endocrine and metabolic disrupting effects. While there is increasing study of chemical mixtures, the effects of complex mixtures mimicking household dust and other environmental matrices have not been well studied and their potential metabolism disrupting effects are thus poorly understood. Previous research has demonstrated high potency adipogenic effects of residential household dust extracts usingin vitroadipogenesis assays. More recent research simplified this to a mixture relevant to household dust and comprised of common co-occurring organic and inorganic contaminants, finding that these complex combinations often exhibited additive or even synergistic effects in cell models. This study aimed to translate our previous in vitro observation to an in vivo model, the developing zebrafish, to evaluate the metabolic effects of early exposure to organic and inorganic chemicals, individually and in mixtures. Zebrafish embryos were exposed from 1 day post fertilization (dpf) to 6 dpf, then metabolic energy expenditure, swimming behavior and gene expression were measured. Globally, we observed that most mixtures did not reflect the effects of individual chemicals; the BFR mixture produced a less potent effect when compared to the individual chemicals, while the PFAS and the inorganic mixtures seemed to have a more potent effect than the individual chemicals. Finally, the environmental mixture, mimicking household dust proportions, was less potent than the inorganic chemical mix alone. Additional work is necessary to better understand the mixture effect of inorganic and organic chemicals combined.
Fragment-based development of small molecule inhibitors targetingMycobacterium tuberculosischolesterol metabolism
Authors: Kavanagh Madeline E. , McLean Kirsty J. , Gilbert Sophie H. , Amadi Cecilia , Snee Matthew , Tunnicliffe Richard B. , Arora Kriti , Boshoff Helena I. , Fanourakis Alexander , Rebello-Lopez Maria Jose , Ortega-Muro Fatima , Levy Colin W. , Munro Andrew W. , Leys David , Abell Chris , Coyne Anthony G. 
Published: October 2024

AbstractMycobacterium tuberculosis(Mtb) is the world’s most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential forMtb’slong-term survivalin vivo.Here, we report the development of antitubercular small molecules that inhibit theMtbcholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule1athat can bind to the heme cofactor of both enzymes. A structure-guided fragment-linking strategy was used to optimize the binding affinity of1a, yielding a potent dual CYP125/142 inhibitor5m(KDCYP125/CYP142 = 0.04/0.16 µM). Compound5mpotently inhibits the catalytic activity of CYP125 and CYP142in vitro(KIvalues < 0.1 µM), and rapidly depletesMtbintracellular ATP (IC50= 0.15 µM). The compound has antimicrobial activity against both drug susceptible and MDRMtb (MIC99values 0.4 - 1.5 µM)in extracellular assays, and inhibits the growth ofMtbin human macrophages (MIC = 1.7 µM) with good selectivity over mammalian cytotoxicity (LD50≥ 50 µM). The combination of small molecule inhibitors and structural data reported here provide useful tools to study the role of cholesterol metabolism inMtband are a promising step towards novel antibiotics targeting bioenergetic pathways, which could be used to help combat MDR-TB.
Application of2H2O to quantify red blood cell protein synthesis rates in young trained and untrained males and females
Authors: Kontro Hilkka , McGlory Chris , MacInnis Martin J 
Published: October 2024

ABSTRACTAimCompare the fractional synthetic rate (FSR) of hemoglobin in trained and untrained humans (Hb FSR).MethodsWe employed deuterated water (2H2O) to measure Hb FSR in young males (n=10) and females (n=10) who were aerobically trained (n=5 per sex) and untrained (n=5 per sex). Overall, participants had a meanof 49.8 [SD: 10.9] mL/kg/min, hemoglobin mass of 775 [180] g, and red blood cell volume of 2370 [550] mL. After an initial loading dose, participants ingested2H2O daily for 28 days to maintain a stable2H body water enrichment (∼0.9 atom percent deuterium (APD)), as measured in saliva samples collected every 2-3 days.2H-enriched alanine was measured in RBC protein using gas chromatography combustion isotope ratio mass spectrometry.ResultsThe increase in APD for Hb protein was nonlinear for the first two weeks, but stabilized from day 14 to day 28, with mean APD reaching 0.033 [0.005] % on day 28. Hb FSR calculated over this 2-week period was 0.84 [0.15] %/day, which equated to an Hb absolute synthetic rate of 6.5 [2.2] g/day and a lifespan of 126 [30] days. Hb FSR was not different trained (0.83 [0.19] %/day) and untrained (0.86 [0.24] %/day, P=0.81) individuals or between males (0.80 [0.25] %/day) and females (0.88 [0.17] %/day), P=0.24).ConclusionHabitual endurance training does not appear to affect Hb FSR, but the use of2H2O to measure Hb FSR in humans has potential applications to many experimental and clinical scenarios.
Monitoring the Coating of Single DNA Origami Nanostructures with a Molecular Fluorescence Lifetime Sensor
Authors: Scheckenbach Michael , Brüggenthies Gereon Andreas , Schröder Tim , Betuker Karina , Wassermann Lea , Tinnefeld Philip , Heuer-Jungemann Amelie , Glembockyte Viktorija 
Published: October 2024

