bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin-1β induces and accelerates human endometrial stromal cell senescence and impairs decidualization via the c-Jun N-terminal kinase pathway
Authors: Taylor Robert N. , Berga Sarah L. , Zou Eric , Washington Jacara , Song Sunyangzi , Marzullo Brandon J. , Bagchi Indrani C. , Bagchi Milan K. , Yu Jie
Published: June 2024

As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory dysfunction and oocyte aneuploidy parallel chronological age, but poor reproductive outcomes in women older than 35 years are also attributed to endometrial senescence. The current studies, using primary human endometrial stromal cell (ESC) cultures as an in vitro model for endometrial aging, characterize the proinflammatory cytokine, IL-1β-mediated and passage number-dependent effects on ESC phenotype. ESC senescence was accelerated by incubation with IL-1β, which was monitored by RNA sequencing, ELISA, immunocytochemistry and Western blotting. Senescence associated secreted phenotype (SASP) proteins, IL-1β, IL-6, IL-8, TNF-α, MMP3, CCL2, CCL5, and other senescence-associated biomarkers of DNA damage (p16, p21, HMGB1, phospho-γ-histone 2 A.X) were noted to increase directly in response to 0.1 nM IL-1β stimulation. Production of the corresponding SASP proteins increased further following extended cell passage. Using enzyme inhibitors and siRNA interference, these effects of IL-1β were found to be mediated via the c-Jun N-terminal kinase (JNK) signaling pathway. Hormone-induced ESC decidualization, classical morphological and biochemical endocrine responses to estradiol, progesterone and cAMP stimulation (prolactin, IGFBP-1, IL-11 and VEGF), were attenuated pari passu with prolonged ESC passaging. The kinetics of differentiation responses varied in a biomarker-specific manner, with IGFBP-1 and VEGF secretion showing the largest and smallest reductions, with respect to cell passage number. ESC hormone responsiveness was most robust when limited to the first six cell passages. Hence, investigation of ESC cultures as a decidualization model should respect this limitation of cell aging. The results support the hypotheses that “inflammaging” contributes to endometrial senescence, disruption of decidualization and impairment of fecundity. IL-1β and the JNK signaling pathway are pathogenetic targets amenable to pharmacological correction or mitigation with the potential to reduce endometrial stromal senescence and enhance uterine receptivity.
Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6
Authors: Shen Yujie , Huang Qiang , Yuan Xiaohui , Gong Hongli , Xu Chengzhi , Du Huaidong , Hsueh Chi-Yao , Zhou Liang
Published: June 2024

Nicotine, a crucial constituent of tobacco smoke, can bind to and activate nicotinic acetylcholine receptors (nAChRs), thereby regulating various biological functions. However, the specific mechanisms through which nicotine mediates nAChRs to regulate the metastasis of laryngeal squamous cell carcinoma (LSCC) remain elusive. In this study, smoking status was found to be closely associated with metastasis in patients with LSCC. In addition, nicotine exposure potentiated the hematogenous and lymphatic metastatic capacity of LSCC cells. Nicotine activates membrane-bound CHRNA5, promoting cell migration and invasion, EMT and cell–ECM adhesion in LSCC. Furthermore, this study demonstrated that the Ras superfamily protein RABL6 directly interacted with CHRNA5, which preferentially binds to the RABL6-39-279aa region, and this interaction was enhanced by nicotine. Nicotine-mediated activation of CHRNA5 enhanced its interaction with RABL6, triggering the JAK2/STAT3 signalling pathway and eventually augmenting the metastatic potential of LSCC cells. This study reveals a novel mechanism through which nicotine-mediated CHRNA5–RABL6 interaction promotes the metastasis of LSCC. The findings of this study may help to develop effective strategies for improving the outcome of patients with LSCC in clinical settings.
The roles of Th cells in myocardial infarction
Authors: Liu Jun , Liu Feila , Liang Tingting , Zhou Yue , Su Xiaohan , Li Xue , Zeng Jiao , Qu Peng , Wang Yali , Chen Fuli , Lei Qian , Li Gang , Cheng Panke
Published: June 2024

Myocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue damage. A significant aspect of this condition is reperfusion injury, which occurs when blood flow is restored but exacerbates the damage. This review first addresses the role of the innate immune system, including neutrophils and macrophages, in the cascade of events leading to myocardial infarction and reperfusion injury. It then shifts focus to the critical involvement of CD4+ T helper cells in these processes. These cells, pivotal in regulating the immune response and tissue recovery, include various subpopulations such as Th1, Th2, Th9, Th17, and Th22, each playing a unique role in the pathophysiology of myocardial infarction and reperfusion injury. These subpopulations contribute to the injury process through diverse mechanisms, with cytokines such as IFN-γ and IL-4 influencing the balance between tissue repair and injury exacerbation. Understanding the interplay between the innate immune system and CD4+ T helper cells, along with their cytokines, is crucial for developing targeted therapies to mitigate myocardial infarction and reperfusion injury, ultimately improving outcomes for cardiac patients.
In-tube micro-pyramidal silicon nanopore for inertial-kinetic sensing of single molecules
Authors: Yang Jianxin , Pan Tianle , Xie Zhenming , Yuan Wu , Ho Ho-Pui
Published: June 2024

Electrokinetic force has been the major choice for driving the translocation of molecules through a nanopore. However, the use of this approach is limited by an uncontrollable translocation speed, resulting in non-uniform conductance signals with low conformational sensitivity, which hinders the accurate discrimination of the molecules. Here, we show the use of inertial-kinetic translocation induced by spinning an in-tube micro-pyramidal silicon nanopore fabricated using photovoltaic electrochemical etch-stop technique for biomolecular sensing. By adjusting the kinetic properties of a funnel-shaped centrifugal force field while maintaining a counter-balanced state of electrophoretic and electroosmotic effect in the nanopore, we achieved regulated translocation of proteins and obtained stable signals of long and adjustable dwell times and high conformational sensitivity. Moreover, we demonstrated instantaneous sensing and discrimination of molecular conformations and longitudinal monitoring of molecular reactions and conformation changes by wirelessly measuring characteristic features in current blockade readouts using the in-tube nanopore device.
Roadblocks confronting widespread dissemination and deployment of Organs on Chips
Authors: Alver Charles G. , Drabbe Emma , Ishahak Matthew , Agarwal Ashutosh
Published: June 2024

Organ on Chip platforms hold significant promise as alternatives to animal models or traditional cell cultures, both of which poorly recapitulate human pathophysiology and human level responses. Within the last 15 years, we have witnessed seminal scientific developments from academic laboratories, a flurry of startups and investments, and a genuine interest from pharmaceutical industry as well as regulatory authorities to translate these platforms. This Perspective identifies several fundamental design and process features that may act as roadblocks that prevent widespread dissemination and deployment of these systems, and provides a roadmap to help position this technology in mainstream drug discovery.
Deep cell phenotyping and spatial analysis of multiplexed imaging with TRACERx-PHLEX
Authors: Magness Alastair , Colliver Emma , Enfield Katey S. S. , Lee Claudia , Shimato Masako , Daly Emer , Moore David A. , Sivakumar Monica , Valand Karishma , Levi Dina , Hiley Crispin T. , Hobson Philip S. , van Maldegem Febe , Reading James L. , Quezada Sergio A. , Downward Julian , Sahai Erik , Swanton Charles , Angelova Mihaela
Published: June 2024

The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations. PHLEX was developed using imaging mass cytometry (IMC) in the TRACERx study, validated using published Co-detection by indexing (CODEX), IMC and orthogonal data and benchmarked against state-of-the-art approaches. We evaluated its use on different tissue types, tissue fixation conditions, image sizes and antibody panels. As PHLEX is an automated and containerised Nextflow pipeline, manual assessment, programming skills or pathology expertise are not essential. PHLEX offers an end-to-end solution in a growing field of highly multiplexed data and provides clinically relevant insights.
Oceanic Anoxic Event 2 triggered by Kerguelen volcanism
Authors: Walker-Trivett C. A. , Kender S. , Bogus K. A. , Littler K. , Edvardsen T. , Leng M. J. , Lacey J. , Riding J. B. , Millar I. L. , Wagner D.
Published: June 2024

Large Igneous Provinces (LIPs) are associated with global warming and carbon cycle perturbations during Oceanic Anoxic Event 2 (OAE2, ~94 Ma) and the Mid-Cenomanian Event (MCE, ~96.5 Ma). However, there is still no consensus on the role volcanism played as a trigger, or its source – previously ascribed to the Caribbean LIP or High Arctic LIP. Here, we use Mentelle Basin sedimentary mercury (Hg) concentrations to determine the timing of volcanism, and neodymium (Nd) and strontium (Sr) isotopes for sedimentary provenance. High Hg concentrations compared to Northern Hemisphere records, and a shift to radiogenic Nd isotopes, indicates Kerguelen LIP volcanic activity and plateau uplift occurred in the lead up to and within OAE2. Whilst we find limited evidence that a volcanic event caused the MCE, pulsed Hg spikes before and during OAE2 imply volcanic emissions were key in driving climate and carbon cycle changes and triggering OAE2.
m5C methylated lncRncr3–MeCP2 interaction restricts miR124a-initiated neurogenesis
Authors: Zhang Jing , Li Huili , Niswander Lee A.
Published: June 2024

