Title: Gene Therapy Makes Inroads Against a Form of Hemophilia
Category: Health News
Created: 7/22/2022 12:00:00 AM
Last Editorial Review: 7/22/2022 12:00:00 AM

Mapping transcriptomic variations using either short- or long-read RNA sequencing is a staple of genomic research. Long reads are able to capture entire isoforms and overcome repetitive regions, whereas short reads still provide improved coverage and error rates. Yet, open questions remain, such as how to quantitatively compare the technologies, can we combine them, and what is the benefit of such a combined view? We tackle these questions by first creating a pipeline to assess matched long- and short-read data using a variety of transcriptome statistics. We find that across data sets, algorithms, and technologies, matched short-read data detects ~30% more splice junctions, such that ~10%–30% of the splice junctions included at ≥20% by short reads are missed by long reads. In contrast, long reads detect many more intron-retention events and can detect full isoforms, pointing to the benefit of combining the technologies. We introduce MAJIQ-L, an extension of the MAJIQ software, to enable a unified view of transcriptome variations from both technologies and demonstrate its benefits. Our software can be used to assess any future long-read technology or algorithm and can be combined with short-read data for improved transcriptome analysis.

Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.7 compared with vehicle 0.3 ± 0.1 (P = 0.01) as determined by tissue mass spectrometry imaging analysis. We hypothesized that increased plasma and kidney levels of IDS could be caused by the simultaneous inhibition of both Slc6a19 and a kidney IDS transporter responsible for excretion of IDS into urine. To test this, we first confirmed the formation of IDS through tryptophan metabolism by feeding rats a Trp-free diet. Inhibiting Slc6a19 with RA836 led to increased IDS in these rats. Next, RA836 and its key metabolites were evaluated in vitro for inhibiting kidney transporters such as organic anion transporter (OAT)1, OAT3, and breast cancer resistance protein (BCRP). RA836 inhibits BCRP with an IC₅₀ of 0.045 μM but shows no significant inhibition of OAT1 or OAT3. Finally, RA836 analogs with either potent or no inhibition of SLC6A19 and/or BCRP were synthesized and administered to rats fed a normal diet. Plasma and kidney samples were collected to quantify IDS using liquid chromatography–mass spectrometry. Neither a SLC6A19 inactive but potent BCRP inhibitor nor a SLC6A19 active but weak BCRP inhibitor raised IDS levels, whereas compounds inhibiting both transporters caused IDS accumulation in rat plasma and kidney, supporting the hypothesis that rat Bcrp contributes to the excretion of IDS. In summary, we identified that inhibiting Slc6a19 increases IDS formation, while simultaneously inhibiting Bcrp results in IDS accumulation in the kidney and plasma.

The PlayStation 5 was the best-selling console in the UK in October, according to GfK Entertainment data reported by GamesIndustry. 

The Xbox Series X|S was the second best-selling console for the month, followed by the Nintendo Switch in third. The Xbox Series X|S has also surpassed the Switch in year-to-date sales.

Sales for the PS5 are up 27 percent month-on-month and down 18 percent year-on-year. Sales for the Switch are up 13 percent month-on-month and down 18 percent year-on-year. Sales for the Xbox Series X|S are down seven percent month-on-month and down 17 percent year-on-year. 

Overall, there were just under 144,000 video game consoles sold (NielsenIQ/GfK panel data) in the UK in October 2024. This is down 18 percent year-on-year.

GSD data shows there were 2.9 million games sold in October 2024, which is up 3.2 percent year-on-year. 

Call of Duty: Black Ops 6 debuted in first place on the software charts (digital and physical combined). Sales are 11 percent lower than the launch month of 2023's 2023's Call of Duty: Modern Warfare III, however, this is most likely due to the number of people playing the game via Xbox Game Pass.

Sales of Call of Duty: Black Ops 6 are up 24 percent year-on-year on PlayStation consoles, while sales dropped on Xbox consoles and PC. 75 percent of total sales were on PlayStation consoles, followed by 15 percent on PC, and just under 11 percent on Xbox consoles.

Dragon Ball: Sparking! Zero debuted in third place with the first four week of sales up 80 percent compared to 2020's Dragon Ball Z: Kakarot.

