16,468 results
Search Results
52. 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
53. 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
54. The free energy landscape of small-world networks of cells.
- Author
-
Gentile F
- Subjects
- Cells metabolism, Energy Metabolism
- Abstract
The properties of organs, tissues, organoids, and other systems of cells, are influenced by the spatial localization and distribution of their elements. Here, we used networks to describe distributions of cells on a surface where the small-world coefficient (SW) of the networks was varied between SW~1 (random uniform distributions) and SW~10 (clustered distributions). The small-world coefficient is a topological measure of graphs: networks with SW>1 are topologically biased to transmit information. For each system configuration, we then determined the total energy U as the sum of the energies that describe cell-cell interactions - approximated by a harmonic potential. The graph of energy (U) across the configuration space of the networks (SW) is the energy landscape: it indicates which configuration a system of cells will likely assume over time. We found that, depending on the model parameters, the energy landscapes of 2D distributions of cells may be of different types: from type I to type IV. Type I and type II systems have high probability to evolve into random distributions. Type III and type IV systems have a higher probability to form clustered architectures. A great many of simulations indicated that cultures of cells with high initial density and limited sensing range could evolve into clustered configurations with enhanced topological characteristics. Moreover, the strongest the binding between cells, the greater the likelihood that they will assume configurations characterized by finite values of SW. Results of the work are relevant for those working the field of tissue engineering, regenerative medicine, the formation of in-vitro-models, the analysis of neuro-degenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
55. 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
56. Method for making thin carbon foam electrodes
- Author
-
Morrison, Robert [Modesto, CA]
- Published
- 1999
57. Strategic Implications of Manufacturing Cell Formation Design
- Author
-
Yang, Jiaqin and Deane, Richard H.
- Published
- 1994
- Full Text
- View/download PDF
58. Automatic Vision-Guided Micromanipulation for Versatile Deployment and Portable Setup.
- Author
-
Yang, Liangjing, Paranawithana, Ishara, Youcef-Toumi, Kamal, and Tan, U-Xuan
- Subjects
MICRURGY ,AUTOMATION ,MICROSCOPY ,OPTICAL information processing ,CELLS - Abstract
In this paper, an automatic vision-guided micromanipulation approach to facilitate versatile deployment and portable setup is proposed. This paper is motivated by the importance of micromanipulation and the limitations in existing automation technology in micromanipulation. Despite significant advancements in micromanipulation techniques, there remain bottlenecks in integrating and adopting automation for this application. An underlying reason for the gaps is the difficulty in deploying and setting up such systems. To address this, we identified two important design requirements, namely, portability and versatility of the micromanipulation platform. A self-contained vision-guided approach requiring no complicated preparation or setup is proposed. This is achieved through an uncalibrated self-initializing workflow algorithm also capable of assisted targeting. The feasibility of the solution is demonstrated on a low-cost portable microscope camera and compact actuated microstages. Results suggest subpixel accuracy in localizing the tool tip during initialization steps. The self-focus mechanism could recover intentional blurring of the tip by autonomously manipulating it 95.3% closer to the focal plane. The average error in visual servo is less than a pixel with our depth compensation mechanism showing better maintaining of similarity score in tracking. Cell detection rate in a 1637-frame video stream is 97.7% with subpixels localization uncertainty. Our work addresses the gaps in existing automation technology in the application of robotic vision-guided micromanipulation and potentially contributes to the way cell manipulation is performed. Note to Practitioners—This paper introduces an automatic method for micromanipulation using visual information from microscopy. We design an automatic workflow, which consists of: 1) self-initialization; 2) vision-guided manipulation; and 3) assisted targeting, and demonstrate versatile deployment of the micromanipulator on a portable microscope camera setup. Unlike existing systems, our proposed method does not require any tedious calibration or expensive setup making it mobile and low cost. This overcomes the constraints of traditional practices that confine automated cell manipulation to a laboratory setting. By extending the application beyond the laboratory environment, automated micromanipulation technology can be made more ubiquitous and expands readily to facilitate field study. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
59. Ultra-rapid preparation of total genomic DNA from isolates of yeast and mould using Whatman FTA filter paper technology – a reusable DNA archiving system.
