8,336 results
Search Results
2. Retraction recommended for enzyme-chip paper.
- Author
-
Abbott A
- Subjects
- Authorship, Enzymes metabolism, Peer Review, Research standards, Reproducibility of Results, Substrate Specificity, Cells enzymology, Enzymes analysis, Protein Array Analysis methods, Retraction of Publication as Topic
- Published
- 2010
- Full Text
- View/download PDF
3. Multiscale topology classifies cells in subcellular spatial transcriptomics.
- Author
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Benjamin K, Bhandari A, Kepple JD, Qi R, Shang Z, Xing Y, An Y, Zhang N, Hou Y, Crockford TL, McCallion O, Issa F, Hester J, Tillmann U, Harrington HA, and Bull KR
- Subjects
- Animals, Female, Humans, Mice, Disease Models, Animal, Fluorescent Antibody Technique, Lupus Nephritis genetics, Lupus Nephritis immunology, Lupus Nephritis metabolism, Lupus Nephritis pathology, Reproducibility of Results, Cells classification, Cells metabolism, Gene Expression Profiling methods, Kidney cytology, Kidney immunology, Kidney metabolism, Kidney pathology, Transcriptome, Intracellular Space genetics, Intracellular Space metabolism
- Abstract
Spatial transcriptomics measures in situ gene expression at millions of locations within a tissue
1 , hitherto with some trade-off between transcriptome depth, spatial resolution and sample size2 . Although integration of image-based segmentation has enabled impactful work in this context, it is limited by imaging quality and tissue heterogeneity. By contrast, recent array-based technologies offer the ability to measure the entire transcriptome at subcellular resolution across large samples3-6 . Presently, there exist no approaches for cell type identification that directly leverage this information to annotate individual cells. Here we propose a multiscale approach to automatically classify cell types at this subcellular level, using both transcriptomic information and spatial context. We showcase this on both targeted and whole-transcriptome spatial platforms, improving cell classification and morphology for human kidney tissue and pinpointing individual sparsely distributed renal mouse immune cells without reliance on image data. By integrating these predictions into a topological pipeline based on multiparameter persistent homology7-9 , we identify cell spatial relationships characteristic of a mouse model of lupus nephritis, which we validate experimentally by immunofluorescence. The proposed framework readily generalizes to new platforms, providing a comprehensive pipeline bridging different levels of biological organization from genes through to tissues., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
4. Abstracts of papers presented at the thirty-first annual meeting of The American Society for Cell Biology. 8-12 December 1991, Boston, Massachusetts.
- Subjects
- Animals, Humans, Cells
- Published
- 1991
5. Abstracts of papers presented at the thirtieth annual meeting of the American Society for Cell Biology. 9-13 December 1990, San Diego, California.
- Subjects
- Animals, Humans, Cells
- Published
- 1990
6. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure
- Author
-
Fabrice Prunier, Péter Ferdinandy, Joost P.G. Sluijter, Sandrine Lecour, Sophie Van Linthout, Linda W. van Laake, Maurizio Pesce, Hans Erik Bøtker, Kirsti Ytrehus, Sean M. Davidson, Felix B. Engel, Rosalinda Madonna, Francesco Fernandez-Aviles, Raffaele De Caterina, Cinzia Perrino, Philippe Menasché, Derek J. Hausenloy, Thomas Eschenhagen, Wolfram-Hubertus Zimmermann, Jonathan Leor, Jean-Sébastien Hulot, and Perrino, C
- Subjects
0301 basic medicine ,Biomedical Research ,Consensus ,Physiology ,Cells ,Cell ,Cardiology ,Myocardial Ischemia ,Cardiac tissue engineering ,030204 cardiovascular system & hematology ,Biomaterials ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Tissue engineering ,Physiology (medical) ,medicine ,Humans ,Regeneration ,Survival rate ,Heart Failure ,Heart failure ,Ischaemic heart disease ,Tissue Engineering ,business.industry ,Myocardium ,Regeneration (biology) ,Position Paper from European Society of Cardiology Working Group ,Recovery of Function ,medicine.disease ,Cell biology ,Transplantation ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Position paper ,Cardiology and Cardiovascular Medicine ,business ,Stem Cell Transplantation - Abstract
Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF. © Published on behalf of the European Society of Cardiology. All rights reserved.
- Published
- 2019
7. Papers presented at the forty-second annual meeting of the Japan Society for Cell Biology. Kyoto, 25-27 October 1989. Abstracts.
- Subjects
- Animals, Cell Physiological Phenomena, Humans, Cells
- Published
- 1989
8. Cellular fluidics.
- Author
-
Dudukovic NA, Fong EJ, Gemeda HB, DeOtte JR, Cerón MR, Moran BD, Davis JT, Baker SE, and Duoss EB
- Subjects
- Absorption, Physicochemical, Carbon Dioxide metabolism, Gases metabolism, Nutrients metabolism, Oxygen metabolism, Plant Transpiration, Videodisc Recording, Water metabolism, Cells metabolism, Microfluidics instrumentation, Microfluidics methods
- Abstract
The natural world provides many examples of multiphase transport and reaction processes that have been optimized by evolution. These phenomena take place at multiple length and time scales and typically include gas-liquid-solid interfaces and capillary phenomena in porous media
1,2 . Many biological and living systems have evolved to optimize fluidic transport. However, living things are exceptionally complex and very difficult to replicate3-5 , and human-made microfluidic devices (which are typically planar and enclosed) are highly limited for multiphase process engineering6-8 . Here we introduce the concept of cellular fluidics: a platform of unit-cell-based, three-dimensional structures-enabled by emerging 3D printing methods9,10 -for the deterministic control of multiphase flow, transport and reaction processes. We show that flow in these structures can be 'programmed' through architected design of cell type, size and relative density. We demonstrate gas-liquid transport processes such as transpiration and absorption, using evaporative cooling and CO2 capture as examples. We design and demonstrate preferential liquid and gas transport pathways in three-dimensional cellular fluidic devices with capillary-driven and actively pumped liquid flow, and present examples of selective metallization of pre-programmed patterns. Our results show that the design and fabrication of architected cellular materials, coupled with analytical and numerical predictions of steady-state and dynamic behaviour of multiphase interfaces, provide deterministic control of fluidic transport in three dimensions. Cellular fluidics may transform the design space for spatial and temporal control of multiphase transport and reaction processes.- Published
- 2021
- Full Text
- View/download PDF
9. The NIH Somatic Cell Genome Editing program.
- Author
-
Saha K, Sontheimer EJ, Brooks PJ, Dwinell MR, Gersbach CA, Liu DR, Murray SA, Tsai SQ, Wilson RC, Anderson DG, Asokan A, Banfield JF, Bankiewicz KS, Bao G, Bulte JWM, Bursac N, Campbell JM, Carlson DF, Chaikof EL, Chen ZY, Cheng RH, Clark KJ, Curiel DT, Dahlman JE, Deverman BE, Dickinson ME, Doudna JA, Ekker SC, Emborg ME, Feng G, Freedman BS, Gamm DM, Gao G, Ghiran IC, Glazer PM, Gong S, Heaney JD, Hennebold JD, Hinson JT, Khvorova A, Kiani S, Lagor WR, Lam KS, Leong KW, Levine JE, Lewis JA, Lutz CM, Ly DH, Maragh S, McCray PB Jr, McDevitt TC, Mirochnitchenko O, Morizane R, Murthy N, Prather RS, Ronald JA, Roy S, Roy S, Sabbisetti V, Saltzman WM, Santangelo PJ, Segal DJ, Shimoyama M, Skala MC, Tarantal AF, Tilton JC, Truskey GA, Vandsburger M, Watts JK, Wells KD, Wolfe SA, Xu Q, Xue W, Yi G, and Zhou J
- Subjects
- Animals, Genetic Therapy, Goals, Humans, United States, Cells metabolism, Gene Editing methods, Genome, Human genetics, National Institutes of Health (U.S.) organization & administration
- Abstract
The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.