Undisputed debuted in fourth place and had the second biggest launch for a sports title in 2024. Only EA Sports FC 24 had a bigger launch.

The remake of Silent Hill 2 debuted in fifth place. Launch sales are 32 percent lower than the remake of Dead Space and 62 percent lower than the remake of Resident Evil 4.

Super Mario Party Jamboree debuted in ninth place. Sales are 11 percent higher than 2018's Super Mario Party, but are four percent lower than 2021's Mario Party Superstar. It should be noted Nintendo doesn't share digital sales with these charts.

Sonic X Shadows Generations debuted in 10th place. Sales for the game are 150 percent compared to 2023's Sonic Superstars, but are down 21 percent compared to 2022's Sonic Frontiers.

Metaphor: Refantazio debuted in 12th place and the new version of Until Dawn debuted in 30th place.

EA Sports FC 25 came in second place with sales down 14 percent year-on-year.

There were over 681,000 accessories and add-on products sold in the UK in October, which is up nearly 16 percent year-over-year, but is down over eight percent month-on-month.

The White DualSense controller was the best-selling accessory, followed by the Midnight Black DualSense controller. The PlayStation Portal Remote Player is up four spots to take fourth place.

Here are the top 10 best-selling games in the UK (Digital + Physical):

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/463042/ps5-best-seller-in-the-uk-in-october-black-ops-6-leads-strong-month-of-new-releases/

In all honesty, Toads Of The Bayou could have been several notches less ribbet-ing than its Steam demo ended up being, because its stylised pixel fly-snatchers are just that good. There’s only one of the three characters available in the freebie (one of the others is a toad nun with a shotgun), but he’s got a little cutlass, a flintlock pistol, and a can-do attitude - at least when it comes to either stabbing or shooting things. The game itself is a little bit deckbuilder, a little bit Into The Breach: turn based strategy with perfect information and various tricks you can pull to make enemies hit each other instead of the thing you’re trying to protect. Indulge yourself on the gourmet tray-tray below.

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A 61-year-old San Antonio man pleaded guilty to two federal charges in the human smuggling incident that led to the deaths of 10 undocumented immigrants this summer.

James Matthew Bradley Jr., who appeared before a U.S. magistrate judge Monday, pleaded guilty to “one count of conspiracy to transport aliens resulting in death and one count of transporting aliens resulting in death,” according to a statement from the U.S. Attorney’s Office for the Western District of Texas.

The office added that Bradley’s “admission of guilt” meant he packed dozens of unauthorized immigrants into a tractor-trailer for financial gain, adding that the suspect confirmed that details from court documents were “factually correct.”

On July 23, San Antonio Police Department officers responded to a call from a Walmart employee shortly past midnight. Once officers arrived, they found 39 immigrants at the scene. Of those carried in the tractor-trailer, eight were found dead in the rear of the trailer, while two died later at nearby hospitals, the statement said.

Survivors of the incident said there was no air conditioning in the overheated trailer and had to take turns to breath through a hole in the back of the truck for air. Bradley also initially told investigators that he was unaware of the immigrants in the trailer until he had stopped at the Walmart in San Antonio for bathroom break.

The attorney’s office also said Bradley faces up to life in prison with the charges and that he is scheduled to be sentenced in January 2018. Immigrants said there were up to 200 people transported on the trailer and that different fees were quoted to them for the ride north from the U.S.-Mexico border, the statement added.

Jason Buch of San Antonio Express-News told the NewsHour earlier this year that Border Patrol agents in Laredo, Texas, reported an uptick of immigrants using tractor-trailers to get pass checkpoints at the border.

“People are usually going on to major metropolitan areas or regions of the country that employ a lot of immigrant laborers, so, areas with large agriculture industries or construction booms,” Buch said.

The NewsHour’s John Yang learned more about the July human smuggling case and immigration politics from Jason Buch of San Antonio Express News.

Shane M. Folden, special agent in charge of homeland security investigations in San Antonio, said in the statement that the proceeding “helps to close the door on one of the conspirators responsible for causing the tragic loss of life and wreaking havoc on those who survived this horrific incident.”

“This case is a glaring reminder that alien smugglers are driven by greed and have little regard for the health and well-being of their human cargo, which can prove to be a deadly combination,” he added.

