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Signs of a Drug Relapse
For most people, signs of a drug relapse will begin with the return of the core self-defeating beliefs that they held about themselves while they were in the throes of their drug or alcohol addiction. Something inside of a former addict may begin to shift during the drug recovery process , and they will no longer feel the self-confidence that they experienced while going through treatment at the drug rehab center; thus, they may no longer feel worthy of having all of the good things that are connected with their sobriety. It is at this point, that the person in recovery may begin to feel that they are not capable of doing what needs to be done in order to maintain their sobriety.
One of the major signs of a drug relapse occurs when a former addict's dysfunctional beliefs are reactivated; consequently they can begin to experience many negative feelings that will appear to be totally out of place with their new found recovery. The former drug rehab patient will attempt to repress these self defeating thoughts, by trying to just push them out of their mind; it is at this point, that the individual's addictive logic will tell them that they must reach for something that will make this pain go away. A person that is in the initial stages of recovery for addiction will have an intense urge to blot out painful thoughts; thus, awakening the echoes of the individual's addictive past, and reminding them of how easy it used to be to medicate with drugs or alcohol. The former addict may then begin to glorify this past, while denying or minimizing the painful negative effects that were related to their substance abuse problem.
Signs of a drug relapse will often include denial about all of the negative effects of addiction and magical thinking about how wonderful it was to get high; it is at this point that a former addict will begin to deny that there is anything good about being sober. They will tell themselves that being high on drugs worked so well for them in the past, that using again will somehow magically fix all of their current problems. In no time, this addictive logic will create an environment in which a former addict will feel justified about backsliding.
Some signs of a drug relapse that indicate that a relapse may be imminent, can often be as subtle as an individual in recovery for substance abuse feeling irritable or becoming extremely tired from a lack of sleep. Other drug relapse warning signs may be unique to an each individual in recovery and will commonly include various changes in their behaviors and moods; many of these specific changes have commonly been referred to as a "drug relapse signature."
Many individuals may exhibit their own unique signs of a drug relapse, that may include, but will not necessarily be limited to, some of the most common signs which are listed below:
- -appearing to be anxious or worried
- -seeming depressed or unhappy
- -appearing to feel unsafe or threatened
- -acting paranoid and thinking that people are talking about them
- -acting irritated, quick tempered or being openly aggressive
- -have obvious problems with concentration
- -dramatic changes in their eating or appetite
- -talking about taking drugs or drinking
- - noticeable changes in sleeping patterns
- -withdrawing socially -isolating themselves from loved ones
- -feeling anxious about going out socially or about going to work
- -talking about hearing voices
- -experiencing disordered thoughts
- -having extreme mood swings-becoming overly excited or acting high
- -feeling suicidal , is commonly reported to be one of the most common signs of a drug relapse
- -romanticizing about past social events where they would get high
- -playing music or TV very loud
Signs of a drug relapse are different for every person that is in recovery for a drug or alcohol addiction problem, so it is important to work out which signs may be relevant to you; doing this with someone who knows you well, like a family member or a close friend can be extremely beneficial. It is even more important to have a plan of what to do should any of these signs appear. Sometimes, a loved one will recognize the signs of a drug relapse, before the individual in recovery does; when this occurs, they should approach the individual about their observations. Many times what may appear to be signs of a drug relapse will only be indications that a former addict is being negatively impacted by a stressful situation. It is at this point, that the person in recovery and their loved ones should take the time to deal with the stressful situation as a group, by taking immediate action to avoid a potential relapse
When a former addict appears to be feeling off-center, out-of-focus, or just plain confused, these situations can often be signs of a drug relapse. A loved one should not avoid talking to the individual in recovery about why they may appear to be out of sorts. The friend or family member may suggest that the former addict begins to keep a written journal; oftentimes, listing on paper what is going on in their lives can help the individual in recovery to be more objective about their particular situation. A person who is in the initial stages of recovery for a drug addiction will often be ruled solely by their thoughts and feelings; thus, writing these thoughts down on paper may give them a greater degree of clarity.
Knowing the most common drug relapse symptoms can help loved ones to take immediate action upon recognizing these behaviors. Listed below are some of the most common signs of a drug relapse:
Noticeable Change in Attitude - One of the most common signs of a drug relapse are when a former addict makes the decision that participating in their recovery program is just not as important as it was in the initial stages of recovery. They may begin to return to what many 12-step programs refer to as "stinking thinking"; it is as this point that the former addict may began to entertain unhealthy or addictive thoughts. When a former addict is going through an episode of "stinking thinking", loved ones will often begin to feel that something is wrong with the person, but may not be able to identify exactly what it is.
Elevated Stress Levels - Predictably, obvious signs of a drug relapse can rear their ugly head when an elevated level of stress is present; this increase in stress in the former addict's life could be due to a major change in circumstances or because they have allowed a series of little things to build up. Returning to the "real world" after a stint at a residential drug rehab center can often present many stressful situations. The danger signs of a drug relapse will often appear when a person who is recovering from an addiction overreacts to those situations. A former addict should be especially mindful if they start to experience extreme positive/negative feelings or mood swings.
Recurrence of Post Acute Withdrawal Symptoms (PAWS)- Anxiety, depression, sleeplessness and memory loss can continue long after an addict has successfully completed their drug treatment program; this condition is commonly referred to as post acute withdrawal symptoms (PAWS) and many of the characteristics of this condition are similar to the signs of a drug relapse. Post acute withdrawal symptoms are particularly dangerous in terms of a potential drug relapse, because an individual in recovery may be tempted to self-medicate with drugs in order to ease some of the uncomfortable symptoms that accompany this condition.
Changes in Daily Routines- One of the most common signs of a drug relapse is when a former drug rehab patient begins to change the daily routine that they developed in early sobriety. These structured routines have been put in place to help an individual in recovery to replace their compulsive drug using behaviors with other healthy alternatives.
Social Breakdown - One of the primary signs of a drug relapse is that a person may start to feel uncomfortable around others and will begin to make excuses so that they do not have to socialize. A person that is recovering from a drug addiction problem may suddenly stop hanging around sober friends and begin to withdraw from family members; additionally, the person in recovery may suddenly stop going to their support group meetings or discontinue the aftercare plan that their drug treatment center has provided.
Loss of Structure -One of the most obvious signs of a drug relapse occurs when a person in recovery from addiction begins ignore their personal hygiene and starts to sleep late many days of the week. When a person is newly sober, structure is vital part of the drug recovery process.
Loss of Judgment - One of the most noticeable signs of a drug relapse is when a former drug user begins to have difficulty making decisions and when they start to openly make unhealthy ones. A newly recovered addict may experience some difficulty managing their feelings and emotions during the initial stages of drug recovery, but consistently making unhealthy choices could be a sign that a drug relapse may be right around the corner. This type of behavior is normal and to be expected in the initial stages of drug recovery; additionally, a person that is new to recovery may sometimes become overwhelmed for no apparent reason, due to all of the changes that are taking place. It is important that loved ones do not judge a former addict during periods of uncertainty; instead, they should be supportive and acknowledge all of the positive changes that the person has made.
Becoming Defensive When Someone Points Out Changes in Behaviors-One of the most common tell-tale signs of a drug relapse signs is a defensive and self-righteous attitude; this occurs when a former addict becomes uncomfortable as others begin to notice their movement back toward a way of living that brought about nothing but misery.
Drug Relapse - One of the most serious signs of a drug relapse is when a former addict attempts controlled, "social" or short-term drug use; because they will quickly lose control again, they will immediately begin to experience overwhelming shame and guilt.
If signs of a drug relapse are left unchecked, they will eventually lead to a full blown relapse, as most newly recovering addicts will instinctively relate "relief" from life's pain to using drugs, rather than "going to any lengths", for sobriety; thus, the initial signs of a drug relapse need to be recognized and dealt with as soon as possible.
Many individuals that are in the initial stages of drug recovery may encounter "stuck points" during their recovery process; but, when they occur, they should be recognized and dealt with as they can often serve as major warning signs of a drug relapse. Former addicts should not get discouraged when they encounter these "stuck points", as recovery from substance abuse is a long-term, skill-building process. Recovery from addiction is not an event that happens instantly; instead it requires that a former addict consistently continues to take positive sobriety-oriented action steps. Recovery initially begins the moment an individual recognizes they have a problem with addictive drug use; but the drug recovery process will not formally begin to take shape until the person begins to develop healthy new behavior patterns, which includes no longer using addictive chemicals.
Relapse does not just happen out of the blue, but the most obvious signs of a drug relapse will generally follow a brief period of irrational thinking and reactions; these reactions are generally based on how the former addict sees life, (thinking), and how they choose to react to their emotions, (feelings). It is easy to see how reacting to thoughts and emotions could easily take a person who has recovered from an addiction in a direction that could prove hazardous to their drug recovery process.
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Marvel Snap has made a significant amount of money, making it one of the company’s most successful mobile games ever. The deck-building superhero game has been consistently downloaded by fans over the past few months, so its success is well-earned.
According to mobilegamer.biz, the free-to-play card battler has made $50 million in revenue. Downloads continue to dominate as well, with over 18 million players getting the game on their phones.
It looks like things won’t be slowing down for Marvel Snap, as the game just launched its new Ant-Man event. Obviously, this is to tie in with the recent Ant-Man movie and we’re sure that a lot of MCU fans will continue supporting it.
Most fans attribute the success of Marvel Snap to how quick and, well, snappy the matches are. The game’s card battles can be finished in a few minutes, making them perfect for mobile phones. It also helps that the game has a massive roster of Marvel characters, something that Square Enix’s Avengers game could have benefitted from.
Constant balancing has also helped make the game feel consistently fair. Overpowered characters like Silver Surfer were recently nerfed, with more likely to happen if fans are vocal about their issues. As long as they don’t force any pay-to-play events like Pokémon GO did, the game’s reputation should continue to flourish.
While multiple mobile games have had similar success, recent shutdowns have shown that a big brand can’t always save a free-to-play app. Square Enix closed down a number of their free-to-play mobile games, a number of which had the Final Fantasy and Mana brands. This goes to show that pay-to-win can only get you so far.
Marvel Snap is readily available on iOS, Android, and Steam. The game continues to be updated, with plenty of gorgeous art from various comic book artists. Whether you like Spider-Man, Iron Man, or Wolverine, this game has something for everyone.

