Donegal Junior LeagueReports Downtown CupMulroy Celtic 3 Cranford United Reserves 1The home side continued their excellent form securing all three points from this match. The first goal came through Packie Mc Elwaine who tapped the ball home from close range. Cranford equalised through Jaydee whose curling free kick evaded everybody to clip in off the far post. Mulroy restored their lead when great battling from Michael Sweeney resulted in him squeezing the ball into the net. Early in the second half the game was wrapped up when Ed Moore pointed to the spot. Up stepped Joe Kerr who dispatched to the bottom corner and continue his hundred percent record from twelve yards this season. Michael Mc Grory marshalled the home defence expertly, Andrew Friel and Shaun McGovern also impressed, Jaydee was best for Cranford Watson Hire Division OneLagan Harps 3 Curragh Athletic 0Lagan started brightly and on five minutes had a good chance when Stephen O’ Donnell fired over from eighteen yards. Lagan won a good few corners and Ronan Sweeney should have scored after meeting a great delivery from Kevin Kelly. Lagan went ahead on twenty minutes after great work by O’ Donnell set up Chris Toner who headed home. Curragh threatened with a few long range efforts from Calvin Bradley and Daniel O’ Brien but neither troubled the Lagan keeper. The second half started with Lagan pressing hard and on fifty minutes O’ Donnell saw his cross expertly dispatched with a wonderful overhead kick by Kenny Doran. On seventy minutes Mickey O’ Brien should have done better after meeting a corner but he headed over. Hilley and Grant dominated the middle of the park and the excellent Ronan Gibson marshalled the Lagan defence, curtailing the Curragh efforts. Lagan lost Stephen O’ Donnell with what looked like a nasty injury but wrapped up the game when the industrious Toner crossed for Himley to tap in from close range, a goal his performance merited.Best for Lagan: Himley and Grant in the middle, Toner and Doran up top but Ronan Gibson was outstanding. For Curragh: O’ Brien and the excellent Calvin Bradley who really showed well. Referee: Michael Connolly.Brian Mc Cormick Sports Premier DivisionRathmullan Celtic1 Cranford United 0Rathmullan showed some true Glenvar Warrior spirit to get the better for Cranford in a typically tight battle at the Flagpole this afternoon. Both teams were in desperate need of the points as they look to move away from the wrong end of the table. Chances came and went at both ends but it seemed as though a stalemate would prevail until Hoops full back Ephrim McFadden unleashed 30-yard strike that clipped a defenders heel and flew into the top corner with three minutes left on the clock. It was harsh on Arthur Lynch’s team but the Seasiders will certainly be feeling like they deserved a break after carrying little luck in home defeats to Kildrum and Drumoghill either side of Christmas. With the breeze behind them, Cranford made the better start. After 20 minutes Brian McVeigh saw his shot fly agonisingly over the crossbar. Minutes later it was the turn of Kyle Black to go close. Before halftime Arthur Lynch saw his glancing header cleared off the goal line by the alert Reggie Miller. At the other end, Ryan Connolly came closed when his mazy run ended with a stinging right-foot drive from 18 yards that was pushed wide by Oisin Blaney. Caretaker manager Dara Patton almost stabbed his team in front when the ball broke to him in the box but his effort went the wrong side of the post after 65 minutes. With twenty minutes left it was Connolly’s turn to take aim when he stayed on his feet in the box only to fire into the side netting. On 87 minutes it fell to Man of the Match McFadden to settle the game. Striding over the half way line he found himself 30 yards out and decided to try his luck. His shot took a slight deflection before finishing high in the net to the delight of the Seaside faithful on a bitterly cold afternoon. Referee: Marty Quinn St. Catherines 5 Drumoghill F.C. 1St. Catherine’s played Drumoghill in the Donegal League Premier Division match on Sunday in Emerald Park. With only three minutes gone Jason Noctor was fouled in the box and he dispatched the spot-kick himself to give the home side the lead. Drumoghill created some half chances and were well in the match until the thirty fourth minute the ball was played down the line and Jason Noctor beat the Drumoghill keeper and squared across the Drumoghill penalty area to Conor Doherty at the back post who taped the ball into the Drumoghill net. Noctor added a third on fifty three minutes to put St. Catherines well into control. Daniel Breslin got their fourth before