bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac autonomic function during exercise and incident Parkinson’s disease
Authors: van Duijvenboden Stefan , Ramírez Julia , Scheurink Job , Darweesh Sirwan K.L. , Orini Michele , Tinker Andrew , Munroe Patricia B. , Thannhauser Jos , Evers Luc , IntHout Joanna , Lambiase Pier D. , Bloem Bastiaan R. , Doherty Aiden , Brouwer Marc A. 
Published: November 2024

AbstractObjectiveTo determine whether established parameters of cardiac autonomic function are associated with incident Parkinson’s disease, independent of clinical characteristics, and established autonomic prodromal features.Methods Population-based cohortstudy of UK Biobank participants who performed a standardized bicycle exercise test (2009-2013), followed until November 2022, and analyzed in January 2024. Heart rate increase from rest to exercise, and the decrease in heart rate from peak exercise to recovery were extracted and associated with incident Parkinson’s disease. Associations were adjusted using multivariable models consisting of clinical characteristics only and combined with prodromal autonomic features.Results69,288 eligible participants (male 48%, mean age 56.8 [SD 8.2]) were followed for 12.5 years (median; IQR 0.3): 319 (0.5%) developed Parkinson’s disease. Median lag time to diagnosis was 9.3 years (IQR 4.4). Both heart rate increase (37.5 [SD 11.5] vs 40.8 [SD 12.4] beats/min, p < 0.001) and recovery (23.4 [SD 8.8] vs. 27.8 [SD 10.3] beats/min, p < 0.001) were significantly lower in incident cases compared to controls. After adjusting for prodromal clinical and autonomic features, heart rate recovery was independently associated with incident Parkinson’s disease, while heart rate increase was not. Specifically, a blunted heart rate lowering during recovery was associated with a 30% higher risk of incident Parkinson’s disease (HR: 1.3; 95% CI 1.1-1.4; p < 0.001 per 10 beats less recovery)InterpretationThese findings suggest that cardiac autonomic dysfunction precedes clinically manifest Parkinson’s disease, and that heart rate recovery might serve as a quantitative prodromal marker.
Epidermal loss of PRMT5 leads to the emergence of an atypical basal keratinocyte-like cell population and defective skin stratification
Authors: Recka Nicole , Simons Andrean , Cornell Robert A. , Van Otterloo Eric 
Published: November 2024

ABSTRACTDuring skin development, ectoderm-derived cells undergo precisely coordinated proliferation, differentiation, and adhesion to yield stratified epidermis. Disruptions in these processes can result in congenital anomalies including ectodermal dysplasia and harlequin ichthyosis. Protein Arginine Methyl Transferase 5 (PRMT5)—an enzyme responsible for methylating arginine residues in histones and other proteins—maintains progenitor status in germ and limb bud cells. Similarly,in vitroevidence suggests that PRMT5 prevents differentiation of basal keratinocytes, leading us to hypothesize that PRMT5 preserves the stem-cell phenotype of keratinocytesin vivo. To test this possibility, we generated conditional knockout (cKO) mice lackingPrmt5in early ectoderm (E7.5), impacting the entire epidermis.Prmt5cKOs exhibited gross skin defects, compromised skin barrier function, and reduced postnatal viability. Histological analyses revealed significant defects in epidermal stratification, without alterations in apoptosis or proliferation. Single-cell RNA and ATAC-seq analysis identified an atypical population of basal keratinocyte-like cells inPrmt5cKOs, that exhibited a senescence-like program, characterized by increasedCdkn1a(p21), elevated senescence-associated secretory phenotype (SASP) molecules (Igfbp2), and decreased developmental transcription factor (Trp63) expression. Our findings suggest that PRMT5 prevents basal keratinocyte senescence by repressingCdkn1a, shedding light on the epigenetic regulation of basal keratinocyte maintenance and senescence in congenital skin disorders.
Paired and solitary ionocytes in the zebrafish olfactory epithelium
Authors: Peloggia Julia , Cheung King Yee , Whitfield Tanya T. , Petkova Mariela D. , Schalek Richard , Boulanger-Weill Jonathan , Wu Yuelong , Wang Shuohong , van Hateren Nicholas J. , Januszewski Michał , Jain Viren , Lichtman Jeff W. , Engert Florian , Piotrowski Tatjana , Jesuthasan Suresh 
Published: November 2024

