text:
TSA: Fliers will face more scrutiny for powders in carry-on bags
TSA is asking foreign airports to match U.S. policy in urging travelers to remove larger containers of powders from carry-on bags for screening
TSA: Fliers will face more scrutiny for powders in carry-on bags TSA is asking foreign airports to match U.S. policy in urging travelers to remove larger containers of powders from carry-on bags for screening Check out this story on USATODAY.com: https://usat.ly/2yvRbbY
Today in the Sky
Bart Jansen, USA TODAY Published 4:43 p.m. ET June 19, 2018 | Updated 8:46 a.m. ET June 20, 2018
A Transportation Security Administration security check is viewed at Wilkes-Barre/Scranton International Airport in Avoca, Pa., on Jan. 19, 2018. (Photo: Jake Danna Stevens, AP)
WASHINGTON – The Transportation Security Administration began scrutinizing containers of powders in fliers' carry-on bags last summer as part of a broader security push, and will soon ask foreign airports that send flights directly to the U.S. to do the same.
The focus is on containers holding at least 350 milliliters of powder, which is about the size of a can of soda. Starting Wednesday, TSA and airlines are going to step up awareness efforts about the change, urging passengers to pack larger containers in checked luggage and remove smaller containers from carry-on bags for separate screening, similar to small containers of liquids.
And, starting June 30, TSA will request foreign airports with non-stop U.S. flights match the effort, much as it did last summer when it began requiring passengers to remove electronics larger than cellphones from carry-on bags for separate screening.
The security effort isn't a ban. But the risk for a traveler returning with a large container of Moroccan spice in a carry-on bag rather than checked luggage is that a checkpoint officer could force the person to throw away a suspicious powder before boarding the plane.
"For ease of travel, TSA recommends placing larger items in checked baggage prior to arriving at the security checkpoint," said Mike Bilello, a TSA spokesman. "The international aviation community and industry's actions represent collaborative approaches that greatly enhance global aviation security."
The main security concern is from improvised explosives, but TSA is also concerned about fentanyl or pepper spray in the cabin.
TSA says powders can include items like cosmetics, baby powder and protein or energy powder mixes, among others. Gun powder remains prohibited from all checked or carry-on luggage.
"We encourage people to divest certain items – especially organic items – in order to get a clearer view of what's going on inside the bag," said Mike England, a TSA spokesman. "It's something we advise people to do. We're asking our foreign partners to do what we're already doing domestically."
The effort is another example of tightening aviation security. Airport checkpoint security was federalized under TSA after the terrorist hijackings Sept. 11, 2001, and has become stricter in recent years with developments of non-metallic explosives.
Earlier steps include:
►September 2006: restricting containers of liquids, gels and aerosols to 3.3 ounces in carry-on bags, after a trans-Atlantic bomb plot that was foiled.
►March 2010: installing full-body scanners at checkpoints that can detect unusual objects beneath a traveler's clothing. The effort to detect non-metallic explosives came after the underwear bomber tried to detonate an improvised explosive device on a flight from Amsterdam to Detroit in December 2009.
►July 2017: requiring travelers to remove all electronics larger than cellphones from carry-on bags for screening, after intelligence revealed terrorists trying to hide bombs in laptops.
More recently, travelers noticed more scrutiny of food in carry-on bags this spring at TSA checkpoints. The challenge for security officials is to get a good look at objects in sometimes cluttered carry-on bags.
Rather than ban snacks or containers of powders, TSA is asking travelers to remove them from carry-on bags for a better view in the X-ray. The alternative is to risk a hand search of the bag, which slows down the traveler and the line.
"Everyday items, including some foods, books and magazines, powders, and large electronics may result in additional screening," Bilello said.
TODAY IN THE SKY: The world's 20 busiest airports (2017)
The world's busiest airports (2017)
20. Denver (DEN): 61,379,396. Rank in 2016: 18th. (Data: Airports Council International, for full-year 2017) Arina Habich, Getty Images/iStockphoto
19. Seoul/Incheon (ICN): 62,157,834 (up 7.5%). Rank in 2016: 20th.(Data: Airports Council International, for full-year 2017) June Yeon-Je, AFP/Getty Images
18. Singapore Changi (SIN): 62,220,000 (up 6%). Rank in 2016: 17th.(Data: Airports Council International, for full-year 2017) Jeremy Dwyer-Lindgren, special for USA TODAY
17. Jakarta/Soekarno-Hatta (CGK): 63,015,620 (up 8.3%). Rank in 2016: 19th.(Data: Airports Council International, for full-year 2017) Bay Ismoyo, AFP/Getty Images
16. New Delhi(DEL): 63,451,503 (up 14.1%). Rank in 2016: 22nd. (Data: Airports Council International, for full-year 2017) Instants, Getty Images/iStockphoto
15. Istanbul Atatürk (IST): 63,872,283 (up 6%). Rank in 2016: 14th. (Data: Airports Council International, for full-year 2017) Bulent Kilic, AFP/Getty Images
14. Frankfurt (FRA): 64,500,386 (up 6.1%). Rank in 2016: 13th. (Data: Airports Council International, for full-year 2017) Nicolas Armer, AP
13. Guangzhou, China (CAN): 65,887,473 (up 10.3%). Rank in 2016: 15th. (Data: Airports Council International, for full-year 2017) ziggy_mars, Getty Images/iStockphoto
12. Dallas/Fort Worth (DFW): 67,092,194 (up 2.3%). Rank in 2016: 11th. (Data: Airports Council International, for full-year 2017) Daniel Slim, AFP/Getty Images
11. Amsterdam Schiphol (AMS): 68,515,425 (up 7.7%). Rank in 2016: 12th. (Data: Airports Council International, for full-year 2017) Lex van Lieshout, EPA
10. Paris Charles de Gaulle (CDG): 70,001,237 (up 6.1%).Rank in 2016: 10th.(Data: Airports Council International, for full-year 2017) Jeremy Dwyer-Lindgren, special to USA TODAY
9. Shanghai Pudong (PVG): 70,001,237 (up 6.1%). Rank in 2016: 9th.(Data: Airports Council International, for full-year 2017) Peter Parks, AFP/Getty Images
8. Hong Kong (HKG): 72,663,955 (up 3.4%). Rank in 2016: 8th. (Data: Airports Council International, for full-year 2017) Jeremy Dwyer-Lindgren, special to USA TODAY
7. London Heathrow (LHR): 78,014,598 (up 3%). Rank in 2016: 7th. (Data: Airports Council International, for full-year 2017) Justin Tallis, AFP/Getty Images
6. Chicago O'Hare (ORD): 79,828,183 (up 2.4%). Rank in 2016: 6th. (Data: Airports Council International, for full-year 2017) Jeremy Dwyer-Lindgren, special to USA TODAY
5. Los Angeles (LAX): 84,557,968 (up 4.5%). Rank in 2016: 4th. (Data: Airports Council International, for full-year 2017) Jeremy Dwyer-Lindgren, special to USA TODAY
4. Tokyo Haneda (HND): 85,408,975 (up 6.5%). Rank in 2016: 5th. (Data: Airports Council International, for full-year 2017) Kazuhiro Nogi, AFP/Getty Images
3. Dubai International (DXB): 88,242,099 (up 5.5%). Rank in 2016: 3rd. (Data: Airports Council International, for full-year 2017) Ben Mutzabaugh, USA TODAY
2. Beijing (PEK): 95,786,442 passengers (up 1.5%). Rank in 2016: 2nd. (Data: Airports Council International, for full-year 2017) Andy Wong, AP
1. Atlanta (ATL): 103,902,992 passengers (down 0.3%). Rank in 2016: 1st. (Data: Airports Council International, for full-year 2017) David Goldman, AP
Read or Share this story: https://usat.ly/2yvRbbY
Miranda Lambert, Mookie Betts and TSA PreCheck: Sign up at music fests, Red Sox games
'Angels exist': Gayle King, Holland Taylor thank Delta employees for finding lost items
Rethinking a Dominican Republic vacation? Airlines waive change fees after tourist deaths
United extends 737 Max cancellations through Sept. 3; check your reservations


James Bellingham, of Levens, who died in 1680, left a large family …. Alan, the eldest, was destined to ruin the estate and die in exile. Henry, the second son, died unmarried in 1687, leaving what he had to leave to his brother Alan. William, the third son, was a barrister, and had he been the eldest things would have been very different. Of the married daughters, Mrs. Johnson and Mrs. Patten seem to have come most in contact with Col. Bellingham. He mentions them frequently in the diary, along with their brother, William Bellingham. He never, however, mentions the unhappy spendthrift who, at the very time the diary commences (1 Aug., 1688) must have been deeply involved, nor is there any allusion to Levens Hall being shut up when the owner had fled to France.
 Leonard Naylor, 'Bellingham, Alan (1656-93), of Levens, Westmld. | History of Parliament Online', accessed 7 April 2016, http://www.historyofparliamentonline.org/volume/1660-1690/member/bellingham-alan-1656-93.