ABSTRACTThe high functionality of DNA nanostructures makes them a promising tool for biomedical applications, their intrinsic instability under application-relevant conditions, still remains challenging. Protective coating of DNA nanostructures with materials like silica or cationic polymers has evolved as a simple, yet powerful strategy to improve their stability even under extreme conditions. While over time, various materials and protocols have been developed, the characterization and quality assessment of the coating is either time consuming, highly invasive or lacks detailed insights on single nanostructures. Here, we introduce a cyanine dye based molecular sensor designed to non-invasively probe the coating of DNA origami by either a cationic polymer or by silica, in real-time and on a single nanostructure level. The cyanine dye reports changes in its local environment upon coating via increased fluorescence lifetime induced by steric restriction and water exclusion. Exploiting the addressability of DNA origami, the molecular sensor can be placed at selected positions to probe the coating layer with nanometer precision. We demonstrate the reversibility of the sensor and use it to study the stability of the different coatings in degrading conditions. To showcase the potential for correlative studies, we combine the molecular fluorescence lifetime sensor with DNA PAINT super-resolution imaging to investigate coating and structural integrity as well as preserved addressability of DNA nanostructures. The reported sensor presents a valuable tool to probe the coating of DNA nanodevices in complex biochemical environments in real-time and at the single nanosensor level and aids the development of novel stabilization strategies.
Territorial behavior as a route of social microbial transmission in an asocial mammal
Authors: Petrullo Lauren , Webber Quinn , Raulo Aura , Boutin Stan , Lane Jeffrey E. , McAdam Andrew G. , Dantzer Ben 
Published: October 2024

ABSTRACTMicrobial transmission is a major benefit of sociality, facilitated by affiliative behaviors such as grooming and communal nesting in group-living animals. The spread of microbial symbionts through these pathways, and their incorporation into host microbiomes, can enhance host health and fitness by contributing to pathogen protection and metabolic flexibility. Are pathways that facilitate microbial transfer across hosts also present in animals that do not form social groups because territoriality limits social interactions and prevents group formation? Here, we addressed this question by combining longitudinal sampling of individual gut microbial communities, demographic data, and dynamic behavioral and spatial measures of territoriality from a non-social, highly territorial small mammal: wild North American red squirrels (Tamiasciurus hudsonicus).As squirrel densities increased, individual gut microbial communities became richer and more phylogenetically diverse, while among-individual differences in composition decreased. This pattern was characterized primarily by increases in obligately anaerobic and non-sporulating taxa with little to no tolerance for oxygen-rich environments, suggesting social rather than environmental routes of transmission. Moreover, territorial intrusions—in which conspecifics were found on within an individual’s territorial space—increased gut microbial diversity among individuals defending larger territorial spaces. Using an intrusion-based social network analysis, we found that that pairs with stronger social association (via intrusions) exhibited higher gut microbial similarity. Taken together, our findings provide some of the first evidence for social microbial transmission in a non-social species, and suggest that increased density and territorial behavior can diversify and homogenize host gut microbial communities despite social isolation.
A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation
Authors: Moon Hyungseok C. , Herschl Michael H. , Pawluk April , Konermann Silvana , Hsu Patrick D. 
Published: October 2024

AbstractEpigenetic regulation involves the coordinated interplay of diverse proteins. To systematically explore these combinations, we present COMBINE (combinatorial interaction exploration), a high-throughput platform that tests over 50,000 pairs of epigenetic effector domains up to 2,094 amino acids in length for their ability to modulate endogenous human gene transcription. COMBINE revealed diverse synergistic and antagonistic interactions between epigenetic protein domains, including a potent KRAB-L3MBTL3 fusion that enhanced gene silencing up to 34-fold in dose-limited conditions and enabled robust bidirectional CRISPR perturbation. Inducible screening showed DNA methylation modifiers are essential for epigenetic memory, with distinct combinations driving long-term silencing, repression, or activation. Notably, we identified TET1-based combinations that induce hit-and-run upregulation for over 50 days, demonstrating long-term transcriptional activation. This systematic analysis of pairwise domain interactions provides a rich resource for understanding epigenetic crosstalk and developing next-generation epigenome editing tools. More broadly, COMBINE offers a generalizable platform to functionally characterize combinatorial biological processes at scale.
A new marker for molecular phylogenetic studies in Odonata including parts of conservative histone H3 and H4 genes and spacer between them
Authors: Mglinets A.V. , Bulgakova VS , Kosterin OE 
Published: October 2024

AbstractA new molecular marker, the histone H3-H4 region, containing partial coding sequences of the genes of histones H3 and H4 and the non-coding spacer between them, is proposed. This marker is potentially useful for molecular phylogenetic studies at generic, species, and even intra-species level in insects. The highly conservative histone coding sequences ensure universality of primers and the ease of primary alignment, while the highly variable non-coding spacer provides enough variation for analyses at short evolutionary distances. In insects, the histone genes reside in the histone repeat which is tandemly repeated in dozens to hundred copies forming the so-called histone cluster. However, the order and orientation of the histone genes in the histone repeat is variable among orders, which exerts some limitation for the new marker use. The marker efficiency is hereby shown for Odonata (dragonflies and damselflies), where it well resolved the families, genera and species involved and provided an insight into the relationship ofSympetrum croceolum(Selys, 1883) andS. uniforme(Selys, 1883).
The Role of Curcumin Supplementation in Patients with Migraine: A Meta-Analysis of Randomized Controlled Trial
Authors: Zhu Xingke 
Published: October 2024

