bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-related decline in neural phase-locking to envelope and temporal fine structure revealed by frequency following responses: A potential signature of cochlear synaptopathy impairing speech intelligibility
Authors: Ponsot Emmanuel , Devolder Pauline , Dhooge Ingeborg , Verhulst Sarah 
Published: December 2024

AbstractAssessing the contribution of cochlear synaptopathy (CS) to the variability in speech-in-noise intelligibility among individuals remains a challenge. While several studies have proposed biomarkers for CS based on neural phase-locking to the temporal envelope (ENV), fewer have investigated how CS affects the coding of temporal fine structure (TFS), despite its crucial role in speech-in-noise perception. In this study, we specifically examined whether TFS-based markers of CS could be derived from electrophysiological responses and psychophysical detection thresholds of spectral modulation (SM) in a complex tone, which serves as a parametric model of speech. We employed an integrated approach, combining psychophysical testing with frequency-following response (FFR) measurements in three groups of participants: young normal-hearing (yNH), older normal-hearing (oNH), and older hearing-impaired (oHI) individuals. We expanded on previous work by assessing phase-locking to both ENV, using a 4 kHz rectangular amplitude-modulated (RAM) tone, and TFS, using a low-frequency (<1.5 kHz) SM complex tone. Overall, FFR results showed significant reductions in neural phase-locking to both ENV and TFS components with age and hearing loss. Specifically, the strength of TFS-related FFRs, particularly the component corresponding to the harmonic closest to the peak of the spectral envelope (∼500 Hz), was negatively correlated with age, even after adjusting for audiometric thresholds. This TFS marker also correlated with ENV-related FFRs derived from the RAM tone, suggesting a shared decline in phase-locking capacity across low and high cochlear frequencies. Computational simulations of the auditory periphery indicated that the observed FFR strength reduction with age is consistent with approximately 50% loss of auditory nerve fibers, aligning with histopathological data. However, the TFS-based FFR marker did not account for variability in speech intelligibility observed in the same participants. Psychophysical measurements showed no age-related effects and were unrelated to the TFS-based FFR marker, highlighting the need for further psychophysical research to establish a behavioral counterpart. Altogether, our results demonstrate that FFRs to vowel-like stimuli can serve as a complementary electrophysiological marker for assessing neural coding fidelity to stimulus TFS. This approach could provide a valuable tool for better understanding the impact of CS on an important coding dimension for speech-in-noise perception.
Effects of an auxin antagonist, PEO-IAA, and an auxin transport inhibitor, NPA, on gametophore development inPhyscomitrium patens(Hedw.) Mitt
Authors: Robinson Shawn R , Ashton Neil W 
Published: December 2024

AbstractAuxin sensing and polar auxin transport (PAT) are required for normal growth and development of stem internodes and leaves of gametophores ofPhyscomitrium(formerlyPhyscomitrella)patens. Auxin is required for the formation of leaf apical cells, and NPA-driven elevation of the intracellular auxin/cytokinin ratio stimulates bifurcation at the leaf margin. Auxin is implicated in the differentiation of the leaf midrib. Auxin sensing and PAT appear not to be needed for the transition of gametophore buds into leafy shoots.
Estimating changes in life expectancy in Hong Kong during the COVID-19 pandemic
Authors: Law Alexandra H. T. , Presanis Anne M. , Cheung Justin K. , Wu Peng , Schooling C. Mary , Cowling Benjamin J. , Wong Jessica Y. 
Published: December 2024

ABSTRACTBackgroundHong Kong has one of the longest life expectancies in the world but was heavily impacted by COVID-19 in 2022.MethodsWe constructed sex-specific life tables from 1998-2023 using parametric bootstrapping to account for statistical uncertainty in mortality rates. We used Arriaga’s decomposition method to estimate age-specific contributions to overall changes in life expectancy over this period. We also estimated cause-specific mortality rates.ResultsHong Kong reported 50666 deaths in 2020, 51354 in 2021, 63692 in 2022, and 54731 in 2023. Estimates of life expectancy in males and females in 2020 and 2021 were similar to the pre-pandemic trend from 1998-2019 but declined significantly in 2022. Life expectancy for males was 82.3 years in 2021 and 80.4 years in 2022, and for females it was 87.9 in 2021 and 86.4 years in 2022. Compared to the pre-pandemic trend, the 2022 values corresponded to reductions by 2.22 (95% CI: 2.08, 2.36) years in males and 2.30 (95% CI: 2.17, 2.43) years in females. The loss in life expectancy in 2022 was mainly attributed to increased respiratory mortality rates in adults aged 65 or above. In 2023 life expectancy increased by 0.60 (95% CI: 0.46, 0.75) years in males and by 1.10 (95% CI: 0.95, 1.26) years in females.ConclusionsIn 2022 a very high respiratory mortality rate in older adults in Hong Kong during the COVID-19 pandemic was associated with a reduction in life expectancy by more than 2 years. In 2023 life expectancy increased towards the pre-pandemic trend.
Decreased interleukin-8 levels in the peripheral blood of Alzheimer’s patients
Authors: Ros Francisco , Martínez Lozano María Dolores , Arnau Javier , Martínez Jacobo , Vericat Alejandro , Sánchez Rafael , Burgos Javier S. 
Published: December 2024

