This guy you're good to go right okay. I will call the August 20th 2018 select board meeting order and invite you to Rise and join us in the Pledge of Allegiance I pledge allegiance to the flag of the United States of America and to the Republic for which it stands one nation under God Indivisible with liberty and justice for all I'd like to welcome everyone to tonight's select board meeting and as always just remind you if you have Cell phone if you could put it to silent or turn it off that would be much appreciated just so it doesn't disturb the meeting So we're gonna go on to the next thing is agenda additions and changes and Greg No additions per se, but just want to draw to your attention the VOCT municipal policy packet This goes with item 5g it was sent to you a little bit late I think you should have received it today, and it should be online, but here's a Okay, but it was on it was online the right yes on the VLCT website Yeah, I believe so and also it's on our website now as well And then the thing from CVE was in our packet. It's just a hard copy right plus the ticket. Okay So we have that one item added Motion to amend the agenda to add the Item to 5g so much second Like any further discussion about many the agenda with that item Very none all those in favor signify by saying aye. Aye. Okay. Most of us is four zero We're down one select man who is out of town. That's Elaine Sopcich. So we'll be Working with the four of us tonight Okay, we're on to public to be heard This is a time for the public to speak to the select board on topics that are not on tonight's agenda Is there anyone here wishing to speak during public to be heard? Okay, then we're going to move on to our first business item, which is 5a and Rick chief Rick Gary is here along to introduce the new captain Ron Huyg Is that close? Well, what's the proper? Well as as it used to be it was Huyg But when I after I moved to Florida I kind of changed the pronunciation to Hogue so either way is fine Which do you prefer Hogue is fine. Oh, okay. Yes. I want people to spell Thank you. Thank you for being here. Thank you for having us You have a memo in your in your packet from from Greg Thank you for the opportunity to come in and and introduce the captain We're excited as I think you've heard very excited to have him here. Yeah, I'm particularly excited for the help And Ron in the last three weeks has been a huge help for us Ron actually started with us back in the 90s as a patrol officer did eight years with us as in uniform Then transferred and went went down south down to Florida. We worked for the sheriff's office down there did nine years down there Transferred back and we almost stuck them back about ten years ago But he ended up in St. Albans where he's done ten years in St. Albans and made his way up through the ranks Being the second command up there as captain working for Chief Taylor who used to work for us So Ron has shown excellent leadership there good decision-making skills and he's going to be a fantastic Resource for so we want to make sure that you came in saw the face and see him Maybe once in a while filling in for me and helping out. So we're excited to have him I don't know if you have questions or if Ron has something anything that you want to know I'm here to answer any questions that you have and thank you very much for for Inviting me to come to the meeting and do this. I don't think I've ever Done this before in my career. I think this is a fantastic thing that you guys have are interested in having me introduce myself So like I select the chief said You know, I started in with Essex or at least I worked with Essex from 93 to 2000 when I went to Florida To find greener pastures and bigger things to do and had the you know The grandeur of more call volume and that type of thing which I got my fill of quickly And then you know while I was there I worked in the traffic unit down there. I became Very involved with the DUI Enforcement unit and with a sheriff's office the sheriff's office there had over 300 enforcement deputies and another 400 jail deputies So we were very it was a big department multitude of different divisions and such And then my wife and I decided to move back here. My wife. It's from Essex and we decided to move back here in 2008 and it was it was a good thing at the time I didn't think so because I certainly miss the weather But since I've been here, it's been it's been good for us and I'm glad to glad to be back My wife was very excited to know that I had the chance to come back and work for the town of Essex So being that her family still lives here. So Actually her dad is Dan Canty who lives up at the corner of 128 and weed road So you're probably familiar with that with that area. Yeah, so he's been there a long long time. So yeah So we'd like to say welcome back. Thank you. Thank you. It's good to be back. It's been been good So so is there any learning from your time in Florida that might be applicable to up here I know it's two different very different type of comments Well, believe it or not. I mean law enforcement is the same from you know from Florida to California to here It's it's all about, you know enforcing law But relation to citizens and that type of thing I would say the biggest thing that I learned in Florida was working in a large Organization and was able to be exposed to a lots of different types of crime major crimes on a on a monthly basis and You know having the opportunity to work in different units got got me able to see how, you know Larger agencies are run also gave me an appreciation for smaller agencies too because there's a lot of advantages To working in a in an agency like ours Where everyone knows each other So that's that's one of the good things that I've enjoyed coming back coming back here So Captain did you did your experience either when you were here or in Florida? Did you spend any particular amount of time in domestic abuse? Cases or anything along that line? Yes, I mean, you know, I mean over the over the years I've never been assigned directly to a domestic violence unit or anything like that But over the years, I've had a lot of training in different types of approaches to domestic violence I can tell you that in St. Albans my experience there That was one of the greatest crimes that we saw on a consistent basis, and I think that's the case In in Vermont throughout Vermont and throughout the nation, I think So to me that that is one of the areas that we have to take the most seriously and make strides in because there's There's just too much of that that's going on Yes Absolutely, thank you So as you can see chief Gary was quite Happy to be able to have somebody that he can now Hand some some workload over absolutely Maybe you could close in on what some of those key things are that are now The after our three-hour meeting on the very first day that I was here where he ran me through everything that that needed to be done I've been the last three weeks. I've been working on Updating a lot of the policies that the police department has I've been working on ordinances And that type of work Also working with some of the officers to get some of their you know, just directing them as to you know Where they want to go in their career? Where where the trouble areas are learning learning that again because some of the things have changed here in the town of Essex and Village? You know since I've been gone So just learning you know the trouble spots and where those need to need to be taken care of so That's that's been in you know, learning about the department itself and the different people that are there so Exactly exactly it's it's been busy the last the last three weeks have been good I've been I've had no time to stop at all. So it's been really good for me Thanks for that. Any other comments or questions? Yeah Okay If you could state your name Betsy, do you have a question or comment for the captain? For Essex and my question for you is how do you feel about restorative justice? And will you have a close working relationship with the community justice center? Yes, it's it's funny that you say that because the chief has kind of assigned me to oversee that that program and I'm very familiar with restorative justice and have worked on an on extensive and close level With the folks in St. Albans. They have a very active RJC there that we have done a lot of work with the police department and Cooperation with them. So I'm very familiar with it with how restorative justice works and the various programs and I'm really supportive of it Okay, there's no other questions again, we want to welcome you back. Well, thank you very thrilled to have you back Thank you. Thank you everyone for having me. I appreciate that. So thank you Thank you, thanks So we're going to move on to our next item of business which is 5b and that's to determine whether to hold the liquor hearing for backstage LLC who wants to kick that one off? I'll be So you the slick word issue day first-class liquor license for fact stage back in April But they had had some issues of concern from the police department through the state as well So the permit was issued in the condition that they come back in for a liquor hearing After making that decision. We found out the state was holding their own liquor board hearing that has since been held and Backstage was penalized with a seven-day suspension that was Appellate or took place in the beginning of this month in August and so after speaking to the police the manager's office they've had no incident since May when this came up and Both police and the manager's office are confident that the state punishment is sufficient And we don't believe they hearing is needed at this point We'll certainly continue to monitor them and see if any of their issues come up and the police are aware of that So if there are other things that come to attention, we can bring them back to you But at this point we do not feel a liquor hearing is necessary I just would like to suggest that because this is a special case because of the violations that had happened that Rather than waiting to the renewal for next year if violations do occur We could when it when you think it's ready We'd like to kind of know about those in advance rather than waiting to the the next year just to kind of keep our thumb on things So we've changed our practice and we are running Incidents reports quarterly on all first-class License holders, okay, so on a quarterly basis if we have an issue we'll be able to report back to you Okay, certainly if there is something that is of an urgent nature. We would bring that to the town manager's attention immediately Thank you, great. Thanks Entertain a motion then so that we can codify this Irene I would move that the select board not hold a liquor license hearing for backstage LLC Doing business as backstage due to the license suspension imposed by the state of Vermont. Do I have a second? Second, okay any further discussion about not Having a liquor license hearing for backstage LLC Okay, hearing none all those in favor signify by saying aye aye opposed. Okay motion passes for zero. Thank you Okay, more for the chief we have approval of resolution for Stephen Dunning and whose Wants to kick that one off Chief do you want to do it or are you asked to do it? Actually, I think you've got the resolution Yeah Officer Stephen Dunning had recently left the Essex police force and But it was after a long long time here. He was initially hired as a full-time officer in June of 2009 He actually started prior to that as a civilian bike patrol member in 2008 I won't read the whole resolution. Let's hit some of the highlights in his time here He was a rad instructor a police medical officer and town exposure control officer In April of 2015 here in the middle of Valor Which is the department's highest honor for risking his life to pull a citizen from a burning building to save her life And he has served Essex in the entire Vermont law enforcement community well over his tenure here in Essex So the chief has put together resolution that Hoping the select board will adopt and just my appreciation for