We report a systematic, cellular phenotype-based antimalarial screening of the Medicines for Malaria Venture Pathogen Box collection, which facilitated the identification of specific blockers of late-stage intraerythrocytic development of Plasmodium falciparum. First, from standard growth inhibition assays, we identified 173 molecules with antimalarial activity (50% effective concentration [EC₅₀] ≤ 10 μM), which included 62 additional molecules over previously known antimalarial candidates from the Pathogen Box. We identified 90 molecules with EC₅₀ of ≤1 μM, which had significant effect on the ring-trophozoite transition, while 9 molecules inhibited the trophozoite-schizont transition and 21 molecules inhibited the schizont-ring transition (with ≥50% parasites failing to proceed to the next stage) at 1 μM. We therefore rescreened all 173 molecules and validated hits in microscopy to prioritize 12 hits as selective blockers of the schizont-ring transition. Seven of these molecules inhibited the calcium ionophore-induced egress of Toxoplasma gondii, a related apicomplexan parasite, suggesting that the inhibitors may be acting via a conserved mechanism which could be further exploited for target identification studies. We demonstrate that two molecules, MMV020670 and MMV026356, identified as schizont inhibitors in our screens, induce the fragmentation of DNA in merozoites, thereby impairing their ability to egress and invade. Further mechanistic studies would facilitate the therapeutic exploitation of these molecules as broadly active inhibitors targeting late-stage development and egress of apicomplexan parasites relevant to human health.

Background:

The associations of abdominal skeletal muscle mass index (SMI), visceral and subcutaneous adipose tissue (VAT and SAT, respectively), and mortality among patients with stage I–III colorectal cancer may differ for men and women, but only few studies stratified their data into men and women. We investigated associations of abdominal SMI, VAT, and SAT with overall mortality among men and among women with stage I–III colorectal cancer.

While you're going to gaming jail, you'll want to listen to our show so you know what games to bring with you. Fallout 76 has a new update, perhaps it'll be a good choice for you. Phantasy Star Online 2 had a wonderful beta, maybe it's the way to go. Unfortunately, Metal Max Xeno: Reborn was delayed so you'll have to wait a bit for that one.

Desmond Mombeyarara, 34, was with his son when officers shot him with a stun gun

Anti-racism protesters have gathered outside a petrol station in Greater Manchester to demonstrate against the stun gun shooting by police of a black man in the company of his distressed son.

Desmond Mombeyarara, 34, was shot with a stun gun by police on Wednesday evening after officers stopped him for allegedly speeding.

Host Aziz Ansari touched upon the Women's Marches, racism and immigration in his monologue.

“Hi, I’m Taylor.” With that greeting, Taylor Swift returned to the stage as the headliner of “DirectTV Now Super Saturday Night” at Club Nomadic on the eve of the Super Bowl.

In a further amendment to the plans for Vuelta a Espana 2020, the race will not travel through Portugal.

Thousands of cyclists took over streets in the centre of the Slovenian capital Ljubljana on Friday evening to protest against the government of Prime Minister Janez Jansa and the restrictions it has imposed to fight the coronavirus.

Long victimized by poaching and deforestation, the primate species is in the midst of a surprising rebound that is sparking new hopes of recovery

New Zealand's Greg Henderson won the 201.5-km first stage of Paris-Nice between St Arnoult-en-Yvelines and Contres on Monday.

Tour de France champion Alberto Contador lost time on the leaders and suffered a painful knock to his leg when he crashed towards the end of the first stage of Paris-Nice on Monday.

The World Health Organisation's chief has warned that most countries are still in the early stages of their coronavirus epidemics and others are starting to see a resurgence in cases.

The High Court is due to give its ruling on the first stage of the Duchess of Sussex's privacy claim against Mail on Sunday today.

The publisher of the Mail on Sunday has won the first High Court skirmish in the Duchess of Sussex's privacy claim against it over publication of a letter to her estranged father.

The Irish Government has shared it plans for reopening society after coronavirus lockdown.

People in countries across Europe are gradually regaining some old freedoms as governments start to lift their coronavirus lockdowns after many weeks.

The second stage of the coronavirus response "will not be easy" and the UK must adjust to a "new normal" to avoid a second peak , Dominic Raab has said.

You can donate at virginmoneygiving.com/fund/FoodforLondonNOW

Figuring out how to stage the nation’s largest and most important political gatherings will be tricky in the COVID-19 era. And while officials in both parties say they’re still planning for in-person conventions, pulling that off will be a lot easier said than done. 

Australian prime minister Scott Morrison has detailed a gradual opening up of society with the timing the stages to be determined by the states

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Scott Morrison and the chief medical officer, Brendan Murphy, have laid out a three-step plan to reopen Australia after the coronavirus crisis. Morrison said he hoped step three could be achieved in July, but it would be up to each state and territory when they moved from one step to the next.

Below are some of the areas that will be opened up at each stage, according to the plan – and you can see the timeline for easing restrictions in each state here.