- Author
-
Borman, Andrew, Linton, Christopher, Miles, Sarah-Jane, Campbell, Colin, and Johnson, Elizabeth
- Subjects
DNA ,GENOMES ,YEAST ,MOLDS (Fungi) ,CELLS - Abstract
Conventional methods for purifying PCR-grade fungal genomic DNA typically require cell disruption (either physical or enzymatic) coupled with laborious organic extraction and precipitation stages, or expensive column-based technologies. Here we present an easy and extremely rapid method of preparing yeast and mould genomic DNAs from living cultures using Whatman FTA filter matrix technology. Aqueous suspensions of yeast cells or hyphal fragments and conidia (in the case of moulds) are applied directly (or after freeze-thawing) to dry FTA filters. Inoculated filters are then subjected to brief microwave treatment, to dry the filters and inactivate the organisms. Filter punches are removed, washed rapidly, dried and placed directly into PCR reactions. We show that this procedure inactivated all of the 38 yeast and 75 mould species tested, and generated PCR-grade DNA preparations in around 15 minutes. A total of 218 out of 226 fungal isolates tested liberated amplifiable DNA after application to FTA filters. Detection limits with yeast cultures were approximately 10 colony-forming units per punch. Moreover, we demonstrate that filter punches can be recovered after PCR, washed and used in fresh PCR reactions without detectable cross-contamination. Whatman FTA technology thus represents a cheap, ultra-rapid method of fungal genomic DNA preparation, and also potentially represents a powerful fungal DNA archiving and storage system. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
60. 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
61. 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
62. 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
63. 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
64. Manual braille writer
- Author
-
Turner, Joe [Knoxville, TN]
- Published
- 1992
65. Absolute entropy and free energy of fluids using the hypothetical scanning method. II. Transition probabilities from canonical Monte Carlo simulations of partial systems.
- Author
-
White, Ronald P. and Meirovitch, Hagai
- Subjects
ENTROPY ,MONTE Carlo method ,ARGON ,ATOMS ,CELLS - Abstract
A variant of the hypothetical scanning (HS) method for calculating the absolute entropy and free energy of fluids is developed, as applied to systems of Lennard-Jones atoms (liquid argon). As in the preceding paper (Paper I), a probability P[sub i] approximating the Boltzmann probability of system configuration i, is calculated with a reconstruction procedure based on adding the atoms gradually to an initially empty volume, where they are placed in their positions at i; in this process the volume is divided into cubic cells, which are visited layer-by-layer, line-by-line. At each step a transition probability (TP) is calculated and the product of all the TPs leads to P[sub i]. At step k, k-1 cells have already been treated, where among them N[sub k] are occupied by an atom. A canonical metropolis Monte Carlo (MC) simulation is carried out over a portion of the still unvisited (future) volume thus providing an approximate representation of the N-N[sub k] as yet untreated (future) atoms. The TP of target cell k is determined from the number of visits of future atoms to this cell during the simulation. This MC version of HS, called HSMC, is based on a relatively small number of efficiency parameters; their number does not grow and their values are not changed as the number of the treated future atoms is increased (i.e., as the approximation improves); therefore, implementing HSMC for a relatively large number of future atoms (up to 40 in this study) is straightforward. Indeed, excellent results have been obtained for the free energy and the entropy. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
66. 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
67. 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
68. Control of Free Methionine Production in Wild Type and Ethionine-Resistant Mutants of Chlorella sorokiniana
- Author
-
Owens, Lowell D.
- Published
- 1974
69. 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
70. Simultaneous route selection and cell formation: a mixed‐integer programming time‐cost model
- Author
-
Sarker, Bhaba R. and Li, Kun
- Published
- 1997
- Full Text
- View/download PDF
71. Beckman Coulter Life Sciences Publishes White Paper for ClearLLab Control Cells, Validating First 10C System for Clinical Lab.
- Subjects
LIFE sciences ,SCIENCE publishing ,CELLS - Abstract
Beckman Coulter Life Sciences Publishes White Paper for ClearLLab Control Cells, Validating First 10C System for Clinical Lab - Beckman Coulter, Inc [ABSTRACT FROM AUTHOR]
- Published
- 2019
72. 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
73. 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
74. Graduate Student Paper Competition-MS.
- Subjects
- *
ANIMAL behavior , *CYTOKINES , *CELLS , *HEIFERS , *RAW materials , *HYPOGLYCEMIC agents - Abstract
The article presents abstracts from papers related to animal behavior that were published in the February 2005 issue of the "Journal of Animal Science." The paper "Effects of Dried Distillers Grains on Heifer Consumption of Low or High Quality Forage," was presented by S. Morik, T. Klopfenstein and D. Adams. The paper "Developmental Potential of Porcine Nuclear Transfer Embryos Using Non-Differentiated Donor Cells," by K. Lee, investigated the developmental potential of early embryos reconstructed using olfactory unsheathing cells (OECs). OECs are located in the olfactory bulb and thought to have remarkable developmental plasticity. The paper "Endocrine and Follicular Dynamics in Beef Heifers Divergently Selected for Peripheral IGF-1 Concentrations," by D. Dauch, K. Fike, M. Mussard, G. Bridges, C. Gasser, D. Grum, M. Davis, and M. Day, compared estradiol concentrations and ovarian follicular dynamics prior to ovulation and subsequent luteal progesterone concentrations between genetic lines of beef heifers divergently selected for peripheral concentrations of insulin-like growth factor-1.
