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This year, there are a few things I will be doing differently.
1) The other teacher teaching Algebra I (she teaches HS and I teach the 8th grade section) and I decided to rearrange our Alg I curriculum. While I have taught Algebra every year since I began teaching, it will be a challenge (and interesting) to change the order of things. We are using a Common Core edition of our textbook to lead the changes we make. I will also be trying to push my 8th graders more than I did last year. This means faster, more challenging, hopefully making them more independent and not afraid to go for it!
2) I am having students write down daily objectives, mark whether they understand after the lesson, and explain or give an example that illustrates the objective(s). Thanks Pinterest for this…it's based off of a first grade teacher's idea via her blog. This will not only help me stay on task, but it will help them see what we covered in any given week. They will fill this out Monday through Thursday, have it to study from for their quiz Friday, and we can go over issues Friday (before quiz).
3) I am making a much bigger effort to have Warm-Ups every day. One of my classes is for Juniors, and part of my job is prepping them for the upcoming PSAE (IL's state assessment). Again, I made a weekly form and am hopeful that that will keep people more accountable to their work. Today's question, for example, was an ACT question. I will also incorporate skills we have learned recently, or review a skill that is necessary for that day's work.
4) Less in class homework time, but more in class practice (structured). Our class periods are 43 minutes, so by the time they write objectives and do a warm-up, we're down to about 38 minutes. This doesn't leave much "let's get started on the assignment" time. I have worked really hard this week to include in class practice so that HW can be shorter, and we don't need to start it during class.
There you have it…a few old ideas that I am trying to do a better job of implementing.
PS…any suggestions on how to best utilize 43 minute class periods?? (Forgot to mention I'm a traveling teacher…so I am never in the same classroom back to back, and passing periods are 3 minutes!) Help wanted/needed!!


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Newton: Hey, our site is wearing a costume for Halloween!
Ashton: That's not a Halloween costume. That's the reason the head peep was at the computer so much recently and used a lot of HBO words. It's the new theme for our site. She says it's better for everybody who visits us on their mobile devices, especially phones.
Newton: People come to visit us on their phone? How do they do that? Did you see how hard it was to stand on the iPad?
Ashton: Sorry, I wasn't really looking. I was hanging out with my new boyfriend. He's kind of sweet on me. Do you think I should play hard to get like I do on vet day?
Have a safe and happy Halloween, friends!

subset: commoncrawl


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Boys Basketball
Chaminade's Jayson Tatum highlights star-studded field at Highland Shootout
In the eight years local organizer Matt Powers has been helping put together the Highland Optimist Shootout, and despite near constant star-level talent and teams, there has never been a complete sellout.
That could change Saturday thanks to an appearance by the Chaminade Red Devils from St. Louis and their No. 1 attraction, 6-foot-9 junior Jayson Tatum. Besides being the No. 1 junior prospect in the country according to Scout.com, Tatum does things that most 6-9 players can only dream about.
"We've never sold this out, but this is a unique year," Powers said.
Tatum is averaging 27.2 points and 9.7 rebounds per game, but also leads the team with 19 3-pointers and 40 assists. He can take defenders right to the rim off the dribble with no problem. Last Friday, Tatum rocked powerful (Lincolnshire) Stevenson from Chicago, the top-ranked 4A team in Illinois that includes All-American point guard Jalen Brunson, for 39 points and 14 rebounds in an 88-81 victory.
That game was in Wheeling, W. Va., and included Kentucky coach John Calipari in the stands as his Wildcats are among 10 finalists for Tatum. Among the others are Duke, North Carolina, Kansas, Arizona, Connecticut, Illinois, Missouri and St. Louis University.
"He's versatile, he's a great rebounder, he can create a shot from anywhere and can create shots for others," Chaminade coach Frank Bennett said. "He's completely unselfish and is the consummate team player. He's always looking to get other people involved. When one of your best players is doing that, you're on to something good."
Tatum and Chaminade are the marquee game at 5:15 p.m. Saturday against a 9-2 (Chicago) St. Rita squad led by Kentucky recruit Charles Matthews, Myles Carter (offers from DePaul, Memphis and Providence), Tulane recruit Kain Harris and Tennessee State recruit Armani Chaney.
Chaminade has five players above 6-6 on its roster, including 6-9 junior Division I recruit Tyler Cook (13.2 ppg) and 6-10 junior Will Gladson. Cook already has offers from Kansas, Florida, Michigan, Michigan State, Missouri and St. Louis U.
St. Rita is ranked third among Illinois 4A teams. St. Rita's only two losses are to nationally ranked teams (St. Joseph of Westchester and New York's Christ the King). The Mustangs also have beaten state powerhouse Chicago Simeon.
"I think that game alone will definitely be standing-room only," Powers said. "It's not only just Tatum, but who they're playing. We've had more demand for advance tickets than we've ever had by far. I think it's because of the opportunity to see him play against the kid that's going to Kentucky. Between both teams you've got eight Division I kids.
"We're planning on setting up some additional seating."
That's almost mandatory since Saturday's attractive schedule highlighted by Chaminade-St. Rita figures to pack the 3,000-seat gymnasium. Tickets are $8 for adults and $5 for students.
Powers said his dream Shootout matchup for next year involves getting Chaminade back to play against Althoff, which will return all but one player from a 12-1 team ranked fourth in the state in 3A.
"I'd like to see that happen, but they've got a lot of people pulling at them," he said.
The 24th annual Highland Shootout continues to be among the most popular in the region. It has given local fans a chance to watch more than 50 eventual Division I players and more than a dozen future NBA players.
A look at other shootout games:
Normal vs. East St. Louis, 1:45 p.m.: Normal was 11-0 before Friday and ranked sixth in the latest 4A state poll. Among Normal's top players are 6-8 Elon recruit Tyler Siebring and 6-7 Division I prospect Alex Peacock, who has an offer from SIU Edwardsville. East St. Louis (9-4 before Friday) is making its eighth appearance at Highland and brings one of the nation's top sophomore prospects in 6-11 center Jeremiah Tilmon (11.7 ppg). The Flyers' other top scoring threats are Antonio Johnson (9.2 ppg), Antony Johnson (8.4 ppg) and Tyrone Riley (7.8 ppg).
CBC vs. Mater Dei, 3:30 p.m.: CBC (6-4 before Friday) is coached by former St. Louis University standout Justin Tatum, father of Jayson Tatum. The Cadets are led by Division I prospects Jordan Barnes (14.3 ppg), Christian Willis (15.6 ppg) and 6-7 senior Kenny Lesley (14.3 points, 8.3 rebounds per game). Mater Dei (8-5 before Friday) has an extremely tall lineup led by 6-8 senior center Nolan Gerling (17.1 points and 7.8 rebounds), 6-4 senior Ben Lampe (12.5 ppg) and 6-7 senior Zach Haake (11.5 ppg).
Highland vs. Fort Zumwalt North, 7 p.m.: The host Highland Bulldogs have only one senior on the roster and are led by junior guard Austin Elledge (14.4 ppg, 34 3-pointers) and junior Brode Portell (7.9 ppg). Austin Peay recruit and senior Zach Glotta (21.9 ppg) is the top player for Fort Zumwalt North.
Highland vs. Jerseyville (girls), noon: The event kicks off with the 14-1 Highland girls team coming off a win over previously unbeaten and 2A top-ranked Central taking on Mississippi Valley Conference foe Jerseyville. Amanda Ponce (13.1 ppg) and Olivia La Porta (11.6 ppg) are the top scorers for Highland, which beat Jerseyville 67-34 earlier this season.


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National Bagelfest Day
THE HOLIDAY: This crunchy on the outside and chewy in the middle bread is very popular in the USA and Canada. Served with a variety of toppings as well as produced in a variety of flavors, bagel shops are a staple in most communities across the country. More
THE ARTIST: Michael Miller


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November 20, 2013
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October 12, 2013
December 7, 2017
Chief Futurist, Cisco
David Evans is chief futurist for the Cisco Internet Business Solutions Group (IBSG). IBSG works with the world's leading companies to help them become more competitive through effective business processes and technology deployment.
A Cisco veteran of more than 21 years, Evans joined IBSG from IT,where he most recently managed the global architecture innovations team, focusing on IP telephony, unified messaging, wireless, networked home, and Internet-related technologies.
Evans has a passion for applying technology innovation to real business needs. He is also respected outside Cisco as an expert in emerging technologies and has numerous relationships with thought leaders, including those in the venture capital community.
Evans has garnered numerous awards and recognitions throughout his Cisco career, including the CEO's "Unsung Hero" award, which he has received twice, and numerous other awards for technology innovation and teaming.
Prior to Cisco, Evans held varied IT positions at both AMD and MMI. Evans has pursued computer science and computer engineering at San Jose University in San Jose, California.
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NEW YORK (CBS.MW) -- News Corp.'s News Digital Media unit said Thursday it will form an investment arm to bolster its Internet holdings.
The division, to be called News Digital Ventures, will make venture capital investments in the Internet category to "leverage News Corp.'s global marketing and distribution platforms," the company said in a statement.
News Digital Ventures will be headed by Kathryn Fink, who will serve as its president.
Fink had been News Digital Media's senior vice president since November 1997.
In that capacity, she managed the business operations of the company's Internet sites, including FoxSports.com, FoxNews.com, FoxMarketwire and Fox.com.
"Creative partnerships and investments are critical in building and extending our digital media assets," said James Murdoch, executive vice president of News. "Kathryn has a deep understanding of News Digital Media and a stellar track record with Internet investments. The creation of News Digital Ventures gives us a vehicle for building on an already substantial base."
U.S.-listed shares of Australia-based News NWS, +0.29% rose 1 1/8 to 36 7/8.


