8,046 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
-
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. 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
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. Cells Best Paper Award 2015.
- Author
-
Kalyuzhny, Alexander E.
- Subjects
- *
CELLS , *HUMAN research subjects ,RESEARCH awards - Published
- 2015
- Full Text
- View/download PDF
21. 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
22. Reduced visual contrast suppression during major depressive episodes
- Author
-
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
23. Evidence for a Pronounced Secretion of Cyclic AMP by Tetrahymena
- Author
-
Nandini-Kishore, S. G. and Thompson,, G. A.
- Published
- 1980
24. Intrarenal arteriosclerosis and telomere attrition associate with dysregulation of the cholesterol pathway
- Author
-
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
25. Prognostic significance of Spinster homolog gene family in acute myeloid leukemia
- Author
-
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
26. Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae
- Author
-
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
27. Method for making thin carbon foam electrodes
- Author
-
Morrison, Robert [Modesto, CA]
- Published
- 1999
28. Gene‐Hydrogel Microenvironment Regulates Extracellular Matrix Metabolism Balance in Nucleus Pulposus
- Author
-
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
29. PI3K inhibition as a novel therapeutic strategy for neoadjuvant chemoradiotherapy resistant oesophageal adenocarcinoma
- Author
-
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
30. Resonant Switching Cell Model for High-Frequency Single-Ended Resonant Converters.
- Author
-
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
31. Haematological quality and age of donor blood issued for paediatric transfusion to four hospitals in sub‐Saharan Africa
- Author
-
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
- Subjects
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.
- Published
- 2019
32. Manual braille writer
- Author
-
Turner, Joe [Knoxville, TN]
- Published
- 1992
33. Micropatterning of planar metal electrodes by vacuum filling microfluidic channel geometries
- Author
-
Stelios, Chatzimichail, Pashiini, Supramaniam, Oscar, Ces, Ali, Salehi-Reyhani, and Rasponi, M
- Subjects
MICROELECTRODES ,Microfluidic Channel ,Science & Technology ,DEVICES ,Science ,FABRICATION ,Electrical Lysis ,Polydimethylsiloxane (PDMS) ,Multidisciplinary Sciences ,MOLECULES ,Laser Micromachining ,SYSTEMS ,PDMS ,CHEMICAL-ANALYSIS ,CELLS ,PAPER ,Science & Technology - Other Topics ,Medicine ,BIOSENSORS ,Microwell Array - Abstract
We present a simple, facile method to micropattern planar metal electrodes defined by the geometry of a microfluidic channel network template. By introducing aqueous solutions of metal into reversibly adhered PDMS devices by desiccation instead of flow, we are able to produce difficult to pattern “dead end” or discontinuous features with ease. We characterize electrodes fabricated using this method and perform electrical lysis of mammalian cancer cells and demonstrate their use as part of an antibody capture assay for GFP. Cell lysis in microwell arrays is achieved using the electrodes and the protein released is detected using an antibody microarray. We show how the template channels used as part of the workflow for patterning the electrodes may be produced using photolithography-free methods, such as laser micromachining and PDMS master moulding, and demonstrate how the use of an immiscible phase may be employed to create electrode spacings on the order of 25–50 μm, that overcome the current resolution limits of such methods. This work demonstrates how the rapid prototyping of electrodes for use in total analysis systems can be achieved on the bench with little or no need for centralized facilities.
- Published
- 2018
34. Early growth response 2 (EGR2) is a novel regulator of the senescence programme
- Author
-
Eleanor J. Tyler, Ryan Wallis, Robert Lowe, Martha R. Stampfer, Cleo L. Bishop, Bethany K. Hughes, Ana Gutierrez del Arroyo, Michael P. Philpott, James C. Garbe, and Jim Koh
- Subjects
0301 basic medicine ,Aging ,senescence ,Regulator ,p16 ,Medical and Health Sciences ,Retinoblastoma Protein ,0302 clinical medicine ,Transcription (biology) ,2.1 Biological and endogenous factors ,cellular senescence ,RNA, Small Interfering ,transcription factor ,Cells, Cultured ,education.field_of_study ,Cultured ,Biological Sciences ,Ink4a ,Phenotype ,Mammary Glands ,Cell biology ,Up-Regulation ,Gene Knockdown Techniques ,EGR2 ,Human ,Protein Binding ,Senescence ,Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,Adolescent ,Cells ,1.1 Normal biological development and functioning ,Population ,Biology ,Small Interfering ,03 medical and health sciences ,Young Adult ,Genetics ,Humans ,replicative lifespan ,education ,Mammary Glands, Human ,Transcription factor ,Cyclin-Dependent Kinase Inhibitor p16 ,Early Growth Response Protein 2 ,Original Paper ,Promoter ,Epithelial Cells ,Cell Biology ,Original Articles ,Fibroblasts ,030104 developmental biology ,Ageing ,RNA ,Tumor Suppressor Protein p53 ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Senescence, a state of stable growth arrest, plays an important role in ageing and age‐related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up‐regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down‐regulates p16 levels and increases the pool of p16− p21− ‘reversed’ cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence., Deep senescence is reversible in normal adult human fibroblasts. Loss of early growth response 2 (EGR2) reverses epithelial and fibroblast senescence. EGR2 levels are up‐regulated in multiple models of senescence and prolonged expression of EGR2 induces fibroblast senescence. Early growth response 2 (EGR2) is a novel master transcriptional regulator of the INK/ARF locus and the senescence programme.