an officer who spent a lot of time here and did a lot of good things here Thank you, and normally we have the clerk read But Well, I'll ask the board if they want it to be read for the record or we just sort of had a synopsis Okay, all right, then what's the board's pleasure on recognizing this Stephen Dunning for this resolution in appreciation Hey, buddy All right, I'll go all right So I move that the select board approve the resolution appreciation in appreciation of Stephen Dunning Sorry, okay, so any further discussion about Approving the resolution and appreciation of Stephen Dunning. All right I've taken the rad course which in case anyone doesn't know stands for rape aggression defense It's fabulous and the instructors Don't have it easy Very physically demanding I would say as a participant of the instructor So congratulations to him for doing that among many other things for us. Thank you Okay, any further discussion Andy. So the our our Clerk is not here, but the document is over there in that folder over there. So I'm assuming that we would we Just reminding us that we need to sign it since we don't have a clerk to ask us to do it Since I'm the past clerk, you know how that could happen Okay, so any other discussion? Okay, hearing none all those in favor of the resolution appreciation of Stephen Dunning signify by saying I I Posed okay motion passes for zero. Thank you. I think we're good. Thank you. Thank you again. And welcome Good luck, okay, we're on to next business item, which is 5d And that's the adoption of the recreation program budget and we'll invite director Ali vile up And maybe you can walk through some of the the highlights If you would one has to promise to give me one since she's not here. I could take care What's up? I'll take care You just want to Do you already have one I don't know the goodies in the goodie bag Elaine I'll take you to have all you have all Yeah President We knew she was smart so that's right So tonight is is just for me to kind of go over a little bit about our Program fund enterprise fund. It's called the couple different things wherever you go this started about eight or nine years ago Where that was taken out of the operating budget and it's that revolving fund for us to use throughout the Years and build up so that we can do bigger and better things our revenue grows So in general, you know, we through this program we employ Approximately 40 individuals within our general summer camp and extended school program fall soccer Programs throughout the year our overall number of seasonal employees is much larger than that, but that's just within programs And then we have approximately 150 unsung heroes There are our volunteers who we couldn't do the programs we do without them We have around 100 fall soccer coaches About 20 Chaperones for the Bolton after-school program 20 coaches for the lacrosse program and all of that and all of them range in price and we've battled over the years of how do we do more than just say thank you and Recognize each and every one of them and some of them are doing all of those roles I just mentioned and some are doing one throughout the year, which is a large commitment of time and energy So what we did is April was actually I think it's volunteer month volunteer appreciation month and It's hard to say a percentage or a dollar amount off of a registration when lacrosse could cost $120 and soccer cost 50 and you can get 10 bucks off And it doesn't really say thank you the same way Sam has been one of our coaches and so And and has volunteered her other time with us that way. So we did this we put together Little swag bag of charger because we don't always have the greatest reception and everyone's phones die When they're helping us out at the tree farm So we want to make sure that their phone can stay charged and then We got them some sunglasses that are pretty neat and we ended up getting a lime green color for all of our staff So that No matter what division you were in all the staff got some sunglasses as well So that was our thank you gift with a really fun little. Thank you personalized card for them So that's that's where that is and it's even customized as Essex Park. That's right I was with my predecessor this weekend. I brought him the staff color pair sunglasses For him to wear so it's very fun and it was just nice to have everybody come in out of the normal season of them helping and you know trying to You know Coax them into coaching again or whatever it may be But just having a good face-to-face Thank you and handshake with everybody and just being able to see them when it wasn't the first thing on their mind Or they may be dreaded signing up to help us So those are unsung heroes We do a ton with them and they do a ton for us. So it's truly appreciated But overall the program fund has provided us, you know the last couple years to Enhance program equipment and uniforms and things like that Outside of the the fiscal year boundaries that we sometimes have So this is a little funky because we're already into fiscal 19, but in fiscal 18 You know, we did there's a whole bunch on the memo that we did we Did expand some program offerings up at Sunset Studio, which is the fitness space that we rent And it's that we'll get to that too a little bit later, but you know We received a donation for the scholarship assistance fund that was in a large amount Which is nice and our requests for assistance continue to grow and grow We were able to provide some additional training opportunities for seasonal staff we have a new assistant program coordinator and that was really important for her to to get to know the staff differently and Enhance their their skills with the kids as well with the extended school program Overall we increased our seasonal offerings by 19 programs over the fiscal year We did our our thank-you gifts. We had a recreation software upgrade including a new splash page when you go on for online Registration that looks much more user-friendly It's easier to guide customers through that aspect Big thing that a couple big things we're really looking to do in this new fiscal year's kind of assess our program output We've gotten to the point where We have a lot of quantity and we're trying to provide the same quality to that level of programs and so we're really looking to still explore new opportunities and new offerings for people but really make sure that it's what the community desires and With the staff that I have making sure that Their capacities are That they're there and that they can really give all to the programs that we're offering so that it's not just Something listed in the book to make it look like we have more and that people actually want to do it and They bring in money and people are happy and there's large enrollment and things like that We also have to really examine the rental space at sunset studio or leases coming up it was the extended two years from the original and That's the big decline in our in our overall program budget when we first went into this endeavor It was highly recommended from management's perspective Just because we have new space to offer and aren't relying on the free school space Let's not increase program prices Well rent costs about rent and utilities costs almost twenty thousand dollars and without really raising that this is what happens So we're using the revenue that we've grown over the years, but we're not The studio is not paying for itself at all And that's that's really tricky and so with a lot of other alignment conversations happening We really need to Reassess how we program and how we price and how we utilize the space and I know that Maybe Dennis is coming in a little bit. No You're talking about the facility space assessment needs What's up? Hey, you're welcome. So instead of maybe paying Into a rental of space that isn't actually the towns It would be nice to get to that point where we have our own facility space that doesn't That isn't paying someone else necessarily that we can sustain on our own would be really nice So we need to do a lot with that You know, we still have we still started the new fiscal year with over seventy two thousand dollars In our program fund But that would only last us a couple more years if we continued to stay where we are and how we're doing things So I do know In my in my budget pages. I do have a comment from last year under travel. So I will get that fixed Because I decreased travel a little bit, but I I forgot to change my comment But if anyone has any questions, I'm happy to do my best to answer those Thanks for that rundown any questions or comments for I'll go first I guess I on the extended school program It's down significantly it's down 14.6 percent from FYE 2018 Could you just say what the significant changes are I read what you had and it wasn't particularly clear to me anyway As to what's going on there Um Yes, that's kind of wrapped into one at the are you on the budget pages? Yeah, I'm online 19 in the budget detail. Yep So what's really funky and how this program budget has often been Presented is it's kind of floated out there. It's either been presented to you all in February right after the regular operating stuff last year it was presented in early May and So those were still estimated numbers. I'm really at this point in the game. I'm going off of actual numbers Pretty close unaudited, but pretty close and so I think we are just One one thing is staffing we hired a new person with a higher skill set and We have certain staff And our increase in staff new staff is really just a turnover We had a lot of people graduate or who won't be available So we're figuring out how our ESP will work this year With the emotional discussion of transportation and getting staff to the schools to help us out. That'll be tricky and Yeah, she's gaining new staff, but it's not really an increase in the number of staff It's just the turnover and that's a big significant change because she has good experience after last year But she's gonna kind of be starting from scratch again in a different way But it's just the realistic aspect of we may not be able to provide things on the Tuesdays with the school changes and You know we we offer I Think ESP is really unique that it offers something Different than what parents working parents or any any parents or guardians that need care for their children But it's not licensed childcare and it's not Three to six or whatever it may be so it's really based on what we offer And when those are all available and for a while We've been doing the same thing and over the last year and a half or so We've seen our enrollment down. So we're really having to just come to switch gears and it's being more realistic ESP is extended school program and PNO is Parents night out. Yeah, so it's kind of date night from 5 30 to 9 and We provide pizza and fun and the movie and all of that and parents drop off and And they come pick up Right at the best time of night Have fun putting them to bed after Well, correct them Thanks, okay. Any other questions for Ali on the budget the program budget The other programs I know in the past youth lacrosse has been one of them is the Essex warriors wrestling also part of that or they aren't they haven't so lacrosse is wrapped in that We've been working with finance to kind of separate out certain line items Essex warriors hasn't come to us specifically of looking for financial assistance and We also don't just send a check to those who are in the budget So sometimes those organizations Haven't build us and we can sometimes give them a little reminder if they want the money they can Send us an invoice We get a Motion to adopt the fyi 2019 recreational program budget So moved Any further discussion about adopting the fyi 2019 recreation program budget Keep up the good work Yeah, this really presents a nice quality of life to our community. Yeah, it's great. Thank you Okay, all those in favor signify by saying aye. I pose. Okay motion passes for zero. Okay. Thank you for the swag We'll put that to good fun to get little shrink hits. Yeah, nice one. Trinkets and bubbles Okay, we're going to move on to