scholarly journals Silver Ions as a Tool for Understanding Different Aspects of Copper Metabolism

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1364 ◽  
Author(s):  
Ludmila V. Puchkova ◽  
Massimo Broggini ◽  
Elena V. Polishchuk ◽  
Ekaterina Y. Ilyechova ◽  
Roman S. Polishchuk
Keyword(s):  
Active Sites ◽  
Large Scale ◽  
Copper Ions ◽  
Copper Metabolism ◽  
Silver Ions ◽  
The Body ◽  
Copper Binding ◽  
Safe Delivery ◽  
Protein Motifs ◽  
Wide Range

In humans, copper is an important micronutrient because it is a cofactor of ubiquitous and brain-specific cuproenzymes, as well as a secondary messenger. Failure of the mechanisms supporting copper balance leads to the development of neurodegenerative, oncological, and other severe disorders, whose treatment requires a detailed understanding of copper metabolism. In the body, bioavailable copper exists in two stable oxidation states, Cu(I) and Cu(II), both of which are highly toxic. The toxicity of copper ions is usually overcome by coordinating them with a wide range of ligands. These include the active cuproenzyme centers, copper-binding protein motifs to ensure the safe delivery of copper to its physiological location, and participants in the Cu(I) ↔ Cu(II) redox cycle, in which cellular copper is stored. The use of modern experimental approaches has allowed the overall picture of copper turnover in the cells and the organism to be clarified. However, many aspects of this process remain poorly understood. Some of them can be found out using abiogenic silver ions (Ag(I)), which are isoelectronic to Cu(I). This review covers the physicochemical principles of the ability of Ag(I) to substitute for copper ions in transport proteins and cuproenzyme active sites, the effectiveness of using Ag(I) to study copper routes in the cells and the body, and the limitations associated with Ag(I) remaining stable in only one oxidation state. The use of Ag(I) to restrict copper transport to tumors and the consequences of large-scale use of silver nanoparticles for human health are also discussed.

scholarly journals Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD. Results HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes. Conclusion HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

scholarly journals Development of a GFP Fluorescent Bacterial Biosensor for the Detection and Quantification of Silver and Copper Ions

2018 ◽  
Author(s):  
Adam R. Martinez ◽  
John R. Heil ◽  
Trevor C. Charles
Keyword(s):  
Environmental Monitoring ◽  
Copper Ions ◽  
Silver Ions ◽  
Silver Ion ◽  
Resistant Bacteria ◽  
Ion Release ◽  
Ionic Silver ◽  
Wide Range ◽  
Further Development ◽  
Detection And Quantification

AbstractIonic silver is known to be an effective antimicrobial agent widely used in the cleaning and medical industries, however, there are several concerns regarding the release of silver pollutants into the environment. Presented here are two engineered bacterial biosensors for the detection and quantification of silver. The biosensors contain a silver resistance operon and a GFP gene that is strictly regulated through silver activated regulatory regions that control expression of thesiloperons. The two biosensors are responsive to a wide range of silver ion concentrations, and a correlation between silver and GFP signal is seen at select concentration ranges. The biosensors were shown to detect silver ions released from silver nanoparticles, and have the potential to become a method for monitoring ion release rates of different nanoparticles. Interestingly, the close homology of the silver resistance and copper resistance genes allowed for the biosensor to also be responsive to copper ions, implying that copper ions activate silver resistance. Further development of this biosensor could lead to commercial applications for environmental monitoring.ImportanceIonic silver is known to have many harmful environmental effects. Silver pollutants have been found in various environmental settings such as natural waterways and tailings from mining operations, raising concern. In addition, persistent exposure to silver in medical and environmental settings has led to the development of silver resistant bacteria, many of which are also resistant to a wide range of antibiotics. Some of these have the potential to develop into human pathogens. It then becomes important to have standardized methods for detecting and monitoring silver concentrations in various environments so that appropriate measures can be taken to prevent further silver ion release. This research shows that bacterial biosensors engineered to detect and quantify silver ions can be developed as effective alternatives to traditional analytical techniques. Further development of such biosensors could result in a commercial system for short and long term environmental monitoring, which is important as products containing silver and other heavy metals become increasingly popular.