AbstractThe sense of smell is generated by electrical currents that are influenced by the concentration of ions in olfactory sensory neurons and mucus. In contrast to the extensive morphological and molecular characterization of sensory neurons, there has been little description of the cells that control ion concentrations in the zebrafish olfactory system. Here, we report the molecular and ultrastructural characterization of zebrafish olfactory ionocytes. Transcriptome analysis suggests that the zebrafish olfactory epithelium contains at least three different ionocyte types, which resemble Na+/K+-ATPase-rich (NaR), Na+/Cl-cotransporter (NCC), and H+-ATPase-rich (HR) cells, responsible for calcium, chloride, and pH regulation, respectively, in the zebrafish skin. NaR-like and HR-like ionocytes are usually adjacent to one another, whereas NCC-like cells are usually solitary. The distinct subtypes are differentially distributed: NaR-like/HR-like cell pairs are found broadly within the olfactory epithelium, whereas NCC-like cells reside within the peripheral non-sensory multiciliated cell zone. Comparison of gene expression and serial-section electron microscopy analysis indicates that the NaR-like cells wrap around the HR-like cells and are connected to them by shallow tight junctions. The development of olfactory ionocyte subtypes is also differentially regulated, as pharmacological Notch inhibition leads to a loss of NaR-like and HR-like cells, but does not affect NCC-like ionocyte number. These results provide a molecular and anatomical characterization of olfactory ionocytes in a stenohaline freshwater teleost. The paired ionocytes suggest that both transcellular and paracellular transport regulate ion concentrations in the olfactory epithelium, while the solitary ionocytes may enable independent regulation of multiciliated cells.
Microbial Partner (MiPner) Analysis
Authors: Bennetzen Jeffrey L. , Canela Josue Fernandez , Elmgreen Vienna , McCann Shaugnessy R. , Norris Mary E. , Deng Xiangyu , Brailey-Jones Phillip 
Published: November 2024

ABSTRACTAlthough a few bacteria have been studied in great depth, relatively little is known about the characteristics of microbe-microbe interactions that occur within ecosystems on a daily basis. A simple, robust technique was developed to set up the foundation for investigating pairwise bacterial-bacterial interactions, using cell-cell binding as a self-selective mechanism to identify interesting bacterial species pairs. Using a Serratia marcescens strain (SMC43) isolated from Georgia soil as a “bait”, specific bacteria were purified by their specificity in binding SMC43 bacteria that were themselves attached to a wooden applicator stick. The isolated Microbial Partners (MiPners) were greatly enriched for members of the generaSphingobiumand Caulobacter. Two out of 24 streaked MiPners were unable to be separated from, and grow on the plate type tested without, SMC43. This suggests that the MiPner technology will be one strategy for purifying bacteria that were previously recalcitrant to culturing.
Prevalence and risk factors for avian influenza in backyard pigeons, ducks, and chickens in District Toba Tek Singh Pakistan
Authors: Shakeel Iram , Rashid Hamad Bin , Ain Quratul , Inayat Alijaan , Shakeel Umer , Awoniyi Adedayo Michael , Chaudhry Mamoona 
Published: November 2024

