The NHL and the players' association suggest that players might be able to engage in small-group activities in May "provided that conditions continue to trend favorably."

The semen of men infected with coronavirus revealed that the disease lingered in only a few patients, suggesting there is a small chance COVID-19 can be transmitted sexually, researchers said.

The semen of men infected with coronavirus revealed that the disease lingered in only a few patients, suggesting there is a small chance COVID-19 can be transmitted sexually, researchers said.

The semen of men infected with coronavirus revealed that the disease lingered in only a few patients, suggesting there is a small chance COVID-19 can be transmitted sexually, researchers said.

Firefighters are warning Londoners not to leave cooking unattended

The coronavirus outbreak has closed malls and most stores. Disputes are brewing over rent. Retail may look quite different in the future, experts say.

The coronavirus pandemic might be a tipping point for small medical practices, which have had trouble staying afloat.

The sprawling shopping center has lost its anchor tenants, Walmart and Sears. A remake will add offices but not the housing that had previously been approved.

Many can now meet payroll for a few weeks – but then what?

From safe bets to long shots, a veteran oddsmaker walks us through the 2020 Oscars odds and tells us why Joaquin Phoenix is worth only $5.

The Studio City home of late composer Jack Smalley, whose credits include 'Murder, She Wrote' and 'The Last of the Mohicans,' is for sale.

'Whenever there's a trillion dollars out on the street that quickly, the fraudsters are going to come out of the woodwork'

The Fiat 500X offers a much sportier driving experience than the Fiat 500 thanks to an all-new 1.3-liter turbocharged engine.

Four high school seniors in the small rural town of Pahokee, Fla., are the subjects of an observational and empathetic new documentary.

Best known to U.S. viewers for "Life of Pi" and "Slumdog Millionaire" Irrfan Khan, who died Wednesday at 53, infused all his characters with hidden depths.

A recent study found that coral reefs will face severe challenges even if average global warming temperature rise is restricted to 2 degrees Celsius. This is a rise that most countries are struggling to negotiate and meet. But reefs are very sensitive to temperature changes, experts fear the window of opportunity to prevent massive reef loss is very small.

Read full article: Nature and Animal Conservation

In recent years, global military expenditure has increased again and is now comparable to Cold War levels. Recent data shows global spending at over $1.7 trillion, despite the global economic conditions. It is still approximately 1% increase since 2008 when the financial crisis began, for example.

Not all nations have felt the impacts of the global financial crisis in the same way. Some have grown economically, including many Asian countries, which has allowed some of them to increase their military spending. There are geopolitical interests at stake for various powers, so economic troubles or not, military spending is seen as important to maintain, or at least to minimize possible reductions.

The highest military spender is the US accounting for 39% of the world’s spending, more than the next top 10 countries combined, and more than all its potential enemies, combined. But this represents a slight decline over previous years as other nations, especially China and Russia, increase their spending. At the same time, the US has reduced military spending for operations in Iraq and Afghanistan, while Western Europe’s austerity programs affect their military spending budgets.

This update includes new and updated figures, graphs and charts exploring this further.

Read full article: World Military Spending

Unilever is recalling Wall’s Mini Calippo (Orange and Lemon-Lime) multi-packs because they may contain small pieces of metal. The presence of metal makes this product unsafe to eat.

WIth the funds for the PPP depleted as of today, as we hope for another tranche of the same amount or more to be approved by the government,  here are some of the issues I have had to address with small businesses I deal with and some of the recommendations I am making to those...

The virus that causes COVID-19 can be found in semen, Chinese researchers report in a small study that doesn't address whether sexual transmission is possible.

While Indiana continues to see a rise in coronavirus cases, a Fishers church will resume in-person services.

"I love from afar, do the best I can from afar but nothing equals a hug," said Eric Ball, funeral director, owner of David A. Hall Mortuary.

The city of Indianapolis and the Indy Chamber announced a $10 million rapid response loan fund for small businesses during the coronavirus pandemic.

The financial disruptions from the coronavirus pandemic are growing. April brings new challenges for renters, homeowners and small-business owners.

Simon Property Group plans to reopen on Saturday Indiana malls shuttered during the coronavirus pandemic, according to a leaked internal memo.

