NIH/NCI/CCR/LCBG Branch Journal Club
Presented Article:
Pencheva N, Tran H, Buss C, Huh D, Drobnjak M, Busam K, Tavazoie SF. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell. 2012 Nov 21;151(5):1068-82.
Central Research Forum: Up-regulation of ERK3 by BRAF and BRAFV600E mutation in Melanoma (with invited talk), Advisor: Dr. Michael Markey, Wright State University. Host: Boonshoft School of Medicine, Dayton, OH, Oct 22, 2015
Canine oncoprotein targets for Melanoma, Breast Cancer, OsteosarcomaSnehal Salunkhe
We can acquire the basic knowledge about canine oncoprotein targets specifically for Melanoma, Osteosarcoma and Breast cancer. I haven't mentioned all the proteins and their targets involved, but just a general overview of these targets with the drugs involved in their treatment/clinical trials.
The proteasome is a proteolytic protein that acts as proteolysis in the body and results in the formation of many invaders.
In this ubiquitin-proteasome pathway play a key role in catalysis of protein.
Many targets are available of the proteasome by which proteasome inhibitors act and lead to several processes like apoptosis etc.
Direct Lineage Reprogramming: Novel Factors involved in Lineage ReprogrammingAhmed Madni
Direct linage reprogramming has got a major focus in biomedical field. The production of specific functional cell type from totally different cell lineage is called lineage reprogramming. In other words, it is induction of functional cell type from another linage without passing through intermediate stage of pluripotent.
HR Practices and Internal Corporate Social Responsibilityscmsnoida5
This paper made an attempt to put forward the
relationship between human resource practices
and internal corporate social responsibility
(CSR) in Indian Service sector. The paper is
based on extensive literature review and has
documented evidences from previous researches,
wherein similar relationship has been shown. We
argue intrinsic corporate social responsibility goes
parallel to human resource practices in order to
attain higher better. Literature review showed
that internal corporate social responsibility in
combination with human resource practices
leads to improvement in outcome. This study
makes a contribution to the relationship between
corporate social responsibility and human
resource practices by suggesting a relational model
that may be tested in further researches.
HR Bundles for Effective Work Life Balance: An Empirical Studyscmsnoida5
Work Life Balance (WLB) is one of the most
important issues at workplace in today’s
competitive business environment. A large
number of studies have been carried out on WLB
in the human resource and other academic fields.
Most of the studies find major factors related to
the work life balance. This paper, however tries
to find the HR bundles related to various factors
of WLB. The bundles basically club the major
items affecting WLB under limited number
of broad constructs. This study basically works
on the variables related to Job Motivation,
Organizational Culture, Flexi Workings, and
Work Culture etc. For the purpose of this study
data has been collected from 125 IT professionals
from Delhi-NCR. The sampling method is
judgmental sampling where only those employees
have been selected that are married and have at
least one child. Factor analysis and Descriptive
have been used for data analysis. The paper
significantly contributes in the literature by establishing relationship between HR bundles
and Work Life Balance. Further, the study
also finds and elaborates the reasons why these
variables have come up the most important and
bundled together under one broad construct.
Central Research Forum: Up-regulation of ERK3 by BRAF and BRAFV600E mutation in Melanoma (with invited talk), Advisor: Dr. Michael Markey, Wright State University. Host: Boonshoft School of Medicine, Dayton, OH, Oct 22, 2015
Canine oncoprotein targets for Melanoma, Breast Cancer, OsteosarcomaSnehal Salunkhe
We can acquire the basic knowledge about canine oncoprotein targets specifically for Melanoma, Osteosarcoma and Breast cancer. I haven't mentioned all the proteins and their targets involved, but just a general overview of these targets with the drugs involved in their treatment/clinical trials.
The proteasome is a proteolytic protein that acts as proteolysis in the body and results in the formation of many invaders.
In this ubiquitin-proteasome pathway play a key role in catalysis of protein.
Many targets are available of the proteasome by which proteasome inhibitors act and lead to several processes like apoptosis etc.
Direct Lineage Reprogramming: Novel Factors involved in Lineage ReprogrammingAhmed Madni
Direct linage reprogramming has got a major focus in biomedical field. The production of specific functional cell type from totally different cell lineage is called lineage reprogramming. In other words, it is induction of functional cell type from another linage without passing through intermediate stage of pluripotent.
HR Practices and Internal Corporate Social Responsibilityscmsnoida5
This paper made an attempt to put forward the
relationship between human resource practices
and internal corporate social responsibility
(CSR) in Indian Service sector. The paper is
based on extensive literature review and has
documented evidences from previous researches,
wherein similar relationship has been shown. We
argue intrinsic corporate social responsibility goes
parallel to human resource practices in order to
attain higher better. Literature review showed
that internal corporate social responsibility in
combination with human resource practices
leads to improvement in outcome. This study
makes a contribution to the relationship between
corporate social responsibility and human
resource practices by suggesting a relational model
that may be tested in further researches.
HR Bundles for Effective Work Life Balance: An Empirical Studyscmsnoida5
Work Life Balance (WLB) is one of the most
important issues at workplace in today’s
competitive business environment. A large
number of studies have been carried out on WLB
in the human resource and other academic fields.
Most of the studies find major factors related to
the work life balance. This paper, however tries
to find the HR bundles related to various factors
of WLB. The bundles basically club the major
items affecting WLB under limited number
of broad constructs. This study basically works
on the variables related to Job Motivation,
Organizational Culture, Flexi Workings, and
Work Culture etc. For the purpose of this study
data has been collected from 125 IT professionals
from Delhi-NCR. The sampling method is
judgmental sampling where only those employees
have been selected that are married and have at
least one child. Factor analysis and Descriptive
have been used for data analysis. The paper
significantly contributes in the literature by establishing relationship between HR bundles
and Work Life Balance. Further, the study
also finds and elaborates the reasons why these
variables have come up the most important and
bundled together under one broad construct.
DNA and RNA Structure
Central Dogma of Life
Protein Engineering (Brief)
Introduction to microRNA (miRNA)
History of miRNA
Biogenesis of miRNA
Conservation of miRNA
Impact of miRNA
miRNA Therapy
Conclusion
Review of Cell Press Article titled:
"Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module."
Jared Toettcher, Orion Weiner, Wendell Lim
Cell. 2013 Dec 5;155(6):1422-34. doi: 10.1016/j.cell.2013.11.004.
Adventure in Science is about exploring our world by doing. Each Saturday during the school year we have hands-on sessions hosted by local experts on some aspect of science or engineering that they find exciting or interesting. During these sessions the students get to experiment with the tools or ideas involved to better understand how they really work. Sometimes those ideas can grow into something new and make a difference in the world. Who says science isn't fun?
During this session we taught kids about the physics of simple machines.
http://www.adventureinscience.org/
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
for beginners, providing thorough training in areas such as SEO, digital communication marketing, and PPC training in Noida. After finishing the program, students receive the certifications recognised by top different universitie, setting a strong foundation for a successful career in digital marketing.
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Advantages and Disadvantages of CMS from an SEO Perspective
11.27.12 - LCBG Department Journal Club
1. Journal ClubJournal Club
Nov 27, 2012
LCBG
Dr. Hunter’s Lab
Farhoud Faraji Kent Hunter, PhD
Your
Picture
here
Your Mentor’s
Picture
here
2. microRNA
Family of post-
transcriptional regulatory
small RNAs
Concepts:
•miR can ‘promiscuously’
bind mRNAs
– Each miR has many targets
•mRNAs can ‘promiscuously’
bind miRs
– Each mRNA is targeted by
many miRs He and Hannon. 2009
5. In vivo Selection of Metastatic Clones
Assumption
Clones only differ from parental line in molecular and
cellular phenotypes related to the metastatic
potential
6. Objective
• Use in vivo selection to find prometastatic
microRNAs in melanoma
Strategy
• Construct highly metastatic lines from poorly
metastatic parental human melanoma lines
• Look for microRNAs with:
– High expression in highly metastatic clone
– Low expression in poorly metastatic parental
7. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. m1908 and m199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
8. MeWo: Melanotic A375: Amelanotic
In vivo Selection of Highly Metastatic
Human Melanoma Cell Lines
9. Identification of Differentially
Expressed miRNAs
Array-based miR Global Profiling Taqman Validation
miR-1908
miR-214
miR-199a
are more highly expressed in
highly metastatic daughter clones
10. Functional Validation: Ectopic Expression
Ectopic expression of miR-1908 and miR-199a enhances the
metastatic potential of the poorly metastatic MeWo parental line.
11. Inhibition of miR-1908, miR-199a-5p, and miR-199a-3p diminishes
the metastatic potential MeWo and A375 highly metastatic clones.
Functional Validation: miR Knockdown
Do not show data for miR expression levels upon knockdown.
12. Blinded Analysis of Clinical Samples of
Human Melanoma
All three miRs are more highly expressed in melanomas
that had metastasized
13. Summary 1
• Highly metastatic clones generated from two
independent human melanoma cell lines
• miR-1908, miR-199a, and miR-214 more highly
expressed in highly metastatic clones
• Ectopic expression of miR-1908 and miR-199a
enhances metastasis.
• Knockdown of m1908, m199a-5p, and m199a-
3p inhibits metastasis.
• m1908, m199a-5p, and m199a-3p more highly
expressed in metastatic clinical samples
14. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. m1908 and m199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
15. miR-199a and miR-1908 impact on primary
tumor and in vitro phenotypes
Anoikis Serum Starvation Colony Formation
Endothelial AdhesionProliferation
18. Each miR required and sufficient for enhanced metastatic nodule
endothelial content and perfusion.
miR-199a and miR-1908 Promote in vivo
Angiogenesis
19. Summary 2
• miR-199a suppresses tumor growth
• miR-1908, miR-199a reduce in vitro tumor cell
proliferation
• miR-1908, miR-199a promote in vitro invasion
and endothelial cell recruitment
• miR-1908, miR-199a promote angiogenesis
and perfusion of metastatic nodules in vivo
20. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. m1908 and m199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
21. Identification of ApoE and DNAJA4 as
Targets of miR-199a and miR-1908
Strategy: find transcripts inversely correlated to miR
expression in all cases.
