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The governor offered a gentle rebuke to protesters: You're not helping.

Indiana Gov. Eric Holcomb's responsibility and obligation is to the citizenry of Indiana, a letter to the editor says.

Indianapolis Mayor Joe Hogsett strained to embody unity Thursday at a time when it would have been easy to perceive friction.

Gov. Eric Holcomb's plan to reopen Indiana puts the burden on individuals instead of government.

Shady Habash, whose video mocked the president, "mistook hand sanitiser for water", prosecutors say.

By Linda Skidmore BSN RNSenior ManagerNorth Lake College Health Services We’re getting a lot of...

Khalil Mack has helped turn the Bears into a solid commodity in the betting market.

Six teams are on a bye this week, giving stars like Saquon Barkley, Odell Beckham Jr., Andrew Luck, Zach Ertz and A.J. Green the week off. Here are three players that could have big games in their stead.

Atlanta is on a five-game losing streak but their offense is scoring 2.3 points per drive in 2018, the fifth-highest rate in the NFL. That should be more than enough against Arizona's awful offense.

The reality TV star wrote that she and her husband, real estate developer Michael Darby, are "savoring every moment."

The former first daughter and her spouse welcomed a son on Monday.

The NBC personality introduced baby Henry Harold to the world on Monday.

Discover the 10 things that you should never do on a cruise ship balcony. Some of them are rules from the cruise line, which if you break you could find yourself thrown off your cruising vacation (or even banned by the cruise line for life!). Some are things that will make your and the other cruisers around you have a more enjoyable cruise. And some even could save you a lot of embarrassment....

** Buy my Cruise T-shirts: http://bit.ly/TFTStore
** USA cruisers get great cruise deals CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise
** UK Cruisers get great cruise deals with CRUISE.CO.UK: http://bit.ly/BookCruiseUK

Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises.

Follow Tips For Travellers on:
- Instagram: http://www.instagram.com/garybembridge
- Facebook: http://www.facebook.com/tipsfortravellers
- Twitter: http://www.twitter.com/garybembridge

I am not suggesting, or recommending, you should sneak booze on your next next cruising vacation as you could, in worst case, risk being refused boarding if caught. However despite this, there are cruisers who use surprising and unusual techniques to smuggle alcohol on to a cruise ship to avoid having to buy drinks on board. In this video I explore the different ways that people are using to sneak their alcohol onto their cruise ship. The cost of drinking on a cruise is increasing, and with some of the drinks packages you could be spending almost as much as the cruise itself costs and some travellers are resorting to innovative methods to bring their own alcohol onto cruise ships. There are even companies making products, devices and accessories specifically designed to assist.

Amino Communications will showcase at TelcoTV 2012 in Las Vegas a new breakthrough version of its Live media gateway that delivers a powerful combination of pay-TV security and exciting Android-based OTT content delivery.

The Live media gateway is the first hybrid/OTT media gateway to be powered by the new Intel Atom CE 5300 media processor. This combines dual core processing power with a range of new enhanced transcoding and encoding capabilities with multi-screen distribution to deliver content seamlessly to TVs, smartphones and tablets around the home.

Now the product has been enhanced – with a secure Linux environment, based on Amino’s proven Aminet software stack, for the delivery of payTV video, and a controlled Android virtual machine to support a wide range of OTT applications and services. The device will utilise the unparalleled hardware virtualisation features available in the Intel CE5300 SoC to run multiple virtual machines at full speed.

TVover.net and Echo Communications are giving away 2 free Expo passes to TelcoTV 2012, Ocotber 24-26, 2012 in Las Vegas, NV, USA. The Expo pass gives you access to Exhibit Hall, Keynotes, and Vendor-Hosted Workshops. For mroe information about TelcoTV 2012 and registration, click here.

Enter to win by emailing us at media@tvover.net with subject line 'TelcoTV 2012 raffle', name, email, company, address and phone number by noon CST, October 21, 2012. The winner will be randomly drawn.

TelcoTV released a preview of results from the annual Heavy Reading State of the Video Consumer Survey. Complete findings from the 2012 survey will be presented at the TelcoTV Conference and Expo taking place October 24 to 26, 2012 at the Las Vegas Hotel, Nevada. Aditya Kishore, Senior Analyst, Heavy Reading will present the findings during his keynote address on Wednesday, October 24, 2012.

Heavy Reading’s highly anticipated State of the Video Consumer Survey, now in its fifth year, is an annual report that reveals consumer opinions about video consumption across device platforms, provider perceptions and satisfaction levels with video services. In years past, it has proven to be a valuable planning tool for any organization serving the video distribution marketplace.

Several factors were key in this northeastern Kansas telephone company's decision to choose APMAX IPTV middleware from Innovative Systems. However, according to Tri-County Telephone Association's General Manager, Dale Jones, putting the customer experience first above everything else was their main goal in making the decision.

Jones stated, "The capabilities that the Innovative solution gives us to reach out and touch the customer from our back office to help them over the phone is critical in the customer experience. Without having to send out a service technician, which takes time and costs more, we are helping our customers in a timely manner and reducing our own operating costs."

Jones likes the fact that Innovative Systems is continually growing their products with new features to help the rural telco market stay on top of a very competitive market. Jones advises other telcos to look to companies that are thinking outside the box especially when it comes to video. Jones says, "Today's business is nothing like it was in the past, if you are going to attract and retain video customers you have to give them the technology that is going to drive that experience."

Public officials today could take a lesson from the former Federal Reserve chair.

While the birds are is still listed as endangered in Canada and Alberta, the population has experienced a comeback in recent years.

We’ve been teaching people how to do remote work well for the better part of two decades. We wrote a whole book about the topic in 2013, called REMOTE: Office Not Required. Basecamp has been a remote company since day one, and our software is sold as an all-in-one toolkit for remote work. Yeah, we’re… keep reading

Restaurants have been struggling to stay afloat since the pandemic hit, but there has been a silver lining: relaxed liquor laws mean customers can get their booze delivered along with their meals.

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

Jeffrey C. Silva
Jan 1, 2006; 5:144-156
Research

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

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.

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.