- Published
- 2021
- Full Text
- View/download PDF
10. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure : Position paper for Cardiovascular Research: Tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure
- Author
-
Madonna, Rosalinda, Van Laake, Linda W, Botker, Hans Erik, Davidson, Sean M, De Caterina, Raffaele, Engel, Felix B, Eschenhagen, Thomas, Fernandez-Aviles, Francesco, Hausenloy, Derek J, Hulot, Jean-Sebastien, Lecour, Sandrine, Leor, Jonathan, Menasché, Philippe, Pesce, Maurizio, Perrino, Cinzia, Prunier, Fabrice, Van Linthout, Sophie, Ytrehus, Kirsti, Zimmermann, Wolfram-Hubertus, Ferdinandy, Peter, and Sluijter, Joost P G
- Subjects
Biomaterials ,Ischaemic heart disease ,Physiology ,Cells ,Physiology (medical) ,Journal Article ,Heart failure ,Cardiac tissue engineering ,Cardiology and Cardiovascular Medicine - Abstract
Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF.
- Published
- 2019
11. A comparative chlorophyll a fluorescence study on isolated cells and intact leaves of Bouteloua gracilis (blue grama grass).
- Author
-
JIMÉNEZ-FRANCISCO, B., STIRBET, A., AGUADO-SANTACRUZ, G. A., CAMPOS, H., CONDE-MARTÍNEZ, F. V., PADILLA-CHACÓN, D., TREJO, C., BERNACCHI, C. J., and GOVINDJEE, G.
- Subjects
- *
CHLOROPHYLL spectra , *FILTER paper , *SUCROSE , *CELLS , *CELL culture , *CELL suspensions - Abstract
Bouteloua gracilis (blue grama grass) is one of the most drought and grazing tolerant plants in the short-grass ecosystem. To obtain information on their photosystem activities, we measured the fast (< 1 s) chlorophyll a fluorescence transient (the OJIP curve) from their leaves, and isolated cells grown photoautotrophically in suspension in a culture medium, or with added sucrose. One of our goals was to study the effect of different sucrose concentrations (0, 0.15, 0.3, and 3%) on PSII activity in isolated cells. Our results on cells suspended in culture medium, using the JIP-test, showed a decrease in PSII activity at increasing sucrose concentrations, while the photoautotrophic cells showed an optimal PSII activity, close to that of the leaves. Further, our data on cells grown in 0, 0.15, and 0.3% sucrose, but with added CO2, and measured while the cells were deposited on filter paper, indicate that supplementary CO2 can increase the PSII activity in the presence of sucrose, although further research is necessary to understand these results. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
12. Transcription factors and 3D genome conformation in cell-fate decisions.
- Author
-
Stadhouders R, Filion GJ, and Graf T
- Subjects
- Animals, Chromatin Assembly and Disassembly genetics, Chromosome Positioning, Gene Expression Regulation, Humans, Organ Specificity genetics, Cell Differentiation genetics, Cells cytology, Cells metabolism, Genome genetics, Transcription Factors metabolism
- Abstract
How cells adopt different identities has long fascinated biologists. Signal transduction in response to environmental cues results in the activation of transcription factors that determine the gene-expression program characteristic of each cell type. Technological advances in the study of 3D chromatin folding are bringing the role of genome conformation in transcriptional regulation to the fore. Characterizing this role of genome architecture has profound implications, not only for differentiation and development but also for diseases including developmental malformations and cancer. Here we review recent studies indicating that the interplay between transcription and genome conformation is a driving force for cell-fate decisions.
- Published
- 2019
- Full Text
- View/download PDF
13. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure : Position paper for Cardiovascular Research: Tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure
- Subjects
Biomaterials ,Ischaemic heart disease ,Physiology ,Cells ,Physiology (medical) ,Journal Article ,Heart failure ,Cardiac tissue engineering ,Cardiology and Cardiovascular Medicine - Abstract
Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF.
- Published
- 2019
14. Detection of Bacillus cereus group bacteria from cardboard and paper with real-time PCR.
- Author
-
Priha, Outi, Hallamaa, Katri, Saarela, Maria, and Raaska, Laura
- Subjects
- *
BACILLUS (Bacteria) , *NUCLEIC acids , *RAPID methods (Microbiology) , *CELLS , *DNA , *MICROBIOLOGY - Abstract
The aim of this study was to develop a PCR-based rapid method to detect Bacillus cereus group cells from paper and cardboard. Primers targeting the 16S rDNA and real-time PCR with SYBR green I detection were used in order to be able to also quantify the target. Both autoclaved cardboard samples spiked with B. cereus vegetative cells or spores and naturally contaminated paper and cardboard samples were studied. Results were compared with culturing verified by commercial (API) tests. Several different methods were tested for DNA isolation from the paper and cardboard samples. Two commercial kits intended for soils, the UltraClean soil DNA kit and the FastDNA spin kit for soil, gave the most reproducible results. In spiked samples, the average yield was 50% of added vegetative cells, but spore yield was only about 10%. PCR results from adding vegetative cells correlated with added colony-forming unit (cfu) values (r=0.93, P <0.001) in the range 100–10,000 cfu g-1. Three out of nine studied paper and cardboard samples contained B. cereus group bacteria, based both on culturing and real-time PCR. The numbers were 102–103 bacteria g-1; and PCR gave somewhat higher results than culturing. Thus, real-time PCR can be used as a rapid semi-quantitative method to screen paper and cardboard samples for contamination with B. cereus group bacteria. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
15. Statistical Analysis of Gastric Cancer Cells Response to Broadband Terahertz Radiation with and without Contrast Nanoparticles.
- Author
-
Schreiner, Oliver Daniel, Socotar, Diana, Ciobanu, Romeo Cristian, Schreiner, Thomas Gabriel, and Tamba, Bogdan Ionel
- Subjects
STOMACH tumors ,RADIOTHERAPY ,DATA analysis ,TREATMENT effectiveness ,MAGNETIC resonance imaging ,MANN Whitney U Test ,CELL lines ,STATISTICS ,SPECTRUM analysis ,RADIATION doses ,CONTRAST media ,NANOPARTICLES ,CELLS - Abstract
Simple Summary: The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. A statistical analysis was conducted towards multiple pairwise comparisons in order to identify the narrow THz frequency ranges where the contrast is enhanced and allows a clear identification of tumor cells in the presence of contrast agents. The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. The THz spectroscopy analysis was comparatively performed under the ATR procedure and transmission measurement procedure. The statistical analysis was conducted towards multiple pairwise comparisons, including a support medium (without cells) versus a support medium with nanoparticles, normal cells versus normal cells with nanoparticles, and, respectively, tumor cells versus tumor cells with nanoparticles. When generally comparing the ATR procedure and transmission measurement procedure for a broader frequency domain, the differentiation between normal and tumor cells in the presence of contrast agents is superior when using the ATR procedure. THz contrast enhancement by using contrast agents derived from MRI-related contrast agents leads to only limited benefits and only for narrow THz frequency ranges, a disadvantage for THz medical imaging. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Autopoiesis and Eigenform.
- Author
-
Kauffman, Louis H.
- Subjects
AUTOPOIESIS ,REFLECTION (Philosophy) ,BIOLOGICAL systems ,CELLULAR automata ,INFORMATION storage & retrieval systems - Abstract
This paper explores a formal model of autopoiesis as presented by Maturana, Uribe and Varela, and analyzes this model and its implications through the lens of the notions of eigenforms (fixed points) and the intricacies of Goedelian coding. The paper discusses the connection between autopoiesis and eigenforms and a variety of different perspectives and examples. The paper puts forward original philosophical reflections and generalizations about its various conclusions concerning specific examples, with the aim of contributing to a unified way of understanding (formal models of) living systems within the context of natural sciences, and to see the role of such systems and the formation of information from the point of view of analogs of biological construction. To this end, we pay attention to models for fixed points, self-reference and self-replication in formal systems and in the description of biological systems. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
17. Modified technique for solving advance-delay differential systems
- Author
-
Ismail, G.A.F.
