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New Insights into the Cause of Neurological Symptoms in Mitochondrial Diseases

neurosciencestuff

Mitochondrial diseases – which affect 1 in 5,000 people – encompass a spectrum of disorders with an array of symptoms. Many patients with a mitochondrial disease experience neurological symptoms, including intellectual disability, childhood epilepsy and autism spectrum disorder, but why dysfunctional mitochondria – the powerhouses of cells –lead to these sorts of symptoms has been unclear.

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In a paper published on March 31 in Cell Reports, BWH investigators shed light on what may be the root cause of these neurological symptoms by tracing the development of interneurons. Interneurons, also known as connector neurons, must migrate long distances during the brain’s development, taking a circuitous path to travel from their neural stem cell origins in the ventral forebrain to their location in the dorsal neocortex. The new study indicates that mitochondria, which provide energy for cells, may play a vital role in this migration. Using preclinical models, the team determined that interneurons have higher energetic requirements than other neurons and that properly working mitochondria move about inside interneurons rapidly during migration. When Ant1, a gene known to play a role in mitochondrial disease, was disrupted, mitochondria did not move about in the same patterns and interneurons migrated more slowly and shorter distances.

The new work suggests that correcting epilepsy or reversing other neurological symptoms in patients with mitochondrial diseases will not be as simple as replacing dysfunctional mitochondria at any time. Instead, these symptoms may be the result of brain developmental defects that took place during embryonic development. Further studies will be needed to validate these results in tissue samples from humans.

“We need to rethink how we strategize caring for patients. Historically, patients have been recalcitrant to therapy, and this new work may explain why,” said Jeffrey Golden, MD, chair of BWH’s Department of Pathology and a co-corresponding author of the study. “This work also provides an insight into rethinking therapeutic strategies.”

Source: bwhclinicalandresearchnews.org
ladyyatexel

on fanfic & emotional continuity

fozmeadows

Writing and reading fanfic is a masterclass in characterisation. 

Consider: in order to successfully write two different “versions” of the same character - let alone ten, or fifty, or a hundred - you have to make an informed judgement about their core personality traits, distinguishing between the results of nature and nurture, and decide how best to replicate those conditions in a new narrative context. The character you produce has to be recognisably congruent with the canonical version, yet distinct enough to fit within a different - perhaps wildly so - story. And you physically can’t accomplish this if the character in question is poorly understood, or viewed as a stereotype, or one-dimensional. Yes, you can still produce the fic, but chances are, if your interest in or knowledge of the character(s) is that shallow, you’re not going to bother in the first place. 

Because ficwriters care about nuance, and they especially care about continuity - not just literal continuity, in the sense of corroborating established facts, but the far more important (and yet more frequently neglected) emotional continuity. Too often in film and TV canons in particular, emotional continuity is mistakenly viewed as a synonym for static characterisation, and therefore held anathema: if the character(s) don’t change, then where’s the story? But emotional continuity isn’t anti-change; it’s pro-context. It means showing how the character gets from Point A to Point B as an actual journey, not just dumping them in a new location and yelling Because Reasons! while moving on to the next development. Emotional continuity requires a close reading, not just of the letter of the canon, but its spirit - the beats between the dialogue; the implications never overtly stated, but which must logically occur off-screen. As such, emotional continuity is often the first casualty of canonical forward momentum: when each new TV season demands the creation of a new challenge for the protagonists, regardless of where and how we left them last, then dealing with the consequences of what’s already happened is automatically put on the backburner.

Fanfic does not do this. 

Fanfic embraces the gaps in the narrative, the gracenotes in characterisation that the original story glosses, forgets or simply doesn’t find time for. That’s not all it does, of course, but in the context of learning how to write characters, it’s vital, because it teaches ficwriters - and fic readers - the difference between rich and cardboard characters. A rich character is one whose original incarnation is detailed enough that, in order to put them in fanfic, the writer has to consider which elements of their personality are integral to their existence, which clash irreparably with the new setting, and which can be modified to fit, to say nothing of how this adapted version works with other similarly adapted characters. A cardboard character, by contrast, boasts so few original or distinct attributes that the ficwriter has to invent them almost out of whole cloth. Note, please, that attributes are not necessarily synonymous with details in this context: we might know a character’s favourite song and their number of siblings, but if this information gives us no actual insight into them as a person, then it’s only window-dressing. By the same token, we might know very few concrete facts about a character, but still have an incredibly well-developed sense of their personhood on the basis of their actions. 

The fact that ficwriters en masse - or even the same ficwriter in different AUs - can produce multiple contradictory yet still fundamentally believable incarnations of the same person is a testament to their understanding of characterisation, emotional continuity and narrative. 

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