Hi, beautiful, thank you for being here today. We're gonna watch some videos together because that is what we love doing the most.  So let's do it. Today I'm gonna be doing X-Mondo colors in garnets. I'm gonna be dyeing my natural hair because I watched his video of him trying to get dark brown hair. Yeah! All right, so I mean, I think the title says it all, but we're watching people color their natural hair without bleaching it at all, a color from the rainbow. Okay, so we got some purple here, and not just purple, it's garnet. Garnet is one of my newest colors. Garnet is this super deep, pigmented, rich purple color. And of course we named it after the gemstone garnet. This is our garnet gemstone, and this is the color. It is magical, and it's going to look so freaking good on this buzz cut. There's not a lot of things I love more than a colorful buzz cut. It looks sick every time. If I didn't have to test products on my hair constantly, I would have shaved my head already, but I must test products, and I must have a head of hair to do that. And we come out more and more than as we go because they just have the most payoff. They're so much fun to create because you guys always love the darker, deeper, purples, reds, pinks, blues. Everything that's really deep toned tends to look incredible on everybody, plus you can use it on darker hair. So we're about to see what happens when she uses garnet on her non-bleached hair. We'll see what happens. So first what I'm doing is Saran wrapping my hand because I didn't have gloves, and I did not know this was a heck, okay? Listen, that definitely will work if you have very short hair. Guys, if you buy my color, the only thing you need is gloves. That's it, okay? I made sure you didn't have to need a bowl or a brush, and you didn't need to be a professional hairdresser to use this stuff. It's very, very easy to use, very simple. Right out of the jar, pick, you'll see it in a sec. I don't want to explain it, but you just need gloves, okay? Because this will stain your hands, and it won't be fun and it won't look good, and you will have it on your hands for a while, and we don't want that, and it's just not a good look. Now I am dyeing my hair. As you see, I'm trying out the different lighting settings, but it's kind of hard to see no matter what I did for the lighting settings because my hair is so dark.  It looks a little purple, but this is the thing with the very dark colors. It's kind of mysterious. It's like, ooh, what's gonna happen? What's gonna be the vibe? Because they're so, so dark. It almost looks like black, but when you rinse it off, the magic happens, okay? So this is good. This is a good sign that it's very dark. It'll be okay. And that is me just rubbing it in, getting it all up in there. I tried to speed through some of this footage because I ended up having to bleach my hair. So I'm just showing you how I did it. I massaged it in my head, and it kind of turned out like this chestnut red, brownie color. Okay. This is turning out different than I expected. I expected it to really work on her dark hair. However, maybe I was a little bit too optimistic. Listen, we do not directly create these colors to be used on natural dark hair. However, a lot of them do work, but this is the reality of it. Her hair was clearly very healthy and very low on the porosity scale. So my permanent colors are probably not gonna stick to it. If your hair is a little more on the damaged side or the dry side, and it's a little bit less dark than this, you're gonna get more color payoff. So it all depends on the person and the hair you're starting with, but this is realistic results, and it looks great. And people always ask me what's gonna happen if they use X-Moto color on darker hair. This is a realistic result. I do really like this color. You see how it kind of tinted her hair? It did not lift her hair color because it is not permanent color and it does not lift, but it did change the overall tone of your hair. Also, one other thing to consider is if your hair is on the healthier side, it will tend to wash out a little bit quicker than if your hair is more porous. So keep that in mind. The more you wash it, the more it will fade. But that is what we like about sign of permanent color is that it's easy to switch out when you wanna change things up. And if you're like me, I wanna change things up all the time. So I love a sign of permanent color. So I don't have to commit to anything and I can do really cool stuff with my hair. Well, I used to. I'm in my kind of natural phase right now, but... I thought it was pretty cute, but I kind of wanted a more vibrant look to it, but maybe I didn't apply enough of it. So I guess we're gonna see her also bleach her hair and then put on the color too. So this is cool. We're gonna see even bigger transformation. You guys get to kind of compare how it looks on darker hair versus bleached hair. So next I'm going in with the Salon Care in the developer 20 and the quick blue powder bleach. Wrap up my hand again.  That means you're gonna get a lot of heat from the scalp. You're not gonna need a 30 volume or a 40 volume to get a really light result. 20 volume is perfect for this case because she has barely any hair on her head. You can apply this within like 20 seconds. Okay, maybe not 20 seconds, like five minutes and get it all on there quickly and everything will process at the same amount of time. And you don't have to worry about certain things over-processing or under-processing. So this is a great choice. I love it. We're doing a great job today. And here I go with the bleach. I did not have any brushes, so I smooshed it in my hair, but I figure since my hair is so short that I can just use my hand and it'd be fine. That is totally fine. I approve you using your hands for bleaching that very short hair. The only thing I would recommend is using a fine-tuned comb on hair this short. It's kind of hard to get on every little strand when the hair is this short. So using a fine-tuned comb going through and then reapplying over that combed hair is always the best idea to ensure extremely perfect coverage. We are going in there with precision work. We are putting this lighter on every single hair strand and I love to see it. We're putting our little Saran wrap glove to work and it is effective and I love it. I'm getting excited because this is gonna be even brighter than what she has now, obviously. Pre-lightening your hair before using Garnet is gonna give you the ultimate best results and we're about to see the vibes. And whenever it gets to this length of me growing out a buzz cut, I feel like it just gets so boring and I need to add some color to it. This is probably the eighth time I've shaved my head. Yeah, so I'm wrapping it with Saran wrap, hopefully trying to insulate the heat. It's a great idea that she put a bag or Saran wrap over her head when this was processing because it's gonna create a hotter environment, a more steamy, humid environment that is great for lightener and a great for getting brighter results and faster results. And then it's at this yellowy color, so I'm like, that's gonna be fine because it's a red, so. Okay, so her hair definitely turned out a little bit yellow. I would have liked it to be a little bit more pure, blonde, blonde, white, not white, but less yellow. She said it's a more red color. It definitely has red tones in it, but Garnet is just a deep purple. It's super deep, very extravagant, royal purple. I don't know how else to explain that. So if you want the most pure, clear results and just as it's depicted on the website with swatches, you're gonna wanna lighten your hair to a really blonde color, but this is still gonna look beautiful. Also, her hair looks to be wet, which I would not apply this color to wet hair. If you want more longevity out of the color and you want a more vibrant color, apply it dry. And there goes the satisfying color. Oh yeah, right up in there. Oh, I'm so excited. This looks amazing already. It's like this dark red. It's so rich and it actually did smell amazing and there were little sparkles in it. Yeah, you know I put sparkles in it.  You want a fun experience when you're coloring your hair, right? You want it to smell good. You wanna feel good. You want your hair to be better quality, post-coloring. You want some bomb booster in there. A little ethically sourced sparkle in there. And I did it for you. I put the sparkle in there. I know you people who watch my videos would follow me by my color. I know you're just like me. You know, anything that sparkles makes me happy in life.  I was shopping the other day and I was producing the aisles and every time I saw something sparkly, I was like, fuck, I want that on my body. But the items that were sparkly in that store were like $7,000. I was not about to spend $7,000 on a sparkly top. Okay, but I will find something else with sparkles and I will wear it. Who else likes sparkles? Comment down below. So it was pretty amazing getting it all in there and you can really just apply it like a conditioner. Just get it all up in there. Okay, she's right. It is a little bit red. I honestly guys, sometimes I forget exactly what tone these colors are until I see it again. I work on so much stuff all year round that like my brain is in 2026 right now. Okay, 2026 products. It's like a purple slash red color. There we go. All right, but it's gonna be even more red on her because she has yellow in her hair still. So the yellow with the purple it's just gonna be a little more red tone. And as you can see from the back I didn't really bleach it that even. Obviously you can see my neck here is a different color but the color ended up being pretty dark on my head. So you couldn't tell that much that I missed any spots. And I wanted to do this color because it is coming into the fall time and I wanted something to more to stand out with.  