Hundreds of thousands of families live in overcrowded homes. What is lockdown life like for them?

Llewellyn Barnes made his debut in a professional golf debut last month, after decades living homeless in South Africa.

Bicycle shops across the UK say demand for new bikes, and repairs for old ones, has risen sharply.

Ana Carmona was quarantined with her parents and siblings in NYC, when she got some big news.

The game doesn’t celebrate winners but those who persevere and endure.

“Arise: A Simple Story” coasts on its gentle visual language, but is a good option for those looking for a family-friendly game.

TidalWave Productions is releasing Buttigieg and Bloomberg comic books to sit alongside its Warren biography.

"Onward" and "Soul" deal with the eternal and the ethereal.

In keeping with the best video game remakes, “Black Mesa” is a perfect complement to your rose-tinted memories, with modern-day graphics and extensive level design tweaks.

"Half Life: Alyx" will transport you to an incredibly vivid science fiction world.

Young medical students and health-care workers simply want to keep contributing in the only home they know.

oscon: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/BM3qufX1PF

velocityconf: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/Z0EetiQshZ

We may not be able to go out during the national lockdown, but that does not mean that we can't attend events.

Meghan Markle is reportedly set to launch her lifestyle website to rival Gwyneth Paltrow's Goop.

Life as an Exchange Student in Northern Italy

The Amateur Traveler talks to Madeline Jhawar from Italy Beyond the Obvious about life as a tour guide for an adventure travel company. Madeline was previously on the Amateur Traveler talking about Travel to Sicily. Madeline talks about her misconceptions about what being a tour guide would be like and the reality of keeping a group of people happy (and not lost). She guided hiking and biking tours primarily in Italy. What skills do you need to be a successful tour guide? It might not be what you think.

M. Wang
Aug 1, 2012; 11:492-500
Technological Innovation and Resources

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.

Members Event

Event participants

Mina Al-Oraibi, Journalist on Middle East affairs
Robin Yassin-Kassab, Author, Burning Country: Syrians in Revolution and War
Chair: Dr Neil Quilliam, Acting Head, Middle East and North Africa Programme, Chatham House

K Schoonjans
May 1, 1996; 37:907-925
Reviews

6 November 2019 , Volume 95, Number 6

In these unprecedented times, we are all spending much more time at home and in our gardens. And, now that spring has well and truly arrived, it's the perfect time to get reacquainted with one of our country's busiest workers - the bee.

We asked Guardian readers living in cities and towns across the world to share their images of the wildlife they can see from their homes. You answered in your droves, from Canada to Cardiff, and here are some of the best.

http://www.biodiversityislife.net/