bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Gut Microbial Diversity Augments Estrogen-driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease
Authors: Chioma Ozioma S. , Mallott Elizabeth , Shah-Gandhi Binal , Wiggins ZaDarreyal , Langford Madison , Lancaster Andrew William , Gelbard Alexander , Wu Hongmei , Johnson Joyce E. , Lancaster Lisa , Wilfong Erin M. , Crofford Leslie J. , Montgomery Courtney G. , Van Kaer Luc , Bordenstein Seth , Newcomb Dawn C. , Drake Wonder Puryear 
Published: February 2023

AbstractAlthough profibrotic cytokines such as IL-17A and TGF-β1 have been implicated in interstitial lung disease (ILD) pathogenesis, interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as phosphorylation of STAT3, have not been defined. Here we show by chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells that regions within theSTAT3locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung. Genetic absence ofESR1or ovariectomy in mice significantly increased pSTAT3 and IL-17A expression in pulmonary CD4+ T cells, which was reduced after repletion of female hormones. Remarkably, there was no significant reduction in lung fibrosis under either condition, suggesting that factors outside of ovarian hormones also contribute. Assessment of lung fibrosis among menstruating females in different rearing environments revealed that environments favoring gut dysbiosis augment fibrosis. Furthermore, hormone repletion following ovariectomy further augmented lung fibrosis, suggesting pathologic interactions between gonadal hormones and gut microbiota on lung fibrosis severity. Analysis in female sarcoidosis patients revealed a significant reduction in pSTAT3 and IL-17A levels and a concomitant increase in TGF-β1 levels in CD4+ T cells, compared to male sarcoidosis patients. These studies reveal that estrogen is profibrotic in females and that gut dysbiosis in menstruating females augments lung fibrosis severity, supporting a critical interaction between gonadal hormones and gut flora in lung fibrosis pathogenesis.
Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis
Authors: Poxleitner Marilena , Hoffmann Sabrina H.L. , Berezhnoy Georgy , Ionescu Tudor , Gonzalez-Menendez Irene , Maier Florian C. , Seyfried Dominik , Ehrlichmann Walter , Quintanilla-Martinez Leticia , Schmid Andreas M. , Reischl Gerald , Trautwein Christoph , Maurer Andreas , Pichler Bernd J. , Herfert Kristina , Beziere Nicolas 
Published: February 2023

AbstractDiet-induced body weight gain is a growing health problem worldwide, leading to several serious systemic diseases such as diabetes. Because it is often accompanied by a low-grade metabolic inflammation that alters systemic function, dietary changes may also contribute to the progression of neurodegenerative diseases. Here we demonstrate disrupted glucose and fatty acid metabolism and a disrupted plasma metabolome in a mouse model of Alzheimer’s disease following a western diet using a multimodal imaging approach and NMR-based metabolomics. We did not detect glial-dependent neuroinflammation, however using flow cytometry we observed T cell recruitment in the brains of western diet-fed mice. Our study highlights the role of the brain-liver-fat-axis and the adaptive immune system in the disruption of brain homeostasis due to a Western diet.
Muscle Preflex Response to Perturbations in locomotion: In-vitro experiments and simulations with realistic boundary conditions
Authors: Araz Matthew , Weidner Sven , Izzi Fabio , Badri-Spröwitz Alexander , Siebert Tobias , Haeufle Daniel F. B. 
Published: February 2023

1AbstractNeuromuscular control loops feature substantial communication delays, but mammals run robustly even in the most adverse conditions. In-vivo experiments and computer simulation results suggest that muscles’ preflex—an immediate mechanical response to a perturbation—could be the critical contributor. Muscle preflexes act within a few milliseconds, an order of magnitude faster than neural reflexes. Their short-lasting activity makes mechanical preflexes hard to quantify in-vivo. Muscle models, on the other hand, require further improvement of their prediction accuracy during the non-standard conditions of perturbed locomotion. Additionally, muscles mechanically adapt by increased damping force. Our study aims to quantify the mechanical preflex work and test its mechanical force adaptation. We performed in-vitro experiments with biological muscle fibers under physiological boundary conditions, which we determined in computer simulations of perturbed hopping. Our findings show that muscles initially resist impacts with a stereotypical stiffness response—identified as short-range stiffness—regardless of the exact perturbation condition. We then observe a velocity adaptation to the force related to the amount of perturbation. The main contributor to the preflex work adaptation is not the force difference but the muscle fiber stretch difference. We find that both muscle stiffness and damping are activity-dependent properties. These results indicate that neural control could tune the preflex properties of muscles in expectation of ground conditions leading to previously inexplicable neuromuscular adaptation speeds.
Interictal epileptiform discharges affect memory in an Alzheimer’s Disease mouse model
Authors: Soula Marisol , Maslarova Anna , Harvey Ryan E , Valero Manuel , Brandner Sebastian , Hamer Hajo , Fernández-Ruiz Antonio , Buzsáki György 
Published: February 2023

AbstractInterictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological disease, such as Alzheimer’s Disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multi-layer hippocampal silicon probes. Both the local field potential features and firing patterns of pyramidal cells and interneurons were similar in mouse and human. We found that as IEDs emerged from the CA3-1 circuits, they recruited pyramidal cells and silenced interneurons, followed by post-IED suppression. IEDs suppressed the incidence and altered the properties of physiological sharp-wave ripples (SPW-Rs), altered their physiological properties, and interfered with the replay of place field sequences in a maze. In addition, IEDs in AD mice inversely correlated with daily memory performance. Together, our work implicates that IEDs may present a common and epilepsy-independent phenomenon in neurodegenerative diseases that perturbs hippocampal-cortical communication and interferes with memory.Significant StatementPrevalence of neurodegenerative diseases and the number of people with dementia is increasing steadily. Therefore, novel treatment strategies for learning and memory disorders are urgently necessary. IEDs, apart from being a surrogate for epileptic brain regions, have also been linked to cognitive decline. Here we report that IEDs in human epilepsy patients and AD mouse models have similar local field potential characteristics and associated firing patterns of pyramidal cells and interneurons. Mice with more IEDs displayed fewer hippocampal SPW-Rs, poorer replay of spatial trajectories, and decreased memory performance. IED suppression is an unexplored target to treat cognitive dysfunction in neurodegenerative diseases.
Vascular oxidative stress causes neutrophil arrest in brain capillaries, leading to decreased cerebral blood flow and contributing to memory impairment in a mouse model of Alzheimer’s disease
Authors: Ruiz-Uribe Nancy E. , Bracko Oliver , Swallow Madisen , Omurzakov Argen , Dash Sabyasachi , Uchida Hiroki , Xiang David , Haft-Javaherian Mohammad , Falkenhain Kaja , Lamont Michael E. , Ali Muhammad , Njiru Brendah N. , Chang Hsin-Yun , Tan Adrian Y , Xiang Jenny Z , Iadecola Costantino , Park Laibaik , Sanchez Teresa , Nishimura Nozomi , Schaffer Chris B. 
Published: February 2023

ABSTRACTINTRODUCTIONIn this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD.METHODSWe inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We usedin vivotwo-photon imaging to measure capillary stalling, penetrating arteriole flow, and vascular inflammation. We also characterized short-term memory function and gene expression changes in cerebral microvessels.RESULTSWe found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways.DISCUSSIONOxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target.
Lipid nanoparticle structure and delivery route during pregnancy dictates mRNA potency, immunogenicity, and health in the mother and offspring
Authors: Chaudhary Namit , Newby Alexandra N. , Arral Mariah L. , Yerneni Saigopalakrishna S. , LoPresti Samuel T. , Doerfler Rose , Strelkova Petersen Daria M. , Fox Bethany , Coon Tiffany , Malaney Angela , Sadovsky Yoel , Whitehead Kathryn A. 
Published: February 2023

AbstractTreating pregnancy-related disorders is exceptionally challenging because many small molecule drugs on the market may cause maternal and fetal toxicity. This potential danger has hindered the development and clinical evaluation of new drugs for several decades. Lipid nanoparticle (LNP)-based RNA therapies with high delivery efficacy, favorable immune response, and minimal transplacental transport can quell maternal-fetal toxicity concerns and propel the development of pregnancy-safe drugs. To this extent, we report potent LNP structures that robustly deliver mRNA to maternal organs and placenta. Using structure-function analysis, we show that LNP efficacy is influenced by the polyamine headgroup, and toxicity is governed by the acrylate tail. Our lead nanoparticle shows robust protein expression via multiple clinically relevant administration routes in pregnant mice. In the placenta, it transfects trophoblasts, endothelial cells, and immune cells. Further, by varying ionizable lipid structure, we demonstrate that LNP immunogenicity affects organ expression and pup health during pregnancy. Immunogenic LNPs show lower efficacy in lymphoid organs in an IL-1β dependent manner in pregnant mice. Further, pro-inflammatory immune responses provoke the infiltration of adaptive immune cells in the placenta and restrict pup growth after birth. Together, our results provide a mechanistic basis for designing safe and potent LNPs that can be administered during pregnancy.
Dual credit assignment processes underlie dopamine signals in a complex spatial environment
Authors: Krausz Timothy A. , Comrie Alison E. , Frank Loren M. , Daw Nathaniel D. , Berke Joshua D. 
Published: February 2023