- Subjects
- *
PAPER , *NEURONS , *CELLS , *AXONS - Abstract
Abstract: In this paper, the numerical treatment for two nonlinear advance delay differential system is discussed. This system arises during the study of conduction of impulses down myelinated axons, incorporating electrical properties of the myelin. This system consists of two coupled first-order equations, one having a delay term and the other having an advance one. The modified difference scheme is used and then applied to some test problems. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
18. Trouble in the laboratory: probing the science of a controversial paper
- Author
-
Margot, O'Toole
- Subjects
Biomedical Research ,Cells ,Research ,Fraud ,Scientific Misconduct ,Federal Government ,Public Policy ,Social Control, Informal ,Research Personnel ,United States ,Social Control, Formal ,National Institutes of Health (U.S.) ,Government ,Government Regulation ,Humans - Published
- 1990
19. Short Paper Expressed sequence tag of Japanese flounder Paralichthys olivaceus skin cells.
- Author
-
Hirono, Ikuo, Yazawa, Ryosuke, and Aoki, Yakashi
- Subjects
- *
FLATFISHES , *PARALICHTHYS , *CELLS , *MESSENGER RNA , *BACTERIOPHAGES , *CLONING - Abstract
Describes an expressed sequence tag analysis of skin cells of Japanese flounder Paralichthys olivaceus. Isolation of messenger RNA of skin; Conversion of phage clones into plasmids; Average sequence length.
- Published
- 2004
- Full Text
- View/download PDF
20. The Bicoid Morphogen Papers (II): Account from Wolfgang Driever.
- Author
-
Driever, Wolfgang
- Subjects
- *
DROSOPHILA , *IMMUNOHISTOCHEMISTRY , *MORPHOGENESIS , *CELLS , *BIOLOGY , *EMBRYOLOGY - Abstract
This article presents information on a gradient of bicoid (bcd) protein in drosophila embryos. According to the concept of positional information, the concentration of a morphogen instructs cells within an embryonic field of their position. The cells then interpret this information by an appropriate program of differentiation. Several models have been proposed that describe the generation of stable gradients of morphogens which could specify subregions of the embryo in a concentration-dependent manner.
- Published
- 2004
- Full Text
- View/download PDF
21. Publication, funding, and experimental data in support of Human Reference Atlas construction and usage.
- Author
-
Kong Y and Börner K
- Subjects
- Humans, Metadata, Cells
- Abstract
Experts from 18 consortia are collaborating on the Human Reference Atlas (HRA) which aims to map the 37 trillion cells in the healthy human body. Information relevant for HRA construction and usage is held by experts, published in scholarly papers, and captured in experimental data. However, these data sources use different metadata schemas and cannot be cross-searched efficiently. This paper documents the compilation of a dataset, named HRAlit, that links the 136 HRA v1.4 digital objects (31 organs with 4,279 anatomical structures, 1,210 cell types, 2,089 biomarkers) to 583,117 experts; 7,103,180 publications; 896,680 funded projects, and 1,816 experimental datasets. The resulting HRAlit has 22 tables with 20,939,937 records including 6 junction tables with 13,170,651 relationships. The HRAlit can be mined to identify leading experts, major papers, funding trends, or alignment with existing ontologies in support of systematic HRA construction and usage., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
22. Melanin as a target for melanoma chemotherapy: pro-oxidant effect of oxygen and metals on melanoma viability.
- Author
-
Farmer, Patrick J, Gidanian, Shirley, Shahandeh, Babbak, Di Bilio, Angel J, Tohidian, Nilou, and Meyskens, Frank L, Jr
- Subjects
Cell Line ,Tumor ,Cell Survival ,Cells ,Cultured ,Copper: chemistry ,Cyclic N-Oxides: chemistry ,Dose-Response Relationship ,Drug ,Electrochemistry ,Electron Spin Resonance Spectroscopy ,Enzyme Inhibitors: chemistry ,Escherichia coli: metabolism ,Humans ,Hydrogen-Ion Concentration ,Indoles: chemistry ,Infant ,Newborn ,Male ,Melanins: metabolism ,Melanoma: drug therapy ,metabolism ,Metals: metabolism ,Oxidants: metabolism ,Oxidation-Reduction ,Oxidative Stress ,Oxygen: metabolism ,Plasmids: metabolism ,Reactive Oxygen Species ,Time Factors ,Zinc: chemistry ,Melanins ,Melanocytes ,Melanoma ,Metal uptake ,Oxygen ,Pro-oxidanthydroxyl radical ,melanin ,metal ,oxidizing agent ,animal cell ,cancer chemotherapy ,cell compartmentalization ,cell viability ,complex formation ,conference paper ,drug effect ,electron spin resonance ,gene targeting ,genetic susceptibility ,melanoma ,nonhuman ,oxidation reduction reaction ,oxidative stress ,oxygen consumption ,receptor affinity ,Cell Line ,Tumor ,Cell Survival ,Cells ,Cultured ,Copper ,Cyclic N-Oxides ,Dose-Response Relationship ,Drug ,Electrochemistry ,Electron Spin Resonance Spectroscopy ,Enzyme Inhibitors ,Escherichia coli ,Humans ,Hydrogen-Ion Concentration ,Indoles ,Infant ,Newborn ,Male ,Melanins ,Melanoma ,Metals ,Oxidants ,Oxidation-Reduction ,Oxidative Stress ,Oxygen ,Plasmids ,Reactive Oxygen Species ,Time Factors ,Zinc ,Animalia - Abstract
Melanoma cells have a poor ability to mediate oxidative stress, which may be attributed to constitutive abnormalities in their melanosomes. We hypothesize that disorganization of the melanosomes will allow chemical targeting of the melanin within. Chemical studies show that under oxidative conditions, synthetic melanins demonstrate increased metal affinity and a susceptibility to redox cycling with oxygen to form reactive oxygen species. The electron paramagnetic resonance (EPR)-active 5,5'-dimethyl-pyrollidine N-oxide spin adduct was used to show that binding of divalent Zn or Cu to melanin induces a pro-oxidant response under oxygen, generating superoxide and hydroxyl radicals. A similar pro-oxidant behaviour is seen in melanoma cell lines under external peroxide stress. Melanoma cultures grown under 95% O2/5% CO2 atmospheres show markedly reduced viability as compared with normal melanocytes. Cu- and Zn-dithiocarbamate complexes, which induce passive uptake of the metal ions into cells, show significant antimelanoma activity. The antimelanoma effect of metal- and oxygen-induced stress appears additive rather than synergistic; both treatments are shown to be significantly less toxic to melanocytes.
- Published
- 2003
23. Synthesis and Evaluation of Europium Complexes that Switch on Luminescence in Lysosomes of Living Cells
- Author
-
Laurent J. Lamarque, Matthieu Starck, David Parker, Jack D. Fradgley, Robert Pal, and Jurriaan M. Zwier
- Subjects
Absorption (pharmacology) ,Luminescence ,Cell Survival ,Cells ,Serum albumin ,chemistry.chemical_element ,Protonation ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Catalysis ,Mice ,Europium ,Live cell imaging ,Animals ,A value ,Serum Albumin ,Full Paper ,biology ,Cell Imaging | Hot Paper ,pH ,010405 organic chemistry ,Organic Chemistry ,3T3 Cells ,General Chemistry ,Full Papers ,Chromophore ,0104 chemical sciences ,chemistry ,biology.protein ,Lysosomes - Abstract
A set of four luminescent EuIII complexes bearing an extended aryl‐alkynylpyridine chromophore has been studied, showing very different pH‐dependent behaviour in their absorption and emission spectral response. For two complexes with pK a values of 6.45 and 6.20 in protein‐containing solution, the emission lifetime increases very significantly following protonation. By varying the gate time during signal acquisition, the ‘switch‐on’ intensity ratio could be optimised, and enhancement factors of between 250 to 1330 were measured between pH 8 and 4. The best‐behaved probe showed no significant emission dependence on the concentration of endogenous cations, reductants, and serum albumin. It was examined in live‐cell imaging studies to monitor time‐dependent lysosomal acidification, for which the increase in observed image brightness due to acidification was a factor of 50 in NIH‐3T3 cells., Watching lysosomes age with a ‘switch‐on’ optical sensor is shown to be possible by using four europium complexes with extended aryl‐alkylnyl pyridine antennae that show very different pH‐dependent behaviour. A ‘switch‐on’ of europium luminescence occurs at low pH, allowing confocal microscopy to reveal increases in image brightness of ageing lysosomes in live‐cell imaging studies.