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Review: Tots Bots Easyfit All-in-One Diaper*
Product Name: Easyfit All-In-One
Company:Tots Bots
Country of Origin: Glasgow, Scotland
Materials:Exterior: 100% Polyester with Polyurethane Laminate; Interior: 50% Rayon from Bamboo, 50% Polyester
Diaper Type: One-Size All-In-One
Weight Range: 8lbs - 35lbs
Height of front rise at each setting (approx.):Infant - 14cm (5.5"); Medium -15.5 cm (6"); Toddler - 17cm (6.75")
Dry weight: 110 grams
Saturated weight**: 283 grams
Absorbency: 173 grams
Available at: Extraordinary Baby Shoppe
Price: $24.75
The Tots Bots Easyfit All-In-One is a great addition to any diaper stash. It is a one-size diaper, intended to fit from 8lbs to approximately 35lbs, and is stuffable for extra absorbency -- a great option for overnights, naps, or other times when a little one may need to be in a diaper longer than usual.
The combination of bamboo rayon and polyester microfiber in the interior of the diaper provide lots of quick-wicking absorbency without compromising on a trim fit. My boys tend to be heavy wetters, so this being stuffable holds a lot of appeal for me. The moisture-proof PUL exterior seems more durable than other PUL covers I've used and it comes in a selection of awesome colours.
The interior is constructed with a special "wick-proof" zone around the absorbent core -- preventing moisture from wicking around the gusset. The absorbent core is cleverly designed as a stuffable "tongue" to allow for optimal washing and rinsing, and allowing it to be folded in a way to place absorbency where it is most needed.
I really like that this diaper uses environmentally-friendly fabrics and is made somewhere other than China. As a consumer, that's something I'm willing to pay a bit more for, though this diaper is comparable in price to some well-known "Made In China" pocket diapers. Something else that I really appreciate is that it isn't lined with a stay-dry lining -- many higher-end diapers are lined with fleece, which allows moisture to pass through into the absorbent core while keeping a dry surface next to the skin. I can always add a layer of fleece if I'm using it overnight, but I want my baby to associate peeing with feeling wet. The texture of the bamboo rayon helps keep any poop "explosions" to a minimum.
I found the fit pretty good, even on a 7lbs6oz newborn (see right) -- clearly, I couldn't wait for my little guy to hit 8lbs before trying out the diaper! The fit is much better now at around 9lbs (see below). It's one of the trimmest pocket/AIO diapers I'm using right now, making it a great choice for the diaper bag! I find that to get the best fit and absorbency for overnight, I need to add a doubler to the pocket, though.
The only cons I see for the Easyfit are as follows:
While I like the fit of the diaper with the extra-wide velcro, I find the tabs often open in the wash -- particularly the 2-sided tab. The polyester anti-wicking fabric inside roughs up very easily from the velcro -- this doesn't impair the function of the diaper, but it does affect the appearance a bit. I also don't care for the feel of the fabric.
The diaper is not absorbent enough for overnights without adding an insert. It is great for daytime use, but overnights require a bit more. It would be nice if the diaper came with its own additional insert, but anything can be added if necessary. This is a minor drawback, really, and I fully admit I'm nit-picking here -- however, if buying from Tots Bots (in the UK),it appears that an additional liner is included. The diapers here in Canada are distributed through Bummis and do not have the extra liner sold with them.
If the diaper isn't a snug enough fit, having good fabric contact with the bum inside, there may be some urine leakage around the legs -- particularly if the baby is lying on his or her side and tends to pee a lot all at once. A good, snug fit is required for urine to be fully absorbed by the bamboo rayon and microfiber and prevent liquid pooling inside. This can be partially addressed by adding more bulk to the diaper by inserting a doubler into the pocket.
This is a one-size diaper and as with any one-size diaper, fitting at all sizes can be a potential problem. While this diaper is working great for us at the lower end of the range, I'm not sure it is big enough to fit at the other end -- obviously, I can't say this for certain for another year or so.
Overall, I'm really happy with this diaper. It's already one of the first ones I grab in the morning, or reserve for the diaper bag. Thankfully, I have two in my stash! The baby and I give this diaper 4 thumbs up! ;)
* Diaper sample provided free of charge in exchange for review.†
** Clean, dry diaper thoroughly soaked in water and then allowed to hang for 15min, until no more water dripped from fabric.
† Full disclosure means I have to admit that I already owned one of these great diapers and was extolling its virtues when a 2nd one was offered to me in exchange for a review. ;)


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Huayco Tinamou is one of the most recently-recognized species in South America, recently split from the widespread Red-winged Tinamou Rhynchotus rufescens. Huayco Tinamou differs from Red-winged Tinamou in voice, range, and some minor plumage differences. Huayco Tinamous are found in central and southern Bolivia and northern Argentina, generally on the east side of the Andean crest. It favors grassy mountain ridges from about 1000 to 3300 meters in elevation.
Little research has been conducted on Huayco Tinamou, so many details of its life history remain unknown. However, given the extent of its range, estimated to be in excess of 113,000 km2, BirdLife International has determined it to be a species of Least Concern.


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Dariana is the Chief Strategist of The Rebelle Agency, a development and management company, that works with clients in the "entertainment, lifestyle, sports, and non-profit industries."
How did you end up choosing a career in your industry?
When I was in college, I was studying to be an investment banker. However, after a summer internship in the field, I quickly realized that it was not my ultimate blessing (although it did highlight my aptitude for numbers and my ability to be a "bulldog"). I was in a transitive point in my life leading into my Junior year, and a Spelman sister of mine asked me to be her Presidential Assistant for a new student organization she founded, the Black Public Relations Student Society (BPRSS). Always up for a challenge, I said yes with no prior knowledge of the industry.


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Comecer Netherlands is a new part of Comecer that brings to the Group the strong and lasting tradition of Veenstra Instruments.
Veenstra Instruments was founded in 1960 when Gerlof Veenstra, started his operation as a high precision mechanical engineer. Since then its core competence matured in mechanical, electrical and software design. The orginal famous oak leaf logo was inspired by the monumental trees that surrounded the first company housing, being a traditional farm.
Over the years it gained a unique know-how in radiation related safety and measurement. Priceless knowledge that translated in many different products and customised solutions. Over the years, Veenstra provided the best possible answers, combining its own products with those of strong, reliable strategic partners. Its mission was to offer customers complete solutions, tailor-made to their specific needs and implemented on site, to enable them to work safely and according to the latest regulatory standards. Now, as Comecer Netherlands, these values have not changed.
Comecer Netherlands is now an internationally known business partner for many nuclear medicine departments, radiochemistry laboratories & industrial radiation laboratories. It has an ISO 9001 and ISO-13485 certified production facility that combines state of the art technology and flexibility to meet constant changes in our field of operation. Comecer Netherlands develops, manufactures and service a broad range of Comecer products for protection, measurement, registration, detection and (quality) control.
The Netherlands
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Making the internet safer for children: the global evidence
6th February 2018
On Safer Internet Day 2018, Global Kids Online partners recognise the pressing need to research and support children's rights in a digital age. To harness the positive potential of children's internet use and to limit the harm, it is vital to understand how children are developing digital skills and citizenship, and to use the evidence to inform future policy and practice in a way that also includes the voices of children and parents.
Brazil: 24.3 million children are now online
28th November 2017
The Regional Center for Studies on the Development of the Information Society (Cetic.br) just launched the results of the latest ICT Kids Online Brazil survey, conducted annually since 2012. Based on home-based computer-assisted interviews with 2,999 children and their parent or guardian, the survey highlights key issues related to internet access, online opportunities, and safe internet use.
Recognising online hurtful behaviour among peers
17th November 2017
Global Kids Online examines a wide set of hurtful behaviours that children encounter online alongside the opportunities that the internet affords. Our approach recognises the connections between online and offline experiences and avoids the assumption that all online risks are inherently harmful. This research brief summarises key comparative findings on hurtful behaviour amongst peers.
Global Kids Online South Africa
24th June 2016
This study was conducted by the Centre for Justice and Crime Prevention (CJCP) and aimed to pilot the Global Kids Online research tools in a low income country, as well as gather rigorous and comparable evidence on the nature of children's internet use in South Africa.
Global expert meeting on cyber-bullying
12th May 2016
At a recent global expert meeting on bullying and cyber-bullying organized by the Office of the Special Representative of the UN Secretary-General on Violence against Children, Sonia Livingstone presented the Global Kids Online project, along with the latest findings showing that cyberbullying represents a growing proportion of bullying overall.
Global Kids Online Argentina
5th May 2016
The study was commissioned by UNICEF Argentina and aimed to gather rigorous and comparable evidence on the nature of children's internet use in Argentina and to inform policy-makers about the benefits of increasing the opportunities and minimising the risks children face online.


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Some people know how to bring the party with them wherever they go. And some people do so on a bike, so offer kudos to your special unicorn with a gift that accessorizes their flair for life.
Walnut Studiolo Six Pack Frame Cinch - Handcrafted out of American leather, this accessory makes it a cinch for your Party Biker to transport a 6 pack of their favorite suds. $36
Outdoor Tech Turtle 3.0 - Small and powerful; waterproof (it floats!) and shockproof; this bluetooth speaker will be anyones new best friend. Did we mention it also serves as power bank and you can charge any micro usb device with it? $99.95
Green Guru Townie Touring Handlebar Cooler - Transport your lunch or a 6-pack of cans in this insulated beauty made from upcycled bike tubes. $38
Park Tool BO-2 - This bottle opener is built to perform under the most demanding conditions; a perfect complement to any tool collection. $6.26
Monkey Light M232 - Stay visible and bring the party (thousands of patterns and 42 themes) to your next group ride. Waterproof, up to 20 hours of runtime, and 32 full color LEDs (200 lumens). Made in the USA and comes with a 2-year warranty. $59.99
Microism Publishing Stickers - Get sassy and say it with a sticker! $2
Cosmic Brightz - Stay visible and turn your bike into the disco. Available in green, blue, red, and pink. $12.99
Microism Publishing Pins - A fun and silly way to express your feels. $2
Bikase Superband - Transport anything on your bike from a speaker to a cell phone; a juice pack or maybe a sausage; CO2 pump, light jacket, sunglasses; the possibilities are endless for only $19.99
Walnut Studiolo Bottle Belts - Transport a bottle of wine or spirits on your top tube with these handcrafted leather belts. $36
King Cage Oliver Flask Cage - Handcrafted in Colorado, we can't guarantee that these are legal but they're definitely fun and will accommodate any 8 oz. flask. $22
Trixie & Milo Stainless Steel 8 oz. Flask - Makes a great partner for the King Cage Oliver or your back pocket. $29
Delta Cargo Net - Stretch web secures varied load sizes and hard to hold items. $8.99


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"You can make friends!"
"You can get a book recommended to you when you didn't even know the book existed."
"I like how you can put books on hold."
"You can look up to see if a book is available in the library before you even get to the library"
"It's really fun that you get to talk to your friends about books"
What is everybody talking about?? What has captured the attention of our upper primary students? It's DESTINY QUEST. Destiny Quest is an online inventory of all of our books in the primary and middle high library. But it's not just that - it's an interactive software where students can make friends, archive their own online library, make book recommendations to their friends, read reviews of books, search for books available in our library and see what their friends are reading. Not only that, Destiny Quest is specifically designed for the HKA library so students can also see the Top 10 List which highlights the most frequently checked-out books, see New Arrivals to our library and browse a shelf without budging an inch. Students can post and share reviews of books in a safe environment because Destiny Quest is in-house and is password protected! What could be better? Ask your child(ren) to explore Destiny Quest with you and see what HKA students are reading!


