The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca²⁺ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca²⁺ currents were inhibited with a log (Ic₅₀) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca²⁺ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca²⁺ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca²⁺ current inhibition was mediated by the Gα_i/o or Gα_q/11 family of subunits. Treatment with both PTX (Ca²⁺ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca²⁺ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα_i/o and Gα_q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca²⁺ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling.

BACKGROUND AND PURPOSE:

Physician-industry relationships can be useful for driving innovation and technologic progress, though little is known about the scale or impact of industry involvement in neuroradiology. The purpose of this study was to assess the trends and distributions of industry payments to neuroradiologists.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for biopanning using multiple display methods. This protocol describes selection from affibody libraries using display on Staphylococcus carnosus. Display of affibodies on staphylococci is very efficient and straightforward because of the single cell membrane and the use of a construct with a constitutive promoter. The workflow involves display of affibody libraries on the surface of S. carnosus cells, followed by screening and selection of binders using fluorescence-activated cell sorting (FACS). The transformation of DNA libraries into S. carnosus is less efficient and more complicated than for Escherichia coli. Because of this, staphylococcal display is suitable for affinity maturation or other protein-engineering efforts that are not dependent on very high diversity, and thus magnetic-activated cell sorting (MACS) is often not required before FACS. However, MACS is an option, and MACS procedures used for E. coli can easily be adapted for use in S. carnosus if needed.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for selection via multiple display methods. This protocol describes selection from affibody libraries by Escherichia coli cell surface display. With this method, high-diversity libraries of 10¹¹ can be displayed on the cell surface. The method involves two steps for selection of binders from high-diversity libraries: magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is used first to enrich the library in target-binding clones and to decrease diversity to a size that can be effectively screened and sorted in the flow cytometer in a reasonable time (typically <10⁷ cells). The protocol is based on methodology using an AIDA-I autotransporter for display on the outer membrane, but the general procedures can also be adjusted and used for other types of autotransporters or alternative E. coli display methods.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library. This is then followed by amplification of the library, which can then be used for biopanning using multiple methods. This protocol describes amplification of affibody libraries, followed by biopanning using phage display and analysis of the selection output. The general procedure is mainly for selection of first-generation affibody molecules from large naive (unbiased) libraries, typically yielding affibody hits with affinities in the low nanomolar range. For selection from affinity maturation libraries with the aim of isolating variants of even higher affinities, the procedure is similar, but parameters such as target concentration and washing are adjusted to achieve the proper stringency.

Affibody molecules are small (6-kDa) affinity proteins folded in a three-helical bundle and generated by directed evolution for specific binding to various target molecules. The most advanced affibody molecules are currently tested in the clinic, and data from more than 300 subjects show excellent activity and safety profiles. The generation of affibody molecules against a particular target starts with the generation of an affibody library, which can then be used for panning using multiple methods and selection systems. This protocol describes the molecular cloning of DNA-encoded affibody libraries to a display vector of choice, for either phage, Escherichia coli, or Staphylococcus carnosus display. The DNA library can come from different sources, such as error-prone polymerase chain reaction (PCR), molecular shuffling of mutations from previous selections, or, more commonly, from DNA synthesis using various methods. Restriction enzyme-based subcloning is the most common strategy for affibody libraries of higher diversity (e.g., >10⁷ variants) and is described here.

Practicing family medicine is really hard; the emotional toll of sharing patients’ distress, vulnerability, and trauma can build up and become overwhelming. A family physician experienced such a moment during one particularly complex morning. Feeling nearly ready to walk out of patient care, she reached out to the team nurse, who helped her get through the moment and re-engage with the waiting patients. Sharing vulnerability in the moment, and later reflecting and deciding to write about it shows the power of prioritizing teamwork in practice.

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

The deadline to claim part of the $15 million Cash App settlement is November 18. Here's what to know.

The driverless vehicles still can't take L.A.'s notorious highways.

WASHINGTON — Secretary of State Rex Tillerson says diplomatic efforts aimed at resolving the North Korean crisis “will continue until the first bomb drops.”

