Victor Nikiforov believed in fitness like it’s a religion. As a former model and owner of his modelling agency VTA by Victor Nikiforov, he had to keep up his image and his body was the best advertisement for his company. The morning run was his way of unwinding, the only the day when was truly alone with Makkachin. Across the way, he usually took a detour to the dog park that was on the way. Makkachin was a very sociable dog, he liked to visit his dog friends every day and that was their routine every morning.
So this past weekend was the VTA (Virginia Theater Association) conference, and one of the special guests was Mike Faist. There was a drawing to be in a workshop with him, and I happened to be one of the ones chosen!!!! Anyways, the group of us were standing outside the room as he started walking up, looking all serious and such. Then, out of the corner of his eye, he spots a baby… and he immediately smiled and veered around towards the baby. He then spends like five minutes with the baby, and it was adorable. That is all.
The Genes and Neural Circuits Behind Autism’s Impaired Sociability
Researchers at Beth Israel Deaconess Medical Center (BIDMC) have gained
new insight into the genetic and neuronal circuit mechanisms that may
contribute to impaired sociability in some forms of Autism Spectrum
Disorder. Led by Matthew P. Anderson,
MD, PhD, Director of Neuropathology at BIDMC, the scientists determined
how a gene linked to one common form of autism works in a specific
population of brain cells to impair sociability. The research, published
in the journal Nature, reveals the neurobiological control of
sociability and could represent important first steps toward
interventions for patients with autism.
Anderson and colleagues focused on the gene UBE3A, multiple copies of
which causes a form of autism in humans (called isodicentric chromosome
15q). Conversely, the lack of this same gene in
humans leads to a developmental disorder called Angelman’s syndrome,
characterized by increased sociability. In previous work, Anderson’s
team demonstrated that mice engineered with extra copies of the UBE3A
gene show impaired sociability, as well as heightened repetitive
self-grooming and reduced vocalizations with other mice.
“In this study, we wanted to determine where in the brain this social
behavior deficit arises and where and how increases of the UBE3A gene
repress it,” said Anderson, who is also an Associate Professor in the
Program in Neuroscience at Harvard Medical School and Director of Autism
BrainNET Boston Node. “We had tools in hand that we built ourselves. We
not only introduced the gene into specific brain regions of the mouse,
but we could also direct it to specific cell types to test which ones
played a role in regulating sociability.”
When Anderson and colleagues compared the brains of the mice
engineered to model autism to those of normal – or wild type (WT) –
mice, they observed that the increased UBE3A gene copies interacted with
nearly 600 other genes. After analyzing and comparing protein
interactions between the UBE3A regulated gene and genes altered in human
autism, the researchers noticed that increased doses of UBE3A repressed
Cerebellin is a family of genes that physically interact with other
autism genes to form glutamatergic synapses, the junctions where neurons
communicate with each other via the neurotransmitter glutamate. The
researchers chose to focus on one of them, Cerebellin 1 (CBLN1), as the
potential mediator of UBE3A’s effects. When they deleted CBLN1 in
glutamate neurons, they recreated the same impaired sociability produced
by increased UBE3A.
“Selecting Cerebellin 1 out of hundreds of other potential targets was
something of a leap of faith,” Anderson said. “When we deleted the gene
and were able to reconstitute the social deficits, that was the moment
we realized we’d hit the right target. Cerebellin 1 was the gene
repressed by UBE3A that seemed to mediate its effects.”
In another series of experiments, Anderson and colleagues
demonstrated an even more definitive link between UBE3A and CBLN1.
Seizures are a common symptom among people with autism including this
genetic form. Seizures themselves when sufficiently severe, also
impaired sociability. Anderson’s team suspected this seizure-induced
impairment of sociability was the result of repressing the Cerebellin
genes. Indeed, the researchers found that deleting UBE3A, upstream from
Cerebellin genes, prevented the seizure-induced social impairments and
blocked seizures ability to repress CBLN1.