I love that idea. It is spring right now. Currently I'm filming this video and I am just seeing all the leaves and the flowers start to blossom around me and I am inspired to do something to my hair. She's making me want a buzz cut, a colorful buzz cut so badly but the colors outside right now are so ready. I need to create a line of colors that are just directly related to spring and like the flowers I see. Be kind of fun. And this is the finished product. I was really happy with how it turned out and I feel like it makes my face glow more. So yeah, 10 out of 10 recommend. Ah! Oh my God, I love you. You look incredible. That looks so awesome on your hair. Honestly, like the bleach version and the non-bleach version look pretty similar. I think you could have even got away with just not doing the bleach. It looks beautiful either way. Super vibrant. I wish we had a little full 360 of that. I wanted to see more of it.  This is why I love color.  I hope it inspires more confidence in people and that's always the eagle. Hey, I'm actually gonna be using Brad Mondeau's super purple hair dye. It definitely lives up to its name, that's for sure. So starting off, she has insanely gorgeous hair. It is so thick. Oh my gosh, I think it's her natural color but maybe it was like a little bit bleached out by the sun. This is a great scenario because obviously when your hair is a little bit lightened by the sun, it's probably more dry and more porous plus you have those lighter pieces to really pick up on that color. So she's still gonna get a lot of color payoff without having to lighten the hair even more than what it is right now. I can't wait to see this. So in case you guys don't know the history of my hair so I've, because obviously you can tell like this is a little bit more red in this lighting than up here. Like two and a half years ago, I did high lift color and then dyed it teal. About a year and a half ago, I dyed it blonde and then like nine months ago, I dyed it red and then it faded super fast because I used X-Mondeau hair color and didn't realize it was steady permanent and I was looking for something that lasted longer. I went and actually got some box dye. It was pleasantly surprised by how well that turned out. I'll put a picture right there. And then I let that fade and I went back to like blonde because that's what will underneath all my hair color. And then I dyed it pink but like barely showed up. Okay. There's a lot more going on here than I thought there was gonna be. So her hair is sort of natural. I mean, it's been many months since she's colored it. So like the top half has her natural color and the bottom half has a bit of pre-lightened color going on from nine months ago covered in box dye. So this color has got a lot of work to do, okay? We got this, bro. She is using super purple. So it is one of our darkest colors and that is great.  So I watched two brand Mondeau videos. So here's one and then here's another. And I also have a whole list of notes that I took. Yes. You win today. You took notes, you watched videos. I hope the notes were correct. I didn't look that closely at them. And you know what? I don't wanna look that closely at them because I'd rather be pleasantly surprised when you do everything right, right? I'm shocked when it's wrong. I don't know. I don't use this section of my hair when I'm doing hair color simply because I don't really see the point in it because then I know if brand Mondeau sees this it's gonna be like so disappointed in me. It's just like, it's hair color. It's not bleach. Bleach is much more specific and that can ruin your hair super fast. Listen, I hear you and I understand why you're saying you don't section it. However, yeah, bleach is definitely more serious but, but, but, but, but, even when we're using side permanent color we wanna section just so that we know we got it on every single hair strand. It is so easy to miss hair when you take a big clump of your hair and just put color on it. I swear, it's so hard to get every single hair strand that way. But if you don't really care about it being even then just apply it however you want to. I'm just telling you how to do things to get the best results. But again, it's up to you. It's up to you, the creator. You hold the results in your hands. With hair color, I'm just like, yeah, you split it in half. You're like, good to go. But I was watching his videos and he said you want to try and split it in half and then, let me see if that one's up in the middle part. You wanna try to split it in half and then in half again. Hell yeah, that's what I said. Quadrants, baby, four of them. I don't think a quadrant can mean less than four, can it? Quadrants is four. So I went ahead and split it in half and that's what it looks like from the back. It's not the best section I've ever done. Okay, that's a lot more purple than I thought it was gonna be. Oh man, okay.  It's called super purple.  No, I would never.  I guarantee it. It's so pretty. It's got glitter in it. And I'm just gonna put it on.  That's like a lot more vibrant than I was expecting it to be. What do you mean it was a lot more vibrant? Did you see our pictures on the website?  We are definitely getting it on the top of the head, right? Definitely, for sure. And where that part is. That is definitely the most important part. You know, I agree with you. However, I'm a little worried about all that hair in between here. It's like we're applying to the surface, but not inwards.  So we made it thicker to be more user-friendly. We really think about everything and I listen to you guys. But because it's thicker, you gotta work section by section. And you know, it's not gonna seep through all the different layers by itself.  I wish I could help you with that. I wish I could find a way to make you guys stop coloring your faces, but it just doesn't seem to be happening like that. Okay, so I'm gonna go rinse my hair out. I just laid with my doggy for like 45 minutes, 15 minutes. I'd rather leave it in longer than not. And I know that some of you guys might be like, it's gonna dry your hair out or mess it up for leaving in too long. But at the same time, Brad Mondo's hair products have a whole bunch of proteins in it. So I'm not entirely concerned leaving it on for almost an hour. Don't be concerned. You can leave it on as long as you want, really. 20 minutes is what we recommend. But you're not going to damage your hair by leaving it on longer. You just might get more pigmentation from the color. It is filled with proteins and bond boosters, shine ingredients and hydration ingredients. So your hair is gonna be better post-coloring. Hey guys, so this is the final result of my hair. It is so vibrant. It's absolutely insane. Ah, the matching nails and the makeup and the hair. Oh, and my hair looks and feels amazing. As I mentioned in the beginning of the video, it was so dead because of the bleach. And then you look at it now. It looks so healthy. It looks so shiny. Like this is probably the best I've seen my hair since it was my natural like virgin hair. It doesn't even look like the same hair texture. What?  Oh, it's so pretty.  I definitely recommend X-Mondu color to anyone who's looking to dye their hair in a normal color. I'm shocked. I'm shook. I love you. Your hair looks incredible. You look amazing with purple hair. I love this color on you. You're right. Your hair does look so much better quality wise. And I am so happy. You loved it as much as I love it. This is your color, girl. Especially with that makeup, absolutely killing it. I feel like, I mean this in the nicest way possible is now even better color. But the color before was kind of washing you out a little bit and kind of was blending with your skin. And now this is really bringing out the vibrancy and the pinker tones in your skin.  Like so cool. If you love me and you love X-Mondu color and you love X-Mondu hair, you know, give me a like or a comment or both or a subscribe. I don't ask a lot for them. If you like hair just reacts, give this video a like. Thank you. I appreciate it very much.  And I love you so very much. Broke freeze. This looks like a bed pan. It is. How long am I gonna be here? Wow. Would you look at that? It's this purple. It's your favorite. Okay. A lot has just happened in the past 30 seconds. So she's dyeing her boyfriend's hair. Her boyfriend has natural sort of like gingery brownish hair. I think it's hard to see in here guys. I complain every week now. This surface has made things a little bit brighter and I can't see anything. But it looks good on camera for you. This is gonna be interesting. She's doing kind of like, I think she's doing purple on his like more orangy toned hair. So the purple will be a little bit warmer obviously.  Some people can be so rude. I think she thought we were just going through stuff. Like this is how we spice up our love life? Yeah. There it is again. Right in the eye. No way. Super blue. Why? I'm thinking of doing like a mixture. Purpley blue? Yeah, but not like that. Like stripes. Like a zebra. But like an EDM one. I gotta tell you guys, I wasn't listening to much they just said because I was just thinking how cool it is that I get to make things.  And it's just the coolest thing ever. And I'm so grateful. So thank you for allowing me to do that and living my ultimate dream. I'm the luckiest person ever. Sorry, they're doing like stripes. Is that what they just said? Okay. This is gonna be very different. But this part of your hair is gonna be completely blue. Either that or pink. I didn't wanna make you look like a gender reveal though. Oh, that smells so good. Hold your tub. Not edible, right? Not edible. Who wants an X-Mondo fragrance? If anybody owns X-Mondo, watching this video currently, comment below and let me know if you want a fragrance version because I'm down.  It smells so good. And I tend to wear my oils on my wrists because I love this scent so much. And we worked very hard perfecting that scent. And it is literally done at the same place that your favorite perfumes are made. So I'm very passionate about fragrance. It's cool. It's so cool to start the shower. It's super blue. We might need some rain wrap. Does it say aggressively rub into? It's implied. She's doing it like a hairdresser would, you know?  