Drumoghill hit the post on sixty five minutes. Barry Rose got the fifth as the home side looked like league leaders. Liam O’ Donnell headed into the Saints net to make the final score 5-1. Best for St. Catherines: Jason Noctor. Best for Drumoghill: Paul Mc CauleyLifford Celtic 2 Milford United 1Lifford won the toss and opted to play with the breeze. The game was an even affair with few chances until Mark Mc Nulty slotted home for Lifford following a well worked short corner on 30 minutes. Lifford almost doubled their advantage as Ross Porter and Kevin Mc Brearty both went close as half time loomed. The second half began as the first did with both midfields battling for possession. Lifford doubled their advantage on 70 minutes as Johnny Mahon played through David Gethins who made no mistake from 20 yards. Milford where awarded a late penalty on 80 minutes but PJ Hagan shot wide of Given’s goal. Gary Merritt did pull a late goal back for the visitors but Lifford held out for a deserved three points. Best for Lifford were Jack Quinn and Johnny Mahon while Gary Merit looked dangerous for Milford. CT Ball Division TwoGlenree United 2 Bonagee United 2After a very competitive match the home side left disappointed after finishing level with the league leaders. It was a tight affair in the first twenty minutes. There were a few chances created but nothing that would worry either keeper. The first half ended all square. Bonagee started the second half the stronger and were knocking the ball around well until the final third were they created few clear cut chances. The breakthrough came when Nick Nelis let fly from 20 yards to give the home side the advantage. Then ten minutes later the same man popped up again, this time from 25 yards to leave the visiting keeper helpless! Glenree were bossing the game and were making chances but not putting the away team to the sword. With 20 minutes left Bonagee resorted to the long ball and it paid off as Aiden Mc Laughlin beat the offside trap to calmly slot past the keeper. This gave the away team hope and they got their second minutes later when a free kick was fired into the box and Peter Mc Namee scored the equaliser. Great team performance by Glenree and a solid performance from Bonagee.Referee: Patrick MartinResultsDowntown CupGlenea United Reserves P v P Arranmore UnitedDrumbar F.C. P v P Donegal Town ReservesSt. Catherines Reserves P v P Erne WanderersDrumoghill F.C. Reserves P v P Castlefin Celtic ReservesTullyvinney Rovers P v P Orchard F.C.Mulroy Celtic 3 v 1 Cranford United ReservesGlenree United Reserves P v P Ramelton MarinersGlencar Celtic P v P Milford United ReservesWatson Hire Division OneLagan Harps 3 v 1 Curragh AthleticBrian Mc Cormick Sports Premier DivisionRathmullan Celtic 1 v 0 Cranford UnitedSt. Catherines 5 v 1 Drumoghill F.C.Lifford Celtic 2 v 1 Milford UnitedWatson Hire Division OneKilmacrennan Celtic P v P Kerrykeel ’71 F.C.CT Ball Division TwoGlenree United 2 v 2 Bonagee UnitedRaphoe Town P v P Ballybofey UnitedDunlewy Celtic P v P Deele HarpsLetterbarrow Celtic P v P Eany CelticFixturesSaturday 24-01-2015 K.O. 2p.m. (Unless Stated)Downtown CupMilford United Reserves v Ramelton MarinersCranford United Reserves v Glenree United ReservesGlencar Celtic v Mulroy CelticOrchard F.C. v Drumoghill F.C. ReservesCurragh Athletic Reserves v Tullyvinney RoversDrumbar F.C. v Fintown Harps AFCArranmore United v Strand Rovers (K.O.1.30)Ulster Junior ShieldMoville Celtic Reserves v St. Catherines Reserves (K.O. 1.30)Sunday 25-01-2015 K.O. 2 p.m. (Unless Stated)Brian Mc Cormick Sports Premier DivisionDonegal Town v Milford UnitedCappry Rovers v Cranford UnitedWatson Hire Division OneCurragh Athletic v Kilmacrennan CelticKerrykeel ’71 F.C. v Castlefin CelticKeadue Rovers v Copany RoversWhitestrand United v Gweedore UnitedCT Ball Division TwoGlenree United v Dunlewey CelticBallybofey United v Letterbarrow CelticUlster Junior Shield K.O. 1.30 p.m.Cockhill Celtic Youths v Deele HarpsBonagee United v Cockhill Celtic ColtsUlster Junior Cup K.O. 1.30 p.m.Aileach F.C. v Convoy ArsenalCootehill Harps v Kildrum TigersMonaghan Town v Glenea UnitedMoville Celtic v Rathmullan CelticGweedore Celtic v Lagan HarpsDrumoghill F.C. v Redcastle F.C.Erne Wanderers v Quigleys Point SwiftsSt. Catherines v Glengad F.C.DONEGAL LEAGUE: ALL THE REPORTS, RESULTS AND FIXTURES was last modified: January 18th, 2015 by StephenShare this:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Reddit (Opens in new window)Click to share on Pocket (Opens in new window)Click to share on Telegram (Opens in new window)Click to share on WhatsApp (Opens in new window)Click to share on Skype (Opens in new window)Click to print (Opens in new window)Tags:Donegal League
