#Epigenetic Modifications

[pebblegalaxy]

Unlocking the Mysteries of Gene Expression: From Genomic Imprinting to Non-Coding RNAs in Biology Class with Dr. Mishra

Unlocking the Mysteries of Gene Expression: From Genomic Imprinting to Non-Coding RNAs in Biology Class with Dr. Mishra #GeneExpression #BiologyClass #GenomicImprinting #NonCodingRNAs #CollaborativeLearning

Dr. Mishra: “Hello there! I see we have a new face in our biology class today. Welcome! We’re so glad you’re here, and I want you to know that this classroom is a friendly and supportive place. If you ever have questions or need assistance, don’t hesitate to ask me or your classmates. We’re all here to learn together and make this an enjoyable experience for you.” Abby: “Hello. My name is Abha…

[buggbuzz]

GUYS I GOT INTO A COLLEGE STUDENT RESEARCH PROGRAM!!

IM GONNA WORK ON A BIG EPIGENETICS PROJECT W/ MY PROFESSOR FOR A YEAR STRAIGHT!!

IN CELEBRATION HERE IS ME IN THE NEW LABCOAT I JUST GOT!! i have wanted my own lab coat for over a decade

[sunset-peril]

I actually tend to hc that all the Links are descended from another at some point.

However, what do you think about epigenetics being a viable reason for such?

You mean epigenetics being the reason they all are similar? Or that epigenetics is the reason they're all descendants of each other? I'm not sure I understand the question.

However, considering that epigenetics regards the condensed-ness (that's not a word but oh well) of the histones and the DNA wrapped around them and that most epigenetic changes are extremely reversible due to being caused by environmental stimuli (the only epigenetic changes that are permanent being CpG methylations in gene promoters, because those control cell differentiation.), I don't think epigenetics would leave a permanent mark on all Links as a whole. If Twilight Princess was Ocarina of Time's grandson or great-grandson, then that would be the only time I could see epigenetics playing a role in more than one Link. However, I think the rest of them are too far apart in the bloodline to have any real epigenetic effect on each other. Generally, epigenetic changes have been reversed after two or three generations, unless whatever stimuli that caused the original modification was persistent. (We used diabetic rats and poor/proper dieting for this study, and research on psychological epigenetics is still very new)

Although now that you mention this, I am curious to see how epigenetics would play a role in BotW/TotK's children.

I hope that answers the question!

For me I definitely hc that Skyward, Ocarina, Twilight Princess and BotW/TotK being all relatives (BotW being descended from TP literally being a foundational piece in my lore). I just don't know enough about the rest of them to decide for the rest of them.

[sproutystudies]

Histone Modifications

Hello, hello! Today's topic is histone modifications. We are continuing on with the epigenetics theme after my previous educational post about DNA methylation. As described in that post, epigenetics is the study of heritable genetic modifications without a change in DNA sequence (Takuno & Gaut, 2012). Similarly to DNA methylation, histone modifications affect gene expression through regulation of accessibility of the DNA for transcription (Bartova et al, 2008). But before we get into these modifications, let's go over a bit of background information!

What is a histone, anyway? A histone is a type of protein involved in DNA compaction and organization. In order to fit a genome's worth of DNA into the nucleus of a cell, that stuff needs to be extremely tightly packed! Histones help with this by forming an octomer called a nucleosome, which the DNA wraps around. These nucleosomes then coil together to form a fiber known as chromatin, which goes on to make up a chromosome. When the chromatin is less tightly packed, it is known as euchromatin and it is available for transcription (Bartova et al, 2008). When it is more tightly packed, it is known as heterchromatin, and polymerase proteins cannot access and transcribe the DNA (Bartova et al, 2008). Histone modifications regulate the transition between heterochromatin and euchromatin (Bartova et al, 2008).

(Above image from humanoriginproject.com)

(Above image from Caputi et al, 2017)

The octomer core of a nucleosome is made up of two copies of each of four types of histones: H2A, H2B, H3, and H4 (Marino-Ramirez et al, 2017). Each of these histones includes an N-terminal tail structure, which is the main site of modification (Marino-Ramirez et al, 2017). The tails are modified through addition and removal of certain functional groups or other small structures. Types of modifications include acetylation by histone acetyltransferases, methylation by histone methyltransferases, phosphorylation by kinases, and ubiquitination (Marino-Ramirez et al, 2017). All of this information is used for naming specific histone modifications: Which histone is modified, which amino acid of the histone tail the modification is on, what type of modification is made, and in what amount. For example, H3K9me2 is the name for di-methylation of the 9th Lysine on an H3 histone's tail.

