This study used the AlfaMC Monte Carlo code to simulate microdosimetry quantities for 211At distributions in single and multiple thyroid follicle models for humans, rats, and mice. The mean and single-hit mean specific energies were calculated for 211At homogeneously distributed in different parts of the follicle models and compared to results from MCNPX and GEANT4 codes. The results from AlfaMC agreed very well with those from MCNPX, demonstrating AlfaMC is a suitable and faster code for these types of alpha particle simulations. Graphs of the single-hit mean specific energy distribution and as a function of 211At source radius in the human multiple follicle model are presented.
Depending on the cell of tissue of origin, exosomes act as many different roles and functions including eradication of obsolete molecules, intercellular communication, antigen presentation, programmed cell death, dissemination of oncogenes from tumor cells, and spread of pathogens, such as prions and viruses from one cell to another, and transfer of tumorigenic proteins, mRNA and miRNA. For example, exosomes from certain cells of the immune system, such as dendritic cells and B cells, containing immunologically active substance can transfer molecules from one cell to another via membrane vesicle trafficking, thereby mediating adaptive immune responses to pathogens and tumors. https://www.creative-biolabs.com/exosome/services.htm
In interactome, basically for interaction of proteins there is certain key elements requited, they are: Interactomics and Proteomics, Complementation groups, Modifier screens 1. Interactomics and Proteomics
Field of interactomics is concerned with interactions between genes or proteins. They can be genetic interactions, in which two genes are mainly involved in the same functional pathway (leading to a particular phenotype), or physical interactions, in which there is direct physical contact between two proteins (or between protein and DNA) (Janga et al.,2008). 2. Complementation groups Using forward saturation genetics, one may recover several independent mutants with the same (or similar) phenotype (Hernández et al., 2007). There are two possibilities: a) Mutations are in the same gene b) Mutations are in different genes involved in the same pathway. Scenario
(b) Can be tested genetically with a complementation test:
Cross two homozygous mutants (samples) and observe heterozygous offspring phenotypes(samples)
Mutations in the same gene will not complement
offspring have mutant phenotype
Mutations in different genes will complement
offspring have wild
Type phenotype
Do pairwise crosses for all mutants to identify complementation groups
Typically each complementation group represents a different gene
If many mutations are recovered in the same genes, this implies saturation
Depending on the cell of tissue of origin, exosomes act as many different roles and functions including eradication of obsolete molecules, intercellular communication, antigen presentation, programmed cell death, dissemination of oncogenes from tumor cells, and spread of pathogens, such as prions and viruses from one cell to another, and transfer of tumorigenic proteins, mRNA and miRNA. For example, exosomes from certain cells of the immune system, such as dendritic cells and B cells, containing immunologically active substance can transfer molecules from one cell to another via membrane vesicle trafficking, thereby mediating adaptive immune responses to pathogens and tumors. https://www.creative-biolabs.com/exosome/services.htm
In interactome, basically for interaction of proteins there is certain key elements requited, they are: Interactomics and Proteomics, Complementation groups, Modifier screens 1. Interactomics and Proteomics
Field of interactomics is concerned with interactions between genes or proteins. They can be genetic interactions, in which two genes are mainly involved in the same functional pathway (leading to a particular phenotype), or physical interactions, in which there is direct physical contact between two proteins (or between protein and DNA) (Janga et al.,2008). 2. Complementation groups Using forward saturation genetics, one may recover several independent mutants with the same (or similar) phenotype (Hernández et al., 2007). There are two possibilities: a) Mutations are in the same gene b) Mutations are in different genes involved in the same pathway. Scenario
(b) Can be tested genetically with a complementation test:
Cross two homozygous mutants (samples) and observe heterozygous offspring phenotypes(samples)
Mutations in the same gene will not complement
offspring have mutant phenotype
Mutations in different genes will complement
offspring have wild
Type phenotype
Do pairwise crosses for all mutants to identify complementation groups
Typically each complementation group represents a different gene
If many mutations are recovered in the same genes, this implies saturation
A normal cell can be transformed into a cancerous cell. Discuss the therapeutic strategies that are employed to target the cellular transformation process for cancer prevention and treatment.
A physical sciences network characterization of non-tumorigenic and metastati...Shashaanka Ashili
To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the
Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic DA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells’ regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.