AbstractDopamine in the nucleus accumbens helps motivate behavior based on expectations of future reward (“values”). These values need to be updated by experience: after receiving reward, the choices that led to reward should be assigned greater value. There are multiple theoretical proposals for how this credit assignment could be achieved, but the specific algorithms that generate updated dopamine signals remain uncertain. We monitored accumbens dopamine as freely behaving rats foraged for rewards in a complex, changing environment. We observed brief pulses of dopamine both when rats received reward (scaling with prediction error), and when they encountered novel path opportunities. Furthermore, dopamine ramped up as rats ran towards reward ports, in proportion to the value at each location. By examining the evolution of these dopamine place-value signals, we found evidence for two distinct update processes: progressive propagation along taken paths, as in temporal-difference learning, and inference of value throughout the maze, using internal models. Our results demonstrate that within rich, naturalistic environments dopamine conveys place values that are updated via multiple, complementary learning algorithms.
Development of a human glioblastoma model using humanized DRAG mice for immunotherapy
Authors: Srivastava Rashmi , Labani-Motlagh Alireza , Chen Apeng , Yang Fan , Ansari Danish , Patel Sahil , Ji Honglong , Trasti Scott , Dodda Meghana , Patel Yash , Zou Han , Hu Baoli , Yi Guohua 
Published: February 2023

AbstractGlioblastoma (GBM) is the most common and lethal primary brain tumor with high mortality rates and a short median survival rate of about 15 months despite intensive multimodal treatment of maximal surgical resection, radiotherapy, and chemotherapy. Although immunotherapies have been successful in the treatment of various cancers, disappointing results from clinical trials for GBM immunotherapy represent our incomplete understanding. The development of alternative humanized mouse models with fully functional human immune cells will potentially accelerate the progress of GBM immunotherapy. In this study, we developed a humanized DRAG (NOD.Rag1KO.IL2RγcKO) mouse model, in which the human hematopoietic stem cells (HSCs) were well-engrafted and subsequently differentiated into a full lineage of immune cells. Using this humanized DRAG mouse model, GBM patient-derived tumorsphere lines were successfully engrafted to form xenografted tumors, which can recapitulate the pathological features and the immune cell composition of human GBM. Importantly, the administration of anti-human PD-1 antibodies in these DRAG mice bearing a GBM patient-derived tumorsphere line resulted in decreasing the major tumor-infiltrating immunosuppressive cell populations, including CD4+PD-1+and CD8+PD-1+T cells, CD11b+CD14+HLA-DR+macrophages, CD11b+CD14+HLA-DR−CD15−and CD11b+CD14−CD15+myeloid-derived suppressor cells, indicating the humanized DRAG mouse model as a useful model to test the efficacy of immune checkpoint inhibitors in GBM immunotherapy. Together, these results suggest that humanized DRAG mouse models are a reliable preclinical platform for brain cancer immunotherapy and beyond.
Structural basis for lysophosphatidylserine recognition by GPR34
Authors: Izume Tamaki , Kawahara Ryo , Uwamizu Akiharu , Chen Luying , Yaginuma Shun , Omi Jumpei , Kawana Hiroki , Sano Fumiya K. , Tanaka Tatsuki , Kobayashi Kazuhiro , Okamoto Hiroyuki H. , Kise Yoshiaki , Ohwada Tomohiko , Aoki Junken , Shihoya Wataru , Nureki Osamu 
Published: February 2023

AbstractGPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron microscopy structures of human GPR34-Gicomplex bound with either the LysoPS analogue S3E-LysoPS, which contains an ethoxy group at thesn-1 position, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. In both structures, the ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster, and the aromatic fatty acid surrogate of M1 forms stable hydrophobic interactions with the cavity, thus acting as a superagonist. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34, suggesting its short signal duration. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.
Spatiotemporal cortical dynamics for rapid scene recognition as revealed by EEG decoding
Authors: Orima Taiki , Motoyoshi Isamu 
Published: February 2023

AbstractThe human visual system rapidly recognizes the categories and global properties of complex natural scenes. The present study investigated the spatiotemporal dynamics of neural signals involved in ultra-rapid scene recognition using electroencephalography (EEG) decoding. We recorded visual evoked potentials from 11 human observers for 232 natural scenes, each of which belonged to one of 13 natural scene categories (e.g., a bedroom or open country) and had three global properties (naturalness, openness, and roughness). We trained a deep convolutional classification model of the natural scene categories and global properties using EEGNet. Having confirmed that the model successfully classified natural scene categories and the three global properties, we applied Grad-CAM to the EEGNet model to visualize the EEG channels and time points that contributed to the classification. The analysis showed that EEG signals in the occipital lobes at short latencies (approximately 80∼ ms) contributed to the classifications other than roughness, whereas those in the frontal lobes at relatively long latencies (∼ 164 ms) contributed to the classification of naturalness and the individual scene category. These results suggest that different global properties are encoded in different cortical areas and with different timings, and that the encoding of scene categories shifts from the occipital to the frontal lobe over time.
Fractal model of thermal contact conductance of rough surfaces based on cone asperity
Authors: Sun Xianguang , Xing Wuce 
Published: February 2023