our next item of business which is 5e disillusion of business liaison group Oh In because of the possibility that discussion about the town's relationship with my employer may come up during this discussion In order to avoid the potential for the appearance of a conflict of interest. I'm going to recuse myself for this Agenda item You need to I'm happy to have a year if you want but okay We'll come get you when we're done. Yeah All right Okay, great. You want to Sure. So the business liaison group formed several years ago 2015 at the time It had the vision to identify and respond to emerging opportunities for business startups growth In improvement and provide a personal face on behalf of the sx community The members will meet with the unified manager from time to time and supplement the ongoing efforts of the economic development commission After they formed the the group met three times as far as I could tell They haven't met since the fall of 2015. So just doing some Housekeeping and cleanup and seeing if they were still necessary. I reached out to the members of the group I heard back from three of them Irene being one of those members The responses are included in your packet, but it kind of ranged from There's no need to I would need to be convinced that there is a need. Um, so Based on that, uh, it doesn't seem like there's too much of a need Um And our recommendation is that you dissolve the business liaison group I think the idea was a good one to start but yeah, you think about it when a company needs a rapid response team Um, a lot of times they want to keep whatever it is pretty confidential and if you bring in This large group with public members and so on that's kind of hard to keep it confidential. So Um, yeah, so comments, but I think Irene we have your letter. So we kind of know where you stand right, um, I I I see no reason to continue it. Um, especially if the members feel as strongly as they do about the fact that It just really hasn't fulfilled its promise Okay, uh, and I'm in agreement that it's the right thing to do is to dissolve it so but to do that we need a motion I move that the select board dissolve the business liaison group Thank you, Mike. Do I have a second? Thank you, Irene. Any further discussion about dissolving the business liaison group? Are you hearing none? All those in favor signify by saying aye. Aye Opposed, okay motion passes three zero with one Epstene, yeah recusal, recusal, okay Welcome back Okay, now we've got Andy back. We're going to move on to business item, uh, five f and that's approval of requests for proposals for building needs analysis Okay, ellie teed me up perfectly. Um This is a real world example, uh, the program recreation department, um, has been using sunset studio for the past two years ellie three years two and a half years It was a chance to try to take a test out some some new space as a school space is becoming less available As you heard it's it does cost money to have that space up there. Um, that's what it wraps into Our idea for a broader building needs building facility needs analysis also working with public works, um, the fire department Uh, the public works department at this point We'll be looking with the village highway department as well to get a sense of space needs This was part of the capital budget that was approved earlier this year Um last fiscal year for this fiscal year There's 40 000 in the capital budget And the idea at this point is to take those, um, four departments recreation town fire, uh, and town and village highway public works, um Have somebody do a study to figure out exactly What are the needs for those departments and the now and going forward not looking yet at space or where to put it Or how to build it just what are the needs how much space is needed Um, Dennis has drafted up a RFP to go out. Um, he's he's not here today, but uh in the interest of keeping this moving along and trying to get some stuff Hopefully out, um sooner rather than later and start to get some responses to move forward That's why i'm bringing it to you tonight Um As part of that the project though and part of the rfp that Dennis put together he he's asking for an addendum To the rfp which would also wrap in village fire and village parks and recreation To us it makes sense to To do it all at once rather than doing part of it now and having to add to it later, so The preference would be to to get some responses that Can study all six of those departments? At one time The issue is just trying to make sure this gets out The capital budget is was to 40 000 for the four So not quite sure what the rfp will come back with those other two departments might Require us to come revisit the the select board and also the trustee to see that george is here tonight Um, potentially ask for some additional money, whether that's from fund balance or capital Potentially some of the village departments, so That is all to be determined, but Again just primarily in the interest of moving this forward Wanted to bring it to your attention tonight get some comments on it So we can take those tweak it it is still in draft form. It's pretty close to done But I wouldn't call it completely final. So if you do agree to move forward tonight Looking for authorization to let staff kind of finalize it and put it out there Okay, so this is an analysis of the the the building needs. It's not a You know come back recommendation. This is what you really need to to do, but it Tells you what the needs are and all for options or looking needs and in how much space so It's you know, we have enough vehicles right now that we can't put everything into one highway garage or the other But it's it you need Square footage and then we can go from there again analysis if you took a look at Our current fire stations you have x amount of trucks You have x amount of bays and you have x amount of equipment and what you but then you ask the chief Well, how you know, what do you look out in the next 20 or 30 years? What What do you need to operate that fire department in the next 20 or 30 years? How big of a training room do you need? Do you need a kitchen? Do you need a you know, what types of spaces do you need in the fire station of the next 20 years? With the rules and regulations parking for those firefighters Um, are you going to want sleeping rooms and if you do how many? Spaces would you need would they be individual rooms? Or do you do a bunk room type of thing? Just for all those things and and so You take that and you say, okay, you've got Couple pumpers couple trucks couple this you need this many bays You're going to need a building of this size with this many parking spaces and then you take it and look at the village Is it similar? Is it different and then if you combined them? What would you need? That's the kind of analysis and maybe a rough drawing Not anything that you could build on but a rough drawing of how much land That space would take Same thing in all the other departments so that you all have something to base decisions off of A rough date of it Okay Mike there were two things that I really liked about this amongst All of them that Dennis writes because he just he puts great He put great he puts great memos together. There were two things number one he was Specific enough and leading enough To talk about the possibility of a two-story. I think he referred to a two-story building For the for the fire department Um, and the other piece that I you know, he in other words, he's kind of steering them It I I think the more detail you can give in an rfp the better you're the better information You're going to get back so to have him kind of Steer the conversation. I think was was a really good move And then including the other departments as an addendum. I think was just do it now Just like you alluded to earlier do it all now And then the third thing was He made a reference to the fact of having whoever wins the rfp Come back with a recommendation on whether existing buildings can be added on to in other words Are they structurally sound enough to be able to do an addition on rather than a whole new building so I'm I'm all in favor of of letting Staff put a bow on this and get it out the door. I think Dennis did a really good job with it Including having the village fire and Mm-hmm. Yes those we have george here george you're on board with that No concerns So I assume My month my assumption is I'd be on board with that, but you know the one thing I would Stress at least if it's going to come to the village is that you you and this is by no means Egotistical, but I would stress that you probably want to besides department heads in those buildings You want to just come and talk to the trustees Not because we have some big insight about buildings, but we might be able to give A little bit background about where we see where we see the department going That might be some disparity there between where the department head sees the building going and we might want to Have that Come out In the report and be dealt within the report rather than have a report that the trustees get and go Wait a second that doesn't Jive with the thing that we had planned or what you were telling us earlier So I I would only stress that the other thing if you're going to do The village fire department in particular They have they have done they I know that they routinely do their own building assessments So that might that information might facilitate this and be available to you the consultant you hire So yeah, be on board with that. Okay. Thank you george Um And just one other thing as ellie mentioned, you know Not only does the rec department rent space But the police department rent space for restorative justice as well So some of the things we want to look at is Maybe we want to look at a facility That you know can reduce what we're paying somebody else And and use that same money to pay ourselves For the space that they're using and maybe even get Better space that has more functionality to it For what we do Do you have an estimate of what it might cost to include these other two village departments? We do not and that's why the RFP is is put out the way it is that we're looking for that price and We have a budget, but we don't know Yeah, because we we have 40 K in the capital budget specifically for this So we'd have to find whatever additional funds from from somewhere But seems like to be a complete package. It would make sense to include that so And then Seeing how it then structured you would have some choices To either do it all do some of it Do it in phases Okay, so will you come back then once you know what the final number is? Or probably not it's it's the I mean I suppose if it's going to be well beyond that 40,000 that we budgeted and we had to go to come to the select board to request additional money from all out from unallocated money in the capital fund or if we're looking for fund balance transfer, then yes, if it's Within that 40,000 or some some money that can come out of operating budget for many of these departments Probably not, but if the preference is to come back to the board no matter what we can I mean, it wouldn't be another 50% more right because it's not adding 50% more work to it it appears And I don't want to put anyone on the spot But I could swear that we had this as a line item in our budget this year There yeah I mean, I'm just I'm it's pertinent to the conversation you're having right now because I thought the village had put some money away The village should put in $10,000 for the Village highway garage So the town had put in $30,000 in the capital 40,000 total So you're right, but it's already accounted for Other questions or comments from the board, okay, what's the board's pleasure? I think it's some of these I moved mr. Chairman that the select board authorized staff to finalize and issue a request for proposals for a building needs analysis A friendly member. Do we want to include? Those two record of those two village departments as well in the motion Well, it's right now written as an addendum. Yeah, it's an addendum We can I can talk to Dennis and we can bring this to