World-wide data exchange in metabolomics, Wageningen, October 2016Christoph Steinbeck
Talk given at the Netherlands Institute of Ecology in Wageningen, where I describe the development of the MetaboLights database and the value of data sharing in Metabolomics and molecular Biology in General
Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal Stem Cells (MSCs) play an important role in tissue homeostasis supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great potential in cancer therapy, also the stem cell exosome and/or microvesicle-mediated tissue regeneration abilities may be used a potential to the therapeutic applications. In this review, use of hMSCs in stem cell-mediated cancer therapy is discussed.
Genes and Tissue Culture Technology Assignment (G6)Rohini Krishnan
The culture of cells in two dimensions does not reproduce the histological characteristics of a tissue for informative or useful study. Growing cells as three-dimensional (3D) models more analogous to their existence in vivo may be more clinically relevant.
Chlorella Vulgaris Alleviates Lead-induced Testicular Toxicity Better than Zi...Prof. Hesham N. Mustafa
Natural products are studied to combat reproductive alterations of Lead. The current work aim to disclose the efficacy of Chlorella vulgaris and Zingiber officinale to alleviate lead acetate induced toxicity. Sixty adult male Wistar rats were distributed into four groups. Group 1 was considered control, group 2 received 200 mg/l PbAc water, group 3 received 50 mg/kg/rat of C. vulgaris extract and 200 mg/l PbAc water, and group 4 received 100 mg/kg/rat of Z. officinale and 200 mg/l PbAc water for 90 days. Testis samples were subjected to ultrastructural examination. It is observed that PbAc caused degenerative alterations in the spermatogenic series in many tubules, with a loss of germ cells and vacuoles inside the cytoplasm and between the germ cells. Mitochondria exhibited ballooning, with lost cristae and widening of the interstitial tissue, destructed nuclear envelopes of primary spermatocytes, and distortion of the axonemes of the mid-pieces of the sperms. With the treatment with C. vulgaris or Z. officinale, there were noticeable improvements in those modifications. It has concluded that both C. vulgaris and Z. officinale represent convincing medicinal components that may be used to ameliorate testicular toxicity in those exposed to lead in daily life with superior potentials revealed by C. vulgaris due to its chelating action. in XXIV International Symposium on Morphological Sciences on 2nd- 6th September, 2015 Oral Presentation [O-02].at Prof. Dr. Cemil Bilsel Congress Hall, Faculty of Science, Istanbul University, Istanbul, Turkey.
Using Pathway Studio in Neurodegenerative diseaseAnn-Marie Roche
Dr. Gabor Juhasz of ELTE University in Budapest discusses use of Pathway Studio in the study of neurodegenerative diseases such as Alzheimer’s Disease.
MRI rat organ Assessment under recurrent Interferon administrationtheijes
This study aims to assess serial and transverse quantitative Magnetic Resonance Imaging (MRI) in four rat groups using different doses of a formulation based on the combinations of IFN alpha 2b and gamma. Axial and coronal T1, T2 and Diffusion MRI images have been performed in order to follow up morphological and tissue texture changes in the rat brain, cerebellum, spinal cord and kidney. As a result, no morphological changes have been observed during 28 days in any of the four groups including the placebo. Yet, doses until 15 times were bigger than the therapeutic dose. This MRI studies is robust and complementary evidence that the pharmaceutical formulation mixing in the same vial IFNs alpha2b and gamma is safe. For the first time, results of a longitudinal MRI study in rats based on the effects of this pharmacological combination are reported.
A normal cell can be transformed into a cancerous cell. Discuss the therapeutic strategies that are employed to target the cellular transformation process for cancer prevention and treatment.
A physical sciences network characterization of non-tumorigenic and metastati...Shashaanka Ashili
To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the
Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic DA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells’ regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.
World-wide data exchange in metabolomics, Wageningen, October 2016Christoph Steinbeck
Talk given at the Netherlands Institute of Ecology in Wageningen, where I describe the development of the MetaboLights database and the value of data sharing in Metabolomics and molecular Biology in General
Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal Stem Cells (MSCs) play an important role in tissue homeostasis supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great potential in cancer therapy, also the stem cell exosome and/or microvesicle-mediated tissue regeneration abilities may be used a potential to the therapeutic applications. In this review, use of hMSCs in stem cell-mediated cancer therapy is discussed.
Genes and Tissue Culture Technology Assignment (G6)Rohini Krishnan
The culture of cells in two dimensions does not reproduce the histological characteristics of a tissue for informative or useful study. Growing cells as three-dimensional (3D) models more analogous to their existence in vivo may be more clinically relevant.
