Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-Cell Hemoprotein Diet Changes Adipose Tissue Distributions and Re-Shapes Gut Microbiota in High-Fat Diet-Induced Obese Mice

We have previously observed that feeding with single-cell hemoprotein (heme-SCP) in dogs (1 g/day for 6 days) and broiler chickens (1 ppm for 32 days) increased the proportion of lactic acid bacteria in the gut while reducing their body weights by approximately 1~2%. To define the roles of heme-SCP in modulating body weight and gut microbiota, obese C57BL/6N mice were administered varied heme-SCP concentrations (0, 0.05, and 0.5% heme-SCP in high fat diet) for 28 days. The heme-SCP diet seemed to restrain weight gain till day 14, but the mice gained weight again later, showing no significant differences in weight. However, the heme-SCP-fed mice had stiffer and oilier bodies compared with those of the control mice, which had flabby bodies and dull coats. When mice were dissected at day 10, the obese mice fed with heme-SCP exhibited a reduction in subcutaneous fat with an increase in muscle mass. The effect of heme-SCP on the obesity-associated dyslipidemia tended to be corroborated by the blood parameters (triglyceride, total cholesterol, and C-reactive protein) at day 10, though the correlation was not clear at day 28. Notably, the heme-SCP diet altered gut microbiota, leading to the proliferation of known anti-obesity biomarkers such as Akkermansia, Alistipes, Oscillibacter, Ruminococcus, Roseburia, and Faecalibacterium. This study suggests the potential of heme-SCP as an anti-obesity supplement, which modulates serum biochemistry and gut microbiota in high-fat diet-induced obese mice.
Aging spinal cord microglia become phenotypically heterogeneous and preferentially target motor neurons and their synapses

Microglia have been found to acquire unique region‐dependent deleterious features with age and diseases that contribute to neuronal dysfunction and degeneration in the brain. However, it remains unknown whether microglia exhibit similar phenotypic heterogeneity in the spinal cord. Here, we performed a regional analysis of spinal cord microglia in 3‐, 16‐, 23‐, and 30‐month‐old mice. Using light and electron microscopy, we discovered that spinal cord microglia acquire an increasingly activated phenotype during the course of aging regardless of regional location. However, aging causes microglia in the ventral but not dorsal horn to lose their spatial organization. Aged ventral horn microglia also aggregate around the somata of motor neurons and increase their contacts with motor synapses, which have been shown to be lost with age. These findings suggest that microglia may affect the ability of motor neurons to receive and relay motor commands during aging. To generate additional insights about aging spinal cord microglia, we performed RNA‐sequencing on FACS‐isolated microglia from 3‐, 18‐, 22‐, and 29‐month‐old mice. We found that spinal cord microglia acquire a similar transcriptional identity as those in the brain during aging that includes altered expression of genes with roles in microglia‐neuron interactions and inflammation. By 29 months of age, spinal cord microglia exhibit additional and unique transcriptional changes known and predicted to cause senescence and to alter lysosomal and ribosomal regulation. Altogether, this work provides the foundation to target microglia to ameliorate aged‐related changes in the spinal cord, and particularly on the motor circuit.
Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study

Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity leads to an enhanced host response to a secondary infection. β-Glucans are structural components of plants, algae, fungi, and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucan curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1β release. WGP dispersible-trained macrophages were stratified into “non-responders” and “responders,” according to their ability to control M. tuberculosis, with “responders” producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and “responders” to WGP training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain β-glucans show promise as immune-training agents.
Influenza A(H5N1) Virus Infections in 2 Free-Ranging Black Bears (Ursus americanus), Quebec, Canada

Wholly Eurasian highly pathogemic avian influenza H5N1 clade 2.3. 4.4b virus was isolated from 2 free-ranging black bears with meningoencephalitis in Quebec, Canada. We found that isolates from both animals had the D701N mutation in the polymerase basic 2 gene, previously known to promote adaptation of H5N1 viruses to mammal hosts.
Stimulator of interferon genes promotes diabetic sarcopenia by targeting peroxisome proliferator activated receptors γ degradation and inhibiting fatty acid oxidation