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SGT Report | Published on Dec 28, 2017
You won't believe how many incredible things are happening right NOW. And a whole bunch of it is quantifiable. If your name it "Hillary Clinton" or "John Podesta" or "Tony Podesta", you should be sh#tting your pants right now. Because according to #Qanon we are seeing the Trump Patriot deep state counter coup against the Satanic elite. Investigative journalist Liz Crokin joins me to discuss.
LUKE 8:17 For there is nothing hidden that will not be disclosed, and nothing concealed that will not be known or brought out into the open.
Here's the link to SD Bullion if you'd like score some PHYSICAL silver or gold: http://sdbullion.com/sgt
Please consider supporting SGT Report on Patron with a monthly contribution: https://www.patreon.com/user?u=5104183
For REAL news 24/7:


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On Pointe
The prima ballerina Alessandra Ferri recently made headlines by emerging from retirement and triumphantly returning to the defining role of her career as the eponymous heroine of the balletic adaptation of 'Romeo & Juliet'. Whilst most of the headlines have focused on Ms. Ferri's age – she is 53, a far cry from the teenager she so expertly and beautifully brings to life onstage in her dancing – her statement on why she continues to dance is illuminating: she dances for pure joy. She dances because it is a way of being – she dances to live, to be alive.
So many people wait for the perfect moment to begin living, putting things off till there is more time, or till they retire, or some other 'very good reason'. This kind of postponement feels justified and necessary, but it is no less of a lie we convince ourselves of. What might happen if we choose to live in the here and now, as is, and stop waiting for our lives to begin?
One potential pitfall of this attitude is a lack of clarity over what it means to live. Each individual carries within them a siren song of the heart – something that makes them feel alive and real. If this song isn't clear to the individual, 'living in the here and now' might result in them living someone else's song rather than their own, and feeling rather miserable for doing so. In counselling, I often encounter clients who work in areas they dislike, who are in relationships with people they feel distant from, or who expend a lot of themselves pursuing something that they aren't sure will make them happy. Unlike Ms. Ferri, they are not living in the 'pure joy' of what is most true for themselves. Counselling and therapy are avenues toward clarifying what it means to be alive, to be in pure joy, and to live.
So many people wait for the perfect moment to begin living, not realizing that the pure joy of living as they are is eternal, present and there for the living at all times. Being alive means not only choosing to live in the moment, but to use that moment to seize purity of purpose with joy.