Bradley’s co-defendant Pedro Silva Segura was also indicted last month with faces two counts of conspiracy and two counts of transporting undocumented immigrants resulting in serious bodily injury and placing lives in jeopardy.

Segura, 47, is an undocumented immigrant who resides in Laredo, Texas.

The post San Antonio truck driver pleads guilty in fatal human smuggling case appeared first on PBS NewsHour.

Ronnie O'Sullivan has agreed to compete in new snooker events.

Who Will Fill the Democratic Vacuum?

From the benefits of fermented foods to diets that promise a better hormone balance, there is a confusing array of dietary advice out there

The former soldier Daniel Khalife has changed his plea to guilty and admitted escaping from Wandsworth prison.

Wildfires have been raging in New York and New Jersey. People in some areas have been asked to prepare for possible evacuations.

Cloud-based business management software (CRM, ERP) can revolutionise an SME.

Destiny 2's digital success could spell long-term trouble for discs

The winter holidays are upon us and despite the festive feelings we might be hoping for, this time of year is often paired with increased stress, worry and anxiety. Fortunately, there are some great tools for helping to manage those negative emotions while promoting positive ones. One of those tools is the Headspace mental health app, which is running a three-week Black Friday deal. From November 12 through December 4, you can snag a Headspace annual plan for half off. This subscription normally costs $70 a year, but during this promotion, you can access the service for $35 billed annually. And what better time than the holiday chaos to gift someone (or heck, to gift yourself) a little bit of mindfulness?

Headspace's service has features to help users with meditation, sleep tools, mindfulness and general mental health. Its holistic approach made Headspace stand out as one of our top picks for meditation apps. Reviewer Lawrence Bonk appreciated how well Headspace created progression across its courses, as well as the chance to pick from different instructors so that any user can find the meditation guidance that will work best for their individual brains. This app is also getting the AI treatment. Headspace has introduced an AI companion named Ebb that can help users by recommending meditations and activities to best match their current challenges. 

Since this is a year-long subscription, it's a gift that keeps on giving for whoever you choose to buy this plan for. Having a happier brain is a present anyone can appreciate.

Follow @EngadgetDeals on Twitter and subscribe to the Engadget Deals newsletter for the latest tech deals and buying advice.

Beyoncé leads the 2025 Grammy Award nominations with 11, bringing her career total to 99 nominations. That makes her the most-nominated artist in Grammy history.

Jardiance is a popular drug used to treat type 2 diabetes and help reduce cardiovascular risk. DTC campaigns […]

Apr 18, 2024

This was originally published in The Hill on April 18, 2024.

Get mortgage help. This is why. MakingHomeAffordable.gov :60

PANDORA Jewelry showed festival goers how to style braided leather bracelets to get #FESTIVALready for Coachella

Turtle Beach Reveals the All-New Elite Pro

World-renowned doctor heads neurosurgery clinic at European Medical Center

Knifedads and youtube celebrities Karate Johnathan and Steeliest Daniel train the Appleton County High Security Elementary School on resisting drugs and witchcraft.

This week, I want to talk about corporations using global tragedy to “get their brand name out there” and otherwise profiteer off of human misery.

The release of Apple’s mixed-reality headset raises questions about hours spent in a virtual replacement of our world

A new technique to make electronic fibers could help solve wearable technology’s flexibility problem

In this week’s podcast episode, we’re looking at the glorious  ads and features for the October/November 1988 issue of RT Magazine. Thank you to Amy M. for this issue! You can also find all the RTRW content at our category page for Romantic Times Rewind.  If you want to listen and follow along with this entry, we have more detail in the audio, but you can click play and listen and read and absorb all … Continue reading Romantic Times Rewind: October 1988 Ads & Features →

It’s time for the Ads & Features of the October 1988 (!!) issue of Romantic Times Magazine. Y’all. We’ve got: Vintage gossip! Blind items that are very easy to guess! Danielle Steel’s two blue Mercedes! Fuchsia covers with giant flowers and startled animals! Riverboat gambler romance heroes! And a truly paltry obituary for an extraordinary author. It’s 1988. Fuchsia. So much fuchsia. Blanket content warning for romances written in the late 80s. Be ready for … Continue reading 637. RT Rewind October 1988 Ads & Features →