Declined skeletal muscle mass and function are inevitable consequences of long‐term diabetes and bring about many adverse events. Muscle fibre atrophy and interstitial fibrosis are major pathological manifestations of diabetic sarcopenia. Stimulator of interferon genes (STING) participates in various metabolic diseases. We aimed to explore whether and how STING regulates the above pathological manifestations of diabetic sarcopenia.
Design, synthesis, conformational analysis, and biological activity of Cα1-to-Cα6 1,4- and 4,1-disubstituted 1H-[1,2,3]triazol-1-yl-bridged oxytocin analogues

Abstract Oxytocin (OT) is a neurohypophyseal peptide hormone containing a disulphide-bridged pseudocyclic conformation. The biomedical use of OT peptides is limited amongst others by disadvantageous pharmacokinetic parameters. To increase the stability of OT by replacing the disulphide bridge with the stable and more rigid [1,2,3]triazol-1-yl moiety, we employed the Cu2+-catalysed side chain-to-side chain azide-alkyne 1,3-cycloaddition. Here we report the design, synthesis, conformational analysis, and in vitro pharmacological activity of a homologous series of Cα1-to-Cα6 side chain-to-side chain [1,2,3]triazol-1-yl-containing OT analogues differing in the length of the bridge, location, and orientation of the linking moiety. Exploiting this macrocyclisation approach, it was possible to generate a systematic series of compounds providing interesting insight into the structure-conformation-function relationship of OT. Most analogues were able to adopt similar conformation to endogenous OT in water, namely, a type I β-turn. This approach may in the future generate stabilised pharmacological peptide tools to advance understanding of OT physiology. Graphical Abstract
Equivalent Neutral Wind

The definition of equivalent neutral wind and the rationale for using it as the geophysical product of a spaceborne scatterometer are reviewed. The differences between equivalent neutral wind and actual wind, which are caused by atmospheric density stratification, are demonstrated with measurements at selected locations. A method of computing this parameter from ship and buoy measurements is described and some common fallacies in accounting for the effects of atmospheric stratification on wind shear are discussed. The computer code for the model to derive equivalent neutral wind is provided.
Prevalence of Radiographic Alveolar Bone Loss as a Function of Age in the Periodontics Clinic Population at the College of Dentistry, King Saud University, Riyadh, Saudi Arabia.

PURPOSE The purpose of the present observational study was to assess the prevalence of radiographic alveolar bone loss (ABL) as a function of age at the Periodontics Clinics at the College of Dentistry, King Saud University, Riyadh, Saudi Arabia. MATERIALS AND METHODS Medical and dental healthcare records of individuals visiting the Periodontics Clinics at College of Dentistry, King Saud University, Riyadh Saudi Arabia were assessed. The following information was retrieved: age, gender, educational status, and systemic diseases (diabetes mellitus [DM], hypertension, osteoporosis and obesity). Digital full-mouth radiographs were retrieved from patients' dental records, and marginal bone loss (MBL) was assessed on the mesial and distal surfaces of all teeth. Logistic regression analyses (LRA) were done to assess the correlation between ABL and gender, age, educational status and duration since diagnosis of the aforementioned systemic conditions. p < 0.05 was considered statistically significant. RESULTS In total, medical and periodontal healthcare records of 495 individuals were retrieved and assessed. All individuals were citizens of the KSA. Among these, 107 were healthy controls and 98, 95, 96 and 99 individuals had a medical diagnosis of type-2 DM, hypertension, obesity and osteoporosis, respectively. There was no statistically significant difference in the mean age and gender of all medically compromised participants. The prevalence of mild, moderate, and severe periodontitis in the total patient population was 51.4%, 37.5% and 36.5%, respectively. Among all healthy controls, the prevalence of mild, moderate, and severe periodontitis was 16.3%, 25.5% and 33.4%, respectively. There was no difference in the prevalence of mild, moderate, and severe periodontitis in relation to advancing age in the entire patient population. CONCLUSION Advancing age did not seem to affect ABL in the present patient population. Patient education, oral hygiene maintenance and SES seem to be more predictable indicators of ABL than increasing age.
Rhéologie, localisation de la déformation et histoire des contraintes dans les calcaires du site de Bure