“If you take away UBE3A, seizures can’t repress sociability or
Cerebellin,” said Anderson. “The flip side is, if you have just a little
extra UBE3A – as a subset of people with autism do – and you combine
that with less severe seizures - you can get a full-blown loss of social
The researchers next conducted a variety of brain mapping experiments
to locate where in the brain these crucial seizure-gene interactions
“We mapped this seat of sociability to a surprising location,“
Anderson explained. Most scientists would have thought they take place
in the cortex – the area of the brain where sensory processing and motor
commands take place – but, in fact, these interactions take place in
the brain stem, in the reward system.”
Then the researchers used their engineered mouse model to confirm the
precise location, the ventral tegmental area (VTA), part of the
midbrain that plays a role in the reward system and addiction. Anderson
and colleagues used chemogenetics – an approach that makes use of
modified receptors introduced into neurons that responds to drugs, but
not to naturally-occurring neurotransmitters – to switch this specific
group of neurons on or off. Turning these neurons on could magnify
sociability and rescue seizure and UBE3A-induced sociability deficits.
“We were able to abolish sociability by inhibiting these neurons and
we could magnify and prolong sociability by turning them on,” said
Anderson. “So we have a toggle switch for sociability. It has a
therapeutic flavor; someday, we might be able to translate this into a
treatment that will helps patients.”
Hi, my name is Millie and I’m an #actuallivingscientist studying how dopamine neurons in the brain respond to different types of stressors, and how these responses may differ between sexes. Upper right: hand- pulled glass recording electrode Lower right: Plate of brain area (VTA) where I find dopamine neurons to record from. #neuroscience #outreach #scicomm #femalescientist #womeninscience #academia #electrophysiology #researcher #STEM
Main armament: 100 mm gun/launcher 2A70 (able to fire shells or the 9M117 Bastion ATGM), 30 mm autocannon 2A72
Secondary armament: 3×7.62 mm PKT machine guns
Engine: UTD-29M diesel 500 hp with a power/weight 27 hp/tonne
Suspension: torsion bar
Operational range: 600 km
Speed: 72 km/h on road, 45 km/h off-road 10 km/h in water.
M3 Bradley Cavalry Fighting Vehicle
Weight: 23–28 metric tonnes
Length: 6.5 meters
Width: 3.2 meters
Height: 3 meters
(commander, gunner, driver) and 2 passengers/troops
Armor: Steel and aluminum
Main armament: 25 mm M242 Chain Gun,dual TOW Anti-Tank Missile Launcher
Secondary armament: 7.62 mm M240C machine gun
Engine Cummins VTA-903
600 hp with a power/weight 19.74 hp/tonne
Suspension: torsion bar
Operational range: 480 km
Speed: 66 km/h on road, 7.2 km/h on water
In everything but armor the BMP beats the Bradley, as she has much better weaponry, in the form of her 100mm gun, capable of both launching missiles (which are easy to reload from inside the vehicle) and conventional AT rounds, coupled with a powerful 30mm cannon, vs the Bradley’s 25mm chaingun, and her couple of TOW missiles, which have to be reloaded from the outside manually once expended.
But the Bradley has much better armor, capable of withstanding 30mm rounds all-around, and reactive armor capable of stopping RPG’s, BUT the BMP can also equip reactive armor, and thanks to her ability to mount the Shtora electro-optical active protection system, she’s effectively inmune to the TOW once equipped, contrary to the Bradley, which has to rely on her armor to defeat any AT missile.
So, the BMP-3 wins, a much more modern design born from the ashes of the Afghan war, VS a committee-designed vehicle plagued with problems from her inception, that still, nevertheless proved her worth against Iraqi second-generation tanks and armor.
The entire block is coffee shops advertising free wifi. You spot a
taqueria in the corner, only to find that it has turned into an
artisanal ice cream shop. It also has free wifi. The overlapping wifi
networks create a pattern that cancels out. You will have to use the
internet from your phone. They say this curse is because everything is
built on Native American remains.
The Caltrain you’re on is stopped. There has been a fatality on the tracks. All your fellow passengers stare impassively into their phone screens as they voice their frustration on twitter: late to work again. A Google Bus drives by. A Facebook bus drives by. An Uber bus drives by. Another typical Monday.