Coordination of neuronal differentiation with expansion of the neuroepithelial/neural progenitor cell (NEPC/NPC) pool is essential in early brain development. Our in vitro and in vivo studies identify independent and opposing roles for two neural-specific and differentially expressed non-coding RNAs derived from the same locus: the evolutionarily conserved lncRNA Rncr3 and the embedded microRNA miR124a-1. Rncr3 regulates NEPC/NPC proliferation and controls the biogenesis of miR124a, which determines neuronal differentiation. Rncr3 conserved exons 2/3 are cytosine methylated and bound by methyl-CpG binding protein MeCP2, which restricts expression of miR124a embedded in exon 4 to prevent premature neuronal differentiation, and to orchestrate proper brain growth. MeCP2 directly binds cytosine-methylated Rncr3 through previously unrecognized lysine residues and suppresses miR124a processing by recruiting PTBP1 to block access of DROSHA-DGCR8. Thus, miRNA processing is controlled by lncRNA m5C methylation along with the defined m5C epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.
Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue
Authors: Baek Sewoom , Ha Hyun-Su , Park Jeong Su , Cho Min Jeong , Kim Hye-Seon , Yu Seung Eun , Chung Seyong , Kim Chansik , Kim Jueun , Lee Ji Youn , Lee Yerin , Kim Hyunjae , Nam Yujin , Cho Sungwoo , Lee Kyubae , Yoon Ja Kyung , Choi Jin Sub , Han Dai Hoon , Sung Hak-Joon
Published: June 2024

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.
Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology
Authors: Mastenbroek Sophie E. , Vogel Jacob W. , Collij Lyduine E. , Serrano Geidy E. , Tremblay Cécilia , Young Alexandra L. , Arce Richard A. , Shill Holly A. , Driver-Dunckley Erika D. , Mehta Shyamal H. , Belden Christine M. , Atri Alireza , Choudhury Parichita , Barkhof Frederik , Adler Charles H. , Ossenkoppele Rik , Beach Thomas G. , Hansson Oskar
Published: June 2024

Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer’s disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.
Stabilized ε-Fe2C catalyst with Mn tuning to suppress C1 byproduct selectivity for high-temperature olefin synthesis
Authors: Qian Fei , Bai Jiawei , Cai Yi , Yang Hui , Cao Xue-Min , Liu Xingchen , Liu Xing-Wu , Yang Yong , Li Yong-Wang , Ma Ding , Wen Xiao-Dong
Published: June 2024

Accurately controlling the product selectivity in syngas conversion, especially increasing the olefin selectivity while minimizing C1 byproducts, remains a significant challenge. Epsilon Fe2C is deemed a promising candidate catalyst due to its inherently low CO2 selectivity, but its use is hindered by its poor high-temperature stability. Herein, we report the successful synthesis of highly stable ε-Fe2C through a N-induced strategy utilizing pyrolysis of Prussian blue analogs (PBAs). This catalyst, with precisely controlled Mn promoter, not only achieved an olefin selectivity of up to 70.2% but also minimized the selectivity of C1 byproducts to 19.0%, including 11.9% CO2 and 7.1% CH4. The superior performance of our ε-Fe2C-xMn catalysts, particularly in minimizing CO2 formation, is largely attributed to the interface of dispersed MnO cluster and ε-Fe2C, which crucially limits CO to CO2 conversion. Here, we enhance the carbon efficiency and economic viability of the olefin production process while maintaining high catalytic activity.
Hebbian priming of human motor learning
Authors: Bjørndal Jonas Rud , Beck Mikkel Malling , Jespersen Lasse , Christiansen Lasse , Lundbye-Jensen Jesper
Published: June 2024

