Autophagy captures intracellular components and delivers them to lysosomes for degradation and recycling. Conditional autophagy deficiency in adult mice causes liver damage, shortens life span to 3 mo due to neurodegeneration, and is lethal upon fasting. As autophagy deficiency causes p53 induction and cell death in neurons, we sought to test whether p53 mediates the lethal consequences of autophagy deficiency. Here, we conditionally deleted Trp53 (p53 hereafter) and/or the essential autophagy gene Atg7 throughout adult mice. Compared with Atg7^/ mice, the life span of Atg7^/p53^/ mice was extended due to delayed neurodegeneration and resistance to death upon fasting. Atg7 also suppressed apoptosis induced by p53 activator Nutlin-3, suggesting that autophagy inhibited p53 activation. To test whether increased oxidative stress in Atg7^/ mice was responsible for p53 activation, Atg7 was deleted in the presence or absence of the master regulator of antioxidant defense nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2^–/–Atg7^/ mice died rapidly due to small intestine damage, which was not rescued by p53 codeletion. Thus, Atg7 limits p53 activation and p53-mediated neurodegeneration. In turn, NRF2 mitigates lethal intestine degeneration upon autophagy loss. These findings illustrate the tissue-specific roles for autophagy and functional dependencies on the p53 and NRF2 stress response mechanisms.

Among the emerging techniques to detect the real footprint of buried ore deposits is isotope tracing. Novel and automated preparation systems such as continuous flow isotope ratio mass spectrometry, off-axis integrated cavity output spectroscopy for isotopic compositions of selected molecules, multi-collector inductively coupled-plasma mass spectrometry (ICP-MS), triple quadrupole ICP-MS, laser ablation ICP-MS, and a multitude of inline preparation systems have facilitated the use of isotopes as tracers in mineral exploration, as costs for isotope analyses have decreased and the time required for the analyses has improved. In addition, the isotope systems being used have expanded beyond the traditional light stable and Pb isotopes to include a multitude of elements that behave differently during processes that promote the mobilization of elements during both primary and secondary dispersion. Isotopes are also being used to understand barren areas that lack a critical process to form an ore deposit and to reveal precise redox mechanisms. The goal is to be able to use isotopes to reflect a definitive process that occurs in association with the deposit and not in barren systems, and then to relate these to something that is easier to measure, namely elemental concentrations. As new generations of exploration and environmental scientists are becoming more comfortable with the application of isotopes to effectively trace processes involved in geoscience, and new technologies for rapid and inexpensive analyses of isotopes are continually being developed, novel applications of isotope tracing are becoming more mainstream.

Thematic collection: This article is part of the Exploration 17 collection available at: https://www.lyellcollection.org/cc/exploration-17

While flagella have been studied extensively as motility organelles, with a focus on internal structures such as the axoneme, more recent research has illuminated the roles of the flagellar surface in a variety of biological processes. Parasitic protists of the order Kinetoplastida, which include trypanosomes and Leishmania species, provide a paradigm for probing the role of flagella in host-microbe interactions and illustrate that this interface between the flagellar surface and the host is of paramount importance. An increasing body of knowledge indicates that the flagellar membrane serves a multitude of functions at this interface: attachment of parasites to tissues within insect vectors, close interactions with intracellular organelles of vertebrate cells, transactions between flagella from different parasites, junctions between the flagella and the parasite cell body, emergence of nanotubes and exosomes from the parasite directed to either host or microbial targets, immune evasion, and sensing of the extracellular milieu. Recent whole-organelle or genome-wide studies have begun to identify protein components of the flagellar surface that must mediate these diverse host-parasite interactions. The increasing corpus of knowledge on kinetoplastid flagella will likely prove illuminating for other flagellated or ciliated pathogens as well.

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Autophagy is a genetically regulated process of adaptation to metabolic stress and was recently shown to be involved in the treatment response of chronic myeloid leukemia (CML). However, in vivo data are limited and the molecular mechanism of autophagy regulators in the process of leukemogenesis is not completely understood. Here we show that Beclin-1 knockdown, but not Atg5 deletion in a murine CML model leads to a reduced leukemic burden and results in a significantly prolonged median survival of targeted mice. Further analyses of murine cell lines and primary patient material indicate that active BCR-ABL directly interacts with BECLIN-1 and phosphorylates its tyrosine residues 233 and 352, resulting in autophagy suppression. By using phosphorylation-deficient and phosphorylation-mimic mutants, we identify BCR-ABL induced BECLIN-1 phosphorylation as a crucial mechanism for BECLIN-1 complex formation: interaction analyses exhibit diminished binding of the positive autophagy regulators UVRAG, VPS15, ATG14 and VPS34 and enhanced binding of the negative regulator Rubicon to BCR-ABL-phosphorylated BECLIN-1. Taken together, our findings show interaction of BCR-ABL and BECLIN-1 thereby highlighting the importance of BECLIN-1-mediated autophagy in BCR-ABL⁺ cells.

Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e. ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.

Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC regulates hematopoietic stem cell self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cell number during aging and their determination towards myeloid progenitors. Furthermore, PrPC protects myeloid progenitors against the cytotoxic effects of total body irradiation. This radioprotective effect was associated with increased cellular prion mRNA level and with stimulation of the DNA repair activity of the Apurinic/pyrimidinic endonuclease 1, a key enzyme of the base excision repair pathway. Altogether, these results show a previously unappreciated role of PrPC in adult hematopoiesis, and indicate that PrPC-mediated stimulation of BER activity might protect hematopoietic progenitors from the cytotoxic effects of total body irradiation.

Human bone marrow stromal cells (BMSC) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSC, down-regulated upon culture, and low in non-colony-forming CD45^neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSC. Overexpression of EGR1 in stromal cells induced potent hematopoietic stroma support as indicated by an increased production of transplantable CD34⁺CD90⁺ hematopoietic stem cells in expansion co-cultures. The improvement in bone marrow stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. Furthermore, EGR1 overexpression markedly decreased stromal cell proliferation whereas EGR1 knockdown caused the opposite effects. These findings thus show that EGR1 is a key stromal transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to co-ordinate the specific functions of BMSC in their different biological contexts.

Soojeong Kim and Isabel K. Darcy

An experimental technique called difference topology combined with the mathematics of tangle analysis has been used to unveil the structure of DNA bound by the Mu transpososome. However, difference topology experiments can be difficult and time consuming. We discuss a modification that greatly simplifies this experimental technique. This simple experiment involves using a topoisomerase to trap DNA crossings bound by a protein complex and then running a gel to determine the crossing number of the knotted product(s). We develop the mathematics needed to analyze the results and apply these results to model the topology of DNA bound by 13S condensin and by the condensin MukB.

The Stenotrophomonas maltophilia complex (Smc) comprises opportunistic environmental Gram-negative bacilli responsible for a variety of infections in both humans and animals. Beyond its large genetic diversity, its genetic organization in genogroups was recently confirmed through the whole-genome sequencing of human and environmental strains. As they are poorly represented in these analyses, we sequenced the whole genomes of 93 animal strains to determine their genetic background and characteristics. Combining these data with 81 newly sequenced human strains and the genomes available from RefSeq, we performed a genomic analysis that included 375 nonduplicated genomes with various origins (animal, 104; human, 226; environment, 30; unknown, 15). Phylogenetic analysis and clustering based on genome-wide average nucleotide identity confirmed and specified the genetic organization of Smc in at least 20 genogroups. Two new genogroups were identified, and two previously described groups were further divided into two subgroups each. Comparing the strains isolated from different host types and their genogroup affiliation, we observed a clear disequilibrium in certain groups. Surprisingly, some antimicrobial resistance genes, integrons, and/or clusters of attC sites lacking integron-integrase (CALIN) sequences targeting antimicrobial compounds extensively used in animals were mainly identified in animal strains. We also identified genes commonly found in animal strains coding for efflux systems. The result of a large whole-genome analysis performed by us supports the hypothesis of the putative contribution of animals as a reservoir of Stenotrophomonas maltophilia complex strains and/or resistance genes for strains in humans.

IMPORTANCE Given its naturally large antimicrobial resistance profile, the Stenotrophomonas maltophilia complex (Smc) is a set of emerging pathogens of immunosuppressed and cystic fibrosis patients. As it is group of environmental microorganisms, this adaptation to humans is an opportunity to understand the genetic and metabolic selective mechanisms involved in this process. The previously reported genomic organization was incomplete, as data from animal strains were underrepresented. We added the missing piece of the puzzle with whole-genome sequencing of 93 strains of animal origin. Beyond describing the phylogenetic organization, we confirmed the genetic diversity of the Smc, which could not be estimated through routine phenotype- or matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF)-based laboratory tests. Animals strains seem to play a key role in the diversity of Smc and could act as a reservoir for mobile resistance genes. Some genogroups seem to be associated with particular hosts; the genetic support of this association and the role of the determinants/corresponding genes need to be explored.

