In this retrospective study, whole-genome sequencing (WGS) data generated on an Ion Torrent platform was used to predict phenotypic drug resistance profiles for first- and second-line drugs among Swedish clinical Mycobacterium tuberculosis isolates from 2016 to 2018. The accuracy was ~99% for all first-line drugs and 100% for four second-line drugs. Our analysis supports the introduction of WGS into routine diagnostics, which might, at least in Sweden, replace phenotypic drug susceptibility testing in the future.

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.

Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.

A neutron star has produced gravitational waves after colliding with an unknown object – it could be the smallest black hole or biggest neutron star ever found

At the centre of our galaxy, six strange clouds that look like dust and gas orbit a black hole so closely that if they were really just clouds they should have been sucked in by now

The enormous black hole at the centre of the Milky Way was active millions of years ago, and its intense X-rays may have formed some molecules necessary for life

A huge black hole from when the universe was less than a billion years old is shooting a powerful jet at Earth, and studying it could help us understand the young cosmos

Our images of deep space are spectacular, but don’t reflect what our eyes would see. Here's what their stunning true colours reveal about the cosmos

When Earth and Venus formed, they both had global magma oceans deep underground. Earth’s has turned solid by now, but Venus’s may still remain hidden

A star that swoops close to the Milky Way’s supermassive black hole has a strange, looping orbit that proves Einstein was right about the gravity of black holes

Astronomers found a star that appeared to be orbiting nothing at all – but it’s actually the closest black hole ever at just 1000 light years away

Rigid IT departments and job-hopping data scientists are just two of the challenges that make implementing machine learning harder than you might think

The SnotBot project uses drones, data, and deep learning to tell us about the health of whales and the oceans

We can’t stop him because we must know what happens next; our curiosity is his source of power.

Faked 'entanglement' result challenges cryptographic technique.

Big show this week as we go over our PAX experience. We’ve also got our Extra Life plans, legion impressions, and Persona 5 jealousy. Now...

Real estate scandals, early DLC announcements, lootbox gambling, and golf rap battles are some of this week’s controversies. Also, Joshua Carpenter makes his first RPG...

Lots of mechs today. Watch out that they don’t break you. Were you a supporter of Obsidian’s last kickstarter? See when you get your reward...

From tiny sunglasses to leather coats, the film’s costume designer Kym Barrett writes about why the film’s look feels so relevant in our uncertain world

• Read more from the spring/summer 2020 edition of The Fashion, our biannual style supplement

I never thought The Matrix would have the impact it has had on fashion. But from long leather coats to so-called “Matrix-style” sunglasses, the costumes I designed in the 90s continue to have influence to this day.

Part of the reason they are still in the ether is because they were so iconic. The silhouettes, for instance, had to be instantly recognisable so that viewers could tell who each character was, even in the dark. All of the costumes are fairly immune to period, which is what makes them relatable, even now.

Obese Europeans who are treated with cholesterol lowering drugs have not only lower values of blood LDL cholesterol and markers of inflammation but in addition a more healthy gut bacteria profile than those obese who are not prescribed statins.

Mark Twain once described golf as "a good walk spoiled." With all due respect, the father of American literature likely would have had a much different take had he joined me ...

Astronomers using the Fiber-fed Extended Range Optical Spectrograph (FEROS) on the MPG/ESO 2.2-m telescope at ESO’s La Silla Observatory have found a stellar-mass black hole in HR 6819 (also known as HD 167128), a naked-eye stellar system located 1,119 light-years away in the constellation of Telescopium. The system is made up of an inner binary [...]

Experts theorize there are between 100 million to 1 billion black holes in the Milky Way

The newfound 'invisible' object is only 1,000 light years from home

Astronomers have spotted the closest black hole to Earth ever discovered and are surprised about its living arrangements - residing harmoniously with two stars in a remarkable celestial marriage that may end in a nasty breakup.

More than a century ago, Einstein predicted how much the star's orbit changes, and now the data collected by scientists exactly matches his theory.

Many countries, including ours, are battling the question of how to lift the lockdown.

Earth's closest black hole has been discovered by astronomers and it is big enough to swallow the whole of Washington DC.

Just 1,000 light years from Earth, its two companion stars are visible to the naked eye.

Scientists predict the explosive behaviour of two supermassive black holes almost to the hour.

An unseen object is found to be lurking in a double-star system a mere 1,000 light-years from Earth.

Scientists usually find black holes by detecting X-rays they emit as they devour nearby stars. But this one was quietly hidden 1,000 light-years away.

Object found in HR 6819 system is the closest to Earth yet known – and is unusually dark

Astronomers say they have discovered a black hole on our doorstep, just 1,000 light years from Earth.

It was found in a system called HR 6819, in the constellation Telescopium.

System could be 'tip of the iceberg' and many more could be waiting to be found, scientists say

Labour Shadow Minister for the cabinet office Rachel Reeves has lead for the party on PPE procurement.

Tracing out the shape of a galaxy may offer clues to the size of its supermassive black hole. And a new study shows citizen scientists are actually better at it than computer algorithms.

This quiet black hole sits just 1,000 light-years from Earth. But the two stars that dance around it are possible to pick out with the naked eye.

Our best bet could be to send a swarm of nanospacecraft — propelled from Earth by a powerful laser — to take a look.

Astronomers believe they have found the closest black hole to our solar system, lying just 1,000 light-years away, which in astronomical terms, is right in our neighbourhood.

A new kind of survival story: Scientists discovered a star that came near a black hole and lived to tell the tale – at least temporarily.

Earlier this week, Tencent announced a big new update for PUBG Mobile (Free) on iOS and Android. The version 0.18.0 …

Continue reading "‘PUBG Mobile’ 0.18.0 Is Rolling Out Now on iOS and Android with Mad Miramar, a New Results UI, and a Whole Lot More"

Paul Scholes believes Manchester United have found their own version of Manchester City's Kevin De Bruyne in Bruno Fernandes.

Marcus Rashford says it would have been a "dream" to play alongside Paul Scholes at Manchester United.

Paul Scholes has been labelled "dumb and dumber" on the official Manchester United podcast after a comical misunderstanding.

Parry labelled Premier League parachute payments as "an evil which needs to be eradicated"

Canceled Wednesday, this year's E3 was particularly anticipated because new consoles from Sony and Microsoft are due to be released by the end of the year.

The closest black hole to Earth has been discovered about 1,000 light-years away, scientists have said.