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Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease.
The formation of tissues and organs involves a complex series of cellular events such as cell proliferation, differentiation, and migration. These processes are orchestrated by a large number of genes, including transcription factors, signaling molecules, and chromatin modifiers. Chromatin-modifying proteins regulate transcription by inducing changes in chromatin structure that affect the accessibility of regulatory DNA sequences to the transcriptional machinery. These regulatory proteins have been identified in many organisms ranging from yeast to humans and are known to form complexes (e.g., NURD/CoREST) with distinct regulatory modes and functions.
The NURD chromatin complex is unique in that it combines the activity of both histone modifiers (histone deacetylases, or HDACs) and chromatin remodelers (Mi-2 ATPase) into one complex. The HDACs deacetylate histone tails, leading to chromatin compaction, whereas the Mi-2 ATPase disrupts the binding of histones to DNA, which allows transcription factors to have easier access to the DNA to control gene expression (Xue et al. 1998). The activity of HDACs is counteracted by another group of enzymes, histone acetyltransferases, that acetylate histone tails and make chromatin more accessible to transcriptional machinery. The balance between HDAC and histone acetyltransferase activity ensures precise control of gene expression, and failure to regulate their activity can cause cancers and metastatic growth. For example, many HDACs are highly expressed in lymphomas of both classical Hodgkin and non-Hodgkin types (Gloghini et al. 2009). HDAC inhibitors have emerged as a powerful new class of small-molecule therapeutics that acts through the regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other nonhistone protein targets. Although HDAC inhibitors have been successfully implemented as therapeutics, the mechanistic details of how these proteins interact with other cellular machinery and signaling pathways during normal development and disease are poorly understood.
The egg-laying system of Caenorhabditis elegans offers many advantages for the study of how chromatin remodelers and histone modifiers regulate gene expression to control tissue morphogenesis. The vulva, a passageway for laying eggs, is formed by 22 cells that arise from successive divisions of three vulval precursor cells (VPCs): P5.p, P6.p, and P7.p. The VPCs are induced by evolutionarily conserved signaling pathways mediated by LET-60/Ras, LIN-12/Notch, and Wnt. The Ras pathway induces a 1° fate in P6.p through an EGF-secreted signal from the overlying anchor cell (AC). This in turn activates the LIN-12/Notch pathway from the P6.p cell in a lateral manner, inducing a 2° fate in both P5.p and P7.p (Greenwald 2005; Sternberg 2005). The Wnt pathway is also involved in 2° fate specification and appears to act in parallel and through crosstalk with the LIN-12/Notch pathway (Seetharaman et al. 2010). In addition to signaling pathway components, genetic screens in C. elegans have also identified a number of genes known as SynMuv (synthetic multivulva) genes, a gene family that interacts with the Ras pathway to negatively regulate vulval cell proliferation (Cui et al. 2006; Cui and Han 2007). SynMuv genes are divided into three different classes (A, B, and C) based on their genetic properties, such that mutations in any one of the classes do not (or rarely) affect the VPC induction pattern, but in combination with the other classes, give rise to a multivulva (Muv) phenotype (Fay and Yochem 2007). Genetic and biochemical studies have shown that class B SynMuv genes encode components of chromatin remodeling complexes, such as let-418/Mi2 and hda-1/hdac1 (Fay and Yochem 2007).
Nucleosome remodeling and deacetylation (NURD) complex proteins in C. elegans play important roles during development. HDA-1 (HDAC1), a catalytic subunit of NURD, is required for embryogenesis, gonadogenesis, germ cell formation, neuronal axon guidance, and vulval development (Dufourcq et al. 2002; Zinovyeva et al. 2006). In the vulva, hda-1 knockdown has been shown to cause a weak Muv phenotype in combination with mutations in any one of the class A and class B SynMuv genes (Lu and Horvitz 1998; Solari and Ahringer 2000). Subsequently, a similar phenotype was reported in hda-1 mutants alone (Dufourcq et al. 2002; Zinovyeva et al. 2006), although the SynMuv interaction was not observed (Dufourcq et al. 2002). In addition, vulval cells in hda-1 animals fail to migrate and form ectopic invaginations (Dufourcq et al. 2002). It is unclear whether the invagination defect is another factor contributing to the Muv phenotype because VPC induction patterns were not examined.
We performed an RNA interference (RNAi) screen to identify the transcription and chromatin-associated factors involved in vulva and vulva−uterine connection formation. The screen identified new genes as well as previously discovered genes, including hda-1. In this study, we investigated the role of hda-1 in detail. The vulval morphology defect in hda-1 animals suggests that hda-1 is involved in cell differentiation and cell migration processes. Furthermore, hda-1 is expressed in vulval cells in a temporally restricted manner. To understand how hda-1 controls vulval development, we searched for interacting genes and found that the fos proto-oncogene family member fos-1b and the LIM-Hox family member lin-11 act genetically downstream of hda-1 in vulval cells.
In addition to vulva development, we found that hda-1 is also involved in the formation of the vulval−uterine connection. In hda-1 mutants the uterine seam cell (utse) fails to form due to defect in π cell fates, as determined by expression analysis of 2 important π lineage-specific transcription factors, lin-11 and egl-13 (SOX family). Further analysis of the role of hda-1 in π cell fate specification revealed that hda-1 acts in the AC to signal ventral uterine (VU) granddaughters to adopt π fates. This process involves egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless ortholog of NHR family)-mediated regulation of lag-2 (DSL ligand) expression, which in turn activates lin-12/Notch signaling in VU granddaughters. Taken together, our findings establish hda-1 as a key regulator of vulva and uterine cell morphogenesis.
Materials and Methods
Strains and general methods
All strains were maintained at 20°. Worm cultures and genetic manipulations were conducted as described previously (Brenner 1974). The mutations and transgene markers used in this study are listed below. The linkage group is indicated when known.
N2 (wild type), arEx1352[lag-2::gfp + pha-4(+)], ayIs4[egl-17::gfp + dpy-20(+)] I, bhEx53[pGLC9(daf-6::yfp) + unc-119(+)], bhEx68[pGLC43(Cbr-hda-1::gfp) + unc-119(+)], bhEx72[pGLC44(hda-1::gfp) + unc-119(+)], deIs4[ajm-1::gfp + lin-39::gfp (yeast DNA) + dpy-20(+)] I, fos-1(ar105) V, hda-1(cw2) V, hda-1(e1795) V, inIs181; inIs182[ida-1::gfp], kuIs29[pWH17(egl-13::gfp) + unc-119(+)] V, nIs408 [lin-29p::lin-29::mCherry + ttx-3p::gfp], qIs56 [lag-2::gfp (pJK590) + unc-119(+)]V, qyIs174 [hlh-2p::gfp::hlh-2 + unc-119(+)], sEx13706[rCes C53A5.3::gfp + pCeh361], syIs49[zmp-1::gfp + dpy-20(+)] IV, stIs11476 [nhr-67::H1-wCherry + unc-119(+)], syls50[cdh-3::gfp + unc-119(+)] X, syIs54[ceh-2::gfp + unc-119(+)] II, syIs80[pPGF11.13(lin-11::gfp) + unc-119(+)] III, syIs123[fos-1a::yfp-TL + unc-119(+)] X, syIs137[fos-1b::cfp-TX + unc-119(+)] III, unc-119(ed4) III, zhEx216.2[egl-43-1.7-lp::gfp + unc-119(+)].
Phenotypic analysis
The vulva and utse phenotypes were examined during the L3 and L4 stages. P(5−7).p cells divide between mid-L3 and early-L4 to generate a total of 22 progeny. The vulval toroids were visualized in mid-L4 animals using ajm-1::gfp. The π cells (on either side of the AC) and their progeny (immediately dorsal to the vulval tissue) were observed during the late-L3 and early to mid-L4 stages. The utse was detected as a thin membrane (hymen) in mid-L4 animals. The expression of lag-2::gfp was quantified in early to mid-L3 stage animals. Worms were scored for egl-43::gfp, nhr-67::wcherry, hlh-2::gfp and lin-29::wcherry expression at the mid-L3 stage.
We looked at four independently isolated stable lines for hda-1::gfp and 3 for daf-6::yfp. All strains showed identical pattern of expression.
We used multiple criteria to ensure that animals were examined at correct stages. The staging was based primarily on gonad morphology (Hall and Altun 2008). Because gonad morphology is defective in hda-1 mutants, the appropriate stage was selected based on developmental timing of control animals. For π cell lineage analysis, we relied on egl-13 and lin-11 markers that show expression in π cells starting mid to late-L3 stage. For examination of π progeny and vulval cells we picked animals at L4 lethargus stage.
Molecular biology and transgenics
The sequences of primers used in this study are as follows (5′ to 3′ orientation). The restriction enzyme sites are underlined.
The hda-1::gfp plasmids, pGLC44 (C. elegans) and pGLC43 (Caenorhabditis briggsae), were made by subcloning an NsiI/HindIII-digested 1024-bp DNA fragment from C. elegans into the Fire lab vector pPD95.69 and an NsiI/PstI-digested 1030-bp DNA fragment from C. briggsae into pPD95.67 (polymerase chain reaction [PCR] primers GL363/GL360 and GL354/GL355, respectively). Because the C. elegans fragment contains all but approximately 250 bp of the DNA region between hda-1 and its upstream gene, ril-1, it is formally possible that gfp expression in the transgenic animals is regulated by both the hda-1 and ril-1 enhancers. However, this is unlikely because ril-1 has no known function in vulva and uterine cells (Hansen et al. 2005; Lemire et al. 2009). To construct daf-6::yfp (pGLC9), we inserted a 3-kb PstI/KpnI-digested 5′ regulatory DNA fragment (amplified by PCR using primers GL176/GL177) into pPD136.61.
Transgenic strains were generated by microinjection (Mello et al. 1991). In all cases unc-119 was used as a rescue marker. The hda-1::gfp transgenic lines are bhEx68, bhEx69, bhEx71 (all containing C. briggsae hda-1), and bhEx72 (containing C. elegans hda-1). The daf-6::yfp lines are bhEx53, bhEx54 and bhEx55.
RNAi experiments were performed using the Ahringer lab bacterial feeding library (Sanger Institute). The protocol has been described previously (Seetharaman et al. 2010). All experiments were repeated at least three times, and batches with similar results were pooled and analyzed. The RNAi phenotypes were compared with published results such as Pvl, defective vulval invagination, and sterility (www.wormbase.org) to ensure quality. The empty vector L4440-containing bacteria served as a negative control. Except where noted, feeding RNAi was performed in L1 larvae, which were synchronized as follows: gravid adults grown at 20° were treated with a hypochlorite solution for 4–5 min. Embryos were washed five times with M9 and then allowed to hatch in M9 for 16–30 hr at 20° with gentle agitation. The L1 worms were placed on feeding RNAi plates and maintained at 20°. The cells were plated on RNAi media plates and allowed to grow overnight before the plates were seeded with L1 worms. For double RNAi experiments, bacterial cultures of hda-1, nhr-67, lin-29, and hlh-2 were mixed in equal proportion as described earlier (Penigault and Felix 2011). In these cases we examined batches in which animals exhibited phenotypes characteristic of both genes.
Worms were mounted on agar pads as described previously (Wood 1988). L4 and young adults were examined under Nomarski optics using a Zeiss Axioimager D1 and a Nikon Eclipse 80i. For GFP reporter-expressing animals, epifluorescence was visualized by a Zeiss Axioimager D1 microscope equipped with the GFP filter HQ485LP (Chroma Technology). Confocal images were captured on a Leica DMI 6000B laser scanning microscope using Leica Application Suite Advanced software. All images were processed using NIH Image J (http://rsb.info.nih.gov/ij) and Illustrator and Photoshop (Adobe Inc.) software.
Analysis of fluorescent reporters
Images of gfp-expressing animals were captured at the subsaturation level by optimizing the exposure time and gain. Green fluorescent protein (GFP) fluorescence in AC was quantified using ImageJ as described earlier (Schindler and Sherwood 2011). To summarize, AC was manually cropped, and the mean pixel intensity was measured (area of AC × mean pixel intensity in that area) after subtracting the background, and the data were plotted as a percentage of fluorescence intensity. For lag-2::gfp expression analysis, two different transgenic lines, qIs56 and arEx1352, were used. In all cases only worms with expression in DTC were selected for analysis. Because hda-1 was earlier shown to act as a class B synMuv gene and class B genes affect transgene expression levels (Hsieh et al. 1999; Wang et al. 2005), hda-1 knockdown may cause transgene silencing globally. However, this possibility is less likely because hda-1 mostly represses transcription (Whetstine et al. 2005). Also, Dufourcq et al. (2002) did not find global transcriptional silencing in hda-1 mutants. In our case, we looked at the expression of marker genes in different tissues. Although the expression was reduced or eliminated in vulva or uterine cells, no obvious change in other tissues was observed.
Data analysis
Statistical analyses were performed using InStat 2.0 (GraphPad Software Inc.) software. Two-tailed P values were calculated in unpaired Wilcoxon/Mann-Whitney tests and values less than 0.05 were considered to be statistically significant.
RNAi screen for genes involved in vulva and vulva−uterine connection formation
We conducted a systematic RNAi screen for a subset of conserved transcription factors and genes involved in chromatin modification (Cui and Han 2007; Haerty et al. 2008). We fed age-synchronized N2 wild-type, L1-staged animals with dsRNA-expressing bacteria and examined the animals for abnormal vulval invagination in the L4 stage, and later, for protruding vulva (Pvl) phenotypes in adults. Of the 171 genes tested, RNAi-mediated knockdown of 34 different genes (20%) caused Pvl and/or vulva rupture defects, as observed under a dissecting microscope; this result was further confirmed by Nomarski microscopy. Vulval morphology was also defective in 16 of 34 of the knockdown strains (Figure 1, Supporting Information, Figure S1, and Table S1). One of these genes, the class I histone deacetylase family member hda-1, is a known negative regulator of vulval cell proliferation (Dufourcq et al. 2002; Lu and Horvitz 1998; Solari and Ahringer 2000).
hda-1 mutants exhibit abnormal vulva and vulval−uterine connections
The hda-1(RNAi) animals have a Pvl phenotype similar to that observed in two viable hda-1 hypomorphs, cw2 and e1795 (Dufourcq et al. 2002; Zinovyeva et al. 2006). Upon careful examination we found that the Pvl penetrance is high in RNAi and e1795 animals but very low in cw2 (Table 1). Earlier, more than half of cw2 animals (62%) were reported to be Pvl (Zinovyeva et al. 2006). This difference may be caused by the way Pvl phenotype was scored. In our case we counted only those protrusions that were big and clearly noticeable (see Figure 1F as an example). In addition to the Pvl defect, hda-1 animals also showed abnormal morphology of the developing vulva. Specifically, vulval cells in L4 stage frequently failed to invaginate and that the vulva lacked the two mirror-symmetric halves characteristic of wild-type animals (compare Figure 1A with Figure 1, B−E). The defect was most severe in hda-1(e1795), followed by hda-1(RNAi) and hda-1(cw2). The hda-1(cw2) phenotype could be further enhanced by RNAi knockdown of hda-1 (Figure 1D, Table 1), which is consistent with cw2 being a hypomorphic allele.