Chlorella Vulgaris Alleviates Lead-induced Testicular Toxicity Better than Zi...Prof. Hesham N. Mustafa
Natural products are studied to combat reproductive alterations of Lead. The current work aim to disclose the efficacy of Chlorella vulgaris and Zingiber officinale to alleviate lead acetate induced toxicity. Sixty adult male Wistar rats were distributed into four groups. Group 1 was considered control, group 2 received 200 mg/l PbAc water, group 3 received 50 mg/kg/rat of C. vulgaris extract and 200 mg/l PbAc water, and group 4 received 100 mg/kg/rat of Z. officinale and 200 mg/l PbAc water for 90 days. Testis samples were subjected to ultrastructural examination. It is observed that PbAc caused degenerative alterations in the spermatogenic series in many tubules, with a loss of germ cells and vacuoles inside the cytoplasm and between the germ cells. Mitochondria exhibited ballooning, with lost cristae and widening of the interstitial tissue, destructed nuclear envelopes of primary spermatocytes, and distortion of the axonemes of the mid-pieces of the sperms. With the treatment with C. vulgaris or Z. officinale, there were noticeable improvements in those modifications. It has concluded that both C. vulgaris and Z. officinale represent convincing medicinal components that may be used to ameliorate testicular toxicity in those exposed to lead in daily life with superior potentials revealed by C. vulgaris due to its chelating action. in XXIV International Symposium on Morphological Sciences on 2nd- 6th September, 2015 Oral Presentation [O-02].at Prof. Dr. Cemil Bilsel Congress Hall, Faculty of Science, Istanbul University, Istanbul, Turkey.
Using Pathway Studio in Neurodegenerative diseaseAnn-Marie Roche
Dr. Gabor Juhasz of ELTE University in Budapest discusses use of Pathway Studio in the study of neurodegenerative diseases such as Alzheimer’s Disease.
MRI rat organ Assessment under recurrent Interferon administrationtheijes
This study aims to assess serial and transverse quantitative Magnetic Resonance Imaging (MRI) in four rat groups using different doses of a formulation based on the combinations of IFN alpha 2b and gamma. Axial and coronal T1, T2 and Diffusion MRI images have been performed in order to follow up morphological and tissue texture changes in the rat brain, cerebellum, spinal cord and kidney. As a result, no morphological changes have been observed during 28 days in any of the four groups including the placebo. Yet, doses until 15 times were bigger than the therapeutic dose. This MRI studies is robust and complementary evidence that the pharmaceutical formulation mixing in the same vial IFNs alpha2b and gamma is safe. For the first time, results of a longitudinal MRI study in rats based on the effects of this pharmacological combination are reported.
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Characterization of embryoid bodies formed with different protocols 使用不同培養方式形...Honey Cheng
That's part of my first year master researching in 2011, National Chung Hsing-University, Taiwan. Mice embryonic stem cells differentiating with embryoid bodies in a unattached formed, so I summarized a slides review. 這是2011年在中興就讀研究所第一年時所研究的方向. 胚胎幹細胞能夠在懸浮狀態形成類胚體與分化, 所以為此我整理了一份簡報, 介紹不同方式形成類胚體之特性.
Epithelial reticular Cells of Egyptian Water buffalo (Bosbubalis)IOSRJAVS
Thymus obtained from10 clinically healthy Egyptian water male buffalo (Bosbubalis). Their ages ranged between 2to 3 years old. The thymus of Egyptian water buffalo was divided by septa into many lobules; each lobule had outer, cortex and inner medulla. The epithelial reticular cells were classified according to their staining affinity, morphology and position into 4 types, three were found within the cortex and one in the medulla. In cortex epithelia reticular cells type I (ER 1) had elongated nucleus of irregular or triangular shape with marginal heterochromatin clumps along the nuclear membrane. Epithelial reticular cells type II(ER II) were irregular in shape with pale stained cytoplasm and the nuclei were large and spherical having euchromatin. Epithial reticular cells type III(ERIII) were characterized by large nucleus of irregular shape having marginal heterochromatin .In medulla epithelial reticular (ER) cells of type IV, they were the largest epithelial cells forming the unique elements of the thymic medulla (Hassall's corpuscles)). Cytoplasm was occupied by many small vacuoles ,very large vacuole appeared in the cytoplasm pushed the nucleus into one side.