Motor learning relies on experience-dependent plasticity in relevant neural circuits. In four experiments, we provide initial evidence and a double-blinded, sham-controlled replication (Experiment I-II) demonstrating that motor learning involving ballistic index finger movements is improved by preceding paired corticospinal-motoneuronal stimulation (PCMS), a human model for exogenous induction of spike-timing-dependent plasticity. Behavioral effects of PCMS targeting corticomotoneuronal (CM) synapses are order- and timing-specific and partially bidirectional (Experiment III). PCMS with a 2 ms inter-arrival interval at CM-synapses enhances learning and increases corticospinal excitability compared to control protocols. Unpaired stimulations did not increase corticospinal excitability (Experiment IV). Our findings demonstrate that non-invasively induced plasticity interacts positively with experience-dependent plasticity to promote motor learning. The effects of PCMS on motor learning approximate Hebbian learning rules, while the effects on corticospinal excitability demonstrate timing-specificity but not bidirectionality. These findings offer a mechanistic rationale to enhance motor practice effects by priming sensorimotor training with individualized PCMS.
Light chain mutations contribute to defining the fibril morphology in systemic AL amyloidosis
Authors: Karimi-Farsijani Sara , Pfeiffer Peter Benedikt , Banerjee Sambhasan , Baur Julian , Kuhn Lukas , Kupfer Niklas , Hegenbart Ute , Schönland Stefan O. , Wiese Sebastian , Haupt Christian , Schmidt Matthias , Fändrich Marcus
Published: June 2024

Systemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To explore whether these mutations may affect the structure of the formed fibrils, we determine and compare the fibril structures from several patients with cardiac AL amyloidosis. All patients are affected by light chains that contain an IGLV3-19 gene segment, and the deposited fibrils differ by the mutations within this common germ line background. Using cryo-electron microscopy, we here find different fibril structures in each patient. These data establish that the mutations of amyloidogenic light chains contribute to defining the fibril architecture and hence the structure of the pathogenic agent.
Single-molecule reconstruction of eukaryotic factor-dependent transcription termination
Authors: Xiong Ying , Han Weijing , Xu Chunhua , Shi Jing , Wang Lisha , Jin Taoli , Jia Qi , Lu Ying , Hu Shuxin , Dou Shuo-Xing , Lin Wei , Strick Terence R. , Wang Shuang , Li Ming
Published: June 2024

Factor-dependent termination uses molecular motors to remodel transcription machineries, but the associated mechanisms, especially in eukaryotes, are poorly understood. Here we use single-molecule fluorescence assays to characterize in real time the composition and the catalytic states of Saccharomyces cerevisiae transcription termination complexes remodeled by Sen1 helicase. We confirm that Sen1 takes the RNA transcript as its substrate and translocates along it by hydrolyzing multiple ATPs to form an intermediate with a stalled RNA polymerase II (Pol II) transcription elongation complex (TEC). We show that this intermediate dissociates upon hydrolysis of a single ATP leading to dissociation of Sen1 and RNA, after which Sen1 remains bound to the RNA. We find that Pol II ends up in a variety of states: dissociating from the DNA substrate, which is facilitated by transcription bubble rewinding, being retained to the DNA substrate, or diffusing along the DNA substrate. Our results provide a complete quantitative framework for understanding the mechanism of Sen1-dependent transcription termination in eukaryotes.
Light regulates nuclear detainment of intron-retained transcripts through COP1-spliceosome to modulate photomorphogenesis
Authors: Zhou Hua , Zeng Haiyue , Yan Tingting , Chen Sunlu , Fu Ying , Qin Guochen , Zhao Xianhai , Heng Yueqin , Li Jian , Lin Fang , Xu Dongqing , Wei Ning , Deng Xing Wang
Published: June 2024

Intron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.
Multiscale and multidisciplinary analysis of aging processes in bone
Authors: Ravazzano Linda , Colaianni Graziana , Tarakanova Anna , Xiao Yu-Bai , Grano Maria , Libonati Flavia
Published: June 2024

The world population is increasingly aging, deeply affecting our society by challenging our healthcare systems and presenting an economic burden, thus turning the spotlight on aging-related diseases: exempli gratia, osteoporosis, a silent disease until you suddenly break a bone. The increase in bone fracture risk with age is generally associated with a loss of bone mass and an alteration in the skeletal architecture. However, such changes cannot fully explain increased fragility with age. To successfully tackle age-related bone diseases, it is paramount to comprehensively understand the fundamental mechanisms responsible for tissue degeneration. Aging mechanisms persist at multiple length scales within the complex hierarchical bone structure, raising the need for a multiscale and multidisciplinary approach to resolve them. This paper aims to provide an overarching analysis of aging processes in bone and to review the most prominent outcomes of bone aging. A systematic description of different length scales, highlighting the corresponding techniques adopted at each scale and motivating the need for combining diverse techniques, is provided to get a comprehensive description of the multi-physics phenomena involved.
Development and validation of a clinical breast cancer tool for accurate prediction of recurrence
Authors: Dhungana Asim , Vannier Augustin , Zhao Fangyuan , Freeman Jincong Q. , Saha Poornima , Sullivan Megan , Yao Katharine , Flores Elbio M. , Olopade Olufunmilayo I. , Pearson Alexander T. , Huo Dezheng , Howard Frederick M.
Published: June 2024