That statement comes despite President Donald Trump’s tweets a couple of weeks ago that his chief envoy was “wasting his time” trying to negotiate with “Little Rocket Man,” a mocking nickname Trump has given the nuclear-armed nation’s leader, Kim Jong Un.

“I think he does want to be clear with Kim Jong Un and that regime in North Korea that he has military preparations ready to go and he has those military options on the table. And we have spent substantial time actually perfecting those,” Tillerson told CNN’s “State of the Union” on Sunday. “But be clear: The president has also made clear to me that he wants this solved diplomatically. He’s not seeking to go to war.”

Recent mixed messaging from the top of the U.S. government has raised concerns about the potential for miscalculation amid the increasingly bellicose exchange of words by Trump and the North Korean leader.

Trump told the U.N. General Assembly last month that if the U.S. is “forced to defend itself or its allies, we will have no choice but to totally destroy North Korea.” Trump also tweeted that Korea’s leadership “won’t be around much longer” if it continued its provocations, a declaration that led the North’s foreign minister to assert that Trump had “declared war on our country.”

Tillerson acknowledged during a recent trip to Beijing that the Trump administration was keeping open direct channels of communications with North Korea and probing the North’s willingness to talk. He provided no elaboration about those channels or the substance of any discussions.

Soon after, Trump took to Twitter, saying he had told “our wonderful Secretary of State, that he is wasting his time trying to negotiate with Little Rocket Man … Save your energy Rex, we’ll do what has to be done!” Trump offered no further explanation, but he said all military options are on the table for dealing with North Korea’s nuclear and missile programs.

Analysts have speculated about whether the president and his top diplomat were playing “good cop, bad cop” with North Korea, and how China might interpret the confusing signals from Washington. Beijing is the North’s main trading partner, and the U.S. is counting on China to enforce U.N. sanctions.

“Rest assured that the Chinese are not confused in any way what the American policy towards North Korea (is) or what our actions and efforts are directed at,” Tillerson said.

Asked if Trump’s tweets undermined Tillerson, the secretary said: “I think what the president is doing is he’s trying to motivate action on a number of people’s part, in particular the regime in North Korea. I think he does want to be clear with Kim Jong Un and that regime in North Korea that he has military preparations ready to go and he has those military options on the table and we have spent substantial time perfecting those.”

He added that Trump “has made it clear to me to continue my diplomatic efforts, which we are, and I’ve told others those diplomatic efforts will continue until the first bomb drops.”

North Korea has launched missiles that potentially can strike the U.S. mainland and recently conducted its largest ever underground nuclear explosion. It has threatened to explode another nuclear bomb above the Pacific.

The post Rex Tillerson says continue diplomacy with North Korea ‘until first bomb drops’ appeared first on PBS NewsHour.

A Dundee ice hockey player has been jailed after being found guilty of raping a teenage girl in his car.

Sir Keir Starmer's beleaguered former chief of staff will no longer take up the position of “envoy to the nations and regions.”

What does 2023's Scottish Health Survey tell us about Scotland's population - from smoking rates to obesity, and alcohol consumption?

Public sector pay increases are outstripping those in the private sector for the first time in four years

A "renowned" restructuring advisory business has been acquired by a major player.

Former MP Joanna Cherry has said that the SNP rules which prevented her from standing for a seat at Holyrood would not block Stephen Flynn from doing the same.  

Sir Andy Murray will swap Centre Court for the stage next summer as he embarks on a tour discussing his illustrious tennis career.

Health Secretary Neil Gray will address concerns around his use of a ministerial car to attend football games at Hampden.

A baroque fiddle believed to have been played by Robert Burns will be performed live on stage in the United States for the first time.

This week we learn not to disturb Kelley's special demon slaying time, get too attached to dogs in games, or disturb the Harvest Moon plushie announcement. We also get your suggestions for series that need to be resurrected. Enjoy Action RPG August!

The post RPG Cast – Episode 552: “Aw ***t, She’s Playing Diablo!” appeared first on RPGamer.