- Published
- 2020
24. Cells Best Paper Award 2015.
- Author
-
Kalyuzhny, Alexander E.
- Subjects
- *
CELLS , *HUMAN research subjects ,RESEARCH awards - Published
- 2015
- Full Text
- View/download PDF
25. Assembly of asparagine-linked oligosaccharides in baby hamster kidney cells treated with castanospermine, an inhibitor of processing glucosidases.
- Author
-
Foddy, Louise and Hughes, R. Colin
- Subjects
OLIGOSACCHARIDES ,HAMSTERS ,GLUCOSIDASES ,CELLS ,GEL permeation chromatography ,PAPER chromatography - Abstract
We have shown previously that the processing of asparagine-linked oligosaccharides in baby hamster kidney (BHK) cells is blocked only partially by the glucosidase inhibitors, 1-deoxynojidmycin and A'-methyl-1-deoxynojidmycin [Hughes, R, C, Foddy, L. & Bause, E. (1987) Biochem. J. 247, 537-544], Similar results are now reported for castanospermine, another inhibitor of processing glucosidases, and a detailed study of oligosaccharide processing in the inhibited cells is reported. In steady-state conditions the major endo-H-released oligosaccharides contained glucose residues but non-glycosylated oligosaccharides, including Man
9 GlcNAc to Man5 GlcNAc, were also present. To determine the processing sequences occurring in the presence of castanospermine, BHK cells were pulse-labelled for various times with [³H]mannose and the oligosaccharide intermediates, isolated by gel filtration and paper chromatography, characterized by acetolysis and sensitivity to jack bean α-mannosidase. The data show that Glc3 Man8 GlcNAc2 is transferred to protein and undergoes processing to produce Glc3 Man8 GlcNAc2 and Glc3 Man7 GlcNAc2 as major species as well as a smaller amount of Man9 GlcNAc2 , Glucosidase-processed intermediates, Glc1 Man8 GlcNAc2 and Glc1 Man7 GlcNAc2 , were also obtained as well as a Man7 GlcNAc2 species derived from Glc1 Man7 GlcNAc2 and different from the Man7 GlcNAc2 isomer formed in the usual processing pathway. No evidence for the direct transfer of non-glucosylated oligosacchaddes to proteins was obtained and we conclude that the continued assembly of complex-type glycans in castanospermine-inhibited BHK cells results from residual activity of processing glucosidases. [ABSTRACT FROM AUTHOR]- Published
- 1988
- Full Text
- View/download PDF
26. Reduced visual contrast suppression during major depressive episodes
- Author
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Erkki Isometsä, Jesper Ekelund, Jari Lahti, Lumikukka Socada, Roope Heikkilä, John J. Söderholm, Viljami Salmela, Department of Psychology and Logopedics, Department of Psychiatry, and HUS Psychiatry
- Subjects
Male ,Bipolar Disorder ,genetic structures ,Audiology ,3124 Neurology and psychiatry ,chemistry.chemical_compound ,GABA ,0302 clinical medicine ,Borderline Personality Disorder ,SCHIZOPHRENIA ,Medicine ,Contrast (vision) ,Pharmacology (medical) ,Prospective Studies ,Major depressive episode ,Prospective cohort study ,Borderline personality disorder ,RECEPTIVE-FIELDS ,media_common ,Middle Aged ,Psychiatry and Mental health ,SELECTIVITY ,Schizophrenia ,Visual Perception ,Major depressive disorder ,Female ,medicine.symptom ,Research Paper ,Adult ,medicine.medical_specialty ,Adolescent ,515 Psychology ,DISORDERS ,media_common.quotation_subject ,OCCIPITAL CORTEX ,MECHANISMS ,03 medical and health sciences ,Young Adult ,Humans ,Bipolar disorder ,BRIGHTNESS ,Biological Psychiatry ,Depressive Disorder, Major ,business.industry ,Retinal ,Bayes Theorem ,medicine.disease ,030227 psychiatry ,chemistry ,CELLS ,ORIENTATION ,business ,030217 neurology & neurosurgery - Abstract
Background: Previous studies have suggested that processing of visual contrast information could be altered in major depressive disorder. To clarify the changes at different levels of the visual hierarchy, we behaviourally measured contrast perception in 2 centre-surround conditions, assessing retinal and cortical processing. Methods: As part of a prospective cohort study, our sample consisted of controls (n = 29; 21 female) and patients with unipolar depression, bipolar disorder and borderline personality disorder who had baseline major depressive episodes (n = 111; 74 female). In a brightness induction test that assessed retinal processing, participants compared the perceived luminance of uniform patches (presented on a computer screen) as the luminance of the backgrounds was varied. In a contrast suppression test that assessed cortical processing, participants compared the perceived contrast of gratings, which were presented with collinearly or orthogonally oriented backgrounds. Results: Brightness induction was similar for patients with major depressive episodes and controls (p = 0.60, d = 0.115, Bayes factor = 3.9), but contrast suppression was significantly lower for patients than for controls (p < 0.006, d = 0.663, Bayes factor = 35.2). We observed no statistically significant associations between contrast suppression and age, sex, or medication or diagnostic subgroup. At follow-up (n = 74), we observed some normalization of contrast perception. Limitations: We assessed contrast perception using behavioural tests instead of electrophysiology. Conclusion: The reduced contrast suppression we observed may have been caused by decreased retinal feedforward or cortical feedback signals. Because we observed intact brightness induction, our results suggest normal retinal but altered cortical processing of visual contrast during a major depressive episode. This alteration is likely to be present in multiple types of depression and to partially normalize upon remission.
- Published
- 2021
27. Modeling the mechanobioelectricity of cell clusters
- Author
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Alessandro Leronni
- Subjects
Osmosis ,Cells ,Poromechanics ,Intracellular Space ,02 engineering and technology ,Models, Biological ,Quantitative Biology::Cell Behavior ,Tight Junctions ,Ion ,Quantitative Biology::Subcellular Processes ,Electro-diffusion ,03 medical and health sciences ,Cluster (physics) ,Ion transporter ,Ion channel ,Membrane potential ,030304 developmental biology ,Physics ,Original Paper ,0303 health sciences ,Mechanical Engineering ,Gap Junctions ,Electro-osmosis ,021001 nanoscience & nanotechnology ,Biomechanical Phenomena ,Electrophysiological Phenomena ,Bioelectricity ,Membrane ,Chemical physics ,Modeling and Simulation ,Finite strain theory ,Thermodynamics ,0210 nano-technology ,Biotechnology - Abstract
We propose a continuum finite strain theory for the interplay between the bioelectricity and the poromechanics of a cell cluster. Specifically, we refer to a cluster of closely packed cells, whose mechanics is governed by a polymer network of cytoskeletal filaments joined by anchoring junctions, modeled through compressible hyperelasticity. The cluster is saturated with a solution of water and ions. We account for water and ion transport in the intercellular spaces, between cells through gap junctions, and across cell membranes through aquaporins and ion channels. Water fluxes result from the contributions due to osmosis, electro-osmosis, and water pressure, while ion fluxes encompass electro-diffusive and convective terms. We consider both the cases of permeable and impermeable cluster boundary, the latter simulating the presence of sealing tight junctions. We solve the coupled governing equations for a one-dimensional axisymmetric benchmark through finite elements, thus determining the spatiotemporal evolution of the intracellular and extracellular ion concentrations, setting the membrane potential, and water concentrations, establishing the cluster deformation. When suitably complemented with genetic, biochemical, and growth dynamics, we expect this model to become a useful instrument for investigating specific aspects of developmental mechanobioelectricity.