You can’t tell if this is a fusion restaurant, a patisserie, or a coffee shop. The menus no longer have decimal points. The menus no longer have English words. The menus are no longer paper. There is no wait staff, only an iPad with Square and Yelp. The food comes: it is three slices of avocado in squid ink. It is 40.
You are developing an app. Your friend is also developing an app. So is your boss. And your dog. And your dogsitter. He says his app is like “AirBnB but for dogs.” You smile encouragingly and ask about the app store approval process. Soon, you tell your app. Soon it will have the sustenance it needs. Your app shimmers ravenously.
There are more white men named Matt on your team than there are women. You think about changing your name – Matt has such a nice ring to it. At work, you high five the other Matts for their excellent choice in geeky t-shirts. The woman has disappeared. You don’t remember anything about her. You invite everyone to play Settlers of Cataan. Even Manpreet. He will be a Matt soon enough.
You have lost track of how many public transit systems you’ve been on in the last 3 hours: VTA, Caltrain, BART, Muni, AC Transit, Samtrans. You are still stuck in Redwood City.
There is a 3 bedroom house for sale for $3 million. The website for the house plays the conversations of the original house owners. They were Japanese immigrants from 1940. They are asking to be let out of the dark box. You click “subscribe.”
Hi! So I have a character who has done heroin, smoked pot, drank a lot of booze, and is now smoking cigarettes because he lost his boyfriend in a gang war. He only used heroin and pot for about 6 months before a friend intervened. What kind of effects would that short use of drugs cause? Or is that time frame of use unrealistic?
This is in the disclaimer page, but I’ll reiterate this here: The information provided here is purely for scientific and intellectual interests and we do not condone the use of psychoactive drugs for recreational purposes. This post is also not an admission of use of illegal/controlled substances- this is purely informative.
This question doesn’t require too technical of an answer for the effect of heroine on the brain, but I’ll very briefly explain how heroin addiction works in the central nervous system- I may make a post later talking more in depth about what is happening on a molecular scale, but I don’t think it’s necessary for this more general post.
Addiction, for our purposes, requires physical dependence on a drug, which includes craving, drug seeking behavior, and withdrawal symptoms when the drug is stopped, which is the result of the brain having come to need the drug to function “normally”. Heroin, an opioid, acts by disinhibiting the ventral tegemental area (VTA), which is part of the brain’s reward circuitry. Among other things, the VTA projects to cortical and “limbic” structures, including the prefrontal cortex, the amygdala, and the hippocampus, and releases dopamine when faced with rewards, things that predict rewards, and unexpected stimuli; in the case of addiction, the VTA mediates the feel-good and motor aspects of drug use. Heroin decreases the release of GABA (an inhibitory neurotransmitter) and makes neurons in the the VTA fire more easily than normal- this disinhibition, then, makes it so that the VTA “relaxes” when heroin reaches the brain, and that it more readily releases dopamine. This tells the brain, basically, “this is good, remember this”. The cortex, meanwhile, is taking in sensory information and associating the place you’re in, your emotions, the tools you’re using, the people you’re with, etc, and ties these to this VTA signal. Over time and with regular use, internal molecular adaptation can lead to hyperactive signalling and a further disinhibited VTA compared to before you started using drugs; while using drugs, however, this balances out and people feel more “normal”. When you stop using them, however, and you go back to a chemical state that was previously “normal”, you’re actually below the needs of your brain, which leads to withdrawal symptoms that are the opposite of the drug effect. Where heroin use makes you dull, sleep, and insensitive to many things, heroin withdrawal is often characterized as hyperactive, hypersensitive, and hyper-aroused.
But these changes take some time and regular usage to take effect.
Thus, the physical symptoms your character would experience would depend on how often he used, I think. If he’s using less than, say, twice a week (recreational use), doesn’t experience withdrawal symptoms between uses, doesn’t use while drinking, uses clean needles (if he uses needles at all), uses decent quality heroin that isn’t cut with anything toxic, and doesn’t overdose at any point, I’d wager to say it’s unlikely there will be significant physical effects after he stops using.
