# BDNF Guide
### This is a research guide I developed for myself to try and write a paper reviewing BDNF.
- What is its name, what organism is it found, and what cell classes does it effect?
- Without BDNF, will I die? If yes, how fast?
- What is its heritability, mother and father. Mitosis vs mieosis.
- What is the epigenomics of it?
- What is its genomics?
- What is its structure?
- What is its reactome?
- What is its spatial transcriptome?
- How could it's reactome be improved?
- What cognitive behaviors are related to BDNF?
- What is the impact score of BDNF research in medicine?
- What is its expression across age, sex, and injury?
- How can it be produced in a culture?
- How can it be produced in a human?
- How can BDNF be packaged?
- How can BDNF be attached to a cell free strucutre, such as plastic, metal, collagen, or sugar.
- Create a correlation coefficient matrix between these questions.
- Can expression level of BDNF or proBDNF across lifetime be correlated with brain volume. Spatial Transcriptome vs Volume change acroos space. Mouse model.
- What chromosomes are it expressed on?
- What diseases are associated with it?

String Network of BDNF
BDNF== Neutrophin-4, 1B8M

#https://string-db.org/cgi/network?taskId=bIk3q3jPfdnR&sessionId=bmqZwFNgMb73

3D structure crystallography
https://www.rcsb.org/structure/1b8m
https://www.ebi.ac.uk/pdbe/entry/pdb/1b8m/index

Dake Hao Abstracts Notes

Suggestion: Integrate stemcell and agnionosis technology with BrainGate2 program.
https://www.clinicaltrials.gov/ct2/show/NCT00912041

Integrate mesenchymal cells into the utah/michigan array.

# Notes

2013/1/8
Optimization of fermentation conditions and properties of an exopolysaccharide from Klebsiella sp. H-207 and application in adsorption of hexavalent chromium

Exopolysaccharide: macromolecules, exreted as capsules or slime layers. Good against desiccation, phagocytosis, cell recognition, phage attack, toxic compounds, and osmotic stress. The polymer contains proteins, DNA, Phospholipids, acetate, glycerol, pyruvate, sulfate, carboxylate, succinate, and phosphates.

How come exopolysaccharide isn't eaten? Its made up of key metabolic components.

Exopolysaccharide is produced by lactic acid bacteria. Lactobacillus, Lactococcus, Bifidobacterium, Leuconostoc, Pediococcus, Streptococcus, Enterococcus and Weissella sp.

Dake used Klebsiella sp. H-207.
Optimized with sucrose 31.93 g/L, KNO3 2.17 g/L and K2HPO4 5.47 g/L. seed age 13 h, with an inoculum size of 10.6% and incubation temperature of 28.9°C.

Need to know what seed age, and inoculum is. Response surface methodology, and why uronic acid matters, and why used metals to discern bioabsorbtion. Ask Dake.

EPS has strong water binding ability, water retention capacity, immense swelling and gelation potential.

2017/4
Highly efficient differentiation of endothelial cells from pluripotent stem cells requires the MAPK and PI3K pathways.

Need to get trained on the protocol, or the protocol they are using in the lab. Paper is from 2017.

"purities (94%-97% CD31+ and 78%-83% VE-cadherin+)" How is this a measure of purity?

Matrigel: Matrigel is the trade name for the solubilized basement membrane matrix secreted by Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells produced by Corning Life Sciences. Matrigel resembles the laminin/collagen IV-rich basement membrane extracellular environment found in many tissues and is used by cell biologists as a substrate (basement membrane matrix) for culturing cells.

A common laboratory procedure is to dispense small volumes of chilled (4 °C) liquid Matrigel onto plastic tissue culture labware. When incubated at 37 °C (body temperature) the Matrigel proteins polymerize (solidify) producing a recombinant basement membrane that covers the labware's surface.

FGF2, VEGF, and BMP4 are cofactors for angiogenesis. Make those happen, you get more vascular progenitors.

MAPK and PI3K pathways are important, most likely regulating ETS family transcription factors. Inhibition of ERK pathway promoted differentiation of smooth muscle cells.

2018/12/1
Engineerin mesenchymal stem cells to improve their eosome efficacy and yield for cell free therapy.

Already read.

2019/11/12
Hypoxic preconditioning enhances survival and proangiogenic capacity of human first trimester chorionic villus-derived mesenchymal stem cells for fetal tissue engineering.

"Due to immunoregulatory properties, self-renewal capacity, and multilineage potential, autologous human placental chorionic villus-derived mesenchymal stromal cells..." Ok, what do we have in the fridge? Do we have mesenchymal, endothelial, chorionic villus derived stem cells? I get that in a textbook, sourcing generally doesn't matter, but in experimentation it does. Whats in the fridge, that I can use, if I were to do an assay of the secretome of stem cells in the fridge.

Mesenchymal: Small spindle-shaped cells with large nuclei, prominent nucleoli and fine chromatin. These are multipotent stem cells that differentiate as progenitor cells for all types of connective tissue, such as fibroblasts, osteoblasts, chondroblasts and preadipocytes. Has proinflammatory, and anti-inflammatory secretions.
Its anti-inflammtory method is to attach nonfunctionally IL-1Ra to IL-1beta receptors on cells, and cap off where B-cell taggers would bind and allow antibodies to bind on the cell. Othewise, it also secretes proteins sTNFR1 and 2, that combine and capture TNF alpha, and preventig binding. Cytokines, chemokines, exosomes, and secretomes

Autologous: Obtained frm the same individual, patient, or organism.

Ischemia:Lack of blood flow, or blood restriction.

"Particularly for the fetal transplantation of CV-MSCs in the naturally hypoxic fetal environment, improving the survival and engraftment of CV-MSCs is critically important. Hypoxic preconditioning (HP) is an effective priming approach to protect stem cells from ischemic damage."

Need to learn the hypoxic preconditioning.

"ELISA results showed HP significantly enhanced the secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by CV-MSCs under an ischemic stimulus. We also found that the environmental nutrition level was critical for the release of brain-derived neurotrophic factor (BDNF). The angiogenesis assay results showed HP-primed CV-MSCs could significantly enhance endothelial cell (EC) proliferation, migration, and tube formation. Consequently, HP is a promising strategy to increase the tolerance of CV-MSCs to ischemia and improve their therapeutic efficacy in fetal clinical applications."

BDNF is incredibly important for plastic changes in learning and memory.

# Review Paper, Background Literature Notes
This markdown is bascially where I write all my literature notes while I am brainstorming my review paper suggestions. Also notes from observing/talking to people in the lab.

Next note title: direction of review paper.
## Idea V3
* "Hebbian learning between MSC derived neurons, and anterior cingulate cortex endogenous neurons."
* "Neuromorphic mesenchymal neurons, methods in anterior cingulate cortex mimicry"
* "Use of mesenchymal stromal cells to mitigate lead fracture, infection, and migration of BDS devices."
* Should I make this a perceptron review paper?*
* This paper is to answer one general question, while by providing answers to some very specific questions.*

### Sub fields
* Biophotonic engrams of Mesenchymal neuronal cells.
* Electromagnetic effects on inducing communication between stem cell neurons and somatic neurons.
* Manipulatability of mesenchymal neurons, can they be coded with machines.
* Does BDNF paly a critical role in Mesenchymal neuron integration?
* Brain wave expression in mesenchymal neuronal cells. *If mesenchymal neuronal cells are influenced by a EMF, then they themselves must exude emf as well. Is it the same spectrum as brain waves?*
* Can mesenchymal neurons mimic the transcriptome and EMF of the ACC of a subject?
* Can mesenchymal neurons respond to radiofrequency lesioning similarly as endogenous neurons? So... if we introduce these new neurons right, how likely are they going to not just mimic expression and integrate with host neurons, but also will they respond like other neurons in response to injury. Will they heal, or induce neurogenesis in response to trauma?
* Growing mesenchymal neuronal cells on hydrogel coated platinum DBS electrodes feasibility

### Wang and Dake lab goals
* Exomes
* Secretomes
* Angiogenesis
* Topology of grafts
* Ligands and binding of stem cells
* Spinabifida
* Neuronal disorder
* Regenerative treatments
* LLP2A/LXW7 proteins bind to *alpha*4*beta*1 and *alpha*v*beta*3
* Bone Morphogenetic protein-2. Good for doing the osteoangiongenesis, bad cause causes inflammation and ectopic bone formation.
* Decellurization, keep extracellular matrix
* Goretex, polyurethane grafts.
* Transdiaphramtic pressure
* Find what the need for the field is.
* Stem cell coated diagphram implants.
* Perhaps trophoblast isolation, to develop mesenchymal cells?