Okay, we gotta get it really deep in there. The thing is, when you're dying short hair like this, or so I've heard because my aunt is a hairdresser, you know her. Because your hair's so short, you kinda have to dig into it like that to really surround and like coat the follicle. Ah, yeah. That is exactly what you do. Great job. Such good advice. What's that one thing Bob Ross does? Speak the down line. I'm doing good. Oh, right into the beard. Thank you. We should do your beard. You should have. I was just saying the same thing. You should color the beard. Please tell me they colored the beard. Oh, babe. I'm sorry, they were stuck. You're the worst. So I've never done this before. I'm gonna do this side blue because if it touches the side hair, then it's okay. Oh, on the way to the roots. You don't want your roots showing. You don't want to be that girl. Okay, so another thing with my color is that you can put colors right next to each other, lay them on top of each other and they will not bleed into each other. Sometimes with like a yellow or an orange, it's a little bit risky, but with darker colors like this, I can pretty much guarantee that they will not run into each other. And I've even done it with yellow and they don't run into it. Because they have that thicker consistency, it tends to really grab on the hair and not slide anywhere. So the colors do not mix. But also if you want them to mix, they're really easy to mix and blend with your fingers. You just want it.  She's doing super blue, super purple, super blue, super purple. That is gonna look so cool. I think over his more gingery brown hair, it might not be a super drastic difference between the two colors, but it's still gonna look very, very interesting. I don't know, I'm excited to see the results because I really don't know what's gonna happen here. This is from Brad Mondo. It sure is. We like Brad Mondo. We love Brad Mondo. He never replies to any of my videos, even though I've done extensive great videos about hair dyeing. You've only done one. But it was good enough to get his attention. Clearly, it wasn't though. I feel like I've seen you guys before. Have I not? I'm so sorry if I haven't. And hi, I love you guys too. And thank you so much for making any kind of content of my color. I appreciate it a lot. And I love watching it. And I feel, I don't know, I've seen, I've definitely seen your videos. So this one is gonna be blue. It's dinner ready. Does it feel right? No. Okay, so we're done. Completely? No. There's some on your beard. I feel like I could do the rest of my fingers. Get into it. Okay, this one will be purple and this one will be blue. It's making me tired. So I'm relaxing you. Uh-huh. Ooh, it's coming along. We are making progress. And we got those stripes of the purple like she imagined. And the vision is coming to life. Reveal your hair. Okay. Babe, it's time to give her purple. What a pet look. What does that look like to you? Uh-oh, take your wavy. So it definitely turned out pretty purple all around. Like I was worried about. I think that doing the two colors next to each other on hair that is not pre-lightened was just risky. So it ended up being all purple. And it is so vibrant. I don't understand how it came out this vibrant. Honestly, I was not expecting this kind of vibrancy with just my color over non-pre-lightened hair. It just goes like Stonehenge. Babe, you look like one of those guys that's like on the posters of barber shops, the hot ones. I like it. Thanks, babe. I like it a lot. I think it's the only one. This looks awesome. I love this purple tone. I actually love it with the orange beard because I don't know, it's like cool and warm. And it's just like so contrasty. And you pretty much never see people do that. It is a very bold, very daring look and only somebody like this man could pull it off. Like the confidence is just next level. Hello, welcome to Hot Topic. What can I help you with?  Cause I have to go to work. My favorite bands are A Day to Remember. I know we're just having a normal conversation, but I still need to do this every fraction of a second. I'm obsessed with this emo hair. You can also really see the vibrancy of the color when he does little things. Like I think it looks incredible. It's definitely super purple and it looks sick. Congrats. Like look at this before and after. That is nuts. Oh my God. Wow, beautiful. So I hope you learned a thing or two from today's video. If you want the best, best, best results when using X-Men of color, you're gonna wanna preline your hair. However, if you're okay with the color not being as vibrant, but you want kind of a fun little change that is very temporary, definitely you can go in on your darker hair. Just know that there's a risk that you won't get as vibrant results as you would if you were to lighten your hair is a little bit more. So my permanent color does not lighten, but you are gonna still get pretty cool results without pre-lightening. Oh, also go with darker colors, especially our new colors. Work our darker new colors. Whoa, I got our blue and purple limited edition shift and our purple and pink limited edition shift. Oh, also we have our red and pink limited edition shift colors. So these are kind of two colors and one that shift with the light. Depending on what kind of lighting you're in, you're gonna see a different tone. So these are great. Definitely go with the blue and purple if your hair is really dark or try our gem line of colors or our super colors. We have so many colors to offer you. It's so pretty. So try them out and please record a video. I would love to watch and maybe react to your video. Do you wanna be in a hairdresser's reacts? Just make a video guys. You can shop X-Men of color in the next one to a hair with the links are down below. That's all. Thank you for watching and I'll see you next time. Bye.


I think he's originally Russian. I don't know if he's on Azerbaijan's team or where. A lot of those Russians, they can't make the national team so they transferred to a different country. It's kind of a Kazimov. He's probably one of the best guys I've ever seen in this position. I think it's Israel Kazimov. If you, in freestyle, this quad pod position is not a take down. I got to get an elbow, a knee, or my head down. This guy is a master there. There's guys that'll single leg you. He'll go down to his quad pod and he'll almost want to let go of his leg. He's that dangerous. He'll cartwheel over the top, catch guys on his back. But what he's good at, right, what he's good at, turn, turn, turn, is when this single leg is up, he's real good at using his foot to move this guy around and his shin to move this guy around. He'll push in with his shin and then pull with his foot. Does everybody see how I'm moving this guy around in this position? Now, it looks like I'm in bad shape. But again, this is a skill set and a position we don't spend a lot of time in. Mark Hall is real good here, too, for somebody that you guys can resonate with a little bit. Penn State wrestler, he's really good here. But what we're going to do is we're going to move in a circle out in front of this guy. Okay? Mommy. What's up? What's up, mommy? You don't look real happy. Just wrestling shoes don't fit her. Oh, man. I thought we were going to scrap the day a little bit. All right. Anyways, so I'm using this foot to pull and push. Again, we're not going to master this thing in a weekend. We're not going to master it in a year. But I'm going to pull and push with my foot. What I want to do is get this guy cleaning forward, falling forward, and then I'm going to snap my foot out, turning face. That's what I want. So this is what we're going to do. My foot is going to be on the inside. I'm not going to have a closed wizard.  I'm going to be in my quad pod here, minus one foot. What I'm going to do is I'm going to hop in a circle, but I'm circling in front. Okay? See, I'm pulling them with my foot as I'm hopping in front. I'm going to hop a little bit, circle in front, and then I'm going to focus on pulling them as hard as I can with my foot, snapping my foot out and turning and trying to face this guy right here. Getting my feet back in the mat and wrestling. It's not something we're going to do slow. We're going to hop, hop, hop, snap, and turn. All right? So this foot's up. Maybe I'm battling here. I'm trying to get my foot to the mat. I mean, ultimately, if I can get here on a high single, that's ideal. Okay? Good single leg guys aren't going to let me be there. So I turn down. I'm hopping, hopping, then I hop, turn, face right here. If he doesn't fall and heads in the way and he's still up on his feet a little bit, right here, boom, I can get back to my attacks. And a lot of times, as I guys fall and forward, we can turn right into a leg attack position. Okay? But again, this is a skill that a lot of times, we just kind of turn down and give up a take down. Instead of knowing what I can do to defend against this guy and even turn it into my own offense. That's kind of what this whole camp is about. Taking my defense and making it offensive. All right? One more time. All right? And again, this guy can give me some feedback and talk about the position, but as I'm circling, I'm pulling with this foot. Plus, he's latched onto my leg. So as I pull it to me, okay, and I turn, all right, he's going to be falling forward. So I'm hopping, pulling, hopping, pulling, then I hop, turn right here. Okay? Whether I wrestle, drag, short offense, hustle to a corner, or end up back 50-50, I'm still in a pretty good spot. I'm getting back to an athletic position. Some guys are going to fall, reach, wrestle different than others. We just get our head in the way of someone. I was just talking to these guys about, talking to Anthony about, I just think about getting my head in between my body and theirs. That's it. The rest can play itself out. So whether I'm hip-heisting and turning or kicking out and turning, if my head's in between my body and his, I'm in pretty good shape. Good? Play around in there. It's going to feel real weird, but I really want you to focus on pulling with your foot. Pulling into you, turning in face. And go. Play there. Circle in front. Pull into you.