Some important histone modifications and their effects include:

H3K9me2: transcriptional activation + maintenance of CHG DNA methylation in plants

H3K9me3: transcriptional repression

H3K9ac: transcriptional activation

H3K4me1 & H3K4me3: transcriptional activation

H3K27me3: transcriptional repression

H4K16ac: transcriptional activation

H3S10p: DNA replication-related chromatin condensation

(He & Lehming, 2003)

Important Terms: histone, nucleosome, heterochromatin, euchromatin, transcription, epigenetics

[blueoaknx]

Mitochondrial Dysfunction in SLC6A1: A Molecular and Cellular Perspective

 SLC6A1 encodes the gamma-aminobutyric acid (GABA) transporter type 1 (GAT1), a crucial component of inhibitory neurotransmission. Pathogenic variants in SLC6A1 lead to neurological disorders, primarily epilepsy, developmental delay, and neuropsychiatric conditions. While its role in GABAergic signaling is well established, emerging evidence suggests an intersection with mitochondrial dysfunction, which exacerbates disease pathology. This article explores the molecular and cellular mechanisms linking SLC6A1 mutations to mitochondrial impairment, highlighting alterations in energy metabolism, oxidative stress, and mitochondrial dynamics.

1. Introduction The SLC6A1 gene encodes the GAT1 transporter, responsible for reuptaking GABA from the synaptic cleft into presynaptic neurons and astrocytes. Disruptions in SLC6A1 impair inhibitory neurotransmission, contributing to hyperexcitability in neuronal circuits. Recent studies indicate a link between SLC6A1 dysfunction and mitochondrial abnormalities, underscoring a metabolic component to disease pathogenesis. The mitochondrial connection is crucial as these organelles regulate neuronal energy homeostasis and apoptosis. Understanding these mechanisms is essential for dissecting the full scope of SLC6A1-related disorders.

2. Role of SLC6A1 in Cellular and Mitochondrial Function Neurons exhibit high metabolic demand, relying heavily on mitochondria for adenosine triphosphate (ATP) production. GABA metabolism interfaces with mitochondrial pathways, influencing oxidative phosphorylation (OXPHOS) and redox balance. SLC6A1 mutations impair GABA uptake, potentially disrupting mitochondrial function through dysregulated Krebs cycle activity, altered ATP synthesis, and excessive reactive oxygen species (ROS) generation. Additionally, GABAergic dysfunction affects calcium signaling, further impacting mitochondrial integrity.

3. Energy Metabolism and ATP Production Mitochondria generate ATP primarily through OXPHOS. Deficient GABA uptake alters cellular excitability, increasing ATP demand while simultaneously impairing ATP synthesis. Studies show that neurons with SLC6A1 mutations exhibit reduced mitochondrial membrane potential (∆ψm), leading to inefficient ATP generation. Moreover, compensatory glycolysis often fails to meet neuronal energy demands, resulting in cellular stress and neuronal dysfunction.

4. Oxidative Stress and ROS Dysregulation Mitochondria are primary sites of ROS production, which serve as signaling molecules in normal physiology but become deleterious when unregulated. SLC6A1 mutations contribute to ROS imbalance, leading to oxidative stress and lipid peroxidation. Elevated ROS levels have been reported in neurons with impaired GABAergic signaling, suggesting that SLC6A1 mutations exacerbate mitochondrial oxidative damage. This process triggers mitochondrial DNA (mtDNA) mutations, protein oxidation, and lipid peroxidation, further compromising mitochondrial integrity.

5. Calcium Homeostasis and Mitochondrial Dysfunction Neuronal activity depends on tightly regulated calcium homeostasis. Mitochondria buffer intracellular calcium, maintaining synaptic function and preventing excitotoxicity. SLC6A1 dysfunction alters calcium flux due to disrupted GABAergic inhibition, leading to excessive mitochondrial calcium uptake. This triggers the mitochondrial permeability transition pore (mPTP), resulting in bioenergetic failure and apoptotic signaling cascades. Elevated cytosolic calcium further dysregulates mitochondrial enzyme activity, exacerbating metabolic dysfunction.

6. Mitochondrial Dynamics and Biogenesis Mitochondria undergo continuous fission and fusion to adapt to cellular demands. Impaired mitochondrial dynamics are observed in neurons harboring SLC6A1 mutations, leading to fragmented and dysfunctional mitochondria. The fusion-fission imbalance results in defective mitochondrial quality control, accumulation of damaged organelles, and impaired biogenesis. Downregulation of mitophagy-related proteins such as PINK1 and Parkin has been documented in models of SLC6A1 dysfunction, suggesting defective clearance of impaired mitochondria.

7. Synaptic Dysfunction and Mitochondrial Interactions Neurotransmission relies on synaptic mitochondria to meet localized energy demands. GABAergic synapses, in particular, require significant mitochondrial support due to their reliance on ATP-dependent vesicular transport and receptor function. SLC6A1 mutations disrupt synaptic mitochondrial positioning, reducing ATP availability at synapses. This impairment contributes to synaptic dysfunction, decreased inhibitory tone, and aberrant excitatory-inhibitory balance, which are hallmarks of SLC6A1-related neurological disorders.

8. Neuroinflammation and Mitochondrial Dysfunction Mitochondria modulate immune responses through ROS production and inflammatory cytokine signaling. Neurons with SLC6A1 mutations exhibit increased inflammatory markers, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), indicative of neuroinflammation. Mitochondrial dysfunction exacerbates this process by activating microglia and astrocytes, leading to chronic neuroinflammatory states. This further damages neuronal mitochondria, perpetuating a vicious cycle of dysfunction and degeneration.