During the L4 stage, vulval cells migrate toward the center and invaginate to occupy stereotypic positions. Similar cell types subsequently fuse, generating toroidal rings that line the vulval cavity. We examined the possibility that abnormal vulval invagination in hda-1(RNAi) animals is caused by improper cell fusion events. To this end, we used an adherens junction marker, ajm-1::gfp, to visualize cell boundaries and vulval toroids (Sharma-Kishore et al. 1999). In wild-type L4 animals, ajm-1::gfp is expressed in seven concentric toroidal rings (vulA to vulF), each corresponding with the boundary between two different cell types (Figure 1H). We found that in the 60% (n = 25) hda-1(RNAi) animals, the vulval rings were defective. Specifically, the toroids were 40% (n = 5) wider than normal (N2, n = 2) and disorganized, and in some cases, had fewer than seven rings (Figure 1, I and J). These phenotypes may arise from abnormal morphogenetic movements and altered cell fates (see next section).
In addition to the vulva abnormalities, we also observed defects in the vulval-uterine connection in the hda-1 animals. In the wild-type animals, a thin membrane consisting of a uterine seam cell (utse) is visible at the apex of the vulva (Figure 1A), whereas in the hda-1(RNAi) animals the membrane could not be clearly observed (Figure 1C). The morphology was only slightly abnormal in hda-1(cw2) animals (Figure 1B) but was clearly defective in hda-1(cw2 RNAi) and hda-1(e1795) animals (Figure 1, D and E). It is unclear whether the utse was absent altogether or was present but could not be identified due to an abnormal morphology. The uterine lumen was also frequently absent (Figure 1, C−E). In some cases, the AC failed to migrate and appeared to be located at the top of the vulval apex (Figure 1G).
Vulval cells fail to differentiate in hda-1 animals
The abnormal vulval morphology and Pvl phenotype in the hda-1 animals, together with defective ajm-1::gfp toroids, led us to further characterize the role of hda-1 in vulval development. For this, we used five vulval cell type-specific GFP-based markers, zmp-1::gfp (zinc metalloproteinase), egl-17::gfp (fibroblast growth factor family), ceh-2::gfp (homeobox family), daf-6::yfp (patched family), and cdh-3::gfp (Fat cadherin family), which are expressed in subsets of differentiating vulval cells (Inoue et al. 2002; Perens and Shaham 2005). egl-17::gfp expression was first observed in mid-L3 animals in P6.p granddaughters, and later, in mid-L4 animals in the presumptive vulC and vulD cells (Figure 2A, A′, and B, B′). ceh-2::gfp and daf-6::yfp showed a more restricted pattern of expression. Although ceh-2::gfp was observed in the presumptive vulB1 and vulB2 cells (2° lineage) (Figure 2, G and G′), daf-6::yfp was observed in the presumptive vulE and vulF cells (1° lineage cells; Figure 2, I and I′). The remaining two markers, zmp-1::gfp and cdh-3::gfp, showed GFP fluorescence in subsets of both 1° and 2° lineage cells. cdh-3::gfp was expressed in presumptive vulE, vulF cells (Figure 2, K and K′), vulC and vulD (not shown) whereas zmp-1::gfp was observed in vulE (Figure 2, E and E′), vulA and vulD cells (not shown).
The analysis of the aforementioned markers in hda-1 animals revealed defects in cell type-specific gene expression (Table 2). Specifically, egl-17::gfp fluorescence was weak and often absent in both the hda-1(cw2) and hda-1(RNAi) animals (Figure 2, C, C′ and D, D′). The zmp-1::gfp level was significantly reduced in presumptive vulE cells (Figure 2, F and F′). The levels of ceh-2::gfp and daf-6::yfp were frequently below the detectable limit (Figure 2, H, H′ and J, J′), whereas cdh-3::gfp was often reduced in the mutants (see vulF in Figure 2, L and L′) or missing (not shown). Changes in marker gene expression revealed that the specification of all vulval progeny was affected. We did not observe any case of VPC fate transformation, i.e., 1° to 2° or vice-versa. These results, together with the abnormal vulval toroids and defects in invagination in hda-1 mutant animals (Figure 1I), demonstrated that hda-1 is necessary for the differentiation as well as correct division patterns of both 1° and 2° lineage cells.
We also examined the expression of two transcription factors, lin-11 and fos-1, in hda-1(RNAi) animals. Both these genes are involved in vulval morphogenesis (Gupta et al. 2003; Seydoux et al. 1993). lin-11 is expressed in all vulval progeny while cells are differentiating and undergoing morphogenetic changes (Gupta et al. 2003). The fos-1 locus encodes three transcripts that have some functional differences. fos-1a (syIs123 fos-1a::yfp) is almost exclusively present in the AC and is the target of hda-1 during AC invasion (Matus et al. 2010). fos-1b(syIs137 fos-1b::cfp) is observed at a low level in several uterine cells, including the AC (Sherwood et al. 2005), and it does not appear to play a role in AC invasion. Another fos-1 transcript, fos-1c, is expressed in uterine π lineage cells and involved in utse formation (Oommen and Newman 2007). We examined syIs123 and syIs137 transgenic animals and found that although fos-1a::yfp was undetectable in vulval cells during the L3 and L4 stages (data not shown), fos-1b::cfp was expressed in a subset of vulval progeny. During the mid-L4 stage, CFP fluorescence was brighter in presumptive vulD cells compared with vulE and vulF cells (Figure 3, A and B). This pattern was dynamic, such that by late-L4 stage, the presumptive vulE and vulF cells were much brighter compared with the presumptive vulD cells (Figure 3, C−H).
We found that lin-11::gfp (syIs80) expression was significantly reduced in hda-1(RNAi) animals (74% faint and 26% animals with no GFP fluorescence, n = 53%; Figure 3, K−N). Expression was uniformly lower, consistent with hda-1 expression requirements in all vulval progeny. Similar to lin-11, fos-1b::cfp fluorescence was also reduced. In mid-L4 animals, the presumptive vulE and vulF cells showed almost no fluorescence, whereas presumptive vulD cells were faintly visible (78% animals defective, n = 16, compared with none in control, n = 25) (Figure 3, I and J). The pattern was similar in late-L4 animals (data not shown). These results demonstrate the importance of hda-1 in regulating lin-11 and fos-1b in vulval cells.
hda-1 is expressed in vulval and gonadal lineage cells
To further characterize the role of hda-1 in reproductive system development, we examined its expression profile by using the gfp reporter transgenic strains sEx13706 and bhEx72. The sEx13706 strain was generated earlier as part of a systematic gene expression-profiling project (Hunt-Newbury et al. 2007). Expression of gfp in sEx13706 animals is directed by a 2.8-kb hda-1 regulatory region that includes the open reading frames and potential cis-regulatory elements (enhancers) of two other hda-1 upstream genes (ril-1 and C53A5.2; Figure S2). The other hda-1::gfp transgenic strain (bhEx72), which was generated by us, contains a much smaller 5′ upstream region of hda-1 (approximately 1.0 kb, pGLC44) and excludes the two genes mentioned above (Figure S2A, also see the Materials and Methods section). The analysis of GFP fluorescence in sEx13706 and bhEx72 animals revealed a similar pattern, although the fluorescence in sEx13706 was much brighter. We found that hda-1 is broadly expressed throughout development (Figure S2, B−O). The earliest expression was detected in gastrulating embryos. The larvae exhibited GFP expression in several neuronal and epidermal cells, primarily in the anterior ganglion and ventral hypodermal regions. Expression persisted in many cells in later larval and adult stages (data not shown).
In the vulva, hda-1::gfp expression was first detected in the progeny of P(5-7).p in mid-L3 animals (Figure 4, B and D). At this stage, GFP fluorescence was absent in other VPC lineages (P3.p, P4.p and P8.p; data not shown). By the L4 stage, almost all vulval cell types were observed fluorescing, with presumptive vulA, vulB1, vulB2, and vulD cells being the brightest (Figure 4E). GFP fluorescence in vulval cells was mostly absent beyond the late-L4 stage, suggesting that hda-1 may not be needed in vulval cells at later stages of development. The broad expression of hda-1 is consistent with the involvement of the gene in multiple developmental processes. This multifaceted role for hda-1 in C. elegans appears to be conserved in C. briggsae because Cbr-hda-1::gfp is expressed in a similar manner (Figure 4F and data not shown).
We also observed hda-1::gfp expression in the AC in L3 animals (Figure 4, B and D) that persisted until the early L4-stage (data not shown). No expression was observed in π cells or their progeny at any developmental stage. Considering that AC movement and the vulval-uterine connection are abnormal in hda-1 mutants (Figure 1, B−E), a simple model could be that hda-1 acts in the AC to control π cell fates and utse formation. The experiments described in the sections to follow support this model.
hda-1 mutants exhibit defects in the specification of uterine π lineage cells
In addition to the vulval defect, hda-1 mutants also lack a functional vulval−uterine connection, as the thin utse membrane-like structure could not be clearly identified in these animals (see Figure 1). In wild-type L3 stage animals, three VU cells divide to produce 12 granddaughters, six of which are induced by the AC to adopt π fates (located in two different focal planes, three on each side). By the early L4 stage, π cells produce 12 daughters, eight of which fuse with each other and the AC to form the utse (Newman et al. 1996). This process is controlled by a number of genes, including the transcription factors egl-13 and lin-11. These two genes play important roles in π cell differentiation and utse formation (Hanna-Rose and Han 1999; Newman et al. 1999).
To characterize the utse defect in hda-1 animals, we examined egl-13 and lin-11 expression in π lineage cells using GFP reporter-expressing transgenic strains (egl-13::gfp kuIs29 and lin-11::gfp syIs80). In wild-type animals, both genes are expressed in π cells and their progeny (Figure 5, A, B, E, F, K, L, O, and P) (Gupta and Sternberg 2002; Hanna-Rose and Han 1999). We found that hda-1(RNAi) and hda-1(cw2) animals have abnormal patterns of egl-13::gfp and lin-11::gfp expression. Specifically, there were more GFP-fluorescing π-like cells (as many as seven) in the mutants (Figure 5, N, R, and S), suggesting that the VU granddaughters failed to limit the expression of egl-13 and lin-11 in hda-1 mutants. Similar to π cells, the number of π progeny also was greater (up to 13) (Figure 5, D and S), although in the case of lin-11::gfp, the overall level of GFP fluorescence was considerably reduced (RNAi-treated: 74% faint and 26% absent, n = 53 animals; e1795: 100% absent, n = 21) (Figure 5, G−J). The π progeny failed to migrate as they normally do in wild-type animals. As egl-13 controls π cell divisions and the number of π progeny (Hanna-Rose and Han 1999), it is conceivable that extra π progeny in hda-1 animals arise in part from a reduction in egl-13 expression. In summary, these results suggest that although more π-like cells are formed in hda-1 mutants, the cells fail to differentiate correctly, resulting in the lack of a functional vulval-uterine connection.
We also examined uv1 cell fate in hda-1 mutants. uv1 cells are specified from among the progeny of π cells during the L3 lethargus stage (Newman et al. 1996). Examination of the uv1-specific marker ida-1::gfp (Zahn et al. 2001) revealed that unlike wild-type animals in which four uv1 cells were visible (Figure 6A), 96% (n = 160) hda-1 mutants showed no such expression, suggesting there is a defect in uv1 differentiation (Figure 6B). Taken together, these results demonstrated that hda-1 plays an important role in π lineage specification, leading to the formation of utse and uv1 cells.
hda-1 mutants show defects in AC fate and fail to regulate lag-2 expression
The expression of hda-1 in the AC and its requirement for AC migration suggested to us that the utse defect in hda-1 animals might be caused by a failure in AC differentiation. Earlier, hda-1 was shown to be required in the AC for cell invasion and expression of lin-3::gfp (EGF ligand) (Matus et al. 2010); however, the role of hda-1 in the AC-mediated utse differentiation process was not investigated. Therefore, we first examined AC fate using a zmp-1::gfp (syIs49) reporter strain. zmp-1 is expressed in the AC starting at L3 and is involved in AC function (Rimann and Hajnal 2007; Sherwood et al. 2005). RNAi-mediated knockdown of hda-1 caused a significant reduction in GFP fluorescence in the zmp-1::gfp animals (Figure 7, A−D, 100% bright in control, n = 35; 64% reduced and 0% absent in hda-1(RNAi), n = 58; 25% reduced and 70% absent in e1795, n= 20), suggesting that the AC was defective in hda-1 animals.
Next, we examined AC-mediated signaling by investigating the expression of lag-2. LAG-2 is a DSL ligand expressed in the AC, and it mediates lin-12/Notch signaling in the presumptive π cells (Newman et al. 2000). The hda-1(e1795) animals were previously shown to have ectopic lag-2::gfp fluorescence in certain unidentified cells beneath the cuticle, suggesting that hda-1 normally represses lag-2 in these cells (Dufourcq et al. 2002). We reasoned that an increase in π cell numbers in the hda-1 mutants could be caused by the over expression of lag-2 in the AC, leading to the inappropriate activation of lin-12/Notch signaling in VU granddaughters. This is in line with previous findings that showed an increase in π cells in lin-12 gain-of-function (gf) mutants in which lin-12 receptor activity is elevated and operates in a ligand-independent manner (Newman et al. 2000). Therefore, we quantified GFP fluorescence in the AC in lag-2::gfp animals at the time of π cell induction. As expected, hda-1(RNAi) animals exhibited a much higher level of GFP fluorescence in the AC compared with controls (average increase of 37% ± 9%, n = 30) (Figure 7, E−I).
nhr-67 and egl-43 act downstream of hda-1 to promote lag-2 expression in the AC and specify π cells
The up-regulation of lag-2::gfp in the AC in hda-1 mutant animals prompted us to search for genes involved in hda-1-mediated lag-2 repression. To pursue this goal, we investigated the roles of four transcription factors: hlh-2 (bHLH family, E/daughterless homolog), lin-29 (C2H2 Zinc finger family), nhr-67, and egl-43. All of these genes are expressed in the AC, and except for egl-43, have been shown to positively regulate lag-2 expression (Karp and Greenwald 2003; Newman et al. 2000; Verghese et al. 2011). We found that the expression of hlh-2::gfp and lin-29::wcherry in the AC was unaltered in hda-1(RNAi) animals, but nhr-67::wcherry and egl-43::gfp fluorescence was reduced (Figure 8). These results suggest that hda-1 positively regulates the expression of nhr-67 and egl-43 in the AC. The other two genes, hlh-2 and lin-29, function in an hda-1−independent manner.
Next, we investigated whether hda-1 regulates the expression of nhr-67 and egl-43 in the AC to specify π cell fates. One possibility is that these two genes act downstream of hda-1 to repress lag-2 transcription. Interestingly, RNAi-mediated knockdown of nhr-67 or egl-43, either alone or in combination with hda-1, caused a significant reduction in lag-2::gfp fluorescence in the AC (Figure 7I). The lag-2::gfp de-repression phenotype of hda-1(RNAi) was fully suppressed by nhr-67(RNAi) and egl-43(RNAi), suggesting that both transcription factors are necessary for hda-1-mediated lag-2 regulation. As expected, the mutant animals also had fewer π cells, as revealed by egl-13::gfp expression (Figure 9). Taken together, these findings allowed us to conclude that nhr-67 and egl-43 act downstream of hda-1 to promote lag-2 expression and π cell fate specification. However, they do not rule out the possibility that hda-1 and nhr-67 act independently in parallel to regulate lag-2 expression in the AC. Furthermore, these results suggest that other unidentified factors might also be involved in mediating hda-1 function in this process (Figure 10).
HDAC1 family members are present in diverse animal phyla and control a wide range of developmental processes. In C. elegans, HDA-1 has been shown to function as a transcriptional repressor and is involved in embryogenesis, gonadogenesis, germline formation, and vulval cell proliferation (Calvo et al. 2001; Dufourcq et al. 2002; Solari and Ahringer 2000; Zinovyeva et al. 2006). In this study, we report new, previously unidentified roles for hda-1 in the specification of the vulva and uterine π cell fates and describe the genetic basis of its function in these two lineages.