AbstractIntroductionMultiple studies have reported variations in inflammatory levels in blood of Alzheimer’s disease (AD), although further research is needed to identify discriminatory biomarkers for AD diagnosis.MethodsA prospective comparative paired study of a group of AD patients compared to normal controls (NC) was carried out in a multicenter study, where age and sex ratio were homogenized to avoid bias. The cohort comprised 39 patients with a diagnosis of AD (64.1% women; mean age 74.8±0.8 years) and 27 matched NC (66.7% women; 74.8±0.8 years). The diagnosis of AD was performed by neurologists using the Mini-Mental State Examination test (MMSE) and classical markers in cerebrospinal fluid (CSF) and/or amyloid-PET. We investigated the discriminatory potential of 13 serological parameters in blood, consisting of seven interleukins (IL-3, IL-4, IL-5, IL-6, IL-8, IL-12p40, and IL-15) and other 6 serological inflammatory markers (EGF, GM-CSF, IP-10, sCD40L, PDGF-AB/BB, and RANTES). Additionally, six sociodemographic variables were examined. Apolipoprotein E (APOE) genotype was also determined.ResultsThe results revealed an inverse association between educational level, number of languages spoken, and physical activity, with the risk of AD. An enrichment of the APOE4 isoform was observed in AD (28 out of 39 AD vs 3 out of 24 NC). All circulating inflammation markers were lower in AD patients than in NC (except for IP-10 and sCD40L, while Il-3 and GM-CSF were undetectable in both groups), with statistically significant differences detected in IL-8, IL-12p40, and PDGF-AB/BB (AD/NC ratios of 0.56, 0.59, and 0.81, respectively). IL-8 was decreased specifically in APOE4 carriers (carriers/non-carriers ratio of 0.73), and in amyloid-positive cases (positives/NC ratio of 0.46), whereas IL-12p40 and PDGF-AB/BB showed positives/NC ratios of 0.56 and 0.83, respectively.DiscussionSerum levels of IL-8, IL-12p40, and PDGF-AB/BB were significantly reduced in AD patients. Additionally, IL-8 decrease was associated with APOE4-carriers and amyloid-positive cases.
The avoidable health burden and healthcare costs related to alcohol consumption in Australia: multistate life table modelling
Authors: Wanjau Mary Njeri , Cobiac Linda , Shahid Mishel , Malawige Amila , Aminde Leopold , Subhi Moosa Al , Nguyen Phuong , Angeles Mary Rose , Ananthapavan Jaithri , Veerman Lennert 
Published: December 2024

