Cell Quality Control Runs a Tight Ship

first_imgWithout the surveillance and rapid response of quality control, cells would collapse and die.  Here are some recently-published examples of nanoheroes in action.Plant checkpoints:  Picture a child watching the wonder of a seedling breaking through the soil into the light for the first time.  Within hours, the ghostly-white stem turns green, and a day later, leaves begin to appear.  Does he or she have any idea what is going on at a scale too small to see?  Not until that kid grows into a modern lab scientist with sophisticated equipment.  The transformation requires the coordinated transportation of key elements through specialized checkpoints, an international team reported in PNAS.1    Without boring the reader with technical terms, what basically happens is this.  The underground seedling contains pre-chloroplast parts in readiness for the arrival into sunlight, but saves its energy by not allowing the light-gathering factories to assemble until it’s time.  “Chloroplasts need to import a large number of proteins from the cytosol because most are encoded in the nucleus,” they reported.  Once there, they have a double membrane to get through.  Specialized gates permit entry of the authenticated parts.  One particular light-sensitive part has its own unique gate.  The team decided to see what happened when they mutated one gene in the process.  The results were not pretty: the light-sensitive molecules accumulated outside the plastid because they couldn’t get into the factory.  “After a dark-to-light shift, this pigment operated as photosensitizer and caused rapid bleaching and cell death,” they found.  “Our results underscore the essential role of the substrate-dependent import pathway” that this protein depends on.  Maybe this error resembles a chemical spill outside a pharmaceutical plant, or pistons firing before they get into the engine.Now hear this:  In a surprise finding that might provide hope for the deaf, scientists publishing in PNAS reported that “Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness.”2  Two protein partners are needed for healthy hair-cell formation in the cochlea of the inner ear.  Mutations in one of them, connexin26, account for about half of all cases of inherited human deafness.  Usually, connexin26 and connexin30 join together to form gap junctions, but if one is mutated, deafness results.  The gap junctions are essential for cell-to-cell communication.  Surprisingly, connexin26 (Cx26) appears able to bridge the gap when connexin30 (Cx30) is missing; therefore, “up-regulation of Cx26 or slowing down its protein degradation might be a therapeutic strategy to prevent and treat deafness caused by Cx30 mutations.”    The scientists suspected that these two isoforms of connexins regulate each other.  They also noted that this partnering occurs in the lens of the eye.  Losing one by mutation, therefore, affects the regulation of the partner.  On a hunch that one of the isoforms could compensate for the loss of the other if allowed to assemble, and could build functional gap junctions on its own, they tried up-regulating the remaining connexin.  To their surprise, hearing was completely restored in mice. Bad translator triggers SOS:  We’ve talked about the DNA translation team a number of times (e.g., 12/28/2006, 07/26/2005, 06/09/2003, 04/29/2003).  The team of 20 aminoacyl-tRNA synthetases, as they are called, have rigid requirements.  “Mistranslation in bacterial and mammalian cells leads to production of statistical proteins that are, in turn, associated with specific cell or animal pathologies, including death of bacterial cells, apoptosis of mammalian cells in culture, and neurodegeneration in the mouse,” said Bacher and Schimmel in PNAS.3  “A major source of mistranslation comes from heritable defects in the editing activities of aminoacyl-tRNA synthetases.”  This is because the protein machines, which snap the right amino acid onto the appropriate transfer-RNA (tRNA), cannot perform their vital role in protein synthesis if broken.    These researchers suspected that broken synthetases could also cause mutations.  They decided to test what happens when they caused an “editing defect” in one of them.  (These enzymes are usually able to proofread their own errors with a high degree of accuracy.)  The result, again, was not pretty: “A striking, statistically significant, enhancement of the mutation rate in aging bacteria was found.”  The bug was like flipping a fire alarm: “This enhancement comes from an increase in error-prone DNA repair through induction of the bacterial SOS response,” they explained.  “Thus, mistranslation, as caused by an editing-defective tRNA synthetase, can lead to heritable genetic changes that could, in principle, be linked to disease.”    Another press release from Ohio State also discussed the neurological disease that can result from mistranslated proteins caused by mutated aminoacyl-tRNA synthetases. 1Pollman et al, “A plant porphyria related to defects in plastid import of protochlorophyllide oxidoreductase A,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0610934104, published online before print January 29, 2007.2Ahmad et al, “Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0606855104, published online before print January 16, 2007.3Jamie M. Bacher and Paul Schimmel, “An editing-defective aminoacyl-tRNA synthetase is mutagenic in aging bacteria via the SOS response,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0610835104, published online before print January 30, 2007.Dear Darwinist, does this increase your faith that random accidents in working systems are going to make things better?  Is this a better way to build a plant, an ear, or a translation system?  If you think terrorism is the best way to build a civilization, reread the 12/14/2006 entry. (Visited 8 times, 1 visits today)FacebookTwitterPinterestSave分享0last_img read more