Un Laboratoire de Recherche Souterrain (URL) a ete construit en 2000 par l’Agence Nationale pour la Gestion des Dechets Radioactifs (Andra) dans le but d’etudier la faisabilite d’un site de stockage de dechets radioactifs dans une formation d’argile a Bure dans la Meuse. L’horizon choisi pour le laboratoire est une couche de 135 m d’epaisseur de roches argileuses du Callovo-Oxfordien (COX) qui s’etend de 420 a 555 m sous le Laboratoire du site de Bure. La couche d’argilites est entouree de bancs calcaires de l’Oxfordien et du Dogger (respectivement, 161,2 a 164,7 Ma et 164,7 a 175,6 Ma). De nombreux stylolites ont ete trouves dans ces horizons calcaires. Le but de ce travail etait d’etudier la rheologie des horizons contenant ces stylolites et d’utiliser ces structures comme marqueurs de contraintes dans la zone proche de l’URL. Pour ce travail, un grand nombre d’echantillons avec et sans stylolites ont ete preleves dans de nombreuses carottes provenant de plusieurs forages dans les formations de l’Oxfordien et du Dogger. Les mesures petrophysiques et les etudes de microstructure mises en œuvre sur ces calcaires revelent la structure microporeuse de toutes ces roches, de porosites comprises entre 4 et 18 %. La presence des stylolites s’accompagne d’une augmentation localisee de la porosite et de variations sensibles de certaines proprietes physiques ainsi que de la resistance mecanique des calcaires. Un modele reliant une longueur caracteristique associee a la morphologie d’un stylolite et la contrainte associee au developpement de cette structure est presente. Pour utiliser ce modele, nous avons developpe une methode pour analyser la morphologie de stylolites a partir du calcul du spectre de puissance de Fourier en prenant en compte toutes les difficultes liees a la geometrie de carottes provenant de forages. Cette methode est appliquee pour des stylolites echantillonnes a des profondeurs differentes, de 158 m a 800 m dans les formations calcaires de l’Oxfordien et du Dogger. Nous avons analyse des profils 1D extraits des contours des carottes. En accord avec les predictions theoriques, nous avons observe sur les spectres resultants des analyses, deux regimes differents pour les petites et grandes echelles separes par une longueur de coupure. Nous avons ensuite determine les paleocontraintes associees aux longueurs de coupures trouvees et aux modules elastiques des roches. En considerant l’evolution geologique des formations du site de Bure, nous discutons pour finir les variations avec la profondeur des paleocontraintes estimees pour les stylolites des formations de l’Oxfordien et du Dogger.
Enhancing Cyber Security Education and Training through Gamification

This PhD thesis revolutionizes cyber security education by harnessing the power of gamification. The research develops standardized methodologies and algorithms to evaluate trainees’ performance across platforms, creating a unified scoring system reflecting educational progress. Diverse gamification techniques are implemented to attract and engage trainees, promoting active participation and continuous improvement. Existing gamification methodologies are analyzed and tailored to specific user profiles, enhancing motivation and learning outcomes. Moreover, the research explores the potential of an AI-assisted co-pilot system that generates personalized exercises based on trainees’ skills, guiding them towards areas requiring improvement. The anticipated outcomes include a standardized evaluation system, enriched learning experiences, personalized training approaches, and an AI-driven co-pilot system. This work advances cybersecurity education, fostering a more effective and engaging learning environment. The motivation for this research arises from the need to enhance learner engagement and improve cyber security education.
Teaching Assembly Tasks to Robots Using a 3D Simulation Environment