Romanian chef Adi Hadean is a TV and radio personality, and a former judge on the Romanian edition of MasterChef cooking show series. He has hosted many cooking shows such as Sare și Piper as well as Rețete fără Secrete, but has never lost touch with his roots. The Masterchef Romania star has long been a champion of traditional Romanian cuisine through his popular food blog and numerous cookbooks. With his involvement in various programmes back in Romania which support developing younger chefs of tomorrow, Chef Hadean's commitment to developing young talent shows no sign of wavering, hoping that it would help encourage younger chefs into becoming stronger, passionate chefs of the future that can take on the mantle of Romania's Household Chef.


text:
Q: How to add a style to taxonomy edit page Is there anyway to load a custom style in specific taxonomy pages?
for example these two pages:
wp-admin/edit-tags.php?taxonomy=news-category&post_type=news
wp-admin/term.php?taxonomy=news-category&..

I added a style to admin but other pager got edited too, how can we load the style when in these two pages of custom post type taxonomy?

A: You can do it like this:
add_action ('admin_enqueue_scripts', 'wpse_style_tax') ;

function
wpse_style_tax ()
{
    // these 3 globals are set during execution of {edit-tags,term}.php
    global $pagenow, $typenow, $taxnow ;

    if (!in_array ($pagenow, array ('edit-tags.php', 'term.php')) {
        return ;
        }
    if ('news' != $typenow) {
        return ;
        }
    if ('news-category' != $taxnow) {
        return ;
        }

    wp_enqueue_style ('wpse_my_handle', 'path_to_css_file', ...) ;

    return ;
}

A: I know there's already an accepted answer, but here's another way to accomplish the same thing using hooks.
//* Make sure we're on the load edit tags admin page
add_action( 'load-edit-tags.php', 'wpse_262299_edit_tags' );
add_action( 'load-term.php', 'wpse_262299_edit_tags' );

function wpse_262299_edit_tags() {

  //* Return early if not the news post type
  if( 'news' !== get_current_screen()->post_type ) {
    return;
  }

  $taxonomies = [ 'news-category', 'other-taxonomy' ];
  //* Add actions to $taxonomy_pre_add_form and $taxonomy_pre_edit_form
  array_filter( $taxonomies, function( $taxonomy ) {
    add_action( "{$taxonomy}_pre_add_form",  'wpse_262299_enqueue_style' );
    add_action( "{$taxonomy}_pre_edit_form", 'wpse_262299_enqueue_style' );
  });
}

function wpse_262299_enqueue_style( $taxonomy ) {
  //* All the logic has already been done, do enqueue the style
  wp_enqueue_style( 'wpse-262299', plugins_url( 'style.css', __FILE__ ) );
}

redpajama_set_name: RedPajamaStackExchange


text:
{-
From: dw@minster.york.ac.uk
To: partain
Subject:    a compiler test
Date:        3 Mar 1992 12:31:00 GMT

Will,
   One of the decisions taken at the FLARE meeting yesterday was that we
(FLARE people) should send you (GRASP people) interesting Haskell programs
to test your new compiler. So allow me to present the following program,
written by Colin Runciman in various functional languages over the years,
which puts propositions into clausal form. The original program was
interactive, but I've made it batch so that you can run it over night.
Here is an example run with the prototype compiler. Note the result is
"a <=".

        hc clausify.hs
        Haskell-0.41 (EXPERIMENTAL)
        Glasgow University Haskell Compiler, version 0.41
        G-Code version
        -71$ a.out
        a <=
        -71$

Cheers,

David
-}

------------------------------------------------------------------------------
-- reducing propositions to clausal form
-- Colin Runciman, University of York, 18/10/90

-- an excellent benchmark is: (a = a = a) = (a = a = a) = (a = a = a)
-- batch mode version David Wakeling, February 1992

module Main(main) where

import Data.Ix
import System.Environment

main = do
  (n:_) <- getArgs
  putStr (res (read n))

res n = concat (map clauses xs)
 where xs = take n (repeat "(a = a = a) = (a = a = a) = (a = a = a)")
       {-# NOINLINE xs #-}

data StackFrame = Ast Formula | Lex Char

data Formula =
  Sym Char |
  Not Formula |
  Dis Formula Formula |
  Con Formula Formula |
  Imp Formula Formula |
  Eqv Formula Formula

-- separate positive and negative literals, eliminating duplicates
clause p = clause' p ([] , [])
           where
           clause' (Dis p q)       x   = clause' p (clause' q x)
           clause' (Sym s)       (c,a) = (insert s c , a)
           clause' (Not (Sym s)) (c,a) = (c , insert s a)

-- the main pipeline from propositional formulae to printed clauses
clauses = concat . map disp . unicl . split . disin . negin . elim . parse

conjunct (Con p q) = True
conjunct p = False

-- shift disjunction within conjunction
disin (Dis p (Con q r)) = Con (disin (Dis p q)) (disin (Dis p r))
disin (Dis (Con p q) r) = Con (disin (Dis p r)) (disin (Dis q r))
disin (Dis p q) =
  if conjunct dp || conjunct dq then disin (Dis dp dq)
  else (Dis dp dq)
  where
  dp = disin p
  dq = disin q
disin (Con p q) = Con (disin p) (disin q)
disin p = p

-- format pair of lists of propositional symbols as clausal axiom
disp (l,r) = interleave l spaces ++ "<=" ++ interleave spaces r ++ "\n"

-- eliminate connectives other than not, disjunction and conjunction
elim (Sym s) = Sym s
elim (Not p) = Not (elim p)
elim (Dis p q) = Dis (elim p) (elim q)
elim (Con p q) = Con (elim p) (elim q)
elim (Imp p q) = Dis (Not (elim p)) (elim q)
elim (Eqv f f') = Con (elim (Imp f f')) (elim (Imp f' f))

-- the priorities of propositional expressions
{- UNUSED:
fpri   (Sym c) = 6
fpri   (Not p) = 5
fpri (Con p q) = 4
fpri (Dis p q) = 3
fpri (Imp p q) = 2
fpri (Eqv p q) = 1
-}

-- insertion of an item into an ordered list
-- Note: this is a corrected version from Colin (94/05/03 WDP)
insert x [] = [x]
insert x p@(y:ys) =
  if x < y then x : p
  else if x > y then y : insert x ys
  else p

interleave (x:xs) ys = x : interleave ys xs
interleave []     _  = []

-- shift negation to innermost positions
negin (Not (Not p)) = negin p
negin (Not (Con p q)) = Dis (negin (Not p)) (negin (Not q))
negin (Not (Dis p q)) = Con (negin (Not p)) (negin (Not q))
negin (Dis p q) = Dis (negin p) (negin q)
negin (Con p q) = Con (negin p) (negin q)
negin p = p

-- the priorities of symbols during parsing
opri '(' = 0
opri '=' = 1
opri '>' = 2
opri '|' = 3
opri '&' = 4
opri '~' = 5

-- parsing a propositional formula
parse t = f where [Ast f] = parse' t []

parse' [] s = redstar s
parse' (' ':t) s = parse' t s
parse' ('(':t) s = parse' t (Lex '(' : s)
parse' (')':t) s = parse' t (x:s')
                   where
                   (x : Lex '(' : s') = redstar s
parse' (c:t) s = if inRange ('a','z') c then parse' t (Ast (Sym c) : s)
                 else if spri s > opri c then parse' (c:t) (red s)
                 else parse' t (Lex c : s)

-- reduction of the parse stack
red (Ast p : Lex '=' : Ast q : s) = Ast (Eqv q p) : s
red (Ast p : Lex '>' : Ast q : s) = Ast (Imp q p) : s
red (Ast p : Lex '|' : Ast q : s) = Ast (Dis q p) : s
red (Ast p : Lex '&' : Ast q : s) = Ast (Con q p) : s
red (Ast p : Lex '~' : s) = Ast (Not p) : s

-- iterative reduction of the parse stack
redstar = while ((/=) 0 . spri) red

-- old: partain:
--redstar = while ((/=) (0::Int) . spri) red

spaces = repeat ' '

-- split conjunctive proposition into a list of conjuncts
split p = split' p []
          where
          split' (Con p q) a = split' p (split' q a)
          split' p a = p : a