domain: game


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Dec 4, 2011; Minneapolis, MN, USA; Minnesota Vikings mascot Ragnar dances during a break in the game against the Denver Broncos at the Metrodome. The Broncos win 35-32. Bruce Kluckhohn-US PRESSWIRE
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When it comes to the vibrant world of music, Nigeria has always been a frontrunner. With its rich cultural heritage and a diverse musical landscape, Nigeria consistently churns out chart-topping hits and sets global trends. As we step into 2024, it's time to take a closer look at the hottest Naija music trends that are shaping the industry this year.
1. Afrobeats Continues to Reign Supreme
Afrobeats, the genre that has taken the world by storm, is showing no signs of slowing down in 2024. Artists like Burna Boy, Wizkid, and Tiwa Savage are not only dominating the African music scene but also making waves internationally. The fusion of African rhythms, hip-hop, and pop elements remains irresistible to music lovers worldwide.
2. Afropop Fusion Gains Momentum
In 2024, we see a significant surge in Afropop fusion. Artists are experimenting with diverse musical influences, creating unique sounds that defy traditional genre boundaries. Expect to hear Afropop infused with reggae, dancehall, and even EDM, resulting in catchy tunes that are perfect for both the dancefloor and your daily playlist.
3. The Rise of New School Artists
The Nigerian music industry has always been a fertile ground for emerging talent, and 2024 is no exception. Keep an eye on the next generation of artists who are reshaping the sound of Naija music. From Bella Shmurda to Omah Lay, these rising stars are pushing creative boundaries and garnering massive followings.
4. Digital Distribution and Streaming
The music industry's digital transformation continues unabated, with streaming platforms like Apple Music, Spotify, and Boomplay leading the way. Nigerian artists are capitalizing on these platforms to reach global audiences. This shift in distribution is not only changing how we consume music but also influencing music production and marketing strategies.
5. Collaborations Across Borders
Collaborations between Naija artists and international stars have become a defining trend. In 2024, we anticipate more exciting cross-border collaborations. Nigerian artists are joining forces with musicians from various countries, resulting in a delightful fusion of sounds and cultures.
6. Music Videos as Art
Music videos have evolved into a form of art in their own right. In 2024, expect visually stunning and conceptually rich music videos that complement the music. Artists are investing heavily in the visual aspect of their work, turning their songs into immersive audiovisual experiences.
7. Lyricism and Storytelling
While catchy beats and danceable rhythms are essential, lyrics and storytelling are making a strong comeback in Naija music. Artists are using their music to address social issues, tell personal stories, and convey powerful messages. This trend is resonating with fans who appreciate music with depth and meaning.
8. Naija Music Festivals
2024 promises to be a fantastic year for the latest Nigeria music festivals in Nigeria. From Lagos to Abuja, music enthusiasts can look forward to a diverse lineup of festivals featuring local and international acts. These events provide a unique opportunity to experience the magic of live Naija music.
9. Naija Music Awards
The Naija music industry has a tradition of honoring outstanding talent, and 2024 will be no different. The Naija music awards season is set to recognize and celebrate the achievements of artists, producers, and other industry professionals who have made significant contributions.
In conclusion, Naija music in 2024 is a vibrant tapestry of genres, talents, and trends. From the global dominance of Afrobeats to the rise of new school artists and the digital revolution, the Naija music scene is as dynamic as ever. So, if you're a music lover, buckle up and get ready to explore the hottest Naija music trends of 2024—it's going to be an unforgettable musical journey.


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We wouldn’t ever think to look to haters for inspiration — but that’s what Selena Gomez actually does.
During the 13 Reasons Why premiere last night, Selena opened up about how she does get inspired and just who gives it to her.
“My family. My little sister, who is 3,” she shared, speaking of her sister Gracie. “A lot of the people who have pushed me down have actually motivated me.”
Although Selena takes their words and turns it into motivation, it doesn’t mean the bullies have stopped at all.
“I can’t allow myself to believe the words that people are saying to me,” she shared.
Selena, pictured below out to lunch with a friend in Los Angeles, is now our inspiration to move past haters.

domain: sociology


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domain: design


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Miles tells booster group Saturday’s game is his last at LSU
BATON ROUGE – LSU coach Les Miles finally let it out Friday.
“Thanks for a great 11 years,” he said at the regular Friday meeting of the Gridiron Club booster group, according to multiple Gridiron Club members at the meeting.
“I’ll always be a Tiger,” Miles said, but added that he was at his last Gridiron Club meeting and that he will not coach the Tigers in whatever bowl game in which they play after this regular season.
LSU officials have continued to refuse to confirm publicly that Saturday night’s regular season finale against Texas A&M will be Miles’ last as LSU’s coach, but signs have pointed to and sounded like the end of an era at LSU throughout this week.
“If you look at the great number of men that I’ve been fortunate to meet and coach at LSU,” Miles waxed as he closed his weekly radio show Wednesday night, “guys that have put team in front of themselves and guys that really grew up and matured and led our team and the many teams that we’ve had and the experiences that we’ve enjoyed, the highs and the lows have been tremendous.”
On the day Miles made those comments, LSU athletic department officials – per a request by USA Today —were trying to decipher the wording of Miles’ buyout in his contract to ascertain whether he would be paid $15 million for being fired by Dec. 31 or $10.7 million, which would be the buyout total less the $4.3 million yearly salary package money he will have received this year by Dec. 31. The contract states, though not clearly, that Miles would get the $15 million minus what he makes in the dismissal year. Miles’ agent George Bass told USA Today that Miles would get $15 million, period.
Meanwhile, Miles has tried, with admittedly not much success, to focus on the game between his Tigers (7-3, 4-3 Southeastern Conference) and Texas A&M (8-3, 4-3 SEC) that kicks off at 6:30 p.m. on the SEC Network in Tiger Stadium.
“I have described the perimeter,” Miles said Wednesday after practice. “I don’t know that I’m very successful in this endeavor. Certainly, we’ve run into distractions before, but this seems to be a pretty prevailing and evident distraction.”
Miles looked back on the early days of his LSU career on his radio show Wednesday night.
“I’ll never forget showing up and seeing Andrew Whitworth and what was said by Tyson Jackson when Katrina hit,” Miles said during the show that included emotional goodbyes from fans.
Whitworth was a 6-foot-7, 325-pound, first team All-SEC offensive tackle as a junior in 2004 whom Miles inherited when he became LSU’s coach on Jan. 1, 2005. Whitworth helped lead Miles’ first team to the SEC West championship despite having to play 10 games in less than 10 weeks because of the postponements of games and relocation of a game due to hurricanes Katrina and Rita. Katrina destroyed or damaged the homes of LSU players from New Orleans such as Jackson.
“I’m not very good with a hammer and nails,” Miles said Jackson told him at the time. “But I’m really pretty good at playing football.”
Miles, 62, has proven to be very good as a coach and will bring in a 110-33 overall record in 11 seasons at LSU for a .769 winning percentage to the Texas A&M game. Miles is 60-27 in the SEC for a .689 winning percentage. He won a national championship and the SEC championship in the 2007-08 season and went 13-1 with a national championship game appearance and an 8-0 SEC championship in the 2011-12 season. He won the SEC West in 2005 and won 10 or more games in 2005, ’06, ’07, ’10, ’11, 12’ and 13.
But he dropped to 8-5 and 4-4 in the SEC in the 2014 season. After a 7-0 start this season and a No. 2 ranking in the College Football Playoffs rankings, the Tigers have lost three straight games by 14 points or more for the first time at LSU since the 1966 season.
In discussing senior night for his players Saturday, Miles could have been talking about himself when he said, “What you have to do is leave the tears alone and regroup, and let’s go play. I think that’ll be very similar in this event.”
Coverage of LSU and Glenn Guilbeau commentary supported by Hebert's Town and Country Auto Dealer in Shreveport located at 1155 E. Bert Kouns. Research your next Chrysler, Dodge, Jeep or RAM at http://www.hebertstandc.com