OAKLAND — After planting his right foot, DeMarcus Cousins leaped as powerful and high as his 6-foot-11, 270-pound frame would allow him. Then, the Warriors center towered over Lakers second-year forward Kyle Kuzma.Finally, the Warriors’ fans had something to cheer about in a game that previously lacked energy. Finally, Cousins’ teammates had something to make them play harder. So, Cousins could not help but stare down Kuzma after the vicious slam.The Warriors considered that play midway …
Legendary jazz musician Hugh Masekela speaks about Africa Day and states his wish for an all year commemoration of the unification of Africans. The South African musician also says Africa would do well to eradicate its internal borders. Watch this video. Click arrow to play video.
An engaging movie filmed against the vast and rugged wilderness of Lesotho – the first feature film produced in the picturesque mountain kingdom – unwraps the mystery and beauty of the region and its people. (Image: The Forgotten Kingdom) • Andrew Mudge Filmmaker and Writer Black Kettle Films firstname.lastname@example.org • Cape Flats gang film an Oscar contender • American film industry on tour • e’Lollipop sequel soon for South Africa • A shot at movie stardom with Jameson • Education at the moviesMelissa Jane CookAn engaging movie filmed against the vast and rugged wilderness of Lesotho – the first feature film produced in the picturesque mountain kingdom – unwraps the mystery and beauty of the region and its people.The Forgotten Kingdom won the Haskell Wexler Award for Best Cinematography in New York at the 14th annual Woodstock Film Festival Maverick Awards in October 2013, and opens on screens across South Africa on 11 April. Carlos Carvalho, the director of photography, won the award for his masterful attention to detail behind the camera.Haskell Wexler, an American cinematographer, film producer, and director who was named one of the industry’s 10 most influential cinematographers by the International Cinematographers Guild, presented the award. “The tough city slum shooting in the film has the realistic edge of a documentary, while the camera moves are smooth, with painterly frames used as part of a transition to the lead characters’ memories of rural youth,” he told the Woodstock Film Festival.“The first frame is a lone man on a cliff, a distant, beautiful shot valid as a still. After a beat of six, the man moves out of frame. A visual transition to the urban. There are strong, other world, even mystical images at the remote mountain village… Carlos Carvahlo is a first-class shooter well deserving of this award. I hope the Woodstock recognition will encourage him to continue pursuing his artful career doing features like The Forgotten Kingdom where the story he tells is as integrated and important as how you tell it,” said Wexler.Carvahlo received $15 000 (about R157 000) worth of film camera equipment rental from Panavision, in New York.View the trailer hereA life on setHe has always been fascinated by the lens. After studying photography at the Port Elizabeth Technikon, Carvalho joined the film industry as a runner in 1992. Using his precise shooting skills, he won a silver lion at the Cannes Film Festival in 2003. He works on TV commercials, feature films, documentaries and corporate infomercials, and has won several awards over the years.In addition to best cinematography, The Forgotten Kingdom also won the jury’s award for Best Feature Narrative, as well as Best Editing of a Feature Narrative. Africa is a hive of activity of international and local film production, and this movie gives Lesotho a moment to shine as well.“The Forgotten Kingdom is a profoundly visual story,” says producer Chris Roland of ZEN-HQ. “The first film ever to be produced in Lesotho, it’s a charming and captivating quest steeped in the history and culture of the Basotho people. We congratulate Carlos Carvalho on this significant win.”The film tells of the journey of an unemployed young man, Atang Mokoeyna, who lives in Johannesburg. He returns to his ancestral land to bury his estranged father, and at once is intrigued and seduced by its mystical beauty and hardships. These are the people he has forgotten.Inspiration from travelsAndrew Mudge, the writer, director and co-producer, says on the film’s website www.forgottenkingdomthemovie.com that the inspiration for The Forgotten Kingdom came from two trips he made to Lesotho and South Africa in 2003 and 2006. “I explored Lesotho’s remote areas, and became fascinated by this little-known country totally surrounded by South Africa. It’s such a visually rich place, it