- Published
- 2021
35. Control of Free Methionine Production in Wild Type and Ethionine-Resistant Mutants of Chlorella sorokiniana
- Author
-
Owens, Lowell D.
- Published
- 1974
36. hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts
- Author
-
Yang Xu, Jingjin He, Dilyana Todorova, Jingfeng Liu, Yue Zhang, Xuemei Fu, and Qu Chen
- Subjects
Graft Rejection ,0301 basic medicine ,Adoptive cell transfer ,lcsh:Medicine ,Cell Communication ,Regenerative Medicine ,Regenerative medicine ,Dendritic cells ,Immune tolerance ,Cell therapy ,Mice ,0302 clinical medicine ,Smooth Muscle ,Myocytes, Cardiac ,Cells, Cultured ,lcsh:R5-920 ,Cultured ,Graft Survival ,General Medicine ,Regulatory T cells ,Allografts ,Adoptive Transfer ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Human embryonic stem cells ,Development of treatments and therapeutic interventions ,lcsh:Medicine (General) ,Cardiac ,Research Paper ,Cells ,Myocytes, Smooth Muscle ,Clinical Sciences ,chemical and pharmacologic phenomena ,Germ layer ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Immunophenotyping ,Immunomodulation ,03 medical and health sciences ,Immune system ,Animals ,Humans ,Stem Cell Research - Embryonic - Human ,Myocytes ,Transplantation ,5.2 Cellular and gene therapies ,lcsh:R ,Stem Cell Research ,Embryonic stem cell ,030104 developmental biology ,Immune system humanized mice ,Immunology ,Humanized mouse ,Allogeneic immune rejection ,Biomarkers - Abstract
Background With their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts. Methods We derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs. The expression of DC-related genes and surface molecules was evaluated, as well as their DCL capacity to stimulate allogeneic T cells and induce regulatory T (Treg) cells in vitro. Using an immune system humanized mouse model, we investigated whether the adoptive transfer of CP DCLs can induce long-term immune tolerance of parental hESC-derived smooth muscle and cardiomyocyte allografts. Findings CP DCLs can maintain immune suppressive properties after robust inflammatory stimulation and induce Treg cells. While CP DCLs survive transiently in vivo, they induce long-term immune tolerance of parental hESC-derived allografts. Interpretation This strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs, and thus it presents a safe and effective approach to induce immune tolerance of allografts derived from any clinically approved hESC line. Funding NSFC, leading talents of Guangdong Province Program (No. 00201516), Key R&D Program of Guangdong Province (2019B020235003), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), National High-tech R&D Program (863 Program No. 2015AA020310), Shenzhen “Sanming” Project of Medicine (SZSM201602102), Development and Reform Commission of Shenzhen Municipality (S2016004730009), CIRM (DISC2–10559).
- Published
- 2020
37. Critics blast ‘premature’ paper on adult stem cells.
- Author
-
Schiermeier, Quirin and Leeb, Martin
- Subjects
- *
STEM cells , *CELLS , *RESEARCH , *BIOLOGISTS , *SCIENCE - Abstract
Reports on the controversy created by a stem cell paper by a team of German biologists published in the 2004 issue of "Applied Physics". Public announcement of the research as a breakthrough in adult stem-cell technology; Protests against research using embryonic lines; Criticisms of the research.