Purpose
The purpose of this paper is to propose a fractal model of thermal contact conductance (TCC) of rough surfaces based on cone asperity.

Design/methodology/approach
A detailed numerical study is conducted to examine the effects of contact load, fractal dimensional, fractal roughness and material properties on the TCC of rough surfaces.

Findings
The results indicate that when the fractal dimension D is less than 2.5, the TCC of rough surfaces increases nonlinearly with the increase of the contact load. However, when the fractal dimension D is greater than or equal to 2.5, the TCC of rough surfaces increases linearly with the increase of the contact load; the TCC of the rough surfaces increases with the increase of the fractal dimension D and the decrease of the fractal roughness G; the material parameters also have an influence on the TCC of the rough surfaces, and the extent of the effect on the TCC is related to the fractal dimension D.

Originality/value
A fractal model of TCC of rough surfaces based on cone asperity is established in this paper. Some new results and conclusions are obtained from this work, which provides important theoretical guidance for further study of TCC of rough surfaces.
Emerging technologies in the construction industry: challenges and strategies in Ghana
Authors: Kissi Ernest , Aigbavboa Clinton , Kuoribo Ewald 
Published: February 2023

PurposeThe momentous contribution of innovative technologies has made a significant impact in several sectors globally. However, the construction industry is undoubtedly lagging when it comes to technology usage. Thus, this study aims to explore the various emerging technologies in the construction industry while noticing stakeholders’ challenges and strategies in its use.Design/methodology/approachThe study used a pragmatism research philosophy together with a quantitative research strategy in determining emerging technologies in the construction industry while noticing stakeholder challenges and strategies. Data were obtained from a total of 80 construction stakeholders through a structured questionnaire survey. The analysis was done with descriptive statistics using mean score ranking and a one-samplet-test.FindingsEach emerging technology challenge was analysed and compared to see how pressing the challenges were as well as the aligned strategies. A key indication of this study is that the familiarity of the various emerging technologies was based on how many occasions one had an encounter with the technology.Practical implicationsThe discussion’s findings contribute to a better knowledge to construction stakeholders on the challenges and strategies for rising technology adoption and implementation competencies.Originality/valueThe study reckoned stakeholders’ challenges on the emerging technologies in the construction industry context and recommended strategies to balloon the adoption of these emerging technologies in a developing country setting.
Creating public value with municipal Wi-Fi networks: a bottom-up methodology
Authors: van den Velden Jenneke , Sadowski Bert M. 
Published: February 2023

Purpose
The purpose of this paper is evaluate the public value of municipal Wi-Fi networks by examining their costs and benefits. Increasing attention has been focused on the digital divide, i.e. inequalities in digital access, use and benefits, to a lesser extent on technologies providing opportunities to overcome these inequalities. Different theoretical traditions have approached the problem of the digital divide, this research represents a synthesis by combining a bottom-up approach to calculating the benefits of municipal Wi-Fi networks with an in-depth analysis of the digital divide in Europe.

Design/methodology/approach
After a systematic literature review, the paper uses a bottom-up methodology to evaluate the public value of a municipal Wi-Fi network by quantifying its potential benefits and costs. In addition, it includes different types of users based on the access opportunities available to them. It develops different scenarios for these users depending on the connection alternatives and the digital skills available across European countries.

Findings
By using data from the euro-28, the paper shows that, in general, the private value of a municipal Wi-Fi network is negative, the public value is positive. However, a greater public value is depending on the extent to which the benefits can be attributed to expectations about the arrival and usage of e-government services.

Research limitations/implications
Based on the quantitative analysis, the authors suggest that municipal Wi-Fi networks can provide the potential to bridge the digital divide. To generate public value, these networks have to be driven by a strong need for e-government services.

Practical implications
However, important factors in the adoption of these services are related to digital skills available in the particular region.

Social implications
In addition, public investment is required to stimulate the growth of broadband infrastructure in a complementary manner to enable public wireless networks.

Originality/value
The paper combines new insights into the cost calculations of municipal Wi-Fi networks with socioeconomic data on digital skills to examine different types of users.