En Caracol Radio estuvo Dilian Francisca Toro, gobernadora del Valle del Cauca

Paula Ximena Henao, directora del Cuerpo Bomberos de Bogotá aseguró en 6AM que los ciudadanos deben tomar medidas para evitar nuevas conflagraciones que afecten los cerros orientales de la capital del país

Montana not only went enthusiastically for Trump for a third time, but took the last statewide seat held by a Democrat. Senator Jon Tester's defeat caps a years-long quest to erase purple from Montana's map.

A stars-bound journey away from the drudgery of everyday ordinariness.

Two reckless initiatives headed for the November ballot, 50 and 108, would gut the resources needed to pay firefighters, recruit and retain volunteers, buy equipment, and respond quickly when you call.

Playing video games has long been a challenge for many people with disabilities, since the traditional controllers for the PlayStation, Xbox or Nintendo can be difficult or even impossible to maneuver when a person has limited mobility. Losing the ability to play doesn’t just mean the loss of a favorite pastime — it can also exacerbate social isolation for a community that already experiences it at far higher rates than the general population. Sony’s new Access Controller, developed with input from accessibility consultants, aims to change that.

Is that a tortilla in your pocket, Travis Hunter? Or are you just happy for CU?

Skyport has introduced an “advanced wildlife control measure” at the airport which “aims to mitigate bird-related safety hazards during critical flight operations such as landing and take-off.” A spokesperson said, “Skyport Facilities and Asset Management is delighted to announce the introduction of an advanced wildlife control measure designed to enhance the Wildlife Management Program at […]

Clarien Bank Limited announced that, pending regulatory approvals, Cornerstone Financial Holdings Ltd or its nominee, will acquire a controlling interest in Clarien Group Limited [CGL]. A spokesperson said, “Clarien Bank Limited [the Bank /Clarien], a leading financial institution on the Island, is pleased to announce that, pending regulatory approvals, Cornerstone Financial Holdings Ltd [Cornerstone] or […]

The Regulatory Authority has approved the change of control of Saturn Solar Bermuda 1 Ltd. to FB Solar, LLC. A statement from the RA said, “In accordance with the Electricity Act 2016, and upon the consent of the Minister of Home Affairs, the Hon. Walter H. Roban, JP, MP, the Regulatory Authority [the RA] has […]

The United Autoworkers (UAW) is on a new campaign. The union plans to organize workers in hither-to non-union foreign-owned automobile plants in the United States. This campaign may or may not work, but in the long run it will prove futile unless the union can compete in the international market, against all international auto workers.

There are 575,000 autoworkers in the U.S. Nearly 20% work for foreign-owned plants. All of these plants are non-union. The foreign-owned plants were intentionally placed in right-to-work areas, many in the South.

The UAW is likely to have some difficulty succeeding with this campaign. The non-union workers already earn highly competitive wages and benefits. To date, these U.S. workers in plants owned by Toyota, Volkswagen, Hyundai and Honda have shown little interest in unionization.

Why would the union be so interested in this initiative? To preserve its membership. The traditional problem with unions is less the rate of wages they demand and more about the work rules they impose. These work rules reduce the productivity of the unionized plants. That has certainly been the case in the U.S. auto industry. As a result, the UAW is losing membership as UAW auto plants in the U.S. close under the onerous costs the UAW plants carry. If the union can succeed in unionizing the domestic foreign-owned auto plants to the same extent they have unionized the domestic manufacturers’ plants, they will be able to impose the same work rules and produce roughly the same productivity. The result should, in the union’s eyes, be a reduction in the rate of jobs lost in the union.

But there is a problem here. The UAW has already seen that it was unable to stop new non-union plants in the U.S. How will it stop future non-union domestic plants? O.K., let’s say they can do that. Will they also be able to stop all foreign non-union plants from becoming established and growing? Certainly not. Unless the union membership can compete on an international basis with competitive costs and productivity, this unionization effort is wasted money. If it succeeds, the U.S. loses more plants to plants located offshore. Union membership still falls.

It seems that one of the problems for unionized employees is one of definition. Union members often call their compatriots in competing companies “brothers and sisters.” These are certainly not brothers and sisters. In a marketplace they are competitors. Union employees have to be able to beat, or at least stalemate, these competitors or lose their jobs. This is true as long as the UAW can not control the entrance of other less expensive competitors, either in the U.S. or elsewhere.