- Published
- 2004
- Full Text
- View/download PDF
38. Static magnetic fields as a factor in modification of tissue and cell structure: a review.
- Author
-
Saletnik, Bogdan, Puchalska-Sarna, Anna, Saletnik, Aneta, Lipa, Tomasz, Dobrzański Jr., Bohdan, and Puchalski, Czesław
- Subjects
MAGNETIC fields ,ION channels ,CELL anatomy ,MAGNETIC field effects ,PLANT plasma membranes ,CANCER cell proliferation - Abstract
This review is intended to contribute to the evidence of the effects of static magnetic field on cells and tissue, as well as to present research results that will elucidate the complex matters involved in the formation and remodeling of cells. The cell characteristics studied in the papers that are reviewed include cell viability and proliferation, aggregation and their differentiation, structure and membrane potential. A moderate static magnetic field in the most commonly used range of 2-80 mT has potential application in the formation and remodeling of plant and human cells. However, in the case of cancer cells, the range of fields commonly used was 0.2-9 T. Magnetism promotes changes in plant cell growth, which prompts the cell to proliferate, thereby ensuring an increased rate of biomass production. Some researches presented the enhancement of the differentiation of plant cells and skeletal muscle tissue by over 30% at 80 mT static magnetic field. Changes in the cell cycle and growth reflect directly on the cell number and viability and provide useful information to detect modifications in the cell machinery. Static magnetic field, depending on its intensity, enhances cell proliferation and thus may improve, among other processes, tissue regeneration, wound healing and the inhibition of cancer cell proliferation. Researchers showed, among other things, that cells under the influence of static magnetic field changed their shape, had a larger chloroplast, stiffer cell wall, density of the cytoskeleton and cytoplasm contained several mitochondria. Numerous studies also discussed the behavior of the cell membrane of plant and animal organisms, including humans, under the influence of an static magnetic field. The effects of static magnetic field on the cell membrane of plant and human cells were similar. The research results indicate that static magnetic fields can significantly change membrane depolarization and its potential that regulates ion movement and thus can have a significant impact on the properties and biological functionality of the cell. Studies have shown that continuous application of static magnetic field caused deformation and damage of cell membrane. Based on the theoretical analyses presented also in this review, it can be concluded that static magnetic field affects cells and tissue, giving them changes in properties and behaviors and modulates, e.g. in the activity of ion channels. Thus it may produce effects leading to changes in the functioning of the cell. It is possible to formulate directions for further research aimed at using static magnetic fields for the non-invasive remodeling and formation of plant and human cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Functional expression and pharmacological modulation of TRPM3 in human sensory neurons
- Author
-
Katrien De Clercq, Patrick Chaltin, Yannick Miron, Laura Vangeel, Catherine M. Verfaillie, Paul E. Miller, Thomas Voets, Melissa Benoit, and Joris Vriens
- Subjects
0301 basic medicine ,Agonist ,Patch-Clamp Techniques ,Sensory Receptor Cells ,medicine.drug_class ,INHIBITION ,TRPM Cation Channels ,Sensory system ,ION-CHANNEL ,GUIDE ,03 medical and health sciences ,Transient receptor potential channel ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Calcium imaging ,Dorsal root ganglion ,Ganglia, Spinal ,REVEALS ,medicine ,TRPM3 ,Animals ,Humans ,Pharmacology & Pharmacy ,COLD ,Pharmacology ,Science & Technology ,RECEPTOR ,Chemistry ,PAIN ,Research Papers ,NOCICEPTION ,DAMGO ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Hyperalgesia ,CELLS ,Nociceptor ,Neuroscience ,Life Sciences & Biomedicine ,030217 neurology & neurosurgery - Abstract
BACKGROUND AND PURPOSE: The transient receptor potential (TRP) ion channel TRPM3 functions as a noxious heat sensor, plays a key role in acute pain sensation and inflammatory hyperalgesia in rodents. Despite its potential as a novel analgesic drug target, little is known about the expression, function and modulation in the humans. EXPERIMENTAL APPROACH: We studied TRPM3 in freshly isolated human dorsal root ganglion (hDRG) neurons and human stem cell-derived sensory (hSCDS) neurons. Expression was analysed at the mRNA level using RT-qPCR. Channel function was assessed using Fura-2-based calcium imaging and whole-cell patch-clamp recordings. KEY RESULTS: TRPM3 was detected at the mRNA level in both hDRG and hSCDS neurons. The TRPM3 