the trustees get their sense on it Which we would be looking to do at some point anyways then figure out if it makes sense to keep it as an addendum or to do it Um to revise the the rfp a little bit more Thank you Mike and Irene any further discussion On um authorizing the rfp for the building needs assessment Okay, hearing none. All those in favor signify by saying aye. Aye. Opposed? Okay. Most passes for zero. Thank you all Thank you. Thanks for being here, George. Appreciate it Okay, we're going to move on to our next business item, which is 5g a point delegate for vlct annual meeting I'm just going to kick that one off I can take that one too So each year the vermont league of cities and towns held an annual meeting and they request that all members Which is I believe every town in vermont Send a voting delegate to the annual meeting other other members can certainly go but just one voting delegate Um this year it's going to be on october 3rd in south brillington and there's some a little bit of information about uh The meeting itself in addition to the annual meeting. There's also some other events conferences workshops that take place um As you got earlier today the draft municipal policy is here. This is what uh would be voted on and Um looking to you to see if you want to send a delegate Every year I've been a select board member It'd be nice if they could do track changes on these We passed that on last year if I remember correctly and I think we were told that They're putting it out. There's too many changes Yeah, what they they want you to read the whole policy not just the changes That's that's why they they they don't send out the track change, but they did say that they would provide it if requested We didn't get it this year Well, if we request it we probably will we should We didn't you have to request it each year. It's not a They're not gonna stand any request Every I would nominate andy to go unless somebody else wants to go instead or if andy doesn't want to go Well, I think there we might need to have an alternate. So yeah, I have a I have a concern because at this point I'm scheduled to be out of town that day Business travel frequently changes so it may it may move so I'm I'm I would be happy to do it if I'm available that day But as max I think was going toward We were we had some discussion before the meeting whether we should appoint an alternate in case I can't make it, right? Yeah We would like to be the altered it so one one comment I guess to make is it doesn't have to be a select board member It could be it could be staff too. I don't know Okay, but I'd like to offer to this select board first if either of you Would like to be the alternate in case andy can't make it that day as was October 1st October 3rd If I can find out what day of the week, so it's a Wednesday. It is a Wednesday Starts at 12 30 in the afternoon on Wednesday the third I I'd I'd be willing to be the alternate. Thank you sure Okay, sounds like we have a settle now. We just need a motion to make it so I mean I would move that we appoint Andy as Delegate and Mike as alternate for the VLCT annual business meeting on October 3rd Hey Gary, do I have a second? I'm checking. Okay Okay, thank you Mike any further discussion about appointing Andy as the primary and Mike as the alternate for the VLCT annual meeting on October 3rd Okay, hearing none all those in favor signifier saying aye. Aye. Aye post. Okay motion passes 4-0 I want to thank you both for stepping forward And Irene for offering that to Mike as well The form for it is over in that full It requires your signature Thanks for the reminder Okay, then we're going to move on to our next item, which is consent items Do I have a motion to approve the consent agenda? Thank you, Irene. Do I have a second? Second Okay, any questions about the check warrants which are in our Consent agenda for august 10th or august 17th Any questions or comments about the check warrants? Okay, well then hearing none All those in favor of the consent Agenda signify by saying aye. Aye. Aye. Opposed. I think motion passes 4-0. Thank you all We're all the way down to the reading file already any Questions or comments about what we have in our reading file again. This is fyi stuff. It's not to be actions taken tonight but Any questions? Um Is there a Do you want to speak to an item in our reading file? Okay, if you could state your name for the record, please And I wanted to speak about the open letter to support the University of Vermont Medical center nurses I am here to ask the select board to consider a resolution supporting a fair resolution to the ongoing negotiation with the nurses We have a lot of nurses in our community and they're important members of our community that sort of heal and And provide support to all of us And I as a Member of this community want to know that I have safe care that's being provided by people who are fairly compensated Betsy was actually here to also support me But she had to go unfortunately before we got to it Both in her role as representative and as a nurse as a former nurse Um And I'm also happy to gather more information if that would be useful. I think I sent an article Burlington has made a resolution to support a fair Resolving of these ongoing negotiations as well. So that's just what I wanted to Bring to you all today. Okay. So why don't we stick to that point for a moment? Um about that what number is it over here? That's a six g. Okay Um I I've thought I read that I thought about it. Um, yeah clear the hospital and the nurses do, you know, incredible job, but um, if the select board and the town was having an issue Their union and management I would not be too thrilled if some outside party came And tried to Get in the middle of it. So I'm putting myself in that same position here And uh saying that's really not I don't see it Not saying it's unimportant, but I don't see it as the select board's fight doesn't mean you couldn't do it individually, but I don't Particularly see it's our fight That's my I have to agree with that. Um, I I really think, um that the select board interjecting themselves, um Into labor negotiations is totally inappropriate. Um, even if it's just A resolution. I just don't feel that that would be appropriate at all So I guess what we should be doing says we're do we want to put this on a future agenda item? Or do we want to at this point say no? I would I would say no I would I would not support putting it on a future agenda item I think any resident of the town can ask us to put it on a future agenda And I don't think it's appropriate for us to say no it can't be on the agenda Well, we're but we're making a decision assuming that that's that that that they will Right you're we're I I'm I'm I'm not comfortable saying You know this this this was brought to our attention and I don't I I don't agree that that we should today Say no, we don't want to talk about this I think I I would I would like to allow an opportunity for those who brought the issue forward to request that it be Put on a future agenda I would agree with that No, um I guess we can put it on agenda Um and and let people talk to it if if we want to be fair and open um rather than just Say no at this point. So Um, did you want to comment on on this item as well? Okay, if you can say your name for the record too, right? I am a member of the community of Lyft here for 13 years as well as having been employed at the University of Vermont Medical Center For 13 years 11 years as the inpatient nursing recruiter in the past two years as a practice supervisor So I have an intimate knowledge of the long hard Sad summer it's been and I would ask that this not be a resolution There are a number of nurses in this community Hundreds of which I have hired personally or had a hand in hiring There's also a large number of practice supervisors leaders and managers and This resolution Made me sad as full of half Accuracies and I do not believe that it is the place of this group to insert themselves in our labor disputes that are going Out the organization the information here is not the full story I have spent more time crying this summer than I have in the previous 13 years combined through the sadness It's clear that there's a divide going on and a lack of trust My community telling me that I am the enemy of the nurses and I don't support nurses by passing this resolution There's nothing but deep in that divide Further and while I appreciate the the thought it is literally my full-time job to support nurses and doctors and administrative support professionals And this is not the support that I think The organization deserves So hearing that any change in bizarre any I'm still on a You know what's our policy for things getting on the agenda? Kind of the select board can ask for things on the agenda. Does it work with the public? So it depends on the issue and manager and select board This is a manager's agenda to put together But select board has the policy that the select board can ask for something to be on an agenda Okay, so I believe our our Policy that the select board has approved and signed that allows a provision for anyone to ask I may be wrong, but that's what I'm the way. I'm remembering it And it's a different time frame whereby an individual Not on the select board can ask but a select board member Think we even it says, you know four days before a published agenda kind of thing And I think from a from a resident it's a It's a slightly longer time frame, but I believe it's specifically stated in our policy that Anyone can ask I'm not saying it either way, you know for or against the resolution I'm just trying to be fair with regard to how we establish our our agendas I know we just adopted it back in April, but I don't remember the detail I I do not remember that line item. Um, that's not to say that it's not there. I just don't recall I need to double check. I know it's any select board member. Can I ask? I know any select board member Is any select been asking for it to be on the agenda tonight? No, so I would say we don't put it on the agenda I would ask that we review unless the pot unless the public asked specifically for it to be on the agenda Which I have not heard I've heard that either, but I also like to make sure we check our our policy. Thank you Anything else in the reading? Yeah, um, uh item H. It says vlct found town fair 2018 brochure. That's the brochure for exhibitors It's not the brochure for participants I don't know if you have gotten that yet because that that's happens in conjunction with the The annual meeting is on the third and the fourth um We'll double check if that was a mistake on our part or if that's the brochure that we have If there's another one, I'll bring it to you. Okay Okay, uh in uh item i with the invitations to the uh to the fair Um, they just need to know that it's elaine is now on the board not sue They have been notified of that. They have been okay. Super. Thanks for being on top of that okay And I guess in the same vein too with the downs raffle and martin if they can be notified that We have a new sheriff in town. You gotta have it instead of pat That'll be probably good for them to know too Anything else in reading pot? Okay, then we'll move on to executive session. I don't think we have any need for executive session Okay, I think we have a record going here. This could very well be Like I mean I remove to adjourn. Do we have a second? Second Like any further discussion about adjourning Are you none? All those in favor of adjourning signify by saying aye. Aye. Aye post. All right. We're done


how to get out of algorithmic jail. You know when you have less than 300 views on all your videos it's so much of the time that's not because your videos are trash it's that the algorithm has no idea what to do with you. One of the ways it can get to know what to do with you is to search your most niche genres hashtags and regularly look through the videos that are in that hashtag you should be appearing in and do interesting stitches or duets with those videos that are doing well in order to train the algorithm that you belong in that niche.