The singer also suggested women aren't encouraged to get into music production from an early age

"An amazing night at Selhurst Park, Liverpool have caved in!"

The King was honored for his extensive philanthropic work

The Britain's Got Talent judges come crashing into tonight's auditions when Simon can't work the breaks - leaving David to claim he has whiplash

The Prime Minister says it's ultimately up to states and territories to decide how much current restrictions are relaxed.

Prime Minister Scott Morrison says he hopes Australia will be mostly reopened by July, and has unveiled the three-step plan agreed to by National Cabinet to get there. Here's how it looks.

THE Cairns Choral Society has not let the demise of the Cairns Civic Theatre stop it from staging its annual musical.

La stratégie déployée vendredi dans la grande région de Montréal nécessitera plus de personnel en santé.

China's interpretation of the 'rule of law' governing Hong Kong is likely to further incite protesters following the arrest of activists.

PTC Therapeutics has reached an agreement to acquire Censa Pharmaceuticals and its lead asset, an experimental metabolic disorder therapy that is now being prepared for a pivotal study. The deal, announced after the market close Wednesday, will bring South Plainfield, NJ-based PTC (NASDAQ: PTCT) another compound for its pipeline of rare disease drugs. Wellesley, MA-based […]

Madhatta Haipe, a citizen of the Philippines, has been extradited from the Philippines to face trial in the District of Columbia for various crimes relating to the hostage taking of U.S. and Philippine citizens in 1995.

Madhatta Haipe, a citizen of the Philippines and founding member of Al-Harakat Al-Islamiyyah, also known as the Abu Sayyaf Group, pleaded guilty today in federal court in the District of Columbia to four counts of hostage taking in connection with the 1995 abduction of 16 people, including four U.S. citizens, in the Philippines.

California-based companies Quicksort Inc., Quicksort LA Inc. and Quicksort Sacramento Inc. have agreed to pay the United States $4.2 million to settle allegations that Quicksort violated the False Claims Act by falsely representing the level to which it had pre-sorted mailings in order to obtain discounted postage rates from the U.S. Postal Service.

Tanja Anamary Nijmeijer, a Dutch national who moved to Colombia and joined the Revolutionary Armed Forces of Colombia (FARC) in 2002, and 17 other members of the FARC designated foreign terrorist organization were indicted by a federal grand jury in Washington, D.C., today on seven counts of terrorism and weapons charges arising out of their participation in the hostage-taking of three American citizens in the Republic of Colombia.

Madhatta Asagal Haipe, a citizen of the Philippines and founding member of Al-Harakat Al-Islamiyyah, also known as the Abu Sayyaf Group (ASG), was sentenced today to 23 years in prison after earlier pleading guilty to four counts of hostage taking in the 1995 abduction of 16 people, including four U.S. citizens, in the Philippines.

Sheena Flores, 34, of Manassas, Va., pleaded guilty before U.S. District Judge Gerald Bruce Lee to one count of transmitting in foreign commerce, with intent to extort money, a communication containing a threat to injure another person.

Sheena Flores, 34, of Manassas, Va., was sentenced by U.S. District Judge Gerald Bruce Lee in the Eastern District of Virginia.

Alexander Beltran Herrera, 35, aka Jhon Alexander Beltrain Herrera, aka Rodrigo Pirinolo, an accused member of the Revolutionary Armed Forces of Colombia (FARC), has been extradited from Colombia to face hostage taking and terrorism charges in the United States.

Alexander Beltran Herrera, 37, a commander of the FARC terrorist organization, pleaded guilty today in the U.S. District Court for the District of Columbia to hostage-taking charges stemming from the 2003 kidnappings of three U.S. citizens in Colombia.

AskBio acquires gene therapy biotech working on treatments for neurodegenerative disorders.

Come on in, the water’s warm. After billions already raised by VC firms since the advent of the pandemic for life science companies, Oberland Capital has tossed more than $1 billion into the pot.

Until millions of Americans can be tested weekly for coronavirus, states will walk blindly into restarts. But NIH director has a plan to ramp up.

Protesters of California's stay-at-home orders returned for another unsanctioned rally Thursday, telling law enforcement officers they are forgiven for arresting them last week.

Stormbreaker Venture, an edtech accelerator, is a common investor in both the companies.

The post Thai Digest: Edtech startups Vonder, Conicle raise early-stage funding appeared first on DealStreetAsia.

The pair announced their first investment on Tuesday into edtech startup Eduka System.

The post Bukalapak co-founders Zaky, Xinuc set up early-stage VC fund Init 6 appeared first on DealStreetAsia.

Innoangel Fund now manages over 3 billion yuan ($425 million).

The post Chinese early-stage tech investor Innoangel Fund closes RMB fund at $51m appeared first on DealStreetAsia.

LetsVenture Plus will allow Indian investors access to investments across growth-stage private companies and global funds.

The post Indian angel investor LetsVenture launches growth-stage platform to tap domestic capital appeared first on DealStreetAsia.

Mouse studies suggest chemically modified carbohydrate conjugates could be useful as antigens for the development of cancer vaccines.