9. Genetic and Epigenetic Influences on Mitochondrial Dysfunction Mutations in SLC6A1 not only affect protein function but also influence mitochondrial gene expression and epigenetics. Studies indicate altered expression of nuclear-encoded mitochondrial genes, including those involved in OXPHOS. Additionally, epigenetic modifications such as DNA methylation and histone acetylation impact mitochondrial biogenesis and function in SLC6A1-related disorders. Dysregulated mitochondrial gene transcription exacerbates bioenergetic failure, compounding neurological deficits.

10. Conclusion Mitochondrial dysfunction is an emerging pathological mechanism in SLC6A1-related disorders, contributing to energy deficits, oxidative stress, impaired calcium homeostasis, defective mitochondrial dynamics, and synaptic dysfunction. Understanding the interplay between SLC6A1 mutations and mitochondrial abnormalities provides insights into disease pathogenesis, paving the way for targeted metabolic and neuroprotective interventions. Future research should focus on elucidating the precise molecular pathways linking SLC6A1 dysfunction to mitochondrial pathology, ultimately aiding in the development of novel therapeutic strategies.

[shamanflavio]

The Alarming Rise of Diabetes: A Call for Integrated Healing Approaches

In the span of a century, the prevalence of diabetes has surged from an estimated 1% to a staggering 11.6%, as reported by the CDC’s National Diabetes Report. This alarming escalation prompts a critical examination of our healthcare paradigms and the role of the American Diabetes Association (ADA), a cornerstone in diabetes research and information dissemination. Despite decades of efforts, we…

[violent138]

I switch up a lot on Jason and his alleged pit madness and what, if any narrative purpose it could serve. But I do love the idea of him being so much more affected by it because the Al-Ghuls, after years and years of exposure, have and pass on epigenetic modifications that make them better at handling the effects of Lazarus pit.

[dandelionsresilience]

Hello I just want to say I really appreciate your dandelion news collections and to ask if you have any that are about tackling covid. I've been super anxious and having more panic attacks over it recently and I need a bit of hope that this nightmare might be over soon

Thanks for reaching out, I’m sorry you’re having a hard time. To get the bad news out of the way first, covid probably won’t ever be “over” at this point, because individuals and governments are doing very little to control it, much less eradicate it. however, there are plenty of ways we can protect ourselves and others even in the presence of covid, and research is ongoing worldwide to help treat and prevent it.

Here’s how we can tackle covid, first what you can personally do and then some of the research that’s happening:

First and foremost, don’t demand perfection from yourself! anything is better than nothing!

Join COVID Advocacy groups

Get a free or low-cost covid shot

Know that the “high-risk” conditions that keep you eligible for the vaccine in 2025 include mood disorders like depression (among many other conditions)

Advocate for the right to mask

Speaking of right to mask, “Illinois could become the first state in the country to ban mask bans.” HELP THIS BILL PASS by indicating support and getting updates, sharing your story of mask-based discrimination, and saying how it would affect similar efforts in your state

Jewish New Yorkers can sign their support to this open letter against mask bans

CleanAirCrew has loads of resources for cleaning your air

Wash your hands thoroughly and frequently

Take a covid test if you think you might’ve been exposed or if you have symptoms

How to get free paxlovid (2024)

Quarantine/isolate for at least 5 days after being exposed to covid, even if you don’t have symptoms yet

One of the best things you can do to protect others is wear a mask.

it’s never too late to start masking again / what to say when people ask why you’re wearing a mask

How to identify fake(non-certified) masks

Here’s where to get good masks of all different kinds - if you find masks uncomfortable, please check out the wide variety of styles!

These ones are specifically marketed as extra-breathable

Canadians can request a free mask here

Encourage others to mask with these free images

Research:

Nasal vaccine that prevents transmission is in phase I trials

Inhaled vaccine is in phase II trials

This filter can capture nanoparticles such as viruses, they’re working on improving air flow for use in masks

They found biomarkers for long covid

A CRISPR modification increases “the stability and effectiveness of mRNA vaccines”

New technology makes mRNA last longer in vaccines, increasing efficacy

New lipid nanoparticle drug-delivery method prevents lung damage

“Students perform equally well in-person or online”

Updated booster shots broaden range of immunity to other related viruses

”mRNA vaccines induce an epigenetic 'training' of innate immune cells,” broadening and extending efficacy

DNA “origami” greatly increases sensitivity of rapid tests

Prevention and long-term effects of covid are being studied

I hope some of this helps, but if the anxiety persists please consider seeking therapy to learn ways to head off panic attacks, or get medication if you need. Here’s a list of mental health hotlines if you need someone to help you through a panic attack. Keep your head up, we will get through this together

[mindblowingscience]

Researchers at the Francis Crick Institute have revealed insight into why embryos erase a key epigenetic mark during early development, suggesting this may have evolved to help form a placenta. Epigenetic changes are modifications to DNA that don't change the underlying DNA sequence, like notes written on a recipe. They keep gene expression in check, affecting which genes are turned on or off.