domain: news


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She’s 17 years old, and two years ago she witnessed something no one should — the mass murder at Marjory Stoneman Douglas High School.
On Tuesday, an attorney for the teenager appeared in court, asking a Broward judge to protect her from lawyers who want her testimony to prepare their defense for the shooter, Nikolas Cruz.
Nearly two years after it happened, the Parkland massacre was so traumatic for those who survived that some are incapable of discussing it, even in professional settings, without putting their own mental health at risk, attorney Jay Cohen said in court papers.
Cohen represents two witnesses in the case who are reluctant to participate in depositions, which are pretrial interviews conducted under oath by lawyers so they can prepare for trial.
One witness, a ninth-grade teacher, was in the 1200 building when Cruz opened fire, eventually killing 17 people and injuring 17 others.
She heard the gunfire and knew many of the victims, and when defense lawyers sent her a subpoena for a deposition, she recoiled at the thought, Cohen said.
Despite her anxiety and concern, the teacher reached an agreement with the defense team to conduct the deposition at her lawyer’s office, lawyers told Broward Circuit Judge Elizabeth Scherer Wednesday.
For the student witness, there has been no agreement, and Cohen could not say when she would be ready to answer questions about the shooting.
“She’s not in any condition or state of mind to discuss the facts," Cohen said. “If she ever reaches the point where, according to her professionals, she can answer questions without regressing, I will be more than happy to present her.”
The young woman’s reluctance to testify complicates Cruz’s defense, given his laywers are legally entitled to interview prosecution witnesses before the trial starts, said Assistant Public Defender Gabe Ermine. If she doesn’t talk, defense lawyers can’t anticipate her testimony and prepare for it.
Breaking News Alerts
Scherer said she didn’t want to order the witness to undergo an interview that would negatively affect her mental health, even asking State Attorney Mike Satz if he would agree not to call the young woman if she never finds herself “ready” for a deposition.
But Satz wouldn’t commit to it, saying the prosecution’s plan includes the teenager as an "A" witness likely to be called to tell her story to the jury.
Wednesday’s hearing ended in a stalemate. Scherer asked the attorneys to work it out in a timely way that would protect the witness and the defendant’s right to a fair trial without having the judge order a reluctant and traumatized girl to testify against her will.
“If she can’t submit to a deposition, then she cannot be called at trial,” the judge said. “I don’t want to order this young person to submit to a deposition before she is ready.”
Cohen hinted that he would be willing to question the need to call his client at all, but stopped short of saying so explicitly. “I don’t need to get into why this particular witness is so critical until we get to the point” where her testimony is compelled, he said.
The judge set no deadline for a deposition, but has warned lawyers that the Stoneman Douglas murder trial will not be postponed indefinitely.
Cruz, 21, faces the death penalty if convicted.


- Beyonce and Jay Z party in New Orleans with her sister Solange - TMZ
- Prince Harry and Meghan Markle are not living together - Gossip Cop
- Vampire Diaries boss just shared tons of series finale spoilers! - Just Jared Jr
- Is Ciara having a baby boy? - Wetpaint
- Idris Elba takes his dog for a walk in the rain on set of his new film - Lainey Gossip
- Leah Remini says Tom Cruise could "end" Scientology - The Hollywood Reporter
Naomie Harris & Jessica Lowndes: Fashion Rules Exhibit Launch!
About Photo #2904306: Naomie Harris gets all dolled up for the Fashion Rules exhibition launch party on Thursday (July 4) at Kensington Palace in London, England. The 36-year-old actress… Read More Here


I have a Winchester 1200 12ga, 2 3/4". I purchased this from a friend over 20 years ago and never fired it. It has a screw in choke at the end of the barrel. It's been in our closet and has a few scratches in the stock that are not visible in the photos. There is one very small surface ding on the barrel, but otherwise a nice gun. The serial number starts with L76. Cash price $200.00, includes a new box of Winchester AA. OR Trade towards: WWII M1 Garand WWII M1 Carbine or an AK type 7.62x39 This would make for a nice bird hunting gun or as a welcoming gift to the uninvited guest in the middle of the night. I am a gun newbie, so thanks for your patience in advance!


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Computer animation of the Sars-CoV-2 coronavirus
Photo: koto_feja / Getty Images
According to a new study, there are restrictions on the treatment of the corona subvariant Omicron BQ.1.1: all currently approved antibody therapies did not work on her, the German Primate Center in Göttingen announced.
The analysis by scientists from the facility and the University of Erlangen-Nuremberg was published in the journal The Lancet Infectious Diseases.
Especially in regions where BQ.1.1 is widespread, doctors should not rely solely on antibody therapies when treating infected high-risk patients, but should also consider other drugs such as Paxlovid, said study leader Markus Hoffmann.
In addition, new antibody therapies would have to be developed.
more on the subject
Mutation of the corona virus: How dangerous is the new variant BQ.1.1?By Julia Köppe
In its current weekly report last Thursday, the Robert Koch Institute pointed to a quadrupling of the new sub-line in Germany within the past four weeks.
The proportion of the pathogen was therefore eight percent.
Guideline advises against use in clinics
In their laboratory studies on cell cultures, the researchers found that BQ.1.1 could not be neutralized either by individual antibodies or by antibody cocktails.
Other subtypes were already immune to some preparations.
The cause of the resistances are mutations of the so-called spike protein of the corona virus, it said.
"The ever-increasing resistance development of Sars-CoV-2 variants makes it necessary to develop new antibody therapies that are particularly tailored to the currently circulating and future virus variants," explained Stefan Pöhlmann, head of the Infection Biology department at the Primate Center.
"Ideally, they should target regions of the spike protein that have little potential for escape mutations."
Antibody therapies against Covid-19 are primarily an option for people who are at high risk of developing a severe course of the disease – for example, patients who have to take medication that suppresses the immune system after an organ transplant.
It is important that so-called monoclonal antibodies are used very early in the course of the disease.
In inpatient settings, the use of monoclonal antibodies has not been recommended for a long time.
The current guideline from September states: "None of the monoclonal antibodies approved for therapy in Europe is currently sufficiently effective against the currently dominant omicron variant BA.5."

domain: medical


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LSU’s Miles: Wish I had done better vs. Alabama
By BRYAN LAZARE
BATON ROUGE, La. — LSU still feels the sting of its loss to top-ranked Alabama and probably won’t forget the setback anytime soon.
Tigers coach Les Miles spent much of his weekly media luncheon Monday dealing with situations which popped up in his team’s 21-17 loss to the Crimson Tide on Saturday.
“We won every statistical category, but the score,” the coach said. “That’s unfortunate. I told the team I wish I would have done a couple of things better.”
The defeat all but mathematically eliminated the ninth-ranked Tigers from winning the Southeastern Conference Western Division championship. LSU has a chance — albeit a slim one — to represent the West in the title game if it somehow manages to end in a three-way tie for first place with Alabama and Texas A&M.
For that unlikely scenario to happen Alabama would have to lose to the Aggies and Auburn, which hasn’t won a SEC game this season. Of course, LSU has to beat its final three opponents — No. 22 Mississippi State, Ole Miss and Arkansas.
The Tigers players had two priorities this season — get a measure of revenge for their 21-0 loss to Alabama in last season’s national title game and return to the national championship game in January.
Now, barring a totally unexpected series of results, there will be no titles for this LSU team.
“You can still have a championship style of effort,” Miles said. “Having a championship style of football team is still our need and want. We still have a chance to do some significant things.”
One of those significant achievements would be an appearance in a BCS bowl game, possibly the Sugar Bowl. But LSU would even need some help for that to happen, including one more loss for both Georgia and Florida, who are ahead of the Tigers in the BCS standings.
“Understand we have a good football team,” Miles said. “In a few ways, Saturday (against Alabama) proved that. We have to play like that the rest of the way and see how things come out. Ending up in a BCS bowl certainly can happen. That’s a possibility.”
LSU must close the regular season with a three-game winning streak. In the loss to Alabama, Zach Mettenberger had his best game of the season by throwing for 298 yards and one touchdown with no interceptions. Moreover, Jeremy Hill rushed for 107 yards.”
The Alabama game “was our most complete game on offense,” Miles said. “Mettenberger and the receivers had great chemistry on his throws and the receivers coming out of their breaks. We rushed the ball OK. It could have been better.
“Our football understands that it didn’t get it done against Alabama. But, let’s play like that again. Throw for 300 yards and run for 200 yards. The defense has to play with the same intensity and eliminate the mistakes. We improved, but we need to keep improving.”
They’re get the chance Saturday against a staggering Mississippi State team.
The 22nd-ranked Bulldogs have experienced a rough past two weeks with lopsided defeats against Alabama and Texas A&M. The Bulldogs had won their first seven games. Last season, LSU struggled to a 19-6 victory at Mississippi State.
“We have a 24-hour rule,” Miles said. “We watch (Alabama) film (Monday) and then we’re done with that one. We’ll take the positives and move on. If we play like that in the next game, I’ll be happy. I’m glad we’re playing a good team. That’s what our football team needs now.”
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domain: sports


A policy is a corporate direction that is formally adopted by Council resolution. Enacting policies provides a framework for decision making ensuring consistency throughout the municipality.
Policies are laws, subject to municipal bylaws and Provincial and Federal law. The supporting legislation for such policy development is the The Municipalities Act which provides Council the authority to develop and evaluate the policies and programs of a municipality.
In comparison to a bylaw, which requires three readings of Council to pass or change, a policy may be passed and amended by a single resolution of Council. A policy may not exist in direct contradiction of any municipal bylaw or other law, but may exist to provide a framework and direction for regulation and implementation of those laws.
The Town of Wadena's Council approved policies are listed below.