‘Address skills, labour reform, corruption’

first_img15 February 2012Opposition MPs, in a National Assembly debate on President Jacob Zuma’s State of the Nation address on Tuesday, welcomed the focus on infrastructure development while urging Zuma to focus more on developing skills, implementing labour reforms and tackling corruption in the country.Debating the address delivered by Zuma in Parliament last Thursday, Congress of the People (Cope) leader Mosiuoa Lekota said South Africa needed to focus more on developing and training its people if it wanted to do away with unemployment and poverty.“Unless we address it, we won’t be able to address the economy and help our people find their way out of the backwardness and squalor that face them,” Lekota said.Infrastructure development would only be effective as a short-stop solution, but would not address the unemployablity of South Africans, he said.Lekota also wanted to know what had happened to the R5-billion youth-wage subsidy that the Finance Minister Pravin Gordhan had mooted in last year’s Budget Speech.Earlier, African National Congress (ANC) chief whip Mathole Motshekga said the development and refurbishment of cultural icons and heritage sites such as memorial sites could help support small businesses, create jobs and back an African cultural renaissance.Lekota agreed that something needed to be done about setting up cultural heritage sites, but questioned the timing of these developments, particularly in a time when South Africa had a large budget deficit.Corruption ‘leading to a dysfunctional state’Inkatha Freedom Party (IFP) leader Mangosutho Buthelezi welcomed the creation of a Durban-Johannesburg trade corridor outlined as one of five regions by Zuma in his State of the Nation Address.But, he said, KwaZulu-Natal’s Department of Transport had ceased all road projects, while the City of eThekweni (Durban) had run up R1.2-billion through bad spending.Buthelezi said Eskom’s build programme should not have been funded by tariff increases, but rather through foreign direct investment, and added that Zuma also made no mention of how to assist small businesses and the declining mining and agricultural sector.Buthelezi said increasing levels of corruption in South Africa meant the country was on the verge of joining the world’s dysfunctional states.He singled out Transparency International’s 2011 report, which revealed that South Africa was becoming more corrupt, and a briefing last year to the justice portfolio committee by former head of the Special Investigating Unit Willie Hofmeyer, who revealed that R25-billion to R30-billion or 20% of all state procurement is lost to corruption every year.South Africa’s economy ‘remains uncompetitive’Leader of the opposition Lindiwe Mazibuko detailed several initiatives to tackle education and the economy that her party would implement if it were in government.She said South Africa’s economy remained uncompetitive, particularly in key sectors such as mining, manufacturing and farming through labour regulation.To boost the economy, the Democratic Alliance (DA) would introduce voluntary exemptions on labour regulations for certain sectors, a youth-wage subsidy and a one-stop business registration office for those looking to set up businesses.Mazibuko said the current black economic empowerment (BEE) model had only succeeded in creating a small elite who had access to finance over and over. Her party wanted to incentivise share ownership across the economy to allow workers to partake more in BEE initiatives, she said.The DA would not choose to focus on particular sectors, as the Industrial Policy Action Plan (IPAP) does, but rather help new businesses to start up by creating targeted incentives and venture capital funds.In education, the party would give schools the “maximum resources” for the first three grade years in schools and carry out assessments on pupils in grades 3, 6 and 9.It was also necessary to limit the ability of teachers to strike and only allow them to go on strike after consulting with the government, Mazibuko said.Minister on Planning in the Presidency Trevor Manuel said it was clear that there was little disagreement on the content of President Jacob Zuma’s speech, but urged the President, who was in attendance, to heed remarks made by opposition members.Manuel said the National Planning Commission was currently getting comments from South Africans on the National Development Plan, which was released in November last year, and added that a final version is expected to come before the President in June or July.Source: BuaNewslast_img read more