Continue Reading.

[tigwalen]

"In the grandchildren of Hama survivors, the researchers discovered 14 areas in the genome that had been modified in response to the violence their grandmothers experienced. These 14 modifications demonstrate that stress-induced epigenetic changes may indeed appear in future generations, just as they can in animals.

The study also uncovered 21 epigenetic sites in the genomes of people who had directly experienced violence in Syria. In a third finding, the researchers reported that people exposed to violence while in their mothers’ wombs showed evidence of accelerated epigenetic aging, a type of biological aging that may be associated with susceptibility to age-related diseases.

Most of these epigenetic changes showed the same pattern after exposure to violence, suggesting a kind of common epigenetic response to stress — one that can not only affect people directly exposed to stress, but also future generations."

I remember a few years ago I heard about a study regarding mice and smelling Cherry blossoms, how associating that cherry blossom with pain and fear is a trait that can be passed down not only to the children, but to the grandchildren mice. The grandchildren exhibited a stress response to the smell of cherry blossoms even if they never had an interaction or even saw the flowers.

When you think about trauma regarding Native Americans, Black people, and minorities that have experienced intergenerational trauma but in particular historical or systemic trauma, these are studies you should be thinking of first and foremost. I am a fan of repeat studies and duplicated results, I've been looking for research that adds on to those mouse study for some time. These things can be considered obvious but studies are concrete proof and evidence that also dictate and shape practice and policy.

[cozyforjate]

It surprises me when people say Chapel doesn’t have a trait, personality, or plotline other than being Spock’s love interest... Let me list all the things we know and have seen about this amazing character.

Christine Chapel is a nurse on The Enterprise. She is on civilian exchange from the Stanford Morehouse Epigenetic Project. She is also a part of Starfleet’s initiative to better observe alien cultures without contamination.

M’Benga treats her as an equal. Pike called her “doctor” in the very first episode which suggests that her medical knowledge and experience must be impressive.

She is an expert on genetic modification. She can mess with your genome and temporarily turn you into an Alien. And she makes it look easy.

She is also interested in archeological medicine. She is doing fieldwork, making discoveries, and writing papers on the subject while doing her other duties on the ship.

Long story short she is quite the genius!

She is outgoing, friendly, witty, funny, adventurous, strong, brave but also compassionate and emotional.

She doesn’t judge, she accepts people for who they are.

She is confident in her abilities. She doesn’t take anyone’s BS. “I don’t think the Vulcan Fellowship is ready for me”… No one, not even Vulcans can bully or make her feel insecure.

But when she was a kid she was bullied. Milo, her Malamute, bit one of those bullies. Good boy!

As it was implied in one of the episodes she is most probably bi.

She has a vulnerable side. She is afraid of commitment. Afraid of romantic relationships getting deep. Perhaps even afraid of falling in love. She uses humor when things get too serious or personal for her. There is a story waiting to unfold in time. And i can’t wait to know more of it!

She was in the Klingon War with M'Benga. They witnessed the ugly face of war and had to make some hard decisions. They used (perhaps even developed) an illegal serum that temporarily gives them enough power and stamina to survive against Klingons. This left a scar on her as much as it did on M'Benga. We will revisit this story in episode 8 (i guess).

She knows how to fight. She is a quick thinker during stressful situations. And she is a badass. For example, she can handle space pirates and all she needs is a hypospray! She can deal with baby Gorns and survive!

She is heroic. She would jump into space without an EV suit to prevent a war.

Oh and she is also Spock's love interest and it's a delicious relationship that enrichens both characters.

This is what we got in 15 episodes. I'm sure we'll learn more about her and she will get new storylines in the seasons to come.

[science-sculpt]

Epigenetics: A Journey Through Inheritance Beyond Genes

For centuries, scientists have been fascinated by the mysteries of heredity and how traits are passed down from generation to generation. DNA, the molecule that stores our genetic code, was once thought to be the sole determinant of our characteristics. However, a new frontier in biology, revealing a captivating layer of complexity beyond the DNA sequence itself: Epigenetics.

What is Epigenetics?

The term "epigenetics" was first coined in the 1940s by British biologist Conrad Waddington, but it wasn't until the late 20th century that its significance truly blossomed. Epigenetics, literally meaning "above genetics," refers to the study of heritable changes in gene expression that occur without alterations to the DNA sequence itself. Imagine DNA as the musical score, but epigenetics are the conductor and musicians who determine how the music is played. Through chemical modifications and adjustments to the proteins around DNA, epigenetics dictates which genes are turned on or off, influencing how cells function and ultimately shaping our health, development, and even behavior. Think of your DNA as the hardware: it contains the basic instructions for building and running your body. But epigenetics acts like the software, fine-tuning those instructions and determining which genes get turned on or off at specific times and in specific cells. These modifications, like chemical tags or changes in the packaging of DNA, don't alter the underlying code itself, but they can have a profound impact on how it's read and interpreted.