AbstractAvian influenza virus (AIV) is a zoonotic disease that can be transferred from birds to humans. Various pandemics of AIV have drastically affected the poultry industry and backyard birds (ducks, chickens, and pigeons) worldwide, such as in Europe, the USA, Africa, and Asia. In Pakistan, numerous outbreaks of H7, H5, and H9 in poultry industries have been documented in commercial and rural areas, resulting in financial losses. The epidemiological status of different AIV subtypes in backyard birds in rural areas is largely unknown. Cross-sectional study was conducted in 2018-2019 with multistage clustering sampling. These tracheal and cloacal pooled swab samples were collected and tested for AIV. Positive AIV pooled swab samples were further evaluated at the individual level. RNA was extracted using the Trizol method followed by multiplex RT‒PCR with primers and probes to identify the M-gene and subtypes of the AI virus. Statistical analysis was performed by using the multivariate logistic regression model. Overall, the prevalence of AIV in backyard chickens, pigeons, and ducks was 13.0%, 7.7%, and 11.3%, respectively. Among AIV subtypes, H7, H9, and HA/Untyped commonly circulated within backyard birds. All cities had nonsignificant differences (p> 0.05) in the prevalence of AIV among pigeons, ducks, and chickens. According to univariate logistic regression analysis, 16 of the 32 risk factors were further selected for the multivariate logistic regression model. Two potential factors were identified to be significantly associated (p< or =0.05). Among the variables, species (pigeon OR 9.2, 95% CI: 1.92-44.2;p=0.006) and chicken (OR 16.2, 95% CI: 2.89-91.5;p=0.006) strongly associated with the incidence of AIV among cities. Another variable, fighting cock, had a moderate association (OR 2.25, 95% CI: 0.99-5.09;p=0.051) with AIV prevalence. Enhancing surveillance, biosecurity, educational intervention, and farm practices to prevent AIV and improve poultry production and public health in Pakistan.
Methanotrophic flexibility of ‘Ca. Methanoperedens’ and its interactions with sulfate-reducing bacteria in the sediment of meromictic Lake Cadagno
Authors: Echeveste Medrano Maider J. , Su Guangyi , Blattner Lucas A. , Leão Pedro , Sánchez-Andrea Irene , Jetten Mike S. M. , Welte Cornelia U. , Zopfi Jakob 
Published: November 2024

AbstractThe greenhouse gas methane is an important contributor to global warming, with freshwater sediments representing important potential methane sources. Anaerobic methane-oxidizing archaea mitigate methane release into the atmosphere by coupling the oxidation of methane to the reduction of extracellular electron acceptors or through interspecies electron transfer with microbial partners. Understanding their metabolic flexibility and microbial interactions is crucial to assess their role in global methane cycling. Here, we investigated anoxic sediments of the meromictic freshwater Lake Cadagno (Switzerland), where ‘Ca. Methanoperedens’ and sulfate-reducing bacteria co-occur, with metagenomics and long-term incubations. Incubations were performed with different electron acceptors, revealing that manganese oxides supported highest CH4oxidation potential but enriched for ‘Ca. Methanoperedens’ phylotypes that were hardly present in the inoculum. Combining data from the inoculum and incubations, we obtained five ‘Ca.Methanoperedens’ genomes, each harboring different extracellular electron transfer pathways. In a reconstructedDesulfobacterota QYQD01genome we observed large multi-heme cytochromes, type IV pili, and a putative loss of hydrogenases, suggesting facultative syntrophic interactions with ‘Ca.Methanoperedens’. We also screened for putative extrachromosomal elements in the ‘Ca. Methanoperedens’ genomes, including BORGs. This research deepens our understanding of the metabolic flexibility and potential interspecific interactions of ‘Ca.Methanoperedens’ in freshwater lakes.
A multivalent adaptor mechanism drives the nuclear import of proteasomes
Authors: Brunner Hanna L. , Kalis Robert W. , Grundmann Lorenz , Hodáková Zuzana , Koskova Zuzana , Grishkovskaya Irina , de Almeida Melanie , Hinterndorfer Matthias , Höfflin Simon , Andersch Florian , Kotisch Harald , Dickmanns Achim , Cuylen-Häring Sara , Zuber Johannes , Haselbach David 
Published: November 2024

