Molecular Machines on Parade

first_imgThe fact that protein machines use energy to undergo conformational rearrangements, and that these “moving parts” perform functional work, places them squarely in the realm of machinery – except on a scale so tiny, their operations are only now coming to light.1.  Valeria V�squez and Eduardo Perozo, “Structural Biology: A channel with a twist,” Nature 461, 47-49 (3 September 2009) | doi:10.1038/461047a.2.  Liu, Gandhi and Rees, “Structure of a tetrameric MscL in an expanded intermediate state,” Nature 461, 120-124 (3 September 2009) | doi:10.1038/nature08277.3.  Cook, Fukuhara, Jinek and Conti, “Structures of the tRNA export factor in the nuclear and cytosolic states,” Nature 461, 60-65 (3 September 2009) | doi:10.1038/nature08394.4.  Guydosh and Block, “Direct observation of the binding state of the kinesin head to the microtubule,” Nature 461, 125-128 (3 September 2009) | doi:10.1038/nature08259.Molecular machines – the very concept is only a couple of decades old.  This is phenomenal.  It is marvelous and wonderful beyond description.  You can almost sense the astonishment and excitement of these biophysicists uncovering these tiny wonders in the cell.  Who could have imagined this is how life works?  Think of the centuries, the millennia, of people going about their business, oblivious to the fact that at scales too tiny to imagine a whole factory of automated molecular machines was keeping them alive.  The few thinkers after the discovery of cells by Robert Hooke envisioned little people (homunculi) doing some of it, but our instruments were too coarse to elucidate the workings inside till recently – till our generation.  Next to the discovery of DNA and the genetic code this must be considered one of the most important discoveries in the history of science.  If Antony van Leeuwenhoek was astonished at what he saw with his primitive hand lens, how much more should we be flabbergasted at what is coming into focus, now that we can discern the activity of individual molecules?    The Darwinists are strangely silent about all this.  In our 9 years of reporting, very few papers on molecular machines have even mentioned evolution (e.g., 10/02/2001, 01/09/2002), and those that did usually just assumed it rather than tried to seriously explain how the most primitive life-forms could have became endowed with factories of mechanical filters, scribes, taxicabs and walking robots by chance (e.g., 09/16/2000, 08/24/2009 08/26/2005).  Search on “molecular machines” in the search bar above and check.  There are lots of examples.  It’s time to cast off that antiquated 19th-century mindset that tried to imagine all this from the bottom up.  Let us regard as silly the tales of miracles of “emergence” occurring mindlessly in “a chance Motion of I don’t know what little Particles,” as Christiaan Huygens, our Scientist of the Month, quipped.  Paley is back with a vengeance.  The contrivances of nature are more wonderful than he or any other philosopher or scientist could have imagined.  It’s a Designed world after all.  Rejoice, give thanks and sing!(Visited 10 times, 1 visits today)FacebookTwitterPinterestSave分享0 Scientific papers continue to exhibit the exquisite mechanisms in the cell for handling all kinds of situations, through the operation of molecular machines.  Here are a few recent examples from this week’s issue of Nature (Sept 3, 2009).Molecular sieve:  What happens when a cell gets bloated?  Too much water entering a cell can increase the pressure against the membrane, “potentially compromising the integrity of the cell,” said Valeria V�squez and Eduardo Perozo in Nature this week.1  They described findings about a molecular sieve named MscL by Liu et al in the same issue of Nature.2  MscL in bacteria is made up of multiple protein parts that form a pore in the cell membrane.  The research team from Caltech and Howard Hughes Medical Institute found that the components flatten out and pivot, opening up the pore like an iris when sufficient pressure is applied.  This is called “mechanosensation” because it operates automatically via mechanical pressure.  “These channels act as ‘emergency relief valves,’ protecting bacteria from lysis [disruption] upon acute osmotic down-shock,” the authors said.  “MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative non-conductive expanded state and at least three sub-conducting states.”  The team’s contribution was to image one of the intermediate states.    The research paper did not mention evolution.  