The versatile actor vaulted to international stardom after playing a police inspector in the 2008 film. Khan, 54, was adored in India despite not being a Bollywood heartthrob.

The Dodger Dog is not available at the ballpark right now, but the Dodgers will be distributing hot dogs from their ballpark.

A new four-legged trainee has joined the ranks of London Fire Brigade’s dog detectives

The journalist has plenty of space in Alabama, but it still gets lonesome. Luckily there's Larry McMurtry, Humphrey Bogart and Jerry Lee Lewis.

A DOG was thrown over a bridge into a river to drown in Romania during the coronavirus lockdown, an animal charity has revealed.

FLUFFY bedding, bowls of treats and a dog shammy awaited our Labrador, Tehya, when we rolled up at Dominoes holiday home in Stoke Gabriel, South Devon - and it wasn't too shabby for Tehya's two-legged friends either, having been luxuriously refurbished just a couple of years ago.

It was vintage Kamar Baldwin against Xavier

The Indianapolis Star is re-posting game stories from the 10-year anniversary of Butler's run to the 2010 NCAA championship game.

Ronald, not known as a shooter, breaks a long dry spell, and Willie Veasley follows with a 3 to push the Bulldogs over the Orange

Hayward scored eight of his 22 points in the closing six minutes, and Butler knocked off Kansas State 63-56 Saturday in the NCAA West Regional final.

The Bulldogs reached the title game with a 52-50 victory over Michigan State

Butler Bulldogs take Duke to the limit in the 2010 national championship game at Lucas Oil Stadium, capped but a famous missed shot

Brownsburg upended Plainfield on Dec. 7 but the Bulldogs will be missing a key player when the two teams meet in the Hendricks County finals.

These Indianapolis-area spots have some delicious sandwiches.

Celebrate National Hot Dog Day with loaded dogs that howl with flavor.

The Bulldogs reached the title game with a 52-50 victory over Michigan State

Butler Bulldogs take Duke to the limit in the 2010 national championship game at Lucas Oil Stadium, capped but a famous missed shot

Celebrate National Hot Dog Day with loaded dogs that howl with flavor.

Oh the joys of dog ownership — like getting your best bud to go to the bathroom in the snow. Here are some ideas.

The Scottish government has asked for the public's thoughts on easing restrictions - but are the ideas any good?

As F1 waits for the 2020 season to begin, drivers have been keeping themselves busy in lockdown with banana costumes, mummy planks and singing dogs.

Boston Dynamics began began leasing their robotic dogs to the public this year. One of their first customers: The Massachusetts State Police.

Hear about travel to the Dordogne region of France as the Amateur Traveler talks to Laurence Norah about this region known for it's picturesque villages and castles. 

In a startling turn for a robot that has long haunted your dreams, Boston Dynamics' Spot has been tasked to encourage healthy behavior. 

According to the Straits Times, the robot "dog" has been assigned to patrol the Bishan-Ang Mo Kio park in Singapore with the express purpose of encouraging social distancing. 

"Let's keep Singapore healthy," sounds a recording from the robot as it trots by two terrified people relaxing on a park bench in the above video. "For your own safety, and those around you, please stand at least one meter apart. Thank you."

Notably, Spot's jaunt is part of a two-week trial that began Friday. The robot will supposedly not collect any personal information on the people it admonishes.  Read more...

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from ¹³C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.

A pet dog repeatedly tested weak positive for the COVID-19 virus, indicating a low-level of infection with the virus, the Agriculture, Fisheries & Conservation Department said today.

The department first collected test samples from the dog on February 26. It detected low levels of COVID-19 virus from its nasal and oral cavity samples on February 27.

The dog also tested weak positive for the virus when the department repeated the test on February 28 and March 2.

Experts from Hong Kong University’s School of Public Health, City University’s College of Veterinary Medicine & Life Sciences and the World Organisation for Animal Health have been consulted, and unanimously agreed that these results suggest that the dog has a low-level of infection and it is likely to be a case of human-to-animal transmission, the department noted.

The dog has not shown any signs of disease related to COVID-19. It is currently under quarantine at the animal keeping facility at the Hong Kong Port of Hong Kong-Zhuhai-Macao Bridge. The department will closely monitor the dog and repeat the test later.

To ensure public and animal health, the department strongly advises that mammalian pets from households with COVID-19 infected people, or close contacts of infected individuals, should be put under quarantine in the department’s facilities.

The department emphasised that there is currently no evidence that pets can be a source of infection of COVID-19 and under no circumstances should people abandon their pets.

(To watch the whole press briefing with sign language interpretation, click here.)

The Agriculture, Fisheries & Conservation Department today said genetic sequencing tests are being carried out on the pet dog of a confirmed COVID-19 patient which could reveal if the virus has mutated or not.

The department's Assistant Director (Inspection & Quarantine) Dr Thomas Sit told a press briefing this afternoon that the coronavirus is what is known as an RNA virus which eventually mutates.