Today, many factories use robots for intensive and repetitive work. Programming these robots is typically costly and time-consuming, and requires specialized expertise, hardware or non-expert employees interacting with expensive robots. In this paper, a new approach for teaching assembly tasks to robots is proposed. The user demonstrates the assembly task using a web browser in 3D and then simulates the robotic execution to promptly assess the outcome of the teaching process. A within-subjects user testing study compared the proposed simulation-based approach against a state-of-the-art computer vision-based approach. Participants were asked to teach a real-world LCD TV assembly task to a robot using both approaches. Results showed that users of the proposed simulation-based system had significantly lower time on task values and were significantly more likely to prefer it compared to the computer vision-based system. No significant difference was observed in task success rates and SUS scores.
The Future of Cognitive Personal Informatics

While Human-Computer Interaction (HCI) has contributed to demonstrating that physiological measures can be used to detect cognitive changes, engineering and machine learning will bring these to application in consumer wearable technology. For HCI, many open questions remain, such as: What happens when this becomes a cognitive form of personal informatics? What goals do we have for our daily cognitive activity? How should such a complex concept be conveyed to users to be useful in their everyday life? How can we mitigate potential ethical concerns? These issues are different from physiologically controlled interactions, such as BCIs, to a time when we have new data about ourselves. This workshop will be the first to directly address the future of Cognitive Personal Informatics (CPI), by bringing together design, BCI and physiological data, ethics, and personal informatics researchers to discuss and set the research agenda in this inevitable future before it arrives.
Understanding the AI-intervened User Interfaces of Online Health Consultation Platforms

This paper aims to investigate patient perceptions (i.e. social presence and trust) of online health consultation (OHC) interfaces with a focus on artificial intelligence (AI) intervention. It describes two studies, which are part of a larger body of research that aims to explore how AI interventions and their interfaces should be designed so that AI can better support the mobile health experience. Study 1 (n=10) was an interview study, which yielded four categories of design features of OHC interfaces. Three categories have been, or would be, strongly intervened by AI and were viewed to have influenced on user perceptions to different extents. Study 2 (n=18) focused on exploring one AI-intervened feature and found that the interface design of AI interventions influenced user perceptions. Our contributions to HCI include empirical insights into how interfaces of AI-intervened OHCs could influence the perceptions of their users, with design implications.
Functional networks of inhibitory neurons orchestrate synchrony in the hippocampus

Inhibitory interneurons are a critical component of cortical circuits. Beyond providing inhibition, they have been proposed to coordinate the firing of excitatory neurons within cell assemblies. While many studies have dissected the function of specific interneuron subtypes, the relationship between interneurons and pyramidal cell synchrony in vivo remains unclear. We use an all-optical approach to simultaneously record hippocampal interneurons and pyramidal cells, and test the network influence of single interneurons. We show that CA1 interneurons form a functionally interconnected network that promotes synchrony through disinhibition during awake immobility without altering endogenous cell assemblies. A network model indicates that cell assemblies and dense but unspecific connectivity between interneurons are necessary ingredients to explain our experimental results. Thus, interneurons may not only operate via division of labor, but also through concerted activity. Our data challenge the idea of a purely decorrelating or segregating function of inhibition.
ESR1 fusion proteins invoke breast cancer subtype-dependent enrichment of ligand independent pro-oncogenic signatures and phenotypes