- Published
- 2005
75. Cell's publisher invites statements in papers about studies' diversity and inclusion efforts.
- Author
-
Moutinho, Sofia
- Subjects
PITCHING (Ideas) ,CELLS ,DIVERSITY in the workplace - Abstract
PHOTO (COLOR): Voluntary declarations in submitted manuscripts can describe gender balance in study samples, for example. "These [manuscript] statements might arguably only be done by those who already understand the importance of equity, diversity, and inclusion", Roessler said. [Extracted from the article]
- Published
- 2021
- Full Text
- View/download PDF
76. 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
77. 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
78. 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
79. 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
80. 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
81. Technology no longer a risk for cells
- Author
-
Kochan, A.
- Published
- 1990
- Full Text
- View/download PDF
82. 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
83. 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
84. 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
85. 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
86. 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
87. Photogalvanic Cells as a Device for Solar Energy Conversion and Storage: An EDTA-New Methylene Blue and Safranine O System.
- Author
-
Yadav, S. and Lal, C.
- Subjects
PHOTOMECHANICAL processes ,CELLS ,ETHYLENEDIAMINETETRAACETIC acid ,PHOTOSENSITIZERS ,METHYLENE blue ,INDICATORS & test-papers ,BIOCHEMICAL mechanism of action ,DYES & dyeing ,ACETIC acid - Abstract
Photogalvanic effect was studied in photogalvanic cells containing EDTA as reductant, new methylene blue, and safranine O as photosensitizer. The photopotential and photocurrent generated were 740 mV and 110 μA, respectively. The observed conversion efficiency was 0.4442% and the maximum output (power) of cell was 81.4 μW. The photogalvanic cell can be used for 95 min in the dark due to the storage capacity of the cell. The effects of various parameters on the electrical output of the cell were observed. The mechanism of generation of the photocurrent in these photogalvanic cells has also been proposed. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
88. 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
89. 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
90. A novel DLX3–PKC integrated signaling network drives keratinocyte differentiation
- Author
-
Anna C Gormley, Maria I. Morasso, Shreya Bhattacharya, Stuart H. Yuspa, Meghan D. Kellett, Elisabetta Palazzo, Christophe Cataisson, Hong-Wei Sun, and Paul W Bible
- Subjects
0301 basic medicine ,Keratinocytes ,Indoles ,Protein Kinase C-alpha ,Cells ,Mice, Transgenic ,Biology ,Transgenic ,Animals ,Antimicrobial Cationic Peptides ,Calcium ,Cell Adhesion ,Cell Differentiation ,Cell Proliferation ,Cells, Cultured ,Chemokines ,Cytokines ,Epidermis ,Homeodomain Proteins ,Humans ,Hyperplasia ,Leukocytes ,Maleimides ,Mice ,Tetradecanoylphorbol Acetate ,Transcription Factors ,Signal Transduction ,03 medical and health sciences ,medicine ,Transcriptional regulation ,Molecular Biology ,Transcription factor ,Protein kinase C ,Original Paper ,Cultured ,integumentary system ,Cell growth ,Wnt signaling pathway ,Cell Biology ,Cell cycle ,3. Good health ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Signal transduction ,Keratinocyte - Abstract
Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C α (PKCα) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting (K5-PKCα), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKCα activation, suggesting a feedback regulation of DLX3 and PKCα. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3–PKCα signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis.