St. Lucia's Forensic Science Laboratory officially attained accreditation from the American Association for Laboratory Accreditation or A2LA in 2022. In 2023, United States Vice President Kamala Harris announced the Department of State will provide technical support and funding to designate St. Lucia's Forensic Science Laboratory, the Center of Excellence for Regional Forensics. Our summit and Center of Excellence launch comes from the vision that the staff at the Forensic Laboratory developed in 2019 and that vision states that we strive to be a recognized Center of Excellence for Forensic Science in the Caribbean region. We have received the support of the U.S. State Department through its Bureau of International Narcotics and Law Enforcement Agency, INL, and they have supported our initiative or our drive to be a Center of Excellence. This event, the summit on the 10th of October, is our first event towards being a Center of Excellence and making a contribution regionally in Forensic Science, but more importantly, establishing ourselves as a Center of Excellence to provide forensic services, accredited forensic services to other countries in the region. The journey to A2LA accreditation status began in 2019 to meet the high threshold for accreditation. The professionals and administrators at the Forensic Science Lab had to ensure the various testing processes and operations conform with the rigorous requirements of the International Organization for Standardization. The benefits of the Forensic Science Lab's accreditation extend to the Eastern Caribbean Supreme Court jurisdiction and other judicial bodies in the Karakom region. Litigants in civil and criminal court proceedings can be further assured of the reliability of the samples processed and analyzed by the Forensic Science Lab. It gives us an assurance that what we do, the results that we give out, are results that can be trusted. The courts need that trust within the evidence that we or the results that we give and so that gives the courts, the police, the public assurance that what they are getting is results that matter. The Forensic Science Laboratory's distinguished accreditation status commands international recognition, designated as the Center of Excellence for Regional Forensics, coupled with A2LA accreditation. Services provided by the Forensic Science Lab affords the government of St. Lucia international leverage and a unique opportunity to generate additional revenue for the country. Office of the Prime Minister


As they said, I am from the Allen Institute in Seattle. We, what we do essentially is create gene atlases of brains. So we have atlases for mice and for macaque and for human. And so today I'm going to talk to you a little bit about that. But because it's atlases of the brain, I was asked to start off with some basic neuroanatomy. The understanding that a lot of people here come more from a math background or an informatics background as opposed to a neuroscience background. So we'll start off, I'll give you an introduction to the Allen Institute and sort of how we work and what our goals are. And then a basic neuroanatomy tutorial, essentially. And I apologize to those of you who do have degrees in biology. It's probably basic enough that there won't be any new information for you. And then the second session we'll move into actually discussing the different atlases and the types of data that we have available for use. All of our atlases are freely accessible. All of the data is freely accessible to the public. And then we'll circle back around and just a couple of quick slides on some specific anatomy that would be helpful for using those atlases. And then in the afternoon, we'll do some walkthroughs to look at some of the main data modalities, how to grab that data out of the web, and look at some visualization tools, and talk very briefly about the API. All right, so the Allen Institute for Brain Science is an institute with a goal of understanding how the human brain works in health and disease. So we use a team science approach. It's not quite like academia. We don't have a PI that defines what the project is. The projects are defined as an institute. And the entire institute's goal is seeing those projects come to fruition. We generate useful public resources, hopefully useful. We drive technological and analytical advances in the way that we display the data and use the data. And our hope is that we can discover some fundamental brain properties by integrating experiments, modeling, and theory. We're independent, nonprofit, medical research organizations, so we don't fund additional research. We do the research, and we make it available for everybody else with the hopes that we can cut back on some of the experiments that you need to do as pilot research for your projects. We're project-focused and milestone-driven. That means that for each of the projects that we have, we have definitive milestones and times for data release that we must meet. And again, an overriding goal of understanding the brain and health and disease. So why does this matter? These are stats from America. I'm going to assume that the numbers aren't going to change too awfully much throughout the world. But over 1 out of 4% of American adults have suffered from some sort of mental disorder, be it depression, bipolar, schizophrenia, autism, Alzheimer's disease. And the numbers are really astounding. So there are more than 1,000 disorders of the brain in the nervous system. And they result in more hospitalizations than any other disease category. And yet we know the least about the brain. So our goal is helping to understand how the brain functions so that disease models can flourish. All right. So oh, goodness, should have checked the contrast. We'll see how some of these pictures go. So our resources are used for advancing disease research in autism, Alzheimer's disease, epilepsy, obesity, multiple sclerosis. As I said, we accelerate the development of promising new research tools. We do things in a high throughput way. So the work that you do at the bench, we do on a very large scale. I want to say we are capable of processing ISH slides on an average. If we were to look at our daily capacity, could be around 600 slides a day. So if we were running at full capacity. And our resources also support classroom teaching. And as I said, our goal is to help you guys save time and resources by providing you data upfront. Our overreaching goal is in understanding these things down at the right consciousness, memory, behavior, thought, and how the brain works. And much like Jim said, starting with things like gene expression, electrophysiology, understanding the different cell types, the connections that they make, who talks to who in the brain that elicits consciousness, memory, and everything that makes us who we are. Yeah, we're really going to have to fix that. Yeah, I don't think that it's going to be a light thing so much as it is. Is it bright things? Oh, god, so cool. Yeah, well, they were working on that to get the pictures to work. So we like to say we use big science to tackle the big questions. We look at development to find out how things come to be. We look at the parts, the genes, the proteins, the synapses of different functional areas to see what's going on. We want to know how things are connected so we look at synapses or direct connections between cells. And we want to know how the parts receive, store, and act on information. And we also want to know what goes wrong in disease. So our tools are designed to answer these questions either in part and specifically at one of these levels or at multiple levels for a given project. What you can't see here is a brain. And these are data points showing gene expression in the human brain. So hopefully we'll get that fixed or else the pictures for the rest of this talk are going to be a little not understandable. And so before I go any farther, our team is currently up to about 225 people that work at the Institute. This is a picture from last year. There was probably about 150 people at this time last year. So we're in a huge expansion mode as we introduce some new projects. Yeah, let's see. OK. Oh, yes, that's much better. Yeah, look, it's a brain. We'll stick with this one. This is the one you're recording the slides, but. OK, but OK. You can probably. You can probably. Try to drill the camera so you can learn a bit more about the human brain. So that's your introduction to the Allen Institute and what we do. And we're going to, as I said, hit the atlases at the second session. But to understand brain atlases, you need to understand a little bit about the brain. So we're going to take a basic neuroanatomy walkthrough. Now, I'll admit two things. I'm an anatomist, not a bioinformatic person. And two, my focus is on the human brain. So although we do mouse brain stuff, a lot of this talk is going to be geared towards the human brain as well as the second one, looking at more of the human experiments. Mostly because that's what I work with on a daily basis. So I understand those tools a lot better. But some people like to think we're just big mice. I'm not sure if I quite fall for that. But it's going to be relatively ubiquitous across. So the basic makeup of the brain involves a cerebrum, this large part here.  And then the third component that you can think of is the hindbrain that consists primarily of midbrain pons and brainstem or medulla. If you were to cut this, you would see that what we have is essentially a cortex or this ribbon of cells that surrounds the brain.  