The Key Players:

DNA methylation: This process involves adding a methyl group to DNA, essentially silencing the gene it's attached to. Imagine it like putting a dimmer switch on a light bulb.

Histone modifications: Histones are proteins that package DNA, and changes in their structure can make genes more or less accessible to the cellular machinery needed for expression. Think of it like adjusting the curtains around a window - open wide for full light, slightly closed for filtered light.

Non-coding RNAs: These are molecules that don't code for proteins but can regulate gene expression in various ways. They're like the backstage crew in a play, ensuring everything runs smoothly.

The Power of Epigenetic Regulation

Epigenetic regulation plays a crucial role in various biological processes, including:

Development: During embryonic development, different cell types emerge from the same DNA blueprint by activating or silencing specific gene sets through epigenetic modifications.

Cellular differentiation: Specialized cells like muscle or nerve cells have unique functions due to differences in their active genes, controlled by epigenetic mechanisms.

Learning and memory: Epigenetic changes in brain cells are thought to be essential for learning and forming memories.

Aging: As we age, our epigenome accumulates changes that can contribute to age-related decline and disease.

Environmental influences: Diet, exercise, stress, and exposure to toxins can leave epigenetic marks on our genes, potentially impacting our health and even the health of future generations.

Epigenetics reminds us that we are not simply products of our genes. Our environment, choices, and experiences leave their mark, shaping who we are and potentially influencing our children's health. This deeper understanding of ourselves opens doors for self-awareness, empowerment, and potentially reshaping our narratives – not just as individuals, but as a species with the potential to leave a healthier legacy for generations to come.

[darkmaga-returns]

An official new study ties mRNA COVID-19 vaccines to rapid genetic changes that trigger cancer and VAIDS (Vaccine-Acquired Immune Deficiency Syndrome). German researchers warn these jabs could rewire human DNA, sparking deadly inflammatory responses in many recipients.

Published last week in Molecular Systems Biology, the peer-reviewed study by 19 scientists reveals how mRNA vaccines may alter genetic structures over the long term. These changes, they argue, could explain rare but severe post-vaccination inflammatory diseases cropping up among a small subset of vaccinated individuals.

Journalist Alex Berenson highlights the study’s grim implications, noting that the genetic shifts could be linked to leukemia and brain tumors. He explains that mRNA vaccines might “train” immune cells to lock into a pro-inflammatory state, setting the stage for these devastating conditions.

Epidemiologist Nicolas Hulscher calls the findings a critical addition to mounting evidence of mRNA’s immune-disrupting power. “This study underscores the potent dysregulating effects of these injections,” he says, urging further scrutiny into their widespread use.

The Defender reports: Hulscher said the study raises “serious concerns about long-term immune homeostasis and the potential for chronic inflammatory disease, autoimmune sequelae, and even oncogenic processes.”

Immunologist and biochemist Jessica Rose, Ph.D., said the study confirms what is already known about the risks of mRNA vaccines. She said:

“Repeat injection leads to a boatload of immunological modifications. This is not new information. We know that these kinds of changes can occur. It is not surprising to me that they found this.

“If the systemic reach goes far enough, such as to stem cells, then repeated injection could potentially induce epigenetic changes in these cells, especially since hematopoietic stem cells are known to develop innate immune memory in response to certain stimuli like infections or other vaccines.”

[fanfoolishness]

Evaluations (The Bad Batch)

A selection of evaluations of the health of CT-9904, as performed by Nala Se. Nala Se POV, Crosshair whump/medical whump, angst at a remove. ~3200 words.

---

Nala Se walks through the long white corridors to the clones’ medical bay.  Troopers march past in tight formation, each one perfectly uniform, created precisely to match their original specifications.  Behind them small cadets trail their older mirrors in imitation, small brown faces all alike, dark hair in the same short military style.  She has only to glance at them all to see her own flawless work marching beside her.

She allows herself a small, secret smile.  There have been some clones with flaws, of course.  Adjustments to obedience, size, intelligence. ability.  She is most curious to see how the clones of the 99 designation fare as they age.

Her work, she suspects, is not unlike that of the artist or musician.  Like them there is an idea she carries in her mind, the delicate dance of DNA and genetic modification, a vision she has planned and put into motion through the work of her own hands and her own vision.  Now there is only the waiting to see the finished product that remains.  She knows what she expects of her enhanced clones one day.  Yet she also anticipates there may be surprises to occur in their development, unexpected interplays of inspiration or epigenetic accidents leading to something greater than the sum of their parts.  It is a pleasant source of anticipation in her day to day, to see the finished music that her work might make.

She reaches the medical bay and the doors slide open for her.  She is mildly taken aback at the scene of disarray that appears.  A clone cadet, bio-equivalent to a seven-year-old human, sits hunched over himself on the floor, surrounded by scattered medical equipment that appears to have been thrown or kicked around the room.  AZI-3 hovers a safe distance away from the clone, and seems relieved to see her.