So, I will tell you a bit more about the book now and then today for those who would like to do something about the book today or during the weeks, the idea is to just figure out what would be interesting topics for you, for each one of you, how we can form groups and just let some topics emerge and then from tomorrow on there will be actual sessions because there are many, many possibilities and I think we have this critical mass of people with different interests and different skills so we should really, really see what's the best things we can do together. So first of all, again, some general words about the book so the idea is to write an open textbook for students and researchers on what we call economic principles and this for us basically means things like resource allocation and scheduling problems in cells but it can also go beyond that so it can also be on the organ level. We want to write this in a bit self-organized way without any commercial interests, without publishers and the book will be available as a PDF for everyone but we also want to make it possible to have copies at a very minimal price as print on demand so this is the first test copy that we made if you're interested you can have a look later and the whole text and book is supposed to evolve by the time and that also means that contributing is relatively easy so you can join and leave but do not depend on specific deadlines and specific single persons which makes everything relatively fluid and yes, also there's not a very strong strict commitment once you join the group. We do the releases all every three months and if you want to contribute it can be any kinds of all kinds of things so you could just join discussions about topics, you can participate in the actual writing, if you want to work on figures, graphics, layout, all these things we need people to do it and so you can see if there's anything that interests you. This is the current list of chapters that we wrote already and that are still going to evolve so at the moment it's really focused on metabolism and cell modeling so there are a couple of chapters that give a general background on cell biology and metabolism then in part two there's really a succession of chapters on different approaches to economics and metabolism meaning FBA so optimizing the fluxes or optimizing the the enzyme efficiency, enzyme investments in part three we start from scratch again with small cell models a few variables models of a growing cell and then see how this can be extended to get to really large models with thousands of variables by incorporating again metabolism and then the later chapters are about more complicated situations on the one hand temporal dynamics on the other hand questions of variability between cells hopefully in the future also communities and at the moment the last chapter is going to the organ level so to see how scaling and resource allocation play out on the level of the lung in this case as an example and between between the cells and this there's a lot of space for new for new topics and so we hope to to really extend this and specifically here it would be interesting to maybe draft a few chapters on interacting cells, cell populations, cell communities and so on so topics really linked to to this school a few points about the work that we possible work that we thought about so it's really for everyone who is interested you can switch between attending tutorials on one day and contributing to book sessions on another day so it's it's relatively free and flexible and this will always take place in the one hour time slot that is on most of the days reserved for for group activities so interactive activities usually at the at the end of the end of the day the idea is to in different groups to think about existing chapters how they can be further developed to think about chapters that have already been drafted but not written so where a structure already exists and where there could be more work on the structure or beginning of writing and then also maybe to to develop the chapters from scratch this is all going to be a bit self-organized so maybe there's one group with just one person who's responsible for chapter and then maybe one or two people join them for for discussing giving feedback in another case it could be a larger group of people yeah just divide the tasks decide upon the structure what are the figures what kind of references and so on so it can be very different between the different groups and of course once you once you start thinking about a chapter in a session you probably also have discussions then during during the day and and think about it yeah you can do that here without any obligation to continue after the workshop in the project but of course if you're interested you're very welcome to also become like a member or a contributor in the on the longer term and so after this introduction as Jacopo said some of you will stay here for the tutorial others the others will meet on the terrace and we will start talking about possible topics and groups there um to organize the sessions we set up a shared doc you have the qr code here your i think it's also it's it's in one of the emails that that we send so if you don't have don't know how to get access to this shared doc just just ask me and we also have um quite a few book authors uh here among us so i i'm not sure that this list is uh is complete i hope so i hope i didn't forget anyone um yeah so if you have questions you can also ask some of these people about their experiences and go on the shared doc you can uh feel free to put stuff there to write your comment so it's really a working document where we uh which we use for for practical exchanges um and for the actual writing there will be separate uh separate docs but everything that concerns the communication and coordination can be can be done there in a freestyle way and now i come to the possible topics that we could think about and the list is way too long so i'm just giving possibilities here and later we have to figure out what makes sense or where there's this interest um so first we have a couple of um potential chapters where we already identified people who would like to work on them so i um i put the um topics and some of the names um there were already more of you who who signaled a bit of interest uh beforehand so these are really the contact persons and we can talk more about this on the terrace then there are three topics which would be new chapters and that are really related to the um to to this course to this workshop um one is cell populations and population dynamics one is um communities symbiosis cross feeding and so on and the third would be cells that are not in a state of maximal growth but rather non-growing growing slowly doing other things and um i think this would be very good for the book because now it's all about growing fast which is interesting but it's way from being like it's not it's not all that we're interested in and i think also politically it's it will be nice to think about um states in which a fast growth is not the is not the aim or not the the main aim oops um then we also have a few chap existing chapter drafts on on different topics just possibilities and for the lecturers i thought that probably many things that you tell us could also be contributions for the book and one possibility if you like for the lecturers would be to think about one thing from your lecture that would fit into one of the chapters and write a little box about it so this could be just one page one uh one figure so not a lot of work and um yeah so you could you could have your little contribution that is directly related to your to your talk here and we can we can talk about what makes sense and how this could be added um okay and then there's also a couple of things that concern mostly the the book authors like the the actual organization team things that we need to discuss anyway so it's about graphics um then jupyter notebooks that we further jupyter notebooks that we want to collect and so on so i hope there will be some occasions for for us for the like the inner core group during this week or the next week to to have a little chat about this and of course everyone else is also invited to to join this is it um and for the rest i think we will just we'll just see what happens when we are on the terrace exactly so um just before we do the we do the division uh just a couple of announcements since then we are going to be in two different places so um this is the program as as you see so now we have the group on work and people that want to go can follow all from to the terrace and then we have the others can stay here for the first um tutorial and then at five we will have the poster session which is going to be just outside the door so probably there are already posters so at five just reconvene here for the poster and then you can stay dispersed discuss with the poster presenters and then we'll meet again today at six forty five on the terrace where we do a little game to know each other that Wolfram is coordinating and Elad is coordinating yes i don't know about the game but i'm very curious so um but there is enough space and then just after that we are gonna


Good morning. We are going to give the second lecture on developmental neuroscience today. The first one was lecture three. Ralph Adolphs did a marvelous job of providing you with an overview. Now that you have a little more experience thinking about molecules and neuroscience, and now that the excitement associated with the Nobel Prize has decreased a bit, I put together this second lecture on developmental neuroscience molecules and mechanisms. Let's go over then the first set of principles that Ralph Adolphs gave you during lecture three. Some of the principles actually derived from the introductory chapters of Kandel. Then he also showed you real human brains during discussion sections, which was as fascinating to me as it was to you, and then began some of the material in chapters 52 and 53. So now let's continue and emphasize these additional points from Kandel. The chapters are very nicely organized by major headings, which are declarative statements in blue. I expect you to be familiar with those declarative statements and to be able to find one example of each declarative statement with the exception that we don't talk about the differences between axons and dendrites. Also in later lectures, we're going to talk about this nifty topic that the development of visual perception requires visual experience, and we will not discuss sexual differentiation of the nervous system at all just because we don't have time. We will certainly talk about repairing the damaged brain in later lectures, and we will certainly talk about the aging brain mostly in the context of neurodegenerative diseases in later lectures. But for today, I'm going to give you a whirlwind tour of these four chapters in Kandel. Going back to this very interesting theme of the Hox genes and homeotic mutations, this word homeotic means a mutation that transforms one body part into another. Here, for instance, is a cross-section of the hind brain of a mouse.  