scholarly journals Sociality and Interaction Envelope Organize Visual Action Representations

2019 ◽  
Author(s):  
Leyla Tarhan ◽  
Talia Konkle
Keyword(s):  
Visual Cortex ◽  
Large Scale ◽  
Functional Neuroimaging ◽  
Action Observation ◽  
The Body ◽  
Whole Body ◽  
Action Perception ◽  
Social Content ◽  
Wide Range ◽  
The Brain

Humans observe a wide range of actions in their surroundings. How is the visual cortex organized to process this diverse input? Using functional neuroimaging, we measured brain responses while participants viewed short videos of everyday actions, then probed the structure in these responses using voxel-wise encoding modeling. Responses were well fit by feature spaces that capture the body parts involved in an action and the action’s targets (i.e. whether the action was directed at an object, another person, the actor, and space). Clustering analyses revealed five large-scale networks that summarized the voxel tuning: one related to social aspects of an action, and four related to the scale of the interaction envelope, ranging from fine-scale manipulations directed at objects, to large-scale whole-body movements directed at distant locations. We propose that these networks reveal the major representational joints in how actions are processed by visual regions of the brain.Significance StatementHow does the brain perceive other people’s actions? Prior work has established that much of the visual cortex is active when observing others’ actions. However, this activity reflects a wide range of processes, from identifying a movement’s direction to recognizing its social content. We investigated how these diverse processes are organized within the visual cortex. We found that five networks respond during action observation: one that is involved in processing actions’ social content, and four that are involved in processing agent-object interactions and the scale of the effect that these actions have on the world (its “interaction envelope”). Based on these findings, we propose that sociality and interaction envelope size are two of the major features that organize action perception in the visual cortex.

Medicine

Buddhism ◽  
2014 ◽  
Author(s):  
C. Pierce Salguero
Keyword(s):  
Health Policy ◽  
Physical Health ◽  
Large Scale ◽  
Medical Knowledge ◽  
Central Place ◽  
The Body ◽  
Medical Systems ◽  
Early 21St Century ◽  
Islamic Medicine ◽  
Wide Range

Knowledge about physical health and disease has held a central place within Buddhist thought, and healing has remained a persistent part of Buddhist practice since the earliest times. Though there is no universally agreed-upon term, Buddhist perspectives on health, disease, healers, patients, and therapies are typically spoken of by East Asian scholars and devotees as “Buddhist medicine” (Ch. foyi佛醫 or fojiao yixue佛教醫學, Jp. bukkyō igaku仏教医学), and this terminology is used here as a convenient shorthand for a complex topic. The earliest expressions of medical doctrine in Indian Buddhist texts are closely related to ideas found in Āyurveda and have suggestive similarities with other Eurasian medical systems (including Hippocratic, Galenic, and Islamic medicine) as well. Integrated into Buddhist philosophy, meditation, and ritual, these core doctrines and perspectives were influential in India and China, and they came to be spread as far as Iran, Mongolia, Japan, and Indonesia. Healer-monks and monastic medical institutions played a major role in this dissemination, as did the large-scale translation of texts concerning a wide range of Buddhist medical topics. In the early 21st century, many of the ideas and practices imported from India continue to lie at the foundation of traditions of medicine in Tibet, Nepal, Thailand, Sri Lanka, and other parts of Buddhist Asia. At the same time that Buddhist medicine can be understood as a transnational or cross-cultural phenomenon, however, it has always been reinterpreted locally through the lenses of the many cultures that have adopted it. Historians working on Buddhist medicine have thus focused both on the transmission of medical knowledge to new cultures and societies, as well as on the unique ideological and rhetorical uses of Buddhism by medical practitioners in many specific historical and modern settings. Social scientists have studied the degree to which Buddhist values continue to inform health policy in Asian countries and the complexities of the relationship between Buddhism and biomedicine. This article includes a selective range of scholarship on the history and modern relationship between Buddhism and medicine, with a focus on the former. Scientific studies on the health benefits of meditation, health policy advocacy, and works of a nonscholarly nature geared toward practitioners and devotees are excluded. Also omitted are topics tangential to matters of physical health, such as mental health, conceptions of the body, bioethics, the science of meditation, and so forth. Many publications of all of the above types are available and are covered in other Oxford Bibliographies in Buddhism articles, such as “Buddhism in Psychology and Psychotherapy,” “Buddhism and the Body,” and “Meditation.”