“Doctor Se,” he says, pitching his voice modulators to a quiet scale.  “You have asked me to inform you of any medical visits regarding clones of the ninety-nine designation.  This is CT-9904, and he is here with a minor injury, but he is proving… difficult.”

Nala Se nods.  CT-9904 would be identifiable from across any room nearly instantly; with his modifications, it is obvious. The clone’s proportions are unusual, thinner and taller than would be expected at this stage of development, and streaks of gray pepper his dark hair despite his young biological age.  She had expected that variation.  On many species her work has shown an inextricable link between hair color and visual development, and humans are no different.  

“CT-9904,” she murmurs.  “Please explain yourself.”

The clone unfolds himself and gets awkwardly to his feet, bowing his head briefly to her before looking down at his boots.  The injuries are apparent, a blue-black bruise swelling his right eye shut, scrapes up and down his rather thin, angular face.  He sniffs, rubbing the back of his hand against his nose.  It comes back bloody.

“There was a fight,” the boy says slowly.  His voice is odd, slightly raspy, with an accent to his Basic that deviates from the norm.  That variation had not been anticipated.  One of her intriguing surprises.

She waits, giving him an expectant look.  He takes a deep breath.  

“The other clones didn’t like that I’m different.”  His fists clench at his sides.  “I beat all of their scores in marksmanship.  It’s so easy.  They got mad… they started it. I tried to finish it, but there were more of them than me.”  He crosses his arms over his chest, scowling, then wincing.  

“Fights are not uncommon at this stage of training,” Nala Se murmurs. “The tendency is typically outgrown.”  Though there is the matter that with his enhanced visual acuity, CT-9904 has been training in marksmanship with clones four cycles older.  Perhaps seeing a clone so much earlier in his development excel has triggered the aggressive response from the standard units.  She turns to AZI-3.  “What is the prognosis?”

“There is a hairline fracture of the right zygomatic arch, but with the rapid growth rate and the improved healing capabilities, this is not expected to have any negative long-term effects.  Which I have tried explaining to him!”

“I don’t believe you!” the boy bursts out.  Nala Se tilts her head to one side, studying him.  

“Why?”

The boy looks furtive, anxious, fidgeting where he stands.  His hands twist together.  At last he stammers, “I can’t see!”  He tries to open the swollen right eye and fails, hissing with the effort.  

“I have informed him that this is temporary,” says AZI-3.  He addresses the clone directly.  “The swelling needs time to come down, and then you will see normally again.  All of the scans indicate that your eye itself was not damaged, only the tissue surrounding it.  You should be back to normal within ten rotations.”

“Are you sure?  But that’s -- it’s all I -- I have to --”  His face is flushed.  “It’s what I’m for!”

“Your vision will return in time, CT-9904.  Your enhancements remain intact.  The droid tells the truth,” says Nala Se.  “There are other skills you may continue training in during this time.  I will see to it that you are assigned extra training in stealth and hand-to-hand combat as you heal.”

The clone gives her a worried look, then nods, letting out a long breath.

“Please help AZI-3 clean up this mess.  After that, you should return to your quarters.  Your fellow cadets should be returning from their own training soon.”

The clone laughs slightly, a small smile shifting on his face.  “Wrecker’s going to be mad he missed the fight.  He could have taken them all out.  I know it.”

“Hmm.”  She sighs.  This is not the first time these particular clones have been at the center of discord among the standard cadets, and she has a strong suspicion it will not be the last.  Yet another unique trait in a batch full of them.  She wonders which one of them will be in here next.

---

CT-9904 is led into the medical bay by red-painted clone troopers, stripped of his armor and walking with his head down.  Nala Se is waiting.  She has been curious to assess the effects of the inhibitor chip on her modified clones; the chips themselves had not been modified or calibrated for the minds of this particular batch, and she had long wondered if she would ever see the effects on them were the chips to be activated.  Here then is her opportunity to learn, though her curiosity feels subdued from what she had anticipated.  Perhaps it is merely that she feels disquieted by the presence of Admiral Tarkin in the chamber beyond.  

My work does not need your supervision, Admiral, she thinks, then turns to the clone at hand.

CT-9904 has only rarely needed medical assistance after completing his training; as his squad’s long-range sniper, he has typically avoided the types of injuries accrued by the others.  It has been multiple cycles since she has last seen him up close, and he sits obediently on the examination table under armed guard, his eyes shadowed, his face grim.

“How do you feel, CT-9904?” she asks.

“I don’t know why I’m here,” he bites out, looking away.  “There’s nothing wrong with me.  Perhaps you should look at Hunter.  He’s been acting irrationally.”

“He will be examined in time,” she assures him.  “There are some questions I am going to ask you.”

He shrugs, sighing.  “All right.”

“Have you had any episodes of seizures?”

He sits up straight, looking at her suspiciously, a wary surprise in his eyes.  “No.”

“Have you experienced any episodes of fainting?”

“No.”

“Have you experienced any disorientation?”