- Published
- 2017
91. Loss of menin in osteoblast lineage affects osteocyte–osteoclast crosstalk causing osteoporosis
- Author
-
Nicole Malkusch, Jeanette Knoll, Sooyeon Lee, Ulf H. Lerner, Jan Tuckermann, Mario M. Zaiss, Mona Neven, Susanne Ostermay, Alexander Rauch, Julia Luther, Philippe Bertolino, Martina Rauner, Chang X. Zhang, Peng Liu, Jean-Pierre David, and Rainer Wittig
- Subjects
0301 basic medicine ,Zelle ,endocrine system diseases ,receptor ,Osteoporosis ,Osteoclasts ,Bone resorption ,Expression ,Cell Communication ,Mice ,DDC 570 / Life sciences ,Osteogenesis ,Cell differentiation ,Femur ,Cells, Cultured ,Gen ,Chemistry ,Osteoblast ,Cell Differentiation ,differentiation ,Maus ,endocrine neoplasia type-1 ,Cell biology ,Crosstalk (biology) ,medicine.anatomical_structure ,Sp7 Transcription Factor ,Osteocyte ,Female ,Chemokines ,musculoskeletal diseases ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,Cells ,Zelldifferenzierung ,Bone Marrow Cells ,Mice, Transgenic ,Osteocytes ,03 medical and health sciences ,Ausdruck ,Osteoclast ,Internal medicine ,ddc:570 ,Proto-Oncogene Proteins ,medicine ,CXCL10 ,Animals ,MEN1 ,Cell Lineage ,Glucocorticosteroide ,gene ,Molecular Biology ,Glucocorticoids ,mouse ,Original Paper ,Cell Biology ,cell ,medicine.disease ,Alkaline Phosphatase ,Antibodies, Neutralizing ,Chemokine CXCL10 ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Genes - Abstract
During osteoporosis bone formation by osteoblasts is reduced and/or bone resorption by osteoclasts is enhanced. Currently, only a few factors have been identified in the regulation of bone integrity by osteoblast-derived osteocytes. In this study, we show that specific disruption of menin, encoded by multiple endocrine neoplasia type 1 (Men1), in osteoblasts and osteocytes caused osteoporosis despite the preservation of osteoblast differentiation and the bone formation rate. Instead, an increase in osteoclast numbers and bone resorption was detected that persisted even when the deletion of Men1 was restricted to osteocytes. We demonstrate that isolated Men1-deficient osteocytes expressed numerous soluble mediators, such as C-X-C motif chemokine 10 (CXCL10), and that CXCL10-mediated osteoclastogenesis was reduced by CXCL10-neutralizing antibodies. Collectively, our data reveal a novel role for Men1 in osteocyte–osteoclast crosstalk by controlling osteoclastogenesis through the action of soluble factors. A role for Men1 in maintaining bone integrity and thereby preventing osteoporosis is proposed., publishedVersion
- Published
- 2017
92. Quantitative proteomics reveals Piccolo as a candidate serological correlate of recovery from Guillain-Barré syndrome
- Author
-
Jesús Vázquez, Lourdes Mateos-Hernández, Marco Trevisan-Herraz, José de la Fuente, Ángel García-Forcada, Ernesto Doncel-Pérez, Francisco Romero Ganuza, Margarita Villar, European Commission, Universidad de Castilla La Mancha, University of Castilla-La Mancha (España), and University of Castilla La Mancha (UCLM)
- Subjects
0301 basic medicine ,Male ,Proteomics ,Proteome ,Disease ,Serology ,MOLECULAR MIMICRY ,0302 clinical medicine ,Medicine ,Biomarker discovery ,ANTIGANGLIOSIDE ,Aged, 80 and over ,Guillain-Barre syndrome ,IMMUNE-MEDIATED NEUROPATHIES ,Research Paper: Immunology ,MULTIPLE-SCLEROSIS ,Guillain-Barré ,Blood Proteins ,Middle Aged ,3. Good health ,Oncology ,Neurology ,Guillain-Barre ,Biomarker (medicine) ,biomarker ,Immunology and Microbiology Section ,Female ,Adult ,Quantitative proteomics ,PEPTIDE IDENTIFICATION ,Guillain-Barre Syndrome ,Models, Biological ,03 medical and health sciences ,Young Adult ,CEREBROSPINAL-FLUID ,Humans ,SYNDROME GBS ,Immune response ,Aged ,business.industry ,Multiple sclerosis ,neurology ,Neuropeptides ,Immunity ,PERIPHERAL NEUROPATHIES ,Reproducibility of Results ,Biomarker ,MASS-SPECTROMETRY ,Recovery of Function ,medicine.disease ,bacterial infections and mycoses ,immunity ,Neuropathy ,Cytoskeletal Proteins ,030104 developmental biology ,Peripheral neuropathy ,Case-Control Studies ,Immunology ,CELLS ,neuropathy ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Guillain-Barré syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of unknown cause. However, about a quarter of GBS patients have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients. Proteomics is a good methodological approach for the discovery of disease biomarkers. Until recently, most proteomics studies of GBS and other neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid (CSF). However, serum represents an attractive alternative to CSF because it is easier to sample and has potential for biomarker discovery. The goal of this research was the identification of serum biomarkers associated with recovery from GBS. To address this objective, a quantitative proteomics approach was used to characterize differences in the serum proteome between a GBS patient and her healthy identical twin in order to lessen variations due to differences in genetic background, and with additional serum samples collected from unrelated GBS (N = 3) and Spinal Cord Injury (SCI) (N = 3) patients with similar medications. Proteomics results were then validated by ELISA using sera from additional GBS patients (N = 5) and healthy individuals (N = 3). All GBS and SCI patients were recovering from the acute phase of the disease. The results showed that Piccolo, a protein that is essential in the maintenance of active zone structure, constitutes a potential serological correlate of recovery from GBS. These results provided the first evidence for the Piccolo's putative role in GBS, suggesting a candidate target for developing a serological marker of disease recovery., This work was partially supported by EU FP7 ANTIGONE project number 278976. LMH was supported by a fellowship from the University of Castilla La Mancha (UCLM), Spain. MV was supported by the Research Plan of UCLM, Spain.