Audio Resources for Filmmakers

first_img4. Recording Awesome Location SoundThese tips from LAvideoFilmmaker.com will help you record better location sound for your project. Specifics covered include how to choose the best mic, optimal microphone placement, recording ambient sound and basic tips for working with audio in post. While you’re on the site be sure to subscribe to their FREE email newsletter on filmmaking tips. 6. Audio Tips for Video Editors 2. Tips for Making Your Film Sound GreatThese tips from the pros at Skywalker Sound were taken from a recent Sundance Film Festival panel on successful sound design. Discover some of the most common sound design mistakes filmmakers make, and how to avoid them. As a bonus they share their top picks for sound design from film history. 3. Videomaker “Audio How To”Although Videomaker is perhaps best known for their coverage of production and post, they offer a ton of info on sound design for filmmakers as well. Covering everything from quick tips to reviews of the latest audio gear, be sure to check out their frequently updated audio “How To” section. All too often, audio work is cast aside in post production in favor of spending more time on achieving impressive visuals. This is a crucial mistake. In this post, you’ll pick up a few tips for optimizing your audio workflow during your video edit. Picking the right audio monitors (speakers), basic sound mixing and essential audio effects are all covered. 10. Mike Russell Adobe Audition TutorialsMike Russell’s free Adobe Audition tutorials teach you practical skills (noise reduction, sweetening audio). Anyone using a Adobe based post production workflow can seriously benefit from his often-updated YouTube channel. Also, be sure to check out his 5 free presets (email) to use in Audition.  As an example, check out his video below on recording high quality voiceovers in Adobe Audition: These online resources will help filmmakers get the best results when working with audio!Sound production is a big part of filmmaking/video production that is often overlooked. Whether you are making films, documentaries, corporate communications or wedding videos, the following resources will help you better understand audio and get better results! 1. FilmSound.orgFilmSound has a helpful FAQ on Audio Post Production, as well as articles from 3 time Oscar winning video and sound editor Walter Murch (Apocalypse Now, English Patient, Cold Mountain). The site is geared toward sound editing and design in feature film production and features excellent resources for those looking to get started in the business. 7. Sound Design & Pre-ProductionLights Online Film School is a great filmmaking resource that we’ve previously covered in our post 10 Filmmaking Sites You Should Be Reading. 5. Audio for FilmIf you’re new to filmmaking or sound design, these basics from MicroFilmmaker are a great primer. In this post, you’ll learn the 3 components of a solid soundtrack (dialog, sound effects and music), as well as some useful info on creating a successful sound mix. 8. Location Sound/Audio Post ForumDVX User is best known as an active camera and filmmaking community, but they also have a forum for Location Sound/Post Audio. Start with the “Audio 101” thread which covers common audio filmmaking questions. If you have a specific audio question be sure to post it in the forum! 9. Sound Series by Clinton HarnFilmmaker and audio pro Clinton Harn teamed up with Zacuto for a info-filled blog series on audio for video. Topics covered include picking the right mic (and the differences between mics), capturing sound in cars and creating a working budget for sound recording and design. 11. NoFilmSchool – Audio with a Crew of 1NoFilmSchool is a wealth of information for filmmakers and video pros.  In a recent post, they tackled the task of recording audio as a one-person crew. Lots of good info here about recording audio with DSLRs to external recorders and mic placement.last_img read more