And separating these are white matter tracts running to and from all the different structures. So the mouse brain has about 75 million neurons, about 4 million of which are in the cortex, cerebral cortex, and 100 billion synapses. The human brain is at a completely different scale. And you're looking at about 85 to 100 billion neurons with around 100 trillion synapses to account for. So human brain, incredibly complex. And of course, we all want to understand how it works, right? In the mammal, organization is relatively conserved, at least as far as the sensory motor cortices go. So what you find is that the olfactory cortex is in the front. Motor cortex tends to be towards the front, followed by a somatosensory cortex, touch, pain, perception, behind it. Auditory cortex is off to the side, and in the very back is the visual cortex. There's topographical organization to these cortices. So what you have here is the homunculus for the mouse. We have the sensory motor, or the sensory strip on this side, motor strip on this side. And as you come around the edge, what you see is that we have different areas devoted to different parts of the body. And for the human, we've got a large amount of our sensory cortex devoted to the face region and to the hand. And our motor strip, you have a similar mirrored homunculus with a lot of space devoted to the face, especially the mouth because we have to talk, as well as the hands, because we have a lot of fine motor skills with our hands. How this homunculus is set up is in parallel with those processes that we use a lot. So if you look at the mouse, a ghost bat, and a short-tailed possum, all of which have brains of roughly the same size. The mouse that gets most of its information through its whiskers and other touch sensors has an enlarged somatosensory cortex as compared to the visual and auditory cortex, whereas the ghost bat that uses echolocation has a much larger area devoted to the auditory cortex. And the short-tailed possum, which apparently has a really good vision, or so I'm told, has much larger area devoted to the visual cortex. So our brains are designed to handle what it is that we do. Or, contrary to that, we do really well what our brain is specialized for. There we go. For the human brain, there are essentially six lobes. We have a dividing central sulcus here.  This contains that motor strip that we talked about. Behind it is the parietal lobe. Down at the bottom is the temporal lobe. And at the very back is the occipital lobe. These lobes fold over. And if you were to pry them apart, what you would see inside is called the insula. So there's a whole layer of cortex. And when you cut chronally, you can see the insula. And on the medial surface, there's this limbic lobe that's comprised of the cingulate gyrus and the perihippocampal gyrus become very important in disease scenarios. Now the bumps on the brain are called gyri. Cingular is gyrus. The divots in between those are the sulci or a sulcus. And each one, if you want to get down to the nitty gritty of gross anatomy, all have a specific name. And you'll see that in the atlases of the macaque and the human where everything is defined by their location. So in the frontal lobe, you'll have a superior frontal gyrus, a middle frontal gyrus, and an inferior frontal gyrus, a superior temporal and middle temporal and an inferior temporal gyrus. So the name gives you some indication of where you're at. Now the cortex is made up of layers. So for those of you who focus on more electrophysiology, you're well aware of this. In general cortex, there are six layers. And what you see here is Maureen Boyle has overlaid in pseudo-colored gene expression for genes that primarily exist in a given layer. And so what you can see very exquisitely is how well layered the mouse cortex is. The human cortex does the same thing. I don't have any pretty pseudo-colored images of the human cortex, at least not healthy human cortex. But what you have here is our sulcus. And we have a relatively cell sparse layer 1, a layer 2 that if you're used to looking at cortex, you might be able to make out. Layer 3, that's comprised primarily of pyramidal cells. Layer 4, which is small and granular. And layers 5 and 6, again composed of primarily pyramidal and multipolar cells. And each of these layers does relatively specific things. So layers 3 and 5 with the pyramidal cells are output layers. Layer 3, you can think of as primarily sending output to other cortical areas, either ipsilateral or adjacent cortices or cortex that it's going to talk to. Layers 2 and 4 are essentially input layers. Layer 4 gets input from the thalamus for the most part. Layers 5 and 6 output back to the sub-cortex, either to the thalamus or down into the brainstem. And these cells all talk to each other in essentially a columnar fashion. So the cells here are going to mainly interact, or I won't say mainly, but have a lot of interactions with cells in the same column as compared to cells outside of the column. So there's a vast network in the cortex where it's just exquisitely organized. And I think when we talk about the visual cortex, you'll probably be getting into a lot more of that. Not all cortex is the same. Just like all the areas are specialized, cortex is specialized. So here we have, essentially right from this part, a cut. And we have the central sulcus coming right through here. What you can see is that this cortex up here, the primary somatosensory cortex, very different from the motor cortex down below. Sensory cortex is going to have input from the thalamus so it has a well-defined layer four. Whereas the motor cortex is sending information out to the rest of the body. And parts of it are characterized by these incredibly large cells sitting in layer five. Those cells are sending axons all the way down to your tailbone to control leg movement. So that's pretty amazing for a single cell. So those guys are awfully big. And because the cortex looks different, people have spent a lot of time trying to parcelate out the cortex based on the arrangement of these cells. So over here you have the most popular cytoarchitectonic map done by Brodman in 1909. And overlaid on it is a separate way of looking at the cortex, which is by high order function. So, which have in blue are the primary sensory motor cortex. Yellow are unimodal association areas. The red or pink are high order association areas where a lot of thinking and computation goes on. And green is our limbic cortex, paralimbic regions that deal with emotion and memory types of things. Variable and not variable.  The division between those cytoarchitectonic areas can vary quite a bit. So, the most variants that I've seen we actually had a case. One of the most prototypical things is this division at the central sulcus where you have motor cortex on one bank and just as you come underneath the bend of the sulcus changes to primary somatosensory cortex. And we had a case that actually motor cortex came all the way up to the top of the post-central gyrus where it had essentially pushed somatosensory way back. So, there is quite a bit of variance and especially when you get into areas like prefrontal cortex or the higher order association areas, those borders can move around a bit but you're never going to find your areas nine 46 of the prefrontal cortex back in the occipital lobe. So, the general pattern stays the same but there is variation and the same goes for the gyral structure of the human brain. Every brain is the same. Everyone's got a central sulcus unless you're diseased.  And that's going to come into play when we talk about the atlases and the difference between doing a reference atlas for a mouse and how we have to deal with those discrepancies in the human. The Brodman map is not the only cytoarchitectonic map. There have been many cytoarchitectonic maps and part of what makes them different is probably the fact that they all looked at different cases but they also looked at different things and went to different levels. So, up here we have the Brodman map and down here is Vonokonimo which is probably the second most used and a lot of anatomists are pushing to go to the Vonokonimo map. Brodman identified 52 areas. Vonokonimo identified 107 and again, not much difference as far as how organization goes. So, a lot of it is a level of fine detail in what they were looking at. You can also parse out by myeloarchitectonic so you can look at the white matter tracks and how myelinated fibers are. This gives a very different pattern to the brain. You can separate out by functional network so you can organize by visual system and auditory system and high order functioning. You can separate out by neurotransmitter network so all of this comes from a wonderful chapter that Zillis and Ammons wrote in Nature. Ammons and Zillis are working on receptor autoradiography and using the different expression of receptors to further parcelate the brain. So, they'll go into what someone typically thinks of as a single Brodman area and separate this out into many more areas based on how the receptors populate it. So, as we move forward in time we're getting finer and finer and finer details of what's going on in the cortex. Each of those regions has a specific function but what really gives us the high level functions are the ability of the brain to talk to different regions. And so, that's all. This is a diffusion tensor imaging of the human brain. Looks at white matter tracks in the directions that they go. So, you can see this large track coming down here in blue which is the pyramidal track goes from motor cortex down to the spinal cord can make out the corpus callosum, all sorts of different tracks. So, what our behaviors are have to do with our functions and our networks, okay? And there's lots of networks in the brain, some of which people talk about