 surrounded by dense stroma, develop around central ducts, retain myoepithelial differentiation, and frequently have squamous metaplasia. Examples include the following: wnt1, wnt10b, APC1, GSK, CKII, B-Catenin, and FGF mice. In contrast, members of the erbB pathway are more likely to resemble human tumors, to be invasive, lose myoepithelial differentiation, form solid nodular asymetrical masses budding from individual ducts, have less stroma, and be less metaplastic. Examples include the following: erbB2, PyV-mT, mutants and bigenics of erbB and PyV-mT, src, and ras. Interestingly, GEM tumors initiated by nuclear factors do not tend to have the characteristics of either of these pathways. Examples: myc and lef1. These observations suggest that the principles of pathway pathology can be applied to human tumors of the breast and other organs. This work was supported by the DAAD (AR, individual grant), the State of California, BCRP JB-0014, and RO1CA89140 from NCI.
DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells
Correspondence to Heinrich Leonhardt: h.leonhardt{at}lmu.de
DNA methylation plays a central role in the epigenetic regulation of gene expression in vertebrates. Genetic and biochemical data indicated that DNA methyltransferase 1 (Dnmt1) is indispensable for the maintenance of DNA methylation patterns in mice, but targeting of the DNMT1 locus in human HCT116 tumor cells had only minor effects on genomic methylation and cell viability. In this study, we identified an alternative splicing in these cells that bypasses the disrupting selective marker and results in a catalytically active DNMT1 protein lacking the proliferating cell nuclear antigenbinding domain required for association with the replication machinery. Using a mechanism-based trapping assay, we show that this truncated DNMT1 protein displays only twofold reduced postreplicative DNA methylation maintenance activity in vivo. RNA interferencemediated knockdown of this truncated DNMT1 results in global genomic hypomethylation and cell death. These results indicate that DNMT1 is essential in mouse and human cells, but direct coupling of the replication of genetic and epigenetic information is not strictly required.
This article has been cited by other articles:A difference in *ambition* is one thing that I’m seeing here, not self esteem. 

What goals do you have? Do you feel passionate about these goals? What would you do to achieve them? Will you stick to them?

She seems to have had some direction in what she wanted to do. Maybe she wanted to be so successful so that she could prove her mother wrong—and she did it. Maybe she wanted to have a successful career—she did it. Maybe she just wanted a lot of money—she did it. All of these are different goals but they achieved the same result. 

Of course challenge and adversity is a good influence, but it could just as easily gone a whole different direction if she didn’t have the ambition or goal to succeed in something. She could have fallen into a spiral and turned out worse.Make yourself 47% cooler with one of these moral patch and sticker combos. The new patches don’t have a raised boarder which makes them perfect for ironing onto clothing and bags. Or your best pair of budgie smugglers.
1x70mm iron on  patch plus 1x50mm vinyl sticker.
Cost includes all taxes and posting.
Wong has Gold Glove Award on his mind
To overlook him now would be a gross oversight, as Wong has, based on just about every defensive metric, been the gold standard at his position this year. He ranks first among all second basemen in defensive runs saved (11), ultimate zone rating (6.2) and defensive runs above average (7.0). The latter measures a player's defensive value relative to league average and allows for comparisons across all positions.
In the NL, only two players -- center fielder Lorenzo Cain and catcher Willson Contreras -- rank better.
"I think it's just the process," Wong said. "I've never been satisfied with my defense. I always try to figure out how I can get better. I think all the years combined, things are starting to come together this year."
Video: SD@STL: Wong flips with his glove, starts double play
There have been other factors besides experience, too. Wong credits Jose Oquendo, who returned to the coaching staff after a two-year hiatus, with "never letting me get lazy or take days off." Wong has also avoided one of his early-career pitfalls of letting offensive results cripple his defensive focus.
That's especially notable given that this has been, to date, the worst offensive year of his career. He entered Wednesday slashing.197/.295/.333 with a.629 OPS, but continues to earn starts because of his defensive contributions.
"There's no question that he's a Gold Glove-caliber talent," manager Mike Matheny said. "What we've seen with Kolten [this year] is a guy who, when he hits a home run, he goes out and plays the same defense as we're seeing if he had a rough at-bat. I think it's maturity. It's been a conscious improvement for him to improve as he has."
Father-son connection
Jose Martinez, eager to add to his mother's collection of mementos, said that he will soon be sending her a baseball from the Cardinals' 11-2 win on Tuesday. Though the night belonged to Matt Carpenter, it also had significance for Martinez.
Martinez's second-inning blast marked the 26th home run of his career. That's one more than his late father, Carlos Martinez, hit over 1,485 games in seven seasons. Jose Martinez, who debuted in 2016, surpassed him in his 556th career game.
Video: CLE@STL: Jose Martinez crushes a 3-run homer to left
"It's very special," said Martinez, whose father died of cancer just before he signed his first professional contract. "There's always something interesting that comes up to help me remember him. My first home run was against the Blue Jays, and his first one was against the Blue Jays. And this one to pass him, it was against the Indians. There's always a connection."
Carlos Martinez spent three years playing for Cleveland.
Worth noting
• Yairo Munoz, who exited Tuesday's game after fouling a ball off his left ankle, remained out of the lineup for Wednesday's series finale vs. the Indians but grounded out as a pinch-hitter in the fourth inning in the Cardinals' 5-1 loss. Greg Garcia drew the start at shortstop in his place.
Video: CLE@STL: Munoz exits game after fouling ball off foot
• With the signing of their fourth-round pick, pitcher Steven Gingery, this week, the Cardinals have now agreed to terms with each of their first 14 selections from the 2018 MLB Draft. Gingery, a lefty who recently appeared in the College World Series with Texas Tech University, agreed to a bonus of $825,000.
• After receiving an injection to stimulate blood flow to his middle right finger on Tuesday, Matt Bowman returned to the mound Wednesday to throw a bullpen session. If the treatment for Raynaud's Syndrome is effective, Bowman is likely to head out on a Minor League rehab assignment soon. He's eligible to come off the disabled list Friday.
Jenifer Langosch has covered the Cardinals for MLB.com since 2012, and previously covered the Pirates from 2007-11. Follow her on Twitter and Facebook.If you’re a real estate agent, or small business owner, or self-employed contractor, you may be missing a powerful tax deduction because your accountant is too conservative.
Too conservative to take meals and entertainment write-offs that are totally legal and 100% compliant with the rules outlined in the IRS code.
Here’s the basic rule. You can deduct as a business expense the cost for meals with abona fide business purpose. This means whenever you have coffee, lunch, etc with clients, prospects, referral sources, and business colleagues.
So let me ask you – when do you ever eat with someone who’s not a client, prospect, referral source, or business colleague?
If you’re in a business like real estate, or you’re a freelancer, or consultant, where you’re marketing yourself, the answer might be “never.” Be as aggressive as you can with what you define as bona fide business discussion!
At Starbucks or your favorite restaurant…
The general rule is, you can deduct 50% of your meals and entertainment, so long as it isn’t “lavish or extraordinary.” The IRS knows you have to eat, so you can’t deduct it all. But they’ll meet you halfway.
At concerts or sporting events….
You can deduct entertainment expenses if they take place directly before or after substantial, bona fide discussion directly related to the active conduct of your business. You can deduct the face value of tickets to sporting and theatrical events, food and beverages, parking, taxes, and tips.
At home…
But let’s take this one step further. How many of you entertain at home? Do you ever discuss business? Are you deducting those meals, too? There’s no requirement that you eat out. Don’t forget to deduct home entertainment expenses too!
At your desk or ‘back office’…
You don’t need receipts for