The long history of the DRAM semiconductor market illustrates this. The U.S. manufacturers of DRAM semiconductors faced intense competition from the Japanese in the 1980s. The domestic industry succeeded in slowing the Japanese by using the International Trade Commission. Then arose new and equally troublesome problems. These problems were DRAM semiconductor facilities in Taiwan and Korea. Eventually, the U.S. industry evolved to the point where it had only one domestic producer of DRAM chips. Intel was one of the early competitors to get out of that market to focus its resources in the more complex, and much more profitable, domestic micro-processor business. SX4MBURBCAJQ

"We Must Do Whatever It Takes!" - Netherlands Reinstates Temporary Border Controls To Curve Illegal Immigration Authored by Thomas Brooke via Remix News, The Netherlands has announced it will reintroduce internal border checks starting Dec. 9 in fresh efforts to manage illegal immigration. The…

Blog Creation for Link Building In the effort to create links for back link profiles and more results, individuals and companies have resorted to tactics of duplicate profile creation, multiple fake profiles and an unsurpassed amount of blog sites with little or no use to anyone looking to gain valuable information. Some examples are WordPress […]

The Coast Guard Exchange has the Spider-Man DualSense controller for $49.99. Also the Spiderman Ps5 bundle is $479. No sales tax. Only available for those active duty, retirees, veterans, and their dependents. 

https://shopcgx.com/electronics-en-2/featured-brands-en/sony/ps5-dualsense-wireless-controller-spiderman2-lmtd-ed-new-age-8-1-23.html

https://shopcgx.com/electronics-en-2/featured-brands-en/sony/ps5-disk-spiderman-2-slim-bundle-d-and-h-10-13-23.html

Photo by Reproductive Health Supplies Coalition The Biden-Harris administration’s proposed rule to expand access to affordable contraception under the Affordable Care Act (ACA) is a timely and essential move, especially in the current political landscape where reproductive rights have been systematically eroded. This proposal would provide over-the-counter birth control without any cost sharing for women with […]

The post Expanding Birth Control Access as the New Front in Reproductive Freedom appeared first on Feminist Majority Foundation.

An ongoing campaign is targeting npm developers with hundreds of typosquat versions of their legitimate counterparts in an attempt to trick them into running cross-platform malware. The attack is notable for utilizing Ethereum smart contracts for command-and-control (C2) server address distribution, according to independent findings from Checkmarx, Phylum, and Socket published over the past few

We all know the struggle – sometimes, no matter how hard we hit the gym or watch our diet, there’s that stubborn tummy bulge that just won’t budge. But don’t worry, we’ve got your back (or should I say, your front?)!  Today, we’re diving into the world of tummy control shapewear, those magical pieces that ... Read more

The post Enhance Your Silhouette: The Top Picks for Best Tummy Control Shapewear appeared first on Star Two.

As wildfires escalate in Western states, authorities are embracing once-outlawed burning practices.

7-minute video shows you how to use the Repeat Signage designer screen to insert controls, e.g. picture control, to create flexible, dynamic, digital signage presentations for display screens.

Passengers who bug airline staff by breaking boarding protocol will be met with an alarm

Thousands of people have been evacuated from their homes in Ventura County, near Los Angeles.

The tales of New York City's rats are legendary. NY Rats are big and smart, and they have lots of babies. The city has a rat czar and recently held a rat summit to discuss the issue. Mayor Eric Adams was undoubtedly happy to talk about the rat problem rather than his own issues. — Read the rest

The post New York feeding rats tasty birth control appeared first on Boing Boing.

Republicans have solidified their control of Washington by retaining control of the House of Representatives. President-elect Donald Trump’s overwhelming victory in the presidential race, coupled with GOP control of the […]

The post Breaking: Republicans Retain Control Over House of Representatives, Handing Trump the Keys to His Agenda appeared first on The Western Journal.

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.

MS Brown
Jul 1, 1980; 21:505-517
Reviews

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews

Expert

The synthesis of cholesterol requires more than 20 enzymes, many of which are intricately regulated. Post-translational control of these enzymes provides a rapid means for modifying flux through the pathway. So far, several enzymes have been shown to be rapidly degraded through the ubiquitin–proteasome pathway in response to cholesterol and other sterol intermediates. Additionally, several enzymes have their activity altered through phosphorylation mechanisms. Most work has focused on the two rate-limiting enzymes: 3-hydroxy-3-methylglutaryl CoA reductase and squalene monooxygenase. Here, we review current literature in the area to define some common themes in the regulation of the entire cholesterol synthesis pathway. We highlight the rich variety of inputs controlling each enzyme, discuss the interplay that exists between regulatory mechanisms, and summarize findings that reveal an intricately coordinated network of regulation along the cholesterol synthesis pathway. We provide a roadmap for future research into the post-translational control of cholesterol synthesis, and no doubt the road ahead will reveal further twists and turns for this fascinating pathway crucial for human health and disease.

Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2–AKT signaling. We observed for the first time a cooperation between different AKT isoforms and focal adhesion kinase (FAK)–dependent adhesion signaling, which either controlled GSIS or prevented insulin secretion under fasting conditions. Indeed, β-cells form integrin-containing adhesions, which provide anchorage to the pancreatic extracellular matrix and are the origin of intracellular signaling via FAK and paxillin. Under low-glucose conditions, β-cells adopt a starved adhesion phenotype consisting of actin stress fibers and large peripheral focal adhesion. In contrast, glucose stimulation induces cell spreading, actin remodeling, and point-like adhesions that contain phospho-FAK and phosphopaxillin, located in small protrusions. Rat primary β-cells and mouse insulinomas showed an adhesion remodeling during GSIS resulting from autocrine insulin/IGF2 and AKT1 signaling. However, under starving conditions, the maintenance of stress fibers and the large adhesion phenotype required autocrine IGF2-IGF1 receptor signaling mediated by AKT2 and elevated FAK-kinase activity and ROCK-RhoA levels but low levels of paxillin phosphorylation. This starved adhesion phenotype prevented excessive insulin granule release to maintain low insulin secretion during fasting. Thus, deregulation of the IGF2 and adhesion-mediated signaling may explain dysfunctions observed in diabetes.