AbstractNuclear protein homeostasis, including the turnover of transcription factors, critically depends on nuclear proteasomes. After each cell division, proteasomes need to be re-imported into the newly formed nucleus in a highly dynamic process that requires the largely unstructured protein AKIRIN2. However, how AKIRIN2 orchestrates this process and, more generally, how large protein complexes are translocated into the nucleus remains poorly understood. Here, we have used an integrated approach combining protein-wide saturation mutagenesis screens, cryoEM, and biochemical reconstitution to characterize AKIRIN2 as a scaffold protein that coordinates the stepwise assembly of an importin cluster around the proteasome. Through surveying every possible single amino acid substitution in AKIRIN2 using FACS- and microscopy-based genetic screens, we establish a comprehensive map of functionally relevant residues and binding interfaces in structured and disordered protein regions. Integrating these results with cryoEM analysis reveals a wing helix in a disordered region of AKIRIN2 that plays a crucial role in stabilizing proteasome interactions. Upon primary binding, AKIRIN2 homodimers recruit the importin IPO9, which in turn facilitates the binding of a second AKIRIN2 homodimer that recruits additional importins. Together, this multivalent molecular assembly amplifies the number of nuclear localisation signals and, thereby, triggers efficient proteasome translocation into the nucleus. Inside the nucleus, RanGTP rapidly dissociates importins, and AKIRIN2 is degraded by the proteasome in a ubiquitin-independent manner. Beyond mechanistically resolving the nuclear import of proteasomes, we propose that multivalent adaptor proteins like AKIRIN2 orchestrate the import of other macromolecular complexes and thereby dynamically control the composition of the nuclear proteome.
Axonal spheroids are regulated by Schwann cells after peripheral nerve injury
Authors: Hunter-Chang Sarah , Kim-Aun Charlene , Karim Heeran , Jones Marieke , Vegiraju Tanvika , Stepanova Ekaterina , Manke Brynn , Kucenas Sarah , Deppmann Christopher 
Published: November 2024

AbstractAxonal spheroids are hallmark features of neurodegeneration, forming along degenerating axons and contributing to disease progression. Despite their ubiquity across degenerative etiologies, the dynamics of spheroid disappearance, as well as their interactions with glial cells, remain poorly understood. Here, using anin vivozebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells. These results describe spheroid dynamics across their lifetimes, establish a role for the extra-axonal environment in altering spheroid outcomes, and identify a cellular mechanism whereby spheroid fates are altered.SummaryAxonal spheroids (also called “dystrophic neurites,” “axonal swellings,” and “axonal beading”) undergo three fates: shrinking, breakdown, and uniform disappearanceSchwann cells ensheath most axonal spheroids and internalize a subset of themSchwann cells regulate axonal spheroid fates, identifying a role for axon-extrinsic processes in spheroid regulationAbstract FigureGraphical Abstract:Following injury, spheroids are more likely to undergo shrinking and breakdown when Schwann cells (SCs) are present on degenerating axons. When Schwann cells are absent, spheroids are more likely to undergo uniform disappearance. Spheroids expose phosphatidylserine, which could facilitate interactions between spheroids and SCs.
Cortical contributions to attentional orienting and response cancellation in action stopping
Authors: Kemp Sarah A , Salomoni Sauro , Bazin Pierre-Louis , Pash Luke , St George Rebecca J , Hinder Mark R 
Published: November 2024

ABSTRACTAction cancellation involves the termination of planned or initiated movement. Contemporary models of action cancellation, such as the Pause-then-Cancel model, propose that this occurs via a two-stage process, initiated in the cortex by the pre-supplementary motor area (preSMA) and inferior frontal gyrus (IFG). Previous experimental work using electromyography (EMG) has identified that the cancellation of actions can involve the partial activation of the responding muscles, which does not result in an overt behavioural response. In this study, we used functional near-infrared spectroscropy (fNIRS) to investigate the neural correlates of these partial responses in a modified stopping task (a response- and stimulus-selective stop-signal task), controlling for the attentional effects that have long confounded action cancellation research by comparing responses to stop stimuli with those to ignore stimuli. We identified stopping-related activity in the preSMA but not the IFG, consistent with predictions of the Pause-then-Cancel model. Additionally, we observed increased preSMA activity in trials where no partial responses occurred, potentially due to the cumulative effect of different inhibitory processes in those trials. This study also highlights the utility of combining fNIRS and EMG in examining the cortical correlates and dynamic processes involved in action cancellation.
Optimizing Lipidomics Analysis Workflows for Biological Fluids and Extracellular Vesicles with Integrated Liquid Chromatography Tandem Mass Spectrometry Approaches
Authors: Vilela Adriana F. L. , Patrício Miguel R. , Defelippo-Felippe Thiago V. , Nardini Viviani , Pontes Nathan N. H. , Carvalho Jonatan C. , Nobre-Azevedo Pedro , Rodrigues Daniel L. , Oliveira Bianca T. M. , da Silva-Neto Pedro V. , Fernandes Ana P. M. , Almeida Fausto , Faccioli Lucia H. , Sorgi Carlos A. 
Published: November 2024

