The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

U.S. President Donald Trump is reportedly demanding US$1.3 billion a year to maintain American troops in Korea. That is a whopping 53.3 percent higher than the W1.4 trillion Korea had to pay last year. A senior U.S. official told the Chosun Ilbo on Thursday, "The U.S. faces many difficulties, includ...

Dentons has advised KPS Capital Partners, a global private equity firm focused on investing in manufacturing and industrial companies across a diverse array of industries, on its acquisition of the Lufkin rod lift solutions business from Baker Hughes. 

Leicester City player Christian Fuchs has recorded an empty JFK airport as he heads back to England ahead of an expected return to training.

A Lufkin, Texas, man pleaded guilty today to charges related to a double homicide that took place in Nacogdoches, Texas, in August 2007.

A Lufkin, Texas, woman was sentenced today by U.S. District Judge Marcia Crone to 180 months in prison for her role in a double homicide that took place in Nacogdoches, Texas, in August 2007.

A Lufkin, Texas, man and woman have been sentenced to federal prison for their part in a double homicide in Nacogdoches, Texas, in August 2007.

A Lufkin, Texas, man was sentenced today to life in prison for his role in a double homicide that took place in Nacogdoches, Texas, in August 2007.

The Tashkent Files
U/A: Mystery
Director: Vivek Angnihotri
Cast: Shweta Basu Prasad, Mithun Chakroborty
Ratings: 

Guess who's watched Steven Spielberg's The Post (2017), based on the New York Times' Pentagon Papers revelation, given that an envelope filled with a certain case-file (in this film) mysteriously lands up on a newspaper reporter's desk, piquing curiosity, and leading finally to an exposé as front-page news the following day. There is also a gravelly voice of the unknown "source", guiding the journalist in this film, all through the case. The anonymous caller refers to the reporter as his Deep Asset. He seems more like Deep Throat himself.

And so the other mother of political-journalistic dramas, Alan Pakula's All The President's Men (1976), on the Watergate scandal, has also been dutifully checked. If anything, the brief for Naseeruddin Shah, who plays a wily minister, spouting one-liners on the murky art of politics, may well have been Kevin Spacey from House Of Cards.

That said, The Tashkent Files, beyond all else, is essentially modelled on Sidney Lumet's courtroom drama 12 Angry Men (1957), which was brazenly, blatantly lifted by Basu Chatterjee's Ek Ruka Hua Faisla (1986) - without any context whatsoever, given that jury trials had already been abolished in Indian courts by late '60s, early '70s.

To be fair, this film provides some background to why a grand-jury/committee has been appointed by the government - with that young newspaper reporter herself on board! Never mind. Actor Shweta Basu Prasad plays this lead role, and she does a fine job, by the way. So does everyone else - Mithun Chakroborty, Pankaj Tripathi, Prakash Belawadi, Pallavi Joshi, Mandira Bedi - in what's a rather fine line-up for any film.

The aim is to probe supposedly strange circumstances under which Lal Bahadur Shastri, India's second Prime Minister, died in his hotel/chalet in Uzbekistan (then USSR), after sealing a deal with Pakistan, post 1965 war. Was Shastri poisoned? Or did he die of cardiac arrest, as officially recorded? The group in the room delves into this mystery, presumably 53 years after the event!

Frankly, call it propaganda if you will, we must welcome this genre, regardless of the quality of recent output, that have mainly targeted folk from Congress - right from a tiny portion of Sacred Games (Rajiv Gandhi), to films like Indu Sarkar (Indira Gandhi), The Accidental Prime Minister (Manmohan Singh, Sonia, plus Rahul Gandhi) - putting faces to actual names, without fear, even if on account of (currying) favour.

Sure, this goes down well with the current dispensation, otherwise trigger-happy with censorship of all kinds, films foremost. The fact is that, barring notable exceptions, Indian, or at least Hindi cinema, has been bereft of robust political commentary, and an iron curtain has been lifted from an unexpected quarter.

God knows deaths of Shastri, or for that matter, Subhash Chandra Bose (also widely referred to in this pic) aren't the only local mysteries. There have been many question marks over possibly political motives behind several prominent deaths, some of them more recent: Haren Pandya, Lalit Narayan Mishra, Justice Loya, Gauri Lankesh … This is apart from a staggering number of politicians who keep dying in either car or copter crashes (Munde, Pilot, Scindia, etc).

The meat of the material (book-quotes, interviews) on Shastri's demise, before the writer-director (Vivek Agnihotri) - most of them apparently accessible to public - is however scant enough to be reproduced (as is, with a voice-over) in a 15-min video. Rather than sit through over a two-and-half-hour long feature, that in its effort to spin a thriller, instead of grabbing you by the eye-balls, throws up such garbled, gunny-bag gyanpatti, so much bak-bak, you constantly feel like stepping out of the hall of darkness, for a smoke break (no; don't wanna know what the filmmakers were smoking).

And so practically everyone sitting in this 12 Angry Men style committee is essentially a terrorist: "intellectual terrorist," (historian), "social terrorist" (NGO activist), "judicial terrorist" (retired judge), "TRP terrorist" (print journalist!), "racial terrorist" (someone who judges people for their religion, which incidentally is not a race anyway)…

If you must know more: There is call-back to 26/11 attacks, parliament attacks, CWG, 2G (scams)… So-called secular folk will apparently come with a fauj (army) to go after everyone in this country. "Bloody, heartless, capitalists," savages will kill us with fries and cola. And socialism is the ultimate evil, anyway.

This, coming from a filmmaker, who I'm told popularised the term "urban naxal" on Twitter, referring to the relatively affluent, who care for the completely marginalised - arguing that this is all done with the intent of destroying the 'nation'! Not going to judge him personally. He's allowed his hate/opinion, or general lack of empathy. Certainly not falling into that Twitter trap.