1. References :
[1] arxiv.org/abs/1211.5960
[2] Josefsson A, Forssell-Aronsson E. Microdosimetric analysis of 211At
in thyroid models for man, rat and mouse. EJNMMI Res. 2012;2(1):29.
Small scale dosimetry for 211At distribution in thyroid follicle models
using AlfaMC Monte Carlo simulations
Romiani A, Chakarova R, Forssell-Aronsson E
Department of Radiation Physics, Institute of clinical Sciences, Sahlgrenska Cancer Center,
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Background
Radionuclide therapy, using radionuclides attached to tumor targeting
carriers, is an increasing therapy method well suited for metastatic tumor
diseases.
The alpha-emitter 211At has been proposed for therapy both as free
radionuclide and attached to tumor-seeking carriers. Regardless of the choice
of chemical form, it is necessary to estimate the distribution of free 211At,
and corresponding absorbed dose to potential risk organs, since 211At can be
released from the carrier molecule in vivo. The thyroid gland is considered to
be one of the vital risk organs, in case of internal contamination of free
211At.
Monte Carlo (MC) technique is an appropriate statistical method for
dosimetric calculations and is well suited to master the stochastic nature of
radiation transport. AlfaMC is a relatively new MC code that was introduced
in 2012 by Luis Peralta and Alina Louro at the Science faculty of the
University of Lisbon [1]. Comparison with other MC codes has shown good
agreement for alpha particles with energies between 1 MeV and 12 MeV [1].
Purpose
To determine microdosimetric quantities for homogeneous and
heterogeneous 211At distribution within different thyroid follicle models
using Monte Carlo code AlfaMC and compare the results with previously
published results from similar studies using MC code MCNPX [2] and
results from MC code GEANT4.
Methods
A single- and a multiple-thyroid follicle model were developed, for man, rat
and mouse [2]. The single-thyroid follicle model (Figure 1a) represents a
single sphere-shaped thyroid follicle and consists of a spherical follicle
lumen, a layer of follicle cells (shaped as a shell around the follicle lumen)
and six spherical follicle cell nuclei distributed symmetrically at equal
distances from the center of the follicle lumen.
The multiple-thyroid follicle model represents the case where the thyroid
follicle is surrounded by neighboring follicles (Figure 1 b). The follicle cells
from the neighboring follicles form a spherical shell around the follicle cells
in the center follicle and around their merged lumens.
Four different locations and distributions of 211At were simulated: 211At was
homogeneously distributed 1) within the follicle lumen, 2) within the follicle
cells, 3) within the follicle cell nuclei, and 4) on the surface of concentric
spheres, with their center located at the center of the follicle lumen
(representing heterogeneous distribution of 211At). In all simulations the
targets were the six follicle cell nuclei.
Conclusion
The overall agreement between results from AlfaMC and MCNPX was
very good. AlfaMC is a faster MC code that showed to be suitable for
these types of simulations.
Results
The mean specific energy, 𝑧 , and the single-hit mean specific energy, 𝑧1 ,
are shown in Table for the single follicle model. The single-hit mean specific
energy distribution, f(z1) is given in Figure 2 for 211At in the follicle cells.
𝑧1 for the human multiple follicle model is shown in Figure 3.
Table. The mean specific energy, 𝒛 , and the single-hit mean specific energy, 〈𝒛 𝟏〉, in the
follicle cell nuclei calculated by AlfaMC, MCNPX [2] and GEANT4 for single thyroid follicle
models, for mouse, rat and man. 211At was homogenously distributed in the follicle lumen.
Data is given as mean (SD). The percentage difference between results from the codes is
presented in the last three rows.
Figure 2. Single-hit mean specific energy distribution, f(z1), in the thyroid follicle cell
nuclei with the follicle cells as the source, simulated with AlfaMC and MCNPX [2]. The
curves simulated with AlfaMC were normalized such that the area under each curve is equal to
1. Due to different normalizations the scale on y-axes differ.
Figure 1. Schematic figures of the a) single- and b) multiple-thyroid follicle
models [2]. The follicle cells, the follicle lumen and the follicle cell nuclei are green, blue
and red, respectively. The multiple-thyroid follicle model is presented to the right, the light
green color represents the neighboring follicle cells. Each component had the density of
liquid water (1.0 g/cm3).
Figure 3. Single-hit mean specific energy as a function of the radius of the 211At
surface source for a human multiple follicle model, simulated with AlfaMC and
MCNPX [2]. The two follicle cell layers are shown by dotted lines. SD is presented as error
bars, but in general smaller than data symbols.
a) b)