That said, I think it’s highly unlikely that he would be using heroin in a safe and responsible way if he’s doing it out of grief. I’m not a psychologist (you can ask @scriptshrink for some help on this part, possibly), but in my own experiences with grieving, it’s very easy to neglect yourself and do things of higher risks without paying attention much to the consequences. I’d find it realistic for him to not care too much about being responsible and following safer drug use guidelines to a T. In that case, if he shares needles, he can easily find himself with HIV, Hep B, or various blood borne diseases. If he’s injecting, he may also end up with scarred skin, abscesses, infection, collapsed veins, etc, depending on his technique and again, how often he used. Given regular use, after stopping heroin use, some people have permanent tremors, sexual dysfunction, insomnia, depression, “foggy” thinking, etc. as part of post-acute withdrawal syndrome. After all, it’s very difficult for your brain and body to get back to the chemical and physical state it was in before you started using, since the changes made to it were so massive. If your character has had an overdose, he will have the worst effects- during an overdose, the amount of oxygen in the blood is so low that brain damage can happen, leading to general cognitive decline (trouble thinking, etc). Finally, even if he stops using, if he became an addict, he’ll be an addict for life- a lot of recovering opiate addicts don’t use pain medications even if they need them, just so they don’t fall back into the habit.
I would also consider perhaps having him use something other than heroin? Most people don’t jump from pot to IV heroin from one moment to the other- maybe consider having a sort of “descent” from other narcotics, like prescription meds, to harder drugs and eventually to heroin. Of course, this varies, but it’s pretty common for people to go from things like oxycodone, morphine, or hydrocodone, start smoking heroin because it’s cheaper, then eventually start needing more and more and start injecting.
As for alcohol, I’d go so far as to say that alcohol addiction is even more dangerous than heroin addiction. Alcohol is legal, thus easier to get, and withdrawal from it can actually kill you (whereas heroin withdrawal is miserable but rarely fatal). Alcohol addiction is similar to heroin addiction in that it acts on the VTA, but actually increases the amount of GABA receptors instead of reducing the amount of GABA (which effectively also disinhibits the VTA), and can lead to subtly different effects in terms of reward. Alcohol also inhibits the release of glutamate in the brain, which is an excitatory neurotransmitter, and this in combination with more GABA action leads to some of the slow, sluggish effects of alcohol. Long term alcohol abuse, of course, tends to lead to brain damage that affects attention, memory, and judgement, and physically can lead to liver problems and pancreatitis. In conjunction with heroin use (especially if he’s doing both at the same time), I would be very concerned for your character’s well-being. If he’s just drinking heavily in binges and occasionally doing heroin recreationally, I’d still be concerned, but I would guess he’s not as much of a ticking time bomb?
Finally, I wouldn’t be too concerned about the pot. He really shouldn’t combine things (I don’t think he’d want to), and there are dangers if he’s, for example, eating a lot of edibles at once just because he might do something really dumb and/or dangerous, but in and of itself, it doesn’t seem to be all that bad in terms of the brain? There are some suggestions that there are effects on memory and learning, especially verbal memory, but nothing conclusive about “this will destroy your brain” as far as I know. It’s hard to gauge the effects with pot too, since again, it depends on how often and how much is used (there are sensitization effects!). But if he’s around or older than 24/25, he should be mostly okay- at least in terms of the effects of pot specifically. Most of the dangers come from younger people using it, since the brain is still in a very plastic state and it may interfere with the connections being made at the time.
Non-neuro, but I’ve written characters before that use drugs and I highly recommend looking through drugs and addiction forums where you can find personal experiences and answers to questions about the emotional, social, and personal aspects of addiction. These are more useful for writing a character than knowing how the drug acts on the brain specifically (though that can certainly be useful!).
Hope this has helped, but let me know if you need more info.
Submission – Unofficial Maps: Bay Area Rail Transit by Lyle Simmons
Submitted via email by Lyle, who says:
The Bay Area has one of the most complex and diverse urban transit systems in the world, including three commuter rail systems, one metro systems, two light rail systems, one heritage streetcar line, and four major bus agencies. Unfortunately, there isn’t an official map linking any of these services together, so I thought I might make one myself.