-- priority of the parse stack
spri (Ast x : Lex c : s) = opri c
spri s = 0

-- does any symbol appear in both consequent and antecedant of clause
tautclause (c,a) = [x | x <- c, x `elem` a] /= []

-- form unique clausal axioms excluding tautologies
unicl a = foldr unicl' [] a
          where
          unicl' p x = if tautclause cp then x else insert cp x
                       where
                       cp = clause p

while p f x = if p x then while p f (f x) else x

redpajama_set_name: RedPajamaGithub


text:
RobertPattinsonFilms.com – Robert Pattinson Movie Network
Queen of the Desert
The Childhood of a Leader
The Trap
Hold On To Me
Past Movies
Happy Birthday Francis Lawrence @hibbits!!
Jen March 26, 2011 Water for Elephants
Wishing you the best birthday yet!
happy birthday @hibbits
Written by Jen
Jen is from LA, that's Lower Alabama. Jen now lives in Las Vegas, by way of San Francisco. She is a wife, mother, small business owner, reality TV junkie, blogger, hoarder of domains, beach bum, far left Democrat, and highly opinionated woman, among other things... Her hobbies include sniffing candles, tweeting Real Housewives, and playing dress up with her 5 year old.
Lynda Motl
Hope you have a very Happy Birthday and thank you for what we all believe will be a very successful movie!! We're all anxious to see it multiple times!!
IVYFIGGY
Happy Birthday Francis!
Alice87
Happy Birthday, Mr. Lawrence!!!
Thank you so much for bringing this wonderful Story to life!
somanywards
**Happy Birthday**
Mr. Lawrence I hope you have the most wonderful day.
Thank you for bringing this beautiful movie to us!
You have no idea the effect it's going to and has already had on us .
jennpattz
HAPPY BIRTHDAY TO A WONDERFUL GUY!!! we wish u a long life of success and prosperitty! we love u!! Thanks for everything! <3
cmdww
Happy Birthday Mr. Lawrence. Thank you so much for making Water For Elephants. I can't wait for April 22nd. I hope you have a wonderful year filled with love and happiness.
Lisa Emig
Mr. Lawrence, I wish you the most spectacular birthday ever – enjoy.
Hope your birthday is super spectacular!!
Happy birthday Francis Lawrence y mucho exito en esta hermosa pelicula que dirigio al cual estoy leyendo el libro y por elegir a los actores que le dan vida a esta hermosa historia.
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redpajama_set_name: RedPajamaCommonCrawl


The Prague Civil Society Centre supports visionary, state of the art projects. We are always on the lookout for innovative, tech-based solutions and fresh approaches to the region's social issues. The Centre has an exceptionally broad definition of civil society that includes activists, campaigners, journalists, bloggers and lawyers, as well as creative professionals such as filmmakers, artists, designers and IT experts. We also support social entrepreneurs and civic-minded businesses. Our aim is to create and nurture a fluid community of activists, professionals and academics that harnesses the diversity, skills and knowledge of those working on civic and social initiatives. Our flexible, inclusive and cross sector approach is aimed to help civil society become more innovative, creative and sustainable so it is better equipped to meet the challenges and opportunities it faces in this unpredictable region.
Conceptualise and initiate a new project.
Anyone from Eastern Europe or Central Asia with proven experience and commitment to civil society in their country or region. This includes experts, researchers, human rights defenders, environmental or urban activists, journalists and members of NGOs and civic-minded groups.
After the selection process, Fellows are asked to provide a specific project output to be agreed before the beginning of the Fellowship. The Prague Civil Society Centre also reserves the right to ask you to assist our projects or activities.


Renowned for his work on the Oscar winning Star Trek and Guardians of the Galaxy: Vol.2 award winning production designer Scott Chambliss talks to Mandy News about how he got into production design and his experiences working on the up and coming movie Godzilla - King of the Monsters.
How did you get involved in Production Design?
It was a natural migration. After working in New York as a set and costume designer on Broadway and the regional theatre circuit I became interested in designing for film. Pursuing that interest led me to Los Angeles, where I've been based ever since.
How did you get involved with Godzilla - King of the Monsters?
Writer/director Michael Daugherty and his writing partner Zach Shields looked at my resume and decided they wanted to meet me. Michael told me later that they figured a designer who could handle J.J. Abrams, Brad Bird, Jon Favreau, and Phillip Noyce could probably handle them…ha!
What is the approach to working on something on such a large scale, what's the timeline for something like this?
You start with the big picture and then over time carefully pull your focus more and onto the details of the task. Prep alone can take from six to nine months before shooting on a project of this scale.
You have also worked on mega franchises like Marvel's Guardians... and Star Trek. Are there rules to how you can operate within these worlds and how do you operate within these boundaries but still bring something fresh and new?
Marvel apparently has rules as their products are all so similar. But even in such a context it is always the task of the director and designer to find together the qualities that make their project unique. Otherwise why bother? In the case of Star Trek, J.J.'s and my self-imposed guidelines were to treat the intentions of Roddenberry's source material with respect, make the story current and accessible to contemporary audiences…and make the film as gorgeous as humanly possible!
What advice do you have for up-and-coming Production Designers?
Getting a degree in the discipline is a shallow foundation. Go out and experience life in the world and discover why you want to be a production designer in the first place. Our job is to be articulate visual storytellers, and you can't be that without stories of your own to tell!
Would you like to become a production designer? Browse our latest production designer jobs we currently have available on Mandy.com.


Royal Street - Home Page - Reich Properties Inc.
1004 Royal Street, Kissimmee, FL 34744. Stand alone building located under the oak trees at the corner of Oak Street and Royal Street, downtown Kissimmee. Approximately 1,200 sq. ft. zoned for commercial office or medical office space.


FIND YOUR Vintage Bridge Assembly.
Mvhigh is the US's #1 online shopping comparison website, helping millions of shoppers save money on various of items. Mvhigh compares millions of products and items, shopping ideas and many more. We gather prices and shopping information on Vintage Bridge Assembly from over 500 of the USA's best-loved online stores, and upload all this information every day so you can find the best price.
Continuing in our series of building a Vintage Spec Fender Stratocaster that rivals a Custom Shop guitar, we install the tremolo using the 6 Callaham steel screws and then stratch the Raw Vintage Springs into place to catch them on the Tremolo Claw.


For Kids, Dear Santa Coloring Page was posted December 5, 2018 at 10:07 pm by swifte.us . More over Dear Santa Coloring Page has viewed by 4623 visitor.
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What suggestions and advice do you give students when their choice of school and goals after high school differ from those of their parents?
This is a common situation we encounter. Parents usually have different opinions from their children when it comes to selecting a college. We listen to the opinions and wishes of both students and parents. We help them open up their perspective and listen to each other so they can reach a clearer understanding and conclusion. We also present viable options to encourage better discussion. Most parents desire happiness and success for their child but the ultimate decision still belongs to the student.


In 2009, we adopted the name Groupama Sigorta, starting a new chapter on a journey that began in 1959. We forge ahead with practices that are constantly evolving and developing, a quality management system, a human-centric approach, and an effective business continuity policy. Get more information.


Jesus multiplied bread loaves and fishes. In the bible, the story is told of how he fed 5000 with only 2 fishes and five loaves of bread.
Orange's Exclusive Content Strategy in Question?
Cisco's Video-Comms, FT's NRA Z0 and is VDSL NGA ?
I'm still struggling for time and I still haven't managed to write my new year blog post. That's when I'm glad I'm French, we have until January 31st to do that in France!


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Pariteten av noll är jämn. Det betyder att i valet mellan jämn och udda, är noll ett jämnt tal.

Det enklaste sättet att bevisa detta är att undersöka hur talet 0 stämmer in på definitionen för jämna tal: Det är en heltalsmultipel av 2, nämligen 0 × 2. Som följd av detta har noll alla de egenskaper som kännetecknar jämna tal: Det är delbart med 2, det är granne på båda sidor med udda nummer (-1 och 1), 0 är summan av ett heltal taget två gånger (0+0=0) och 0 kan delas i två lika stora delar, se bilden till höger.

Varför noll är jämnt
Standarddefinitionen av jämna tal kan direkt användas för att bevisa att talet noll är jämnt. Ett tal är jämnt om det är en heltalsmultipel av 2. Exempelvis är talet 10 jämnt eftersom det är lika med 5 · 2. På samma sätt är noll jämnt eftersom det är lika med 0 · 2. Ekvivalent med den definitionen är att ett tal är jämnt om man kan dela det i två grupper med lika många i varje. Talet noll är då jämnt eftersom man kan dela det i två grupper med noll i varje.