“No.”

“Have you experienced any headaches?”

A short, sharp intake of breath.  His eyes focus beyond her, fixating in the direction of the Admiral, and a guilty look crosses his face.  “...yes.”  

“Thank you, CT-9904.  The examination will begin.”

One of her new medical droids hovers forward, extending a long hypodermic.  The clone’s eyes widen.  “Is that necessary?”

“Yes, it is.”  The droid injects him in the shoulder.  He grimaces, but then his expression slides into something dreamy, a placid, half-lidded stare.  He slumps where he sits and the droid eases him onto his back, preparing him for imaging.  Nala Se recuses herself to the outer chamber.

She has read CT-9904’s report of Kaller, contradicting the reports from his squadmates.  They have informed her of his attempts to convince his squad to follow orders.  It is a fascinating finding.  CT-9904’s chip may be working -- she will run the necessary tests to confirm, but the headaches are the earliest stage of an incomplete chip activation -- yet loyalty to his squad appears to be superseding its commands.  

Admiral Tarkin waits for her as the test commences.  As she has suspected, the chip is partially working, but CT-9904’s mutations have muted its effectiveness.  She transmits the order to amplify the chip’s effects as the Admiral looks on.  

The amplification process is one that she has never used before in practice, though it was developed for theoretical use in an event such as this one.  As she watches it becomes plain that the dose of sedative has been insufficient for such a procedure.  CT-9904 trembles, hands curling beside him, his chest rising and falling jerkily.  She assesses his vitals.  They are stable enough, but the elevated heart rate and erratic breathing are consistent with pain.  

She considers adding further sedation, but the process is nearly complete, and she refrains.

The arms of the machine retract.  She checks her datapad.  The clone’s vitals have returned to normal, and he is starting to stir. 

“Did it work?” Admiral Tarkin asks, voice clipped with impatience.  “If not, you may begin the decommissioning process.  But if it has worked, I would like the same procedure performed on the remaining squad.”

“Understood, Admiral.  I will assess him myself.”

By the time she enters, CT-9904 is clumsily sitting up, breathing hard.  He raises one hand to his right temple, shaking his head.  “What happened?” he asks.

“You have been found clear to return to duty.  With your squad.”

CT-9904 frowns, his face going cold.  “My squad disobeyed orders.”  He gets off the table, swaying slightly, and straightens up.  “Good soldiers follow orders.”

“And if your squad does not?”

“Then they need to be eliminated,” CT-9904 says evenly.  His eyes are blank, devoid of the suspicion and wariness that had been plain earlier.  She nods, feeling a slight pang.  She would have preferred to have had the time to study the interplay between the clone’s mind and the partially activated chip in case there were new insights to be gleaned.  Observing him for several weeks would have been most intriguing.  But she is certain now that in this regard, at least, CT-9904 is no longer unique.

---

“Status report,” Nala Se asks, gazing down at the unconscious clone in recovery.

The medical droid catalogs the clone’s injuries while removing the field bandages marred by strikethrough.  The list is long and troubling.  Ion burns to the chest, hands and face.  Concussion to the right temple.  Corneal abrasions.  Right shoulder dislocation, replaced in the field.  Inhalation injury.  It is disheartening to see such a unique specimen in such shape.  The corneal abrasions are the most concerning, given the nature of his enhancements, but the droid’s readings confirm that they are thankfully superficial and should heal without issue.

“How did this occur?”

“Exposure to an ion engine, Doctor,” says a human woman with a clipped, stern voice, her helmet carried under her arm.  “We were shocked he survived.  None of the other clones with him made it.”  Nala Se gives her a cool look.  One of Admiral Tarkin’s conscripts, her training nonstandardized, her breeding unknown.  She does not understand the Admiral’s obsession with ‘updating’ the army of the Republic, no, Empire, and it is an affront to have one of those inferior soldiers here in her own medical bay.  

The soldier is still standing at attention.  “Will the Commander be all right?” she asks, and there is something calculating in her eyes. Nala Se frowns.  Clones would never show such hints of naked ambition.

“Yes.  There is extensive treatment to be done, but he will likely be fully rehabilitated within a matter of weeks.”  They have repaired far more grievous injuries to their clones over the years.  Kaminoan work was strong, and it was reparable when desired.  “CT-9904 is valuable to the Empire, and he will recover.”

The soldier frowns.  “Even with the seizures?”

Nala Se gives her her full attention.  “He has had seizures?”

“Two, on the journey back from Bracca,” she says.  “I thought the medic told you.  Is that from the head injury?”

“There will be no further questions,” Nala Se says.  “You may leave.”

The woman shoves her helmet back on, nodding, and finally leaves.  Nala Se immediately locks the laboratory door behind her.

There is a faint groan from the bed.  CT-9904 raises his left hand weakly before it drops back against his chest.  He coughs, the sound amplified in the oxygen mask looped over his face.  

She casts her eyes over the blistered flesh above his right ear, then directs the medical droids to set up the imaging device to assess the chip.  CT-9904’s breathing rattles in the confines of the imaging chamber.  It is disconcerting.    