- Published
- 2020
28. Evidence for a Pronounced Secretion of Cyclic AMP by Tetrahymena
- Author
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Nandini-Kishore, S. G. and Thompson,, G. A.
- Published
- 1980
29. Intrarenal arteriosclerosis and telomere attrition associate with dysregulation of the cholesterol pathway
- Author
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Tim S. Nawrot, Evelyne Lerut, Ellen Winckelmans, Dries S. Martens, Katrien De Vusser, Dirk Kuypers, and Maarten Naesens
- Subjects
Senescence ,Male ,medicine.medical_specialty ,Aging ,Intimal hyperplasia ,Geriatrics & Gerontology ,senescence ,cholesterol pathway ,chemistry.chemical_compound ,COENZYME-A REDUCTASE ,Renal Artery ,LIPID-METABOLISM ,Internal medicine ,medicine ,LENGTH ,INJURY ,Humans ,HUMAN ATHEROSCLEROSIS ,RISK ,Kidney ,Science & Technology ,SERUM CREATININE ,arteriosclerosis ,Cholesterol ,business.industry ,aging ,Arteriosclerosis ,Cell Biology ,Middle Aged ,Telomere ,medicine.disease ,telomeres ,Transplantation ,Endocrinology ,medicine.anatomical_structure ,chemistry ,CARDIOVASCULAR-DISEASE ,Cohort ,CELLS ,Female ,business ,Life Sciences & Biomedicine ,Research Paper - Abstract
BACKGROUND: Recently, we demonstrated that arteriosclerosis in the smaller intrarenal arteries is associated with shorter telomere length, independently of history of cardiovascular events and calendar age. This suggests that intrarenal arteriosclerosis reflects replicative senescence, although the underlying molecular alterations remain unclear. RESULTS: Shorter intrarenal telomere length associated significantly with the presence of renal arteriosclerosis (T/S ratio 0.91±0.15 vs. 1.20±0.23 with vs. without arteriosclerosis, p=0.007, test cohort; T/S ratio 0.98 ±0.26 vs. 1.03 ±0.18 with vs. without arteriosclerosis, p=0.02, validation cohort). The presence versus absence of intrarenal arteriosclerosis was associated with differential expression of 1472 transcripts. Pathway analysis revealed enrichment of molecules involved in the superpathway of cholesterol biosynthesis as the most significant. The differential expression of these genes was confirmed in the independent validation cohort. Furthermore, the specific mRNA expression of the molecules in the superpathway of cholesterol biosynthesis associated significantly with intrarenal telomere length, and with history of cardiovascular events. INTERPRETATION: Our study illustrates that the superpathway of cholesterol biosynthesis interacts with the previously published association between shorter telomere length and arteriosclerosis. METHODS: This study included a test cohort of 40 consecutive kidney donors (calendar age 48.0 ± 15), with biopsies obtained prior to transplantation. Intrarenal leucocyte telomere length content was assessed using quantitative RT-PCR. Whole genome microarray mRNA expression analysis was performed using Affymetrix Gene 2.0 ST arrays. We investigated the associations between mRNA gene expression, telomere length as marker of replicative senescence, and intrarenal arteriosclerosis (Banff "cv" score = vascular fibrous intimal thickening = intimal hyperplasia) using adjusted multiple regression models. For biological interpretation and pathway overrepresentation analysis, we used Ingenuity Pathway Analysis. The significant pathways and genes were validated in an independent validation cohort of 173 kidney biopsies obtained prior to transplantation. ispartof: AGING-US vol:12 issue:9 pages:7830-7847 ispartof: location:United States status: published
- Published
- 2020
30. Old but not obsolete: an enhanced high-speed immunoblot
- Author
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Haruna Nagase, Craig S Pearson, Kazuya Yagyu, Yasuhiro Katagiri, Herbert M. Geller, and Sayuri L Higashi
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Cells ,Blotting, Western ,Immunoblotting ,Tissue membrane ,01 natural sciences ,Biochemistry ,Antibodies ,law.invention ,Incubation period ,Mice ,03 medical and health sciences ,Western blot ,law ,medicine ,Animals ,Humans ,Molecular Biology ,Incubation ,Cells, Cultured ,030304 developmental biology ,Chemiluminescence ,0303 health sciences ,biology ,medicine.diagnostic_test ,Chemistry ,010401 analytical chemistry ,Regular Papers ,Proteins ,General Medicine ,Antigen binding ,Corrigenda ,Molecular biology ,Biomedical Enhancement ,0104 chemical sciences ,Mice, Inbred C57BL ,Blot ,biology.protein ,Antibody - Abstract
The immunoblotting technique (also known as western blotting) is an essential tool used in biomedical research to determine the relative size and abundance of specific proteins and protein modifications. However, long incubation times severely limit its throughput. We have devised a system that improves antigen binding by cyclic draining and replenishing (CDR) of the antibody solution in conjunction with an immunoreaction enhancing agent. Biochemical analyses revealed that the CDR method reduced the incubation time of the antibodies, and the presence of a commercial immunoreaction enhancing agent altered the affinity of the antibody, respectively. Combination of the CDR method with the immunoreaction enhancing agent considerably enhanced the output signal and further reduced the incubation time of the antibodies. The resulting high-speed immunoblot can be completed in 20 min without any loss in sensitivity. Further, the antibodies are fully reusable. This method is effective for both chemiluminescence and fluorescence detection. Widespread adoption of this technique could dramatically boost efficiency and productivity across the life sciences.
- Published
- 2020
31. Prognostic significance of Spinster homolog gene family in acute myeloid leukemia
- Author
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Longzhen Cui, Lin Fu, Wenhui Huang, Chaozeng Si, Xu Ye, Yan Liu, Tiansheng Zeng, Chaojun Liu, Zhiheng Cheng, Tingting Qian, and Cong Deng
- Subjects
0301 basic medicine ,SPNS2 ,SPNS1 ,medicine.medical_treatment ,Disease ,Hematopoietic stem cell transplantation ,SPNS3 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Gene family ,Adverse effect ,Chemotherapy ,Acute myeloid leukemia ,business.industry ,TRANSPLANTATION ,Myeloid leukemia ,SPHINGOSINE-1-PHOSPHATE TRANSPORTER SPNS2 ,Prognosis ,Sphingolipid ,Transmembrane protein ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,CELLS ,Cancer research ,business ,Research Paper - Abstract
Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by proliferation of immature myeloid cells, with impaired differentiation and maturation. Spinster homolog (SPNS) is a widely distributed transmembrane transporter, which assists sphingolipids in playing their roles through the cell membrane. However, the expression and clinical implication of the SPNS family has not been investigated in AML. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and SPNS1-3 expression data were contained in our study. In patients who received chemotherapy only, high expressions of SPNS2 and SPNS3 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P<0.05). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in OS between the high and low SPNS3 expression groups (P=0.001), while other SPNS members showed no effect on survival. Multivariate analysis indicated that high SPNS2 expression was an independent risk factor for both EFS and OS in chemotherapy patients. The results confirmed that high expression of SPNS2 and SPNS3 were poor prognostic factors, and the effect of SPNS2 can be neutralized by allo-HSCT.
