The Northern Territory Government is trying something new to entice remote school students back to class at the start of Term 3 just in time for the head-count that determines how much school funding comes from Canberra.

A year after her murder, Toyah Cordingley's name still hangs in shop windows, on posters strung up on trees, and stickers on car bumpers in nearly every street in Cairns.

(United States Ninth Circuit) - Reversed the dismissal of a shareholder class action against Toshiba Corp. filed by investors who alleged securities fraud. The district court dismissed their claims on jurisdictional grounds and, on appeal, the plaintiffs argued that the district court misapplied principles regarding extraterritorial applicability of U.S. securities laws set forth in Morrison v. Nat'l Australia Bank Ltd., 561 U.S. 247 (2010). The Ninth Circuit agreed with plaintiffs and reversed and remanded with instructions to allow the plaintiffs to amend their shareholder complaint against the Japanese firm to overcome the jurisdictional hurdle.

(United States Sixth Circuit) - In a trademark and trade dress infringement suit filed against a toy company by GMC involving a series of toy vehicles resembling GMC's Hummer, summary judgment for GMC is affirmed where: 1) despite the district court's failure to adequately discuss the Frisch factors, summary judgment was appropriate on the trademark infringement claim due to the weight of the factors in favor of a finding a likelihood of confusion; 2) GMC established that there were no material issues of fact as to any of the three elements of trade dress infringement; and 3) denial of summary judgment on laches and estoppel defenses was proper.

The Broncos had five picks among the top 95 selections in the NFL draft, and director of football operations John Elway couldn’t find a single prospect at offensive tackle worth taking? If Garett Bolles or Elijah Wilkinson is the answer at left tackle, the real question is: Can quarterback Drew Lock stay healthy for 16 regular-season games?

LeToya Luckett wouldn’t date a man who wears makeup.

Did Trina just cheat on Kevin?

Tune in to Lift Every Voice at 10A/9C on Sunday!

She lost her siblings to a grisly crime in 2016.

“Even after weeks of staying home, my kids are just not interested in all the stuff we have. Let’s be honest. If a toy isn’t getting any action amid this distraction-free, stuck-at-home living, chances are it’s never getting touched again.” Liz Russell figures out what really engages and changes kids during the quarantine, and will […]

2019.9.15うす塁斗どうも富山公演終えたんだよ！今日もいい公演でした(^ ^)楽しいいい雰囲気の会場でしたそう富山！めっちゃ癒される街並みとか水美味いしなんかいいし綺麗だしそうそうたぶんまた来たいランキングトップ3には入った！(^^)北海道民としてはなんか街のとかの感じが少し似てて親近感とともにだいぶ好き(^^)そうそう急いでパッキングしたキャリーケースを開けて気づいた事があった稽古着のリハ着のパンツがない！！！事がわかった！でも、大丈夫！ハーフパンツがある！それでの続きをみる

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Gerson Monje holds up his cellphone to proudly show off his online sex shop. A red banner reading "sold out!" is plastered across half of the products.

Her résumé also includes "Brave," "The Book of Life," "Elf," and an eight-year stint as a layout artist during the Disney Renaissance.

The post RIP Denise Blakely Fuller, Matte Painter On ‘Toy Story 3,’ ‘The Book Of Life,’ ‘Hotel Transylvania’ appeared first on Cartoon Brew.

All-Star hitter helped the Dodgers reach the World Series in 1974.

If sex-toy sales are any indication, people are seeking sexual pleasure during this anxiety-fraught period of extended social isolation.

From sex-coach apps to teledildonics, options for sexual intimacy are right at your fingertips

No other studio has more than three wins in the category; no other franchise has collected two.

Toyota has recalled millions of hybrid gas-electric cars, mostly Prius models, around the world to fix electronic defects.

A jury ordered Toyota to pay $15.8 million to a dealer who alleged the company's recalls failed to remedy safety defects in its popular Prius models.

The 2020 Toyota Land Cruiser is a big lumbering luxury SUV.

Products for the popular character from the Disney Plus hit "The Mandalorian" are about to hit stores.

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If Instagram is to be believed, then self care for women basically amounts to face masks and daily affirmation apps.

Hot take: Sex toys are the ultimate self-care purchase.

Orgasms release oxytocin, the anti-stress hormone that gets you warm and fuzzy when cuddling, while dopamine, a neurotransmitter that regulates sleep, also makes an appearance. It stands to reason, then, that "I need to get laid" is a thing that actually makes sense to say when you're having a rough week. Read more...

