When Axons Meet GPS Robot Cops

When Axons Meet GPS Robot Cops

Robo: Alright team, let's get these axons where they need to go. Slit, you're up first.


Slit: Alright, alright, don't rush me. Let me just activate my molecular mechanisms real quick.


Comm: Oh here we go, Slit and his molecular mechanisms. Always showing off.


Axon: Hey, can someone explain to me what's going on?”


Robo: Don't worry little guy, we're here to guide you. Slit is going to help you navigate to your destination.


Slit: That's right. I'm Slit, named after the slit-like spaces that I bind to. Not the most glamorous name, but hey, it's better than being called "sticky" like some other proteins. 


Comm: Hey, don't be dissing my molecular mechanisms. They may not be as flashy as yours, but they get the job done.”


Axon: I don't mean to interrupt, but what do you do, Comm?


Comm: Oh, me? I'm the commissure, here to make sure you cross the midline properly. But my full name is commissural neuron guidance molecule, which makes me sound like some sort of cop.


Robo: And I'm Robo, short for Roundabout. I know, I know, I sound like a robot. But hey, I'm the protein that helps guide you around obstacles and keep you on the right path.


Slit:  And together, we make a great team. The protein trio of axon guidance GPS. 


Axon: so I’m gonna interrupt again. But why do I need to cross the midline at all? Why do you need to guide me. What’s going on here and where am I going?”


Robo: Well Axon, to answer your earlier question about the big picture, it's all about forming the correct connections in the nervous system. The brain is made up of billions of neurons, and each neuron needs to make connections with other neurons to form a functional network. These connections allow us to do everything from sensing our environment to controlling our movements and thoughts.


Comm: And that's where we come in. We help guide axons to their appropriate targets, ensuring that the connections are made correctly. Without us, the nervous system would be a chaotic mess.


Slit: Exactly. And that's why it's so important for us to do our job correctly. Even a small mistake can lead to a misconnection that could have serious consequences for the individual.


Axon: Wow, I had no idea that I was part of such a complex process. It's kind of overwhelming.


Robo: Don't worry, little guy. We've got your back. Just trust us, and we'll guide you to where you need to go.


Slit: And who knows? Maybe someday you'll become a fully-formed neuron, making connections with other neurons and contributing to the functioning of the nervous system.


Comm: Yeah, and maybe you'll even be guiding another axon someday.


Axon: That sounds amazing. I can't wait to see where this journey takes me.


Robo: Alright team, let's get back to work. We have some important connections to make.


Axon: Wait, I have one more question. How did you all become proteins that guide axons?


Slit: Oh, it's a long story. It all started when we were just humble genes, waiting to be transcribed and translated.


Comm: And then one day, we were lucky enough to be selected to play a crucial role in axon guidance.


Robo: It's not the most glamorous job, but hey, someone's got to do it.


Axon: Well, I'm grateful for you guys. Thanks for guiding me through this crazy nervous system.


Slit: Anytime, dude. That's what we're here for.


Axon: Hey Robo, have you ever thought about what life would be like if you weren't proteins?


Robo: I can't say I have, Hey Slit and Comm. Do you want to be something else?


Slit: I don't know, maybe a neurotransmitter or something. Imagine how cool it would be to transmit information between neurons.


Comm: And I could be a transcription factor in a different system altogether. I could be regulating gene expression in a plant or something.


Robo: Oh come on, you guys. We're perfectly happy being proteins that guide axons. Let's not get too carried away with these fantasies.


Slit: Fine, fine. But you have to admit, it would be pretty cool.


Comm: Now let's get back shaping the intricate architecture of the nervous system. Lots of traffic to manage. 

Equanimity is the stillness that allows us to listen to our hearts.

Contemplation, one line a day. This month on Equanimity #MentalHealth


 

Empathy is the art of caring for someone else's feelings as if they were your own.

Contemplation, one line a day.Towards a more humane society, an empathic society. 

 

EQUANIMITY

Towards a more Humane Society.  Contemplating  one line each day. #MentalHealth. This month is EQUANIMITY 


Equanimity

-Hari Srinivasan


Equanimity is the calm at the center of the storm.

Equanimity is the balance that allows us to move forward.

Equanimity is the anchor that keeps us grounded.

Equanimity is the serenity that comes from within.

Equanimity is the clarity that helps us see things as they are.

Equanimity is the inner strength that allows us to face life's challenges.

Equanimity is the acceptance that all things pass in due time.