V�squez and Perozo, however, said, “free-living cells have evolved a variety of mechanisms to deal with sudden variations in the physicochemical properties of their surroundings,” and later said, “Most prokaryotes (bacteria and archaea) have therefore evolved a ‘pressure-release valve’ mechanism in which changes in membrane tension open up channels to form large, aqueous pores in the membrane,” but they did not explain how evolution could have accomplished this.  They made it sound like the bacteria purposely employed evolution (whatever they meant by the term) to solve a real problem.  They did not explain how bacteria got through osmotic down-shock without the pressure release valves.Molecular taxicab:  Transfer RNAs (tRNA) are made in the nucleus but need to commute to work outside, in the cytoplasm, where the ribosomes are.  They are small enough to barely squeeze through the nuclear pore complex (NPC) – the complicated gates in the nuclear membrane that control traffic in and out – but they don’t avail themselves of that freedom, lest their exposed parts interact with the authentication mechanisms of the NPC.  Instead, they hale a taxicab to escort them through.  That taxicab, or “tRNA export factor,” is called Xpot.    Xpot is a complex molecule that fits around the exposed parts of the tRNA.  It literally “wraps around” the tRNA, undergoing conformational changes as it clamps on.  Imagine a taxicab wrapping around you, and you get the picture.  Xpot is general enough to fit all 20 kinds of tRNAs, but specific enough to protect their delicate active sites.  It is also able to recognize and reject tRNAs that are immature.  Only tRNAs that have passed a processing exam are allowed in the taxi.  The authors of a paper in Nature who studied Xpot said, “Xpot undergoes a large conformational change on binding cargo, wrapping around the tRNA and, in particular, binding to the tRNA 5′ and 3′ ends.  The binding mode explains how Xpot can recognize all mature tRNAs in the cell and yet distinguish them from those that have not been properly processed, thus coupling tRNA export to quality control.”3  As an additional control, Xpot does not interact with tRNA except in the presence of another factor in the nucleus called RanGTP.  After safe transport through the nuclear pore complex, another factor in the cytoplasm unlocks the RanGTP, allowing the Xpot taxicab to unwrap from the tRNA.  The tRNA then heads off to the ribosome to fulfill its work shift as a scribe, translating the genetic code into the protein code.  “Transfer RNAs are among the most ubiquitous molecules in cells,” they said, “central to decoding information from messenger RNAs on translating ribosomes.”    The authors of the paper did not discuss how Xpot originated, but six times they said that parts of Xpot are either “conserved,” “evolutionarily conserved” or “highly conserved” (i.e., unevolved) throughout the living world.Molecular sherpa:  Kinesin is among the most fascinating molecular machines in the cell, because it literally “walks” hand-over-hand on microtubule trails, carrying cargo.  In doing this, it converts chemical energy from ATP into mechanical work.  Writing in this week’s Nature,4 Guydosh and Block of Stanford described direct observation of the binding state of the hands (called heads) of kinesin to the microtubule.  They found that it walks tiptoe on the tightrope: “Here we report the development of a single-molecule assay that can directly report head binding in a walking kinesin molecule, and show that only a single head is bound to the microtubule between steps at low ATP concentrations.”  The rear head has to unbind before the forward head can bind.  This keeps the kinesin from getting stuck with both feet (heads) on the tightrope.  If you can stand some jargon, here is what they said about the complexities of how this works:The inability of one head to bind the microtubule offers a natural explanation for the observation that the microtubule-stimulated release of ADP is inhibited until the microtubule-attached head binds ATP and docks its neck linker (Fig. 4, state 2).  Strain produced by an unfavourable neck-linker conformation also explains the observation that ATP does not bind prematurely to the front, nucleotide-free head of a 2-HB kinesin molecule (Fig. 4, state 3).  Any tight binding of ATP is disfavoured because it is coupled to neck-linker docking and, therefore, to the generation of a strained configuration in which both neck linkers are docked (Fig. 4, S3).  We anticipate that the single-molecule techniques presented here will be applicable to the study of dynamic properties of other motors and macromolecules that undergo analogous conformational rearrangements.last_img read more