more often than others. Probably the most talked about is language involves auditory cortex so that we can process what we're hearing and a connection to motor cortex so that we can move our mouth and produce speech that is understood by people. And you can damage this area, you can damage this area or you can damage the white matter connections in between and get what's called an aphasia where you either can't understand what's being said, can't produce words that are understandable or a combination of that. Whoops. There's a frontal parietal network that involves the ability for us to direct our attention either internally or externally to the world, right? So, in front of temporal dementias that damage the frontal part of this network people look internally, they don't really much care about the external world and you get some very strange behaviors like we had one woman who wore a cow outfit to work and was not Halloween. She saw nothing wrong with this, right? So, when you damage these networks you start having behavioral issues. The most studied network is probably the visual system and you're gonna hear a lot about that later in the week. Primary visual cortex is mostly on the medial surface of the brain but it does come around to this tail end here and spreads out and propagates across the brain. So, what we have are fibers coming from the eyes, going to the thalamus, the lateral geniculate nucleus actually and then coming back to the middle part of the brain. Primary visual cortex or V1 then sends processes to V2, to V3, to V4, to area MT, to a variety of areas in what are essentially two different paths. The ventral path is the what path and is involved with identification of objects, naming objects, types of things, whereas the dorsal path is the where path. So, again, this attentional portion of that frontopriatal network, now we're getting attentional where things are in space. Gets more complex. This is a diagram from Chun-Jin Wang who is now at the Institute heading up our Connectional Atlas. Here's your primary visual cortex in the mouse and these other areas are all V2. They're all subdivisions of V2 and they talk back and forth to V1. They talk to each other and in fact, this is essentially a network model of what's going on in the visual cortex and it's not even at the finest level of intricacy here. This is considered a relatively moderate level. I've got your visual cortex down here and a variety of cortical regions and you can see that there's a lot of crosstalk in those networks back and forth, not just within the visual system, but up to the frontal cortex of the frontal eye fields to area 46 in the prefrontal gyrus, area 36 in the temporal lobe that's involved in integrating with the limbic system. So, what's going on here in the brain is not a one-stop thing. What goes on here depends on what's going on elsewhere in the brain. There is some lateralization in the human brain, most often talked about with language, so we just showed the language network going from the auditory or vernachies area to the motor frontal brokas area and anatomically, you see this lateralization as well so this area of cortex tends to be larger on the left and sit at a different angle. So, the anatomy, the function, go hand in hand, but language is not just on the left hemisphere, spoken language tends to be on the left hemisphere, on the opposite hemisphere tends to be non-spoken language in a very similar way. So, in the back you have perception of things like facial expressions and emotional content of language and in the front you have the production of these same things. So, you can damage the right side, still be able to talk, but really not be able to know whether or not someone's coming up and telling you something humorous or whether they're serious or be able to interpret stuff like that. And like I said, the behavioral neuroanatomy of these networks follows along with disease. So, in Alzheimer's disease it's the medial temporal regions that control memory functions that are affected primarily and early on in the disease. Aphasia is the language system, you have disruption of that network between the temporal parietal region and that frontal region. Visual spatial disorders affect the regions of visual cortex back in the parietal and inferior lobes. Attentional disorders, ability to direct your attention throughout space as opposed to just one side shows up when you get damaged parietal lobes. And frontal temporal dementias that generally affect the prefrontal regions in the same medial temporal regions of Alzheimer's disease can give you a wide range of behavioral problems from wearing cow suits to doing stuff like hiking up your skirt to fix your hose or something like that out in the middle of public. You just don't really have this perception of the outside world watching you.  It seems to have locked up. All right, so that's the cortex. But as I mentioned, we've got a sub-cortex too. And so I'm gonna talk about the sub-cortex mostly so that as you're going through the atlases and you're seeing these words, if you're not familiar with neuroanatomy, you're not completely lost. Sub-cortex sits, as I said, deep inside the cerebrum for the cerebral sub-cortex. And you can see it progress through. And these are cells that are grouped in the clusters called nuclei. And the nuclei themselves cluster to form larger structures. So you have the thalamus made up of multiple nuclei that do specific things, hypothalamus, basal ganglia. And each of these nuclei are involved with different networks in the brain as well. So we'll start off with the claustrum, mostly because I would be remiss in skipping the claustrum or putting it anywhere else. Christoph Kott, who is our new chief science officer, has done a lot of work with Francis Crick in the realm of consciousness and understanding consciousness. And he works a lot with the claustrum. The claustrum is the sheet of cells that sits between the basal ganglia, which we'll talk about next, and the cortex. It tends to run into cortex and some people have wondered whether or not it's just a seventh layer of the insula. It integrates various modalities. We think it's involved in consciousness. And what Christoph likes to talk most about are his Marilyn Monroe cells. The claustrum have these very interesting cells that will fire and respond to a single concept. So you can have a cell that will respond when you see a picture of Marilyn Monroe, when you think about a movie of Marilyn Monroe, when you hear a sound clip from Marilyn Monroe, but it won't respond from Michael Jackson or anyone else. You've got a different cell that responds for that. So each of these cells is very finely tuned and is integrating data from a lot of different modalities. Striatum and basal ganglia are pretty much some of the largest structures subcortically. The striatum consists of the caudate and putamen, as well as the nucleus accumbens, which is considered the ventral striatum. When you add in the globus pallidus, which sits in here, you have the group of structures termed the basal ganglia. Sometimes the subthalamic nucleus and the substantia nigra are included in that. And these guys are involved in, there we go, quite a few different functions. So striatums involved in a motor loop, which is probably the most famous as this is the loop that is affected in Parkinson's disease. So there's been a lot of work with that. But it's also involved in an executive loop with the prefrontal cortex. So involved in executive functioning and day-to-day functioning of your life, as well as the limbic loop. So involvement with emotion and memory formations. The basal forebrain is this area sitting right in here. It consists of a couple of really small nuclei, primarily cholinergic. And the cholinergic innervation of these nuclei go throughout the cerebral cortex. It helps modulate activity within the cerebral cortex. So it's involved in a lot of memory and learning processes. It's one of the areas that has affected fairly early in Alzheimer's disease. And most of the therapeutics that are used right now for Alzheimer's disease that involve colon S-race inhibitors are designed to counteract the fact that the cells that send out the acetylcholine are in the process of dying and not sending out quite as much as they used to. So by altering the colon S-race activity in the rest of the brain, you can keep the neurotransmitter in the synaptic clef a little bit longer until these cells die. And then those medications don't work too well at all. The thalamus is the other big one in the cerebrum. It is the relay station of the brain. And with the exception of olfaction, all of your sensory processes go first through the thalamus before being divvied out to the cortex. And thalamus, as I said, is made up of quite a few smaller nuclei and each of those nuclei have individual subdivisions themselves. But each of these nuclei receive specific input of a specific modality and send it out to help integrate stuff. Motor directions also go to the thalamus before being shuttled out to the body for a lot of things. The hypothalamus sits ventral two and anterior to the thalamus. It's the other half of the diencephalon which is actually comprised of four components rather than just two. It links the nervous system to the endocrine system or the pituitary gland. And so it's involved with a lot of metabolic processes. It's secretes our neurohormones. It helps regulate body temperature, hunger, thirst, circadian rhythm, sleep. And it's interesting because there are nuclei in the hypothalamus that are sexually dimorphic, meaning that in males and females, it'll be different sizes or different densities of cells or nuclei that can fluctuate