Given high costs of Oncotype DX (ODX) testing, widely used in recurrence risk assessment for early-stage breast cancer, studies have predicted ODX using quantitative clinicopathologic variables. However, such models have incorporated only small cohorts. Using a cohort of patients from the National Cancer Database (NCDB,n = 53,346), we trained machine learning models to predict low-risk (0-25) or high-risk (26-100) ODX using quantitative estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 status, quantitative ER/PR status alone, and no quantitative features. Models were externally validated on a diverse cohort of 970 patients (median follow-up 55 months) for accuracy in ODX prediction and recurrence. Comparing the area under the receiver operating characteristic curve (AUROC) in a held-out set from NCDB, models incorporating quantitative ER/PR (AUROC 0.78, 95% CI 0.77–0.80) and ER/PR/Ki-67 (AUROC 0.81, 95% CI 0.80–0.83) outperformed the non-quantitative model (AUROC 0.70, 95% CI 0.68–0.72). These results were preserved in the validation cohort, where the ER/PR/Ki-67 model (AUROC 0.87, 95% CI 0.81–0.93,p = 0.009) and the ER/PR model (AUROC 0.86, 95% CI 0.80–0.92,p = 0.031) significantly outperformed the non-quantitative model (AUROC 0.80, 95% CI 0.73–0.87). Using a high-sensitivity rule-out threshold, the non-quantitative, quantitative ER/PR and ER/PR/Ki-67 models identified 35%, 30% and 43% of patients as low-risk in the validation cohort. Of these low-risk patients, fewer than 3% had a recurrence at 5 years. These models may help identify patients who can forgo genomic testing and initiate endocrine therapy alone. An online calculator is provided for further study.
Computational morphogenesis for liquid crystal elastomer metamaterial
Authors: Li Weichen , Zhang Xiaojia Shelly
Published: June 2024

Liquid crystal elastomer (LCE) is a type of soft active material that generates large and reversible spontaneous deformations upon temperature changes, facilitating various environmentally responsive smart applications. Despite their success, most existing LCE metamaterials are designed in a forward fashion based on intuition and feature regular material patterns, which may hinder the reach of LCE’s full potential in producing complex and desired functionalities. Here, we develop a computational inverse design framework for discovering diverse sophisticated temperature-activated and -interactive nonlinear behaviors for LCE metamaterials in a fully controllable fashion. We generate intelligent LCE metamaterials with a wide range of switchable functionalities upon temperature changes. By sensing the environment, these metamaterials can realize maximized spontaneous area expansion/contraction, precisely programmable enclosed opening size change, and temperature-switchable nonlinear stress–strain relations and deformation modes. The optimized unit cells feature irregular LCE patterns and form complex and highly nonlinear mechanisms. The inverse design computational framework, optimized material patterns, and revealed underlying mechanisms fundamentally advance the design capacity of LCE metamaterials, benefiting environment-aware and -adaptive smart materials.
Dry immersion rapidly disturbs iron metabolism in men and women: results from the VIVALDI studies
Authors: Horeau Mathieu , Navasiolava Nastassia , Van Ombergen Angelique , Custaud Marc-Antoine , Robin Adrien , Ropert Martine , Antunes Inês , Bareille Marie-Pierre , Billette De Villemeur Rebecca , Gauquelin-Koch Guillemette , Derbré Frédéric , Loréal Olivier
Published: June 2024

Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity.
Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies
Authors: Dellarole Ilaria Linda , Vacchi Elena , Ruiz-Barrio Inigo , Pinton Sandra , Raimondi Andrea , Rossi Stefania , Morandi Sara , Bianco Giovanni , Begum Bacinoglu Merve , Lombardo Annalisa , Celauro Luigi , Staedler Claudio , Galati Salvatore , Pagonabarraga Javier , Kulisevsky Jaime , Legname Giuseppe , Gobbi Claudio , Kaelin-Lang Alain , Moda Fabio , Melli Giorgia
Published: June 2024

Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson’s disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0.825), while CBD vs HC / PD (AUC 0.797), and PSP vs MSA (AU 0.778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.
Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers
Authors: Tan Wenzhi , Thiruppathi Jayalakshmi , Hong Seol Hee , Puth Sao , Pheng Sophea , Mun Bo-Ram , Choi Won-Seok , Lee Kyung-Hwa , Park Hyun-Sun , Nguyen Duc Tien , Lee Min-Cheol , Jeong Kwangjoon , Zheng Jin Hai , Kim Young , Lee Shee Eun , Rhee Joon Haeng
Published: June 2024

