A 'SHAPE-SHIFTING' UFO has been spotted over Columbia, according to conspiracy theorists who claim it was a living being.

The coronavirus outbreak is pummeling LGBTQ Americans, leaving a population already vulnerable to health care and employment discrimination suffering.

Indianapolis native Doug Jones takes his creature craft to new heights in Guillermo del Toro's "The Shape of Water."

Para Mirian Goldenberg, que pesquisa envelhecimento há 20 anos, "estamos assistindo horrorizados a discursos sórdidos, recheados de estigmas, preconceitos e violências contra os mais velhos".

In Saudi Arabia, you can try authentic apple-flavored Budweiser. (Non-alcoholic, of course.)

The Franklin Skeleton Crew is connecting small businesses with the community in an unconventional way.

Zambia is the ninth African state to gain independence from the British crown.

A chronology of key events

Key facts, figures and dates

A chronology of key events

A chronology of key events

A chronology of key events

Key facts, figures and dates

Key facts, figures and dates

Key facts, figures and dates

A chronology of key events

Key facts, figures and dates

The "Megatron" rapper is set to perform in the country next week despite calls to quit the gig over the government's alleged human rights violations.

The rapper said she wanted to support women's and LGTBQ rights.

Human rights advocates have urged artists not to perform in the country because of its dismal human rights record.

The host made news of his own with questionable jokes, an eye roll and whispers of another wrong winner.

Announced back in July, Nokia’s new flagship N8 smartphone began shipping on the last day of September to those that had pre-ordered the device (it’s now available on most UK networks). As did the first review units sent out with almost military provision to chosen technology bloggers, this writer included. Having already declared “Nokia is [...]

Vancouver, Birtish Columbia (plus Victoria, Whistler)

Colombia

The Amateur Traveler talks to Carla, Jason and Janie about their trip to Nambia. While traveling in southern African to attend some of the games of the World Cup the three made a visit to nearby Namibia after hearing from friends that it was one of their favorite African countries. Come with us as we learn about a country that is perhaps surprisingly prepared for tourists. We will talk about seeing 4 out of the "big 5" safari animals. Our trio talks about miles of sand, sand storms and riding camels but also talks about visiting the show and seal colonies. The camping was easier than expected and the food was more diverse (you won't believe what they found on pizza).

The Amateur Traveler talks to Shawn Farris about his trip to Serbia and Kosovo. Shawn either visited two countries (or one) in this contested area of the Balkans.

The Amateur Traveler talks to David Lee about his parttime home, the “City of the Eternal Spring”, Medellin Colombia. If you just Medellin as a dangerous city and the home of drug lords, then your information is about 20 years out of date

Hear about travel to Victoria Falls as the Amateur Traveler talks to Nir Ben-Dov about his trip to this spectacular falls on the border of Zimbabwe and Zambia. This was Nir’s second trip and his wife’s first trip from their home in Israel to this famed set of falls in southern Africa.

Hear about travel to Namibia's Skeleton Coast as the Amateur Traveler talks again to Susan Portnoy of theinsatiabletraveler.com about her trip to this memorable reagion of Africa. Namibia is the size of France and Great Britain combined but with only 2 million people.

Hear about travel to 4 national parks in British Columbia as the Amateur Traveler talks to Carolyn B. Heller author of "Moon Vancouver & Canadian Rockies Road Trip".

Hear about travel to Zambia as the Amateur Traveler talks to Graham Wales from outboundclan.com about their epic honeymoon in Africa and how they fell in love with Zambia.

Hear about travel to the coffee region of Colombia as the Amateur Traveler talks to Alejandro from Bogota about an area of his country that he thinks doesn't get enough attention.

Hear about travel to Serbia as the Amateur Traveler talks to Stephanie Craig and Allison Green from sofiaadventures.com about one of the Balkan countries that they love.

Hear about travel to Namibia as the Amateur Traveler talks to Karthik Iyer about his most recent trip to this desert country.

Hear about travel to West Africa to Senegal and the Gambia as the Amateur Traveler talks to Brian Asher from theworldhiker.com about this under-visited region.

Research Event

Event participants

Tim Jinks, Head of Drug-Resistant Infections Programme, Wellcome
Jim O’Neill, Chair, Review on Antimicrobial Resistance; Chair, Chatham House
Haileyesus Getahun, Director of Global Coordination and Partnership on Antimicrobial Resistance, World Health Organization 
Juan Lubroth, Chief Veterinary Officer, Food and Agriculture Organization (Videolink)
Jyoti Joshi, Head, South Asia, Center for Disease Dynamics, Economics & Policy
Estelle Mbadiwe, Coordinator-Nigeria, Global Antibiotic Resistance Partnership
Charles Clift, Senior Consulting Fellow, Chatham House; Report Author

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.

4 March 2020 , Volume 96, Number 2

4 March 2020 , Volume 96, Number 2

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.