- Published
- 2016
93. Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence
- Author
-
Shuya Yano, Michael Bouvet, Kiyoto Takehara, Shinji Miwa, Robert M. Hoffman, Shunsuke Kagawa, Yasuo Urata, Hiroshi Tazawa, Toshiyoshi Fujiwara, and Hiroyuki Kishimoto
- Subjects
0301 basic medicine ,Telomerase ,Gene Expression ,Triple Negative Breast Neoplasms ,Complete resection ,Metastasis ,Green fluorescent protein ,Mice ,Computer-Assisted ,0302 clinical medicine ,Recurrence ,Transduction, Genetic ,Triple-negative breast cancer ,Cells, Cultured ,Microscopy ,Cultured ,Tumor ,Optical Imaging ,adenovirus ,nude mice ,3. Good health ,Oncology ,Surgery, Computer-Assisted ,030220 oncology & carcinogenesis ,Female ,fluorescence-guided surgery ,Research Paper ,medicine.medical_specialty ,Cells ,Oncology and Carcinogenesis ,Genetic Vectors ,Green Fluorescent Proteins ,survival ,Fluorescence ,triple negative ,Cell Line ,Adenoviridae ,Transduction ,03 medical and health sciences ,breast cancer ,Breast cancer ,Genetic ,Cell Line, Tumor ,medicine ,Animals ,Humans ,orthotopic ,Animal ,business.industry ,Cancer ,GFP/RFP ,medicine.disease ,Xenograft Model Antitumor Assays ,Surgery ,Disease Models, Animal ,030104 developmental biology ,Microscopy, Fluorescence ,Disease Models ,Cancer cell ,business ,fluorescence-guided surgery (FGS) ,telomerase dependent - Abstract
// Shuya Yano 1, 2, 3 , Kiyoto Takehara 1, 2, 3 , Shinji Miwa 1, 2 , Hiroyuki Kishimoto 3 , Hiroshi Tazawa 4 , Yasuo Urata 5 , Shunsuke Kagawa 3 , Michael Bouvet 2 , Toshiyoshi Fujiwara 3 , Robert M. Hoffman 1, 2 1 AntiCancer, Inc., San Diego, CA, USA 2 Department of Surgery, University of California San Diego, CA, USA 3 Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan 4 Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan 5 Oncolys BioPharm Inc., Tokyo, Japan Correspondence to: Robert M. Hoffman, email: all@anticancer.com Toshiyoshi Fujiwara, email: toshi_ f@md.okayama-u.ac.jp Keywords: fluorescence-guided surgery (FGS), telomerase dependent, adenovirus, GFP/RFP, survival Received: July 07, 2016 Accepted: September 06, 2016 Published: September 28, 2016 ABSTRACT We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model.
- Published
- 2016
94. Diffusion in tight confinement: A lattice-gas cellular automaton approach. II. Transport properties.
- Author
-
Demontis, Pierfranco, Pazzona, Federico G., and Suffritti, Giuseppe B.
- Subjects
LATTICE gas ,PROPERTIES of matter ,DIFFUSION ,CELLS ,MOLECULAR dynamics ,PHYSICAL & theoretical chemistry - Abstract
In this second paper the authors study the transport properties of the lattice-gas cellular automaton presented in Paper I [J. Chem. Phys. 126, 194709 (2007)] to model adsorption and dynamics of particles in a lattice of confining cells. Their work shows how a surprisingly simple parallel rule applied to a static network of cells joined by links set in space and time can generate a wide range of dynamical behaviors. In their model the cells are the elementary constituent objects of the network. They are a portion of space structured in sites which are energetically different. Each cell can accommodate a given maximum number of particles, and each pair of neighboring cells can exchange at most one particle at a time. The predictions of the model are in qualitative agreement with both experimental observations and molecular dynamics simulation results. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
95. Loss of TLE3 promotes the mitochondrial program in beige adipocytes and improves glucose metabolism
- Author
-
Anne Loft, Claudio J. Villanueva, Stephanie Pearson, Prashant Rajbhandari, Susanne Mandrup, Judith Simcox, Sanghoon Lee, and Peter Tontonoz
- Subjects
Male ,Adipose tissue ,White adipose tissue ,Inbred C57BL ,Medical and Health Sciences ,Mice ,0302 clinical medicine ,Gene expression ,Basic Helix-Loop-Helix Transcription Factors ,Adipocytes, Beige ,Cells, Cultured ,0303 health sciences ,Cultured ,diabetes ,Thermogenesis ,thermogenesis ,Biological Sciences ,Cell biology ,Mitochondria ,030220 oncology & carcinogenesis ,beige adipocytes ,Co-Repressor Proteins ,Biotechnology ,Research Paper ,Cells ,1.1 Normal biological development and functioning ,adipocytes ,Oxidative phosphorylation ,Biology ,Metabolic and Endocrine ,Diet, High-Fat ,03 medical and health sciences ,Genetics ,Animals ,Obesity ,Enhancer ,development ,Transcription factor ,Nutrition ,030304 developmental biology ,Beige ,Psychology and Cognitive Sciences ,Diet ,Mice, Inbred C57BL ,High-Fat ,Glucose ,Gene Expression Regulation ,TLE3 ,Insulin Resistance ,Energy Metabolism ,metabolism ,Chromatin immunoprecipitation ,Gene Deletion ,Developmental Biology ,Genome-Wide Association Study - Abstract
Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional mechanisms that promote remodeling in adipose tissue during the cold are not well understood. Here we demonstrate that the transcriptional coregulator transducin-like enhancer of split 3 (TLE3) inhibits mitochondrial gene expression in beige adipocytes. Conditional deletion of TLE3 in adipocytes promotes mitochondrial oxidative metabolism and increases energy expenditure, thereby improving glucose control. Using chromatin immunoprecipitation and deep sequencing, we found that TLE3 occupies distal enhancers in proximity to nuclear-encoded mitochondrial genes and that many of these binding sites are also enriched for early B-cell factor (EBF) transcription factors. TLE3 interacts with EBF2 and blocks its ability to promote the thermogenic transcriptional program. Collectively, these studies demonstrate that TLE3 regulates thermogenic gene expression in beige adipocytes through inhibition of EBF2 transcriptional activity. Inhibition of TLE3 may provide a novel therapeutic approach for obesity and diabetes.
- Published
- 2019
96. Effect of ambient temperature and intracellular pigmentation on photothermal damage rate kinetics
- Author
-
Amanda J. Tijerina, Cherry C. Gonzalez, Benjamin A. Rockwell, Giovanna Gamboa, Michael L. Denton, Gary D. Noojin, and Elharith M. Ahmed
- Subjects
Paper ,Materials science ,Hot Temperature ,microthermography ,Biomedical Engineering ,Irradiance ,Retinal Pigment Epithelium ,01 natural sciences ,Models, Biological ,law.invention ,010309 optics ,Biomaterials ,Reaction rate ,symbols.namesake ,photothermal ,law ,0103 physical sciences ,medicine ,Humans ,Computer Simulation ,Absorption (electromagnetic radiation) ,General ,Cell damage ,Cells, Cultured ,Arrhenius equation ,Lasers ,Epithelial Cells ,Photothermal therapy ,medicine.disease ,Laser ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Arrhenius ,retinal pigment epithelial ,kinetics ,Thermography ,symbols ,Biophysics ,cells - Abstract
Computational models predicting cell damage responses to transient temperature rises generated by exposure to lasers have implemented the damage integral (Ω), which time integrates the chemical reaction rate constant described by Arrhenius. However, few published reports of empirical temperature histories (thermal profiles) correlated with damage outcomes at the cellular level are available to validate the breadth of applicability of the damage integral. In our study, an analysis of photothermal damage rate processes in cultured retinal pigment epithelium cells indicated good agreement between temperature rise, exposure duration (τ), and threshold cellular damage. Full-frame thermograms recorded at high magnification during laser exposures were overlaid with fluorescence damage images taken 1 h postexposure. From the image overlays, pixels of the thermogram correlated with the boundary of cell death were used to extract threshold thermal profiles. Assessing photothermal responses at these boundaries standardized all data points, irrespective of laser irradiance, damage size, or optical and thermal properties of the cells. These results support the hypothesis that data from boundaries of cell death were equivalent to a minimum visible lesion, where the damage integral approached unity (Ω=1) at the end of the exposure duration. Empirically resolved Arrhenius coefficients for use in the damage integral determined from exposures at wavelengths of 2 μm and 532 nm and durations of 0.05–20 s were consistent with literature values. Varying ambient temperature (Tamb) between 20°C and 40°C during laser exposure did not change the τ-dependent threshold peak temperature (Tp). We also show that, although threshold laser irradiance varied due to pigmentation differences, threshold temperatures were irradiance independent.
- Published
- 2019
97. Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics
- Author
-
Coenen-Stass, Anna M. L., Pauwels, Marie J., Hanson, Britt, Perez, Carla Martin, Conceição, Mariana, Wood, Matthew J. A., Mäger, Imre, and Roberts, Thomas C.