AbstractLipidomics, a subfield of metabolomics, involves the comprehensive analysis of lipids within biological systems and has become a cornerstone of biomedical research, driven by recent technological advancements. Lipids are crucial biomolecules in cellular functions and have been increasingly recognized for their roles in physiological and pathological processes. This study focuses on innovative strategies for developing, validating, and applying comprehensive analytical methods for untargeted lipidomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in human plasma and extracellular vesicles (EVs). We describe improvements based on analytical validation parameters, including inter-day repeatability, limit of quantification, precision, accuracy, recovery, and matrix effects. Plasma samples were used as a proof-of-concept study, and the method was ultimately applied to human macrophage-derived EVs. Samples preparations were achieved through four liquid-liquid extraction methods for lipids in order to achieve a broad coverage of lipid classes as well as high recovery and repeatability. Additionally, we demonstrated that a sonication-assisted homogenization step effectively facilitates lipid extraction from EVs. Through untargeted lipidomics, our study identifies and quantifies a diverse range of lipid species in human plasma (225 molecular lipids) and macrophage-derived EVs (124 molecular lipids) within different classes. Overall, we present an innovative methodology that combines pre-analytical lipid extraction techniques with high-resolution LC-MS/MS to enhance lipidomics research. This approach holds promise for personalized medicine and the discovery of novel lipid cargo associated with the various biological pathways involved with EVs biogenesis.
KDM5C is a sex-biased brake against germline gene expression programs in somatic lineages
Authors: Bonefas Katherine M. , Venkatachalam Ilakkiya , Iwase Shigeki 
Published: November 2024

AbstractThe division of labor among cellular lineages is a pivotal step in the evolution of multicellularity. In mammals, the soma-germline boundary is formed during early embryogenesis, when genes that drive germline identity are repressed in somatic lineages through DNA and histone modifications at promoter CpG islands (CGIs). Somatic misexpression of germline genes is a signature of cancer and observed in select neurodevelopmental disorders. However, it is currently unclear if all germline genes use the same repressive mechanisms and if factors like development and sex influence their dysregulation. Here, we examine how cellular context influences the formation of somatic tissue identity in mice lacking lysine demethylase 5c (KDM5C), an X chromosome eraser of histone 3 lysine 4 di and tri-methylation (H3K4me2/3). We found maleKdm5cknockout (-KO) mice aberrantly express many tissue-specific genes within the brain, the majority of which are unique to the germline. By developing a comprehensive list of mouse germline-enriched genes, we observedKdm5c-KO cells aberrantly express key drivers of germline fate during early embryogenesis but late-stage spermatogenesis genes within the mature brain. KDM5C binds CGIs within germline gene promoters to facilitate DNA CpG methylation as embryonic stem cells differentiate into epiblast-like cells (EpiLCs). However, the majority of late-stage spermatogenesis genes expressed within theKdm5c-KO brain did not harbor promoter CGIs. These CGI-free germline genes were not bound by KDM5C and instead expressed through ectopic activation by RFX transcription factors. Furthermore, germline gene repression is sexually dimorphic, as female EpiLCs require a higher dose of KDM5C to maintain germline silencing. Altogether, these data revealed distinct regulatory classes of germline genes and sex-biased silencing mechanisms in somatic cells.
Income convergence clubs in the Eurozone: a tale beyond the core/periphery divide
Authors: García Solanes José , Beyaert Arielle , Lopez-Gomez Laura 
Published: November 2024

Purpose
This paper aims to examine income convergence among the Euro members from 1995 to 2021.

Design/methodology/approach
This study uses Phillips and Sul’s test (2007, 2009) extended by Lyncker and Thoennessen’s (2017) algorithm jointly with

β and

σ  – convergence analysis and a traditional growth equation.

Findings
This analysis identifies three clubs of countries in terms of gross domestic product (GDP) per capita with notable disparities between and within them, which implies that the theory of optimal currency areas has not been fulfilled.

Originality/value
These results rule out the core/periphery divide as presented in the literature to date. Finally, by estimating an endogenous economic growth model, this study finds the primary factors underpinning the differences between the three stationary states: labor productivity, physical and human capital, investment and international trade.