Man kan också förklara varför noll är jämnt utan att hänvisa till den formella definitionen. Följande förklaringar hänvisar till fundamentala egenskaper hos tal för att beskriva jämna tal och hur de kan appliceras på noll.

Grundläggande förklaringar

Om man har ett antal objekt kan man använda tal för att beskriva hur många objekten är. Talet noll beskriver då att man inte har några objekt alls. Mer formellt beskriver det den tomma mängden. Om man då kan dela upp objekten i två grupper är talet jämnt när det inte blir något objekt över. Blir det ett objekt över är talet istället udda. Om man har noll objekt kan de delas i två grupper där båda grupperna innehåller noll objekt och det inte heller blir något objekt över, alltså är noll ett jämnt tal. Detta kan illustreras genom att rita objekten i par. Det kan vara svårt att illustrera noll grupper av par eller att det inte då blir något objekt över. Därför kan man rita flera olika antal och jämföra dem med noll. Till exempel för talet fem blir det två par och en som blir över. Alltså är fem udda. För fyra blir det också två par men inget objekt över och fyra är ett jämnt tal. För talet ett blir det inga par men ett objekt över så ett är udda. För noll blir det inget objekt över så noll är jämnt.

Tal kan också visas på en tallinje. Om då udda och jämna tal särskiljs syns tydligt ett mönster, särskilt om också de negativa talen tas med:

Eftersom jämna och udda tal alternerar kan man om man börjar med ett jämnt tal räkna upp eller ner med två i taget alltid nå andra jämna tal och då också noll. Samma sak gäller för udda tal, men då kan noll inte nås.

Livliga diskussioner om det jämna talet noll
Det har tidvis rått livliga diskussioner på internet och i media om nollan som jämnt tal. Emellanåt blir resultaten av diskussionerna rätt godtyckliga.

Den amerikanske lingvisten Joseph Grimes menar att frågan "Är noll ett jämnt eller udda tal?" är en bra fråga att ställa till gifta par, om man vill få dem att gräla.

Personer som menar att noll varken är jämnt eller udda använder bevisen för att noll är ett jämnt tal som bevis på att varje regel har sitt undantag.

Vid millennieskiftet kom ett par ovanliga milstolpar i medialt fokus. Det gällde "1999-11-19" som var det sista datum som inom överskådlig tid bestod av enbart udda siffror. Det gällde vidare "2000-02-02" som var det första datum med enbart jämna siffror som skulle inträffa, på mer än ett årtusende.

Eftersom dessa påståenden baserades på att noll är ett jämnt tal, opponerade sig många läsare, till exempel:

I prov- och testsituationer är det klokt att komma ihåg att noll är ett jämnt tal.

I länder där ransonering enligt udda–jämnt-metoden förekommer, blir frågan om nollan som jämnt tal viktig. Metoden för ransonering används för att halvera förbrukningen, till exempel av drivmedel till bilar. I det fallet får registreringsskylten avgöra. För att fördela drivmedel till halva fordonsparken är det givet att låta 0, 2, 4, 6, 8 på jämnt datum följas av 1, 3, 5, 7, 9 på udda, med noll naturligt placerat bland de jämna talen.

Men 1977 ledde systemet vid en ransonering i Paris till att polisen avvisade förare med registreringsskyltar som slutade med siffran 0, eftersom de var osäkra på om noll var ett jämnt tal.

För att undvika sådan förvirring lagstiftar länder ibland att nollan är ett jämnt tal. Det har skett i bland annat Maryland i östra USA och i Nya Sydwales i Australien.

På amerikanska flottans fartyg är hytterna på babords sida numrerade med jämna nummer. Noll är dock reserverat för hytter efter centrumlinjen.

I roulette räknas nollan varken som jämn eller udda och ger kasinot en liten fördel. På samma sätt kan regeln om nollan ska räknas som jämnt tal eller inte inverka på oddsen i ett antal olika hasardspel.

Också leken "Udda och jämnt" påverkas: Om båda spelarna visar noll fingrar blir det totala antalet fingrar noll, varför den spelare som valt jämnt vinner.

Referenser

Externa länkar

 Is Zero Even? - Numberphile, En film med Dr. James Grime, University of Nottingham (engelska)

Elementär aritmetik
Paritet
0 (tal)

redpajama_set_name: RedPajamaWikipedia


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why in the heck hasn't that guy come out with his own set of clubs called "Tiger Woods"?
he's smirking, isn't he? I think he's smirking. aren't the libs against smirking? or was that only if you're wearing a MAGA hat?
WTF? I have a lot of fun on the Internet.... why are you calling me stupid? what is wrong with you?
LOL... that's freaking funny.... I just love it when people misuse or combine words to paint bad ideas into a good light. "fair" tax.... really? why not just call it what it is... a consumption tax. I'm neither for nor against, but there is not really fair about it.


Dr. Jay Ven Eman, Ph.D.
Jay Ven Eman, Ph.D., joined Access Innovations in December, 1978. He holds a B. A. in Finance from the University of Washington in Seattle, an M.B.A. from the University of New Mexico, and a doctorate in business from the University of Colorado at Boulder. He uses his dissertation topic of Long range Planning and Organizational Effectiveness in Hospitals to good advantage at Access. As Chief Executive Officer, he has contributed to every aspect of the business. At Access he guides the sales, marketing and strategic planning departments. Access Innovations' database production services where he was responsible for the design and conversion of large, legacy databases for a variety of government and private organizations. He writes, conducts workshops, consults, and helps build large scale, complex, information rich databases. A past president of ASIDIC, Jay is a popular speaker and has given many presentations, workshops and seminars on ontologies, topic maps, database development, legacy file conversions, SGML, HTML, XML, and other related topics.


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Tinie Tempah explains decision to pull out of MOBO Awards
Nick Levine Nov 5, 2016 11:51 am GMT
The rapper had been booked to perform, but pulled out at the eleventh hour and was replaced by Professor Green.
Tinie Tempah has blamed "music industry politics" for his decision not to grace the stage at the MOBOs last night (November 4).
The rapper had been booked to perform at the annual awards ceremony in Glasgow, but pulled out at the eleventh hour and was replaced by Professor Green.
"I will not be performing at this years Mobos for reasons that are outside of mine and the Mobos' control," Tempah wrote in an Instagram post. "The Mobos is a ceremony I have grown up watching and take pride in. It's given a platform to so many artists who have inspired me. So I always go above and beyond to attend. I am gutted to not be performing."
He continued: "I didn't go into this much detail because I want to have a moan. I wrote this because my music and my culture is very important to me and this has been the same issue year after year. It is frustrating when music industry politics dictate my ability to celebrate either. It's been a great year for British music, especially the underground. I will be watching and supporting. TT."
Good luck to all the nominees at this years @moboawards I'll be watching and supporting. 🙏🏾
A photo posted by Tinie Tempah (@tiniegram) on Nov 4, 2016 at 5:34am PDT
Winners at last night's MOBO Awards included recent NME cover star Lady Leshurr, who was named Best Female Act, and Craig David, who was named Best Male Act.
Kano won Best Album for 'Man In The Mirror', while Drake was given the Best International Act award.
However, organisers were forced to apologise after the Best Song award was mistakenly handed out to the wrong act.
Mason Ramsey, Lil Nas X and Young Thug. Credit: Erika Goldring/Getty Images, Jason Kempin/Getty Images, Lorne Thomson/Redferns
Lil Nas X releases another remix of 'Old Town Road' with Young Thug and Mason Ramsey
K-pop sensation BTS are seen at Jimmy Kimmel Live on November 15, 2017 in Los Angeles, California Credit: PG/Bauer-Griffin/GC Images
Big Hit, BTS' label, is reportedly building its own streaming platform
Cardi B hits out at Jermaine Dupri: "I rap about my pussy because she's my best friend"