agonists pregnenolone sulphate (PS) and CIM0216 evoked robust intracellular Ca2+ responses in 52% of hDRG and 58% of hSCDS neurons. Whole-cell patch-clamp recordings in hSCDS neurons revealed pregnenolone sulphate (PS)- and CIM0216-evoked currents exhibiting the characteristic current-voltage relation of TRPM3. PS-induced calcium responses in hSCDS neurons were reversed in a dose-dependent manner by the flavonoid isosakuranetin and by antiseizure drug primidone. Finally, the μ-opioid receptor agonist DAMGO and the GABAB receptor agonist baclofen inhibited PS-evoked TRPM3 responses in a subset of hSCDS neurons. CONCLUSION AND IMPLICATIONS: These results provide the first direct evidence of functional expression of the pain receptor TRPM3 in human sensory neurons, largely mirroring the channel's properties observed in mouse sensory neurons. hSCDS neurons represent a valuable and readily accessible in vitro model to study TRPM3 regulation and pharmacology in a relevant human cellular context. ispartof: BRITISH JOURNAL OF PHARMACOLOGY vol:177 issue:12 pages:2683-2695 ispartof: location:England status: published
- Published
- 2020
40. miR‐181a negatively modulates synaptic plasticity in hippocampal cultures and its inhibition rescues memory deficits in a mouse model of Alzheimer’s disease
- Author
-
Masashi Kitazawa, Frank M. LaFerla, Carlos J. Rodriguez-Ortiz, Alessandra C. Martini, David Baglietto-Vargas, Laura Trujillo-Estrada, Stefania Forner, Gilberto Aleph Prieto, and Carl W. Cotman
- Subjects
0301 basic medicine ,Male ,Aging ,long‐term potentiation ,Long-Term Potentiation ,Hippocampus ,amyloid‐beta oligomers ,Hippocampal formation ,Neurodegenerative ,Inbred C57BL ,Alzheimer's Disease ,Medical and Health Sciences ,Mice ,0302 clinical medicine ,Receptors ,AMPA ,2.1 Biological and endogenous factors ,AMPA receptor ,Aetiology ,Cells, Cultured ,Neurons ,Translin ,Cultured ,RNA-Binding Proteins ,Long-term potentiation ,Biological Sciences ,spatial memory ,microRNAs ,Up-Regulation ,DNA-Binding Proteins ,GluA2 ,Neurological ,trax ,amyloid-beta oligomers ,Biotechnology ,Signal Transduction ,Cells ,1.1 Normal biological development and functioning ,Biology ,Transfection ,03 medical and health sciences ,Downregulation and upregulation ,Underpinning research ,Alzheimer Disease ,Memory ,microRNA ,Acquired Cognitive Impairment ,Animals ,Learning ,Receptors, AMPA ,Original Paper ,Memory Disorders ,Amyloid beta-Peptides ,Animal ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Cell Biology ,translin/trax ,Brain Disorders ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Synaptic plasticity ,Disease Models ,Synapses ,Dementia ,translin ,Neuroscience ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
MicroRNAs play a pivotal role in rapid, dynamic, and spatiotemporal modulation of synaptic functions. Among them, recent emerging evidence highlights that microRNA‐181a (miR‐181a) is particularly abundant in hippocampal neurons and controls the expression of key plasticity‐related proteins at synapses. We have previously demonstrated that miR‐181a was upregulated in the hippocampus of a mouse model of Alzheimer's disease (AD) and correlated with reduced levels of plasticity‐related proteins. Here, we further investigated the underlying mechanisms by which miR‐181a negatively modulated synaptic plasticity and memory. In primary hippocampal cultures, we found that an activity‐dependent upregulation of the microRNA‐regulating protein, translin, correlated with reduction of miR‐181a upon chemical long‐term potentiation (cLTP), which induced upregulation of GluA2, a predicted target for miR‐181a, and other plasticity‐related proteins. Additionally, Aβ treatment inhibited cLTP‐dependent induction of translin and subsequent reduction of miR‐181a, and cotreatment with miR‐181a antagomir effectively reversed the effects elicited by Aβ but did not rescue translin levels, suggesting that the activity‐dependent upregulation of translin was upstream of miR‐181a. In mice, a learning episode markedly decreased miR‐181a in the hippocampus and raised the protein levels of GluA2. Lastly, we observed that inhibition of miR‐181a alleviated memory deficits and increased GluA2 and GluA1 levels, without restoring translin, in the 3xTg‐AD model. Taken together, our results indicate that miR‐181a is a major negative regulator of the cellular events that underlie synaptic plasticity and memory through AMPA receptors, and importantly, Aβ disrupts this process by suppressing translin and leads to synaptic dysfunction and memory impairments in AD., In the hippocampus, neuronal stimulation produces upregulation of translin, reduction of miR‐181a, and an increase in the protein levels of its target GluA2 leading to synaptic plasticity. This plasticity mechanism is impaired by amyloid‐beta (Aβ) toxic species.