It's a slightly quieter week after the mass dump of games that was February and the first week of March. Kelley doesn't want her mom to think she's watching hentai, while Anna Marie insists our reviewers don't hate every game. Josh will one day be free of the epic grip of Cold Steel IV, but not before Chris convinces him if he just lifts a truck, he can find a new orbment.

The post RPG Cast – Episode 577: “Eclipse, I Love You, but GO AWAY” appeared first on RPGamer.

Jonathan Stringer joins us in an attempt to sell his copy of Mugen Souls. Josh is launching his Kickstarter for his new documentary, Legacy of the Bitcoins. And Chris has lost his Epic Games launcher, thanks Windows 11.

The post RPG Cast – Episode 616: “Garland Does It His Way” appeared first on RPGamer.

This week on RPG Cast, Kelley falls asleep for four years and misses the announcement of Kingdom Hearts 4. Chris is a five year old with beefy fists. Sam tells us how her video game marriage life works. And we all agree that Bidoof is our buddy.

The post RPG Cast – Episode 627: “Maybe His Feet Are Nobodies” appeared first on RPGamer.

Kelley is a complicated person when it comes to PC gaming. Josh is a quiet English man, slightly constipated. And Chris takes a Steam Deck to the face.

The post RPG Cast – Episode 649: “Away With You, Stadia!” appeared first on RPGamer.

Chris performs a ritual that needs more hands. Kelley has to clean just one more car. Ryan likes to think he can't be replaced by Bing yet. And Jason just keeps yelling, "Barrel!"

The post RPG Cast – Episode 668: “Nacho Chakotay” appeared first on RPGamer.

Kelley dishonors herself in Baldur's Gate 3 and retreats to Vampire Survivors. Chris goes on the hunt for Dr. Robotminsc. Robert hits level 50 before the third scripted battle.

The post RPG Cast – Episode 690: “Spay and Neuter Your Owlbear Cubs” appeared first on RPGamer.

Chris dresses Pikachu up like a schoolboy with a camera. Josh wants his flight stick, he needs a HOTAS. Kelley wants Final Fantasy VII Rebirth to end like an episode of JoJo. Follow Solstice Warriors on their Myspace music page.

The post RPG Cast – Episode 691: “Hello, What Did Scamper Do Today?” appeared first on RPGamer.

Chris launches his new brand, Elsa coffee. Kelley's Pokémon demand she finds a caramel apple and a teacup. Ryan apparently got left in Seattle and is still at PAX West.

The post RPG Cast – Episode 693: “The Brew Never Bothered Me Anyways” appeared first on RPGamer.

Chris believes rabites are full of juice. Kelley's furry tank game bias is exposed. Robert gets to be the Snivey he always was inside. Rock flautist.

The post RPG Cast – Episode 702: “He Plays Flute Like Your Mom Plays SNES” appeared first on RPGamer.

Chris kink-shames Red XIII. Kelley violates the time space continuum with cat cafes. Josh is better at keeping things afloat than Embracer Group. Robert fails at being family friendly.

The post RPG Cast – Episode 711: “I’ve Always Wanted a Gaming Napkin” appeared first on RPGamer.

Chris gets hit by the valley girl truck-kun and can't leave the hinterlands. Sam makes a Sony Pony Button in order to become the true Unicorn Overlord. Kelley becomes a cat and pantomimes WoW lore while building Lego Minifigures that can punch dinosaurs.

The post RPG Cast – Episode 727: “PlayStation go VRRR” appeared first on RPGamer.

Kelley tells us about her new clawed abomination: the cat-raptor. Chris tries to figure out who cross Ross is and why he's so angry. Robert is "surprised" to find horse girls show up on the sheet. Josh is definitely here for the icons.

The post RPG Cast – Episode 730: “Never Played a JRPG” appeared first on RPGamer.

Publisher Xbox Game Studios and developer The Coalition have announced John DiMaggio, the voice actor for Marcus Fenix, and Carlos Ferro, the voice actor for Dom Santiago, will reprise their roles for the prequel Gears of War: E-Day.

"On today's 18th anniversary of Gears of War, we're proud to share that John DiMaggio and Carlos Ferro are reprising their roles as the iconic voices of Marcus Fenix and Dominic Santiago in Gears of War: E-Day," announced the developer.