Stacey N Keenan
Dec 17, 2020; 0:jlr.RA120001126v1-jlr.RA120001126
Research Articles

Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, α-β hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism, such as fatty acid oxidation, de novo lipogenesis and triglyceride secretion. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism

S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.

Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair.

Who says neuroscience can’t be fun? The toy giant Mattel makes Mindflex, a toy that lets players control a ping pong ball with their brain waves. I wrote about the toy way back in 2009, and was surprised to find it was still selling. It seemed like a gimmick when introduced, and I didn’t expect […]

The post Mattel Mindflex Game: Brain-controlled Neuro-Toy appeared first on Neuromarketing.

Abnormal neuronal morphological features, such as dendrite branching, axonal branching, and spine density, are thought to contribute to the symptoms of depression and anxiety. However, the role and molecular mechanisms of aberrant neuronal morphology in the regulation of mood disorders remain poorly characterized. Here, we show that neuritin, an activity-dependent protein, regulates the axonal morphology of serotonin neurons. Male neuritin knock-out (KO) mice harbored impaired axonal branches of serotonin neurons in the medial prefrontal cortex and basolateral region of the amygdala (BLA), and male neuritin KO mice exhibited depressive and anxiety-like behaviors. We also observed that the expression of neuritin was decreased by unpredictable chronic stress in the male mouse brain and that decreased expression of neuritin was associated with reduced axonal branching of serotonin neurons in the brain and with depressive and anxiety behaviors in mice. Furthermore, the stress-mediated impairments in axonal branching and depressive behaviors were reversed by the overexpression of neuritin in the BLA. The ability of neuritin to increase axonal branching in serotonin neurons involves fibroblast growth factor (FGF) signaling, and neuritin contributes to FGF-2-mediated axonal branching regulation in vitro. Finally, the oral administration of an FGF inhibitor reduced the axonal branching of serotonin neurons in the brain and caused depressive and anxiety behaviors in male mice. Our results support the involvement of neuritin in models of stress-induced depression and suggest that neuronal morphological plasticity may play a role in controlling animal behavior.

Some business owners in Charlottetown have made suggestions for increasing the city’s housing supply, but not everyone is happy with their recommendations when it comes to rental properties.

COSMOS wins readers' nod in software and information integration category

Names SolidWorks Corporation's suite of COSMOS design analysis software one of the top innovations of 2004

A woman recommits her life to God as a result of His provision through the team and a visit they hadn’t even planned to do.

In the spirit of Women’s Month in August, Tamryn Lamb, head of retail distribution at Allan Gray, shares a few lessons she has learnt over the years to help other women to take control of their finances.

Voice assistants (VAs) like Alexa and Siri continue to gain popularity in households and on personal devices. According to digital trends research company Emarketer, the number of VA users will surpass 150 million in 2025. Despite the ubiquity, companies haven’t been able to work around users’ strong negative reactions to advertising on these applications. A research team, including scholars from Penn State, may have a solution.

Patients like it more when "AI doctors" recall their social information and offer privacy control, according to a new study led by Penn State researchers.

Delaware Secretary of State Jeff Bullock has placed xylazine, also known as “Tranq”— a non-opioid drug used primarily in veterinary medicine—in Schedule III of the Uniform Controlled Substance Act. Tranq has been used increasingly as an additive in opioid abuse to create a “zombie-like” condition for users. Secretary Bullock’s actions follow a recommendation from the […]

The Delaware Forest Service plans to conduct a 48-acre controlled burn in the City of Lewes on Friday, April 23, beginning around mid-morning. Residents and visitors in the area might see smoke and should not be alarmed. The 48-acre site is primarily coastal marsh with phragmites and other vegetation. The purpose of the burn is to reduce hazardous fuel buildup and restore native marsh habitat. The area was last burned in 2008. The area has been treated several times over the past ten years to control phragmites, (Phragmites australis), which outcompetes native vegetation and lowers the local plant biodiversity.

The Delaware Department of Natural Resources and Environmental Control is working with the Delaware Department of Agriculture to execute a controlled burn at Brandywine Creek State Park in February or March. This prescribed burn will help manage nearly 30 acres of meadowland near the park’s nature center.

DOVER, DE (MAY 9, 2022) – The Delaware Division of Public Health’s (DPH) Diabetes & Heart Disease Prevention & Control Program (DHDPC) and the Delaware Diabetes Coalition are co-sponsoring the 20th Annual Diabetes Wellness Expo on May 10, 2022, at the Delaware State Fairgrounds in Harrington, Delaware. The event is free to the public and will be […]