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Frontiers in Microbiology
Microbial Immunology
Amy Rasley
Lawrence Livermore National Laboratory, United States Department of Energy (DOE), United States
Maryam Dadar
Razi Vaccine and Serum Research Institute, Iran
Mayara Fernanda Maggioli
United States Department of Agriculture (USDA), United States
Morphology and Life Cycle
Characteristics and Metabolism
Host Specificity
Effect on Host Microbiome
Effect on Host Immunity
Segmented Filamentous Bacteria in Turkeys
Front. Microbiol., 24 August 2018 | https://doi.org/10.3389/fmicb.2018.01991
Segmented Filamentous Bacteria – Metabolism Meets Immunity
Grant A. Hedblom1†, Holly A. Reiland1†, Matthew J. Sylte2, Timothy J. Johnson3,4 and David J. Baumler1,4,5*
1Department of Food Science and Nutrition, University of Minnesota Twin Cities, Saint Paul, MN, United States
2Food Safety and Enteric Pathogens Research Unit, USDA-ARS National Animal Disease Center, Ames, IA, United States
3Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, Saint Paul, MN, United States
4The Microbial and Plant Genomics Institute, University of Minnesota Twin Cities, Saint Paul, MN, United States
5The Biotechnology Institute, University of Minnesota Twin Cities, Saint Paul, MN, United States
Segmented filamentous bacteria (SFB) are a group of host-adapted, commensal organisms that attach to the ileal epithelium of vertebrate and invertebrate hosts. A genetic relative of the genus Clostridium, these morphologically unique bacteria display a replication and differentiation lifecycle initiated by epithelial tissue binding and filamentation. SFB intimately bind to the surface of absorptive intestinal epithelium without inducing an inflammatory response. Rather, their presence impacts the generation of innate and differentiation of acquired immunity, which impact the clearance of extracellular bacterial or fungal pathogens in the gastrointestinal and respiratory tracts. SFB have recently garnered attention due to their role in promoting adaptive and innate immunity in mice and rats through the differentiation and maturation of Th17 cells in the intestinal tract and production of immunoglobulin A (IgA). SFB are the first commensal bacteria identified that impact the maturation and development of Th17 cells in mice. Recently, microbiome studies have revealed the presence of Candidatus Arthromitus (occasionally designated as Candidatus Savagella), a proposed candidate species of SFB, in higher proportions in higher-performing flocks as compared to matched lower-performing flocks, suggesting that SFB may serve to establish a healthy gut and protect commercial turkeys from pathogens resulting in morbidity and decreased performance. In this review we seek to describe the life cycle, host specificity, and genetic capabilities of SFB, such as bacterial metabolism, and how these factors influence the host immunity and microbiome. Although the role of SFB to induce antigen-specific Th17 cells in poultry is unknown, they may play an important role in modulating the immune response in the intestinal tract to promote resistance against some infectious diseases and promote food-safety. This review demonstrates the importance of studying and further characterizing commensal, host-specific bacteria in food-producing animals and their importance to animal health.
The distal gastrointestinal tract of all animals is colonized by a diverse array of bacterial, fungal, and protozoan species. An animal host maintains a mutualistic relationship with its microbial inhabitants in which the microbes provide protection from pathogenic bacteria through competing for ecological niches and fostering a stable environment for the development of host immunity (Bäckhed et al., 2005). Many vertebrate intestines (such as mice, rats, chickens, humans, and turkeys) harbor commensal organisms named segmented filamentous bacteria (SFB) that bind specifically to the host intestinal epithelium. These organisms are closely related to the genus Clostridium, and appear as long, segmented filaments that bind tightly to the host epithelium via a specialized structure (Chase and Erlandsen, 1976). These bacteria were initially detected through microscopic examination of the gastrointestinal epithelium of mice (Davis and Savage, 1974). SFB drew the attention of researchers due to their unique morphology, life cycle and binding location (Schnupf et al., 2013). Since their discovery, a large body of research has been generated to characterize these bacteria and understand their role in the host-microbiome relationship. Through examining mouse and rat models, it has been revealed that these bacteria play an important role in adaptive and innate immunity of the host.
Segmented filamentous bacteria are Gram-positive, spore-forming bacteria that possess the capability to develop into long filaments, which are divided via the production of transverse septa (Ericsson et al., 2014). These bacteria exist in a developmental or vegetative form, which are characterized by the presence of intrasegmental bodies and spores, respectively (Figure 1). SFB produce intrasegmental bodies, which can appear as either a spore or a holdfast. The distinction between these morphologies indicates that the holdfast form serves as the vegetative form, while the spore serves as the dormant form (Chase and Erlandsen, 1976).
FIGURE 1. Gram stain of Candidatus Arthromitus from turkey ileum containing intrasegmental bodies (1,000× magnification) (Reiland, 2016).
Segmented filamentous bacteria selectively attach to the ileal epithelium of the host species via the production of rounded, nipple-like projections called holdfasts. The holdfast serves as an anchoring mechanism and point of filament elongation, attaching to host enterocytes in the mucous membrane of the epithelium, without penetrating the host cell wall (Sanford, 1991). This structure leads to the displacement and destruction of the intestinal microvilli surrounding the point of attachment (Snellen and Savage, 1978), and leads to alterations in the electron density of both the host cell plasma membrane and apical cytoplasm (Ericsson et al., 2014). Once attached, actin polymerization occurs directly underneath the holdfast structure and creates a pedestal-like formation similar to the adherence mechanism of Salmonella enterica serovar Typhimurium (Jepson et al., 1993; Ericsson et al., 2014). Though this attachment mechanism resembles that of pathogenic bacteria, it does not damage the host cell and causes no inflammatory response in the lamina propria (Caselli et al., 2010). Once attached to the host epithelium, the filament begins to extend from the distal end, releasing additional holdfasts and spores from the maturing filament (Chase and Erlandsen, 1976). The life cycle of an SFB filament is assumed to be about 2–3 days based on the rapid shedding of the intestinal epithelium of rodents, and longitudinal studies have shown that SFB appear in juvenile mice that are around 20 days in age (Davis and Savage, 1974). At this stage of development, SFB proliferate to become a dominant gut microbe and then recede in mature vertebrates to lower levels. During the early stages of colonization, SFB are transiently colonized with rod-shaped bacteria (Schnupf et al., 2013). It is believed that the spread of SFB then occurs via vertical transmission of spores from parents to offspring, as these bacteria are widely considered to be obligate anaerobes and have also appeared in the intestinal tissue of weaning mice (Schnupf et al., 2013). Colonization occurs in mouse and rat hosts at the onset of the weaning process and has been found to be the same in arbitrary human microbiome studies (Ericsson et al., 2014). Studies performed on human subjects ages 0 months to 75 years old revealed that 25% of individuals carry SFB in their gut from ages 0–6 months, 75% carry SFB from ages 7–12 months, and only 6.2% carry SFB from ages 3–75 (Yin et al., 2013). The age-related drop in SFB intestinal carriage may be pharmaceutically reversed. For example, transient feeding mice rapamycin enhanced their lifespan, while dramatically increasing the prevalence of SFB in the small intestine (Bitto et al., 2016). In chickens, SFB colonization peaked at approximately 2 weeks of age, and decreased as they aged to 6 weeks of age. The decrease was inversely proportional to the amount of intestinal IgA present (Liao et al., 2012). It is unknown whether increasing the prevalence of SFB in the intestinal tracts of adults is beneficial, or may result in autoimmunity (e.g., rheumatoid arthritis) (Wu et al., 2010).
Segmented filamentous bacteria spores germinate in the host's gut to produce teardrop-shaped, single-celled bacteria referred to as intracellular offspring (Schnupf et al., 2013). Amongst intestinal commensals and symbionts, SFB are unique because they penetrate the intestinal mucus layer and intimately associate with host cells without invading the host (Chase and Erlandsen, 1976; Sanford, 1991). It is assumed that the intracellular offspring use flagella to reach the apical surface of polarized epithelium (Kuwahara et al., 2011). Though cellular flagella have not been observed microscopically, an analysis of a SFB genome revealed a full set of chemotaxis and flagellin biosynthesis genes, strongly suggesting the presence of flagella in the early stages of spore maturation (Kuwahara et al., 2011). Intracellular offspring attach to absorptive epithelial cells via their holdfast and induce condensed actin rearrangements underneath the point of attachment while displacing some of the neighboring microvilli structures (Chase and Erlandsen, 1976). Before luminal attachment, the nucleoid region of the intracellular offspring appears condensed, suggesting reduced amounts of transcription. However, when the intracellular offspring attaches to the host, the nucleoid region decondenses and allows for genomic transcription (Chase and Erlandsen, 1976).