Mutations in protein-coding genes are well established as the basis for human cancer, yet how alterations within noncoding genome, a substantial fraction of which contain cis-regulatory elements (CRE), contribute to cancer pathophysiology remains elusive. Here, we developed an integrative approach to systematically identify and characterize noncoding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage–associated CREs and mutation discovery, we uncovered 1,836 recurrently mutated CREs containing leukemia-associated noncoding variants. By enhanced CRISPR/dCas9–based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor-suppressive CREs in human leukemia. Noncoding variants at KRAS and PER2 enhancers reside in proximity to nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently colocalize with noncoding variants across cancer types. Hence, recurrent noncoding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.

Website bán đồ trang trí nội ngoại thất Wayfair của Mỹ vừa công bố danh sách top 5 xu hướng thiết kế cho bếp và phòng tắm sẽ lên ngôi trong năm 2019 dựa trên cơ sở dữ liệu người dùng của mình.

Renting privately can be a great option. You have much more choice about the type and location of property you end up living in.

Writing a home for sale listing is not an easy task, especially for those who are doing it for the first time, but if you can manage to avoid the worst words in a home for sale listing, rest assured that you will be one step closer to selling your home in a timely manner.

In fact, reasonable investments in home improvement and repair can significantly increase the value of a home when it is sold. However, do you know which improvements should be focused to achieve the highest value and avoid losses? The infographic below will tell you.

Choosing good location, prestigious investor, reasonable price; considering legal issues and focusing on infrastructure are the secrets for investors to gain high profit from investing in land.

Dù mất dần vị trí vào tay các tỉ phú công nghệ, nhóm tỷ phú đi lên từ bất động sản vẫn đang nắm giữ những khối tài sản khổng lồ. Theo cập nhật mới nhất từ Forbes, top 5 người giàu nhất trong lĩnh vực bất động sản cũng thay ngôi nhanh chóng.

Grand Theft Auto V has once again taken the top spot on the EMEAA charts for week 17, 2020. XCOM: Chimera Squad is in second place, Call of Duty: Modern Warfare is in third, Alien: Isolation is in fourth, and Animal Crossing: New Horizons rounds out the top five.

Here are the top 5 best-selling titles (combined physical and digital sales) in EMEAA:

1. Grand Theft Auto V
2. XCOM: Chimera Squad
3. Call of Duty: Modern Warfare
4. Alien: Isolation
5. Animal Crossing: New Horizons

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443399/grand-theft-auto-v-once-again-tops-the-emeaa-charts/

The official Twitter account for the hugely popular free-to-play battle royale game, Fortnite, announced the game now has over 350 million registered players. In April, players spent over 3.2 billion hours in game. 

Epic Games plans to "the party going with our Party Royale Premiere LIVE on May 8 at 9pm ET." It will feature Deadmau5, Steve Aoki and Dillon Francis. The Party Royale will last an hour and take place on the big screen at the Main Stage. 

If you miss the Party Royale it will be rebroadcasted on May 9 at 2pm ET. 

Read an overview of the Party Royale below:

Let’s get ready to party! The Party Royale Premiere arrives on Friday, May 8, at 9 PM ET.

Dillon Francis, Steve Aoki, and deadmau5 are coming to Party Royale with back-to-back-to-back sets LIVE on the big screen at the Main Stage. Hit the dance floor, chill with friends, or jump into activities in Party Royale.

No RSVP Necessary

If you can’t make it right at 9 PM ET, you can still catch the rest of the live show as long as you join before it ends at 10 PM ET.

Bring on the Encore

If you're still busy, don’t worry — the Party Royale Premiere will return for a rebroadcast. On May 9 from 2 PM to 3 PM ET, you can catch the full show once again at the Main Stage.

And just like the first airing, you can still jump in during the show. 

Party Favors

The Party Royale Premiere also has a party favor. Anyone who logs into Fortnite from Friday, May 8 at 6 PM ET to Monday, May 11 at 10 AM ET will get the new, music-reactive Neon Wings Back Bling for free! Perfect for wearing at the show.