Alzheimer’s disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.
Immune escape of avian oncogenic Marek’s disease herpesvirus and antagonistic host immune responses
Authors: Zhu Zhi-Jian , Teng Man , Liu Yu , Chen Fu-Jia , Yao Yongxiu , Li En-Zhong , Luo Jun
Published: June 2024

Marek’s disease virus (MDV) is a highly pathogenic and oncogenic alpha herpesvirus that causes Marek’s disease (MD), which is one of the most important immunosuppressive and rapid-onset neoplastic diseases in poultry. The onset of MD lymphomas and other clinical diseases can be efficiently prevented by vaccination; these vaccines are heralded as the first demonstration of a successful vaccination strategy against a cancer. However, the persistent evolution of epidemic MDV strains towards greater virulence has recently resulted in frequent outbreaks of MD in vaccinated chicken flocks worldwide. Herein, we provide an overall review focusing on the discovery and identification of the strategies by which MDV evades host immunity and attacks the immune system. We have also highlighted the decrease in the immune efficacy of current MD vaccines. The prospects, strategies and new techniques for the development of efficient MD vaccines, together with the possibilities of antiviral therapy in MD, are also discussed.
A multimodal framework for extraction and fusion of satellite images and public health data
Authors: Moukheiber Dana , Restrepo David , Cajas Sebastián Andrés , Montoya María Patricia Arbeláez , Celi Leo Anthony , Kuo Kuan-Ting , López Diego M. , Moukheiber Lama , Moukheiber Mira , Moukheiber Sulaiman , Osorio-Valencia Juan Sebastian , Purkayastha Saptarshi , Paddo Atika Rahman , Wu Chenwei , Kuo Po-Chih
Published: June 2024

In low- and middle-income countries, the substantial costs associated with traditional data collection pose an obstacle to facilitating decision-making in the field of public health. Satellite imagery offers a potential solution, but the image extraction and analysis can be costly and requires specialized expertise. We introduce SatelliteBench, a scalable framework for satellite image extraction and vector embeddings generation. We also propose a novel multimodal fusion pipeline that utilizes a series of satellite imagery and metadata. The framework was evaluated generating a dataset with a collection of 12,636 images and embeddings accompanied by comprehensive metadata, from 81 municipalities in Colombia between 2016 and 2018. The dataset was then evaluated in 3 tasks: including dengue case prediction, poverty assessment, and access to education. The performance showcases the versatility and practicality of SatelliteBench, offering a reproducible, accessible and open tool to enhance decision-making in public health.
The Global Historical Climatology Network Monthly Precipitation Dataset, Version 4
Authors: Applequist Scott , Durre Imke , Vose Russell
Published: June 2024

The Global Historical Climatology Network (GHCN) monthly precipitation dataset contains historical time series for thousands of land surface stations worldwide. Initially released in 1992 and revised in 1998, the dataset has been employed in a variety of applications over the past three decades, including operational monitoring, applied research, and international assessments. This paper describes the data and methods used to compile the latest edition (version 4), which has three major enhancements. The first enhancement is to the station network, which increased in size by a factor of five due to the inclusion of dozens of new source datasets, most notably GHCN Daily (GHCNd). The second improvement is the application of a rule-based algorithm to compare and merge records representing the same location. The third enhancement is to the quality assurance approach, now consisting of 18 new checks based on GHCNd and other operational systems. Updated monthly, the resulting dataset consists of time series of monthly precipitation totals at more than 120,000 worldwide stations, including more than 33,000 active observing sites.
Development of a model to predict the age at breast cancer diagnosis in a global population
Authors: Kim Ha Young , Mullaert Jimmy , Tondreau Ambre , Park Boyoung , Rouzier Roman
Published: June 2024