- Published
- 2020
41. Echinococcus multilocularis (Cestoda, Cyclophyllidea, Taeniidae): functional ultrastructure of the penetration glands and nerve cells within the oncosphere
- Author
-
Jordi Miquel, Samira Azzouz-Maache, Zdzisław Świderski, Anne-Françoise Pétavy, and Universitat de Barcelona
- Subjects
0301 basic medicine ,Cèl·lules ,Cells ,Cestoda ,Functional ultrastructure ,Biology ,03 medical and health sciences ,Oncospheral nerve cells ,Echinococcosis ,Animals ,Tapeworms ,Oncospheral penetration glands ,Cell Nucleus ,Neurons ,Original Paper ,General Veterinary ,Cestodes ,Oncosphere ,Taeniid cestodes ,General Medicine ,Viral tegument ,030108 mycology & parasitology ,biology.organism_classification ,Cell biology ,Mitochondria ,Infectious Diseases ,Cytoplasm ,Insect Science ,Ultrastructure ,Taeniidae ,Cytochemistry ,Parasitology ,Echinococcus multilocularis ,Cyclophyllidea ,Ribosomes - Abstract
The fine structure of the infective hexacanths of Echinococcus multilocularis was examined with particular emphasis on the functional ultrastructure of penetration glands and nerve cells directly involved in the mechanism of initial host infection. The oncosphere contains two types of penetration glands, PG1 and PG2, that differ slightly in size and form a large U-shaped bi-nucleated syncytial structure. The arms of each gland at each end of the U, directed towards the hook region, exit into the tegument peripheral layer between the median and lateral hook pairs. The lobate nuclei of PG1 and PG2 contain prominent spherical nucleoli surrounded by several large electron-dense islands of heterochromatin. The syncytial cytoplasm of both types of glands is rich in free ribosomes, polysomes, several mitochondria, and heavy accumulations of discoid secretory granules of moderate to high electron density. The secretory granules, sg1 and sg2, differ in their ultrastructure and electron density; the sg2 are much smaller and more flattened in shape. A common characteristic for sg1 and sg2, evident under high magnification, is their high electron density and discoidal shape, with two bi-concave surfaces. Both sg1 and sg2 are frequently grouped in characteristic parallel stacks, the “rouleau”-shaped assemblages with sometimes six to ten granules. Two nerve cells of neurosecretory type are situated in the central part of the hexacanth, each one in a deep U-shaped invagination between the two penetration glands. The nuclei of nerve cells contain several large heterochromatin islands closely adjacent to their nuclear membranes. Their cytoplasm is characterized by having membrane-bound, dense-cored neurosecretory-like granules not only in nerve cell perikarya but also in the elongated nerve processes frequently adjacent to gland arms and to both somatic or body musculature, including the complex system of hook muscles. The results of the present study, when supported with literature data on oncospheres of other cestode species, allow for a better understanding of the important role and coordinated functions of three structural components, i.e., oncospheral hooks, penetration glands, and nerve cells, in the mechanism of intermediate host infection. Presence or absence of nerve cells in oncospheres of various cestodes is reviewed, and perspectives on the value and application of research on functional morphology of oncospheres are discussed.
- Published
- 2018
42. High photon count rates improve the quality of super-resolution fluorescence fluctuation spectroscopy
- Author
-
Giulia Ossato, Iztok Urbančič, M. Julia Roberti, Erdinc Sezgin, Dilip Shrestha, B. Christoffer Lagerholm, Frederick Hecht, Christian Eggeling, Pablo Hernández-Varas, and Falk Schneider
- Subjects
Paper ,STED nanoscopy ,Photon ,Microscope ,Acoustics and Ultrasonics ,fluorescence correlation spectroscopy ,Fluorescence correlation spectroscopy ,Context (language use) ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,law.invention ,03 medical and health sciences ,law ,Stimulated emission ,Diffusion (business) ,membrane ,photon detection ,030304 developmental biology ,0303 health sciences ,diffusion ,STED microscopy ,Apical membrane ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Special Issue on Stimulated Emission Depletion Microscopy ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,cells ,0210 nano-technology ,Biological system - Abstract
Probing the diffusion of molecules has become a routine measurement across the life sciences, chemistry and physics. It provides valuable insights into reaction dynamics, oligomerisation, molecular (re-)organisation or cellular heterogeneities. Fluorescence correlation spectroscopy (FCS) is one of the widely applied techniques to determine diffusion dynamics in two and three dimensions. This technique relies on the temporal autocorrelation of intensity fluctuations but recording these fluctuations has thus far been limited by the detection electronics, which could not efficiently and accurately time-tag photons at high count rates. This has until now restricted the range of measurable dye concentrations, as well as the data quality of the FCS recordings, especially in combination with super-resolution stimulated emission depletion (STED) nanoscopy. Here, we investigate the applicability and reliability of (STED-)FCS at high photon count rates (average intensities of more than 1 MHz) using novel detection equipment, namely hybrid detectors and real-time gigahertz sampling of the photon streams implemented on a commercial microscope. By measuring the diffusion of fluorophores in solution and cytoplasm of live cells, as well as in model and cellular membranes, we show that accurate diffusion and concentration measurements are possible in these previously inaccessible high photon count regimes. Specifically, it offers much greater flexibility of experiments with biological samples with highly variable intensity, e.g. due to a wide range of expression levels of fluorescent proteins. In this context, we highlight the independence of diffusion properties of cytosolic GFP in a concentration range of approx. 0.01–1 µm. We further show that higher photon count rates also allow for much shorter acquisition times, and improved data quality. Finally, this approach also pronouncedly increases the robustness of challenging live cell STED-FCS measurements of nanoscale diffusion dynamics, which we testify by confirming a free diffusion pattern for a fluorescent lipid analogue on the apical membrane of adherent cells.