feels like a frontier, and reminded me of how the American West must have been 150 years ago.”The American says he wanted to capture this place on film, and tell a story that had elements of magical realism, a reflection of the mystical nature of the country itself. “The storyline came to me when I learned about men who leave Lesotho to go work in the goldmines of South Africa, and only return home in their coffins, usually victims of HIV/Aids. I suddenly had the image of a tough city kid building a coffin for his father, and his reluctant return to the motherland. That was the launching point of writing the story.”Mudge conjures up images of horsemen wrapped in blankets moving through snow-peaked valleys and thatched-hut villages lost in time. “I wanted to make a film that was primarily visual, told through the colours of the land and the faces of the Basotho people. My own experience of discovering this mostly overlooked country called Lesotho was like finding something exquisitely beautiful and unique. I wanted to convey that experience to an audience through the journey of the main character, Atang Mokoenya. This is a man who unwillingly experiences a life transformation when he returns to a place that had he long ago chosen to forget.”He spent nearly a year living in Lesotho before filming, he adds, collecting stories from the people, many of whom gave valuable feedback to keep the story culturally genuine. Despite financial incentives for filming in South Africa, he never considered making this movie anywhere but in Lesotho. It was never an option to have the characters speak anything but Sesotho. “The film is a universal story, but it is told from a unique perspective. My producers and I embraced the challenges of making a feature film in a country with mostly rough dirt roads, no professional actors, and no film industry (yet!). Like all journeys, it was a voyage into the great unknown.”The lead roles are played by Zenzo Ngqobe and Nozipho Nkelemba, both known for their work in numerous TV productions, including the e.tv soap opera Rhythm City. Big-name supporting roles include Jerry Mofokeng and Lillian Dube.
Discover the recent changes to the audio meters in Adobe Premiere Pro CS6. The improved meters are much easier to use and able to provide better info for audio editing. Here’s the scoop…Audio is a very important part of video production simply because good audio carries the message and reinforces the images we work with. Don’t make the mistake of overlooking the audio in your video editing project! In this post, we’ll cover the changes made to the audio meters in Adobe Premiere Pro CS6 and how they can be used to improve the audio quality in your video editing.As you can see from the following pictures there have been big changes to the audio meters in Premiere Pro CS6 from previous versions.One of the biggest changes is that the meter in the main user interface now fits whatever size you make it whereas in previous versions it always stayed the same size and orientation.CS6 Audio Meters WideCS6 Audio Meters Placed Wide at the Bottom of the Work SpaceYou can see at once that this ability to re-size and fill whatever gap it is given aids tremendously in getting a far better layout for you work-space as well as allowing you to have a greater sensitivity in your view (i.e. in general longer bars are easier to see and work with than shorter bars).Another great change is that this ability to resize has been added to the whole Audio Mixer Panel which means that no matter how large you make it the meters will scale accordingly. While not going beyond a certain point, the meters will also scale into a very small space and still be visible in CS6:CS5.5 Audio Mixer Panel LengthenedCS6 Audio Mixer Panel LengthenedCS6 Audio Mixer Panel Shortened Premiere Pro Audio Mixer PanelAs well as making the graphs much easier to use, Adobe have also added a new right-click menu which means we can have even more feedback and use out of these meters.NOTE: Make sure you are right-clicking on the black bar in the middle and not on the scale to one side as the only option you will get at that point is the ‘Safe During Write’ option.New Right-Click Menu (Audio Mixer Panel)If you choose any of the other ranges than the default 60 dB Range it won’t change the audio. Instead it will show either a wider or a more limited range in the meter itself. So, if you have some very sensitive audio you want to work with you may find having a wider range such as the 120 dB Range easier to work with than the typical 60 dB range.Dynamic and Static Audio PeaksPeaksThe default setting in Adobe Premiere Pro is as shown above – Dynamic Peaks. What