- Subjects
Serum ,half-life ,RNA Stability ,BIOMARKERS ,Muscle Fibers, Skeletal ,Preservation, Biological ,SERUM ,VESICLES ,Cell Line ,Extracellular Vesicles ,Mice ,CIRCULATING MICRORNAS ,Medicine and Health Sciences ,Animals ,Humans ,miRNA ,EXOSOMES ,PLASMA ,microRNA ,Temperature ,Biology and Life Sciences ,MUSCULAR-DYSTROPHY ,MicroRNAs ,MIRNAS ,Extracellular microRNA ,kinetics ,Culture Media, Conditioned ,CELLS ,ex-miRNA ,MUSCLE REGENERATION ,Female ,Research Paper - Abstract
Multiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile extracellular environment, when stored at 4oC or lower. Here we show that many ex-miRNAs are rapidly degraded when incubated at 37oC in the presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from similar to 1.5 hours to more than 13 hours. Notably, ex-miRNA half-lives calculated in two different biofluids (murine serum and C2C12 mouse myotube conditioned medium) were highly similar, suggesting that intrinsic sequence properties are a determining factor in miRNA stability. By contrast, ex-miRNAs associated with extracellular vesicles (isolated by size exclusion chromatography) were highly stable. The release of ex-miRNAs from C2C12 myotubes was measured over time, and mathematical modelling revealed miRNA-specific release kinetics. While some ex-miRNAs reached the steady state in cell culture medium within 24 hours, the extracellular level of miR-16 did not reach equilibrium, even after 3 days in culture. These findings are indicative of miRNA-specific release and degradation kinetics with implications for the utility of ex-miRNAs as biomarkers, and for the potential of ex-miRNAs to transfer gene regulatory information between cells.
- Published
- 2019
98. Higher lactate production from glucose in cultured adipose nucleated stromal cells than for rat adipocytes
- Author
-
Ana-Cecilia Ho-Palma, Floriana Rotondo, José Antonio Fernández-López, Xavier Remesar, Marià Alemany, María del Mar Romero, and Universitat de Barcelona
- Subjects
Male ,Cell ,Adipose tissue ,White adipose tissue ,Fatty Acids, Nonesterified ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,lcsh:Physiology ,chemistry.chemical_compound ,Adipocyte ,Glycolysis ,Cells, Cultured ,Rates (Animals de laboratori) ,Adiposity ,lcsh:QP1-981 ,lcsh:Cytology ,glycaemia ,glycolysis ,medicine.anatomical_structure ,Anaerobic exercise ,Research Paper ,medicine.medical_specialty ,Histology ,Stromal cell ,Adipose Tissue, White ,adipocytes ,Cèl·lules ,Cells ,Rats as laboratory animals ,glycerol ,Cell Line ,Internal medicine ,Glycerol ,medicine ,Animals ,Lactic Acid ,Obesity ,lcsh:QH573-671 ,Rats, Wistar ,lactate ,lcsh:RC648-665 ,Adipose tissues ,Cell Biology ,Rats ,Teixit adipós ,Glucose ,Endocrinology ,chemistry ,nervous system ,Stromal Cells - Abstract
White adipose tissue (WAT) nucleated stromal cells (NSC) play important roles in regulation, defense, regeneration and metabolic control. In WAT sites, the proportions and functions of NSC change under diverse physiological or pathologic conditions. We had previously observed the massive anaerobic wasting of glucose to lactate and glycerol in rat epididymal adipocytes. To test site variability, and whether the adipocyte extensive anaerobic metabolism of glucose was found in NSC, we analyzed, in parallel, subcutaneous, mesenteric and epididymal WAT of male adult Wistar rats. Adipocytes and NSC fractions, were isolated, counted and incubated (as well as red blood cells: RBC) with glucose, and their ability to use glucose and produce lactate, glycerol, and free fatty acids was measured. Results were computed taking into account the number of cells present in WAT samples. Cell numbers were found in proportions close to 1:13:100 (respectively, for adipocytes, NSC and RBC) but their volumes followed a reversed pattern: 7,500:10:1. When counting only non-fat cell volumes, the ratios changed dramatically to 100:10:1. RBC contribution to lactate production was practically insignificant. In most samples, NSC produced more lactate than adipocytes did, but only adipocytes secreted glycerol (and fatty acids in smaller amounts). Glucose consumption was also highest in NSC, especially in mesenteric WAT. The heterogeneous NSC showed a practically anaerobic metabolism (like that already observed in adipocytes). Thus, NSC quantitative production of lactate markedly contributed (i.e. more than adipocytes) to WAT global use (wasting) of glucose. We also confirmed that glucose-derived glycerol is exclusively produced by adipocytes.