- Published
- 2019
- Full Text
- View/download PDF
43. HIV Activates the Tyrosine Kinase Hck to Secrete ADAM Protease-Containing Extracellular Vesicles
- Author
-
Tapio Kesti, Thomas Harrer, A.S. Baur, B. Simon, Jung-Hyun Lee, Kalle Saksela, Heiko Bruns, Christian Ostalecki, Zhe Zhao, Medicum, Department of Virology, University of Helsinki, Infection Biology Research Program, Kalle Saksela / Principal Investigator, and HUSLAB
- Subjects
0301 basic medicine ,Male ,HIV Core Protein p24 ,lcsh:Medicine ,HIV Infections ,LIVER FIBROSIS ,SH3 domain ,ANTIRETROVIRAL THERAPY ,SH3 DOMAIN ,lcsh:R5-920 ,INFECTED PATIENTS ,ADAM17 ,Chronic HIV infection ,Hck ,Chemistry ,Effector ,GOLGI ,virus diseases ,Translation (biology) ,General Medicine ,3. Good health ,Cell biology ,Liver ,HUMAN-IMMUNODEFICIENCY-VIRUS ,Myeloid cells ,Host-Pathogen Interactions ,symbols ,Proto-Oncogene Proteins c-hck ,lcsh:Medicine (General) ,Tyrosine kinase ,Research Paper ,Proteases ,IMMUNE ,Plasma extracellular vesicles ,Context (language use) ,ADAM17 Protein ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,symbols.namesake ,Extracellular Vesicles ,Humans ,Secretion ,nef Gene Products, Human Immunodeficiency Virus ,TYPE-1 ,Nef ,lcsh:R ,Golgi apparatus ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,Case-Control Studies ,CELLS ,Hepatocytes ,3111 Biomedicine - Abstract
HIV-Nef activates the myeloid cell-typical tyrosine kinase Hck, but its molecular role in the viral life cycle is not entirely understood. We found that HIV plasma extracellular vesicles (HIV pEV) containing/10 proteases and Nef also harbor Hck, and analyzed its role in the context of HIV pEV secretion. Myeloid cells required Hck for the vesicle-associated release of ADAM17. This could be induced by the introduction of Nef and implied that HIV targeted Hck for vesicle-associated ADAM17 secretion from a myeloid compartment. The other contents of HIV-pEV, however, including miRNA and effector protein profiles, as well as the presence of haptoglobin suggested hepatocytes as a possible cellular source. HIV liver tissue analysis supported this assumption, revealing induction of Hck translation, evidence for ADAM protease activation and HIV infection. Our findings suggest that HIV targets Hck to induce pro-inflammatory vesicles release and identifies hepatocytes as a possible host cell compartment., Highlights • Hck is found along with HIV Nef and ADAM17 in plasma extracellular vesicles (pEV) from HIV-infected individuals. • Hck is required for the secretion of ADAM17 via pEV from myeloid cells and hepatocytes. • Liver tissue from HIV infected individuals revealed induction of Hck expression and presence of Nef.