this means is that the little lines shown above will move to show the highest level that your audio gets to for a short time before falling back or moving up to a new level several seconds later. The idea behind this is to give you feedback as to how dynamic your audio is being with a peak staying put for a short while as an indication while the rest of the meter moves.However, if you want to see the maximum values for the whole piece you can change this to ‘Static Peaks‘ from the right-click menu which will mean that these peak indicators will move to the maximum level your audio gets to and simply stay there for the rest of the playback or until you right-click again and choose ‘Reset Indicators’. This can be helpful, but my own preference is to use dynamic peaks and keep the audio below the RED limit level.RED Distortion or ‘Over’ IndicatorsIf you get either of these RED indicators showing at the top of your audio meters it means that your audio for that channel has distorted and should be turned down. It is very bad to get audio peaking in this RED zone as it will play back very badly on any equipment further down the line and so should be avoided.Show Valleys in Premiere Pro‘Show Valleys‘ is very similar to the peak indicators mentioned above. The only real difference is that these indicators show the lowest point of your audio instead of the highest point. Once again, if you choose Dynamic or Static Peaks this will affect both the high peaks and the valley peaks making them persistent or transitory as needed.Audio Color GradientsThe last right-click option on an audio meter in the Premiere Audio Mixer Panel is that of either showing a color gradient or having the colors in the bar change in steps. The image below shows what it looks like with the option in steps (unchecked).Color Gradient Unchecked As you can see, the -18 dB and the -6 dB levels are really clear if you uncheck this option. However, I prefer to leave this option checked in general as it gives a nicer look to my eye and I don’t generally need to be too precise about these levels – that said, should I need to be more precise I now have the option to turn off the gradient if I wish.Lastly, if you right-click on the main Audio Meter in the normal user interface you will find that you have a couple of extra options that don’t come up when you right-click in the Audio Mixer Panel. These include:Extra Options in the Right-Click Menu for the Main UI Audio MixerSolo Channel OptionsAnother interesting feature Adobe has added, which is especially helpful when dealing with multi-channel masters and 5.1 surround-sound masters, is the ability to solo selected channels right from the audio meters. As you can see from the image below, the default setting is to have all the channels ‘soloed’ such that hitting any of the little ‘S’ buttons will turn that channel off.Monitor Mono Channels This option will only work with adaptive clips played in the Source Monitor and for sequences which have multichannel masters played in either the Source Monitor or the Timeline. What it does is allow you to play mono clips through both speakers at the same time – which can be a lot easier on the ear!Monitor Stereo PairsThis function will only work if you have a multichannel master played from the Timeline and what it does is allow you to listen to stereo linked channels instead of all the channels at the same time. For example, if your stereo pair was on channel 7 & 8 you could select to just listen to them with this option.Well, that’s a quick look at the very well redesigned audio meters in both the main user interface as well as in the Audio Mixer Panel. As you can see, these audio improvements in Premiere Pro CS6 can be quite useful in working with audio in your video editing projects.
Liverpool midfielder Wijnaldum: Klopp can be hard on youby Paul Vegas10 months agoSend to a friendShare the loveLiverpool midfielder Gini Wijnaldum insists manager Jurgen Klopp is no soft touch.The Dutchman says Klopp can be a hard taskmaster.He told the Liverpool Echo: “I can’t speak for every player but I have a good relationship with him. He has helped me a lot. He can be hard because he’s always on your case and saying what he thinks. But he’s honest and I like that. It’s always in the right way, always for the right reason. It’s not to make you feel bad or anything like that.”He’s really hard but on the other side he keeps your confidence high. He says that mistakes are just part of football. I remember against Leicester City I made a mistake and it led to a goal. He wasn’t angry about the mistake, he was more angry about my reaction afterwards. He thought I was too busy thinking it, rather than just putting it behind me.” About the authorPaul VegasShare the loveHave your say