- Published
- 2019
99. Does butein affect adipogenesis?
- Author
-
Dries Bauters, Ilse Scroyen, Christine Vranckx, H. Roger Lijnen, and Bianca Hemmeryckx
- Subjects
Male ,EXPRESSION ,Chalcone ,Histology ,WHITE ADIPOSE-TISSUE ,Anti-Inflammatory Agents ,INHIBITION ,Adipose tissue ,Butein ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,lcsh:Physiology ,adipogenesis ,Andrology ,PATHWAY ,chemistry.chemical_compound ,Mice ,Endocrinology & Metabolism ,Chalcones ,Gene expression ,Adipocytes ,Oil Red O ,Animals ,lcsh:QH573-671 ,Cells, Cultured ,Uncoupling Protein 1 ,adipocyte differentiation ,browning ,Thrombospondin ,Metalloproteinase ,lcsh:RC648-665 ,Adipogenesis ,Science & Technology ,lcsh:QP1-981 ,lcsh:Cytology ,INDUCTION ,INFLAMMATORY RESPONSE ,Cell Biology ,3T3 Cells ,Mice, Inbred C57BL ,chemistry ,ADAMTS5 ,CELLS ,ADAMTS5 Protein ,Life Sciences & Biomedicine ,Research Paper - Abstract
Butein is a plant flavonoid chalcone, with presumed anti-adipogenic properties. It was reported to impair preadipocyte differentiation, limit adipose tissue (AT) development and enhance white AT browning in rodents. In this study, we investigated the hypothesis that these effects of butein may occur via reduction of ADAMTS5 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 5) expression. Murine 3T3-L1 or 3T3-F442A preadipocytes were differentiated into mature adipocytes in the presence of butein or vehicle. At regular time intervals RNA was collected for gene expression studies. Male hemizygous mice for Tg(Ucp1-luc2,-tdTomato)1Kajim (ThermoMouse) were exposed to butein or vehicle, after which ATs were analyzed for Adamts5 and uncoupling protein-1 (Ucp-1) mRNA level changes. During preadipocyte differentiation, butein (25 - 50 mM) did not affect Adamts5 or Ucp-1 expression. Oil Red O analysis and monitoring of differentiation markers failed to demonstrate effects of butein on the differentiation extent. Furthermore, butein administration to the ThermoMouse (10 or 20 mg/kg, 4 days) or to the C57BL6/Rj mice (20 mg/kg, 4 weeks) did not enhance Adamts5 or Ucp-1 expression. Thus, we could not demonstrate marked effects of butein on the preadipocyte differentiation extent or AT development and browning, nor on Adamts5 or Ucp-1 gene expression during these processes. ispartof: ADIPOCYTE vol:8 issue:1 pages:209-222 ispartof: location:United States status: published
- Published
- 2019
100. Delayed γH2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect
- Author
-
Anna Espinal, Joan Repullés, Mark A. LaBarge, Anna Genescà, Teresa Anglada, Martha R. Stampfer, and Marta Martín
- Subjects
Genome instability ,Aging ,DNA Repair ,Physiology ,Histones ,chemistry.chemical_compound ,Basal (phylogenetics) ,Double-Stranded ,DNA Breaks, Double-Stranded ,γH2AX ,Cells, Cultured ,Cultured ,Genome integrity ,Middle Aged ,Mammary Glands ,Double Strand Break Repair ,Cell biology ,genome integrity ,Double-strand break repair ,double-strand break repair ,Female ,Human ,Research Paper ,Adult ,Adolescent ,DNA damage ,DNA repair ,gamma H2AX ,1.1 Normal biological development and functioning ,Cells ,Oncology and Carcinogenesis ,Breast Neoplasms ,Biology ,Young Adult ,Human mammary epithelial cells ,Genetics ,Humans ,Mammary Glands, Human ,Aged ,DNA Breaks ,aging ,Epithelial Cells ,Cell Biology ,human mammary epithelial cells ,Constant factor ,chemistry ,Gene Expression Regulation ,Biochemistry and Cell Biology ,DNA ,Developmental Biology - Abstract
Aging is a degenerative process in which genome instability plays a crucial role. To gain insight into the link between organismal aging and DNA repair capacity, we analyzed DNA double-strand break (DSB) resolution efficiency in human mammary epithelial cells from 12 healthy donors of young and old ages. The frequency of DSBs was measured by quantifying the number of γH2AX foci before and after 1Gy of γ-rays and it was higher in cells from aged donors (ADs) at all times analyzed. At 24 hours after irradiation, ADs retained a significantly higher frequency of residual DSBs than young donors (YDs), which had already reached values close to basal levels. The kinetics of DSB induction and disappearance showed that cells from ADs and YDs repair DSBs with similar speed, although analysis of early times after irradiation indicate that a repair defect may lie within the firing of the DNA repair machinery in AD cells. Indeed, using a mathematical model we calculated a constant factor of delay affecting aged human epithelial cells repair kinetics. This defect manifests with the accumulation of DSBs that might eventually undergo illegitimate repair, thus posing a relevant threat to the maintenance of genome integrity in older individuals.
- Published
- 2019
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.