Doesn’t matter where I play, just want to play cricket: Sachin

first_imgHe has been playing cricket for over 20 years now, but Sachin Tendulkar says he remains as passionate about the game as he was in his initial days in the sport.”The passion doesn’t disappear. You know it is as strong and above all I respect cricket. It doesn’t matter where I play. I will always play to the best of my ability, because I care about playing cricket …good, quality cricket. I always wanted to go out and compete hard,” the Mumbai Indians skipper told ESPN-Star ahead of the Champions League Twenty20 match against Highveld Lions here.”Playing for Mumbai has always meant special for me and playing for India also has been extremely special. It was a dream and I am living that dream…and when Mumbai and India are combined together it becomes Mumbai Indians,” he added.Talking about the disappointment of losing the IPL final to Chennai Super Kings after being almost unbeatable in the league stages, Tendulkar said, “You know I was determined like every other time I was determined. My preparations were exactly the same.”Sometimes you score runs sometimes you don’t but I can assure you the efforts put in was always the same,” he added.last_img read more

Matson Inks Deals for 6 Cranes for Honolulu Terminal

first_imgzoom US-based shipping company Matson informed that a subsidiary of Matson Navigation Company has signed contracts with Paceco Corporation for the purchase of three new 65 long-ton capacity cranes and modifications to upgrade three existing cranes at its Sand Island Terminal in Honolulu Harbor. As explained, the investments are part of a broader USD 60 million terminal expansion and modernization program Matson is undertaking to prepare its operational hub in Hawaii for the arrival of four new ships the company has on order. The vessels have a combined value of approximately USD 930 million and their deliveries are expected to start next year.The new cranes will be built by Mitsui Engineering & Shipbuilding (MES), delivered next year and installed at Matson’s Sand Island Terminal in Honolulu in early 2019.They will have greater lifting capacity, height and reach than Matson’s existing cranes, enabling full service of the company’s new larger Hawaii vessels going into service over the next three years.Matson said it will use the new cranes to replace three older and smaller cranes, while upgrading three other existing 40 long-ton cranes.Matson’s investments in these terminal improvements are said to be a cornerstone of the State of Hawaii’s Harbor Modernization Plan, which includes the reinforcement of berths in Honolulu Harbor to support the expansion of Matson’s Sand Island Terminal.The company has two Aloha Class ships under construction at Philly Shipyard in Philadelphia with deliveries scheduled for the third quarter of 2018 and first quarter of 2019, respectively. The 850-foot long, 3,600 TEU vessels will be Matson’s largest ships and the largest containerships ever built in the US, according to the company.In addition, Matson has also ordered two Kanaloa Class vessels from General Dynamics NASSCO in San Diego with deliveries scheduled for the end of 2019 and mid-year 2020. These ships will be combination container and roll-on/roll-off (Con-Ro) vessels built on a 3,500 TEU vessel platform 870 feet long and 115 feet wide, with enclosed garage space for up to 800 vehicles.“Our new Aloha Class and Kanaloa Class ships are being built specifically to meet Hawaii’s freight needs into the future while reducing our environmental impact and improving our efficiency for decades to come,” Matt Cox, Chairman and CEO of Matson, commented.All four new vessels will have a fuel efficient hull design, environmentally safe double hull fuel tanks, fresh water ballast systems and dual-fuel engines, meaning that they will be able to operate on either conventional fuel oils or liquefied natural gas (LNG).With delivery of the Kanaloa Class ships, along with its two new Aloha Class ships, Matson will have completed the renewal of its Hawaii fleet, allowing it to retire seven older vessels that will no longer comply with environmental regulations in 2020 without substantial modification.last_img read more