AbstractBackground and AimsExcessive use of alcohol is one of the leading risks for mortality and disability globally. In Australia, alcohol was the fifth-highest risk factor contributing to disease burden in 2019. Estimates of the avoidable (future) alcohol related burden can help make the case for investment in preventive measures. This analysis aims to estimate the avoidable burden related to alcohol consumption in Australia.Design, setting, participants and interventionThe Alcohol Policy model (TAP),a proportional multi-state lifetable model was developed and used to estimate the avoidable alcohol-related disease, injury and healthcare cost burden by comparing a scenario where the Australian adult population (aged ≥ 15 years) continues to drink alcohol at current rates to an identical population that consumes no alcohol. Taking 2020 as the base year, an open cohort was modelled over a 60-year time horizon.MeasurementsChanges in population alcohol consumption are modelled to lead to changes in 1) incident cases and mortality from alcohol-related diseases and injuries, 2) long-term health outcomes summarised as health adjusted life years (HALYs) and 3) healthcare costs. Results are reported in single years, over 25 years and 60 years (for HALYs and healthcare costs). No discounting was applied.FindingsOver the first 25 years, elimination of alcohol consumption at the population level could prevent over 25.9 million incident cases of alcohol-related diseases and injuries (89% acute causes, 1% cancers and 10% other modelled chronic diseases). This translates to 5.1 (95% uncertainty interval [UI] 4.0 to 6.2) million HALYs gained and AUD 55 (95% UI 36 to 75) billion saved in healthcare costs. Over a 60-year period, the potential health benefits increase to 17 (95%UI 14 to 21) million HALYs and is associated with AUD 68 (95%UI 9.6 to 130) billion in healthcare cost-savings.ConclusionOur findings show that the avoidable alcohol-related disease, injury and healthcare cost burden in Australia is substantial. These findings reinforce the need for investment in effective and cost-effective polices that reduce alcohol consumption.
Deep profiling of plant stress biomarkers following bacterial pathogen infection with protein corona based nano-omics
Authors: Coreas Roxana , Sridhar Nikitha , Lin Teng-Jui , Squire Henry J. , Voke Elizabeth , Landry Markita P. 
Published: December 2024

AbstractDetection and remediation of stress in crops is vital to ensure agricultural productivity. Conventional forms of assessing stress in plants are limited by feasibility, delayed phenotypic responses, inadequate specificity, and lack of sensitivity during initial phases of stress. While mass spectrometry is remarkably precise and achieves high-resolution, complex samples, such as plant tissues, require time-consuming and biased depletion strategies to effectively identify low-abundant stress biomarkers. Here, we bypassed these reduction methods via a nano-omics approach, where gold nanoparticles were used to enrich time- and temperature-dependent stress-related proteins through biomolecular corona formation that were subsequently analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). This nano-omic approach was more effective than a conventional proteomic analysis using UHPLC- MS/MS for resolving biotic-stress induced responses at early stages of pathogen infection inArabidopsis thaliana, well before the development of visible phenotypic symptoms, as well as in distal tissues of pathogen infected plants at early timepoints. The enhanced sensitivity of this nano-omic approach enables the identification of stress-related proteins at early critical timepoints, providing a more nuanced understanding of plant-pathogen interactions that can be leveraged for the development of early intervention strategies for sustainable agriculture.
Habitat filtering but not microbiota origin controls microbiome transplant outcomes in soil
Authors: Causevic Senka , Tackmann Janko , Sentchilo Vladimir , Malfertheiner Lukas , von Mering Christian , van der Meer Jan Roelof 
Published: December 2024

ABSTRACTHuman activities cause global losses of soil microbiome diversity and functionality. Microbiota transplants offer a potential solution, but the factors influencing transplant success remain unclear. We investigated how microbiota origin affects microbiome mergers, hypothesizing that native strains through niche preference are better adapted to their habitat and will outcompete non-native ones. To test this, we contrasted transplants between soil microcosm-cultured topsoil or lakewater communities with a community of 21 soil bacteria (SynCom). In both cases, SynCom transplant increased resident productivity but permanently shifted compositions, although its abundance dropped from an initial 50-80% to <1% within two months. Both merged and non-merged communities resembled natural soil microbiota in comparisons with over 81,000 soil, sediment and lake compositional data. Our results show that habitat filtering and niche competition, more than microbiota origin, determine transplant outcomes. Despite the limited proliferation of SynCom transplants, their capacity to instill lasting community trajectory changes opens new paths for microbiome engineering.TEASEREven transiently present microbiota transplants can alter resident microbiome composition through processes governed by habitat filtering.
Enhanced Yield and Gentle Purification of HIV for Cryo-Electron Tomography Analysis of Virion Maturation
Authors: Preece Benjamin , Peppel Wiley , Gallegos Rodrigo , Yassasi Gillian , Clinger Gabe , Bohn Nicole , Adhikary Broti , Mendonça Luiza , Belnap David , Vershinin Michael , Saffarian Saveez 
Published: December 2024