hda-1 controls vulval morphogenesis
Previously, hda-1 was shown to be required for vulval invagination, possibly by controlling the division axes of certain vulval cells (Dufourcq et al. 2002). We used five GFP-based cell fate markers to characterize the vulva phenotype in mutant animals and found that the cells in hda-1 animals failed to acquire correct identities. We also used a cell junction marker, ajm-1::gfp, to examine vulval toroids and found wider and sometimes missing rings, which is consistent with altered cell fates in hda-1 animals. In addition to cell fate specification studies, we also examined hda-1::gfp expression during development. GFP fluorescence was first detected in P(5−7).p daughters, and the expression continued in their progeny in the L3 and L4 stages, when cells acquire a specific fate (vulA to F) and undergo morphogenetic changes. Together, these results demonstrate the importance of hda-1 in vulval morphogenesis.
To identify hda-1 targets, we investigated the roles of two important transcription factors, lin-11 (LIM-HOX family) and fos-1b (fos proto-oncogene family). Mutations in these two genes cause defects in the differentiation and invagination of vulval progeny (Ferguson et al. 1987; Gupta et al. 2003; Marri and Gupta 2009; Seydoux et al. 1993). Our finding that hda-1 is required for the expression of lin-11::gfp and fos-1b::cfp in vulval cells provides evidence that hda-1 act upstream of both genes in vulval morphogenesis.
hda-1 is necessary for utse differentiation
We uncovered a new role for hda-1 in the formation of the vulval-uterine connection. Unlike in the wild-type animals, a thin utse membrane above the vulva cannot be observed in hda-1 animals. Our results showed that this defect is caused by the misspecification of π cell fates, as assessed by the expression of the transcription factors lin-11 and egl-13. The hda-1 mutants showed an increased number of π cells, suggesting that hda-1 normally limits the π fate of VU granddaughters. This defect was accompanied by the lack of uv1, as determined by the analysis of ida-1::gfp marker expression. Because VU precursors divide to give rise to the π cells that ultimately form the utse and uv1, these results demonstrate that hda-1 plays an important role in VU lineage specification.
The π cell phenotype in hda-1 animals is caused by defects in AC differentiation. We found that hda-1 is expressed in the AC at the time of π cell fate specification. Additionally, zmp-1::gfp expression was not observed in the AC of hda-1 mutants. These results, in combination with those involving the role of hda-1 in AC invasion (Matus et al. 2010), demonstrate a broad requirement for hda-1 in AC-mediated processes.
Genetic studies have shown that AC-mediated LIN-12/Notch signaling is necessary for the specification of π cell fate. The AC produces the DSL ligand lag-2, which activates the lin-12 pathway in VU cells. Therefore, alterations in lag-2 expression are likely to impact lin-12 signaling and π cell fate specification process. To address the role of hda-1 in utse formation, we examined the lag-2::gfp pattern in the AC and found it to be de-repressed in hda-1(RNAi) animals. Thus, hda-1 appears to limit the level of lag-2 transcription in the AC, thereby preventing inappropriate activation of LIN-12/Notch signaling in VU cells. We have found evidence for both positive and negative control mechanisms in hda-1−mediated regulation of lag-2. Although the genes that negatively regulate lag-2 expression are currently unknown, the positive regulation of lag-2 involves two important transcription factors: egl-43 and nhr-67 (Figure 10). The roles of egl-43 and nhr-67 have been studied previously in different developmental contexts. In the reproductive system, egl-43 regulates nhr-67 expression in the AC and nhr-67 in turn regulates lag-2-mediated AC and utse fate specification (Rimann and Hajnal 2007; Verghese et al. 2011). However, their relationship with hda-1 was unknown. Our study provides the first genetic evidence of an interaction between hda-1, nhr-67, and egl-43 in AC-mediated π cell fate specification processes. More work is needed to understand the precise nature of the interactions between these three genes.
In summary, we have demonstrated the crucial role of hda-1 in regulating LIN-12/Notch signaling in π fate specification. Antagonistic interactions between HDAC1 and the Notch pathway have been previously observed in various developmental contexts, such as neurogenesis and smooth muscle differentiation (Cunliffe 2004; Tang et al. 2012; Yamaguchi et al. 2005). Although the molecular basis of the HDAC1−Notch interaction remains unclear, HDAC1 co-repressor complexes (e.g., NURD) may play a role in some cases (Cunliffe 2008; Hayakawa and Nakayama 2011). Further analysis of the role of hda-1 in π fate specification processes could help clarify the mechanism of interaction between hda-1 and the LIN-12/Notch pathway.
HDAC1 and NURD complex genes in reproductive system development in C. elegans
Studies of HDAC1 have shown that it is part of the NURD protein complex that controls gene transcription by altering chromatin structure (Denslow and Wade 2007). Other NURD complex components include Mi2 ATPase, retinoblastoma-associated factors RbAp46/48, metastasis tumor associated factor, and the accessory protein p66. The C. elegans genome contains corresponding family members of these genes, all of which play important roles in the formation of the vulva and in other developmental processes (Dufourcq et al. 2002; Herman et al. 1999; Poulin et al. 2005; Unhavaithaya et al. 2002; von Zelewsky et al. 2000; Zhao et al. 2005). Because most C. elegans NURD genes are members of the SynMuv family, which interacts with Ras pathway components, their function has been primarily studied in the context of Ras-mediated vulval cell proliferation (Fay and Yochem 2007). Whether these genes have additional roles in the vulva and uterus has yet to be fully explored. von Zelewsky et al. (2000) previously showed that mutations in the Mi2 genes let-418 and chd-3 affect cell division and the invagination of vulval cells. Together with our work on hda-1, these results lend support to the conclusion that the NURD complex components play important roles in the morphogenesis of the vulva and vulva-uterine connection. In the future, characterization of hda-1 interactions with other NURD components should reveal whether hda-1 acts as part of the chromatin complex or through some other mechanism in reproductive system morphogenesis. The results will ultimately contribute to a better understanding of HDAC1-mediated gene regulation events in C. elegans and other eukaryotes.
We thank Ahmad Jomaa for help in the initial characterization of the hda-1 phenotype and Navid Khezri and Hyoung Kim for various RNAi screens. Vibha Raghavan assisted in some of the gfp expression experiments. The hda-1(e1795), hda-1(cw2), and lag-2::gfp strains were kindly provided by Jonathan Hodgkin, Wayne Forrester, and Iva Greenwald, respectively. We are thankful to Takao Inoue for the critical reading of an earlier version of the manuscript. This work was supported by an NSERC Discovery grant to BPG. Some of the strains used in this study were obtained from the CGC, which is funded by the National Institutes of Health.
Supporting information is available online at http://www.g3journal.org/lookup/suppl/doi:10.1534/g3.113.006999/-/DC1.
Communicating editor: B. J. Andrews
- Received October 27, 2012.
- Accepted June 2, 2013.
- Copyright © 2013 Ranawade et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Himalaya Darshan Resort Kausani, Kausani
Kausani – Bhatariya Road Kausani Estate.
Phone Number 9719247224 www.himalayadarshankausani.com
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What travellers are saying about this hotel
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Value For Money:
Reviews (110)
Top Reviews
Great location with beautiful scenery
Himalaya darshan is defiantly one of the finest resorthotels in India . . First of all it has a great location with beautiful scenery, and the rooms and restaurants are designed with excellent taste! The owner and staff are kind and thoughtful - they did everything they can to make us feel comfortable . It is the best place to spend time in when you are on a honey moon (they have amazing suites !! ). I definitely recommend this place to everyone who comes to visit in Kausani.
Friendly staff and good service
The resort is beautifully located on a hill-side and you would get a complete view of the mighty Himalayas from your room. The rooms are all in cottage style and that ensures that all other distraction and noise is away. The rooms are walloped and are quite comfortable. The bathrooms are very neat and decked up. The food is also quite good though the choice is a bit limited. The staff is well mannered and friendly. The property has lot of trees and birds keep flocking around.
Very scenic and serene location
It was a leisure trip to Kausani for a single day. This property is located out of the Kausani town, away from market area in the hills and forests. The hotel has beautiful cottages all facing the mighty Himalayas. The cottage gives a beautiful view of the Himalayas by sitting on the bed itself through the glass windows The food served is homely and great. Host and staff are more than welcoming and friendly and ready to help. We took an inclusive plan so didn't have to pay extra for the meals. There wont be any other option to eat as the hotel is located out of the town. Its better to have a car at your disposal.
Soul-Rejuvenating stay, with the Himalayas looking straight at you
How would you feel to wake up and view the Mighty Himalayas gleaming at you with a tinge of orangish-golden reflection of the sun? Heavenly, isn't it Well, that's what Himalaya Darshan Resort has to offer After a long journey through the mountains, this resort serves as a very peaceful and serene place to relax your soul. Nature at its best, Himalaya Darshan Resort provides everything a nature lover can wish for. Surrounded by lush green forests, loads and loads of mountainous birds and a candid view of the Himalayas, and the only sound of your breathing, this is nature at its very best. Brilliant service and food to go along with the humbleness of the hosts is very admirable and praiseworthy. It's a brilliant place for all age-group of people to go and stay, however, if you are a couple, this place is a 'must-go' one The only point which I found could have been better was if the dinner could have been served in the room, since it was very cold outside in the night; rest all was simply great. Me, and my wife; would definitely like to go and stay here once again; but this time for a longer period of time.
Leisure trip with good hospitality by owner
Our purpose of visit was of leisure trip. No. Of Pax were 6 adults with 2 children. Amenities offered are Cottages, Buffet breakfast and dinner and Evening Snacks. Activities available are Badminton play area and Trees with fruits. Hospitality by the owner of the property (Mr. Manoj) is a nice person and his hospitality is commendable and also the staff was courteous. Advice to travellers, choose the right weather to go to this place and preferred time to go in as per my opinion is in October - November and then January - February .
Himalaya Darshan Resort Kausani is ranked #1 among the 49 hotels in Kausani with an average rating of 6.1 out of 7. It is one of the 17, 3-star Resorts in Kausani. On HolidayIQ, it has a total of 66 photos and 110 text reviews. it is rated top for its Service, Location and Appearance. It was also named winner of the Better Holiday Awards in 2017 under Great Location.
The online booking price of the hotel ranges between Rs 5,300 to Rs 5,300 per night. The hotel offer 8 rooms to check availability or to avail complimentary breakfast, we recommend contacting the hotel to check if the final tariff includes it.
The ambience and the location of the hotel makes it a suitable option for variety of travellers. Family (46%) and Couple (33%) are the most common type of travellers that like to stay here. 55% of guests enjoy the hotel's relaxed environment, whereas 21% have rated the ambience as romantic.
Although the hotel is a suitable stay option throughout the year for travellers, book your accommodation in the months of Apr, May and June for the best experience.
Himalaya Darshan Resort Kausani is located at Kohina . Anasakti Ashram (3 Kms) is the most popular sightseeing attractions located near the hotel.
The hotel ensures you are well taken care of during your stay. By providing free wifi access, the hotel makes sure you are always connected to the internet.
Other amenities include Backup Generator, Breakfast Services, Doctor On Call, Laundry Services and Parking Facility. For checkin and checkout time, we suggest contacting the hotel.
If you are in need for airport transfers or require a car for sightseeing around the city or you have to do an early check-in, then we recommend contacting the hotel directly and requesting for these additional services. All of the available amenities ensure your stay is enjoyable and free from any hassles.
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January 7, 2015
CLIENT TYPE: A global IT services company
LOCATION: Chihuly Gallery, Las Vegas
Our client was looking to host a brand enhancing experience at CES with interesting content and activities in a unique setting. Since CES is a large trade show with many hospitality events, it was important to create an experience that stood out from the crowd and one that would leave a lasting impression.
Given the large volume of people who attend CES, we sought to find an environment where we could create a haven away from the masses. After a thorough venue search, we decided to host the event at the Chihuly Gallery given its off the beaten path feel and central location on the Las Vegas Strip. Dale Chihuly is a world renowned glass sculptor and his works often move into large scale installations. This gallery in particular showcased many of his large colorful glass installations making the setting a unique visual environment.
In order to provide a unique and engaging activity for the guests during the reception portion of the evening, we produced a Wine Sensory Experience wherein guests could experience all the sensory elements of wine individually, including even through music. In this activity, we also deconstructed structural elements of wine including Aroma, Tannin, Acid, and Body. and even music. We also paired each wine with a different style of song for the guests to experience wine through music.
Our client was keen on featuring content that is topical and trending at CES, but also fun and insightful for a mainstream audience. Our guest speaker for the evening was Gary McCoy, a sports scientist from Catapult Sports. Gary led a lively discussion about how wearable devices are used on athletes in both college and professional sports teams to improve performance. The topic of the future of wearable devices was trending heavily at CES, so our event content was very much spot on for our guests and they enjoyed learning about the practical application of these technologies for some of their favorite teams and athletes.
We strived to create an environment that was sophisticated, yet comfortable. To facilitate interaction during the dinner, we served dinner family style and encouraged questions during the presentation by Gary McCoy. Catering was provided by the Mandarin Oriental Las Vegas and they did an excellent job of creating an elegant food experience offsite.
The Wine Sensory experience allowed guests to think about wine in a different way, and much like the art in the gallery, discover that wine can be subjective and interpreted differently. The guests had a great time discovering new ways to enjoy and learn about wine. The presentation led by Gary McCoy resulted in a lively discussion about wearable devices and professional sports teams. The guests were so captivated by the content that the presentation ended up being more of a conversation as there were so many questions. This was definitely a one of a kind experience of art, wine, and technology. The guests left feeling rewarded by the experience.


