The chromodomain regions of HP1 and Polycomb (PC) protein families play a critical role in chromatin remodeling by binding to methylated lysine residues on histone tails. Computational analyses found these regions to be highly similar structurally, with key residues important for interacting with histone marks. Molecular dynamics simulations provided insights into how individual chromodomains recognize trimethylated lysine marks. These findings further understanding of epigenetic regulation by these proteins and could aid development of small molecule inhibitors for diseases where they are dysregulated, such as cancer.
Inhibition of glutathione by buthionine sulfoximine enhanced the anti-cancer ...Ashujit
Multiple myeloma (MM) is an incurable blood cancer. Melphalan is an alkylating agent given prior to stem cell transplantation to MM patients. Increased glutathione confers resistance to melphalan. This study investigate the effect of inhibition of glutathione by BSO in preclinical models of MM. Pretreatment with BSO enhanced the anti-cancer effect of melphalan in cell lines and animal models. BSO and melphalan combination was well tolerated by animals and enhanced the survival as compared to controls, BSO and melphalan alone. BSO enhanced depth and duration of responses induced by melphalan. In the combination group, majority of treated animals achieved complete response (CR) and more than 20% had maintained CR. Also, the survival of animals was doubled after combination treatment as compared to BSO or melphalan alone. Mechanistic investigation demonstrated that BSO enhanced melphalan induced DNA damage, caspase cleavage and apoptosis. The combination also achieved multi-logs of cells kills in nine human multiple myeloma cell lines and primary MM cells isolated from blood and bone marrows. Interestingly, the effect of BSO and melphalan combination was abolished when cells were treated with N-acetyl cysteine and sodium thiosulfate but not with vitamin C and vitamin E. This observation suggests that effect of BSO is primarily driven by its ability to deplete glutathione and therefore preventing melphalan detoxification. Together, this study provides framework for testing the combination in a Phase I trial.
Annals of Mutagenesis is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Mutagenesis.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Mutagenesis. Annals of Mutagenesis accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of mutagenesis.
Annals of Mutagenesis strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Inhibition of glutathione by buthionine sulfoximine enhanced the anti-cancer ...Ashujit
Multiple myeloma (MM) is an incurable blood cancer. Melphalan is an alkylating agent given prior to stem cell transplantation to MM patients. Increased glutathione confers resistance to melphalan. This study investigate the effect of inhibition of glutathione by BSO in preclinical models of MM. Pretreatment with BSO enhanced the anti-cancer effect of melphalan in cell lines and animal models. BSO and melphalan combination was well tolerated by animals and enhanced the survival as compared to controls, BSO and melphalan alone. BSO enhanced depth and duration of responses induced by melphalan. In the combination group, majority of treated animals achieved complete response (CR) and more than 20% had maintained CR. Also, the survival of animals was doubled after combination treatment as compared to BSO or melphalan alone. Mechanistic investigation demonstrated that BSO enhanced melphalan induced DNA damage, caspase cleavage and apoptosis. The combination also achieved multi-logs of cells kills in nine human multiple myeloma cell lines and primary MM cells isolated from blood and bone marrows. Interestingly, the effect of BSO and melphalan combination was abolished when cells were treated with N-acetyl cysteine and sodium thiosulfate but not with vitamin C and vitamin E. This observation suggests that effect of BSO is primarily driven by its ability to deplete glutathione and therefore preventing melphalan detoxification. Together, this study provides framework for testing the combination in a Phase I trial.
Annals of Mutagenesis is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Mutagenesis.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Mutagenesis. Annals of Mutagenesis accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of mutagenesis.
Annals of Mutagenesis strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Los modelos teóricos presentados en este artículo pretenden mostrar porqué el exponente de ¾ de la ley de Kleiber puede surgir de las restricciones que impone distribuir los recursos a través de redes de ramificación jerárquica
The Effects of Genetic Alteration on Reprogramming of Fibroblasts into Induc...remedypublications2
Induced Pluripotent Stem Cells (iPSCs) can be generated from somatic cells by ectopic expression of
Yamanaka factors (
Oct4
,
Sox2
,
Klf4
and
c-Myc
) or combination of other factors. Genetic alteration
of fibroblasts exhibits an effect on reprogramming efficiency through multiple signaling pathways,
including epigenetic modifications, metabolic shifts, Mesenchymal-To-Epithelial Transition
(MET) and cell proliferation. In order to better understand the underlying mechanisms in cell fate
determination, in this review we will summarize several genetic alterations involved in the regulation
of reprogramming fibroblasts into iPSCs.
Reading circle of Epigenome Roadmap: Roadmap Epigenomics Consortium et. al. I...Itoshi Nikaido
Reading circle of Epigenome Roadmap
Roadmap Epigenomics Consortium et. al. Integrative analysis of 111 reference human epigenomes, doi:10.1038/nature14248
Los modelos teóricos presentados en este artículo pretenden mostrar porqué el exponente de ¾ de la ley de Kleiber puede surgir de las restricciones que impone distribuir los recursos a través de redes de ramificación jerárquica
The Effects of Genetic Alteration on Reprogramming of Fibroblasts into Induc...remedypublications2
Induced Pluripotent Stem Cells (iPSCs) can be generated from somatic cells by ectopic expression of
Yamanaka factors (
Oct4
,
Sox2
,
Klf4
and
c-Myc
) or combination of other factors. Genetic alteration
of fibroblasts exhibits an effect on reprogramming efficiency through multiple signaling pathways,
including epigenetic modifications, metabolic shifts, Mesenchymal-To-Epithelial Transition
(MET) and cell proliferation. In order to better understand the underlying mechanisms in cell fate
determination, in this review we will summarize several genetic alterations involved in the regulation
of reprogramming fibroblasts into iPSCs.
Reading circle of Epigenome Roadmap: Roadmap Epigenomics Consortium et. al. I...Itoshi Nikaido
Reading circle of Epigenome Roadmap
Roadmap Epigenomics Consortium et. al. Integrative analysis of 111 reference human epigenomes, doi:10.1038/nature14248
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.
Crimson publishers-5-MethylcytosineDNA Methylation Patterns among Gut Predomi...CrimsonpublishersMedical
5-MethylcytosineDNA Methylation Patterns among Gut Predominate Commensal Escherichia coli and Lactobacilli from the Balbas and Mazekh Domestic Sheep Breeds by Pepoyan AZ* in Research in Medical &Engineering Sciences
Identification of the Enrichment Pathways of Catalase in Multiple Primary Tumorsdaranisaha
Reactive oxygen species (ROS) has been detected in almost all cancers, which it involves many aspects of carcinogenesis and tumor progression. We previously reported a novel oncogenic role of manganese superoxide dismutase (MnSOD; SOD2) in invasive lung adenocarcinoma (LUAD) by upregulating forkhead box protein M1 (FOXM1) and matrix metalloproteinase-2 (MMP2) expression. In this study, we used a comprehensive analysis and further evaluated the effects of a hydrogen peroxide (H2O2) scavenger, catalase (CAT) in The Cancer Genome Atlas (TCGA) datasets of the different cancer types.
Research Paper Presentation- Systematic protein location mapping reveals five...Sneha Verghese
A presentation of the findings of the 2010 research paper- "Systematic protein location mapping reveals five principal chromatin types in drosophila cells"