- Published
- 2018
44. Analyzing the influence of kinase inhibitors on DNA repair by differential proteomics of chromatin-interacting proteins and nuclear phospho-proteins
- Author
-
Malte Kriegs, Kai Rothkamm, Cordula Petersen, Lisa Gleißner, Laura Myllynen, Hartmut Schlüter, Marcel Kwiatkowski, Pascal Steffen, and Nanomedicine & Drug Targeting
- Subjects
0301 basic medicine ,DNA repair ,DNA damage ,EGFR ,Biology ,differential proteomics ,03 medical and health sciences ,0302 clinical medicine ,Stable isotope labeling by amino acids in cell culture ,HEAD ,Nuclear protein ,phospho-proteins ,DAMAGE ,RECEPTOR ,Kinase ,Chromatin binding ,Chromatin ,Cell biology ,SORAFENIB ,030104 developmental biology ,Oncology ,STRAND BREAK REPAIR ,030220 oncology & carcinogenesis ,chromatin bound proteins ,Cancer cell ,CELLS ,head and neck cancer ,Research Paper - Abstract
The combination of radiotherapy and pharmacological inhibition of cellular signal transduction pathways offers promising strategies for enhanced cancer cell inactivation. However, the molecular effects of kinase inhibitors especially on DNA damage detection and repair after X-irradiation have to be understood to facilitate the development of efficient and personalized treatment regimens. Therefore, we applied differential proteomics for analyzing inhibitor-induced changes in either chromatin-bound or phosphorylated nuclear proteins. The effect of the multi kinase inhibitor sorafenib on DNA repair, chromatin binding and phosphorylation of nuclear proteins was analyzed in UT-SCC 42B head and neck cancer cells using metabolic labeling based differential proteomics (SILAC). Sorafenib significantly inhibited DNA repair but failed to significantly affect chromatin interactions of 90 quantified proteins. In contrast, analyzing nuclear phospho-proteins following sorafenib treatment, we detected quantitative changes in 9 out of 59 proteins, including DNA-repair proteins. In conclusion, the analysis of nuclear phospho-proteins by differential proteomics is an effective tool for determining the molecular effects of kinase inhibitors on X-irradiated cells. Analyzing chromatin binding might be less promising.
- Published
- 2017
45. Resistive RAM With Multiple Bits Per Cell: Array-Level Demonstration of 3 Bits Per Cell.
- Author
-
Le, Binh Q., Grossi, Alessandro, Vianello, Elisa, Wu, Tony, Lama, Giusy, Beigne, Edith, Wong, H.-S. Philip, and Mitra, Subhasish
- Subjects
STATIC random access memory ,CELLS ,COMPUTER architecture - Abstract
We demonstrate, for the first time, resistive RAM (RRAM) arrays where each cell can store 3 bits. Such full array-level demonstration is possible through special techniques (e.g., that exploit RRAM-specific characteristics of variations in cell resistances), presented in this paper, which efficiently allocate resistance range corresponding to each bit combination (required for proper write operation) while maintaining appropriate sensing margin (required for proper read operation). Our techniques are not restricted to 3 bits-per-cell only (and, in this paper, we demonstrate 2 bits-per-cell at the array level as well). Our measured results are based on multiple 4 Kbit arrays of 1T1R HfOx-based RRAM integrated in the back end of the line of 130-nm silicon CMOS technology. We achieve 3 bits-per-cell (2 bits-per-cell) RRAM with 11 (3) programing iterations on average. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
46. Making the paper: Elaine Fuchs.
- Subjects
- *
RNA , *SKIN , *CELLS , *EPIDERMIS , *PROTEIN binding , *MESSENGER RNA , *NUCLEIC acids , *PROTEIN synthesis , *STEM cells - Abstract
The article reports on the study concerning the significance of ribonucleic acid (RNA) fragments on skin. It cites that cultured cells and animals studies have been used to examine the details of how cells migrate through the epidermis. It reveals that single-stranded RNA molecules have turned down the certain proteins' production by binding to the mRNA that serves as recipe for the synthesis of the protein. It shows that the therapeutic potential of microRNA could be even greater if microRNA has turned out to be broadly important in controlling the balance between differentiation and stem cells.
- Published
- 2008
- Full Text
- View/download PDF
47. Making the paper: Paul Bieniasz.
- Author
-
Bieniasz, Paul
- Subjects
- *
RETROVIRUSES , *VIRAL proteins , *HIV , *CELLS , *ANTIVIRAL agents , *HUMAN genetic variation , *DISEASE susceptibility , *VIROLOGISTS - Abstract
The article reports on the identification of tetherin, a protein factor that stops human immunodeficiency virus-1 (HIV) stuck to surface of human cells and unable to spread. Virologist Paul Bieniasz at the Aaron Diamond AIDS Research Center and Laboratory of Retrovirology at the Rockefeller University in New York investigated cell-surface proteins that might keep to HIV-1 in the absence of viral protein U (VPU). It is said that there is much to learn about tetherin for there are hints that it has broad antiviral activity. Moreover, there is a need for investigations whether genetic variation in tetherin might affect susceptibility to HIV infection.
