Archan Chakraborty, Wei-Cheng Lin, Yu-Tsun Lin, Kuang-Jing Huang, Pei-Yu Wang, Yi-Feng Chang, Hsiang-Iu Wang, Kung-Ting Ma, Chun-Yen Wang, Xuan-Rong Huang, Yen-Hsien Lee, Bi-Chang Chen, Ya-Ju Hsieh, Kun-Yi Chien, Tzu-Yang Lin, Ji-Long Liu, Li-Ying Sung, Jau-Song Yu, Yu-Sun Chang, and Li-Mei Pai

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under Gln deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that SNAP29 regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of synaptosome-associated protein 29 (SNAP29) interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.

Olivia R. Grafinger, Genya Gorshtein, Tyler Stirling, Megan I. Brasher, and Marc G. Coppolino

Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr⁵⁶⁷. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion.

Kelly L. Dunlevy, Valentina Medvedeva, Jade E. Wilson, Mohammed Hoque, Trinity Pellegrin, Adam Maynard, Madison M. Kremp, Jason S. Wasserman, Andrey Poleshko, and Richard A. Katz

A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via "tethering proteins" that function to bridge heterochromatin and the nuclear membrane or nuclear lamina. We identified previously a human tethering protein, PRR14, that binds heterochromatin through an N-terminal domain, but the mechanism and regulation of nuclear lamina association remained to be investigated. Here we identify an evolutionarily conserved PRR14 nuclear lamina binding domain (LBD) that is both necessary and sufficient for positioning of PRR14 at the nuclear lamina. We also show that PRR14 associates dynamically with the nuclear lamina, and provide evidence that such dynamics are regulated through phosphorylation-dephosphorylation of the LBD. Furthermore, we identified a PP2A phosphatase recognition motif within the evolutionarily conserved PRR14 C-terminal Tantalus domain. Disruption of this motif affected PRR14 localization to the nuclear lamina. The overall findings demonstrate a heterochromatin anchoring mechanism whereby the PRR14 tether simultaneously binds heterochromatin and the nuclear lamina through two separable, modular domains. The findings also describe an optimal PRR14 LBD fragment that could be used for efficient targeting of fusion proteins to the nuclear lamina.

File: (L-R) "The Sarah Silverman Program" writer Harris Wittels, comedian Sarah Silverman, executive producer/head writer Dan Sterling and actress Laura Silverman, arrive at Comedy Central's Emmy Awards party at the STK restaurant Sept. 21, 2008 in Los Angeles.; Credit: Ethan Miller/Getty Images

Harris Wittels, a comedy writer who worked on "Parks & Recreation," has died at 30, the Los Angeles Police Department's Jane Kim tells KPCC.

Wittels was discovered by his assistant around 12 p.m., Kim said, and was already dead. Kim said that Wittels' death was a possible overdose, but that the Coroner's Office would determine the cause of death. Wittels had attended drug rehab twice.

Comedy Central, where Wittels worked on "The Sarah Silverman Program" and "Secret Girlfriend," confirmed Wittels' death, as did the comedy show he appeared at Wednesday night.

Comedy Central tweet

Meltdown Show tweet

Wittels was also well known for his @Humblebrag Twitter account and later book, helping to popularize the idea online of the false modesty of bragging while trying not to look like you're bragging.

Wittels had spoken about his struggles with addiction in places including Pete Holmes's podcast "You Made It Weird" in a November episode.

"I just really stopped caring about my life," Wittels said on "You Made It Weird," explaining how he got into doing drugs. "I just really started to think, well, if I'm only here for 80 years, then who cares if I spend it high or not?"

Wittels received his first big break when Sarah Silverman saw him performing comedy and gave him a job writing for her Comedy Central show.

Wittels also wrote for HBO's "Eastbound & Down," several MTV awards shows and the American Music Awards. He had a recurring role on "Parks & Recreation" and was a regular guest on the "Comedy Bang Bang" podcast.

Comedians, actors and fans mourned Wittels' death online.

Harris Wittels Storify

See Wittels in a scene from "Parks & Recreation":

Wittels on Parks & Recreation

Listen to Wittels on "Comedy Bang Bang":

Wittels on Comedy Bang Bang

This story has been updated.

This content is from Southern California Public Radio. View the original story at SCPR.org.

In just a few years, digital technologies have allowed faster mobilization in response to humanitarian crises, better documentation of war crimes in conflict zones like Syria and Yemen, and more accessible platforms for organizing peaceful demonstrations around the world.

A standardised method to help choose the most cost-effective measures to remediate contaminated sites has been developed by Austrian researchers. The method takes into account a wide range of factors, including the principles of sustainability.

As the media environment changes, the way scientists communicate their work must also evolve. This study explored the effect of public communication on the scientific ‘impact’ of America’s most highly cited nanotechnology researchers. It provides the first evidence that outreach activities, such as speaking to journalists and being mentioned on Twitter, can increase a scientist’s impact.

A study has evaluated three types of media campaign conducted by a large UK supermarket to encourage shoppers to reduce their food waste. These used social media, an e-newsletter and a print/digital magazine, respectively. Although they all appeared to lead to reductions in food waste to some extent, similar behavioural changes were also seen for customers who had not participated in any of the campaigns.

Monitored natural attenuation (MNA) is a long-term, ‘hands-off’ approach to cleaning up contaminated land. New research has surveyed the current development of MNA in Europe and demonstrates a clear need for practitioners to systematically collect and learn from each other’s experiences with this form of brownfield remediation.

Compared with traditional remediation techniques used to remediate brownfield sites, supporters of phytoremediation argue that it is cheaper and more environmentally-friendly. A new analysis has reviewed its strengths, weaknesses, opportunities and threats, and suggests it is well suited to cleaning up sites with low to medium levels of contamination.