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

David A. Mitchell
Jun 1, 2006; 47:1118-1127
Thematic Reviews

S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.

dlberek posted a photo:

dlberek posted a photo:

S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

Deanna L. Davis
Apr 1, 2020; 61:505-522
Research Articles

This week our host Scott Carey catches up with Sean Bradley and Dominic Preston fresh off the back of the International Consumer Electronics Show (CES) in Las Vegas.

Dom explains why he was surprised, both in a good and bad way, by the latest foldable screen technology and Sean talks about what is going on in the gaming laptop space, as Alienware looks to soften its image.

Then Dom talks about a piece of connected wood and the gang break down the big controversy from the show floor regarding a certain innovative dildo.

We are also announcing the sad news that the UK Tech Weekly Podcast will be going on an indefinite hiatus while we reassess our podcasting output. We would like to thank anyone that has taken the time to listen to us for these one hundred and twelve (112!) episodes and rest assured we will be back in some guise soon.

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Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis have not been well characterized in oligodendrocytes, the myelin-producing cells of the CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, and biochemical assays, we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we characterized sphingolipid production in isolated oligodendrocytes. We analyzed sphingolipid distribution and levels of critical enzymes and regulators in the sphingolipid biosynthetic pathway, with focus on the serine palmitoyltransferase (SPT) complex, the rate-limiting step in this pathway. During myelination, levels of the major SPT subunits increased and oligodendrocyte maturation was accompanied by extensive alterations in the composition of the SPT complex. These included changes in the relative levels of two alternative catalytic subunits, SPTLC2 and -3, in the relative levels of isoforms of the small subunits, ssSPTa and -b, and in the isoform distribution of the SPT regulators, the ORMDLs. Myelination progression was accompanied by distinct changes in both the nature of the sphingoid backbone and the N-acyl chains incorporated into sphingolipids. We conclude that the distribution of these changes among sphingolipid family members is indicative of a selective channeling of the ceramide backbone toward specific downstream metabolic pathways during myelination. Our findings provide insights into myelin production in oligodendrocytes and suggest how dysregulation of the biosynthesis of this highly specialized membrane could contribute to demyelinating diseases.

S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

This is a two part SOLIDWORKS tutorial to create an Afternoon Tea Ferris Wheel Toy. In Part 1 of this tutorial you can learn how to draw and create the parts for a moving Ferris Wheel. The decals for the design are available to download in the description below. The Afternoon Tea Food Accessories are also available to download to be used in Part 2 of the tutorial.

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The post Afternoon Tea Ferris Wheel Toy Blog Part 1 appeared first on SOLIDWORKS Tech Blog.

This is a two part SOLIDWORKS tutorial to create an Afternoon Tea Ferris Wheel Toy. In Part 2 of this tutorial you can learn how to assemble parts, and run a motion analysis to create a moving Ferris Wheel. The decals for the design are available to download in the description below. The Afternoon Tea Food Accessories are also available to download to be used in Part 2 of the tutorial.

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The post Afternoon Tea Ferris Wheel Toy Blog Part 2 appeared first on SOLIDWORKS Tech Blog.

For this SOLIDWORKS tutorial, you can follow to create a Goldfish shaped Cat Treat Toy ready for 3D printing. The DXF files for this tutorial are available to download from the blog below. You can also download and 3D print this design yourself as the STL files are also available to download.

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The post Cat Treat Toy Tutorial appeared first on SOLIDWORKS Tech Blog.

OM worker discovers unlikely friendships among a group of 'misfit toys' in North Africa.

The CPT1A p.P479L variant is common to northern aboriginal populations, leads to reduced enzyme activity, and may be associated with increased infant mortality rates.

The p.P479L variant is common in British Columbia First Nations with a coastal distribution correlated with regions of high infant mortality. Homozygotes display an altered acylcarnitine profile and are overrepresented in cases of sudden unexpected infant death in these areas. (Read the full article)

If you're looking for an economical and fuel-efficient hybrid vehicle for safe, reliable commuting, it's hard to beat the no-frills 2020 Toyota Corolla Hybrid.

The Japanese company is building the 'Woven City' in 2021, which will be used to test robotics, personal mobility, smart homes and artificial intelligence in a real-world environment populated by 2000 of its employees and researchers.