scholarly journals An integrated cell, tissue and whole organ profile of kidney morphogenesis

2017 ◽  
Vol 145 ◽  
pp. S152-S153
Author(s):  
Alexander Combes ◽  
James Lefevre ◽  
Kieran Short ◽  
Adler Ju ◽  
Kylie Georgas ◽  
...  
1991 ◽  
Vol 66 (05) ◽  
pp. 559-564 ◽  
Author(s):  
Jerome M Teitel

SummaryAn experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.


1965 ◽  
Vol 13 (01) ◽  
pp. 035-046 ◽  
Author(s):  
R. L Henry

SummaryWhite blood cells can no longer be considered simple trapped inclusions within thrombi. Their numbers in thrombi relative to blood counts increase with time. They appear to come from the blood flowing past the thrombus. They appear to migrate by amoeboid movement into the thrombic mass. Polymorphonuclear neutrophils have been shown to be lytic to fibrin and other proteins and thus can contribute to thrombus dissolution. There is increasing evidence that neutrophils may impart important cytotrophic function to proliferating cells during thrombus organization. Eosinophils are known to carr profibrinolysin and will release this precursor at sites of fibrin deposition. Mononuclear leukocytes can transform into fibroblasts in tissue culture and I consider a thrombus an ideal tissue culture medium. All of these cells can contribute to thrombus dissolution simply by mechanical weakening of the mass by migration into it, releasing enzymes, and allowing blood flow to carry away pieces of the thrombus as emboli. I extend my perspective on thrombosis by considering these intravascular solids as cell tissue cultures rather than simple blood clots or platelet aggregates.


Author(s):  
Parag A Pathade ◽  
Vinod A Bairagi ◽  
Yogesh S. Ahire ◽  
Neela M Bhatia

‘‘Proteomics’’, is the emerging technology leading to high-throughput identification and understanding of proteins. Proteomics is the protein equivalent of genomics and has captured the imagination of biomolecular scientists, worldwide. Because proteome reveals more accurately the dynamic state of a cell, tissue, or organism, much is expected from proteomics to indicate better disease markers for diagnosis and therapy monitoring. Proteomics is expected to play a major role in biomedical research, and it will have a significant impact on the development of diagnostics and therapeutics for cancer, heart ailments and infectious diseases, in future. Proteomics research leads to the identification of new protein markers for diagnostic purposes and novel molecular targets for drug discovery.  Though the potential is great, many challenges and issues remain to be solved, such as gene expression, peptides, generation of low abundant proteins, analytical tools, drug target discovery and cost. A systematic and efficient analysis of vast genomic and proteomic data sets is a major challenge for researchers, today. Nevertheless, proteomics is the groundwork for constructing and extracting useful comprehension to biomedical research. This review article covers some opportunities and challenges offered by proteomics.   


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonas Albers ◽  
Angelika Svetlove ◽  
Justus Alves ◽  
Alexander Kraupner ◽  
Francesca di Lillo ◽  
...  

AbstractAlthough X-ray based 3D virtual histology is an emerging tool for the analysis of biological tissue, it falls short in terms of specificity when compared to conventional histology. Thus, the aim was to establish a novel approach that combines 3D information provided by microCT with high specificity that only (immuno-)histochemistry can offer. For this purpose, we developed a software frontend, which utilises an elastic transformation technique to accurately co-register various histological and immunohistochemical stainings with free propagation phase contrast synchrotron radiation microCT. We demonstrate that the precision of the overlay of both imaging modalities is significantly improved by performing our elastic registration workflow, as evidenced by calculation of the displacement index. To illustrate the need for an elastic co-registration approach we examined specimens from a mouse model of breast cancer with injected metal-based nanoparticles. Using the elastic transformation pipeline, we were able to co-localise the nanoparticles to specifically stained cells or tissue structures into their three-dimensional anatomical context. Additionally, we performed a semi-automated tissue structure and cell classification. This workflow provides new insights on histopathological analysis by combining CT specific three-dimensional information with cell/tissue specific information provided by classical histology.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Azita Alipour ◽  
Moslem Mansour Lakouraj ◽  
Hamed Tashakkorian