A new study -- the first to look at social media's effect on memory -- suggests posting personal experiences on social media makes those events much easier to recall.

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A standardised method to help choose the most cost-effective measures to remediate contaminated sites has been developed by Austrian researchers. The method takes into account a wide range of factors, including the principles of sustainability.

Pioneering methods used in the Netherlands combine remediation of brownfield sites with the use of groundwater for heat cold storage (HCS, or ATES: Aquifer Thermal Energy Storage) to achieve both low-cost remediation and sustainable use of energy.

The Internet consumers are becoming more aware of their personal data and 82 per cent users have tried to remove private information from websites or social media channels, according to a report by cybersecurity firm Kaspersky.

‘Safe harbour protection’ only if intermediaries facilitate and not modify such content, including ads

The advent of new rules for social media applications - like Instagram, Twitter, Facebook and WhatsApp - could spell the end for privacy in the Indian internet space. Despite push back from major internet companies, the Indian government is all set to go ahead with the new regulations. The rules are a bid to quell the spread of fake news and trace anti-social elements in the Indian internet ecosystem faster.

The proposed alliance — to be named the Information Trust Alliance (ITA) — will be a grouping of digital platforms and publishers, fact checkers, civil society and academia that will aim to control the spread of harmful content, including fake news and hate speech. So far, discussions have taken place among Facebook, Google, Twitter, Byte-Dance, ShareChat and YY Inc.

​​Companies are seeking to balance freedom of expression with the potential for damage to their business, not for the first time, but more gingerly perhaps, given the level of polarisation. ​​

Government officials remained tightlipped on the reasons and said the PM would reveal more in a day or two. It was also not clear whether Modi, who has used social media to communicate directly with the masses, would be giving up the platforms for a long time or only for a day on Sunday — which also happens to be the International Women’s Day.

The Silicon Valley tech giants have asked employees and contractors to work from home if possible, to slow the fast-spreading respiratory disease

The government asked social media platforms to start awareness campaigns, remove misinformation from the platform and promote authentic information

Discarding – returning unwanted catches to the sea – is seen as wasteful, but banning the practice would remove an important food source for many marine organisms. This study modelled the effects of gradually reducing and abruptly banning discards using data from a protected bay in Australia. The researchers recommend gradual reduction of discards in order to maintain ecosystem stability.

Natural wetlands can provide effective long-term remediation of contamination from abandoned mines, new research suggests. The study examined a natural wetland receiving water from a copper mine in the UK, and showed that the water’s acidity and levels of toxic metals were significantly reduced once it had passed through the wetland.

An investigation into the attitudes of Canadian soil-remediation experts has shown that they tend to prefer conventional remediation methods over phytoremediation — which relies on plants to clean soils — despite evidence that the latter can have advantages. The researchers behind the study highlight that this ‘status-quo bias’ poses a barrier to the uptake of novel technologies such as phytoremediation, and that scientists may need to find different ways of disseminating evidence to increase the use of new techniques among practitioners.

New low cost methods using bacteria to remove toxic metals from groundwater have been investigated using both actual contaminated groundwater and artificially controlled systems. Environmental conditions, such as changing levels of acidity or alkalinity, can have a significant effect on the removal of toxins, results show.

The effects of antibiotic contamination may be attenuated by the common reed, new research shows. The study found that the common reed (Phragmites australis), sourced from a temperate estuary with brackish water, had capacity for the bioremediation of the veterinary antibiotic enrofloxacin (ENR). The authors suggest that salt-marsh plants and their associated micro-organisms could be a valuable asset in the recovery of contaminated estuary environments.

Microbes and biocatalytic enzymes could offer useful tools for cleaning soils polluted with polycyclic aromatic hydrocarbons (PAHs), suggests a new review of remediation approaches. However, risk assessments and further work are needed before their use can be extended beyond the lab to realworld situations. This comprehensive overview of available and novel methods indicates their constraints and potential for future development and research.

Following a roller coaster four years in the job, some members of Nine Entertainment’s board are now pushing openly for the removal of company CEO Hugh Marks.

An Olivier Award-nominated comedian is going back on tour this year.

SPRINGFIELD, Va. – Drivers along the Franconia-Springfield Parkway (Route 289) bridge over Accotink Creek now have better protection from oncoming...

Classroom management gets social with sites like Twitter, Facebook and Pinterest helping teachers and students communicate and share knowledge.

How you use Facebook, Twitter, LinkedIn and other social media sites may change depending on the format — and who you're talking to.

From Rebecca Martinson's rabid sorority letter to Tom Cruise's manic couch-pouncing, some mortifying moments take on a life of their own.

Survey data reveals that 90% of customers would recommend a brand after a positive social media interaction.

Will social media monitoring protect kids online or is it just plain spying?

Love can be confusing and heart-wrenching — but it can also be funny!

Why are government officials still blocking journalists from documenting the Gulf oil spill? What are they hiding, and why is Obama letting it happen?

To commemorate the 50th anniversary of the 1962 World's Fair in Seattle, Habitat for Humanity constructs a prefab-hybrid home that incorporates various future-t

The Organic Trade Association is hosting an online organic discussion and inviting everyone to participate in the #OrganicFestival.

Theses six apps can help you add hours back to your day.

Mold and water go hand-in-hand, so learn how to find mold and prevent it.

It's been a good week for MNN in the press as cofounder Chuck Leavell hits Jimmy Fallon's show and the pages of The Daily Beast and Reuters.

If Google is making users stupid, then social networks like Facebook may be making people seem smart without actually being so.

We know photos in magazine ads and TV commercials are altered, but are you aware of the Photoshopping on your friends' selfies?

Sometimes a Facebook post or a tweet can make all the difference for a shelter dog.