- Published
- 2020
32. A COX-2/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation
- Author
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Bruce D. Hammock, Xiao-Qin Luo, Yong Zhou, Cha-Xiang Guan, Jian-Xin Jiang, Jia-Xi Duan, Yan-Feng Zhang, Hui-Hui Yang, Chen-Yu Zhang, Sung Hee Hwang, Chen-Chen Sun, Shao-Kun Liu, Xin-Xin Guan, Ping Chen, Jian-Bing Xiong, and Wen-Jing Zhong
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Lipopolysaccharide ,Inflammasomes ,Medicine (miscellaneous) ,Pharmacology ,Inbred C57BL ,medicine.disease_cause ,Pathogenesis ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,oxidative stress ,2.1 Biological and endogenous factors ,Aetiology ,Enzyme Inhibitors ,Acute Respiratory Distress Syndrome ,Lung ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Cells, Cultured ,Epoxide Hydrolases ,Cultured ,Chemistry ,Inflammasome ,respiratory system ,5.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Development of treatments and therapeutic interventions ,medicine.symptom ,Research Paper ,medicine.drug ,Epoxide hydrolase 2 ,Cells ,Oncology and Carcinogenesis ,Acute Lung Injury ,Inflammation ,NLR Family ,Lung injury ,03 medical and health sciences ,Rare Diseases ,Downregulation and upregulation ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Cyclooxygenase 2 Inhibitors ,Animal ,Macrophages ,COX-2/sEH dual inhibitor ,Pyrin Domain-Containing 3 Protein ,NLRP3 inflammasome ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Cyclooxygenase 2 ,Disease Models ,Oxidative stress - Abstract
Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive. In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice. Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice. The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI. Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro. Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge. Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs). The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated. Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells. Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice. PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro. Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion: The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI. The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.
- Published
- 2020
33. PU-91 drug rescues human age-related macular degeneration RPE cells; implications for AMD therapeutics
- Author
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M. Cristina Kenney, Marilyn Chwa, Sudhakar R. Subramaniam, Anthony B. Nesburn, Sonali Nashine, Howard J. Federoff, and Baruch D. Kuppermann
- Subjects
Drug ,Aging ,Mitochondrial DNA ,FDA-approved drugs ,genetic structures ,Physiology ,Cells ,media_common.quotation_subject ,Oncology and Carcinogenesis ,PGC-1α ,Retinal Pigment Epithelium ,Neurodegenerative ,Mitochondrion ,Pathogenesis ,Macular Degeneration ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Medicine ,Aetiology ,age-related macular degeneration ,Cells, Cultured ,media_common ,age-related macular degeneration (AMD) ,Cultured ,business.industry ,PGC-1 alpha ,Drug Repositioning ,Cell Biology ,Macular degeneration ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,eye diseases ,Mitochondria ,mitochondria ,Mitochondrial biogenesis ,5.1 Pharmaceuticals ,Cell culture ,Cancer research ,RPE ,Biochemistry and Cell Biology ,sense organs ,Development of treatments and therapeutic interventions ,business ,Esterase inhibitor ,Research Paper ,Developmental Biology - Abstract
Since mitochondrial dysfunction is implicated in the pathogenesis of AMD, this study is based on the premise that repurposing of mitochondria-stabilizing FDA-approved drugs such as PU-91, might rescue AMD RPE cells from AMD mitochondria-induced damage. The PU-91 drug upregulates PGC-1α which is a critical regulator of mitochondrial biogenesis. Herein, we tested the therapeutic potential of PU-91 drug and examined the additive effects of treatment with PU-91 and esterase inhibitors i.e., EI-12 and EI-78, using the in vitro transmitochondrial AMD cell model. This model was created by fusing platelets obtained from AMD patients with Rho0 i.e., mitochondria-deficient, ARPE-19 cell lines. The resulting AMD RPE cell lines have identical nuclei but differ in their mitochondrial DNA content, which is derived from individual AMD patients. Briefly, we report significant improvement in cell survival, mitochondrial health, and antioxidant potential in PU-91-treated AMD RPE cells compared to their untreated counterparts. In conclusion, this study identifies PU 91 as a therapeutic candidate drug for AMD and repurposing of PU-91 will be a smoother transition from lab bench to clinic since the pharmacological profiles of PU-91 have been examined already.
- Published
- 2019
34. Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae
- Author
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George, Jack, Tuomela, Tea, Kemppainen, Esko, Nurminen, Antti, Braun, Samuel, Yalgin, Cagri, Jacobs, Howard T., Centre of Excellence in Stem Cell Metabolism, Nutrient sensing laboratory, Institute of Biotechnology, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, Laboratoriopalvelut - Laboratory Services, and Tampere University
- Subjects
DICHLOROACETATE ,protein synthesis ,Biolääketieteet - Biomedicine ,translation ,TRANSGENIC RNAI ,larva ,Pyruvic Acid ,Animals ,Drosophila Proteins ,BIOSYNTHESIS ,GENE-EXPRESSION ,MELANOGASTER ,Gene Expression Regulation, Developmental ,ALTERNATIVE OXIDASE ,Mitochondria ,mitochondria ,MODEL ,lactic acidosis ,Drosophila melanogaster ,PLASMA-MEMBRANE ,CELLS ,1182 Biochemistry, cell and molecular biology ,ENZYMES ,respiration ,Research Paper - Abstract
The Drosophila bang-sensitive mutant tko25t, manifesting a global deficiency in oxidative phosphorylation due to a mitochondrial protein synthesis defect, exhibits a pronounced delay in larval development. We previously identified a number of metabolic abnormalities in tko25t larvae, including elevated pyruvate and lactate, and found the larval gut to be a crucial tissue for the regulation of larval growth in the mutant. Here we established that expression of wild-type tko in any of several other tissues of tko25t also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko25t, producing developmental delay and bang-sensitivity. These findings imply the existence of a systemic signal regulating growth in response to mitochondrial dysfunction. Drugs and RNAi-targeted on pyruvate metabolism interacted with tko25t in ways that implicated pyruvate or one of its metabolic derivatives in playing a central role in generating such a signal. RNA-seq revealed that dietary pyruvate-induced changes in transcript representation were mostly non-coherent with those produced by tko25t or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level.
- Published
- 2019
35. Method for making thin carbon foam electrodes
- Author
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Morrison, Robert [Modesto, CA]
- Published
- 1999
36. Abstracts of papers presented at the joint meeting of the American Society for Cell Biology and the American Society for Biochemistry and Molecular Biology. 29 January-2 February 1989, San Francisco, California
- Subjects
Biochemical Phenomena ,Cells ,Animals ,Humans ,Biochemistry ,Molecular Biology ,Cell Physiological Phenomena ,Subcellular Fractions - Published
- 1988
37. Papers presented at the 1983 thirty-sixth annual meeting of the Japan Society for Cell Biology held in Kyoto, December 5-7
- Subjects
Cells ,Cytological Techniques ,Animals ,Humans ,In Vitro Techniques ,Cell Physiological Phenomena - Published
- 1983
38. Abstracts of papers presented at the twenty-third annual meeting: the American Society for Cell Biology. San Antonio, Texas, 29 November-3 December 1983
- Subjects
Cells ,Animals ,Humans ,Cell Physiological Phenomena ,Subcellular Fractions - Published
- 1983
39. Abstracts of papers presented at the twenty-ninth annual meeting of the American Society for Cell Biology. 5-9 November 1989, Houston, Texas
- Subjects
Biochemical Phenomena ,Cells ,Animals ,Humans ,Biochemistry ,Molecular Biology ,Cell Physiological Phenomena - Published
- 1989
40. Papers presented at the forty-second annual meeting of the Japan Society for Cell Biology. Kyoto, 25-27 October 1989. Abstracts
- Subjects
Cells ,Animals ,Humans ,Cell Physiological Phenomena - Published
- 1989
41. Abstracts of papers presented at the twenty-seventh annual meeting of the American Society for Cell Biology. 16-20 November 1987, St. Louis, Missouri
- Subjects
Cells ,Animals ,Humans ,Cell Physiological Phenomena ,Subcellular Fractions - Published
- 1987
42. Abstracts of papers presented at the twenty-fourth annual meeting. The American Society for Cell Biology. Kansas City, Missouri, 12-16 November 1984
- Subjects
Cells ,Animals ,Humans ,Cell Physiological Phenomena ,Subcellular Fractions - Published
- 1984
43. Gene‐Hydrogel Microenvironment Regulates Extracellular Matrix Metabolism Balance in Nucleus Pulposus
- Author
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Dandan Zheng, Lianfu Deng, Wei Chen, Hongxing Shen, Hao Chen, Wenguo Cui, Hongbo Zhang, Yuhui Zhang, Hélder A. Santos, Division of Pharmaceutical Chemistry and Technology, Helsinki One Health (HOH), Drug Research Program, and Nanomedicines and Biomedical Engineering
- Subjects