AbstractIn this work, band gap, photoluminescence and biological properties of new bionanocomposites based on polyaniline (PANi)/hydrolyzed pectin (HPEc)/cadmium sulfide (CdS) QD nanoparticles (NPs) were studied. In order to improve the morphology and properties, CdS NPs were modified with epichlorohydrin to obtain the modified CdS (mCdS). The CdS@HPEc-g-PANi and mCdS@HPEc-g-PANi samples were synthesized via heterogeneous chemical polymerization and characterized by FTIR, 1HNMR, SEM/XRD, EDX/TEM/EDX-mapping and TGA analyses. The objective of this work is the study of physical, optical and cytotoxicity properties of the nanocomposites and comparison between them. The SEM, XRD and TGA images showed that the modification of NPs resulted in homogeneous morphology, increase of crystalline structure and high thermal stability which influenced on physical and biological property. According to UV-DRS analysis, the mCdS@HPEc-g-PANi indicated lower energy gap compared to the CdS@HPEc-g-PANi nancomposite. The presence of conductive polymer and synergy effect between the PANi and CdS caused higher PL intensity in the CdS@HPEc-g-PANi nanocomposite compared to pure CdS. The emission intensity in the mCdS@HPEc-g-PANi nanocomposite was reduced since the organic modifying agent cause reducing emission intensity. The mCdS@HPEc-g-PANi nanocomposite, due to more compatibility of organic agent with cellular walls of biological cells that help to the diffusion of metal CdS NPs into cell tissue indicated more toxicity effect on cell growth.


2021 ◽  
Vol 22 (3) ◽  
pp. 1386
Author(s):  
Jerzy Wiater ◽  
Marcin Samiec ◽  
Maria Skrzyszowska ◽  
Daniel Lipiński

This study was conducted to explore whether trichostatin A-assisted epigenomic modulation (TSA-EM) can affect the expression of not only recombinant human α1,2-fucosyltransferase (rhα1,2-FT) and α-galactosidase A (rhα-Gal A) immune system enzymes but also Galα1→3Gal epitopes in ex vivo proliferating adult cutaneous fibroblast cells (ACFCs) derived from hFUT2×hGLA bi-transgenic pigs that had been produced for the needs of future xenotransplantation efforts. The ACFC lines were treated with 50 nM TSA for 24 h and then the expression profiles of rhα1,2-FT and rhα-Gal A enzymes were analyzed by Western blot and immunofluorescence. The expression profiles of the Galα1→3Gal epitope were determined by lectin blotting and lectin fluorescence. The ACFCs derived from non-transgenic (nTG) pigs were served as the negative (TSA−) and positive (TSA+) control groups. For both hFUT2×hGLA and nTG samples, the expression levels of α1,2-FT and α-Gal A proteins in TSA+ cells were more than twofold higher in comparison to TSA− cells. Moreover, a much lower expression of the Galα1→3Gal epitopes was shown in TSA− hFUT2×hGLA cells as compared to the TSA− nTG group. Interestingly, the levels of Galα1→3Gal expression in TSA-treated hFUT2×hGLA and nTG ACFCs were significantly higher than those noticed for their TSA-untreated counterparts. Summing up, ex vivo protection of effectively selected bi-transgenic ACFC lines, in which TSA-dependent epigenetic transformation triggered the enhancements in reprogrammability and subsequent expression of hFUT2 and hGLA transgenes and their corresponding transcripts, allows for cryopreservation of nuclear donor cells, nuclear-transferred female gametes, and resultant porcine cloned embryos. The latter can be used as a cryogenically conserved genetic resource of biological materials suitable for generation of bi-transgenic cloned offspring in pigs that is targeted at biomedical research in the field of cell/tissue xenotransplantation.


Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 146
Author(s):  
Takahiro Nakayama ◽  
Toshiyuki Fukutomi ◽  
Yasuo Terao ◽  
Kimio Akagawa

The HPC-1/syntaxin 1A (Stx1a) gene, which is involved in synaptic transmission and neurodevelopmental disorders, is a TATA-less gene with several transcription start sites. It is activated by the binding of Sp1 and acetylated histone H3 to the −204 to +2 core promoter region (CPR) in neuronal cell/tissue. Furthermore, it is depressed by the association of class 1 histone deacetylases (HDACs) to Stx1a–CPR in non-neuronal cell/tissue. To further clarify the factors characterizing Stx1a gene silencing in non-neuronal cell/tissue not expressing Stx1a, we attempted to identify the promoter region forming DNA–protein complex only in non-neuronal cells. Electrophoresis mobility shift assays (EMSA) demonstrated that the −183 to −137 OL2 promoter region forms DNA–protein complex only in non-neuronal fetal rat skin keratinocyte (FRSK) cells which do not express Stx1a. Furthermore, the Yin-Yang 1 (YY1) transcription factor binds to the −183 to −137 promoter region of Stx1a in FRSK cells, as shown by competitive EMSA and supershift assay. Chromatin immunoprecipitation assay revealed that YY1 in vivo associates to Stx1a–CPR in cell/tissue not expressing Stx1a and that trichostatin A treatment in FRSK cells decreases the high-level association of YY1 to Stx1a-CPR in default. Reporter assay indicated that YY1 negatively regulates Stx1a transcription. Finally, mass spectrometry analysis showed that gene silencing factors, including HDAC1, associate onto the −183 to −137 promoter region together with YY1. The current study is the first to report that Stx1a transcription is negatively regulated in a cell/tissue-specific manner by YY1 transcription factor, which binds to the −183 to −137 promoter region together with gene silencing factors, including HDAC.


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