• miR OE
• miR KD
• parental vs metastatic clone
26. Summary 3
• ApoE and DNAJA4 expression inversely
correlates with miR-1908 and miR-199a
expression
• miR-1908 and miR-199a directly target ApoE
and DNAJA4
27. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. m1908 and m199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
28. ApoE and DNAJA4 Knockdown Promotes
Invasion and Endothelial Cell Recruitment
29. ApoE and DNAJA4 Expression Inhibits
Invasion and Endothelial Cell Recruitment
30. Knockdown of miR targets in the context of miR-1908 and
miR-199a knockdown rescues in vitro phenotypes
31. Knockdown of ApoE and DNAJA4 in the context of miR-
1908 & miR-199a knockdown rescues metastasis in vivo
32. Overexpression of ApoE and DNAJA4 suppresses miR-
1908-induced invasion and endothelial cell recruitment
33. Overexpression of ApoE and DNAJA4 suppresses miR-
199a-induced invasion and endothelial cell recruitment
34. Concurrent Knockdown of ApoE and DNAJA4 in the
Context of Triple miR Knockdown Rescues in vitro
Invasion and Endothelial Cell Recruitment
35. Concurrent Knockdown of ApoE and DNAJA4 in the
Context of Triple miR Knockdown Rescues Angiogenesis
and Metastatic Nodule Perfusion in vivo
36. ApoE and DNAJA4 Inhibit Metastatic Effect of
miR-1908 Expression in vivo
37. Summary 4
• ApoE and DNAJA4 expression inversely
impacts invasion and endothelial cell
recruitment in vitro
• ApoE and DNAJA4 epistatically interact with
miR-199a and miR-1908 to regulate:
– in vitro invasion and endothelial recruitment
– in vivo angiogenesis and metastatic coloinzation
38. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. m1908 and m199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
39. ApoE Secretion is Inversely Correlated with
miR-199a and miR-1908 Expression
42. Recombinant ApoE rescues
inhibition of in vitro invasion and
endothelial cell recruitment in the
context of DNAJA4 knockdown
Neutralizing ApoE
antibody rescues
in vitro invasion
and endothelial cell
recruitment in the
context of DNAJA4
expression
44. Pretreatment with Recombinant ApoE
Suppresses Metastatic Potential
Suggests a role for ApoE
downstream signaling in
metastasis suppression
45. ApoE Expression is Reduced in Nodal and
Distal Metastases Relative to Primary Tumor
46. Genetic Inactivation of ApoE
Promotes Metastasis
Pretreatment with ApoE inhibits metastatic colonization.
• Implicates stromal ApoE in metastasis suppression
47. Summary 5
• Extracellular ApoE Inhibits in vitro invasion
and endothelial cell recruitment
• DNAJA4 regulates ApoE expression
• Pretreatment with recombinant ApoE
suppresses metastatic potential
• ApoE expression is reduced in nodal and distal
metastases relative to primary tumor
• Absence of stromal ApoE promotes metastatic
colonization
48. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. m1908 and m199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
55. ApoE null mice have increased endothelial
cell density in metastatic nodules
ApoE suppresses of in vivo angiogenesis of metastatic nodules
56. Summary 6
1. LRP1 mediates ApoE-mediated suppression
of in vitro invasion in melanoma cells
2. LRP1 mediates ApoE-mediated suppression
of metastasis in vivo
3. LRP8 mediates ApoE-mediated suppression
of in vitro migration of endothelial cells
4. ApoE suppresses angiogenesis in metastatic
nodules in vivo
57. Outline
1. Endogenous miR-1908, miR-199a-3p, and miR-199-5p
Promote Human Melanoma Metastasis.
2. m1908 and m199a Promote Invasion, Endothelial
Recruitment, and Angiogenesis.
3. m1908 and m199a Convergently and Cooperatively
Target ApoE and DNAJA4
4. ApoE and DNAJA4 Mediate m199 and m1908-
Dependent in vitro and in vivo Metastatic Phenotypes
5. ApoE Suppresses Invasion, Endothelial Recruitment, and
Metastasis
6. Extracellular ApoE Divergently Targets Melanoma Cell
LRP1 and Endothelial Cell LRP8 receptors
7. miR-1908 and miR-199a are Robust Prognostic and
Therapeutic Targets in Melanoma Metastasis
64. Summary 7
1. miR-199a and miR-1908 predict distant
metastasis free survival in patient cohorts
2. Transfection with anti-miR LNAs suppresses
metastasis of intravenous and intra-cardiac
injected melanoma cells
3. Systemic treatment with anti-miR LNAs
suppresses metastasis
65. Model
miR-199a and miR-1908 are robust prognostic and therapeutic targets.
ApoE is a potent suppressor of melanoma metastasis via its effects on
tumor cell invasion and metastatic endothelial cell recruitment