Knowing the mean age at diagnosis of breast cancer (BC) in a country is important for setting up an efficient BC screening program. The aim of this study was to develop and validate a model to predict the mean age at diagnosis of BC at the country level. To develop the model, we used the CI5plus database from the IARC, which contains incidence data for 122 selected populations for a minimum of 15 consecutive years from 1993 to 2012 and data from the World Bank. The standard model was fitted with a generalized linear model with the age of the population, growth domestic product per capita (GDPPC) and fertility rate as fixed effects and continent as a random effect. The model was validated in registries of the Cancer Incidence in Five Continents that are not included in the CI5plus database (1st validation set: 1950–2012) and in the most recently released volume (2nd validation set: 2013–2017). The intercept of the model was 30.9 (27.8–34.1), and the regression coefficients for population age, GDPPC and fertility rate were 0.55 (95% CI: 0.53–0.58, p < 0.001), 0.46 (95% CI: 0.26–0.67, p < 0.001) and 1.62 (95% CI: 1.42–1.88, p < 0.001), respectively. The marginal R2 and conditional R2 were 0.22 and 0.81, respectively, suggesting that 81% percent of the variance in the mean age at diagnosis of BC was explained by the variance in population age, GDPPC and fertility rate through linear relationships. The model was highly accurate, as the correlations between the predicted age from the model and the observed mean age at diagnosis of BC were 0.64 and 0.89, respectively, and the mean relative error percentage errors were 5.2 and 3.1% for the 1st and 2nd validation sets, respectively. We developed a robust model based on population age and continent to predict the mean age at diagnosis of BC in populations. This tool could be used to implement BC screening in countries without prevention programs.
Interaction energy flow paths analysis of PMSG-based wind power integrated systems during LVRT and its parameter adjustment strategy
Authors: Xing Chao , Xi Xinze , He Xin , Deng Can , Zhang Mingqiang
Published: June 2024

To solve the problem of oscillation instability in permanent magnetic synchronous generator (PMSG)-based wind power connected systems during low-voltage ride through (LVRT) process, a parameter adjustment strategy based on interaction energy path optimization is proposed in this paper. Firstly, a modular state-space model of PMSG under fault transient conditions is constructed, and the system is divided into five subsystems. Then, the dynamic energy function of subsystems reflecting the oscillation stability of the system is derived. Based on that, the dynamic energy flow path is described considering the introduction of LVRT control. On this basis, the interaction energy between LVRT control links and subsystems is analyzed, and the coupling mechanism of voltage support and damping characteristics in the LVRT process is explained. Further, aiming at the optimal change rate of the total interaction energy in the LVRT process, the adjustment strategy of LVRT control parameters is constructed to meet voltage and damping requirements. Finally, a PMSG-connected system model is built on the MATLAB/Simulink platform to verify the effectiveness of the adjustment strategy. The results show that the proposed method can effectively improve the damping level under the fault transient condition, as well as supporting system voltage.
Novel CTD tag establishes shark fins as ocean observing platforms
Authors: Pagniello Camille M. L. S. , Castleton Michael R. , Carlisle Aaron B. , Chapple Taylor K. , Schallert Robert J. , Fedak Michael , Block Barbara A.
Published: June 2024

Animal-borne tags are effective instruments for collecting ocean data and can be used to fill spatial gaps in the observing network. We deployed the first conductivity, temperature, and depth (CTD) satellite tags on the dorsal fin of salmon sharks (Lamna ditropis) to demonstrate the potential of sharks to monitor essential ocean variables and oceanographic features in the Gulf of Alaska. Over 1360 km and 36 days in the summer of 2015, the salmon shark collected 56 geolocated, temperature-salinity profiles. The shark swam through a plume of anomalously salty water that originated from the “Blob” and encountered several mesoscale eddies, whose subsurface properties were altered by the marine heatwave. We demonstrate that salmon sharks have the potential to serve as submesoscale-resolving oceanographic platforms and substantially increase the spatial coverage of observations in the Gulf of Alaska.
Preparation of porous biochar from fusarium wilt-infected banana straw for remediation of cadmium pollution in water bodies
Authors: Gao Chengxiang , Lan Yi , Zhan Yaowei , Li Yuechen , Jiang Jiaquan , Li Yuanqiong , Zhang Lidan , Fan Xiaolin
Published: June 2024