Holdfast attachment to enterocytes in the terminal ilea causes the intracellular offspring to increase in size, reaching up to 5 μm in length before bacterial division commences through transverse septum formation (Chase and Erlandsen, 1976). Filaments continue to grow and divide from their distal end, reaching their maximum length of around 50–80 μm (Martin et al., 2009; Schnupf et al., 2013). Once the filament reaches its maximum length, a second round of symmetric division begins from the distal end to divide each original segment in half into secondary undifferentiated cells. These secondary cells range in length from 1 to 1.7 μm, forming segments containing 30–80 cells (Chase and Erlandsen, 1976). After elongation, the filament will often separate from the holdfast segment and enter into the ileum. These secondary segments then undergo differentiation form a mother cell and a daughter cell (Klaasen et al., 1992). Differentiation of these filaments appears to be more pronounced in the presence of slightly aerobic conditions, when oxygen concentrations range from 1 to 2.5% environmental oxygen (Schupf et al., 2015). Once differentiated, the mother cell engulfs and houses the daughter cell, where the daughter cell undergoes division into two intracellular offspring (Klaasen et al., 1992). The intracellular offspring contained within the mother cell are then subject to two fates, dispersal from the filament or sporulation (Davis and Savage, 1974; Klaasen et al., 1992). If favorable growth conditions are present, the septa that separate individual mother cells are degraded to form a tube in which the intracellular offspring are dispersed into the host's intestinal tract. These released offspring are then allowed to colonize additional host tissue and undergo filamentation and differentiation, thus completing the SFB lifecycle (Martin et al., 2009; Schnupf et al., 2013). When an unfavorable or hostile environment is presented, the two intracellular offspring produce a single spore coat that covers both of the cells. Once coated with the layer of peptidoglycan, the spore matures into a complete endospore inside of the mother cell, and is released from the filament (Martin et al., 2009; Schnupf et al., 2013). These spores lack the ability to colonize the host until favorable environmental conditions, such as appropriate concentrations of oxygen are presented, and shed in the host's feces. Once shed, the spores can be transmitted to another host via horizontal transmission (Davis and Savage, 1974).
Though it was previously proposed that the entire SFB lifecycle occurred while attached to the host tissue (Chase and Erlandsen, 1976), filaments containing intracellular offspring have not been observed in published TEM and SEM images of filaments attached to enterocytes (Caselli et al., 2010). Alternatively, filaments containing differentiated intracellular offspring only appeared as detached and free-floating, indicating that maturation and differentiation of segments occur independently from host tissues. These filaments are separated from the holdfast segment, which then penetrates the epithelium until it undergoes endocytosis, phagocytosis, or transcytosis (Caselli et al., 2010). The ingestion of the holdfast segment presents a great number of bacterial antigens to antigen presenting cells and lymphocytes contained within the ileal epithelium (Caselli et al., 2010). In rare cases, a small number of segments may remain attached to the holdfast, but these segments often exhibit irregular morphologies and present enlarged intrasegmental junctions (Caselli et al., 2010).
The genome of a rat-isolated SFB and a number of mice SFB isolates have recently been sequenced and published (Kuwahara et al., 2011; Prakash et al., 2011; Sczesnak et al., 2011; Pamp et al., 2012). These SFB genomes are highly similar but do contain several species-specific genes of unknown function that may be involved in the species-specificity of SFB colonization (Prakash et al., 2011). All sequenced SFB have displayed a small genome size of 1.5–1.62 Mbp, low G+C content (27.9%), and around 1,350–1,400 protein encoding genes (Prakash et al., 2011). SFB possess a highly reduced genome similar to their genetic relatives within the genus Clostridium (Ericsson et al., 2014). The biosynthetic pathways of most amino acids, vitamins and cofactors (such as B1, B2, and B12, pyridoxine, nicotinamide, pantothenate, and biotin) are incomplete or absent altogether in SFB genomes (Kuwahara et al., 2011; Sczesnak et al., 2011; Pamp et al., 2012). SFB are also unable to synthesize nucleotides independently; instead they utilize alternative pathways that rely on the uptake of nucleotide bases (Prakash et al., 2011). To obtain nucleotides, amino acids, and peptides from the environment, SFB genomes contains genes encoding two extracellular nucleases as well as a list of proteases and peptidases, 20 of which are membrane associated and 4 to 6 that are thought to be secreted (Kuwahara et al., 2011; Sczesnak et al., 2011). In addition, SFB genomes contain numerous open reading frames (ORFs) thought to encode a large number of transporters and permeases for small molecules and ions (such as amino acids, oligopeptide, dipeptides, manganese, zinc, iron, and phosphate) compared to other organisms with small genomes (Sczesnak et al., 2011). A particularly strong requirement for iron uptake was noted by Sczesnak et al., since six different ORFs for iron transporters are found in the mouse genome as well as three ORFs for ferric iron regulator family proteins (Sczesnak et al., 2011). SFB also have several ORFs for phosphotransferase systems predicted for uptake of sugars such as mannose, cellobiose, mannitol, and fructose (Prakash et al., 2011; Sczesnak et al., 2011). Finally, the SFB genomes contain genes for the non-oxidative pentose phosphate pathway and a complete glycolysis pathway to convert glucose to pyruvate, but are deficient for genes encoding almost all components of the Krebs cycle, which is required for aerobic respiration (Prakash et al., 2011; Sczesnak et al., 2011). However, SFB can tolerate small concentrations of oxygen and counteract oxidative stress, as SFB genomes contain genes predicted for two catalases, a peroxidase (rubrerythrin), and an arginase, which might limit nitric oxide production through catabolism of arginine (Kuwahara et al., 2011; Pamp et al., 2012). These protective mechanisms are likely essential, given the replicative niche of SFB at the surface of the small intestinal epithelium where the oxygen tension is estimated to be around 1.4% (He et al., 1999).
There are several factors that have been discovered about SFB that explain their auxotrophic nature. The genome of SFB isolated from a rat host (Rat-YIT) contains 28 putative genes predicted to encode for proteases and 53 for peptidases along with many other genes through to be involved with sporulation and germination (Prakash et al., 2011). Peroxidase and catalase genes were also found, which explains the potential for SFB to exist in microaerophilic environments (Prakash et al., 2011). The genomes of SFB sequenced from mice and rat hosts revealed several Clustered Regularly Interspaced Palindromic Repeat (CRISPR) loci, which serve as a prokaryotic defense mechanism, indicating that SFB genomes may have had exposure to invading DNA throughout their evolutionary history (Prakash et al., 2011). Flagellar, pilus, and chemotactic genes have been found in SFB genomes that suggest motility, which explains the organism's ability to penetrate the mucus layer lining of intestinal epithelial cells (Prakash et al., 2011; Schnupf et al., 2013) We have generated a representation of the metabolic and physiological predicted capabilities inferred from the genome contents of publicly sequenced genomes of SFBs (Figure 2).
FIGURE 2. Metabolic features of Candidatus Arthromitus through inference of genome contents from annotated genomes through use of Rapid Annotation using Subsystem Technology (Reiland, 2016).
An extensive body of work has evidenced the presence of SFB in a large number of animal species, such as horses, cattle, pigs, turkeys, chickens and even humans (Ericsson et al., 2014). In nearly all of the mammalian species studied for the presence of SFB, the bacteria selectively colonize the ileum of the host, with the exception of fish species that lack a well-defined ileum (Ericsson et al., 2014). In poultry, SFB colonizes ileum (Figure 1), the cecal tonsil or cecum (Figure 3; Rahimi et al., 2009; Bohorquez et al., 2011; Liao et al., 2012). Attempts to colonize an animal species with SFB from another species have been unsuccessful. When germ-free mice and rats were inoculated with ileal homogenates containing SFB from both species, animals became colonized with SFB from their own species, indicating that SFB are host-specific and host selective (Tannock et al., 1984). Host-specificity of SFB may be due to differences in the sequences of flagella genes fliC3 and flicC4, which show greater variability than fliC1 and fliC2 (Chen et al., 2017). It is not known with which host proteins the SFB flagella proteins interact to become adherent, however, SFB flagellar proteins may induce Th17 cells by signaling through Toll-like receptor 5 (TLR5) in a subset of CD11chiCD11bhi intestinal dendritic cells (Uematsu and Akira, 2009). For most animal species, holdfast cells have the capability to attach to goblet cells, M-cells, absorptive enterocytes, and cellular junctions of the ileal epithelium (Meyerholtz et al., 2002), whereas less is known for poultry. Species to species variance exists in the preferred cell of attachment. For example, SFB in rats and pigs attach to follicle-associated epithelial cells (over Peyer's Patches) and absorptive ileal villi (Tannock et al., 1984). In mice and horse, attachment occurs primarily to follicle-associated epithelial cells and mainly to absorptive ileal villi for rabbits, cattle and canines (Pamp et al., 2012). SFB are unique amongst intestinal commensals and symbionts because they penetrate the intestinal mucus layer and intimately associate with host cells, but do not invade the host (Sanford, 1991). The exact mechanism of host specificity remains unclear, but it is believed that initial binding of the holdfast segment to the host epithelium serves as a ligand-receptor interaction, triggering a response from the host (Kuwahara et al., 2011). SFB binding elicits actin polymerization and condensation at the point of attachment (Chase and Erlandsen, 1976), suggesting a specific host response. Host specificity of SFB suggests that these bacteria have coevolved with their hosts to promote the commensal relationship that exists between the two species.