Dubai, a city renowned for innovation, is embarking on two groundbreaking transportation projects. The Roads and Transport Authority (RTA) has partnered with global experts to develop sustainable transport solutions. The first project focuses on the Floc Duo Rail system, and the second aims to introduce a solar-powered rail bus system. These initiatives demonstrate Dubai’s dedication to advanced technology, sustainability, and the future of urban mobility.
In the last 15 years, Dubai has seen incredible changes, like the Dubai metro in 2009 and stunning landmarks such as the Burj Khalifa and Palm Jumeirah Islands. The UAE has made its mark, especially with the man-made islands. Dubai keeps pushing boundaries, combining luxury with technology. It’s also committed to sustainability, promoting initiatives to lessen environmental impact.
The Floc Duo Rail system, made with help from the UK’s Urban-Mass Company, will transform city transport. It uses driverless electric pods on an elevated track, cutting the need for big construction projects like tunnels and stations. Its double-track setup allows fast, efficient travel in cities and can be adjusted to fit different urban areas, from small neighborhoods to entire cities.
The Floc Duo Rail system is powered by solar energy, fitting Dubai’s sustainable goals. It’s flexible, ranging from small local links to city-wide networks, with customizable stations to match rider needs. Pods are driverless, adjusting capacity smartly for energy efficiency. Ricky Sandhu, CEO of Urban.Mass, highlights the partnership’s importance, showing the UK and UAE’s dedication to fighting climate change. Their collaboration aims to introduce sustainable transit tech, changing how people move around the city.
Solar-Powered Rail Bus System:
In another move, Dubai’s RTA partnered with Rail Bus Inc. from the US to create a solar-powered rail bus system. It uses small, driverless electric vehicles on elevated tracks, making it lightweight and adaptable. This system can be fitted into different settings, providing an eco-friendly and efficient transport option. It’s like a smaller version of a metro but with a focus on sustainability.
Dubai’s move toward the future with the Floc Duo Rail and solar-powered rail bus systems shows its dedication to advanced tech and sustainability. By leading in urban mobility, Dubai sets the scene for a greener, tech-savvy future. These efforts improve city life and spark global discussions on the advantages of innovative, eco-friendly transportation solutions.


SciAps, Inc., is a Boston-based instrumentation company specializing in portable analytical instruments to measure any element, any place on the planet. With groundbreaking innovations for geochemistry like the world’s first handheld LIBS for analyzing lithium in rocks and brines, and the REE-optimized X555 pXRF, SciAps is leading the way in field portable elemental analysis. Regardless of the element, SciAps has you covered.
SciAps is also featuring the newly released Z-9 Liquidator, the world’s first in-field lithium brines analyzer. The Z-9 Liquidator is powered by the SciAps Z-903 handheld LIBS analyzer, equipped with factory built lithium brines calibration. Users can also develop a custom calibration via the Profile Builder software to further optimize performance.


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Rossville, Pennsylvania facts for kids
Quick facts for kids
|Lua error in Module:Location_map at line 412: attempt to index field 'wikibase' (a nil value).|
|Elevation||509 ft (155 m)|
|Time zone||UTC-5 (Eastern (EST))|
|• Summer (DST)||UTC-4 (EDT)|
|GNIS feature ID||2756699|
Rossville is an unincorporated community in Warrington Township in York County, Pennsylvania, United States. Rossville is located at the intersection of Pennsylvania Route 74, Pennsylvania Route 177, and Old York Road northeast of Wellsville and southwest of Gifford Pinchot State Park.
Rossville, Pennsylvania Facts for Kids. Kiddle Encyclopedia.

domain: geography


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In this study, we investigated the relationship between obesity and absenteeism and found that obesity increased the incidence rate ratio of absenteeism by 31% in our study cohort, independent of other risk factors, including chronic disease and unhealthy lifestyle choices. Obese women, in particular, are more likely to miss work, especially those with white-collar professions, and we estimate that absenteeism due to obesity imposes a considerable financial burden on states, totalling an additional €236 million per year in Portugal.
In previously published study, obesity was found to increase the absenteeism incidence rate ratio by approximately 27%, than normal weight peers.(23). Some authors, when applying a longitudinal methodology to understand the causal relationship between obesity and absenteeism, found that obesity could act both as a direct explanatory variable and as a mediator for other variables linked to loss of productivity, as obesity is also considered a risk factor for several chronic diseases(6, 23). These results are consistent with our findings showing similar degrees of obesity-associated effects on absenteeism, both when it is evaluated separately and when associated with other risk factors, such as chronic diseases and lifestyle habits. However, as has been recommended by other authors, prospective analyses are necessary to determine the time of occurrence, that is, whether diseases occur before or after an individual has become overweight or obese. Such studies would help to establish a clear causal framework for a meaningful attribution of the indirect costs of obesity(6).
Obese workers are more likely to report poor work ability or limitations in the amount, type, or quality of work they perform than their normal-weight counterparts (24). In the present study, we found that obese women were 68% (P < 0.01) more likely to miss work than normal-weight women, with significant increases in likelihood of absenteeism observed for women in both white- and blue-collar professions (82% and 48%, respectively). However, although similar trends were observed with men, the differences were not significant. Consistent with these results, a study from the United States found that the probability of missing work was significant across all professional categories for obese women, although among men, the results varied by occupation (4). This discrepancy with our findings for men may be due to the higher prevalence of obesity observed in the American study population, reported to be 23% among men; in contrast, male obesity rate in our study was 6.59%(25). Among women, similar rates of obesity were noted in both studies. This may be due to biological aspects related to the process of body fat accumulation, which begin at puberty and continue throughout life, as well as the complex interactions between genetic, epigenetic, and hormonal issues, and may explain the similar results reported in both studies [21, 23]
Numerous studies have shown that obesity is strongly associated with absenteeism. In one case, Finkelstein et al. reported that grade-I obese women (BMI, 30–34.9) in the United States miss 5.2 days per year due to illness or injury, which is 1.8 days more than normal-weight women, while grade-II (BMI, 35–39.9) and grade-III (BMI, ≥40) obese women miss 3.0 and 4.8 more days, respectively, than normal-weight women, with all increases statically significant (25). In contrast, grade-II and grade-III obese men miss approximately two more workdays per year than normal weight men, similar to what has been found in other studies(4, 25). Here, we found that obese individuals miss 10.2 workdays on average per year—3.8 more than their normal-weight peers. Obese women and men lose 12 and 8 working days per year, respectively, which is 4.6 and 3.5 days more, respectively, than their normal weight counterparts, with only results for women showing statistical significance. Similarly, a study conducted in London reported a loss of 9.5 workdays per year for obese workers. European countries have many common characteristics, relating to population distribution, sociodemographic characteristics, and prevalence of obesity itself. Thus, it makes sense that our results are more similar to those reported in London (26) than to findings from the United States(4, 24, 25). Regardless, all these studies report the key finding that obesity has a substantial impact on lost working days (4, 26). Adiposity and fat distribution are closely associated with whole body metabolism and long-term health, and consequently, obese individuals often have more chronic conditions associated with poor health status. Thus, we expect that this is the reason that people with obesity display greater absence from work due to sickness, as well as increased healthcare consumption, relative to their non-obese counterparts.
Critically, absenteeism due to obesity imposes a considerable financial burden on states. In this study, we estimated that obese workers incur an additional cost of €236 million per year when compared to non-obese workers. These costs range from to €297 to €467 per year for each obese employee and are higher for women than men (€398.6 vs. €361.5, respectively). A previous study by Pereira et al. estimated the total indirect cost of obesity in Portugal in 2002 at €199,8 million, indicating that obesity causes considerable economic losses for the country . Comparison with our findings reveals a difference of €37 million between the study by Pereira et al. and our estimate for obesity-associated costs due to absenteeism per year, despite that, it is important to say, that the methodology between the two studies is different, while Pereira et al used Attributable Risk to calculate the number of deaths attributable to obesity, taking into account the relative risk of obesity prevalence estimates, (27), in our study we used absenteeism as main outcome and estimated the costs through the HCA extrapolating to all population using the prevalence of obesity in the years of study.
In Europe, the estimated cost of absenteeism varies from €117 to €1873, depending on cost category or comparison group (11), and worldwide, this same trend is observed (6, 12, 13, 26, 28). Further, international studies have attributed increases in health sector spending ranging from 30–60% to absenteeism, with indirect costs reaching $8.65 billion per year in 2012(23, 25). Thus, the economic impact of obesity on both the health sector and society as a whole is undeniable, and numerous studies have reported this issue as a critical problem that is increasing in prevalence. We therefore expect that the implementation of strategies to prevent obesity could generate gains in productivity, as well as reduce the economic burden imposed by this disease.
We note, however, that this study has several limitations. First, the BMI values were based on self-reported weight and height, which could generate systematic bias, as people often underreport their weights and overestimate their heights (29). Second, our dependent variable, absenteeism, had a high number of zero observations, which substantially reduces the sample size of the study. However, by using appropriate statistical modelling and comparing different statistical approaches, we trust that our data are sufficiently robust to support our conclusions (21, 22). An additional challenge arises from the fact that, to the best of our knowledge, there is no standard methodology reported in the literature for evaluating the indirect cost of absenteeism due to obesity (7, 11, 12). Further, it is important to note that the salary values in this study were estimated based on the imputation of average worker wage data corresponding to the evaluation period of the EpiDoC and may therefore not be completely accurate. In addition, we assessed the cost of obesity with the HCA, which takes both an individual and societal perspective and has often been criticized for overestimating loss of productivity (19).
Despite these limitations, our study also has a number of key strengths. In particular, our data were obtained from a cohort representing the entire adult Portuguese population, and repeated measures can evaluate changes in outcomes over time. We also evaluated costs using obesity as the main predictor variable, whereas most other studies evaluated costs related to obesity-related diseases, and not just obesity. For this reason, we expect that our study is less prone to confounding bias and thus, better able to determine associations between obesity and absenteeism, as well as to estimate its costs. Furthermore, our dataset containing information relating to days absent, chronic diseases, and lifestyle factors is quite robust for indirect cost estimates and allows for a comprehensive analysis of obesity-associated factors.