Fatigue-driven boulder exfoliation as a driving mechanism for Bennu’s activity

2020 ◽  
Author(s):  
Jamie Molaro ◽  
Carl Hergenrother ◽  
Steve Chesley ◽  
Romy Hanna ◽  
Chris Haberle ◽  
...  
Keyword(s):  
Thermal Fatigue ◽  
Large Scale ◽  
Thermal Strain ◽  
Rotation Period ◽  
The Body ◽  
Thin Layers ◽  
Stress Fields ◽  
Driving Mechanism ◽  
Rock Composition ◽  
Wide Range

<p><strong>Abstract:</strong> Thermally driven fracture processes, such as thermal fatigue, have been hypothesized to drive rock breakdown and regolith production on asteroid surfaces [e.g., 1-7]. Thermal cycling induces mechanical stresses in rocks that drive the propagation of microcracks, which may grow into larger-scale features. This can drive the development of morphological signatures such as surface fracturing and disaggregation, and through-going fractures that split boulders apart. The nature and rate of boulder breakdown is controlled by rock composition, as well as the rotation period and solar distance of the body, suggesting its signature varies widely across the diverse asteroid population. Understanding how the process operates is critical to characterizing their surface properties and evolution.</p><p>Images from the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS-REx) spacecraft of the surface of Bennu provide the opportunity to search for in situ evidence of thermal breakdown over a wide range of scales. Recent works by the authors [7-9] show observations of boulder morphologies consistent with terrestrial observations [e.g., 10] and models of fatigue-driven boulder exfoliation [e.g., 11], i.e., the flaking of thin layers or shells of material from boulder surfaces. Relating these observations to thermally induced stress fields in phyllosilicate boulders reveals that such features develop via the propagation of surface-parallel fractures during periods of day when boulder surfaces are heating. The magnitude of these stress fields ranges from ~0.3 to 3 MPa for boulders up to 6 m in diameter, which is comparable to the tensile strengths of terrestrial phyllosilicate rocks (e.g., serpentinite) and sufficient to drive subcritical crack growth (thermal fatigue). The thickness of resulting exfoliation layers predicted by the model ranges from ~1 mm to 10 cm, which is consistent with terrestrial observations of exfoliation cracks [10] and with the thicknesses of exfoliation layers observed on Bennu’s boulders [9].</p><p>Further, we explore how boulder exfoliation may lead to the ejection of particles observed at Bennu’s surface [9] in an analogous manner to mobilization of rock fragments during large-scale, terrestrial dome exfoliation events [12]. We have observed particle ejection events from Bennu’s surface repeatedly since first entering orbit in January 2019. Observed particles range in size from <1 to 10 cm [7], consistent with our predictions for exfoliation. We quantified the available thermal strain energy in boulders beyond what is needed to propagate cracks and converted it to kinetic energy to constrain the speed of ejected particles. We find particles may be ejected with speeds up to ~2 m/s for boulders smaller than or equal to 6 m in diameter, which is comparable to the maximum observed particle speed of 3.3 m/s [7]. These results suggest that fatigue-driven exfoliation is a viable mechanism for producing or contributing to the activity observed at Bennu.</p><p><strong>Acknowledgements:</strong> This material is based upon work supported by NASA under Contract NNM10AA11C issued through the New Frontiers Program, and under Contract NNH17ZDA001N-ORPSP through the Participating Scientist Program. We are grateful to the entire OSIRIS-REx Team for their hard work in making the encounter with Bennu possible.</p><p><strong>References:</strong> [1] Molaro, J.L., et al., 2017. Icarus 294, 247-261. [2] El-Mir, C., et al., 2019. Icarus, 333, 356-370. [3] Hazeli, K., et al., 2018. Icarus, 304, 172-182. [4] Jewitt and Li, 2010. The Astronomical J., 140(5), p.1519. [5] Delbo, M. et al., 2014. Nature 508, 233–236. [6] Graves, K. J., et al., 2019. Icarus, 10.1016/j.icarus.2019.01.003. [7] Lauretta, D.S., Hergenrother, C.W., et al., 2019. Science, 366(6470). [8] Molaro, J.L., et al., 2020. Nat. Commun., 11(1), 1-11. [9] Molaro, J.L., et al., in review with JGR: Planets. [10] Martel, S.J., 2017. J. Structural Geol., 94, 68-86. [11] Holzhausen, G. R. (1989), Eng. Geol., 27(1-4), 225–278, 10.1016/0013-7952(89)90035-5. [12] Collins, B.D., et al., 2018. Nat. Commun., 9(1), 1-12.</p>