AbstractHIV is a lentivirus characterized by the formation of its mature core. Visualization and structural examination of HIV requires purification of virions to high concentrations. The yield and integrity of these virions are crucial for ensuring a uniform representation of all viral particles in subsequent analyses. In this study, we present a method for purification of HIV virions which minimizes forces applied to virions while maximizing the efficiency of collection. This method allows us to capture between 1,000 and 5,000 HIV virions released from individual HEK293 cells after transfection with the NL4.3 HIV backbone, a 10 fold advantage over other methods. We utilized this approach to investigate HIV core formation from several constructs: pNL4-3(RT:D185A&D186A) with an inactive reverse transcriptase, NL4.3(IN: V165A&R166A) with a type-II integrase mutation, and NL4.3(Ѱ: Δ(105-278)&Δ(301-332)) featuring an edited Ѱ packaging signal. Notably, virions from NL4.3(Ѱ: Δ(105-278)&Δ(301-332)) displayed a mixed population, comprising immature virions, empty cores, and cores with detectable internal density. Conversely, virions derived from NL4.3(IN: V165A&R166A) exhibited a type II integrase mutant phenotype characterized by empty cores and RNP density localized around the cores, consistent with previous studies. In contrast, virions released from pNL4-3(RT:D185A&D186A) displayed mature cores containing detectable RNP density. We suggest that the purification methods developed in this study can significantly facilitate the characterization of enveloped viruses.
A Novel Method for Testing Antifungal Interactions: Assessing Synergy and Antagonism inCandida albicansClinical Isolates
Authors: Lundvik Hanna , Santini Ramona , Unalan Altintop Tugce , Özenci Volkan , Andersson Dan I. , Fatsis-Kavalopoulos Nikos 
Published: December 2024

AbstractThe rise in antifungal resistance has limited treatment options for serious fungal infections, emphasizing the need for effective combination therapies. However, low-cost and rapid systems to evaluate synergy and antagonism in antifungal combinations are lacking. Here, we introduce a novel in vitro testing method for assessing antifungal interactions in C.albicans, enabling the simultaneous testing of three antifungal agents in a single agar plate with overnight results. This method, validated against the checkerboard assay, provides consistent fractional inhibitory concentration (FICi) measurements with reduced variability and workload. We applied this method in a comprehensive screen of 92 clinical C.albicansisolates for three antifungals—amphotericin B, fluconazole, and anidulafungin—yielding assessments of a total of 276 distinct combinations of antifungals and isolates. Results revealed isolate-specific interaction patterns, with amphotericin B and fluconazole showing synergy in 1% of isolates, anidulafungin and fluconazole in 19.5%, and amphotericin B and anidulafungin in 23.9%. These findings underscore the need for isolate-specific testing in clinical settings, which this scalable, high-throughput assay can facilitate effectively.
Cell type mapping of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy using single-nucleus multiomics
Authors: Galvão Isabella C. , Lemoine Manuela , Kandratavicius Ludmyla , Yasuda Clarissa L. , Alvim Marina K. M. , Ghizoni Enrico , Blümcke Ingmar , Cendes Fernando , Rogerio Fabio , Lopes-Cendes Iscia , Veiga Diogo F. T. 
Published: December 2024

ABSTRACTObjectiveMild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) are brain lesions associated with focal epilepsy and characterized by increased oligodendroglial density, heterotopic neurons, and hypomyelination in the white matter. While previous studies have implicated somatic mutations in theSLC35A2gene, the cellular and molecular mechanisms underlying MOGHE pathogenesis remain elusive. To address this gap, this study aimed to systematically characterize the cell type composition and molecular alterations of MOGHE lesions at cellular resolution using single-nucleus multiomics profiling.MethodsWe performed single-nucleus multiomics sequencing to obtain paired gene expression and chromatin accessibility profiles of > 31,000 nuclei from gray matter and white matter regions of MOGHE lesions, and compared the results with publicly available neurotypical control datasets.ResultsThe analysis of gray and white matter regions from two MOGHE patients revealed significant cellular composition alterations, including an oligodendrocyte expansion and heterotopic neurons within the subcortical white matter. We identified a distinct population of MOGHE-associated oligodendrocytes characterized by expressing genes related to immune response, myelination disruption, and epilepsy-related pathways. These oligodendrocytes shared a common transcriptional signature with oligodendrocytes in other neurological conditions involving white matter abnormalities. Further analysis of heterotopic neurons in MOGHE revealed the upregulation of genes associated with neuronal migration and the Wnt signaling pathway, suggesting a mechanism underlying their atypical localization.SignificanceThis high-resolution cell type mapping of MOGHE lesions in clinical samples unveils neuronal and glial populations affected by the disease, and provides novel insights into the pathophysiological mechanisms of MOGHE.Key PointsWe provide a multimodal cellular atlas of the human cortical and subcortical regions affected in MOGHEMOGHE-associated oligodendrocytes exhibit immune response and myelination dysfunctionNeuronal migration and Wnt signaling are upregulated in heterotopic neurons
Metabolic modeling of a plant-pathogen interaction quantifies the metabolic bottlenecks underlying bacterial wilt
Authors: Gerlin Léo , Genin Stéphane , Baroukh Caroline 
Published: December 2024