Transit Maps says:
There’s a lot to like about the look that Lyle has created for this series of maps – it’s more curvaceous and spacious than many diagrammatic transit maps, which gives everything a nice languid, flowing feel. That said, there’s a few usability and design issues that I can see, not the least of which is the relative spacing of stations on the maps.
Let’s start with the first map of the whole Bay Area. The relative simplicity of each of the individual systems means that they can each be shown with a minimum of fuss – only BART needs to have its lines enumerated, as Muni Metro and VTA light rail are expanded upon in the two following maps. If the three maps are to be presented as a series, then an outline around the SF peninsula and Santa Clara areas pointing people to those more detailed area maps could be a nice addition.
The end points for Muni could be handled better: the inclusion of major stops down Market Street after Church and the scale of the map means that the lines overshoot Balboa Park station by a long distance. Lyle’s attempted to mitigate this by including destination notices – “To West Portal”, “To Balboa Park” – but they’re not much help to those unfamiliar with Muni. Similarly, the “To Fisherman’s Wharf” label isn’t really really required on a map of this scale: just loop the line around a bit and add a terminus station marker for it.
Muni’s “T” line down to Sunnydale Avenue reveals the biggest problem with this map (and to a lesser extent, the other two as well) – the relative location of stations. Lyle’s dropped the “T” straight down, and as a result, Sunnydale is nowhere near the Bayshore Caltrain station (they’re about half-a-mile apart in real life, and the previous Muni stop at Arleta is directly adjacent to the Caltrain station!). Yes, this is a diagram, not a map, but care still needs to be taken to retain some semblance of spatial awareness. This is even more obvious over on the east side of the bay, where the Fremont BART and Amtrak/ACE stations are shown a huge distance apart, when they’re actually just two miles apart and on a direct east-west line from each other. The two Hayward stations are even closer – less than a mile! – but Lyle has placed the Amtrak Hayward station level with the South Hayward BART station instead.
This placement problem is repeated on the San Francisco peninsula map, with the “T” line still out of whack with the Caltrain station at Bayshore: Arleta should be directly adjacent to Bayshore on the left side of the Caltrain tracks, with Sunnydale a little further south. There’s plenty of room to adjust the location of the Bayshore station along the length of the line to make this work without seeming cramped.
There’s also a slight problem with the interesting approach to the Muni Metro Duboce & Church stop, as it makes it look the historical streetcar “F” line also stops there. The Muni lines at Balboa Park are still a little unclear: we can work out that the “M” travels past San Francisco State, but which branch do the “J” and “K” take to get back to the city? Minor error – Lyle corrected his spelling of “Embarcadero” on the actual map, but left it as “Embarkadero” in the legend.
The Santa Clara map probably works the best because of the simplicity of the light rail system: it’s still easy to work out where each light rail route goes, even with the one common colour. However, don’t VTA’s light rail route numbers start with “9”, not “5″? I probably would have dropped both the Amtrak and ACE route lines to the south side of the Caltrain line through Santa Clara, rather than hacing one on either side. This would have put the label for College Park closer to its station dot, and prevented the awkward crossover of the ACE and Caltrain lines just before San Jose Diridon.
This map will certainly become more interesting once BART finally makes it down to San Jose, that’s for sure.
Our rating: I really like the visual style that this series of maps has, it just needs some tightening up – especially when it comes to the location of stations – to make it really sing. Two-and-a-half stars in its cirrent form, but I see lots of potential here. Keep working on this, Lyle!
Gert Holstege ha studiato mediante tomografia ad emissione di positroni (PET) 11 uomini sottoposti a stimolazione del pene, da parte delle loro partners, fino all’eiaculazione. Durante la fase di fuoriuscita dello sperma, l’area tegmentale ventrale (VTA) andava incontro ad un’attivazione così intensa e massiccia da non avere uguali
La VTA, come è noto, è la principale stazione del sistema neuronico che media il piacere. Le sue intense attivazioni osservate da Holstege durante l'orgasmo maschile, sono accostabili a quelle che si hanno per effetto di dosi cospicue di eroina
E questa è la prova provata dei benefici di un pompino ben fatto