These are the bulges of the developing neural tube within the hind brain region during development. Now, in a wild-type mouse, in a wild-type mouse, one of the eight units, projecting outside the brain, in this case, the trigeminal nerve, and the facial nerve, the rhombomers are numbered one through eight. A Hox1B mutant mouse has an interruption in the Hox, sorry, B1 gene. Ralph told you, and I will emphasize today, that we have distinct ways of describing genes, which have really developed historically. If the gene is in a fly, it's all lowercase. If it's in a mouse, it is capitalized, the first letter, and if it's in a human, all letters are capitalized. That's the way things have grown up, and you can't change this. Well, I don't have the energy to change this. So, what does a Hox1B mutant mouse means? It means there's been an interruption in the HoxB1 gene, less HoxB1 protein. The result of that mutation, less HoxB1 protein, is that in a rhombomere where HoxB1 is strongly expressed in the wild-type, it is not strongly expressed in the mutant, and the result is that the default pattern for this rhombomere number four is that it has a pattern very similar to that of rhombomere number two. It sends its axons to and from the trigeminal nucleus. So, a homeotic mutation transforms one body part into another. That's the definition of a homeotic mutation. We should point out that homeotic is a general statement for phenotype, that is the phenomenon that results from a genotype. So, that phenotype is homeotic, the genotype is a mutation in the HoxB1 gene. For those of you who have not yet taken the HoxB1 gene by 120, by 122. Of course, the facial, the cranial nerves have been named for hundreds of years. Some, and there are various mnemonics for how to remember those cranial nerves. Most of these mnemonics are scatological, and you can read some of those scatological mnemonics here in Wikipedia, the olfactory, et cetera, down to the 12th nerve, which is, I believe, hyperglossal. No, 12th nerve. I'm not sure what it is. Anyway, you can read and you don't need to memorize this. It's for your own edification, but if you're going to go to medical school, you'll have to learn this sooner or later. So, a rhombomere is one of the segmental units. You could also call it a bulge. The reason that a rhombomere forms, the reason that the bulge forms is that the neurons in the center of the rhombomere proliferate a bit faster than the ones at the edges, so it bulges out. So, these are homeotic mutations and the genes have these names. And let's go on to analyze the homeotic gene a little more. A little bit of terminology, most homeotic mutations, that is, transformation of one body part to another, occur in genes which are transcription factors. A transcription factor is a gene whose gene product, the protein, controls the expression of another gene, typically by binding to DNA. So, all transcription factors are DNA binding proteins. All Hox genes contain a homeodomain, which is in the protein, and it's a type of DNA binding protein domain. And naturally, all homeodomains are found in transcription factors because transcription factors are by far the largest number of proteins that bind to DNA, although some of the chromatin proteins do as well. So, Hox genes have DNA sequences in them called homeoboxes which encode homeodomains. So, we have Hox genes, we have homeotic mutations, homeoboxes and homeodomains, and evidently, the H in Hox gene comes from homeotic mutation. Kandel and many other books show you details of a slide that Ralph Adolfs has always shown you on regionalization of the nervous system, in drosophila, fruit flies, and in mammals. So, there are Hox genes, depending on how you spell them, both among invertebrates and among all known vertebrates. Among vertebrates, there are actually four clusters of Hox genes in mice. They are on different chromosomes. Presumably, chromosomes arose by duplicating each other many times, often in vertebrate genes. So, this is like a figure in Kandel. The Hox genes then control the identity of segments, rhombomeres in the hind brain. Interestingly enough, this in the drosophila, the antedipedia complex is among the Hox genes. There's also the bithorax complex discovered here at Caltech by Ed Lewis. Okay, now, here's a tough one for today. Which body part do you think is duplicated in bithorax? Nobody wants to hazard that one. Yes, it's the thorax. Okay. So, the mutation in the bithorax gene produces two copies of the thorax. And of course, the Hox genes encode transcription factors which bind to DNA and have homeoboxes that participate in the binding to DNA. And Hox gene expression along the anterior posterior axis determines cell fate. And furthermore, Hox gene expression along the body is collinear with the Hox gene order along the chromosome. So, at the three prime end of this chromosome, we have the most anterior genes, and at the five prime end of the DNA, we have the most posterior genes. So, just to put the Hox genes in context, the Hox gene expression patterns produce rhombomere borders. There are other gene transcription factors that control themselves control the expression of Hox genes. And then there are other target genes for the Hox proteins that have rhombomere specific expression patterns. Those include the f-kinases and the efferens. And you may remember that we have discussed the f-kinases and the efferens in the context of axonal pathfinding, more of which we will discuss later today. Okay. So, question for class discussion. I've never asked this before, and so the answer is open. What is the selective advantage of having gene clusters that confer selectivity in neural development? I have not looked up the answer to this question, so let's have some ideas, and I don't even know if the answer exists. Any ideas? Yes, Matthew. So, Matthew has suggested that if the genes are all transferred at the same time, presumably from one organism, which is arising as a species from another, having them all there prevents one from being deleted. Okay. Okay. I like that very much. Any embroidery on that? Any further ideas? Well, wouldn't you say that having just one Hox gene does no good at all, or even two or three? So, we need a number of genes to make a pattern. So, we need a number of genes to make a pattern, and the most robust way for a nature pattern, for instance, to make the eight rhombomeres, we need six or eight genes, and so the most robust way for nature to do that is by transferring them all at once. So, I think you were saying part of the idea, and I simply completed the idea. Any other ideas? Okay. So, let's take that one and use it next year for the course, or write a paper about it. Good. But, we still have this question, number two, which is the selective advantage of co-linearity in the Hox genes. What is the advantage that arranging them from 3.5 that they have the same order from 3 prime to 5 prime as the body segments? I want you to realize that I don't know the answer. So, give me the answer. Come on. You guys could all warm toast with your brains. Give me the answer. All right. Well, if you think of it, email me. Okay. The next 10 slides or so, we're going to discuss growth cones and the molecules that bind them. So, this is somewhere between Ralph Adolf's question. Okay. We got to the vicinity of the target. How do we refine our destination at the target, and how do we make the correct synapses? And so, let's have some terminology here. The leading edge of a growth cone, of a growing axon is called the growth cone. And you've seen some wonderful pictures in Candel. It spreads out and gets very thin. And the growth cone has microtubules and extending into its base. I'll show you a picture of that. But, it's Lamellae in Philadelphia. The end of the growth cone have only actin filaments, which are a lot daintier than microtubules. So, Lamellae is a double parallel membrane. So, it's a thin extension that doesn't have much. And the filipodia is filamentous little feet. That's what filipodia means. Okay. So, when a growth cone is moving rapidly along a pathway, it has a narrow profile. But, when it makes decisions at a junction, it radiates filipodia and becomes wider and more complex. And the adhesion molecules on the filipodia contact the substrate. Now, in an experiment in vitro, the substrate would be a culture dish. In life, it's the surface of other cells. And that helps to nucleate actin polymerization. Then microtubules invade the region with a newly stable actin cytoskeleton. Moves the axonal shaft forward. There are, and I'm going to show you a diagram of this in a moment. So, mini-cell surface molecules function in growth cone guidance. And many are conserved, which is really cool, between invertebrates and vertebrates and among vertebrates and among invertebrates. Now, the context, and Ralph has emphasized this as well, the context of the Q given by a given molecule can either be guidance or guidance receptor. And the result of this contact can be a version or attraction, depending on the context, very much the way a transmitter molecule can be either excitatory or inhibitory, depending on its receptor. Looking greater detail, I've combined several versions of candel to give you what I think is the clearest view. So here is a growth cone. And the theme here is that there are several types of motors. We have a few microtubules invading the growth cone. And if we look in greater detail, here is one of the microtubules. And the microtubule through the membrane of the growth cone has adapters that allow it to contact a substrate, either a culture dish or another cell. The microtubules, as you know, from bite by nest can extend themselves. And this makes the growth cone a little longer. And then desiccalfusion adds membrane to the leading edge of the filipodium. After a while the cytoplasm in the trailing edge of the filipodium contracts. And so we have a new growth cone, new axonal growth, which has moved the, which has moved the growth cone forward. And this is helped by actin polymerization. So we have a couple of engines, motors. We have microtubules being polymerized and deep polymerized, mostly polymerized here. We have actin forming and being dissolved and moving forward. So our growth cone is a very complex machine. And it is constantly sampling the environment and making decisions about where to turn or where to avoid. So among the families involved here are two of the most famous. There are generally called cell adhesion molecules, sometimes just cams or cell adhesion molecules. They have immunoglobulin domains or they have fibronectin repeats. They're all single past transmembrane proteins. So what we are looking here at here is cell