“That is why the University of Hong Kong School of Public Health needs to do a genetic analysis to compare this dog’s genetic sequencing to the virus isolated from the patient so that they can compare. So if it is totally identical, then there is no mutation. The testing is still ongoing.”

Dr Sit reiterated that international experts agreed that the dog has a low level of infection, despite its blood tests not being ready yet.

“From the first sample to our last sample tested, it has already (been) six days. The dog’s nasal or oral mechanism, their secretion they should have - if contaminated - they should have a way to clean the virus, it would not stay for that long if it was just a contamination.

“I think it will take at least five or seven days for the blood results because it is not an easy test, it is not a quick test. We need to grow a virus and then neutralise the serum, so it takes some time.”

He added that it was too early to say whether animal-to-animal transmission was a possibility.

“At this stage, we do not have enough data to have a 100% answer as to whether it is infectious to other dogs or not. But if the dog’s owner is positive, it is better to take precautionary measures to prevent onward transmission.”

Dr Sit also advised dog owners to wash their hands, wear gloves and try to stop their dogs from licking their surroundings to prevent the virus from spreading further.

The Agriculture, Fisheries & Conservation Department (AFCD) today said a pet dog has tested positive for the COVID-19 virus. 

The case involves a German Shepherd dog whose owners live in Pok Fu Lam. This follows an earlier case in which a 17-year-old Pomeranian dog tested weak positive during repeated tests for the virus.

When the German Shepherd's owner was confirmed with COVID-19, it was sent for quarantine with another mixed breed dog from the same residence to the animal keeping facility at the Hong Kong-Zhuhai-Macao Bridge's Hong Kong Port yesterday.

No positive results were obtained from the mixed breed dog and neither dog has shown any signs of the disease.

The department will continue to closely monitor both dogs and conduct repeated tests on them.

It strongly advises that mammalian pet animals including dogs and cats from households with people confirmed as infected with COVID-19, or close contacts of COVID-19 infected people, should be put under quarantine in AFCD facilities.

The department emphasised that there is currently no evidence pet animals can be a source of COVID-19 for humans or that this virus can cause the disease in dogs.

Pet owners are reminded to maintain good hygiene practices and under no circumstances should they abandon their pets.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.

Delphine Fontaine
Apr 7, 2020; 0:jlr.RA120000634v1-jlr.RA120000634
Research Articles

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage (i.e. plasmalogens [Pls]) at the sn1 position of the glycerol backbone and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs), and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions.

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from ¹³C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.

Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. Here we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine Il-10 and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors is controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced. We propose that in those states exacerbated beta cell activity due to increased insulin demand and increased cell death produces high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.

playing games but now I am being repeatedly harassed and accused of being a troll named Sophie. Well you all can just keep this grimy pool. I am not wasting my time or energy. Enjoy yourselves.

Officials have not done enough to prevent fraud in Head Start programs, the GAO said. The findings prompted Rep. Virginia Foxx, R-N.C., the ranking member of the House education and labor committee, to call for a hearing on the federally funded preschool program for low-income children.

Federal watchdogs find that Utah inflated its high school graduation rate in the last of a series of reports warning states not to make end runs around the rules for calculating graduation rates.

Dogs -- Breeding -- Great Britain -- History -- 19th century.

c.1929?

c.1929?

London : printed for Knight and Lacey, 1826.

[Paris?] : Mac. S. [le tout dirigé & mis au jour, par les soins de Eugene Mac-Swiny], [1741?]

London : Stacy Bias, 2019.

Middletown, DE : Amazon, 2018.

The Office of Special Counsel is recommending that ousted vaccine official Dr. Rick Bright be reinstated while it investigates his case, his lawyers announced Friday.Bright while leading coronavirus vaccine development was recently removed from his position as the director of the Department of Health and Human Services' Biomedical Advanced Research and Development Authority, and he alleges it was because he insisted congressional funding not go toward "drugs, vaccines, and other technologies that lack scientific merit" and limited the "broad use" of hydroxychloroquine after it was touted by President Trump. In a whistleblower complaint, he alleged "cronyism" at HHS. He has also alleged he was "pressured to ignore or dismiss expert scientific recommendations and instead to award lucrative contracts based on political connections."On Friday, Bright's lawyers said that the Office of Special Counsel has determined there are "reasonable grounds to believe" his firing was retaliation, The New York Times reports. The federal watchdog also recommended he be reinstated for 45 days to give the office "sufficient time to complete its investigation of Bright's allegations," CNN reports. The decision on whether to do so falls on Secretary of Health and Human Services Alex Azar, and Office of Special Counsel recommendations are "not binding," the Times notes. More stories from theweek.com Outed CIA agent Valerie Plame is running for Congress, and her launch video looks like a spy movie trailer 7 scathing cartoons about America's rush to reopen Trump says he couldn't have exposed WWII vets to COVID-19 because the wind was blowing the wrong way

Erin E. Hecht
Sep 25, 2019; 39:7748-7758
BehavioralSystemsCognitive