Breast cancer is a leading cause of female mortality and despite advancements in diagnostics and personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. Fortunately, identification of mechanisms of therapeutic resistance have rapidly transformed our understanding of cancer evasion and is enabling targeted treatment regimens. When the druggable estrogen receptor (ER, ESR1), expressed in two-thirds of all breast cancer, is exposed to endocrine therapy, there is risk of somatic mutation development in approximately 30% of cases and subsequent treatment resistance. A more recently discovered mechanism of ER mediated endocrine resistance is the expression of ER fusion proteins. ER fusions, which retain the protein’s DNA binding domain, harbor ESR1 exons 1-6 fused to an in-frame gene partner resulting in loss of the 3’ ER ligand binding domain (LBD). In this report we demonstrate that in no-special type (NST) and invasive lobular carcinoma (ILC) cell line models, ER fusion proteins exhibit robust hyperactivation of canonical ER signaling pathways independent of the ligand estradiol or anti-endocrine therapies such as Fulvestrant and Tamoxifen. We employ cell line models stably overexpressing ER fusion proteins with concurrent endogenous ER knockdown to minimize the influence of endogenous wildtype ER. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably the MYC pathway. The heterogeneous 3’ fusion partners, particularly transcription factors SOX9 and YAP1, evoked varying degrees of transcriptomic and cistromic activity that translated into unique phenotypic readouts. Herein we report that cell line activity is subtype-, fusion-, and assay-specific suggesting that the loss of the LBD, the 3’ fusion partner, and the cellular landscape all influence fusion activity. Therefore, it will be critical to generate additional data on frequency of the ER fusions, in the context of the clinicopathological features of the tumor. Significance ER fusion proteins exhibit diverse mechanisms of endocrine resistance in breast cancer cell lines representing the no special type (NST) and invasive lobular cancer (ILC) subtypes. Our emphasize upon both the shared and unique cellular adaptations imparted by ER fusions offers the foundation for further translational research and clinical decision making.
Role of C2-domain protein CAR1 in the plasma membrane ABA signaling response

Plasma membrane (PM)-associated abscisic acid (ABA) signal transduction is an important component of ABA signaling. The C2-domain ABA-related (CAR) proteins have been reported to play a crucial role in recruiting ABA receptor PYR1/PYL/RCAR (PYLs) to the PM. However, the molecular details of the involvement of CAR proteins in membrane-delimited ABA signal transduction remain unclear. Here, the GUS-tagged materials for all Arabidopsis CAR members were used to comprehensively visualize the extensive expression patterns of the CAR family genes. Based on the specificity of CAR1’s response to ABA, we determined to use it as a target to study the function of CAR proteins in PM-associated ABA signaling. Single-particle tracking showed that ABA affected the spatiotemporal dynamics of CAR1. The presence of ABA prolonged the dwell time of CAR1 on the membrane and showed faster lateral mobility. Surprisingly, we verified that CAR1 could directly recruit Hypersensitive to ABA1 (HAB1) and SNF1-related protein kinase 2.2 (SnRK2.2) to the PM at both the bulk and single-molecule levels. Furthermore, PM localization of CAR1 was demonstrated to be related to membrane microdomains. Collectively, our study revealed that CARs recruited the three main components of ABA signaling to the PM to respond positively to ABA. This study deepens our understanding of ABA signal transduction.
ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection

A large body of research accumulated over the past three years dedicated to our understanding and fighting COVID-19. Blocking the interaction between SARS-CoV-2 Spike and ACE2 receptor has been considered an effective strategy as anti-SARS-CoV-2 therapeutics. In this study, we developed ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. These ACE2-VLPs exhibited high neutralization capacity even when applied at low doses, and displayed superior efficacy compared to extracellular vesicles carrying ACE2, in the in vitro pseudoviral assays. ACE2-VLPs were stable under different environmental temperatures, and they were effective in blocking all tested variants of concern in vitro. Finally, ACE2-VLPs displayed marked neutralization capacity against Omicron BA.1 in the Vero E6 cells. Based on their superior efficacy compared to extracellular vesicles, and their demonstrated success against live virus, ACE2-VLPs can be considered as vital candidates for treating SARS-CoV-2. This novel therapeutic approach of VLP coating with receptor particles can serve as proof-of-concept for designing effective neutralization strategies for other viral diseases in the future. Graphical Abstract In our study, we demonstrate the prevention of SARS-CoV-2 infection through the use of Ace2-coated VLPs.