based on a variety of things. Hippocampus is technically, well, it's a cortical structure in my mind. There's always arguments about that. But people tend to talk about the hippocampus as an entity itself, so I'm gonna cover it with the subcortical stuff. You know, it's a continuation of the cerebral cortex. It is involved in memory function, input and retrieval. Memories are not stored in the hippocampus per se. They need the hippocampus to get memories in. You need the hippocampus to get memories back out. It's also the location of place cells which are studied quite a bit. And these are cells at fire when you're in a distinct position. So they do a lot of studies in mice thing where they fire when they're in a box. There is this layer of dense granule cells called the dentate gyrus. And it is involved in the hippocampus functioning, but also just underneath it in the subgranular layer of the dentate gyrus is where there is still some adult neurogenesis going on. So there are new cells being born in the hippocampus. It's a lot of studies going on with that. The hippocampus itself is divided into four main sectors, CA1, standing for Cornus Amonus or Ammon's horn, CA2, CA3 and CA4 that sits inside the dentate gyrus. Each of these sectors has multiple layers. Primarily the largest of these layers is composed of pyramidal cells. So it's called the pyramidal cell layer, but there's also layers of fibers running through there. There are thinner layers, the stratomorions. It contains very few cells and is essentially a layer that is a single cell thick. And then the final component of the hippocampal complex is the subiculum or the bed that the hippocampus sits on. And this is transition cortex into entorhinal cortex and the rest of the neocortex of the brain. As soon as it goes, it stops. All right, and then finally the last one we'll talk about and this is not in any way a complete list of all the subcortical nuclei. But the other big player tends to be the amygdala, which is the sister component to the hippocampus of the core limbic system. And it's involved in processing memory of emotional reactions. It's been shown in mice to be important in fear conditioning. So that's the cerebral subcortex. The cerebellum in the back. I think we've got a couple of lectures on the cerebellum as well this week. It's located here at the base of the brain and it, like the cerebrum, has a cortical and subcortical components. It's involved in fine motor control, so timing, precision, coordination. Damage to the cerebellum tends to give you different motor syndromes compared to, say, Parkinson's disease, where you have a constant shake. Damage to the cerebellum can give you issues with being able to fine tune at the very end of grasping types of things. While the cortex and the cerebrum is six-layered, for the most part, in the cerebellum, you have three main layers. You have a cell sparse molecular layer. You have a layer of large, bodied, purkinje cells that line up in a single layer and then you have this very densely packed granule cell layer made up of granule cells. The fact that this layer is so dense means that in the human brain of those 85 to 100 billion neurons, about 70 billion of them, reside just in the cerebellum. Here we have a nistle. You can see the large purkinje cells. This is an SMI-32 stain, which stains neurofilaments. These are actually some of the most beautiful cells in the brain. You've probably all seen pictures of them without knowing it. Beautiful tree-like arbor. Subcortex contains three to four nuclei, depending on how you name them, largest of which is the dentate nucleus, and these nuclei are involved in communication with the rest of the brain sending out to the cerebellum. The brainstem and hindbrain. There are different levels here. We've got midbrain, pons, and medulla. It's where the cranial nerve nuclei live. So there are 12 cranial nerves. With the exception of the first two, olfactory and the optic nerve, they all terminate back here in the hindbrain. So starting with the oculomotor, all the way down to nerve 12. They do integrative functions, so they're involved in cardiovascular control, respiratory control, alertness, awareness, consciousness, and damage to this is very bad for you when you can't have control of those functions. So it's a very important structure, and it's comprised of white matter tracks and individual nuclei, and there's quite a few of them. The only other thing to really touch on in preparation for the atlases is a bit of neurodevelopment because we do have developmental atlases that look at prenatal function. Developmentally, we start off with a neural groove. It folds into a neural tube. Got an aller and a basal plate on that. And then you can think of this tube as becoming segmented from one end to the other. And those segments go on to develop into different areas of the brain. And so essentially the prosimeric model is this segmentation and looking at how those different segments evolve during development. And so as you get farther along in development, those segments can be parsed out finer and finer and finer until we have individual nuclei. This is a little different than the way that we tend to talk about the adult brain. Additionally, because the cortex is still forming during development, we have structures that are considered transient structures, many of which go away either by birth or shortly after birth. Mainly the ventricular zone, which is where cells are born and the ganglionic eminences, the medial and lateral ganglionic eminences. These eminences are the birthplace for cells that are going to go become the striatum and become cortical inner neurons, whereas the ventricular zone is essentially the birthplace for cortical neurons and those cells are gonna migrate out and do what's called tangential migration around the cortex and then they're going to change their path and do radial migration of astrocytic processes until they reach the cortex. The cortex is born essentially in an inside-out manner so that first layer is formed and then the sixth layer and then as the cells are born, they layer in and push that sixth layer down. The result being that when you're looking at prenatal brains, we generally don't have a sixth layer cortex and so we have cortex layered differently. We start off with the ventricular zone. We've got a subventricular zone which can be divided into an inner and outer zone, an intermediate zone. There's a lot of trafficking of these cells as they migrate. There's a subplate zone where there's additional divisions going on and the cortical plate as the cells are moving up, differentiating and maturing, to the very outside we have a marginal zone and a subgranular zone. The marginal zone is likely to become layer one in the adult cortex. So the previous one was in the middle of the of the previous disease. The what? The previous one, the previous picture was in the middle of the pregnancy. Let me zoom back here. So this is, if I can. Of the other, but the previous one was around. This one? Yeah. So what you're looking at in the next picture is essentially right here. Okay, all right. So one of the questions that comes up and I'll touch back on this again when we talk about the atlases. Because there's so many different ways of organizing the brain, so many different ontologies people always ask, why can't you just have a single ontology so that I can go into the mouse brain and then look at it in the human or why'd that just call the same thing in the developmental stuff? And this is essentially what ends up happening. There's about 14 competing standards and someone comes along and says, well that's ridiculous, we need to combine them all and they make a system and now there's 15 competing standards. It's very, very difficult to get all these ontologies into a single entity and there are attempts going on. But especially when you throw that fourth dimension of time in there and you start dealing with structures that will no longer exist in the adult brain or you're looking at adult structures that just simply don't exist yet in the developmental brain, it becomes very, very difficult. Yes. I'm related to this big picture question of how we even approach this whole thing. This was throughout your very nice introduction that there's kind of like this tension between structure and function, right? And so there's a lot of description based on what different cell types do I see and then there's a lot based on, okay, if I knock out this part of the brain and it affects this capability. So I'm not in that area, but I have a sense that it's going more and more structural, is that right? You can tease apart more and more different cells. It really depends on which direction you're coming from, right? So the clinicians will continue to see syndromes which will indicate areas that are damaged. But if you're in looking at how cells themselves respond then you have to really look at the different cell types and see who's connected to who, which informs back to the clinical picture and what's going on. So it really is a combination of both and unfortunately those two camps until very recently haven't discussed much. So to speak. Maybe you head up the famous Vanessa and the thing of the usual cortex where it's like five to two million different areas with 50 million different things. And so I think there may not necessarily be a simple match of like structure to how a function is going to be done. And part of that is having to divide out function into cellular function and network function and behavior, right? Because those are all on three very different levels. And so even in talking to colleagues who for instance look at interneurons in the cortex