Stem cells in neurobiology
18 important questions on Stem cells in neurobiology
To which manifestations leads lower motor neuron degeneration?
To which manifestations leads upper motor neuron degeneration?
Which two types of ALS are there?
- Sporadic (90%) --> no familial history
- Familial (10%)
- Higher grades + faster learning
- Never study anything twice
- 100% sure, 100% understanding
For my 1st exam I got a C. Then, I started looking for ways to learn better and I came across Study Smart. Since then I have scored a A+, A, A- and another A. I highly recommend it to everyone who wants to hear it. I am so happy with it!!
I was struggling to finish all my first-year subjects for 3 years. Then I discovered Study Smart, which helped me to finish all of them within 3 months.
Because of StudySmart, things are going well in many ways. Before, I always had study stress and no time for anything. Now I feel calm and confident (because of the program). I used to score a B, now I usually score an A or A+.
Hey Chris, I really want to thank you very much for developing the platform, I usually got around C for my exams, now I scored an A+, an A and a A- !!
Since using Study Smart, my average has increased significantly. I even completed a statistics course with a A+ while I'm bad at statistics. I took on extra courses this year, because of Study Smart. Thanks so much!
Ever since I started studying with StudySmart I passed all my exams !!! No more re-sits!! At first, I was happy with a pass and now I only get good grades. Many thanks!
I aced all the courses I studied with Study Smart. For law, I first scored a D, and now an A! I’m 100% sure that I’ll pass all the courses I study with Study Smart.
I always thought I studied well. My grades were fine. I could never have imagined that applying these study skills would have such a huge and direct impact on my grades, my speed and the pleasure I have in learning.
For the first time, I finally feel totally confident about the way I learn. I have the perfect overview and make great progress in terms of speed and the grades I get. Thanks, Chris!
I immediately started to enjoy learning again, and my grades soared. All of a sudden, everything went better. I highly recommend Study Smart to all students..
Being able to create my materials online made the process of studying so much smoother and quicker. I no longer have to spend a huge amount of my time on creating my summaries.
At first, my notes were a mess. Now I use Study Smart to take my notes in a perfectly structured way. It helps me to save a lot of time and do other things I enjoy.
Students that study with Study Smart get better grades. The system applies all the learning methods in such a way that both well-performing students and students who struggle perform much better.
Hi Chris, I would like to thank you very much. Last year I scored C on a course, and this year I got an A+ thanks to your method! Thank you very much!
The largest effect is that my child is more enthusiastic about school! Every parent wants their children to be happy at school, Study Smart made it happen.
In high school, I failed several exams, and that has really changed now. I actually needed this tool very much back then. Since I started studying with StudySmart, I haven't had any D's. My average score is now an A and those are results I would have never had in the past
With my old method, I passed only 3 out of 8 courses. Since I started taking my notes digitally in Study Smart, I have passed all my courses on the first try. For me, StudySmart takes away the stress of wondering if I will pass or not.
Thanks to StudySmart, I passed all my exams, and with better grades than before! On top of that, I have mastered a very good study method now, which I am confident will help me earn my degree.
Which classes of genes can be affected in ALS?
In which 2 ways can iPCSs derived from FUS-ALS patients and healthy controls be generated?
- Skin punch biopsy of dermis
- Fibroblasts from dermis --> dedifferentiation/reprogramming into iPSCs, by adding OKSM/Yamanaka factors (delivered using a retro- or lentiviral vector
Method 2:
- Plucked human hair
- Convert into keratinocyte culture
- Add Yamanaka factors to keratinocytes --> iPSCs
How can iPSCs be characterized?
- Karyotyping --> euploidy verification via microarray profiling of SNPs --> checking whether all 46 chromosomes (human) are present
- Genotyping
- Immunostaining for pluripotency markers (e.g. Nanog, Oct4, Sox2, SSEA4, TRA-1-60)
- Pluripotent differentiation potential: formation of embryoid bodies and differentiation into the three different germ layers + verification by immunostainings for markers
How is motor neuron differentiation verified?
What are the pro's of iPSC-derived models of diseases?
- They recapitulate the genetic situation in patients
- They are human cells --> no evolutionary distance
- the disease-relevant cell type(s) can be generated
- Key hallmarks of the disease can be recapitulated
- E.g (neuro)pathological hallmarks, e.g loss of neuronal populations, formation of cytoplasmic protein aggregates (in the case of FUS)
- Electrophysiological deficits
What are the cons of iPSC-derived models of disease?
- They are cultured cells --> the in vivo cellular context is missing, and behavior cannot be evaluated
- However: clinical data of the patient from whom cells were derived is usually available, including data from imgaging, diagnostic tests, EMG (electomyography), etc.
- The human genome is variable (outbred background) -->
- Two sources of variation when comparing patients to controls:
- The disease-causing mutation
- The genetic background
- BUT: it is possible to generate isogenic controls
What are isogenic controls?
What are the functional domains of FUS mutations?
What is a mutation within NLS causing?
What is the difference in the classical NLS and PY-NLS mechanism?
What are the two pathways that influence FUS nucleocytoplasmic shuttling?
- Transportin (TNR)-mediated nuclear import of FUS
--> modulated by arginine methylation of the FUS RGG3 domain: inhibition of protein N-argininemethyltransferase1 (PRMT1) restores TRN-mediated nuclear import of FUS PY-NLS mutants
- DNA-PK mediated nuclear export of FUS
--> this is mediated by phosphorylation of the FUS N-terminus
How can FUS-ALS motor neurons be characterized?
- Subcellular localization and cytoplasmic aggregation of FUS
- Electophysiology --> hypoexcitability of FUS-ALS motor neurons
- Age-dependent distal axonal degeneration
- Age-dependent motor neuron apoptosis
How does the culturing of hiPSC-derived motor neurons in microfluidic chambers work and why is this done?
Motor axons will grow towards higher gradient of growth factors (which is higher in distal compartment). Then, by imaging, differences between proximal and distal axons can be analyzed.
In ALS: distal axons degenerate as 1st, all the way back to the cell body --> 'dying back' mechanism.
What are the advantages of compartmentalized cultures?
- Gradients of e.g growth factors can be established
- cell bodies and promixal/distal axons can be imaged separately, including in vivo imaging
- cell bodies and or axons can be harvested separately for biochemical or omics approaches
- Compounds can be selectively added to axons or cell bodies
- By adapting the relative volume of the medium in proximal vs distal wells, the direct of the medium flow can be determined.
In which 3 ways can axonal transport be studied?
- Labeling of mitochondria or lysosomes in live cells --> by mitotracker or lysotracker
- in vivo imaging
- analysis of movies (time-lapse) to determine displacement and speed
The question on the page originate from the summary of the following study material:
- A unique study and practice tool
- Never study anything twice again
- Get the grades you hope for
- 100% sure, 100% understanding