But this is the sort of know-all, grand con-spiracy theory picture - regurgitating catch-phrases like "presstitutes", "Lutyens Delhi," "fake news" - that emanates from a world-view wholly derived from spending far too much time on social media.

The gist of this juvenilia (that 15-min vid) is at best, currently Juhu-Versova's version of JFK then, ideally forwarded on your uncle's Whatsapp group. No, nobody's reopening any files for this, or getting rattled up to relook at laws (as was the case with the Oliver Stone masterpiece). A whole lot might just get bored, though. I'm just waiting for this genre to grow. Baby steps, I guess.

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Consumer Confidence in Germany decreased to -23.40 points in May from 2.70 points in April of 2020. Consumer Confidence in Germany averaged 6.28 points from 2001 until 2020, reaching an all time high of 16.80 points in March of 2001 and a record low of -23.40 points in May of 2020. The GfK Consumer Climate Indicator is based on a survey of 2000 individuals age 14 and above. The questionnaire focuses on income expectations, buying propensity and savings. The components of the indicator are calculated as the difference between positive and negative answers to the questions asked. Their value can vary between minus 100 and plus 100 points with 0 representing the long term average. This page provides the latest reported value for - Germany Consumer Confidence - plus previous releases, historical high and low, short-term forecast and long-term prediction, economic calendar, survey consensus and news.

We find ourselves in a time when certain businesses are being asked to scale to levels they never imagined. Sometimes that increased usage comes in bursts, which means you don’t want to pay for permanent extra capacity you might not always need. Today, Confluent introduced a new scale-on-demand feature for its Apache Kafka cloud service […]

The 39-year-old reality star and her sister Kourtney have a habit of rocking the kind of floor-length black coats and sunglasses that would appear in the Wachowskis' $1.6B-grossing sci-fi trilogy

She split from boyfriend Playboi Carti after one year of dating. And on Wednesday, Iggy Azalea was spotted enjoying a shopping spree at JFK airport in New York City upon her arrival to NYC.

The 24-year-old Grammy nominee tweeted that she 'loved' the 22-year-old Englishman, who blasted Russia's 2013 'gay propaganda' policy in Moscow

FKA twigs, 32, didn't disappoint when she walked the Grammy Awards 2020 red carpet in Los Angeles on Sunday in a black and pink hooded gown.

She hosted her album release party on Tuesday. And on Wednesday, Selena Gomez, 27, made her way out of New York as she was spotted at John F. Kennedy International.

Hillary Clinton appears on the cusp of a potentially commanding victory over Donald Trump as she leads with 14 percentage points among likely voters, 51-37, according to an Associated Press-GfK poll.

The Truth and Reconciliation Committee (TRC) has called for probes into deaths of John F. Kennedy, Robert F. Kennedy, Martin Luther King Jr. and Malcolm X, on the occasion of MLK day.

The Diamonds hitmaker, 31, was a woman on a mission as she jetted into New York's JKF Airport for her work commitments on Saturday afternoon.

She's something of a style chameleon and Rihanna had styled her hair into braids as she headed to JFK airport on Sunday. 

On Wednesday Trump insisted it was 'not such a bad thing' to promote a National Enquirer story that suggested Rafael Cruz appeared in a 1963 picture with the future killer.

Rafael Cruz won't say a word about Donald Trump's attacks on him on the eve of his son's prime time speech before the Republican convention – but Ted Cruz will say Trump's name.

A CNN reporter on a White House conference call asked if the John F. Kennedy assassination documents could shed light on a Trump-fueled conspiracy theory about Sen. Ted Cruz's dad.

After President Donald Trump accused Pastor Rafael Cruz of playing a part in the assassination of JFK, Ted Cruz's dad was recently quoted as telling a Dallas luncheon: ‘Oh, yes - I shot J.R.!’

After dominating the runway during Milan Fashion Week in multiple sensational ensembles, Kendall Jenner opted to dress down in an over-sized sweater while arriving at JFK on Monday.

Rafael Cruz won't say a word about Donald Trump's attacks on him on the eve of his son's prime time speech before the Republican convention – but Ted Cruz will say Trump's name.

The 40-year-old actress and fashion entrepreneur smiled as she cuddled the 11-month-old cutie she shares with her actor beau, 33, as they jetted out of the busy airport in New York on Sunday.

Ford made headlines during a trip to Gotham in September of 2017, when he exited a limo he was in to help direct traffic amid a jam caused by a nearby accident.

Priyanka Chopra looked fresh-faced and fantastic as she strutted through JFK airport on Friday, with husband Nick Jonas nowhere in sight.

Police have found the body of Robert F. Kennedy's missing great-grandson, six day after he went missing while canoeing with his mother. 

A jury is not a body out to seek vengeance or play tit-for-tat. It appears hardly plausible that the jury would have deliberately avoided some movies.

According to the recent study by GFK, there are around 41 million hyper-connected consumers in India, with major cities like Delhi and Mumbai reporting the highest concentration of consumers belonging to this segment. The study says that hyperconnected consumers spend

Cham : Palgrave Macmillan, c2019.

Online Resource

Dewey Library - HD9502.A2 R537 2019

Online Resource

Browsery HM743.R447 L34 2018

Guernica author Elana Wolff recently gave an interview with The New Quarterly about the inspiration behind her essay, “Paging Kafka’s Elegist”, which is this year’s winner of the Edna Staebler Personal Essay Contest. Susan Scott introduces the interview by stating “I describe the first-place essays as a gift. I say this less because our eclectic […]

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