Beyond the Main Stage

Shows at the Main Stage are just some of the many attractions at Party Royale. In this new experimental and evolving space, there are many things to do and places to explore. For example: take on aerial obstacle courses at Skydive Rift, participate in boat races at Fishsticks’ Boat Race, and grab items at The Plaza such as the new Paint Launcher.

There are no weapons or mats in Party Royale — it’s all about just hanging out and having fun. No Sweat. All Chill. Let’s Party!

Fortnite is available on the Nintendo Switch, PlayStation 4, Xbox One, Windows PC, iOS, and Android.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443407/fortnite-tops-350-million-registered-players/

Sony has released the US PlayStation Store downloads charts for March 2020. Final Fantasy VII Remake topped the PS4 charts, Beat Saber topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Here is the complete list of charts:

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443430/final-fantasy-vii-remake-tops-the-us-playstation-store-downloads-in-april-2020/

Sony has released the Europe PlayStation Store downloads charts for April 2020. Grand Theft Auto V topped the PS4 charts, Blood and Truth topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Final Fantasy VII Remake debuted in fourth on the PS4 charts. Resident Evil 3 debuted in 10th place.

Here is the complete list of charts:

PlayStation 4

1. Grand Theft Auto V (3)
2. EA SPORTS FIFA 20 (2)
3. Call of Duty: Modern Warfare (1)
4. FINAL FANTASY VII REMAKE (New)
5. NBA 2K20 (RE)
6. Call of Duty: Modern Warfare 2 Campaign Remastered (20)
7. EA SPORTS UFC 3 (RE)
8. Minecraft (5)
9. Marvel’s Spider-Man (RE)
10. RESIDENT EVIL 3 (New)
11. MONOPOLY PLUS (RE)
12. Rocket League (11)
13. Assassin’s Creed Odyssey (10)
14. Days Gone (RE)
15. TOM CLANCY’S RAINBOW SIX | SIEGE (RE)
16. Red Dead Redemption 2 (19)
17. The Crew 2 (13)
18. Tom Clancy’s The Division 2 (RE)
19. eFootball PES 2020 (RE)
20. Need for Speed Heat (RE)

PlayStation VR

1. Blood and Truth (5)
2. Beat Saber (1)
3. Creed: Rise to Glory (9)
4. Job Simulator (2)
5. RICK AND MORTY: VIRTUAL RICK-ALITY (RE)
6. ASTRO BOT Rescue Mission (RE)
7. Until Dawn: Rush of Blood (RE)
8. BOXVR (RE)
9. Farpoint (RE)
10. SUPERHOT VR (4)

DLC

1. Fortnite – The Iris Pack (1)
2. Fortnite – Bassassin Challenge Pack (3)
3. GTA Online: Criminal Enterprise Starter Pack (5)
4. Marvel’s Spider-Man: The City That Never Sleeps – Season Pass (RE)
5. Assassin’s Creed Odyssey – Season pass (RE)
6. Fortnite: Save the World – Standard Founder’s Pack (10)
7. The Division 2 – Warlords of New York – Expansion (2)
8. Need for Speed Heat – McLaren F1 Black Market Delivery (6)
9. Modern Warfare – Atlanta FaZe Pack (New)
10. Assassin’s Creed Origins – The Hidden Ones (RE)

Free-to-Play

1. Call of Duty: Warzone (1)
2. Fortnite (2)
3. Apex Legends (3)
4. Brawlhalla (5)
5. DON’T EVEN THINK (New)
6. eFootball PES 2020 LITE (4)
7. Destiny 2 (New)
8. WORLD OF WARSHIPS: LEGENDS (7)
9. DRAGON BALL XENOVERSE 2 Lite Version (6)
10. Paladins (9)

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443431/gtav-tops-the-eu-playstation-store-downloads-in-april-2020-final-fantasy-vii-remake-debuts-in-4th/

Generative visuals and eerie sound design based on height maps of glaciers, canyons and estuaries. London-based motion graphic designer Sophie Marschner transforms real-world data into a delicate digital topography in Monolith. By using the height maps of various large-scale landmarks, including glaciers, canyons and estuaries, Marschner maps the outside world into a more intimate, digital […]

The post Sophie Marschner turns real-world data into a digital topography in Monolith appeared first on FACT Magazine.

Two Windsor men face multiple drug, property and weapon charges after police pulled over a vehicle for a traffic violation Thursday night. At around 8 p.m., officers from the Windsor police property crimes unit in the area of Tecumseh Road East and Mercer Road saw a black Chrysler 300 commit a traffic violation, police said […]

Please, I implore you: jump on this bandwagon.