Equanimity is the non-judgmental awareness of our thoughts and emotions.

Equanimity is the gentle acceptance of ourselves and others.

Equanimity is the ability to maintain our inner peace in the face of adversity.

Equanimity is the steady hand that guides us through life's ups and downs.

Equanimity is the stillness that allows us to listen to our hearts.

Equanimity is the wisdom that sees through the illusion of our fears.

Equanimity is the patience to wait for the right moment.

Equanimity is the trust that life will unfold as it should.

Equanimity is the surrender to what is and what we cannot change.

Equanimity is the gratitude for all that life has to offer.

Equanimity is the self-awareness that allows us to grow and learn.

Equanimity is the forgiveness that frees us from the past.

Equanimity is the openness to new experiences and perspectives.

Equanimity is the presence of mind that allows us to live in the moment.

Equanimity is the inner peace that radiates outwards.

Equanimity is the self-love that allows us to love others.

Equanimity is the self-compassion that allows us to heal our wounds.

Equanimity is the stillness that allows us to find our inner voice.



See posts for other months. 
Jan [JOY] Feb [EQUANIMITY] March [EMPATHY] April [KINDNESS]

Atmospheric Rivers

 https://youtu.be/cdhEwAZP-gI


An explanation of the crazy weather pattern this winter in California

Delta Notch Numb: Neurogenesis Society

A humorous science skit. 

Delta Notch Numb: Neurogenesis Society



Delta: Hey guys, have you ever wondered why we have such unusual names? I mean, put together, we sound like a Notched-up college Greek Society; a bunch of undergrads that go totally Numb after an exhausting Rush.

SWAN - Strengths and Weaknesses of ADHD Symptoms and Normal Behavior

Lexicon [Measures]- SWAN


The SWAN is more for ADHD and not designed specifically for autism. 

The SWAN (Strengths and Weaknesses of ADHD Symptoms and Normal Behavior) Rating Scale is a tool to assess ADHD symptoms in children and adolescents. 


The SWAN Rating Scale consists of 18 items that capture various domains of ADHD symptoms, including inattention, hyperactivity, and impulsivity. It uses a Likert-type scale ranging from 0 (far below average) to 3 (far above average) to rate the presence and severity of each symptom. The scale can be completed by parents, teachers, or other caregivers who have regular contact with the child.

Scoring of the SWAN involves summing the ratings for each item to obtain a total score. Higher scores indicate greater ADHD symptomatology. The scale also allows for the calculation of subscale scores for inattention and hyperactivity/impulsivity. 


Limitations with its use in autism. 
  • Lack of specificity: The SWAN focuses on ADHD symptoms and may not capture the full range of challenges and behaviors associated with autism. Autistics may exhibit ADHD symptoms as part of their broader autism profile, but there may be additional symptoms and impairments not assessed by the SWAN.
  • Difficulty differentiating symptoms: Some symptoms of ADHD, such as inattention, can overlap with symptoms of autism, making it challenging to disentangle the two conditions based solely on the SWAN. 

The SWAN Rating Scale was developed by Dr. Stephen J. Kupper in 2006. 

Constant Overload


Being bombarded by the sensory system
A constant overload, it never ends
Sensory overwhelmed, a feeling of prison
Trapped in my own mind, with no friends.

Poor somatosensory body mapping
A constant confusion, a foggy haze
I struggle to understand my own body
A feeling of being lost, in a daze

Words get stuck, inside my head
Apraxic, struggles to speak
A feeling of frustration, so very unique
As talking eludes me, instead

It can be a struggle, to navigate
This world that's full of sensation

I need to find a way
… with determination

Chilling on a houseboat

 


This is where I would like to be today on my birthday. 
Chilling on a houseboat in the Kerala backwaters
(photo taken a few years back)


Chilling on a houseboat in Kerala's backwaters
Coconut trees sway along the shore
The sun dips low, painting the sky with colors
A serene moment, that I'll forever adore.


A moment of peace


Two deer in my yard
Wandering from woods at the back 
Gentle, graceful steps 
Moment of peace, nature's gift

The gentle creatures graze
Unfazed by noise and haste
Their presence brings me ease
In this tranquil, natural space.



And Thank You to everyone who sent me wishes today (Feb 22) - for taking that one breath and one moment to send "happy" positive vibes my way, on my birthday.

Equanimity is the inner peace that radiates outwards

Towards a more humane society. #MentalHealth. Contemplation, one line a day.