scholarly journals DICOM Imaging Router: An Open Deep Learning Framework for Classification of Body Parts from DICOM X-ray Scans

2021 ◽  
Author(s):  
Hieu H. Pham ◽  
Dung V. Do ◽  
Ha Q. Nguyen
Keyword(s):  
Deep Learning ◽  
Large Scale ◽  
Imaging Modality ◽  
The Body ◽  
Superior Performance ◽  
Body Parts ◽  
Deep Convolutional Neural Networks ◽  
X Ray ◽  
Wide Range ◽  
Dicom Imaging

AbstractX-ray imaging in Digital Imaging and Communications in Medicine (DICOM) format is the most commonly used imaging modality in clinical practice, resulting in vast, non-normalized databases. This leads to an obstacle in deploying artificial intelligence (AI) solutions for analyzing medical images, which often requires identifying the right body part before feeding the image into a specified AI model. This challenge raises the need for an automated and efficient approach to classifying body parts from X-ray scans. Unfortunately, to the best of our knowledge, there is no open tool or framework for this task to date. To fill this lack, we introduce a DICOM Imaging Router that deploys deep convolutional neural networks (CNNs) for categorizing unknown DICOM X-ray images into five anatomical groups: abdominal, adult chest, pediatric chest, spine, and others. To this end, a large-scale X-ray dataset consisting of 16,093 images has been collected and manually classified. We then trained a set of state-of-the-art deep CNNs using a training set of 11,263 images. These networks were then evaluated on an independent test set of 2,419 images and showed superior performance in classifying the body parts. Specifically, our best performing model (i.e., MobileNet-V1) achieved a recall of 0.982 (95% CI, 0.977– 0.988), a precision of 0.985 (95% CI, 0.975–0.989) and a F1-score of 0.981 (95% CI, 0.976–0.987), whilst requiring less computation for inference (0.0295 second per image). Our external validity on 1,000 X-ray images shows the robustness of the proposed approach across hospitals. These remarkable performances indicate that deep CNNs can accurately and effectively differentiate human body parts from X-ray scans, thereby providing potential benefits for a wide range of applications in clinical settings. The dataset, codes, and trained deep learning models from this study will be made publicly available on our project website at https://vindr.ai/datasets/bodypartxr.

scholarly journals Appearance of the imprinting effect on the specific pattern of intracellular distribution of copper ions in the liver after exposure to high concentrations of copper sulfate

2010 ◽  
Vol 56 (2) ◽  
pp. 195-208 ◽  
Author(s):  
A.I. Bozhkov ◽  
V.I. Sidorov ◽  
V.L. Dlubovskaya ◽  
M.Ya. Shevtsova ◽  
Yu.N. Surov
Keyword(s):  
Rat Liver ◽  
Copper Sulfate ◽  
Liver Cell ◽  
Copper Ions ◽  
Specific Pattern ◽  
Intracellular Distribution ◽  
The Body ◽  
Copper Binding ◽  
Copper Binding Protein ◽  
High Concentrations