zoomIllustration; Image Courtesy: Algoma Owner and operator of dry and liquid bulk carriers Algoma Central Corporation inked a definitive agreement to acquire the interest held by Oldendorff Carriers GMBH & Co. in the CSL International Pool, including the three vessels owned by Oldendorff operating in the pool. As a result of the transaction, Algoma’s interest in the pool will increase to approximately 40%. The company currently owns five vessels operating in the pool.The pool consists of 18 self-unloading vessels ranging from handy-sized to panamax and provides specialized shipping services to customers along the coasts of the Americas and in the Caribbean.As a result of this transaction, Algoma will acquire the handy-sized m/v Alice Oldendorff, and the m/v Harmen Oldendorff and the m/v Sophie Oldendorff, both of which are panamax vessels, for USD 100 million. The deal is expected to close late in the second quarter of 2019.“Increasing our participation in the pool has been a strategic interest for Algoma for some time and the completion of this transaction is aligned with that intent,” said Ken Bloch Soerensen, President and Chief Executive Officer of Algoma.“During 2018, we assumed technical management of our existing pool ships and opened a new office in Fort Lauderdale with an expanded technical staff. We expect to assume technical management of these three ships seamlessly on closing.”Algoma expects to fund the transaction principally from the proceeds of the refund guarantees from the cancellation of four Croatian shipbuilding contracts.“Redeploying the proceeds of the refund guarantees in this manner enables us to put those funds to work quickly in a business we know well with attractive returns,” said Peter Winkley, Chief Financial Officer of Algoma.“Although a decision is pending on the replacement of the vessels that were to have been built by Uljanik shipyard, we expect to fund any instalments required on such replacement contracts from operating cash flows and available credit facilities.”The company cancelled four ships at Uljanik last year as the struggling Criatian shipyard was making very slow progress on the construction. The first contract for the construction of one Equinox self-unloader was rescinded in September 2018. Three more cancellations of Equinox vessel contracts followed suit in October 2018.According to Soerensen, the cancellations eliminated CAD 145 million (USD 110 million) of commitments and CAD 112 million of installment refunds was expected.
Digital terrestrial television is booming in Latin America and will be in 94.5% of homes by 2020, according to a new report.This means 132 million DTT homes will be added in the region in the decade between 2010 and 2020, according to the Digital TV Latin America report, and that DTT will account for half of all digital TV homes added by 2020.In comparison, just 18.1% of homeswere DTT-enabled four years ago.“Much of this growth is being driven by satellite TV, especially lower-cost and prepaid packages – although these subscribers are forcing down average ARPU figures,” said Simon Murray, principal analyst at Digital TV Research, the report’s creator.Nearly 14.4 million satellite pay TV households will be added between 2013 and 2020, with 3.1 million added this year alone. Pay satellite TV penetration will be 21.1% by end-2014 – up from 9.6% in 2010 – and up to 25.8% in 2020, which indicates much of the fastest growth has already taken place.Free-to air DTT will overtake pay satellite in 2015, Digital TV Research predicts. This will see the number of primary DTT homes rocket from 4.3 million at end-2010 (3% penetration) to 27.1 million (18%) in 2014 and on to 71.1 million (42%) by 2010.Brazil, Mexico and Argentina are predicted to dominate the region. Brazil alone will add 37 million digital TV households between 2013 and 2020, with Mexico contributing 15 million and Argentina nearly seven million more.Digital TV households will also increase rapidly in the other 16 countries covered in this report – collectively adding 34 million digital homes between 2013 and 2020.The report studied trends in 19 territories across the region, and each will see rapid increases in digital FTA uptake, with a collective 34 million homes added between 2013 and 2020. Pay TV penetration will also rise, but not as significantly – up 12% in 2010 from year-end-2013.Pay TV revenues will be US$4.5 billion higher in 2020 than in 2013, taking an overall US$24.7 billion. Satellite will remain the largest contributor at US$17.6 billion, while cable will add US$6.1 billion.