Gears of War: E-Day is in development for the Xbox Series X|S, PC, and Xbox Game Pass.

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463012/marcus-and-dom-voice-actors-to-return-for-gears-of-war-e-day/

ublisher Bethesda Softworks and developer MachineGames have released a gameplay deep dive video for Indiana Jones and the Great Circle that is nearly 15 minutes in length.

"From locations and puzzles to gear and combat, MachineGames Audio Director, Pete Ward, takes us on a whirlwind journey through the world of The Great Circle," reads the description to the video. "Get ready for launch with this look at Indy’s grand adventure."

View the gameplay deep dive below:

Indiana Jones and the Great Circle will launch for the Xbox Series X|S, PC via Steam and Microsoft Store, and Xbox Game Pass on December 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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463033/indiana-jones-and-the-great-circle-gets-gameplay-deep-dive/

Nintendo has announced its Black Friday 2024 deals. 

Dozens of games will be discounted including The Legend of Zelda: Tears of the Kingdom, Super Mario Maker 2, Animal Crossing: New Horizons, Pikmin 4, Nintendo Switch Sports, Kirby and the Forgotten Land, Super Mario Odyssey, Pikmin 1 + 2, and more.

The Neon Red and Neon Blue Joy-Con controllers and the Nintendo Switch Pro Controller will be discounted by $20, while the Nintendo Switch Carrying Case & Screen Protector - The Legend of Zelda: Tears of the Kingdom Edition will be discounted by $10.

The Nintendo Switch: Mario Kart 8 Deluxe Bundle will once again return for $299.99, while the new Nintendo Switch – OLED Model: Mario Kart 8 Deluxe Bundle will be available for $349.99. Both bundles include a digital download of Mario Kart 8 Deluxe and a 12-month Nintendo Switch Online Individual Membership.

The Nintendo Switch Lite: Hyrule Edition with Bonus Nintendo Switch Online + Expansion Pack will be available for $209.99. The bundle includes a 12-month Nintendo Switch Online + Expansion Pack Individual Membership.

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463045/nintendos-black-friday-2024-deals-revealed/

Liam Payne, a former member of the boy band One Direction, was found dead in a hotel courtyard in Buenos Aires, Argentina on Wednesday evening, according to CNN and La Nacion, both of which cited local police.

The singer died after an apparent fall from the balcony of his third-floor hotel room. Argentinian authorities told Good Morning America that Payne had been staying at the hotel CasaSur in the upscale neighborhood of Palermo.

He was 31.

Read more at The Daily Beast.

A collective gasp echoed like a thunderclap in a valley in our Daily Beast newsroom late Wednesday afternoon at the news that singer Liam Payne, who became famous as a member of the group One Direction, died at age 31.

TMZ reports that Payne fell from a hotel balcony in Argentina, where he had reunited with bandmates at 1D-er Niall Horan’s concert. He had, according to the site, been behaving “erratically,” earlier in the day, and was spotted smashing a laptop in the hotel lobby and having to be carried back to his room. He had been in headlines on gossip blogs over tension with his ex-fiancée Maya Henry, who, TMZ says, alleged “he'd left her after asking her to get an abortion.”

In the shock of his death, fans couldn’t ignore the eerie nature that Payne had just connected with his One Direction bandmates. Dark questions emerge when a celebrity dies so young: What role did the often horrific toll of fame have on a person like Payne, who has been open about addiction and suicidal ideation? But there’s also an impulse to go back to the roots of a person’s talent, to revisit what it was that we all fell in love with—and was their passion—in the first place.

Read more at The Daily Beast.

In a contentious interview with Democratic presidential nominee Kamala Harris, Fox News host Bret Baier spent no time going after the vice president with a laundry list of the subjects often highlighted by former President Donald Trump on the campaign trail.

Immediately after the interview kicked off, Baier opened by asking: “How many illegal immigrants would you estimate your administration has released into the country over the last three and a half years?”

