Shi-Zhong Du
Proc. Amer. Math. Soc. 148 (2020), 2631-2643.
Abstract, references and article information

Moacir Aloisio, Silas L. Carvalho and César R. de Oliveira
Proc. Amer. Math. Soc. 148 (2020), 2509-2523.
Abstract, references and article information

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.

Invitation Only Research Event

Event participants

Arancha González, Executive Director, International Trade Centre
Chair: Marianne Schneider-Petsinger, Research Fellow, US and the Americas Programme, Chatham House

Colombia has more internally displaced persons (IDPs) than any other country in the world, the result of a 52-year civil war. Beyond improving the lives of its 7.3 million IDPs, the country faces a number of crucial migration issues as it works to achieve stability in the wake of an historic peace accord signed in late 2016. This country profile examines historical trends and current and future migration challenges in Colombia.

This report summarizes the economic and social development policy achievements of Central American countries over the past 20 years, as well as the notable obstacles to development that remain. The author identifies long-term challenges and outlines how they can be incorporated into a new development agenda.

Wayne Sanstead, who has been North Dakota's state schools superintendent for nearly three decades, has decided not to run for an eighth term this fall.

State data show more than 200 of Michigan's private schools have closed over the past decade, and many school leaders are blaming a shrinking student population, fewer resources, and rising costs.

Researchers found that almost half of the mountain lions they tested showed signs of plague infection

The prickly perch is an exciting sign of success for the birds, which came off the endangered species list in 2007

A study of microbial communities at the site of a 1989 deep-sea mining test suggests the fragile ecosystem may take half a century to fully recover

How do you select one image to represent half a century of photography and art? You don’t

A physiotherapist in Thunder Bay, Ont., has had his licence suspended until September, as part of a disciplinary hearing.

It's not often people want to hang onto winter, but a Summerside, P.E.I. woman has kept a piece of it in her freezer for over a decade: a snowball in a ziplock bag.

Progreso, Mexico :: A stalwart captain who's served on all four vessels reflects on 38 years of incredible experiences for his family at sea.

Neonatal mortality rate and causes of death have been relatively stable in recent years. Decision-making practices preceding death of sick neonates affect the circumstances of death. These practices vary worldwide according to the team approach and local population background.

Although our population is mostly religious, we observed a decline in maximal intensive care along with increasing redirection of care over a decade. Changes in the team approach and increasing level of parental involvement influence type and duration of treatment. (Read the full article)

A large and growing literature has demonstrated significant associations between the use of spanking and later child aggression, but we know less about paternal spanking, effects of spanking on cognitive development, and longer-term effects.

Accounting for a broad array of risk factors, spanking predicts both aggression and receptive vocabulary across the first decade of life. Importantly, we include paternal spanking, cognitive outcomes, and a longitudinal span longer than that of much of the literature. (Read the full article)

It had been 19 years since Germany lost a qualifier but Iceland ended that run in stunning style with a 3-2 away win that finished some incredible runs by the twice world champions.

When Penn State decided in early March to cancel all in-person classes, staff at the Dutton Institute were already weeks into a plan to assist faculty members with the transition. They had the snow-day protocol complete with teaching tools from hundreds of learning designers with decades of experience creating courses for the virtual world.

The scientists noted that the loss of such key stone species may lead to a rapid and dramatic change in the landscape within our lifetime.

Lower fertility rates will boost economic growth, according to a demographic model developed by Renaissance Capital. 

When two U.K. power plants shut down almost simultaneously in London’s first major blackout for a decade, it triggered a storm of questions about how to avoid another failure.

The global energy supply is turning greener.

The global energy supply is turning greener.

Utilities across the country are increasingly taking a proactive role on initiatives to advance clean energy and grid modernization. But to hear a utility CEO like Kipp focus unequivocally on one of the most critical drivers for the growth of solar and storage was striking — and yet another sign of the sector’s ongoing transformation.

Italy must more than double its capacity to store electricity if it wants to slash pollution from burning fossil fuels, the head of the nation’s power transmission network said.

When two U.K. power plants shut down almost simultaneously in London’s first major blackout for a decade, it triggered a storm of questions about how to avoid another failure.

The global energy supply is turning greener.

You may have noticed that MATLAB Mobile now sports a different UI. For this post, I’d like to welcome Geeta Sonigra, our User Experience designer to talk about what’s changed. ... read more >>

Kolkata and ADB are working systematically to update the city’s ancient urban systems after years of piecemeal approaches

The 2010s saw huge advancements across science and technology. Relive the best moments with our definitive ranking of the decade

In a new photography book, the home computer revolution of the 1970s, 1980s and 1990s is told through nostalgic industrial-design images

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ABSTRACT

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.

IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.

Multienvironment trials (METs) are widely used to assess the performance of promising crop germplasm. Though seldom designed to elucidate genetic mechanisms, MET data sets are often much larger than could be duplicated for genetic research and, given proper interpretation, may offer valuable insights into the genetics of adaptation across time and space. The Cooperative Dry Bean Nursery (CDBN) is a MET for common bean (Phaseolus vulgaris) grown for > 70 years in the United States and Canada, consisting of 20–50 entries each year at 10–20 locations. The CDBN provides a rich source of phenotypic data across entries, years, and locations that is amenable to genetic analysis. To study stable genetic effects segregating in this MET, we conducted genome-wide association studies (GWAS) using best linear unbiased predictions derived across years and locations for 21 CDBN phenotypes and genotypic data (1.2 million SNPs) for 327 CDBN genotypes. The value of this approach was confirmed by the discovery of three candidate genes and genomic regions previously identified in balanced GWAS. Multivariate adaptive shrinkage (mash) analysis, which increased our power to detect significant correlated effects, found significant effects for all phenotypes. Mash found two large genomic regions with effects on multiple phenotypes, supporting a hypothesis of pleiotropic or linked effects that were likely selected on in pursuit of a crop ideotype. Overall, our results demonstrate that statistical genomics approaches can be used on MET phenotypic data to discover significant genetic effects and to define genomic regions associated with crop improvement.