Valerie Landriscina - RAND Engineering and Architecture
As Project Architect on RAND Engineering & Architecture’s Facade & Roofing Team, Valerie Landriscina, RA provides design, specification, and construction administration services on exterior repair and upgrade projects. Since working at RAND, Valerie managed over $45 million in exterior repair, restoration and capital improvement work. One of Valerie’s passions lies in historic preservation projects. Her work at 153 Lincoln Place, a 10-unit condominium with severe leakage issues that was built in 1887 in Park Slope Historic District, won the 2017 Park Slope Civil Council’s Evelyn and Everett Ortner Preservation Award for excellence in exterior restoration. Over the past couple of years, she has worked on restoring several Finnish cooperatives in the Sunset Park neighborhood of Brooklyn including 549-561 41st Street, 702-712 45th Street, and the first and oldest housing cooperative in New York City, 816 & 826 43rd Street, also known as the Alku & Alku Toinen. In addition, Valerie spearheaded the efforts to nominate Alku & Alku Toinen to the National Register of Historic Places, resulting in the listing of the property in 2019. Valerie received her Master of Architecture from Pratt Institute’s School of Architecture and her Bachelor of Arts in Urban Design and Architecture Studies from New York University. She is Registered Architect in New York State, a Qualified Exterior Wall Inspector (QEWI), and is certified as a Level 1 Infrared Thermographer.


To fight the rise in Covid-19 cases, Libya began a strict three-day lockdown as the country prepares to celebrate the Muslim New Year.
Ten days ago, the North African country introduces a partial curfew from 18:00 to 06:00 local time.
This measure will be implemented in the centre and west of the country, including the capital Tripoli, the government announced.
Since the start of the pandemic, the country has officially recorded 262,948 cases of infection, and 3,663 deaths.
Libya has only vaccinated a few hundred thousand people out of about seven million population against the virus.
The north African country recently received 2 million doses of vaccine from China and is expecting another 1.5 million doses in the coming weeks.