The problem of cadmium pollution and its control is becoming increasingly severe issue in the world. Banana straw is an abundant bio raw material, but its burning or discarding in field not only causes pollution but also spreads fusarium wilt. The objective of this paper is to utilize biochar derived from the wilt-infected banana straw for remediation of Cd(II) pollution while to eliminate the pathogen. The activity of wilt pathogen in biochar was determined by PDA petri dish test. The Cd(II) adsorption of the biochar was determined by batch adsorption experiments. The effects of KOH concentration (0.25, 0.5 and 0.75 M) on the physicochemical characteristics of the biochar were also observed by BET, SEM, FTIR, XRD and XPS. Results showed that pristine banana straw biochar (PBBC) did not harbor any pathogen. The specific surface area (SSA) and Cd(II) adsorption capacity of 0.75 M KOH modified banana straw biochar (MBBC0.75M) were increased by 247.2% and 46.1% compared to that of PBBC, respectively. Cd(II) adsorption by MBBC0.75M was suitable to be described by the pseudo-second-order kinetic model and Freundlich isotherm. After Cd(II) adsorption, the CdCO3 were confirmed by XRD and observed through SEM. The weakness and shift of oxygen-containing functional groups in MBBC0.75M after Cd(II) adsorption implied that those groups were complexed with Cd(II). The results showed that pyrolysis could not only eliminate banana fusarium wilt, but also prepare porous biochar with the wilt-infected banana straw. The porous biochar possessed the potential to adsorb Cd(II) pollutants.
Detection of Parkinson disease using multiclass machine learning approach
Authors: Srinivasan Saravanan , Ramadass Parthasarathy , Mathivanan Sandeep Kumar , Panneer Selvam Karthikeyan , Shivahare Basu Dev , Shah Mohd Asif
Published: June 2024

Parkinson’s Disease (PD) is a prevalent neurological condition characterized by motor and cognitive impairments, typically manifesting around the age of 50 and presenting symptoms such as gait difficulties and speech impairments. Although a cure remains elusive, symptom management through medication is possible. Timely detection is pivotal for effective disease management. In this study, we leverage Machine Learning (ML) and Deep Learning (DL) techniques, specifically K-Nearest Neighbor (KNN) and Feed-forward Neural Network (FNN) models, to differentiate between individuals with PD and healthy individuals based on voice signal characteristics. Our dataset, sourced from the University of California at Irvine (UCI), comprises 195 voice recordings collected from 31 patients. To optimize model performance, we employ various strategies including Synthetic Minority Over-sampling Technique (SMOTE) for addressing class imbalance, Feature Selection to identify the most relevant features, and hyperparameter tuning using RandomizedSearchCV. Our experimentation reveals that the FNN and KSVM models, trained on an 80–20 split of the dataset for training and testing respectively, yield the most promising results. The FNN model achieves an impressive overall accuracy of 99.11%, with 98.78% recall, 99.96% precision, and a 99.23% f1-score. Similarly, the KSVM model demonstrates strong performance with an overall accuracy of 95.89%, recall of 96.88%, precision of 98.71%, and an f1-score of 97.62%. Overall, our study showcases the efficacy of ML and DL techniques in accurately identifying PD from voice signals, underscoring the potential for these approaches to contribute significantly to early diagnosis and intervention strategies for Parkinson’s Disease.
Carbon utilization and storage through rehabilitation of groundwater wells
Authors: Patil Vivek V. , Basso Gabriella , Catania Steven , Catania Christopher , Ostapuk Timothy , Vince Robert
Published: June 2024

According to the Intergovernmental Panel on Climate Change (IPCC) of the United Nations (UN), rise in atmospheric concentration of carbon dioxide (CO

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) due to anthropogenic factors is considered as the primary driver for global climate change. With almost every major corporation around the world working towards their “net-zero goals”, it is becoming increasingly important to have more technologies that can help reduce carbon footprint. Achieving sequestration of CO

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in the subsurface through Carbon Capture Utilization and Storage (CCUS) technologies like CO

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-Enhanced Oil Recovery, CO

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-Enhanced Geothermal Systems, CO

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-Enhanced Coal Bed Methane, etc. is well accepted. We introduce yet another attractive CCUS opportunity through well rehabilitation. Aqua Freed® and Aqua Gard® are well-known well rehabilitation and preventive well maintenance technologies that utilize (inject underground) liquid CO

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for the purpose. The goal of this study was to quantify the storage capacity of Aqua Freed® and Aqua Gard®, and establish their CCUS credentials. Depending on the well being serviced, these technologies can inject up to 40 US tons of CO

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per well. Based on field data collection and statistical modeling, we estimated that 82–96% (median 90%) of the injected CO

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remains in the subsurface post injection. Overall, our results and analysis of the US market suggest that using CO

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for well rehabilitation and maintenance has a storage potential of several megatonnes of CO

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annually in the US alone.
HALP score as a novel prognostic factor for patients with myelodysplastic syndromes
Authors: Gursoy Vildan , Sadri Sevil , Kucukelyas Hatice Demirci , Hunutlu Fazıl Cagri , Pinar Ibrahim Ethem , Yegen Zafer Serenli , Alkış Nihan , Ersal Tuba , Ali Ridvan , Ozkocaman Vildan , Ozkalemkas Fahir
Published: June 2024

Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients’ median age was 68 (19–84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34–49.88) months by the Kaplan–Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS.