Feb 17 is Random Act of Kindness Day

 Saw this on Canva. Did not know that there was a day. But a good thought nonetheless. 

Loneliness

The room is empty

Loneliness creeps in slowly
Empty walls surround

Silence echoes all around

DNA Repair

Pollina et al. 2023 
The paper describes a new method called sBLISS-seq for identifying DNA damage sites in cells. The authors used this method to study the role of a protein called Ep400 in repairing DNA damage.

The paper suggests that the link between neuronal activity and DNA repair mediated by NPAS4-NuA4 may be relevant to NDD like autism. This is because damage at activity-dependent regulatory elements may be a source of neuronal dysfunction in these disabilities.

Key Takeaways & Contributions.

- Discovery of a specialized chromatin regulatory mechanism in the brain that couples synaptic activity to genome preservation. 

- Identification of a link between neuronal activity and DNA repair mediated by NPAS4-NuA4, which suggests that damage at activity-dependent regulatory elements may be a source of neuronal dysfunction in NDD and autism . 

- Potential role of NPAS4-NuA4 in sustaining neuronal vitality over time and contributing to cellular and organismal longevity. 

- Development of a new method called sBLISS-seq for identifying DNA damage sites in cells

Methods

• The development of a new method called sBLISS-seq for identifying DNA damage sites in cells. 
• The use of 
• chromatin immunoprecipitation (ChIP) to study the binding of proteins to DNA. 
• CRISPR-Cas9 genome editing to create knockout cell lines. 
• RNA sequencing (RNA-seq) to study gene expression. 
• immunofluorescence to study protein localization in cells. 
• comet assays to measure DNA damage.

Questions raised

• What is the full extent of the role of NPAS4-NuA4 in sustaining neuronal vitality over time and contributing to cellular and organismal longevity? 
• How does the link between neuronal activity and DNA repair mediated by NPAS4
• NuA4 contribute to NDD & autism, and can this mechanism be targeted for therapeutic purposes?  
• What other proteins and pathways are involved in the regulation of DNA repair in response to neuronal activity, and how do they interact with NPAS4-NuA4? 
• How can the sBLISS-seq method be further optimized and applied to other cell types and experimental conditions? 
• Findings implications in understanding relationship between neuronal activity and genome preservation in the brain?

Haikus for the love of spring

  Its feb 14 and spring is upon us. I see flowers bloom on my neighbor's tree. 

In the midst of bloom, 

Petals entwine, a sweet embrace, 

Love's essence inhaled.

TBI Regressive Autism

Ameliorating Hemianopia with Multisensory Training (Rowland et al., 2023)

Quick Summary of paper . An  visual-auditory stimulation therapy was used on two older males  who has loss of vision in the left hemifield (hemianopia). The cause was brain trauma (TBI) rather than lesion.  Prior to joining the study both had been referred to PT and OT as rehabilitation measures. 

• 64 year old JM joined the study 14 months after stroke  (2 infracts)
• 74 year old CW joined the study ~18 months after 1 infract (better sighted field compared to JM). 
• Therapy took place over 8 months /10 sessions 

The results were dramatic. Both patients recovered the ability to detect and describe visual stimuli throughout their formerly blind field within a few weeks. They could also localize these stimuli, identify some features, and perceive multiple visuals simultaneously in both fields. (more detail on paper here link)

Relating all this back to Autism

So impressive about being able to restore sight in a matter of 8 months, given therapy was started 14-18 months after infract and not immediately and it was in older adults. 

Why is regressive autism not thought to be TBI at 18 mo, where there is a sudden loss of learned skills. 

• If TBI --> can those lost skills not be regained through targeted therapy. If you can restore skills in 60-70 yr old, should be able to, in a younger more plastic brain. 
• If TBI -->  is this related to CW & JM having practice with vision for 60-70+ years vs toddlers who only have practice with the skills for 18 mo.

Rethink Traditional Therapies

• CW & JM  had PT/OT for 14-18 mo before joining study; implication these therapies not that useful for regaining lost skills. 
• Autistics kids are in insane amounts of therapy (childhood stuffed with ABA/speech/OT every waking hr with little advances to show for it other than the $$$ spent and lots of career advancement for therapists). 
•  Maybe we need rethink early childhood therapy to be more targeted to restore lost skills. Even regaining that level of lost skills improves quality of life, let alone moving beyond.

One big vagary

Vagaries ubiquitous in autism.
Nothing standard, fractured light in a prism.
Can we conclude then, so far…..
… no evidence in any evidence really
….no clues. What’s going on in this gallery.
inexplicable me. I continue to be one big vagary.

Cellular neuroscience is tough.

Cellular neuroscience  is tough. 

=====

I'm like a library book, overdue
My brain's so full, it's about to bust in two
I feel like I'm stuck in a never-ending test
Studying so much, I'm starting to feel depressed!
Will it bring success to my quest?



This was the response from my friend in my neuroscience cohort. Thank you for the encouragement and empathy. 

Will it bring success to my quest?
Simply stated, my answer is yes

Battling through the constant stress, through days, months, years of duress
Though now life may seem like a mess, the quest is not to be the best,
Prioritize self-care, remember to rest

Is it worth it, when all I see, are cloudy skies up over me?
Yes I say, the world will see, what's possible with a degree,
The journey to a PhD is sprinkled serendipity,
But even more importantly, be free to show YOU empathy!

Hari,
Above all you are my friend, one that will be there 'til the end,
Remember I am here for you, day in, day out, through and through.