FIGURE 3. Scanning electron micrograph of a SFB filament attached to epithelium in the cecum of a 28-day old male turkey poult, also pictured are additional unidentified bacteria (2,500× magnification).
Though initially considered to be common commensal members of the host microbiota, recent research suggests that SFB serve an important role in modulating host microbiome and immunity. SFB are unique amongst intestinal commensals and symbionts because they penetrate the intestinal mucus layer and intimately associate with host cells without invading the host (Chase and Erlandsen, 1976; Lee et al., 2011; Mortha et al., 2014; Atarashi et al., 2015; Bunker et al., 2015; Farkas et al., 2015; Furusawa et al., 2015; Sadler et al., 2017). The holdfast binding of SFB to the ileal mucosa does not elicit a strong inflammatory response (Klaasen et al., 1991). Several interactions between the host and SFB have been investigated, indicating almost entirely positive associations between the SFB and the host, with rare exceptions. Intestinal colonization of SFB in Rainbow trout may produce a fatal disease called Rainbow Trout Gastroenteritis (RTGE), where SFB expand to large numbers in the intestinal tract and cause enterocytes to detach (Del-Pozo et al., 2010). SFB were not always present near to all intestinal RTGE lesions, suggesting that SFB affects intestinal barrier function and other bacteria may not be crucial for producing RTGE lesions. Experimental infection of susceptible Rainbow trout stock with feces from RTGE animals induced colonization and characteristic histopathological lesions containing SFB and an unidentified Gram-negative coccus, suggesting that SFB, in part, may be the etiological cause of RTGE (McCarthy et al., 2016). Recent advances have identified different methods to culture SFB in vitro, accelerating research to study the interaction of SFB with different members of the intestinal microbiota (Ericsson et al., 2015; Schupf et al., 2015).
A large amount of research has demonstrated the indispensable role that SFB play in the maturation of the host gut immune barrier, inducing both innate and adaptive immune responses (Ivanov et al., 2009; Sonnenberg et al., 2011; Mortha et al., 2014; Atarashi et al., 2015; Bunker et al., 2015; Farkas et al., 2015; Furusawa et al., 2015; Edelblum et al., 2017; Schnupf et al., 2017). Immune modulation of SFB may extend beyond the intestinal tract in the blood, or to other mucosal barriers (McAleer et al., 2016). Mice colonized with SFB were more resistant to sepsis secondary to experimental cecal ligation and puncture injury (Cabrera-Perez et al., 2016). Oral vancomycin treatment to mice diminished the number of intestinal Gram-positive bacteria (including SFB), which negatively impacted anti-fungal Th17 immunity in the respiratory tract (McAleer et al., 2016). These data suggest that the composition of intestinal microbiota, especially SFB, is vital for impacting immunity to bacterial and fungal pathogens beyond the intestinal tract.
Segmented filamentous bacteria are best known for their ability to induce the differentiation of naïve CD4+ T cells to form antigen-specific Th17 CD4+ cells (Schnupf et al., 2013) in the terminal ileum of mice (Farkas et al., 2015). Ivanov et al. first demonstrated that conventionally raised B6 mice purchased form Taconic Farms were highly colonized with SFB; these bacteria were absent from conventional raised mice purchased from the Jackson Laboratory (Ivanov et al., 2009). Introduction of SFB to B6 mice from the Jackson Laboratory induced IL-17A and IL-22 production from intestinal CD4+ T cells, which became refractory to colitis induced by the intestinal pathogen Citrobacter rodentium (Ivanov et al., 2009). IL-22 is a cytokine that enhances production of antimicrobial peptides from intestinal epithelial cell and prevent bacterial pathogens from inducing attaching and effacing lesions (Schupf et al., 2015). SFB are not the only bacteria capable of inducing Th17 CD4+ T cells in the intestinal tract of animals. Virulent Shiga-toxin producing E. coli (O157) and Citrobacter rodentium induced a Th17 response in the murine intestinal tract, and was dependent on bacterial adherence to host cells (Atarashi et al., 2015), as well as the commensal Bifidobacterium adolescentis (Tan et al., 2016). Th17 cells are a subset of CD4+ T cells that are distinguished by the expression of T cell receptor CD3, nuclear transcription factor RAR-related orphan receptor gamma T (RORγt) and production of interleukins IL-17A, IL-17F, IL-21, and IL-22 (Schnupf et al., 2017). Other immune cells present in the intestinal lamina propria are capable of secreting IL-17A and IL-22 or express RORγt [e.g., innate lymphoid cells type 3 (ILC3) and lymphoid tissue inducer-like cells (LTi)], but these cells lack expression of CD3 (Sonnenberg et al., 2011; Mortha et al., 2014). However, ILC3 and LTi are not dependent on SFB for their induction. In the intestinal epithelium, IL-17A and IL-17F help to modulate neutrophil chemotaxis through producing CXCL chemokines via binding interactions with IL-17 receptors IL-17RA and IL-17RC. IL-17A and IL-17F additionally aid in regulating the activation and differentiation of host neutrophils, and stimulate the production of host-defense peptides (Schnupf et al., 2017). Systemic depletion of neutrophils in mice caused increased production of IL-17A and ileal SFB colonization (Flannigan et al., 2017). Thus, neutrophil recruitment may lessen IL-17A and chemokine production, and serve as a negative feedback loop to limit SFB colonization. The regulation of these immune-stimulatory compounds and cell types is essential in combatting intestinal colonization and infection from microorganisms. Th17 cells provide colonization resistance to other pathogenic bacteria present at mucosal barriers, such as Escherichia coli in the intestinal tract (Zheng et al., 2008; Edelblum et al., 2017) and respiratory fungi (McAleer et al., 2016).
In newborn or germ-free mice, the presence of Th17 cells in the lamina propria is rare, appearing only after colonization by microbes (Gaboriau-Routhiau et al., 2009). The role of SFB in Th17 cell production was initially demonstrated when mice were inoculated with mouse, rat, and human microbiota containing bacterial spores similar to that of the genus Clostridium. Only the experimental mice inoculated with a mouse-derived bacteria were shown to produce Th17 cells in response to colonization. Mice colonized with rat- and human-derived bacteria produced much less of a Th17 response when compared to the mouse-derived microbiome treatment, indicating host-specific bacteria (such as SFB) as the causative agent of the immune response (Gaboriau-Routhiau et al., 2009; Chung et al., 2012). This association was also confirmed when 16S rRNA sequencing was performed on the gut microbiome of mice presenting ileal Th17 cells, revealing the presence of SFB (Ivanov et al., 2009). In experiments testing the reactivity of mouse lamina propria against a SFB expression library, two proteins of unknown function elicited a Th17 cell response (Yang et al., 2014). It was predicted that these unknown proteins may serve as cell surface proteins, potentially elucidating the role that SFB attachment may serve in stimulating host immunity (Yang et al., 2014). Proteins from SFB, secreted or bacterial-associated, are believed to interact with host cells and modulate immunity include ADP-ribosyltransferases and a myosin-cross reactive antigen (Pamp et al., 2012). The exact antigen presenting cell responsible for immune modulation by SBF is controversial, but it appears that SFB antigens presented to both intestinal macrophages (Panea et al., 2015) or CD103+ intestinal dendritic cells (Goto et al., 2014) are involved. Because of the intimal relationship of SFB with intestinal epithelium, it is possible that metabolites from SFB may also impact the differentiation of Th17 cells. Intestinal macrophages, and not intestinal dendritic cells, appear to be vital for generating SFB-specific Th17 responses in the murine ileum (Panea et al., 2015). Analysis of the T cell receptor repertoire of Th17 cells recognize peptide antigens produced by SFB (Yang et al., 2014). The addition of the Th1-indcing bacterial pathogen Listeria monocytogenes failed to impact induction of Th17 cells in SFB colonized mice (Yang et al., 2014), suggesting that the match of T-cell effector function with antigen specificity is driven by the type of bacteria that produce the antigen. Th17 cell differentiation is additionally mediated through the production of serum amyloid A (SAA) and reactive oxygen species (ROS) produced in response to SFB binding. Production of SAA in the host epithelium is initiated by SFB binding and subsequent actin rearrangements, leading to a signal amplification via IL-22 and ILC3, both of which aid in Th17 cell differentiation (Schnupf et al., 2017). SAA also stimulates intestinal antigen presenting cells to secrete IL-23, which assists in Th17 activation and survival (Schnupf et al., 2017), but IL-23 also has as an antagonistic effect on development of Th17 immunity (Shih et al., 2014). ROS produced as a consequence of SFB binding to enterocytes helps to create a chemical environment that promotes Th17 differentiation, as demonstrated in mice treated with ROS scavenging compounds having lower amounts of Th17 cells in vivo (Atarashi et al., 2015). SFB flagellar proteins may induce Th17 cells by signaling through TLR5 in a subset of CD11chiCD11bhi intestinal dendritic cells (Uematsu and Akira, 2009). The flagellar binding motifs that are targeted by TLR5 appear to be highly conserved in SFB and is nearly absent from other similar Clostridium species, suggesting a specific role for SFB to modulate Th17 immunity (Prakash et al., 2011). Although SFB-induced Th17 immunity may benefit the animal host, there are long-term consequences. SFB-induced Th17 immunity is linked to the development of autoimmunity in susceptible breeds of mice (Lee et al., 2011; Yang et al., 2014; Teng et al., 2016) by inducing differentiation and egress of T follicular cells from Peyer's patches (Teng et al., 2016). It is unknown whether natural colonization by SFB in poultry is capable of promoting autoimmunity, but it must be considered if SFB, or its antigens are utilized as immunomodulators for food-producing animals.