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The E3 ubiquitin ligase Hace1 is required for early embryonic development in Xenopus laevis
BMC Developmental Biology volume 16, Article number: 31 (2016)
HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) regulates a wide variety of cellular processes. It has been shown that one of the targets of HACE1 is the GTP-bound form of the small GTPase Rac1. However, the role of HACE1 in early development remains unknown.
In situ hybridization revealed that Xenopus laevis hace1 is specifically expressed in the ectoderm at the blastula and gastrula stages and in the epidermis, branchial arch, kidney, and central nervous system at the tailbud stage. Knockdown of hace1 in Xenopus laevis embryos via antisense morpholino oligonucleotides led to defects in body axis elongation, pigment formation, and eye formation at the tadpole stage. Experiments with Keller sandwich explants showed that hace1 knockdown inhibited convergent extension, a morphogenetic movement known to be crucial for body axis elongation. In addition, time lapse imaging of whole embryos during the neurula stage indicated that hace1 knockdown also delayed neural tube closure. The defects caused by hace1 knockdown were partly rescued by knockdown of rac1. Moreover, embryos expressing a constitutively active form of Rac1 displayed phenotypes similar to those of embryos with hace1 knocked down.
Our results suggest that Xenopus laevis hace1 plays an important role in early embryonic development, possibly via regulation of Rac1 activity.
HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) was identified as a gene located in an affected region of chromosome 6q21 in human Wilms’ tumor . It has been shown that HACE1 expression is reduced in multiple human tumors, and forced expression of HACE1 in human tumor cell lines inhibits cell growth in vitro and in vivo . Moreover, Hace1 −/− mice develop spontaneous late-onset cancer . Therefore, HACE1 is considered to be a tumor suppressor gene. HACE1 protein is a HECT family E3 ligase and is known to regulate multiple cellular processes. The most investigated target of HACE1 is Rac1. HACE1 specifically recognizes GTP-bound Rac1, an active form of Rac1, and promotes its degradation through the ubiquitin-proteasome pathway . Rac1 degradation by HACE1 is important in regulating cell migration and reactive oxygen species (ROS) production [4, 5]. In addition, Rab GTPases are binding partners of HACE1 . HACE1 regulates Golgi membrane dynamics during the cell cycle by interacting with Rab proteins . One Rab GTPase Rab11a is activated by HACE1-mediated ubiquitination and subsequently promotes recycling of the β2-adrenergic receptor . In addition, HACE1 has protective actions against oxidative stress in the brain and hemodynamic stress in the heart [8, 9]. Thus, these findings have demonstrated HACE1 functions in diverse cellular processes. However, the roles of HACE1 during vertebrate embryonic development have not been previously reported in any model organism.
Here, we show that Xenopus laevis hace1 is mainly expressed in the ectoderm and plays an important role in embryonic development. Hace1-depleted Xenopus laevis embryos displayed defects in multiple developmental processes. Analysis with Keller sandwich explants revealed that Xenopus laevis hace1 is essential for convergent extension.
Xenopus laevis hace1 is mainly expressed in the ectoderm during early embryogenesis
To investigate a role of HACE1 in early embryonic development, we first cloned a Xenopus laevis HACE1 homolog (accession number AB894419) with a 2739 bp open reading frame. Compared with the reported sequence of Xenopus laevis hace1 in GenBank (accession number NM_001093608), the Xenopus laevis hace1 sequence that we obtained had five silent point mutations and a 96 bp deletion. These silent mutations may be single nucleotide polymorphisms. The 96 bp deletion may be caused by alternative splicing, because the human HACE1 gene deposited in GenBank (accession number NM_020771) has a similar deletion. We thus concluded that the obtained Xenopus laevis hace1 clone is a splicing variant. Human HACE1 protein shares 90 % and 87 % amino acid identity with our Xenopus laevis Hace1 protein and the previously reported protein, respectively. Hence, we used our clone in this study.
Whole-mount in situ hybridization was performed to determine the expression pattern of Xenopus laevis hace1. Maternal transcripts of hace1 were localized to the animal region (Fig. 1a). The expression was high in the presumptive ectoderm at the gastrula stage (Fig. 1b). At the neurula stage, hace1 was weakly expressed in the dorsal ectoderm (Fig. 1c). At the early tailbud stage, hace1 showed a spotty expression pattern in the epidermis and a uniform expression pattern in the neural tube (Fig. 1d). At the late tailbud stage, hace1 was expressed in the brain, eye, neural tube, branchial arch, ear vesicle, and kidney (Fig. 1e).
Knockdown of hace1 causes shortening of the body axis and inhibition of eye and pigment formation
We next performed knockdown experiments in developing Xenopus laevis embryos by using an antisense morpholino oligonucleotide against hace1 (HACE1 MO). We designed HACE1 MO to target the sequence containing the translation initiation AUG of hace1 mRNA. To evaluate the specificity and efficiency of HACE1 MO, we performed immunoblotting analysis. HACE1 MO blocked the translation of C-terminally Myc-tagged hace1 (hace1-myc) mRNA containing the HACE1 MO target sequence (Fig. 2a, left two lanes). We then injected HACE1 MO into the animal region of dorsal or ventral blastomeres at the 4-cell stage and observed the embryos at the tadpole stage (stage 40–41). Embryos that were dorsally injected with HACE1 MO displayed a number of defects, including a shortened body axis, a reduction of pigments, and a reduction of eye size (Fig. 2b, middle panel), whereas embryos that were ventrally injected with HACE1 MO exhibited no significant phenotype (data not shown). According to the extent of each defect, we classified embryos into three groups: severe, mild, and normal (Fig. 2c, d). Coinjection of HACE1 MO and N-terminally Myc-tagged hace1 (myc-hace1) mRNA, which was MO-resistant because of the insertion of two Myc tags near the MO recognition site (Fig. 2a, middle and second right lanes), resulted in milder defects than the injection of HACE1 MO alone (Fig. 2b–f), indicating that the phenotypes observed in the HACE1 MO-injected embryos were primarily caused by Hace1 depletion. Thus, these results suggest that hace1 has an important role in early Xenopus laevis embryonic development.
Hace1 is required for convergent extension
In early Xenopus laevis development, dorsal mesodermal and ectodermal cells converge toward the midline and mediolaterally intercalate, and this process, called convergent extension, leads to elongation of the anterior-posterior body axis . Therefore, it can be hypothesized that the shortened body axis observed in hace1 knockdown embryos is caused by aberrant convergent extension. To test whether hace1 regulates convergent extension, we used Keller sandwich explants, in which convergent extension can be reproduced in culture . Explants from embryos injected with control MO (Fig. 3a, left panel) elongated normally, whereas those from embryos injected with HACE1 MO displayed little elongation (Fig. 3a, middle panel). The inhibition of elongation by HACE1 MO was rescued by coinjection of myc-hace1 mRNA (Fig. 3a, right panel). To evaluate the elongation of explants, we measured the length-to-width ratio of explants. The length-to-width ratio was significantly reduced by HACE1 MO, and this reduction was significantly rescued by coinjection of myc-hace1 mRNA (Fig. 3b). These results suggest that Hace1 regulates convergent extension.
Hace1 depletion causes a delay in neural tube closure
Because HACE1 MO inhibited convergent extension in Keller sandwich explants, we examined the effect of HACE1 MO on gastrulation and neural tube closure, which are two major morphological events involving convergent extension, in whole embryos. An injection of 30 ng of HACE1 MO did not lead to an apparent defect in gastrulation (data not shown), but it led to a delay in neural tube closure at the neurula stage (Fig. 4a). To examine this phenotype in detail, we performed time-lapse imaging of neurulating embryos. At the 4-cell stage, HACE1 MO was injected into the right dorsal blastomere, and control MO was injected into the left dorsal blastomere (Fig. 4b–d, indicated as HACE1 MO). As a control, uninjected embryos were also observed (Fig. 4b–d, uninjected). Embryos at stage 13 were placed on a culture dish, and images were collected every 5 minutes until neural tube closure was completed (Fig. 4b–d and see also Additional file 1: Movie S1 and Additional file 2: Movie S2; uninjected embryos and MO-injected embryos, respectively). The neural plate was likely to be formed in the HACE1 MO-injected right side (Fig. 4b, 0 min). However, the elevation of the neural fold was much less apparent in the HACE1 MO-injected side than in the control MO-injected side (Fig. 4b, the middle panel at 60 min). Although the neural fold became visible at 30 to 60 min in the HACE1 MO-injected right side, the ridge of the neural fold in the right side was much less prominent than that in the control MO-injected left side (Fig. 4b, 120 min). We measured the maximum distance between the dorsal midline and the inner edge of the neural folds. In uninjected embryos, the distance in the right side was roughly equal to that in the left side (Fig. 4c, d). However, the distance in the HACE1 MO-injected right side was markedly longer than that in the control MO-injected left side (Fig. 4c, d), thus indicating that knockdown of hace1 led to a significant delay in neural tube closure. These results suggest that hace1 is required for normal neural tube closure.
Phenotypes of hace1 morphants are specific for loss of hace1
Knockdown by antisense morpholino oligonucleotides may be accompanied by off-target effects . Although we performed rescue experiments (Fig. 2b–f), we further evaluated the specificity of hace1 knockdown. We designed HACE1 MO2 as a second non-overlapping morpholino oligo for hace1. Whereas HACE1 MO targets a region from −1 to +24 from the translational start site, HACE1 MO2 targets a region from −79 to −55 from the translational start site. Embryos dorsally injected with HACE1 MO2 displayed a shortened body axis, a reduction of pigments, and a reduction of eye size (Fig. 5a–e). We next examined the effect of HACE1 MO2 at an early developmental stage. Similarly to the results from the injection of HACE1 MO, the injection of HACE1 MO2 did not lead to an apparent defect in gastrulation (data not shown), but it did lead to a delay in neural tube closure at the neurula stage (Fig. 5f). Thus, knockdown of hace1 by HACE1 MO2 led to essentially the same phenotype as that by HACE1 MO. These results further confirmed the specificity of morpholino-mediated knockdown of hace1.
Developmental defects in hace1 morphants are largely caused by an excess of active Rac1
HACE1 ubiquitinates GTP-bound RAC1 and causes its degradation . Thus, it is possible that the phenotype of hace1 morphants is caused by an increase in active Rac1. To investigate the relationship between hace1 and rac, we first attempted to analyze the expression pattern of the rac family genes: rac1, rac2 and rac3. It has previously been shown that Xenopus laevis rac1 is expressed in neural tissues at the neurula and tailbud stages . Our qRT-PCR analysis showed that rac1 is expressed throughout early development, and rac2 expression starts from the early tailbud stage (Fig. 6a). The full-length coding sequence of Xenopus laevis rac3 has not been deposited in GenBank, and we were unable to find Xenopus laevis EST sequences corresponding to rac3. In addition, we were unable to amplify any DNA fragments from Xenopus laevis embryos in our RT-PCR experiments using primers that were designed on the basis of the rac3 sequence from the closely related species Xenopus (Silurana) tropicalis, thus suggesting that rac3 may be absent or weakly expressed in Xenopus laevis embryos. These results indicate that rac1 is predominantly expressed among rac family members at the neurula stage. Thus, it is possible that hace1 targets rac1 in Xenopus laevis neurulation.
We next asked whether the defects observed in hace1 morphants could be rescued by reducing Rac1 activity. We used Rac1 MO to reduce the total Rac1 protein level. Immunoblotting analysis confirmed that Rac1 MO reduced the protein level of endogenous Rac1 by more than half (Fig. 6b). We injected HACE1 MO with control MO or Rac1 MO into embryos and fixed them at the tadpole stage (stage 40–41). Embryos coinjected with HACE1 MO and Rac1 MO displayed milder defects in eyes and pigments than did embryos coinjected with HACE1 MO and control MO, although these double MO-injected embryos displayed more severe phenotypes than embryos injected with HACE1 MO alone, possibly because of overdosing of MOs (Fig. 6c–e). In addition, embryos coinjected with HACE1 MO and Rac1 MO had a longer body length than did embryos coinjected with HACE1 MO and control MO (Fig. 6f, g). These results suggest that the defects in hace1 morphants are at least partly caused by an excess of active Rac1.