AbstractDuring plant infection, complex metabolic interactions take place between the plant and the pathogen, among which occurs a true battle for resources. On one side, the pathogen harvests nutrients at the expense of the plant to sustain its growth and virulence. On the other side, the plant tries to prevent pathogen multiplication by competing for nutrients or using anti-microbial compounds. Plants and pathogens have thus contrary objectives in an intertwined system that is particularly difficult to untangle experimentally. To help decipher this interaction, we used genome-scale metabolic modeling by combining a multi-organ model of a plant, a model of a pathogen, quantitative data and a mathematical approach using sequential flux balance analyses (FBAs). We applied this modelling strategy to the interaction between the pathogenic bacteriumRalstonia pseudosolanacearumand its natural host the tomato plant. This allowed, for the first time, quantitative modeling of the fluxes of matter occurring during plant infection. The model showed that, for the pathosystem studied, i) the plant’s photosynthetic capacity is a more stringent environmental condition than minerals for bacterial proliferation ii) reduction of the plant transpiration is what limits and then stops plant growth and later pathogen growth, iii) hijacking stem resources can boost bacterial growth but is accessory, and iv) pathogen-excreted putrescine is predicted to be directly reused for plant biomass. This study provides the first holistic and quantitative view of a plant-pathogen interaction, and highlighted the criticality of water flow when the bacteria responsible of the infection is a fast-growing, xylem-colonizing one.Significance statementWhen a plant is infected by a pathogen, a true battle for resources occurs between the two organisms. On one side, the pathogen harvests nutrients at the expense of the plant to sustain its growth and virulence. On the other side, the plant tries to prevent pathogen multiplication by competing for nutrients or using anti-microbial compounds. To help understand this complex metabolic interaction, we used mathematical modelling to model bothRalstonia pseudosolanacearumand tomato plant metabolism. This allowed, for the first time, a quantitative insight on metabolic interactions and consequences on physiology of the plant during an infection. Among other results, the model showed that plant transpiration decline is what limits and then stops plant growth and later pathogen growth.
Polyphosphate as a Novel Regulator of Super-Enhancer Complexes: Disruption of Phase Separation and Gene Expression
Authors: Yang Zhiyun , Jia Zongchao 
Published: December 2024

SummaryInorganic polyphosphate (polyP) is a highly conserved linear polymer of orthophosphate, present across nearly all living organisms. Its functional diversity, particularly through recently discovered post-translational modifications, has garnered increasing scientific interest. However, its role in gene regulation, especially in mammalian systems, remains unexplored. In this study, we present findings that demonstrate that polyP multi-targets the super-enhancer complex to regulate gene expression, marking a novel mechanism of transcriptional control. We show that polyP modifies key components of the complex, including the Mediator subunit MED1, the coactivator Bromodomain-containing protein 4 (BRD4), and the transcriptional regulator Yin Yang 1 (YY1). This polyP-mediated modification not only disrupts their ability to undergo phase separation but also downregulates the expression of MED1 and BRD4, as well as impairs the nuclear localization of YY1. Furthermore, polyP inhibits YY1 dimer formation and disrupts YY1-mediated DNA looping, leading to suppressed gene expression. These discoveries highlight polyP as a novel regulator of super-enhancer-driven gene transcription and provide new insights into the broader role of polyP in epigenetic regulation. This work uncovers a previously unknown layer of gene control, positioning polyP as a critical player in transcriptional regulation through its interaction with transcription factors and coactivators.Graphical abstractHighlightsPolyP modifies key components of the super-enhancer complex BRD4, MED1 and YY1 by targeting their His-rich, Lys-rich or PASK sequencesPolyP disrupts phase separation of BRD4, MED1 and YY1PolyP impairs YY1’s recruitment of BRD4 and MED1 and disrupts nuclear localization, dimerization, DNA looping and DNA binding to YY1PolyP attenuates gene expression mediated by YY1 and BRD4