General Chemical Engineering ,extracellular matrix ,116 Chemical sciences ,General Physics and Astronomy ,Medicine (miscellaneous) ,02 engineering and technology ,Matrix metalloproteinase ,010402 general chemistry ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Extracellular matrix ,DELIVERY ,REGENERATION ,microRNA ,Gene expression ,IMPROVES ,General Materials Science ,gene-hydrogel microenvironment ,BIOMATERIALS ,lcsh:Science ,hydrogels ,gene‐hydrogel microenvironment ,INTERVERTEBRAL DISC ,Full Paper ,Chemistry ,Regeneration (biology) ,General Engineering ,technology, industry, and agriculture ,Transfection ,Full Papers ,DEGENERATION ,021001 nanoscience & nanotechnology ,gene therapy ,0104 chemical sciences ,Cell biology ,MODEL ,Intervertebral disk ,317 Pharmacy ,Self-healing hydrogels ,CELLS ,Agomir ,lcsh:Q ,221 Nano-technology ,0210 nano-technology - Abstract
Gene therapy provides an ideal potential treatment for intervertebral disk degeneration by delivering synthetic microRNAs (miRNAs) to regulate the gene expression levels. However, it is very challenging to deliver miRNAs directly, which leads to inactivation, low transfection efficiency, and short half‐life. Here, Agomir is loaded in hydrogel to construct a gene‐hydrogel microenvironment for regulating the synthesis/catabolism balance of the tissue extracellular matrix (ECM) to treat degenerative diseases. Agomir is a cholesterol‐, methylation‐, and phosphorothioate‐modified miRNA, which can mimic the function of miRNA to regulate the expression of the target gene. Agomir874 that mimics miRNA874 is synthesized to down regulate the expression of matrix metalloproteinases (MMPs) in nucleus pulposus (NP). At the same time, a polyethylene glycol (PEG) hydrogel is synthesized through Ag‐S coordination of 4‐arm PEG‐SH and silver ion solution, which has injectable, self‐healing, antimicrobial, degradable, and superabsorbent properties and matches perfectly with the mechanism of intervertebral disk. By delivering Agomir‐loaded PEG‐hydrogel to a degenerative intervertebral disk, a gene‐hydrogel microenvironment is constructed in situ, which reduces the expression of MMPs, regulates the synthesis/catabolism balance of ECM in the NP of the intervertebral disk, and improves the tissue microenvironment regeneration., In degenerative diseases, microenvironment deterioration is often followed by a vicious circle of cell death and aggravation of microenvironment deterioration. To break the cycle, a gene‐hydrogel microenvironment is constructed in situ, which regulates the synthesis/catabolism balance of extracellular matrix in the nucleus pulposus of the intervertebral disk and improves the tissue microenvironment regeneration.
- Published
- 2020
44. PI3K inhibition as a novel therapeutic strategy for neoadjuvant chemoradiotherapy resistant oesophageal adenocarcinoma
- Author
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Sarah D. Edge, Isaline Renard, Stephen J. Archibald, Andrew W Beavis, Chun Li, Emily Pyne, Hannah Moody, Christopher Cawthorne, Stephen G. Maher, Isabel M. Pires, and Rajarshi Roy
- Subjects
EXPRESSION ,Oncology ,medicine.medical_specialty ,Standard of care ,Esophageal Neoplasms ,medicine.medical_treatment ,Treatment outcome ,GDC-0941 ,MEDLINE ,Oesophageal adenocarcinoma ,Adenocarcinoma ,PATHWAY ,ACTIVATION ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Neoadjuvant therapy ,030304 developmental biology ,Therapeutic strategy ,0303 health sciences ,Science & Technology ,Full Paper ,CHEMORESISTANCE ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Radiology, Nuclear Medicine & Medical Imaging ,PATHOLOGICAL RESPONSE ,General Medicine ,CANCER ,Neoadjuvant Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,CELLS ,METASTASIS ,Female ,business ,Life Sciences & Biomedicine ,PREOPERATIVE CHEMORADIOTHERAPY ,Neoadjuvant chemoradiotherapy - Abstract
Objective: Neoadjuvant chemoradiotherapy (neo-CRT) prior to surgery is the standard of care for oesophageal adenocarcinoma (OAC) patients. Unfortunately, most patients fail to respond to treatment. MiR-187 was previously shown to be downregulated in neo-CRT non-responders, whist in vitro miR-187 overexpression enhanced radiosensitivity and upregulated PTEN. This study evaluates the role of miR-187 and downstream PI3K signalling in radiation response in OAC. Methods: The effect of miR-187 overexpression on downstream PI3K signalling was evaluated in OAC cell lines by qPCR and Western blotting. PTEN expression was analysed in OAC pre-treatment biopsies of neo-CRT responders and non-responders. Pharmacological inhibition of PI3K using GDC-0941 was evaluated in combination with radiotherapy in two-dimensional and three-dimensional OAC models in vitro and as a single agent in vivo. Radiation response in vitro was assessed via clonogenic assay. Results: PTEN expression was significantly decreased in neo-CRT non-responders. MiR-187 overexpression significantly upregulated PTEN expression and inhibited downstream PI3K signalling in vitro. GDC-0941 significantly reduced viability and enhanced radiation response in vitro and led to tumour growth inhibition as a single agent in vivo. Conclusion: Targeting of PI3K signalling is a promising therapeutic strategy for OAC patients who have repressed miR-187 expression and do not respond to conventional neo-CRT. Advances in knowledge: This is the first study evaluating the effect of PI3K inhibition on radiosensitivity in OAC, with a particular focus on patients that do not respond to neo-CRT. We have shown for the first time that targeting of PI3K signalling is a promising alternative therapeutic strategy for OAC patients who do not respond to conventional neo-CRT.
- Published
- 2021
45. Resonant Switching Cell Model for High-Frequency Single-Ended Resonant Converters.
- Author
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Lee, Kyung-Hwan and Ha, Jung-Ik
- Subjects
ZERO voltage switching ,ELECTRIC inductance ,CELLS ,DC-to-DC converters - Abstract
This paper proposes a resonant switching cell model to analyze and design the single-ended resonant dc–dc converters. The single-ended zero-voltage switching (ZVS) converters such as the Class E converter are efficient for megahertz switching because they feature low turn-on and turn-off switching losses. Also, they use only a ground-referenced switch, allowing a simple gate drive circuit. In this paper, we investigate the single-ended resonant converter with the small input inductance, whereas the conventional Class E converter has a large input inductance. The main contribution of this paper is to propose the resonant switching cell as an analytic model that simplifies the analysis and the design of the resonant dc–dc converters. Furthermore, this paper presents the design method of the resonant switching cell model for minimizing the resonant current magnitude and conduction loss while the converter maintains ZVS property. The experimental results from a 10-MHz GaN-based prototype demonstrate the feasibility and effectiveness of the analysis and design based on the proposed resonant switching cell model. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
46. Fourier transform infrared spectroscopic imaging of colon tissues: evaluating the significance of amide I and C–H stretching bands in diagnostic applications with machine learning
- Author
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Robert D. Goldin, Martha Z. Vardaki, Cai Li Song, and Sergei G. Kazarian
- Subjects
Infrared ,K-means clustering ,02 engineering and technology ,computer.software_genre ,01 natural sciences ,Biochemistry ,09 Engineering ,COLORECTAL-CANCER ,Fourier transform infrared spectroscopic imaging ,Analytical Chemistry ,Machine Learning ,Fingerprint ,Correcting lens approach ,Spectroscopy, Fourier Transform Infrared ,k-means clustering ,Prognosis ,021001 nanoscience & nanotechnology ,Random forest ,Chemistry ,Physical Sciences ,Colonic Neoplasms ,symbols ,03 Chemical Sciences ,0210 nano-technology ,Life Sciences & Biomedicine ,Research Paper ,Biochemistry & Molecular Biology ,TRANSMISSION ,Colon ,Mie scattering ,Machine learning ,Biochemical Research Methods ,symbols.namesake ,SPECTRA ,Fourier transform infrared spectroscopy ,Random forest supervised classification ,Science & Technology ,Scattering ,business.industry ,Chemistry, Analytical ,010401 analytical chemistry ,06 Biological Sciences ,0104 chemical sciences ,FT-IR ,Colon polyps and cancer ,Fourier transform ,CELLS ,Artificial intelligence ,business ,computer - Abstract
Fourier transform infrared (FTIR) spectroscopic imaging of colon biopsy tissues in transmission combined with machine learning for the classification of different stages of colon malignancy was carried out in this study. Two different approaches, an optical and a computational one, were applied for the elimination of the scattering background during the measurements and compared with the results of the machine learning model without correction for the scattering. Several different data processing pathways were implemented in order to obtain a high accuracy of the prediction model. This study demonstrates, for the first time, that C–H stretching and amide I bands are of little to no significance in the classification of the colon malignancy, based on the Gini importance values by random forest (RF). The best prediction outcome is found when supervised RF classification was carried out in the fingerprint region of the spectral data between 1500 and 1000 cm−1 (excluding the contribution of amide I and II bands). An overall prediction accuracy higher than 90% is achieved through the RF. The results also show that dysplastic and hyperplastic tissues are well distinguished. This leads to the insight that the important differences between hyperplastic and dysplastic colon tissues lie within the fingerprint region of FTIR spectra. In this study, computational correction performed better than optical correction, but the findings show that the disease states of colon biopsies can be distinguished effectively without elimination of Mie scattering effect. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00216-019-02069-6) contains supplementary material, which is available to authorized users.