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What would you like to do now?
Bedrooms: 5
Bathrooms: 4.5
Sq Feet: 4,653
City: Scottsdale
Zip: 85255
Sub Division: Grayhawk Parcel 2G (A) East
Property Description
Amazing 5 bed/4.5 bath single level custom home located in the heart of one of North Scottsdale's most desirable communities, Retreat at Grayhawk! Sitting on a large private cul-de-sac lot(35,000+sqft), this open concept masterpiece has a lot to offer including: Courtyard entrance, vaulted ceilings, entertainment area with a bar & dual sliders that open to a resort style yard with pool, putting/chipping green, & stunning mountain views. Master suite with his & hers closets, wrap-around shower & separate bathtub. Family room with fireplace that opens to a large kitchen with island & dining nook. Oversized garage for multiple vehicles and toys. Solar Panels to reduce costs. The Location is perfect with easy access to shopping & entertainment!
General Information
School Information
Community Information
Lot Information
- Directions:
- Head north on N Pima Rd, Turn left onto E Thompson Peak Pkwy, Turn right onto N Grayhawk Dr, Turn right onto N 81st St, Continue onto E Overlook Dr.
- Cross-Streets:
- N Pima Rd & E Thompson Peak Pkwy


text:
All NASA Ames workers
may not get back pay
Re: "California leaders move to help federal workers during the shutdown — but how far can they go?" (Mercurynews.com, Jan. 18):
An under-reported aspect of the government shutdown is that far more than federal workers have been directly affected.
At NASA Ames, for instance, many in the workforce are not civil servants but are employed by services contractors or university grants. Such workers include highly trained research scientists and assistants, software engineers, systems administrators and San Jose State students working on scientific degrees.
These workers, too, have been kept from working for the past month and continuing to support technologies development and aerospace research that benefits national transportation safety enhancements.
Unlike their federal colleagues though, these workers have no guarantee they'll receive back pay once this political brouhaha is concluded.
Kevin Gregory
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When you think of fried chicken, you'll never associate it with veganism. Hence, this recipe is actually using cauliflower as the 'fried chicken'. You'll get just as much crunch but healthier and easy to prepare!
This recipe serves 2 people.
1 head cauliflower
1 tbsp virgin sesame oil
200ml water
2 tbsp brown sugar
1 tbsp Korean chili paste (Gochujang)
1 tbsp soy sauce
½ medium to large onion, chopped
3 cloves garlic, minced
1 scallion, chopped
Sesame seeds, peanuts and sliced chilli to garnish (optional)
Photo credit: SORTEDfood
- Pre-heat oven to 180℃.
- Cut cauliflower into bite-sized chunks and toss in virgin sesame oil. Bake in oven for about 20 minutes or until edges are slightly brown.
- Mix brown sugar, Korean chilli paste and soy sauce in a bowl.
- In a pan, add a tablespoon of water and water-fry onions and garlic. After a few minutes, add the paste mixture and scallion. Let it boil on medium heat until the sauce thickens.
- Toss cauliflower into sauce then garnish with sesame seeds and chilli. Enjoy!