AbstractObjectivesMigraine is a repeated, chronic and neurovascular disease that adversely affects the quality of life and increases the risk of cerebral lesion. Curcumin, the orange-yellow substance of turmeric, may possess anti-headache performance according to several studies. Thus, this study set out to meta-analytically access the anti-headache effect of curcumin supplementation in patients with migraine.MethodsFive databases were searched as of September 30, 2022 to identify all eligible randomized controlled trials. The random-effect Hunter-Schmidt model was used to calculate the effect sizes based on the heterogeneity. The PROSPERO registration number for this meta-analysis is CRD42023409829 (https://www.crd.york.ac.uk/PROSPERO/).ResultsFour studies involving 170 patients finally met our inclusion criteria. In the results, curcumin supplementation showed a significant difference in the severity of migraine symptoms compared with placebo (Hedges’s g= -0.75, 95% confidence interval (CI) =-1.44 to -0.07,P= 0.03).ConclusionsCurcumin supplementation may relieve the severity of headache symptoms in migraine sufferers.
From subthalamic local field potentials to the selection of chronic deep brain stimulation contacts in Parkinson’s disease - A systematic review
Authors: Muller Marjolein , van Leeuwen Mark F.C. , Hoffmann Carel F. , van der Gaag Niels A. , Zutt Rodi , van der Gaag Saskia , Schouten Alfred C. , Contarino M. Fiorella 
Published: October 2024

AbstractBackgroundProgramming deep brain stimulation (DBS) of the subthalamic nucleus for optimal symptom control in Parkinson’s Disease (PD) requires time and trained personnel. Novel implantable neurostimulators allow local field potentials (LFP) recording, which could be used to identify the optimal (chronic) stimulation contact. However, literature is inconclusive on which LFP features and prediction techniques are most effective.ObjectiveTo evaluate the performance of different LFP-based physiomarkers for predicting the optimal (chronic) stimulation contacts.MethodsA literature search was conducted across nine databases, resulting in 418 individual papers. Two independent reviewers screened the articles based on title, abstract, and full text. The quality of included studies was assessed using a modified Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were categorised in four classes based on the predictive performance with respect to thea priorichance.ResultsTwenty-five studies were included. Single-factor beta-band predictions demonstrated positive performance scores in 94% of the outcomes. Predictions based on single non-beta-frequency factors yielded positive scores in only 25% of the outcomes, with positive results mainly for high frequency oscillations. Multi-factor predictions (e.g. machine learning) achieved accuracy scores within the two highest performance classes more often than single beta-based predictions (100% versus 39%).ConclusionPredicting the optimal stimulation contact based on LFP recordings is feasible and can improve DBS programming efficiency in PD. Single beta-band predictions show more promising results than non-beta-frequency factors alone, but are outperformed by multi-factor predictions. Future research should further explore multi-factor prediction for optimal contact identification.
TXNIP mediates LAT1/SLC7A5 endocytosis to reduce amino acid uptake in cells entering quiescence
Authors: Kahlhofer Jennifer , Marchet Nikolas , Seifert Brigitta , Zubak Kristian , Hotze Madlen , Egger Anna-Sophia , Manzl Claudia , Weyer Yannick , Weys Sabine , Offterdinger Martin , Herzog Sebastian , Reiterer Veronika , Kwiatkowski Marcel , Wortmann Saskia B. , Nemati Siamak , Mayr Johannes A. , Zschocke Johannes , Radlinger Bernhard , Thedieck Kathrin , Huber Lukas A. , Farhan Hesso , de Araujo Mariana E.G. , Kaser Susanne , Scholl-Bürgi Sabine , Karall Daniela , Teis David 
Published: October 2024

AbstractEntry and exit from cellular quiescence require dynamic adjustments in nutrient acquisition, yet the mechanisms by which quiescent cells downregulate amino acid (AA) transport remain poorly understood. Here, we demonstrate that cells entering quiescence select plasma membrane-resident AA transporters for endocytosis and lysosomal degradation, to match AA uptake with reduced translation. We identify the α-arrestin TXNIP as a key regulator of AA uptake during quiescence, since it mediates the endocytosis of the SLC7A5-SLC3A2 (LAT1-4F2hc) transporter complex in response to reduced AKT signaling. Mechanistically, TXNIP interacts with HECT-type ubiquitin ligases to facilitate transporter ubiquitination. Loss of TXNIP disrupts this regulation, resulting in dysregulated AA uptake, sustained mTORC1 signaling, and accelerated quiescence exit. A novel TXNIP loss-of-function mutation in a patient with severe metabolic disease further supports its role in nutrient homeostasis and human health. These findings highlight TXNIP’s role in controlling SLC7A5-SLC3A2 mediated AA acquisition with implications for quiescence biology and disease.