X-37B? Sorry, I thought you said your name was X Æ A-12.

STATE PENSIONS are calculated by National Insurance contributions - but can you top up any missed years?

Premier League clubs are fearful that a significant number of first-team stars may refuse to return to action if the league's Project Restart plan gets the green light.

When asteroid Armageddon is upon us, we can't just call Bruce Willis. Meet the people who really do watch the skies – and make detailed plans for our survival

The Solar Orbiter spacecraft, set to launch on 7 February, will give us our first clear views of the sun’s poles and help unravel the mystery of the solar wind

A group of astronomers has called for legal action to stop the launch of thousands of satellites designed by companies like SpaceX and OneWeb to beam high-speed internet around the world

Thousands of dead satellites and chunks of debris in orbit are a threat to active satellites, but rockets that launch clouds of talcum powder may prevent a disastrous collision

There is something deeply unsettling about the lionization of Andrew Cuomo and his handling of the epidemic, especially in the light of the raw statistics

Leaders in Silicon Valley—both the real one and the fictional one on HBO—started this week by debating the responsibilities of tech companies

Hindsight is 20/20, even if you’re smizing.

Anna Marie struggles with “The Toad Hand”. Alex Fuller continues to abstain from seasonal Madden play. Chris gets two wife’s worth of criticism. And Shawn...

This week’s cast discusses multiple Dragon Quests, a Dragon Quest mod for a non-Dragon Quest game, squishy things that aren’t Dragon Quest slimes, and many delays for games coming out…in Japan?

C&A, Adidas/Reebok, Esprit and M&S round out top five as average scores increase year on year, but Max Mara, Pepe Jeans and Tom Ford fall flat

The H&M Group, C&A, Adidas/Reebok, Esprit, Marks & Spencer and Patagonia are the world’s most transparent major fashion brands, according to the 2020 fashion transparency index from the campaign group Fashion Revolution.

The annual report, now in its fifth year, ranks the amount of information companies disclose about social and environmental policies, processes and effects within their operations and supply chains.

After analyzing 95 million traffic stop records, filed by officers with 21 state patrol agencies and 35 municipal police forces from 2011 to 2018, researchers concluded that 'police stops and search decisions suffer from persistent racial bias.'

In the wake of Covid-19, We Are One: A Global Film Festival is taking the experience online. But cinema is a bigger encounter

Every year, at Cannes (and other festivals) there’s a plaintive argument about what Cannes (or other festivals) are really all “about”. Some Savonarola-type person will dash the glass of rosé out of your hand, throw your canape into the Med and tell you Cannes is not about red-carpet narcissism, not about stars preening in the flashbulb glare of celeb-worship, not about L’Oréal sponsorship, not about getting drunk at a million late-night parties. It’s about the movies, about cinema itself.

Of course. And that’s what the new Covid-19-related We Are One: A Global Film Festival appears to offer: the 10-day online festival, beginning 29 May, curated by Jane Rosenthal of the Tribeca film festival, featuring arthouse films (though not the big-ticket Hollywood items) from Cannes, Venice, Berlin and many more, streaming for free in return for an optional donation to the World Health Organization’s Covid-19 fund. So there you have it. A festival with all the frills and extras and flummeries stripped away. Just you, in your bedroom, with your laptop, communing with cinema. Isn’t that what it’s all about?

The actor, best known for playing Gollum in the Lord of the Rings and Hobbit films, will read the entire JRR Tolkien novel

Andy Serkis is to give a continuous, live reading of The Hobbit – lasting around 12 hours – in aid of charity. The actor, best known as Gollum in the Lord of the Rings and Hobbit films, will read the entire book from start to finish with no breaks.

Money raised from the performance will be split equally between NHS Charities Together and Best Beginnings.

Now that the COVID-19 pandemic has forced millions into isolation, video games are seeing a surge in usage as people seek entertainment and social interaction. When we surveyed gaming-focused VCs in October, Andreessen Horowitz partner Jonathan Lai predicted that “next-generation games will be bigger than anything we’ve seen yet,” eventually reaching “Facebook scale.” This month, […]

U.S. Vice President Mike Pence's press secretary, the wife of one of President Donald Trump's senior advisers, has tested positive for the coronavirus, raising alarm about the virus' potential spread within the White House's inner most circle.