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Henok Wendirad Mengistu
In late 2011, Henok Menistu began a journey pursuing an entrepreneurial endeavor. He co-founded a promotion and marketing company, and reports that despite failing six times in the past six years, he has gained an enormous amount of learning and experience in business and entrepreneurship. Currently he is working as a General Manager in a social enterprise that he co-founded named Mak-Addis Tutors P.L.C. The company mainly provides a tutor-student matchmaking service all over Addis Ababa for students ranging from kindergarten to 12th grade. The company also serves as an incubation center for the tutors by enabling them to innovate different educational materials, including instructional board games.
Tina Medina
(619) 260-7568


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OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.
Pathophysiology: Several biologic theories are postulated for the pathogenesis of phobic disorders, most focusing on the dysregulation of endogenous biogenic amines. Sympathetic nervous system activation is common in phobic disorders, resulting in elevations in heart rate and blood pressure, as well as symptoms such as tremor, palpitations, sweating, dyspnea, dizziness, and paresthesias.
Major Research: At Mayo Clinic, researchers are carrying out procedures to find out the way to erode phobias.
Statistics: 45% of people are with any kind of phobias.


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This past year I've noticed "sitting is the new smoking of our generation" is a popular topic trending in the media. As we all have heard, sedentary behavior, such as sitting for extended periods of time is negatively detrimental to both physical and mental health. Sedentary behavior increases the risks of all-cause mortality, metabolic syndrome, cardio-metabolic biomarkers, triglycerides, cholesterol levels, blood pressure, diabetes, obesity and cancer. In addition, it is also negatively associated with mental health and psychosocial well-being (Owen, et al., 2010; Steinberg, et al., 2014). Despite the widely acknowledged health detriments associated with sedentary behavior, many of us, including myself, are still guilty of sitting most of our day!
While sitting at my desk for 5 consecutive hours I realized that the majority of my day was spent seated. We spend the majority of our days sitting during the morning commute, sitting at our work desk, sitting during our lunch break, sitting during our evening commute and finally finishing off the day sitting on our couch watching TV.
Of course we take breaks, go for a stroll, stretch, workout, etc., but when there is a massive pile of work on your desk, many of us are likely to forget these important breaks. Is there a way we can still get our work done but avoid being seated the entire time?
The modern standing desks are one method that allows one to work while standing to avoid being seating the entire day. Before we run to the mall to purchase these, let's consider the risks and benefits of standing desks. Are they a good alternative to sitting desks? Should they be used in combination with sitting desks? Are they comfortable? Do they have to be set up individually for each person?
Research from The Take-A-Stand Project (2011) has shown that when installed within the workplace, standing desks can significantly reduce sitting time. In addition to increasing non-sitting time, they were effective in reducing upper back and neck pain, and improving mood states within a 2-week period (Pronk, et al., 2011). MacEwan, et al. (2014) also noted the psychological well-being associated with increased standing and little impact on work performance was indicated. Individuals using standing desks had a significant increase in caloric expenditure while compared to sitting desks (Reiff, 2012). These desks are gaining acceptance and popularity within workplaces due to the health benefits associated with increased standing time (MacEwan, 2014).
In summary, research shows that these desks increase calorie expenditure, reduce postural discomforts due to prolonged sitting and improve mood, all the while having little impact on your productivity level.
Personal experiences of individuals using standing desks revealed that these desks are hard on the feet. Standing for extended periods of time can cause feet soreness, especially if you are standing for the entire workday. Additionally, standing for an expected period of time also causes fatigue (Mullis, 2012). It is also important to set up these desks appropriately for each user to ensure they are at the appropriate height and will not cause other problems in the upper extremities.
In conclusion, although these standing desks are a great solution to our problem of sitting for too long, they need to be used with caution. It may not be feasible to stand for a 10-hour work-day, nor is it comfortable to do so. It is best to alternate between sitting and standing throughout the day. It is also very important to consider your physical restrictions. If you have back or foot problems, this standing desk may not be the best option. It is important to consider both the risks and benefits before making the decision to incorporate the standing desk within your workplace. Consider an ergonomic assessment with an occupational therapist to assess what workstation is best for you!
We would love to hear your thoughts about these new trendy desks. If you have used them, what were your personal experiences? Would you recommend them? Why or why not?
- MacEwen, B., T., MacDonald, D, J., Burr, J. F. (2015). A systematic review of standing and treadmill desks in the workplace. Prev Med., 70, 50-8. doi: 10.1016/j.ypmed.2014.11.011.
- Mullis, G. (2012). What Are The Advantages And Disadvantages Of Standing Desks? Forbes. Retrieved from http://www.forbes.com/sites/quora/2012/07/16/what-are-the-advantages-and-disadvantages-of-standing-desks/
- Owen, N., Genevieve, H. N., Mathews, C. E., Dunstan, D. W. (2010). Too Much Sitting: The Population-Health Science of Sedentary Behavior. Exerc Sport Sci., 38(3), 105-113.
- Pronk, N. P., Katz, A. S., Lowry, M., Payfer, J.R.(2011). Reducing occupational sitting time and improving worker health: the Take-a-Stand Project. Prev Chronic Dis, 9:110323. DOI: http://dx.doi.org/10. 5888.pcd9.110323
- Reiff, C., Marlatt, K., Dengel, D. R. (2012). Difference in caloric expenditure in sitting versus standing desks. J Phys Act Health, 9(7), 1009-11.
- Steinberg, S. I., Sammel, M. D., Harel, B. T., Schembri, A., Policastro, C., Bogner, H. R., Negash, S., & Arnold, S. E. (2014). Exercise, Sedentary Pastimes, and Cognitive Performance in Healthy Older Adults. American journal of Alzheimer's disease and other dementias, 30(3), 290-298. doi: 1533317514545615.


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The creative school
for the cultural industry
We offer learners aged 14 to 19 a different kind of education to mainstream secondary provision. As the industry school specialising in creative media arts, performance and production technologies, alongside our vital core offer in English, Maths and Science, we equip our learners to be credible and successful within the creative and cultural industries such as television, film, theatre and digital media productions.
EUTC Updates


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Jharkhand JAC TET 2019 Online Application and Imp dates. JHARKHAND TEACHERS ELIGIBILITY TEST which is also to be known as JAC TET 2019. This TET is being regulated by the Central Regulating Authority and is being realized by the Department of School Education.
Jharkhand JAC TET 2019 Application
The candidates must acquire 60 % marks in order to clear this JAC TET examination.
The government of Jharkhand is recruiting the teachers who are eligible to teach mainly at primary level i.e. classes from (I TO V) and at upper primary level i.e. classes from (VI TO VIII). This TET is compulsory for the candidates to clear in order to be liable to become a teacher.
- Applicants must be required to get 45% marks in their Senior Secondary Examination.
- The candidates must possess the 4yrs degree of B.ED.
- The candidates must score 50% marks in their degree courses like B.SC, B.A and the B.ED.
- Special Education qualifications were also being eligible to apply for this examination and the applicants who were being appearing in the 2yr of Elementary Educations can also apply for this TET.
- 1ST level consists at the primary level.
- 2nd level is at the upper primary level.
- The candidates who are interested in teaching classes from (I TO VIII) can also apply for it.
- The paper consists of 150 marks with each part is of 30 marks.
- The duration for the examination is 1 hour and 30 minutes.
- The question paper constitutes of questions related to child development, language-1, language-2, math's and the environment based questions.
Jharkhand JAC TET 2019 Application Correction:-
The candidates can make changes in application form at given time interval. Candidates can make changes in the name, date of birth, father name, category, address, year, educational details.
Jharkhand TET 2019 Rejection list:
Jharkhand Board of School Education will be issued the list of rejected candidates. Those candidates make mistakes during filling application form (still after the application correction) are rejected by the authority.
Jharkhand JAC TET 2019 EXAMINATION DATE:-
The exam of JAC TET was held in the month of November 2019 which has already being gone. The candidates may prepare for the upcoming session 2019 and they can take the help of sample papers and from this yr question paper which is available on the official website (jac.nic.in).
Examination Dates JAC TET 2019:
|Online Application form will be issued
|September 2019
|Last Date of Application form
|October 2019
|Admit Card
|November 2019
|Examination Date
|November 2019
|Answer key will be announced
|December 2019
|Result will be announced
|December 2019
Admit Card JAC TET 2019 Exam:
- E-admit card will be available at official site of Jharkhand Board of School Education
- Admit card will be published in the mid of November 2019.
- Admit card carry all details about the examination.
- E-Admit card will be updated before 15 days of Exam.
- There will be no offline mode to collect admit card.
Answer key JAC TET 2019 Exam:
- Answer key will be announced after the written examination.
- Applicants can download from official site.
- Official answer key will be published after the 30-45 days of examination.
Result JAC TET 2019 Examination:
- Result will be announced in the month of December 2019.
- Candidates can download the result through official site.
- Candidates needs to enter their credential and submit.
- Result and marks statement will be displayed.
- Selected candidates will be given certificate.


text:
The Cleveland Gladiators are an arena football team in Cleveland Ohio, and I have the absolute pleasure of working with them on a Facebook PPC campaign to get 10,000 fans by the end of the season.
There are a lot of things that make working for the Gladiators fun. Of course the season ticket don't hurt, and the fact that the sport is actually really exciting so I can honestly say I enjoy the games. Then the fact that so far they are having an excellent year makes it even more fun.
The next reason why I like this project so much is the people I work with are wonderful. They are a fun group who is optimistic and excited about what they do. They are very supportive of us and of each other. There is always a feeling of comradery and a true desire to do a good job on everyone's part.
The last thing that makes the Gladiators a blast are the fans. Having a group of people who are that supportive of an organization is really amazing to work with. Because most of our campaign focuses on the Facebook Fan Page keeping up with the posts is imperative on our part. It is great to hear all the positive comments of how much the fans enjoy the games, but what I get an even greater kick out of is how the fans will defend the team as if the guys playing are their own flesh and blood! It really shows the power of Social Media.
Besides running the PPC campaign on Facebook the Gladiators have someone in charge of monitoring and engaging visitors on the Fan Page. This is a great place where they can get feedback and find out what people really want.
Give to receive is another thing the Cleveland Gladiators embrace. They ar currently running a Military Night to honor all the men and women who have dedicated themselves to protecting our freedom. Thank you to all our Armed Forces!
Thank you and have a terrific week,