Source:https://www.mcgill.ca/newsroom/channels/news/anti-tb-drugs-can-increase-risk-tb-re-infection-295658 Reviewed by Kate Anderton, B.Sc. (Editor)Mar 22 2019Current treatments for tuberculosis (TB) are very effective in controlling TB infection caused by Mycobacterium tuberculosis (Mtb). They don’t, however, always prevent reinfection. Why this happens is one of the long-standing questions in TB research.So why are our bodies unable to generate permanent immunity to TB, – the leading infectious disease killer worldwide? A team of scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) and McGill University may have found the answer… in the gut. In a study published recently in Mucosal Immunology, they showed that anti-TB drugs caused changes to gut microbiota – the diverse community of microbes living our intestines — and increased susceptibility to Mtb infection.Gut microbiota are critical to keeping us healthy; they help to digest food, combat pathogenic microbes and reinforce our immune system. Recent research has shown that chronic use of antibiotic leads to disruption of this community, which can in turn lead to dysregulation of the immune system. It remains unclear, however, whether changes in the composition of the microbes living in our gut have an influence on TB infection.Impact of anti-TB drugs on microbiome To find out, Drs. Irah King and Maziar Divangahi from the Meakins-Christie Laboratories at the RI-MUHC, with colleagues from McGill’s Macdonald Campus, treated mice with the most commonly used anti-TB drugs – isoniazid, rifampicin and pyrazinamide – for a period of eight weeks. They found that while all three drugs significantly altered the composition of the mice’s gut microbiome, only mice treated with isoniazid combined with pyrazinamide showed an increase in susceptibility to Mtb infection.To make sure the vulnerability of the host to Mtb infection was due to a compromised gut microbiota, the researchers looked at… feces. By transplanting feces from mice that had been treated with anti-TB drugs (specifically isoniazid and pyrazinamide) into untreated mice prior to infection, they were able to show for the first time that fecal transplant was sufficient to compromise immunity to Mtb.Related StoriesScientists discover how resistance to the chemotherapy drug 5-fluorouracil arisesArtificial DNA can help release active ingredients from drugs in sequenceA Portable Solution for the On-scene Identification of KratomRelationship between the gut microbiome and the lungsKing and his colleagues also wanted to better understand the gut-lung axis – a bidirectional communication system between microorganisms residing in the gastrointestinal tract and the lungs – in order to how this might be involved in Mtb infection and immunity.To do so, they evaluated a number of lung cell types known to be important for resistance to Mtb infection. Following anti-TB treatment, alveolar macrophages, a type of immune cell located in the airways of mice and humans and the first cell to encounter Mtb upon infection, were compromised in their ability to kill Mtb.”We need to do more research in order to understand how the microbiome affects alveolar macrophages because these cells are critical for controlling early TB infection. We also need to identify the molecular pathways involved in the gut-lung axis,” explains King.”Anti-TB therapies have been incredibly efficient in controlling the TB epidemic by decreasing morbidity and mortality associated with Mtb,” says King. “Now, this work provides a basis for novel therapeutic strategies exploiting the gut-lung axis in Mtb infection.”Researchers are already thinking of monitoring patients who are being treated with these drugs to see how their gut microbiota changes over time and once treatment has stopped. The idea will be to control changes to the microbiome in combination with drugs that are effective at killing Mtb.
Reviewed by James Ives, M.Psych. (Editor)Jun 7 2019Organisms on this planet, including human beings, exhibit a biological rhythm that repeats about every 24 h to adapt to the daily environmental alteration caused by the rotation of the earth. This circadian rhythm is regulated by a set of biomolecules working as a biological clock. In cyanobacteria (or blue-green algae), the circadian rhythm is controlled by the assembly and disassembly of three clock proteins, namely, KaiA, KaiB, and KaiC. KaiC forms a hexameric-ring structure and plays a central role in the clock oscillator, which works by consuming ATP, the energy currency molecule of the cell. However, it remains unknown how the clock proteins work autonomously for generating the circadian oscillation.Related StoriesResearch sheds light on sun-induced DNA damage and repairResearch on cannabis use in women limited, finds new studyTrump administration cracks down on fetal tissue researchThe research groups at Graduate School of Pharmaceutical Sciences of Nagoya City University and Exploratory Research Center on Life and Living Systems (ExCELLS) and Institute for Molecular Science (IMS) of National Institutes of Natural Sciences investigated this mechanism by native mass spectrometry and nuclear magnetic resonance spectroscopy. They found that KaiC degrades ATP into ADP within its ring structure, which triggers the leaping out of the tail of KaiC from the ring. KaiA captures the exposed KaiC tail, facilitating ADP release from the ring, thereby setting the clock ahead.This “fishing a line” mechanism explains the clockwork interplay of the KaiA and KaiC proteins. Elucidating this mechanism will provide deep insights into not only the circadian clock in cyanobacteria but also that in plants, animals, and humans under physiological and pathological conditions, including jet lag and sleep disorders.Source: National Institutes of Natural SciencesJournal reference: Yunoki, Y. et al. (2019) ATP hydrolysis by KaiC promotes its KaiA binding in the cyanobacterial circadian clock system. Life Science Alliance. doi.org/10.26508/lsa.201900368.