Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias.

Declaring it has been “pained” by the Jodian Fearon situation, the embattled Andrews Memorial Hospital (AMH) is speaking out, saying it has never been approached for or rejected efforts at registration or certification since it began operating 76...

Losses within the entertainment industry are already estimated to be in the billions as the sector continues to reel from the impacts of COVID-19. Major events like Reggae Sumfest, which has already been cancelled this year, had an estimated...

Almost five years ago, lawmakers on a bipartisan committee of Parliament agreed unanimously to amend the law to give the Independent Commission of Investigations (INDECOM) the power to arrest and prosecute cops. That proposed amendment, which was...

https://diazhub.com/news/boris-johnson-will-tell-public-to-stay-alert-control-the-virus-and-save-lives/

Taping of Season 11 of "Valerie's Home Cooking" was shut down due to the coronavirus pandemic, but host Valerie Bertinelli can't wait for viewers to see the 10 episodes she finished.

Testimony of Marc R. Rosenblum, Deputy Director, U.S. Immigration Program, before the House Committee on Homeland Security Subcommittee on Oversight and Management Efficiency.

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Alberta reported 59 new cases of COVID-19 on Saturday, marking a full week of daily new cases remaining in the double digits.

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No method is infallible when trying to reduce Bible poverty among the least reached, an OM worker discovers as he distributed Bibles.

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Source: www.mprnews.org - Saturday, May 09, 2020
A barber cuts a woman's hair at a salon amid the coronavirus pandemic in Round Rock, Texas, on May 8, following a slow reopening of the Texas economy. Sergio Flores | AFP via Getty Images As of Friday, in Texas you can go to a tanning salon. In Indiana, houses of worship are being allowed to open with no cap on attendance. Meanwhile places like Pennsylvania are taking a more cautious approach, only starting to ease restrictions in some counties based on the number of COVID-19 cases. By Monday at least 31 states will have partially reopened after seven weeks of restrictions. The moves come as President Trump pushes for the country to get back to work — while many public health experts warn that it's too soon. "The early lesson that was learned, really, we learned from the island of Hokkaido in Japan, where they did a really good job of controlling the initial phase of the outbreak," said Bob Bednarczyk, assistant professor of Global Health and Epidemiology at the Rollins School of public Health at Emory University in Atlanta. COVID-19 in Minnesota Full coverage from MPR News Tracking the spread Minnesota and the Upper Midwest COVID-19 How it compares with other diseases in 5 charts But then because of that success many of the restrictions on the island were lifted. Cases and deaths surged in a second wave of infections. Twenty-six days later, the island was back on lockdown . "That's the concern that we have right now," he said.

No method is infallible when trying to reduce Bible poverty among the least reached, an OM worker discovers as he distributed Bibles.

James Dillard, distinguished professor of communication arts and sciences at Penn State, describes strategies to help regulate emotions during the stress and uncertainty of the coronavirus pandemic.

No method is infallible when trying to reduce Bible poverty among the least reached, an OM worker discovers as he distributed Bibles.

No method is infallible when trying to reduce Bible poverty among the least reached, an OM worker discovers as he distributed Bibles.

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Even a 25% fall in their incomes due to the lockdown will make 354 mn more people poor. fixing this with cash transfers will cost the govt Rs 19,500 cr per month.

After successfully topping our all-time battery life chart, with the 5,000 mAh pack inside the Realme 6i, which you can read more about here, the Chinese company apparently has its sight set even higher. A TUV certification filing for a particular BLP793 battery pack has now been brought to light. Mainly since its rated capacity is a whopping 6,000 mAh. Well, 5,860mAh, to be precise, with a typical capacity of 6,000 mAh. But, the point stands. Battery certification The jury is now out on which phone we can expect to see this pack in. That's more guess-work than anything else,...

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While our immediate priority must be to protect people from the pandemic and contain its spread, ensuring food security and preventing more people to fall below poverty line (BPL) should also be on focus.

As per the current goods and services tax (GST) audit guidelines, taxpayers have been broadly categorised into three groups based on their annual turnover -- large, medium and small.

The sale of fertilisers shot up by 45.1 per cent on-year in April 2020.

“With Covid-19 onslaught, the government has shown tremendous resolve to counter the fallout through socio-economic packages ranging from direct cash transfer to poor and farmers to free food to the needy.”

The recommendations are part of a report titled 'COVID-19: Challenges for the Indian Economy - Trade and Foreign Policy Effects'.

Dear Experts Pranam!

My dad has been puchased a land with a small old house (its very old, so may not required consider as a house - or in a demolishing stage) in Kottayam, Kerala, 10+ years back from a person, named as Mr.SELLER and has been registered at the concerned Sub Reg. Office (SRO). And till the last year there is no issue on this and since its a land we will do frequent visit over there to check the fencing etc. are ok and whether it is secured/safe. But last year when we tried to make an attempt to sell and tried find a buyer for the same through some local persons BUT got a news that it is in a despute and some legal issues are there in the court which is surprised us. And after an enquiry we met a person named as Mr.SON who is filed the case on this land. The case was against his Mrs.MOTHER stating that she does not have any legal rights to sell the land to the so called Mr.SELLER (as above) since that land originaaly owned by her husband named as Mr. HUSBAND (he is already expired) and his two siblings/heirs - one sister and a brother. What we understand and told by Mr.SON is, he filed the case in 2014 and now in 2019 mid, as per the court order the case has been won by him and the property will be attached to him and the above siblings. Please be noted that the case was only between him and his mother. Unfortunately his mother also expired prior to the case finals, i,e. his winning.

We have consulted with a legal adviser and got a temperory stay/injection (saying that Mr.SON and siblings been interuupting/disturbing us from staying/residing at our property, so please do the needful to stop their torturing) for the immediate Attachment and so the court has been sent notices to Mr.SON and his siblings/heirs to let the hon.court know about their statements or sayings about this issues by producing their valid documents. THere are 6 persons from the siblings side in this case other than Mr.SON. 2 of them not interested to receive the notice and so become ex.pat. Other three persons addresses are not reachable and so repeated notices two times sent again. Mr. SON was escaping each time by not receving the Notice from Ameen and in the third time he informed the Ameen that he will not receive the notice and Ameen has been noted the info and communicatd to the Hon,Court on the same. THe most important part of this is other than Mr. SON, no one including the above said siblings are not interested in this case but it is by the compulsion of Mr. SON only did involve. by the meantime very unfortunately Mr.SON is expired, recently. He is having wife and two kids.

In this scenario now we are not much interested to drag this case further and wish to make a out of court settlement if possible without any legal issues. is it possible otherwise what else are the BEST and immediate Resulting solutions in this case. I am asking this to know about your opinions in this case please.

Thanking you  in advance, Regards

Krishnan 

Five labourers died and 11 got injured after the truck they were travelling in overturned in Patha village in Narsinghpur on an intervening night of Saturday and Sunday.

The owner of a bakery in Chennai has been arrested for an advertisement he allegedly posted on WhatsApp which was discriminatory against Muslims. The baker, who does business online, had shared an...

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