- Published
- 2008
- Full Text
- View/download PDF
48. Making the paper: Sunney Xie.
- Subjects
- *
GENE expression , *CELLS , *TWINS , *PERSONALITY - Abstract
The article focuses on gene expression in cells. A study was conducted at Sunny Xie laboratory at Harvard University to determine the reasons behind the different personalities of persons who have the same set of genes, commonly called as identical twins. Xie proposed the use of β-galactosidase, a bacterial enzyme to monitor the expression of a single protein in a living cell.
- Published
- 2006
- Full Text
- View/download PDF
49. Author Correction: Genetic mapping of cell type specificity for complex traits.
- Author
-
Watanabe, Kyoko, Mirkov, Maša Umićević, de Leeuw, Christiaan A., van den Heuvel, Martijn P., and Posthuma, Danielle
- Subjects
CELLS ,AUTHORS ,GENE mapping - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
50. Impact of inducible nitric oxide synthase (iNOS) expression on triple negative breast cancer outcome and activation of EGFR and ERK signaling pathways
- Author
-
Elaine M. Walsh, Grace Callagy, Mark Webber, Aliaa Shalaby, Nessa Keane, Pablo Garrido, Francis J. Sullivan, M. Keane, Michael J. Kerin, Aideen E. Ryan, and Sharon A. Glynn
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,growth ,EGFR ,Translational research ,survival ,Metastasis ,prostate-cancer ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Breast cancer ,nitric oxide ,Internal medicine ,nf-kappa-b ,inhibitors ,medicine ,metastasis ,Epidermal growth factor receptor ,Triple-negative breast cancer ,biology ,business.industry ,Gene signature ,medicine.disease ,030104 developmental biology ,randomized phase-ii ,inflammation ,030220 oncology & carcinogenesis ,triple negative breast cancer ,Immunology ,biology.protein ,cells ,progression ,business ,Biomedical sciences ,Research Paper - Abstract
// Pablo Garrido 1, 7 , Aliaa Shalaby 1 , Elaine M. Walsh 1 , Nessa Keane 1 , Mark Webber 1 , Maccon M. Keane 2 , Francis J. Sullivan 3 , Michael J. Kerin 4 , Grace Callagy 1 , Aideen E. Ryan 5, 6 and Sharon A. Glynn 1, 3, 7 1 Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Republic of Ireland 2 Medical Oncology, Galway University Hospital, Galway, Republic of Ireland 3 Prostate Cancer Institute, National University of Ireland Galway, Galway, Republic of Ireland 4 Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Republic of Ireland 5 Discipline of Pharmacology and Therapeutics, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Republic of Ireland 6 Regenerative Medicine Institute (REMEDI), Biomedical Sciences, National University of Ireland Galway, Galway, Republic of Ireland 7 Apoptosis Research Centre, National University of Ireland Galway, Galway, Republic of Ireland Correspondence to: Sharon A. Glynn, email: sharon.glynn@nuigalway.ie Keywords: triple negative breast cancer, EGFR, inflammation, metastasis, nitric oxide Received: January 17, 2017 Accepted: July 03, 2017 Published: July 26, 2017 ABSTRACT Inflammation is implicated in triple negative breast cancer (TNBC) progression. TNBC carries a worse prognosis than other breast cancer subtypes, and with the clinical and molecular heterogeneity of TNBC, there is a lack of effective therapeutic targets available. Identification of molecular targets for TNBC subtypes is crucial towards personalized patient stratification. Inducible nitric oxide synthase (iNOS) has been shown to induce p53 mutation accumulation, basal-like gene signature enrichment and transactivation of the epidermal growth factor receptor (EGFR) via s-nitrosylation. Herein we report that iNOS is associated with disease recurrence, distant metastasis and decreased breast cancer specific survival in 209 cases of TNBC. Employing TNBC cell lines representing normal basal breast, and basal-like 1 and basal-like 2 tumors, we demonstrate that nitric oxide (NO) induces EGFR-dependent ERK phosphorylation in basal-like TNBC cell lines. Moreover NO mediated cell migration and cell invasion was found to be dependent on EGFR and ERK activation particularly in basal-like 2 TBNC cells. This occurred in conjunction with NF-κB activation and increased secretion of pro-inflammatory cytokines IL-8, IL-1β and TNF-α. This provides substantial evidence for EGFR as a therapeutic target to be taken into consideration in the treatment of a specific subset of basal-like TNBC overexpressing iNOS.
- Published
- 2017
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.