number one and cell number two. And here the cell adhesion molecules are extending through the membrane. Some of the cell adhesion molecules called canterans mediate calcium dependent adhesion. They also signal in various ways inside the cell and are attached in various ways to the actin cytoskeleton. So we shouldn't see a cell adhesion molecule is simply anchored in the membrane and allowing the cell to float around it. Actually, these molecules all get anchored to the cytoskeleton and in some places can influence the formation or breakdown of the cytoskeleton. For instance, here's a cyclic AMP signaling system. This is a guanylate kinase signaling system. So in terms of growth cone guidance, growth cones can respond to attractive guidance cues. That's green by increased outgrowth or by turning toward the cue source. We've seen that. They mostly respond to repellent guidance cues by collapsing. The guidance cues can be diffusable and we haven't seen those yet. There are examples in cantile and cell surface and we've seen two examples of those. So they're either proteins. Again, they are single pass transmembrane receptors or small molecules. And I will give you an example of that later in the talk as well. So growth cones can be guided by these various phenomena and they are propelled then by their motors. Let's turn to this very interesting topic that Ralph also brought up, which is chemo affinity. You remember that he discussed Roger Sperry's chemo affinity hypothesis, which was derived from cutting optic nerves to the frog and watching the behavior of the frog. Some of these experiments were also done in Goldfish in the optic tectum, which is the lower vertebrates equivalent of the superior colliculus. And so Sperry said, whenever fibers were disconnected and transplanted or just scrambled, regrowth always led to orderly functional recovery. And so Sperry said, it seemed a necessary conclusion from these results that the cells and fibers of the brain must carry a kind of individual identification tag. And Ralph's heart of the story are the efferents in the eff kinases, which are basically not chemo affinity, but chemo repulsion. And so this is a modification to the Sperry hypothesis in which a gradient of molecules repel each other. And there are various experiments that Ralph told you about, about transplanting one region of the tectum to another and finding that the usual partner avoids that region. And so all of these are phenomena associated with efferents, which are the peptid ligands, and the eff kinases, which are the tyrosine kinase receptors. Well, chemo affinity molecules, not repulsive molecules, but chemo affinity molecules, these would in principle allow a much more selective pairing between cells. And so for this, we turn to the fly visual system run by Kaisen's lab. In fact, these experiments are just going on. They will be published soon. Kaisen is a Caltech professor, and he has collaborated with non-Caltech people. And he has solved the chemo affinity problem, found a group of genes, which were previously called the defective proboscis extension response, DPR.  And you know from looking at the spelling of the gene that this is an invertebrate. And in fact, this is Drosophila. So there are 21 DPR genes, and they interact with nine DPR interaction proteins. And since they're called DPR interaction proteins, they are labeled DIPs or DIPs.  And so you sometimes just name them with what they bind to. There are addition, in addition, the DPR and the DIP complex interacts with a leucine rich repeat, CDIP. Okay, so search for the chemo molecules in the fly visual system involves the retina of the fly, the laminar, which is a first stage below it, the medulla in the inner medulla, the molecules that Zin and his collaborators have identified govern interactions among the cells, finding their postsynaptic partners in several of these layers. The interactions between these molecules. So this is a DPR molecule. And here is its binding partner, DIP. This is a particular DPR molecule, cleverly enough called DPR6, and a particular DIP molecule. They make a typical, a pattern that is similar in the nervous system and in other organs throughout the body among vertebrates and invertebrates. For instance, there are C. elegans synapses that have the tips of these two molecules interacting with each other. The function of the gene family in C. elegans has not been described the way it has in flies, but there certainly is a similar molecular interaction. And even in the immune system, molecules that neutrophils that contact other cells have a similar interaction. So again, the DPR6 molecule in blue, the DIP alpha molecule in red, the two of them interacting with each other. So this is the chemo affinity part right here. This is the specific labels on one cell contacting another cell. The interface is interestingly enough almost all hydrophobic. The molecules have to fit together. They have various amino acids in one part and another part that allow them to fit together. And so this then becomes the chemo affinity mechanism at least among fruit flies. Moving on, so that's a rather nice story about Sperry's hypothesis and it really is quite a breakthrough. And those slides were provided by Kaizen. In addition, there are other molecules involved in growth cones. There are the semaphorens and the netrons. Again, they can mediate either attraction or repulsion. So this figure, which is like a figure from Kandel, has a nice growth cone extending its filipods, sensing the environment in here. As a result of a semaphoren interaction, this growth cone has retracted and it's not going to go in this direction anymore. Again, the semaphorens and the net here, the semaphorens are either attached to one of the cells by a single past transmembrane protein or it can be cleaved from that single past membrane protein and diffuse highly locally and interact with the receptors, their heteromultimers, between a molecule called a neuropillan and a molecule called a plexon. And so the semaphorens interact with the receptors in ways that are not yet understood but do cause growth cone attraction or repulsion, either effluorescence of the growth cone or repulsion involves actin depolymerization, the growth cone collapses. Attraction may involve the formation of new actin filaments as the growth cone extends, and there are a number of small molecule GTPases that seem to be involved in making the actin depolymerize or grow. They are called row GTPases and we're going to talk about other G proteins but the small molecule GTPases are different. So simplified view would be that one of these small molecule GTPases row favors collapse and rack favors growth but that may be too simple. So as usual we have complex signal transduction systems, you won't be responsible for knowing these signal transduction systems but as I write the development question for the midterm, I'd like you to be able to find an example of one or more of these. So in addition, let's go to the other topic of the nerve muscle synapse formation. You may remember that in previous lectures we said that many basic principles of chemical transmission were discovered at the nerve muscle synapse and I might add that many basic principles of synaptic development were also discovered at the nerve muscle synapse. So here we have the motor neuron making the end plate or the nerve muscle synapse and this is all a figure that you've seen before from Kandel. We've also seen from Kandel this highly organized figure of the presynaptic terminal, the glial cell in the postsynaptic folds and so now one asks the question how does all this arrive and how does all this arise and the answer is as you several steps. The growth cone reaches the muscle fiber, we've discussed how that occurs, it reforms to make a semi-flat contact with the muscle fiber. A hero of the story very much is the basal lamina that's different from the lamina we discussed in the Drosophila retina which is actually a group of cells. This is a kind of extracellular matrix and it begins to form. Receptors for acetylcholine then cluster under the forming synapse, the nascent synapse. The Schwann cell comes in and wraps the synapse. In the beginning and this is going to be a common theme. Several axons innervate the muscle but later all but one withdraws. So at the mature synapse we have the three cells, the motor neuron, the muscle cell, Schwann cell. Between these cells we have the basal lamina, the postsynaptic membrane is infolded, the acetylcholine receptors are at the top of the folds, sodium channels at the bases and acetylcholine esterase is in the basal lamina. We've said all of this before, acetylcholine esterase. I haven't told you that the acetylcholine channels are at the bases of the folds but they are. So how does all this occur? Acetylcholine receptors which are normally not very well localized before the nerve fiber arrives become localized underneath the nerve fiber. There are several mechanisms. First of all the nerve secretes signals that cluster pre-existing receptors at the synapse and I'll tell you about that in subsequent slides. Also the nucleus as you know a muscle fiber is a fusion of many cells with many nuclei. So this is a cell that has many nuclei and there are signals that tell the nuclei near the synapse to make additional acetylcholine receptors and also receptor expression gets turned off at the other nuclei. All of this is amplified by action potentials in the muscle fiber which presumably occur only if the synapse is working and the presumption in almost every case for activity dependent signaling in the nervous system is calcium influxes either directly toward by the receptor itself or produced by action potentials which activate calcium channels. So here we have the acetylcholine receptor transcription increases but away from the synapse it decreases. Excuse me that phone call was from the person who installed an alarm in our house yesterday so I should tell him. I mentioned the basal lamina of connective tissue collagen like tissue extracellularly. A very interesting set of experiments that go back several decades is that if you cut the nerve destroy the muscle the muscle fiber that's pretty interesting and it turns out that some of the attractive cues occur because while you have destroyed the muscle fiber but you have kept the basal lamina intact and so it is actually the basal lamina a particular laminin variant that is enriched in the synaptic extracellular matrix that attracts the nerve back. How this all occurs is not entirely clear. One of the signals secreted from the nerve is called agrin, eating protein, activates a postsynaptic tyrosine kinase called musk muscle specific kinase which in turn activates another molecule called rapsin and the rapsin actually physically clusters the receptors in response to the nerve. So if we have a cultured muscle fiber with no agrin it has uniform acetylcholine receptor