Fractions of copper-binding protein (CBP) specifically bound copper ions were extracted from the rat liver cell cytosole. These fractions of 10-14 kDa proteins are involved in specific pattern of intracellular distribution of copper ions. The imprinting effect of specific pattern of copper ions intracellular distribution has been found. The effect was detected 30 days after sequented injections of copper sulfate into the body. It was shown, that after primary injection of copper the ability of CBP to bind copper ions could increase tenfold, regardless of schemes of copper sulfate injection.

scholarly journals Hyaluronate – Black Phosphorus Conjugates as a Copper Chelating Agent for Wilson Disease Treatment

2021 ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background: Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods: We developed hyaluronate - black phosphorus (HA-BP) conjugates for capturing copper ions accumulated in the liver for the treatment of WD.Results: HA-BP conjugates showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-BP conjugates to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-BP conjugates.Conclusion: HA-BP conjugates would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

scholarly journals Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

2018 ◽  
Author(s):  
Gábor Erdős ◽  
Bálint Mészáros ◽  
Dana Reichmann ◽  
Zsuzsanna Dosztányi
Keyword(s):  
Disulfide Bonds ◽  
Active Sites ◽  
Large Scale ◽  
Redox Regulation ◽  
Underlying Mechanism ◽  
Zinc Ion ◽  
Disordered Proteins ◽  
Functional Behavior ◽  
Wide Range ◽  
High Level

AbstractRecently developed quantitative redox proteomic studies enable the direct identification of redox-sensing cysteine residues that regulate the functional behavior of target proteins in response to changing levels of reactive oxygen species (ROS). At the molecular level, redox regulation can directly modify the active sites of enzymes, although a growing number of examples indicate the importance of an additional underlying mechanism that involves conditionally disordered proteins. These proteins alter their functional behavior by undergoing a disorder-to-order transition in response to changing redox conditions. However, the extent to which this mechanism is used in various proteomes is currently unknown. Here, we use a recently developed sequence-based prediction tool incorporated into the IUPred2A web server to estimate redox-sensitive conditionally disordered regions on a large scale. We show that redox-sensitive conditional disorder is fairly widespread in various proteomes and that its presence strongly correlates with the expansion of specific domains in multicellular organisms that largely rely on extra stability provided by disulfide bonds or zinc ion binding. The analyses of yeast redox proteomes and human disease data further underlie the significance of this phenomenon in the regulation of a wide range of biological processes, as well as its biomedical importance.

scholarly journals Ankyrin repeats in context with human population variation

2021 ◽  
Author(s):  
Javier S Utges ◽  
Maxim I Tsenkov ◽  
Noah JM Dietrich ◽  
Stuart A MacGowan ◽  
Geoffrey J Barton
Keyword(s):  
Protein Interactions ◽  
Human Population ◽  
Large Scale ◽  
Population Variation ◽  
Evolutionary Constraint ◽  
Ankyrin Repeats ◽  
Protein Protein Interactions ◽  
Protein Motifs ◽  
Missense Variants ◽  
Wide Range

Ankyrin protein repeats bind to a wide range of substrates and are one of the most common protein motifs in nature. Here, we collate a high-quality alignment of 7,407 ankyrin repeats and examine for the first time, the distribution of human population variants from large-scale sequencing of healthy individuals across this family. Population variants are not randomly distributed across the genome but are constrained by gene essentiality and function. Accordingly, we interpret the population variants in context with evolutionary constraint and structural features including secondary structure, accessibility and protein-protein interactions across 383 three-dimensional structures of ankyrin repeats. We find five positions that are highly conserved across homologs and also depleted in missense variants within the human population. These positions are significantly enriched in intra-domain contacts and so likely to be key for repeat packing. In contrast, a group of evolutionarily divergent positions are found to be depleted in missense variants in human but significantly enriched in protein-protein interactions. Our analysis also suggests the domain has three, not two surfaces, each with different patterns of enrichment in protein-substrate interactions and missense variants. Our findings will be of interest to those studying or engineering ankyrin-repeat containing proteins as well as those interpreting the significance of disease variants.

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