 

Hints of green

On brown trees, hints of green 
A herald of spring
Softly appears, shy and demure,
A promise of new life, fresh and pure


The brain is a Giant Prediction Machine

Poem follows Prof Mark Wallace's comment in class "The Brain is a giant prediction machine" after a discussion on the growing popularity of Bayesian Statistical Models in research. 


The brain is a giant prediction machine

Bayesian model-like, it constantly schemes

Past experiences and memories in its grasp

Current sensory input, processed in a flash.

 

A bundle of irrational worry

I am a bundle of irrational worry
Each day i wake up with dread and hurry
Fears and doubts consume, a constant flurry
Hope still flickers in internal jury

STAT: Screening Tool for Autism in Toddlers and Young Children

The Screening Tool for Autism in Toddlers and Young Children (STAT) is a play-based screening measure designed to identify early signs of autism  in toddlers and young children. It t assesses social communication and play behaviors associated with ASD in children between 24 and 36 months of age.

Limitations
The STAT is a screening tool and not a diagnostic instrument. A comprehensive evaluation by a qualified professional is necessary for a definitive autism diagnosis.

Scoring and Interpretation
The STAT includes a series of play-based activities and social interactions between the child and the examiner. The examiner observes and scores the child's behaviors in different domains, such as joint attention, pretend play, and social responsiveness.

The STAT scoring involves rating specific behaviors observed during the play-based interactions. The scoring criteria may vary depending on the specific version or adaptation of the STAT being used. There are established cutoff scores that help identify children who may be at risk for ASD and require further evaluation by a qualified professional.

History and Revisions:
The STAT was developed by Wendy Stone, Barry L. Prizant, and Samuel P. Openden in 2008. 


Citation:
Stone, W. L., Prizant, B. M., & Openden, S. (2008). The Screening Tool for Autism in Toddlers and Young Children (STAT). Retrieved from https://www.researchgate.net/publication/228625486_STAT_Screening_Tool_for_Autism_in_Toddlers_and_Young_Children

WISC - Wechsler Intelligence Scale for Children

Lexicon [Measures] - WISC

WISC-V (Wechsler Intelligence Scale for Children) is an IQ test used in children (age 6-16 yrs 11 mo) and takes approximately 60-85 minutes. It was developed by David Wechsler (5th Ed 2014).

Limitations wrt Autism
Autistic children may have specific challenges related to social communication, sensory sensitivities, and executive functioning, which can impact their performance on certain subtests. [Also see post on Why IQ Testing especially problematic in the Autistic Population]

WISC has 10 Subtests that fall under 5 index score categories

  1. Verbal Comprehension Index (VCI): 
    • Similarities: verbal reasoning and concept formation by assessing the ability to identify how two words or concepts are similar.
    • Vocab: language development and word knowledge by asking the child to define or explain the meaning of various words
    • Information: general knowledge and comprehension of factual information by asking questions about a wide range of topics.
  2. Visual Spatial Index (VSI)
    • Block Design: Assesses spatial perception, visual-motor integration, and problem-solving abilities through block imitation
  3. Fluid Reasoning Index (FRI): 
    • Matrix Reasoning: nonverbal reasoning & fluid intelligence by asking child to identify patterns and complete visual matrices. 
    • Picture Concepts 
    • Picture Concepts: analyze visual stimuli, recognize relationships, and form abstract concepts by asking the child to identify common features and group pictures based on concepts.

  4. Working Memory Index (WMI): 
    • Digit Span: attention and working memory through ability to repeat a series of digits forwards and backward.
    • Picture Span: working memory through recall of sequence of pictures in correct order
  5. Processing Speed Index (PSI)
    • Coding: measure visual-motor speed and attention by child copying symbols paired with numbers within a specified time limit
    • Symbol Search: visual scanning and processing speed by asking the child to identify target symbols within a specified time limit.
Scoring and Interpretation
Index scores are derived from specific combinations of subtests and provide an overall assessment of an child's cognitive strengths and weaknesses in those domains.

The Full-Scale IQ (FSIQ) is the combination of the index scores. It represents overall intellectual functioning and is calculated based on the combined performance across all subtests.

Interpretation involves comparing an individual's performance to normative data (percentile ranks, confidence intervals, and descriptive categories), considering the person's age and the index and subtest scores obtained. 

Citation
Wechsler, D. (2014). Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V). San Antonio, TX: Pearson.

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?