To further test this possibility, we expressed rac1-V12, a constitutively active mutant of rac1, in the presumptive neural plate to examine the effect of excessive active Rac1 on neurulation. Nearly half of the embryos injected with rac1-V12 mRNA displayed a phenotype similar to that of embryos injected with HACE1 MO, such as a shortened body axis (Fig. 6h, compare with Fig. 2b, middle), thus supporting our idea that developmental defects in hace1 knockdown embryos are at least partly due to excessive active Rac1. Because it has previously been reported that exogenous expression of rac1-V12 in the mesoderm (1 or 2 ng of rac1-V12 mRNA into the marginal zone of embryos) results in gastrulation defects , we carefully observed the effect of rac1-V12 on gastrulation and showed that injection of rac1-V12 mRNA in our experimental condition (30 pg of mRNA was injected into the animal region of two dorsal blastomeres at 4-cell stage) did not affect gastrulation (data not shown).
Excess of active Rac1 causes a delay in neural tube closure
To further characterize the phenotype of the embryos injected with rac1-V12 mRNA, we performed time-lapse imaging and quantified the delay in neural tube closure. Embryos in which rac1-V12 mRNA was injected into the right side showed a significant delay in neural tube closure in the injected side, as compared with uninjected embryos (Fig. 4b–d and see also Additional file 1: Movie S1 and Additional file 3: Movie S3; uninjected embryos and rac1-V12 mRNA-injected embryos, respectively). These results support our hypothesis that hace1 regulates Xenopus laevis neural tube closure through Rac1 degradation.
hace1 has a role in regulating differentiation to neural ectoderm
Although the results shown above suggest that convergent extension is a major process affected by hace1 depletion, it is possible that hace1 regulates cell fate specification, such as differentiation into the epidermal ectoderm, neural ectoderm, and mesoderm. To test this possibility, we analyzed the expression of marker genes of cell fate specification in hace1 depleted embryos. HACE1 MO was injected into the right side, and control MO was injected into the left side; the expression of marker genes was detected by in situ hybridization. Whereas the expression of the epidermal ectoderm marker epidermal keratin and the mesoderm marker Xbra were unaffected on the HACE1 MO-injected side (Fig. 7a, c), hace1 depletion resulted in a moderate or slight decrease in the expression of the neural ectoderm marker sox2 at stage 12 (late gastrula) or stage 15 (early neurula), respectively (Fig. 7b). Additionally, the distribution pattern of all of these marker genes was essentially unaffected in HACE1 MO-injected side. According to the extent of reduction, we classified embryos into four groups: severe, moderate, slight, and normal (Fig. 7a–c). These results suggested that hace1 is likely to be involved in differentiation to the neural ectoderm. Although it is difficult to determine whether this level of decrease in Sox2 affects the subsequent neural tube closure event, hace1 might regulate neural tube closure through controlling differentiation to the neural ectoderm.
In this study, we investigated the role of the E3 ubiquitin ligase Hace1 in early embryonic development. We showed that Xenopus laevis hace1 is expressed in neural tissues and the kidney. High-throughput in situ hybridization in mouse embryos has revealed that Hace1 is expressed in neural tissues in mice at embryonic day 11.5 (E11.5), E15.5, and postnatal day 7 . In humans, HACE1 is expressed in adult tissues including the heart, brain, and kidney . These data suggest that HACE1 expression in neural tissues is common in vertebrates.
Hace1 depletion in Xenopus laevis embryos led to a shortened body axis. The process of body axis elongation is known to involve convergent extension [10, 16, 17]. Our analysis with Keller sandwich explants showed that knockdown of hace1 inhibited convergent extension. These results suggest that Xenopus laevis hace1 may control body axis elongation through regulation of convergent extension. Convergent extension occurs in both dorsal mesodermal and posterior neural tissues. Whereas convergent extension in the dorsal mesoderm mainly regulates gastrulation, convergent extension in the neural ectoderm mainly regulates neurulation. It has been shown using transplantation experiments that inhibition of convergent extension in only the neural ectoderm leads to a shortened body axis . Because knockdown of hace1 did not affect gastrulation, inhibition of convergent extension in the neural ectoderm by hace1 depletion might lead to a shortened body axis.
Notably, Hace1 −/− mice do not display any developmental defects , whereas knockdown of hace1 in Xenopus laevis led to severe developmental defects. This discrepancy might be explained by the possibility that other proteins with roles redundant with that of HACE1 may compensate for HACE1 function during embryonic development of Hace1 −/− mice. For instance, the activity of Rac1, one of the targets of HACE1, is negatively regulated by GAP and other E3 ubiquitin ligases targeting Rac1, such as IAPs [19–21]. Ectodermal tissues in mouse embryos might express these proteins to provide robustness to loss of Hace1 protein. Most recently, it has been reported that knockdown of hace1 using a splice-blocking MO causes ROS production in zebrafish . Although this report has not described the effects of the MO on zebrafish embryonic development, the gross morphology of embryos injected with the MO is apparently normal. Whereas a splice-blocking morpholino inhibits only zygotic expression but not maternal expression, a translation blocking morpholino, which was used in our study, inhibits both maternal expression and zygotic expression. This might explain the difference between our results and those from the previous study in zebrafish.
hace1 depletion in Xenopus laevis embryos led to diverse developmental defects, including a shortened body axis and the inhibition of eye and pigment formation. These defects were at least partly rescued by rac1 inhibition. In addition, we showed that overexpression of active Rac1 in the presumptive neural plate led to a delay in neural tube closure and a number of subsequent developmental defects, which are similar to hace1 morphants. The migration of neural crest cells, which give rise to pigment cells, is disturbed by constitutively active or dominant negative forms of Rac1 . Therefore, the inhibition of pigment formation may result from impaired neural crest migration. Additionally, conditional knockout of Rac1 in the surface ectoderm results in a failure of neural tube closure in mice . Thus, fine tuning of Rac1 activity may be important for neural tube closure. However, the detailed molecular mechanism by which excessive active Rac1 affects neural tube closure is unclear. Rac1 regulates a variety of biological processes, including cytoskeleton remodeling and PCP signaling regulation [24, 25]. PCP signaling plays an important role in neural tube closure , and there may be crosstalk between RhoA and Rac1 signaling in the regulation of actin cytoskeleton . It would be interesting to investigate the presence of the crosstalk and, if it is present, to clarify the regulation mechanism of the PCP pathway through RhoA and Rac1 signaling during neural tube closure.
In summary, our study show that the E3 ubiquitin ligase Hace1 plays an important role in early developmental processes in Xenopus laevis. Detailed analyses of downstream targets of Hace1 should be performed in future studies.
Molecular cloning and plasmid construction
Primers were designed on the basis of the Xenopus laevis hace1 sequence (GenBank accession NM_001093608) as follows: F, 5′-GGTAGATCTATGGAGAGAGCAATGGAGCAACTC-3′; R, 5′-GGTAGATCTTTATGCCATTGTGTAGCCGTAGCT-3′, and the Xenopus laevis rac1 sequence (GenBank accession NM_001095863) as follows: F, 5′- CGGAAGATCTGTAGGGAGAGCAAAGAAGAGGGAGGGAG-3′; R, 5′- TCCGGAATTCAGGGACAGAAGAAAAGATGGCATGTGGG-3′. PCR was performed with complementary DNAs derived from embryos at stage 2 for hace1 and stage 13 for rac1. The entire amplified coding sequences were cloned into the expression vector pCS2+. A constitutively active form of Xenopus rac1 was constructed by replacing glycine 12 with valine by site-directed mutagenesis.
Whole mount in situ hybridization
Whole-mount in situ hybridization was performed on albino Xenopus laevis embryos according to a standard protocol  using a robot (InSituPro, Intavis). The digoxigenin-labeled probes were synthesized from hace1-pCS2+.
Xenopus laevis embryos were obtained by in vitro fertilization and cultured in 0.1 × MBS at 15 or 22 °C. Embryos were staged according to Nieuwkoop and Faber . Antisense morpholino oligonucleotides (MOs) and mRNAs were injected into the animal region of one or two dorsal blastomeres at the four-cell stage in 4 % Ficoll in 0.1× MBS. In vitro synthesis of capped mRNA was performed using the mMESSAGE mMACHINE (Ambion). MOs were purchased from Gene Tools. The MO sequences were as follows: HACE1 MO, 5′- GAGTTGCTCCATTGCTCTCTCCATC-3′; HACE1 MO2, 5′- AGAGGCTCAGCAGTTCCTAAGCAGT-3′; Rac1 MO, 5′-CCACACATTTAATGGCCTGCATGGC-3′; and a standard control oligo (Control MO), 5′-CCTCTTACCTCAGTTACAATTTATA-3′. The animals were bred and handled with care, according to a published laboratory manual . Xenopus laevis experiments complied with the Regulation on Animal Experimentation at Kyoto University and were approved by the Animal Experimentation Committee of Kyoto University.
Embryos were lysed in a buffer consisting of 20 mM Tris–HCl, pH 7.5, 150 mM NaCl, 1.5 mM MgCl2, 2 mM EGTA, 25 mM β-glycerophosphate, 10 mM sodium pyrophosphate, 1 % Nonidet P-40, 10 mM NaF, 1 mM vanadate, 1 mM DTT, and 1× Protein Inhibitor Cocktail (Sigma). Extracts were then centrifuged, and supernatants were collected. Anti-Myc (A14, Santa Cruz), anti-GFP (JL8, Clontech), anti-Rac1 (23A8, Millipore) or anti-α-tubulin (DM1A, Sigma) antibodies were used as primary antibodies, and anti-mouse IgG HRP-conjugated (1:10,000; GE healthcare) and anti-rabbit IgG HRP-conjugated (1:10,000; GE healthcare) were used as secondary antibodies.
Quantification of body length
Embryos were fixed in MEMFA [100 mM MOPS (pH 7.4), 2 mM EGTA, 1 mM MgSO4, 3.7 % formaldehyde] at stage 40–41. Embryos were placed on agarose gel, and images were collected. The body length was measured along the dorsal midline using the AxioVision (Zeiss) measure tool.
Keller sandwich explant analysis
Keller sandwich explant experiments were performed as previously described . MOs and mRNA were injected into the animal region of two dorsal blastomeres at the four-cell stage. Injected embryos were grown to stage 10.5 for preparation of Keller sandwich explants. Explants were cultured in Sater’s modified blastocoel buffer containing 0.1 % BSA until uninjected embryos reached stage 19. The length and width of explants were measured using cellSens software (Olympus).
Time-lapse analysis of neural tube closure
Embryos injected with MOs or mRNAs were grown to stage 13 and placed dorsal side up in a 60 mm culture dish. This dish contained 2 % agarose with a groove made by an acrylic comb. Images were collected with an Olympus SZX16 microscope, and time-lapse movies were obtained using cellSens software. For quantitative analysis of the delay in neural tube closure, the maximum distance between the dorsal midline and the left (i) or right (ii) inner edge of the neural fold was measured at the time point 60 min after start of time-lapse imaging, as shown in Fig. 4c. At the time point 60 min after start of time-lapse imaging, embryos reached stage 17. The inner edge of the neural fold was easily visible, owing to pigmentation.
Quantitative RT-PCR analysis
Total RNA isolation and cDNA synthesis were performed as previously described . The gene expression levels were normalized to those of odc1 (ornithine decarboxylase 1). The sequences of primers used were as follows: Xenopus laevis rac1 (NM_001095863) (F, CATGCACATGTCAAGCCAGTTC; R, ATGGCAAGTCCCTGAGGATAGG); Xenopus laevis rac2 (NM_001092288) (F, ACCAGTAAACTTGGGCTTGTGG; R, CTCATAAGATGCCGGACTCACC); Xenopus laevis odc1 (NM_001086698) (F, TGAAAGTGGCAAGGAATCACCC; R, GATACGATCCAGCCCATCACAC).
HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1
Inhibitors of apoptosis protein
Reactive oxygen species
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We thank members of the Nishida laboratory for technical advice and helpful discussions.
This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to MK) and the Takeda Science Foundation (to MK).
Availability of data and materials
All supporting data are presented in the main manuscript and supplementary data files.
AI, FY, TS, and TE designed experiments. AI, FY, and TE performed experiments. AI, FY, TS, EN, and MK wrote the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
Xenopus laevis experiments complied with the Regulation on Animal Experimentation at Kyoto University and were approved by the Animal Experimentation Committee of Kyoto University.
About this article
Cite this article
Iimura, A., Yamazaki, F., Suzuki, T. et al. The E3 ubiquitin ligase Hace1 is required for early embryonic development in Xenopus laevis . BMC Dev Biol 16, 31 (2016). https://doi.org/10.1186/s12861-016-0132-y
- Early development
- Xenopus laevis