uniform acetylcholine receptor density but if we add agrin those receptors cluster. So rapsin is an abbreviation for receptor associated protein at synapses. Again you have to name these something. There are a few molecules then necessary for clustering acetylcholine receptors and really these clustered acetylcholine receptors and the development of the nerve muscle synapse is actually a lesson for the development of all synapses. So in a wild type mouse you have these wonderful plaques in plates that are nicely compact along the nerve. In an agrin knockout even though the main function of agrin is said to be postsynaptic those exons spread out looking for other synapses and does anybody here want an explanation of what a knockout mouse is? Okay a knockout mouse Ellen is a mouse whose genome has been modified to interrupt a particular gene so that gene has been knocked out. The mutants that we discussed earlier in this lecture such as the homeob the home the hox gene mutants are naturally occurring knockouts typically. Sometimes those knockouts are helped along by irradiating the parents so that there are more mutations caused but in any case those are that's the way that one does forward genetics by knocking out genes. Now in a mouse it's a little more complicated you need to do some fancy molecular biology to knock out a specific gene but you can do it and so if you want to get rid of the action of agrin best way to do it is to knock out the agrin gene this is done with base pairing and other ways to manipulate DNA. A musk knockout gene has a very similar phenotype and the rapson knockout has a bit more compact exons but still nothing like the wild type and so we need the function of all three of these genes to have a nice well organized nerve muscle synapse. Any questions again the phenotype I've just showed you differs from the genotype which is the knockout of the gene so the phenotype is the phenomenon associated with the genotype the knockout of the gene it is possible as many of you know to produce much more subtle changes in genes than simply eliminating them entirely you can make one more active you can change its function etc but for today we're just talking about eliminating the gene yes sir so the question is what is the difference between knockdown and knockout a knockdown experiment is typically done in the animal after birth and it's a partial knockout the way it's done is typically by injecting RNA that base pairs with the RNA made by the animal this causes a set of enzymes to come and destroy the endogenous RNA so the knockdown experiment is easier to do because you don't have to work with embryonic stem cells and with lots of mouse mutations but it takes a lot of experimentation to get the right knockdown simple hairpin RNA so that it does a good job of knocking down a knockdown experiment is rarely complete but usually informative enough to give a phenotype any other questions called acetylcholine receptor inducing activity which actually makes more acetylcholine receptors it was first discovered and called aria acetylcholine receptor inducing activity discovered at the nerve muscle synapse secreted by the nerve it is a member of an extremely interesting family called the nuregulans nuregulans is a transmembrane protein which is proteolyzed to release a growth factor and it is really the founding member of the nuregulans family because this family has been implicated strongly in schizophrenia we'll get to that later on when i talk about schizophrenia egf is epidermal growth factor now we come to the topic of synapse elimination during a baby's first two years of life those 10 to the 11th synapses uh those 10 to the 11th neurons are getting an average of a thousand um synapses a piece 10 to the 14th divided by the number of seconds in two years come you get to the conclusion that you get about a million synapses forming per second actually more than that form because many are eliminated and so as we said a few minutes ago uh growth cones typically get directions not to innovate specific muscle fibers but only a group of fibers so this is called polysynaptic innovation it typically just disappears soon after birth uh and it is a competitive process the neuron that's best able to drive the muscle wins out to become the sole neuron so each neuron then commits its resources to a group of fibers and it abandons the others it had initially innovated and you can bias this with various chemical and activities so obviously this is an extremely interesting phenomenon and one of the hypotheses one of the mechanisms of synapse elimination is called the limiting neurotrophic factor hypothesis here not at the muscle but in a peripheral ganglion when gets the same kind of thing more neurons appear than are required to innovate the target cells and there is a hypothesis that the target cell has a limited supply of a neurotrophic factor that is a factor that allows neurons to form and as ralph told you uh during lecture three one of those neurotrophic factors is nerve growth factor NGF uh the neurotrophin uh then acts uh there are several examples of neurotrophin NGF is one of them another one is called appropriately enough neurotrophin number three another one is called BDNF that's mostly in the brain another one's called glial derived neurotrophic factor uh they distinct sub types of neurons then depend on different neurotrophic factors there are four major ones actually there are many major ones and they are listed here fiberglass fiberglass growth factor glial derived neurotrophic factor number three uh and um NGF ralph showed you this slide which is the tyrosine receptor kinase class of receptors for neurotrophins we've named a couple of these neurotrophins here uh they are uh four uh they are there are four of them recognized by three TRKs tyrosine receptor sub types uh they're actually less specific that specific than one would like there is some crosstalk between them so neurotrophins regulate neuronal survival they regulate proliferation of precursors differentiation growth branching transmitter synthesis synaptic efficacy and rearrangement and uh BDNF is one that is particularly interesting to neuroscientists these days because it may in fact be a pretty good antidepressant but when there is by acting on track B tyrosine receptor kinase B but also too much BDNF causes epilepsy so again the context in which a growth factor a neurotrophin acts is important and the time that it acts is also important so BDNF brain derived neurotrophic so trans signaling pathways are rather complex uh they all involve tyrosine phosphorylations that's why they're called TRK here's the plasma membrane ultimately many uh neurotrophin pathways lead to the activation of transcription factors by phosphorylating them into the activation of target genes that's pretty interesting because in addition other growth factors instruct cells to continue in the cell cycle so we have growth factors that tell a cell to continue in the growth in the cell cycle by activating genes associated with proliferation and with division of neurons and so this can turn in and of course this is the basis for which some uh TRK genes are all oncogenes because they continue to tell a cell to participate in the cell cycle and cells to proliferate even when they should not so some growth factor receptors are indeed oncogenes they can cause cancer we also should mention notch signaling and I'll briefly say that notch and delta signaling occur because the notch and delta uh partners in a cell uh they are polarized but all cells in a region may express both notch and delta however the ones in the middle of the region seem to express slightly more delta and slightly less notch and so a signaling imbalance occurs and the neat thing about notch and delta is that they reinforce each other so that uh notch decreases the activation of delta and as a result one gets a sharpening of a boundary uh so one can now sharpen a boundary in another way we have the f in the efferents the f the efferents in the efferent kinases we have this wonderful set of cell adhesion molecules and then we have boundaries which are sharpened by lateral inhibition uh and michael elowitz at caltech with his mastery of transcription factors mastery of gene activation and of differences between cells is making nice contributions to this pathway even though he does not consider himself a neuroscientist um two more points first there's a famous example discovered by paul paterson here at caltech in which you can actually change the phenotype of a cell that is whether it's cholinergic or adrenergic depending on the target the target secretes neurotrophic factors for instance the most famous example is the sweat gland and the sweat gland is at first during development is adrenergic the sorry the neuron that innervates it is adrenergic but based on the neurotrophic factors that it releases the sweat gland induces the cell to become cholinergic to release acetylcholine and the result is that acetylcholine becomes the major transmitter activating the sweat glands so this switch takes place after birth after the cell has reached the neuron has reached the target and has innovated the target final complication in developmental neuroscience and i promise that this is the final complication at least for today is that cells can actually change whether they are excited whether they are excited or inhibited by GABA we usually think of GABA as an inhibitory transmitter that depends on having a high internal chloride concentration the internal chloride concentration is governed by pumps the cell starts out in many cases with a low chloride concentration sorry just the reverse it starts out with a high internal chloride concentration that means that the chloride in the cell intracellular is equal to the extracellular chloride as a result the Nernst potential for chloride is near zero so that early in life in many cases GABA actually produces depolarizations and activate cells and then when the full complement of pumps for chloride and bicarbonate get established in the cell the intracellular concentration of chloride drops the chloride gets pumped out by transporters as a result we have more chloride outside than inside the same is true for sodium but the sign of chloride differs from that of sodium as a result the Nernst potential for chloride is actually quite negative and so chloride becomes a GABA which activates chloride channels becomes a hyperpolarizing or inhibitory transmitter and the result is that we have a switch from excitatory actions of GABA to inhibitory actions of GABA this is thought to be important in whether early on in life a cell gets activity dependent signals that help it to develop normally so again these are all examples that I'd like you to look at in candel but you won't be responsible for regurgitating many examples for each point and I will have my office hours as usual outside the red door today see you Wednesday