Harris began a carefully worded answer, but Baier consistently interrupted her before she could finish a sentence.

Read more at The Daily Beast.

Prior to his untimely death in Argentina on Wednesday, One Direction’s Liam Payne, 31, was in the middle of a legal spat with his ex-fiancée Maya Henry.

On Monday, The Sun reported that Henry, 23, had lawyered up in an attempt to stop Payne from constantly messaging her family and friends.

“Maya Henry issued a cease and desist last week to Liam Payne following the emergence of new and concerning information…She has retained attorneys Marco Crawford and Daniel Cerna to represent her. At this time, that is her only comment on the matter,” a spokesperson for Henry told the tabloid.

Read more at The Daily Beast.

Republican vice presidential candidate JD Vance boldly said “no,” Donald Trump did not lose the 2020 election, when pressed on the issue at a campaign event Wednesday in Williamsport, Pennsylvania.

The Ohio senator has avoided directly denying the results over the past few weeks.

When quizzed by The New York Times about the results over the weekend, for example, he refused multiple times to answer the question, on one occasion claiming he was “focused on the future”—echoing an answer he gave to Democratic opponent Tim Walz at the vice presidential debate.

Read more at The Daily Beast.

The Real Housewives of Salt Lake City is TV’s best soap opera, week after week offering twists more shocking than secret twins and characters returning from the dead. That’s because it’s all real, happening in the most haunted suburb in the continental United States.

Where else do two women connect over knowing the long-lost birth father of one’s child? Is there another city where women squabble over body positivity in a parking lot off the side of a snowy mountain? Surely, there’s no other place on Earth where Lisa Barlow could come across anywhere near a voice of reason.

But that all happens here in Salt Lake City. Five episodes in, Season 5 has continued to evolve into the most captivating season in modern Real Housewives history, carried by the ever-changing bonds between our OGs and a team of wonderfully bizarre newbies.

Read more at The Daily Beast.

MSNBC’s Chris Hayes called out Fox News for not showing the full context of Donald Trump’s “enemy within” comments during Vice President Kamala Harris’ interview on the network earlier Wednesday.

The anchor of All In opened his broadcast by calling attention to something that Harris herself did in the sit-down with Fox’s Bret Baier. The clip that the right-wing network showed to Harris as part of Baier’s question was of Trump during his all-female town hall event in Georgia—the one where Trump bizarrely argued he was the “father of IVF.”

In the clip that Fox aired directly to Harris during her interview, Trump wasn’t heard talking about how former House Speaker Nancy Pelosi or Rep. Adam Schiff are the “enemy within.” Instead, Fox made it so Harris had to react to him talking more mildly about “phony investigations.” The network omitted Trump’s line about “the enemy within.”

Read more at The Daily Beast.

Liam Payne was seemingly having a “lovely day in Argentina” just hours before his death on Wednesday, according to what appear to be a series of final posts made to his Snapchat account.

The former One Direction member was found dead in the courtyard of a Buenos Aires hotel, having apparently plunged 13 to 14 meters from his balcony, according to local police. A cause of death has not officially been determined, and it was unclear whether the fall was accidental or intentional.

On his Snapchat Story, however, it would have appeared to any fan that Payne was having a relaxing vacation. In since-deleted posts in the hours before his death, he posted a front-facing video in which he told followers, “It’s a lovely day here in Argentina. This is the breakfast table. Just enjoying coffee and breakfast even though it’s 1 p.m.”

Read more at The Daily Beast.

Former President Donald Trump said Wednesday that Jan. 6, 2021— the day his supporters occupied Congress in a failed insurrection to try to stop lawmakers from certifying Joe Biden’s election victory—was a “day of love.”

Trump made the baffling claim during a televised election town hall hosted by Univision.

Ramiro González, a construction worker from Tampa, told the meeting he deregistered as a Republican because he found Trump’s “inaction” during both Jan. 6 and the COVID-19 pandemic “disturbing.” He asked Trump to square his controversial behavior during the attack on the U.S. Capitol—and the fact that many of his own former administration officials don’t support him any longer—with why he should be re-elected.

Read more at The Daily Beast.