domain: literature


- The Street Division is responsible for providing the repair of over 327 miles of streets within the City Limits.
- Responsible for the repair of street cuts made by Sewer, Water, Sanitation, Street and Gas Companies.
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- Repair Cave-ins along and under streets, Sidewalks and Driveways caused by Sewer or Storm Drain leaks.
- Due to the types of equipment housed at the Street Department this division assist other division in their daily operations.


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In this area you can look up past and present wedding traditions, customs and folklore from around the world. Search by keyword, alphabetically or just check out the result that comes up randomly when this page is reloaded.
Throwing The Garter - This ritual dates back to a time when woman wore hose with a garter belt. It was a chance for the single men to share in the good fortune of the groom. Today, it is believed that the man who catches the garter when it is thrown will be the next to marry. In the 14th century, is was customary for the bride to toss her garter to the men, but sometimes the men got too drunk, and would become impatient and try to take the garter off her ahead of time.
Site Note: All information shared via Romance 101 is completely 100% confidential and never will be sold or given away. This site is kept fully funded by all the advertising you see on this site. It is the advertising you see that keeps Romance 101 free for your enjoyment.

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Miss America pageant returns to Atlantic City
ATLANTIC CITY, New Jersey (AP) - There she is, Miss America, headed back to Atlantic City.
The Miss America pageant, a staple in Atlantic City for decades before it was moved to Las Vegas in 2006, is making a return, Governor Chris Christie's spokesman Michael Drewniak confirmed on Wednesday. Lieutenant-Governor Kim Guadagno was scheduled to make a formal announcement on Thursday at Atlantic City's Boardwalk Hall.
The Miss America pageant started as little more than a bathing suit revue. It broke viewership records in its heyday and bills itself as one of the world's largest scholarship programmes for women. But, like other pageants, it has struggled to stay relevant as national attitudes regarding women's rights have changed.
The news of the pageant's return to Atlantic City came as a surprise to the Las Vegas Convention and Visitors Authority, which sponsored the pageant on the Las Vegas Strip in January, spokesman Courtney Fitzgerald said in a telephone interview. In a subsequent statement, she said the tourism organisation wished the pageant well in its new home.


Being in the payment business, we often feel the heavy burden of testing on different terminals. 2 years ago, the Payworks Team started a project where we automated some of the testing process using a LEGO Mindstorms EV3, you can read about that more here. The limitations with this solution were quickly reached and we started looking for something more reliable.
Great Robotic Assistant Necessary for Testing (GRANT)
A challenger arose: I built the first iteration of a robotic solution to automate testing the products being developed at the company. GRANT, compared to the LEGO invariant, is now capable of using both NFC and magnetic stripe, and the terminal being tested is easy to replace. GRANT is triggered by commits and it is kept busy by continuous development which helps our developers focus on improving our product.
This project is the love child of wood and plastic: I used wood to fix the components to their place and custom 3D printed parts to convert the circular movement from the servos. Just switching the softer plastic of LEGO to PLA made a huge improvement.
Let’s see the recipe:
- 1 Raspberry Pi 3 Model B: this runs the Python code to control the robot. There’s an API exposed to it, so you can trigger movement with simple HTTP GET requests e.g.: /arm/1234 or /icc/use. I also generated a website so positions for the buttons can be recorded. This is super important if you want to switch terminals — different devices have different dimensions, for example, the buttons are aligned differently and their sizes can also be different.
- 7 smart servo motors: Four of them give 2–2 degrees of freedom for the arm, 1 taps the NFC card on the terminal, 1 inserts the card and 1 swipes. The servos I’ve chosen are Daisy-chainable, which is really convenient for the arm. You just have to connect the servo to the one next to it, saving you a lot of trouble from cable management. They are all connected to a serial hub, which also feeds them the juice: the power supply barrel is connected to a 12V5A PSU (this equals to roughly 4 pieces of Lithium-ion AAA battery).
The distant vision of automation in the company is to have the capability of doing test cases from suites such as ADVT and M-TIP. Currently we do our tests with emulated cards, however, it’s not only our SDK which is required to be tested, but we also have to ensure that our software works as intended after integrating into other solutions. For this, there are specific test scenarios which have to be performed. The test environment has a built-in server, so I was able to create a command line interface to remotely start a test case, show the info bound to that specific test (e.g. what kind of validations to look out for), allow for card simulation to be automatically triggered through the start of the test, and as soon as the command line tool gets the details of the test case from the server, I automatically trigger a transaction on a terminal with the amount defined in the test case.
In short: you only have to select the test case in the tool, then insert the card in the terminal. After this, the tool collects some of the data required by the test case (e.g. the currency, sometimes the TSI, TVR, etc.), sends you the customer/merchant receipt, gets the card logs if they exist.
This solution is already capable of making use of the magnetic stripe simulator attached, therefore I will be able to use any kind of card which has an image defined by the major brands (e.g. MasterCard).
What does the future hold?
For starters, since the first iteration is constantly being used in our continuous delivery flow, I need to build a second robot. Sneak peek: no more wood.
Second: software-side improvements. Currently, the results can only partially be evaluated automatically. This mainly happens when the terminal shows some behavior which we can’t process on our side, if it beeps/shows some text, the test doesn’t necessarily specify all the steps precisely, but the terminal gives you instructions (e.g. when you need to select an application). There are so many possible combinations of such scenarios that starting to do “exception-driven development” sounds like the least reasonable option.
But wait! Python? Raspberry? I already have the 2 main ingredients for a deep learning system! Adding a camera to the mix, letting the robot run and collect errors — after a while, it’ll learn which steps will lead to a successful test! Python supports a lot of incredibly efficient, open source image recognition and deep learning libraries (e.g. TensorFlow), which will make it easier to implement such a system.
Stay tuned for more developments!
Written by Pal Szentgyorgyi, Automation Engineer at Payworks
First published on Medium on 11-10-2017


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Blackmores Daily Magnesium 150g
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Relieve muscle cramps & mild spasms when dietary intake is inadequate
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domain: chemistry


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Discover our range of natural beef tendon treats for dogs. From Beef Tendon to Limited Natural Beef Tendon Dog Treat, we have the perfect treat for your furry friend. Shop now and provide your pup with the ultimate delicious snack!

domain: pet


December 18, 2012
I'm Still Fighting for You: Joint Finance Appointments
By Senator Lena C. Taylor
In August, I became the first ever African-American woman to Co-chair the Joint Committee on Finance. The JCF is one of the most powerful and important committees in the Wisconsin Legislature, and I was honored to have served my constituents by leading the committee. Unfortunately, my first tenure on the committee would not last long.
I am disappointed but admittedly not shocked by the Democratic leadership’s recent appointments to the Joint Finance Committee for the 2013 session. I regret to say that I was not reappointed to the committee, though my regret is not for my own standing but rather for the African-American community and other minority communities in Wisconsin. I have long done everything in my power to properly represent minorities and the African-American community, so I feel that we have lost a strong voice in government.
Long have Wisconsin Democrats recognized the crucial and unique needs of minorities. In return, minority communities have often overwhelmingly political support they have received from those communities. In every session since 1983, Senate Democrats have maintained the presence of an African-American legislator on this important committee. The committee has a hand in almost every important decision affecting the whole of Wisconsin, whether economic or social. 2013 will mark the first year in over three decades that Senate Democrats will not make such an appointment.
This does not mean that the work will end nor the fights that need to be fought will die away. Our state and its issues are far too important to me and my Democratic colleagues for any of us to simply surrender. My pledge is to continue to represent the hard-working men and women of my district that are still waiting on the promises that equality should bring them- an education that actually educates, a right to vote that is not impeded, a health care system that heals, and a government which favor the needs of the least of these among us. That agenda will not leave the Senate because of this appointment.
To my colleagues in both houses, in both parties, on the Joint Committee on Finance and elsewhere, I say thank you for the opportunity to serve with you on this most important committee. It has been the joy of my first eight years of service of Wisconsin. And to my constituents: I will never stop fighting for you! I look forward to the work that is laid before the Legislature this year and our mutual collaboration to achieve results for the people of Wisconsin.


Using Technology for the Competitive Delivery of Education Services
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This paper considers the use of information technology as a source of competitive advantage for education service providers operating in international markets, with particular reference to Australia. It draws upon the findings of a survey of 315 education institutions in five countries engaged in the export of international education. The importance of effective use of information technology as a source of competitive advantage is highlighted. Current use of information technology within education institutions is examined and technologically mediated learning is proposed as a viable means of promoting, administering and delivering education services to international markets. In particular, the potential of the Internet to provide graduate business education is given close scrutiny. It is argued that a virtual university business faculty is economically viable in this context. Business schools are advised to invest in hardware and software applications to ensure the communications needs of their clients are met.
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