Segmented filamentous bacteria mono-associated mice display rapid growth and development of Peyer's patches, and SFB can also stimulate the formation of lymphoid follicles and tertiary lymphoid tissues in the host (Lecuyer et al., 2014). This activation of the host's intestinal immunity causes a drastic increase in fecal concentrations of secretory Immunoglobulin A (sIgA), as the number and activity of IgA secreting B-cells rises (Klaasen et al., 1991). Germ-free mice monoassociated with SFB triggers the production of IgA serum levels equivalent to that of specific pathogen free, SFB-negative mice (Klaasen et al., 1993). The expansion and stimulation of germinal centers present in Peyer's patches is not entirely unique to SFB and has been seen to occur in other commensal bacteria such as Morganella morganii and Bacteroides distasonis, however, the response from SFB is much greater than these other organisms (Schnupf et al., 2013). Both T-cell dependent (B-2 cell) and T-cell independent (B-1 cell) production of sIgA occurs in SFB mono-associated mice (Schupf et al., 2015). The amount of SFB-specific IgA produced by the host in response to bacterial colonization is as high as 1.4% of the total IgA of the organism (Talham et al., 1999). IgA transmitted by nursing mice to suckling pups has been shown to inhibit SFB colonization, and only after weaning do SFB populations begin to increase, coinciding with the time in which SFB colonization is typically recognized in mice (Jiang et al., 2001). The induction of sIgA by SFB may serve as a negative feedback mechanism to prevent overcolonization by SFB and dysbiosis in older animals (Ohashi et al., 2010; Liao et al., 2012).
Light Turkey Syndrome (LTS) is growing problem facing commercial turkey production in the United States. LTS is a condition in which turkey flocks fail to meet their genetic potential weight, yielding birds that are 4–5 pounds below the industry standard for average flock weight (Danzeisen et al., 2013). Birds affected by LTS display symptoms similar to poult enteritis complex (PEC), a disease in which birds experience weight loss, diarrhea, lethargy, and depression (Mor et al., 2013). However, LTS is dissimilar to PEC in that birds do not experience watery and pale intestinal contents or distended ceca, indicating differences between the syndromes (Morishita et al., 1992). The causative agent of PEC is suspected to be microbial in nature, as inoculation of healthy birds with fecal homogenates derived from birds experiencing PEC produced light weight poults when compared to un-inoculated birds, but a single responsible microbe has yet to be determined (Mor et al., 2013). Similarly, inoculating healthy birds with fecal homogenates derived from turkeys with LTS produced birds that were lighter than the control groups (Mor et al., 2013). The two conditions are not dependent on each other, as LTS can occur in the absence of PEC (Danzeisen et al., 2013). There exist a number of potential factors that may lead to the development of LTS, such as colonization by pathogenic bacteria, viral infection, stunting of immune system development, inhibited nutrient absorption, and alterations to gut microbiome (Danzeisen et al., 2013). Typically, LTS/PES affects birds less than 3 weeks of age (Morishita et al., 1992). A higher number of different pathogenic organisms are found in these younger birds than in birds aged 4–9 weeks. Virus strains such as astrovirus, reovirus, and rotavirus types were detected in the host, and are not associated with poult mortality. Coronavirus, which is commonly associated with mortality, was not detected in LTS/PES poults (Morishita et al., 1992).
In an attempt to understand the microbial basis of LTS, Danzeisen et al. performed 16S rRNA microbiome analysis of low-performing and high-performing (based upon flock weights) flocks to determine the role of microbial succession in promoting digestive health Samples were sequenced to discern the presence and abundance of dominant OTUs present in higher-performing flocks as compared to lower-performing flocks (Danzeisen et al., 2013). After analysis it was determined that at the age of 2–3 weeks, higher-performing turkey flocks harbored significantly higher proportions of Clostridium bartlettii and Candidatus division Arthromitus, a SFB (Danzeisen et al., 2013). Previous studies regarding SFB colonization of poultry have identified SFB as a causative agent in intestinal disease (Goodwin et al., 1991), but SFB was later ruled out as a causative agent (Sell et al., 1992). Also, SFB belong to several microbial taxa and are not considered a homogeneous group (Thompson et al., 2013). As demonstrated in mice and rat models, SFB have been proven to be potent stimulators of host immunity and ileal health. Though the role of SFB (in particular Candidatus Arthromitus) in the digestive health of turkeys is not quite understood, the evidence provided by Danzeisen et al. suggests that epithelial binding of these bacteria may promote early digestive health (Danzeisen et al., 2013). The potential for Candidatus Arthromitus to serve as an immunostimulatory probiotic makes it an organism of great interest to poultry researchers, as the turkey production industry is in need of alternatives to promote animal health in this age of restricted use of antibiotics in food-producing animals and increasing antimicrobial resistance.
Since their initial characterization in the 1970s, SFB have transitioned from being considered an interesting and unique member of the gut microbiome with a unique morphology, to serving as a model organism to study immunomodulatory symbiotic bacteria and their effects on the host. The host-specific binding mechanism employed by these bacteria to attach to ileal epithelium is similar to that of enteric pathogens. Unlike enteric pathogens, SFB do not harm the host epithelium and instead live in a commensal, if not mutualistic manner. Intimate binding to the host mucosal epithelium allows SFB to receive nutrients from the host, satisfying their auxotrophic requirements, while delivering antigens to the host. Epithelial binding also initiates several immune responses from the host. As demonstrated in mice and rat models, SFB have been shown to stimulate the maturation of the host's Th17 and IgA responses, improving the ability of the host to protect against invading pathogens. Additionally, SFB compete with other members of the intestinal microbiota by modulating access to nutrients and occupying available ecological niches. The fitness-bolstering effects produced by SFB in mouse models are well-understood, but little is known about the roles these bacteria play in the other vertebrate animals. It has been suggested through microbiome analyses of turkeys that SFB, specifically Candidatus Arthromitus, may provide a protective role in preventing the onset of the enteric condition LTS, the cause of which is not well understood. The role of SFB in turkeys must be better elucidated to determine the beneficial effects these bacteria have in disease prevention and in ileal health. Developing an understanding the role that commensal microorganisms, like SFB, play in the overall function of the gut microbiome will aid in our understanding the interplay between microbiome and host, providing insights into digestive health and the development of immunity.
HR and GH contributed equally to the writing of the manuscript. MS, TJ, and DB also helped to write the manuscript.
We would like to thank USDA-AFRI award #2016-67015-24911 and also the Department of Food Science and Nutrition and the College of Food, Agricultural and Natural Resource Sciences at the University of Minnesota for providing the funds needed to perform and complete this study.
We thank Judi Stasko (USDA ARS National Animal Disease Center) for technical assistance with scanning electron microscopy.
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Keywords: segmented filamentous bacteria, SFB, Candidatus Arthromitus, turkey (Meleagris gallopavo), microbiome and immune system
Citation: Hedblom GA, Reiland HA, Sylte MJ, Johnson TJ and Baumler DJ (2018) Segmented Filamentous Bacteria – Metabolism Meets Immunity. Front. Microbiol. 9:1991. doi: 10.3389/fmicb.2018.01991
Received: 29 September 2017; Accepted: 07 August 2018;
Published: 24 August 2018.
Amy Rasley, Lawrence Livermore National Laboratory, United States Department of Energy (DOE), United States
Mayara Fernanda Maggioli, United States Department of Agriculture, United States
Maryam Dadar, Razi Vaccine and Serum Research Institute, Iran
Copyright © 2018 Hedblom, Reiland, Sylte, Johnson and Baumler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: David J. Baumler, dbaumler@umn.edu
†These authors have contributed equally to this work