The machine whirs, its testing cycle complete, and it retracts to leave CT-9904 back in the open.  She frowns at the results on her datapad.  

“The inhibitor chip is damaged,” she tells the medical droid at the clone’s side.  “Swelling in the brain has interfered with its functioning.  The seizures are the result of an improper connection.”

CT-9904 fumbles at the oxygen mask on his face, making a garbled noise.  He manages to pull off the mask, and rasps, “Take it out, then.”

Nala Se stiffens.  

She has made a mistake.  

She has never spoken of the chips in the presence of a clone beyond Omega.  Now in her curiosity, with CT-9904 so wounded as to appear unconscious, she has erred.  She turns to him, wondering how she should proceed.  Despite what she had said about CT-9904’s value to the Empire, she is certain there would be no repercussions if he were to not survive his injuries.

“What do you mean?”

“I know…” He swallows, coughing, flecks of blood-tinged fluid dotting his lips.  “I know about the chip.  They told me.”

“Who?”

“Clone Force 99,” he manages.  “Said it’s… controlling me.  But I don’t --”  He presses the oxygen mask against his face again, taking in several deep breaths before removing it again.  He squints up at her through blepharospasm, eyelids struggling to open despite the pain of the abrasions.  “I don’t need a chip to be loyal.  To --”  His chest heaves.  “To be a good soldier.”

CT-9904 suddenly stares off into space, his good eye transfixing on the ceiling.  His jaw slackens, and she recognizes the prodromal signs of an impending seizure.  Nala Se gives a swift look to the medical droid.  “He will need an anticonvulsive.  Immediately.”  The droid complies, heading off the seizure before it can truly begin.  

Nala Se hesitates.  There are three paths remaining to her now.  Euthanasia of the enhanced clone to prevent possible awareness of the chip from being spread to other clones; treating the injuries but leaving the clone in his current state, potentially compromised by seizures and prone to worsening degradation of the chip; or --

She makes her choice, recalling the clone’s words.  CT-9904 and his cohort have always represented a new era in experimentation for her.  Perhaps by removing his chip now, she may continue to be surprised.

---

The walls of Tantiss press in around her, a windowless narrow world of her cell and the hallway beyond.  Tipoca City lies beneath the waves of her homeworld, her lab, her work, her calling buried in the sea; and now there is only the Empire and its brutal destruction.  

She has been a fool.  She had so buried herself in her work that she had blinded herself to the dangers of being indispensable.  She knows that she will never leave this planet alive.

The days are endless, the monotony almost worse than the clumsy efforts of the Empire to extract the information they needed by force.  Their interrogation droids had been programmed for human physiology, and while unpleasant, their methods had failed to force her to share her scientific knowledge.  They have since given up on that, and now Hemlock attempts to use the clone Omega as a bargaining chip, despite having no idea of her whereabouts.  

Nala Se cares little for his efforts.  She cares little for anything at all, now.

The one slight bit of interest in her day is her daily walk.  They bring her to the lab once daily under heavy guard and supervision, perhaps hoping she will be enticed by the technology to resume her old work.  She has no interest in the lab, refusing to examine its machines and capabilities, but she watches closely the clones walking by under their own guard, amusing herself with guessing which batches they had arisen from.  She has no way to confirm her guesses, but to her trained eye, subtle changes in the degree of aging -- the appearance of fine wrinkles starting at the edges of the eyes and corners of the mouth, a slight shift in glossiness of the hair, faint alterations to the gait -- provide significant clues.  It puts her in mind of happier times, when she could truly focus on science and take pride in the results of her labors.  

One day -- or perhaps night, there is no way to tell -- she awaits the lift with her captors and a group of clones stops beside them, waiting for the same lift.  She turns to study them and is taken aback.  One clone stands above the others, several inches taller despite the slump in his shoulders.

Her mind swirls with questions.  Had the removal of CT-9904’s chip -- omitted from his final medical report after his injuries on Bracca -- come to light?  Was he sent here for betrayal of the Empire?  Or had he merely been injured and deemed unfit to return to duty, so was sent here for study to remain useful?  

He does not meet her gaze.  She is not sure he has even noticed she stands beside him.  His face is skull-like, his skin sallow from lack of sunlight, deep shadows etched beneath his eyes.  A flicker of movement catches her eye and she notes a fine tremor, nearly imperceptible, along the edge of his hand.  He shakes his hand almost subconsciously, a small, subtle jerk she is not sure that even he has detected.  There are no obvious injuries, but there is an emptiness that is apparent, a lack of something vital.

She does not know what has brought him here, but she knows that he is a soldier no longer.

The lift arrives and the guards herd them within.  Force is not required; the prisoners know their place.  They stare down at the floor, heads bowed.  

Nala Se gazes away from the ruined clone beside her.  The music she had once carried in her head, the clever dance of DNA and ingenuity, the spark of creativity, of creation, falls silent.  She does not speak to him, nor he to her.  

There is simply nothing to say.