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- 2019
47. Haematological quality and age of donor blood issued for paediatric transfusion to four hospitals in sub‐Saharan Africa
- Author
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Uyoga, S, Mpoya, A, Olupot-Olupot, P, Kiguli, S, Opoka, R, Engoru, C, Mallewa, M, Kennedy, N, M'Biya, B, Kyeyune, D, Wabwire, B, Bates, I, Gibb, DM, Walker, AS, George, E, Williams, T, Maitland, K, Medical Research Council (MRC), Medical Research Council, Wellcome Trust, MRC Australia, Engineering & Physical Science Research Council (EPSRC), and Imperial College London
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Quality Control ,haematocrit ,Malawi ,Quality Assurance, Health Care ,Blood Donors ,Pediatrics ,Specimen Handling ,Hemoglobins ,donor blood pack ,Refrigeration ,Humans ,Transfusion Medicine and New Therapies ,Blood Transfusion ,Uganda ,Child ,blood transfusion services ,Randomized Controlled Trials as Topic ,Original Paper ,anaemia ,Science & Technology ,Reproducibility of Results ,1103 Clinical Sciences ,Anemia ,Hematology ,haemoglobin ,Hospitals ,Cardiovascular System & Hematology ,Hematocrit ,CELLS ,Blood Banks ,Corrigendum ,Life Sciences & Biomedicine - Abstract
Background and Objectives Paediatric blood transfusion for severe anaemia in hospitals in sub‐Saharan Africa remains common. Yet, reports describing the haematological quality of donor blood or storage duration in routine practice are very limited. Both factors are likely to affect transfusion outcomes. Materials and Methods We undertook three audits examining the distribution of pack types, haematological quality and storage duration of donor blood used in a paediatric clinical trial of blood at four hospitals in Africa (Uganda and Malawi). Results The overall distribution of whole blood, packed cells (plasma‐reduced by centrifugation) and red cell concentrates (RCC) (plasma‐reduced by gravity‐dependent sedimentation) used in a randomised trial was 40·7% (N = 1215), 22·4% (N = 669) and 36·8% (N = 1099), respectively. The first audit found similar median haematocrits of 57·0% (50·0,74·0), 64·0% (52·0,72·5; P = 0·238 vs. whole blood) and 56·0% (48·0,67·0; P = 0·462) in whole blood, RCC and packed cells, respectively, which resulted from unclear pack labelling by blood transfusion services (BTS). Re‐training of the BTS, hospital blood banks and clinical teams led to, in subsequent audits, significant differences in median haematocrit and haemoglobins across the three pack types and values within expected ranges. Median storage duration time was 12 days (IQR: 6, 19) with 18·2% (537/2964) over 21 days in storage. Initially, 9 (2·8%) packs were issued past the recommended duration of storage, dropping to 0·3% (N = 7) in the third audit post‐training. Conclusion The study highlights the importance of close interactions and education between BTS and clinical services and the importance of haemovigilance to ensure safe transfusion practice.
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- 2019
48. Falling from grace: HPRT is not suitable as an endogenous control for cancer-related studies
- Author
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Kim L. O'Neill, Stephen R. Piccolo, Michelle H. Townsend, Abigail M. Felsted, Richard A. Robison, and Zac E. Ence
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0301 basic medicine ,Cancer Research ,Guanine ,cells ,genetic processes ,Endogeny ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,stomatognathic system ,medicine ,Inosine ,Nucleotide salvage ,nutritional and metabolic diseases ,Cancer ,medicine.disease ,Housekeeping gene ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,Housekeeping ,Biochemistry ,chemistry ,Hypoxanthine-guanine phosphoribosyltransferase ,030220 oncology & carcinogenesis ,Molecular Medicine ,Research Paper ,medicine.drug - Abstract
HPRT is a housekeeping enzyme involved in recycling guanine and inosine in the purine salvage pathway. As a housekeeping gene, HPRT has been widely used as an endogenous control for molecular studies evaluating changes in gene expression. Yet, recent evidence has shown that HPRT exhibits high variability within malignant samples. We designed this study to determine whether this observed upregulation is consistently found, therefore rendering hprt an unsuitable normalization control in cancer. Utilizing protein and RNA-seq expression, we found that malignant and normal patient samples vary significantly both within the same tissue type and across organ sites. Upon staining for HPRT via immunohistochemistry, we found that expression is highly variable in malignant samples (Lung; 89.2–111.8, Breast; 66.7–98.3, Colon; 85.3–129.7, Prostate; 90.8–155.4, Pancreas; 74.1–132.1). Similarly, we observed high variability across cell lines via western blotting (p
- Published
- 2019
49. Manual braille writer
- Author
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Turner, Joe [Knoxville, TN]
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- 1992
50. Self-Orienting Hydrogel Micro-Buckets as Novel Cell Carriers
- Author
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Jan H. van Esch, Yiming Wang, Dadong Yan, Kai Zhang, Meng Zhao, Eduardo Mendes, Benjamin Klemm, Qian Liu, and Serhii Mytnyk
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Materials science ,Cells ,cell carriers ,Microfluidics ,Cell ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,Smart material ,01 natural sciences ,Catalysis ,medicine ,Humans ,Soft matter ,Self orientation ,soft matter ,010405 organic chemistry ,Communication ,RGD peptide ,Hydrogels ,General Medicine ,General Chemistry ,021001 nanoscience & nanotechnology ,Communications ,0104 chemical sciences ,Soft Matter | Hot Paper ,medicine.anatomical_structure ,Self-healing hydrogels ,self-orientation ,0210 nano-technology - Abstract
Hydrogel microparticles are important in materials engineering, but their applications remain limited owing to the difficulties associated with their manipulation. Herein, we report the self‐orientation of crescent‐shaped hydrogel microparticles and elucidate its mechanism. Additionally, the microparticles were used, for the first time, as micro‐buckets to carry living cells. In aqueous solution, the microparticles spontaneously rotated to a preferred orientation with the cavity facing up. We developed a geometric model that explains the self‐orienting behavior of crescent‐shaped particles by minimizing the potential energy of this specific morphology. Finally, we selectively modified the particles’ cavities with RGD peptide and exploited their preferred orientation to load them with living cells. Cells could adhere, proliferate, and be transported and released in vitro. These micro‐buckets hold a great potential for applications in smart materials, cell therapy, and biological engineering.
- Published
- 2018
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