Simon Property Group has published protocols to keep shoppers safe during coronavirus. Here's what changes the shopping mall owner is planning.

Indianapolis officials say they have concerns about Simon Property Group's timelines to reopen shopping malls in Marion County.

Simon Property Group has changed the opening date for malls in Indianapolis to May 16. Its other shopping centers in Indiana will reopen earlier.

Indiana is reopening its economy after its coronavirus closures. Here's what shoppers should know about how malls, stores, salons and gyms will return

Customers ranged from enthusiastic to wary on first day they were able to shop again at suburban Indianapolis malls during the coronavirus pandemic.

The pilot told deputies he had mechanical difficulties and had to make a rough landing in the cornfield.

With most stores remaining closed, Greenwood Park Mall reopened to the public on the first day of Phase 2 of Gov. Holcomb's coronavirus pandemic plan.

Simon executives are furious at Indianapolis officials.

One of the hardest tasks in Earth observation is tracking tiny changes in the shape of the ground.

Government spending grew at its fastest pace since the Great Recession.

Traveling with Small Children

The Amateur Traveler talks to Deanna about cruising to Alaska aboard a small boat from Cruise West In a nights ashore / days at sea program.

The coronavirus pandemic has many of us nostalgic for a simpler time — maybe when we were teenagers and/or watching our favorite early oughts sitcoms. 

Actress Cobie Smulders seems to be feeling that itch, and sensed we are too. The former How I Met Your Mother actress decided to recreate her character Robin Scherbatsky's hit song from the series, "Let's Go to The Mall."

For those who need a refresher, "Let's Go to The Mall" was released during Robin's short career as a pop star (under the name Robin Sparkles) in her homeland of Canada. While it has all the flair of an '80s banger — jelly bracelets, worshipping the mall — it was released in the '90s because apparently that's when '80s culture reached Canada.  Read more...

The Northern Pudu (Pudu mephistophiles) is the world's smallest deer. This little inhabitant of the Andes Mountains weighs in at only 3 to 6 kg, or 7 to 13 pounds. The Northern Pudu lives and plays across Columbia, Ecuador, and Peru. They prefer to stay in the higher elevations of the Andes Mountain range. Most of them live at least 2000 meters above sea level. The climate here is a temperate rainforest, with a wet winter and arid summer.

What Do They Look Like?

These little deer have a stocky body and slim legs. They average 32 - 35 cm, or 13 - 14 inches tall. They are approximately 85 cm or 33 inches long. They are slightly larger than a small house dog or a large cat. They have a Southern branch of the family that lives in Chili and Argentina. This species is slightly larger. Their fur is thick, stiff and lays close to the body. They range in color from a reddish brown to a darker brown. The males sport backward curving antlers that do not split.

How Do They Survive?

The Pudu is a solitary animal interacting socially only to mate. They are nocturnal by nature and thrive on leaves, shrubs, sprouts, blossoms and bark. They do not eat meat. They are adept at climbing, jumping and sprinting which helps them evade predators. They tend to move slowly and purposefully through the lush climate, utilizing dense vegetation to hide. Predators include owls, foxes, and large wild cats.

How Many Young Do They Have?

Mating season is short, lasting from April to May each year. Once done they return to their solitary existence. The female Pudu carries her young six to seven months. Most mothers have only one baby, but twins do occur with some regularity. Pudu young will stay with their Mommas for between 8 - 12 months before heading out on their own. Most of them have an average lifespan of 8 - 10 years.

Why Are They Endangered?

The Pudu is listed as vulnerable on the ICUN red list. The main causes of death are disease, loss of habitat, and over hunting. The Pudu is prone to become infected with various types of worms such as the round worm and heart worms. The worms multiply rapidly overcoming their small bodies. Loss of habitat has lead to a decline in mating and death from road accidents. Adding to the problem are hunters. The Pudu is eagerly sought due to the skill needed to track and kill them. Conservationist are working to restore and preserve the habitat for these precious little deer.

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

Ivan Matic
Jan 1, 2008; 7:132-144
Research

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.

Research Event

Event participants

HE Dr Motsoahae Thomas Thabane, Prime Minister of Lesotho
Chair: Ian Lucas MP, Shadow Minister for Africa and the Middle East

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.