primarily, to them if you alter the function of one interneuron now you've altered the circuit, right? From a behavioral perspective I'm not sure that one interneuron being altered is sufficient to affect behavior in the long run, right? So there is this question of at what point do we hit that tipping point of individual cells being altered to the point that they're not functioning correctly before it affects the circuit as a whole. So it is quite complicated. And again if you go back to the very beginning and where we're trying to get to in the end and the understanding of the brain you really have to take those other 10 things into account. Our initiatives in the future are moving towards more understanding how the cells connect to each other and the intracellular pathways that are going on in them. So we're kind of moving into the next step and the next phase for us as well in helping with this understanding. So hopefully within a couple of years the goal is to understand how every cell in the cortex works and who talks to who. And that's quite an endeavor. So the timeline is quite aggressive, I will say. And there's actually, if you wanna find out more about the future of that I'm gonna show you how to get to our YouTube channel and there is the press release and the press conference that was held as we started to get into this and you can hear Kristoff talk a little bit more about the objectives of this new program. In a few years in neuroscience doesn't necessarily mean two, so. But hopefully a lot earlier than we had. Just to press harder on this issue, don't you think that the Allen Institute is sort of uniquely situated to try to promulgate one or a small set of standards? Yeah. And many of us outside thought that some of the initial choices in the two systems, for example, were a bit idiosyncratic. Yeah. But regardless, be that as it may, it's sort of analogous to the early days of the genome where there were again competing standards and it's not like the adaptation is finished in perfect even for genomes. But still, I think there's room for it to be a lot better.  It's not fair. Yeah, no, you know, our first thing that we are trying to address is not necessarily a universal ontology to use across everything, but ways to link them so that you can... There's more facility at moving between the different species and the different apocys. It is not a small endeavor by any account, but it is something that we have talked about and is kind of always in the back of our mind. Part of the problem is that for each of these projects, to do it to the best of that project's ability means that you need to take into account the limitations and structure the entire project around that. So for instance, with the human atlas, where there was a lot of talk about, you know, how deep do we go and what ontologies do we use, what atlas do you use. We had lots of problems with this. There's no major standard atlas that everyone accepts for the human brain. And yet for each of the major structures, there are gold standards that people will point to. And so we tried to pool those gold standards in for each of the structures. That doesn't include any sort of time reference. And when you move to the developmental atlas, since the focus is on time, you really need to address it in a time manner, which gives you a completely different ontology. So we have this sort of a, this is a great overview of the human brain. We obviously know a lot of it. There's also a lot of data that we don't yet have. So can you just think a little bit more about, you know, over the next four or five years, the types of data that we expect to have? Yeah, and some of that's in the second talk. So we are working on data for connectivity. For instance, we have a connectivity atlas that is in progress. It will be looking at injection sites in, I think it's like up to 500 different spots in the mouse that you can then look and trace back to see exactly where all the projections go to. That is going to go through the end of next year, I believe. And so that data is going to continue to come out for a while. We are adding on fetal time points to our macaque developmental atlas, which right now is all postnatal. And there'll be fetal time points to that. So kind of working with this developmental scheme and now being able to have a mouse development, a macaque development, a human development to move between. That's, well, yeah, so that will be microarray, I believe. So again, looking at all the genes and the ability to get a comprehensive picture. The new initiatives are more focused on things like electrophysiology and mapping that back in to different cell types. So looking at firing patterns and individual connectivity and synapses and finding a way to map that back to specific cell types. So in conjunction with our transgenics a lot to figure out how individual cells work and talk. So. That's quite labor intensive and the flexibility we're used to doing that. So how do you kind of pull up together with existing and how does that make sense to you? Yeah, I'm waiting to hear, you know, we've all got ideas but that initiative is just getting underway and so there is still a lot of discussion at this point on exactly which directions it's gonna go and how we're going to be able to integrate a lot of different things. There will be EM, there will be calcium signaling and stuff so hopefully and again a lot of work with these transgenics that have been developed so that we can look at very specific cell types that are highlighted by the transgenics to get a better understanding of individual cell properties. So fingers crossed. But yes, a very large initiative. They're looking at doing that in the mouse visual cortex as in mapping out all of V1 in that way. So and hopefully I haven't given away too much that's confidential and I don't think so. But I think that pretty much and now we're not too far behind now but other questions about the anatomy and again we'll start diving into the atlases after the coffee break so you can see what kinds of data we have. So we have some damage in some part of the brain we lose some functionality. So what is the plasticity for example? Is it possible, I mean, what are the cases when some other part takes over? Yeah, part of that depends a little bit on development. So for instance, you can take a small child that has epilepsy and needs a surgery to remove half the brain and you would expect this child to not be able to move one side of their body and they will develop into a fully functional individual if that surgery is done early enough. Later in age when you start looking at stroke that ability to reorganize is not nearly as strong. And so there are some studies that show that with therapies some of those areas that were affected surrounding areas may start to take over some of the functions but I don't think that that happens on a timescale that would necessarily get us to for instance recovery of stroke in old age type of thing but there is a lot of plasticity that goes on and it's very different to say change the plasticity between two cells that are connected to each other versus changing an entire network to do something else. So the plasticity is there. The capacity changes as we age. It lessens somewhat as we age but I don't know if we were to live till we were 200 maybe we would be able to see some of that but there are functional imaging studies that look at shifts in function in surrounding tissue to strokes and it does look like there is something that goes on there. Not quite clear what it is.


Moments before Gospel star Deborah Fraser passed away. A dark silence has descended on the local entertainment industry. The legendary, multi-award-winning gospel singer Dr. Deborah Fraser, 56, has passed away. A few weeks ago she told the publication she was hopeful she would get better, but that was not to be. In a short statement, Fraser's family said she passed away on Sunday, May 15, just after midday, surrounded by her family and friends. Speaking on behalf of the family, Nontando Moffises said, It is with deep sadness to inform you of the passing of our beloved mother, sister, aunt, and friend, and gospel musician, Deborah Fraser following a short illness. Moffises said as the Fraser family they would like to be given space to process and deal with the very tragic situation. On April 22, Deborah opened up to the People's Paper that she was not doing well and that was the reason why she could not walk anymore. Fraser revealed that she has been in and out of the hospital and in February she was hospitalized for two months. Although she was ill, she was hopeful she would get better as she was getting all the support from the doctors and nurses. The Umsa Maria hitmaker had revealed over the years that she was diabetic. In 2009, her mother succumbed to diabetes. Former public relations manager at Universal Records, the vice-o-McWattie, told Daily Sun he was still in shock after hearing the news. He said he worked with Fraser for over 23 years. I will go see the family tomorrow, now I don't have the energy to talk," he said. Fellow gospel artist Leuander Rehmitzwe said he was heartbroken by the news. He said Fraser was like a mother to him. She played a huge role in my music career, he said. I'm lost for words. I spoke to her on Friday when she invited me to prayers at her house but I couldn't go because my spirit wasn't feeling right. That was the last time I spoke to her. The veteran singer began her career in 1985 as a backing singer and recorded her own album titled Abanyi Bayambana in 2000. The album has sold over one million copies. Luhambo was her 10th studio album with 14 songs, including the hit Jikunji Yekyukufendaza.