Filing your tax returns

first_img13 June 2003The SA Revenue Service (Sars) has urged South Africans earning over R60 000 per annum to submit their income tax returns before July 11 – and has simplified the process for individuals by issuing a new, user-friendly form called the IT 12S.Sars will be running kiosks at shopping centres around the country, staffed by officials and consultants to help customers complete the new returns.If you’re looking for online help with filling in your form, MyTax.co.za carries a link to the PSIberASSESS personal tax assessment assistant. You can also check out Sars’ guide for completing your IT 12S.Note, though, that electronic filing for individuals is not yet available – though it is for certain other categories of taxpayers: see the Sars e-filing page.Employees earning R60 000 per annum or more are required to complete and submit their income tax forms. Employees first need to obtain an IRP5 certificate from their employer that reflects how much they earn per annum and deductions pertaining to medical aid, pension and housing. The IRP5 certificates should be attached to the income tax forms.Sars spokesperson Christo Henning said those who could not meet the July 11 deadline should ask their local revenue offices for an extension – or apply for an extension online. Failure to do so could result in penalties.“We will do our best to cater for everyone, especially those who will be needing assistance in as far as filling in the forms is concerned”, Henning said.Sars’ publicity drive seeks to reduce the number of requests from taxpayers for extensions and help customers complete their tax returns correctly. Roughly 30%of tax returns received by Sars are either incorrectly completed, partially completed or without the necessary substantiating documentation.There are 3 856 498 individuals and trusts, 1 209 665 companies, 503 905 Value-Added Tax (VAT) vendors, and 251 775 Pay-As-You-Earn cases registered with Sars.Sars had issued 3.8 million returns by the end of May – a 6.84% growth in the total tax base since the last financial year.For fiscal year 2002/2003, Sars electronically paid out R7.3-billion in refunds to 911 416 taxpayers, and about R6.028-billion in refunds issued via secure mail and the post to about 961 674 taxpayers. The recipients included trusts, individuals and companies.For more information, visit the Sars website – click on “income tax” in the left menu.Easy guide for completing your IT 12SFor online help with filling in your form, MyTax.co.za carries a link to the PSIberASSESS personal tax assessment assistant.Online extensionsSouthAfrica.info reporterlast_img read more

Play Your Part, appreciate and observe our human rights

first_imgJohannesburg, Thursday 20 March 2014 – South Africa will commemorate its 20th Human Rights Day tomorrow Friday 21 March 2014 and the ultimate sacrifice of those who were killed when they protested for the right to free movement in Sharpeville in 1960. Speaking on the eve of Human Rights Day, Brand South Africa CEO Miller Matola said, “South Africa has moved from a culture of oppression and intolerance to a culture of respect and acceptance. Our Constitution and our Bill of Rights attest to how far we have come in enabling all the people of this country to express their human rights as free and equal citizens.” “We must all play our part to make sure that we appreciate and observe the human rights principles enshrined in our Constitution and these become part of our collective national psyche.” “This will be essential to ensuring the durability of our democracy,” concluded Mr Matola.Note to EditorsThe Constitution of South Africa can be accessed at: http://www.gov.za/documents/constitution/1996/a108-96.pdf About Brand South Africa Brand South Africa is the official marketing agency of South Africa, with a mandate to build the country’s brand reputation, in order to improve its global competitiveness. Its aim is also to build pride and patriotism among South Africans, in order to contribute to social cohesion and nation brand ambassadorship. Further resources from Brand South AfricaMedia are invited to visit http://www.southafrica.info/ for further resources which can be reproduced without any copyright infringement.  Kindly attribute to Brand South Africa. Join the conversation at:Follow Brand South Africa@Brand_SAhttps://twitter.com/Brand_SAhttps://www.facebook.com/BrandSouthAfricaTell us how you Play Your Part@PlayyourpartSA http://www.playyourpart.co.za/tellus-someone For more information or to set up interviews, please contact: Sandisiwe GugushePublic Relations International: Brand South AfricaTel: +27 11 712 5007 Mobile: +27 (0) 73 126 9128Email: sandisiweg@brandsouthafrica.comlast_img read more

Big Day for LivingSocial, with $10 Off a $20 Amazon Gift Card

first_imgTags:#Amazon#web Related Posts 8 Best WordPress Hosting Solutions on the Market Why Tech Companies Need Simpler Terms of Servic… A Web Developer’s New Best Friend is the AI Wai… Top Reasons to Go With Managed WordPress Hosting audrey watters Today looks to be a record-breaking day for the daily deal site LivingSocial. It’s offering a nationwide deal: a $20 Amazon gift card for $10. In just the first few hours of the sale, users have already purchased over 243,000 coupons. Some are predicting the deal is on a course to outperform the previous blockbuster daily deal, when Groupon offered $25 off a $50 purchase at the Gap. That resulted in some $13 million worth of coupons being sold. The LivingSocial deal still has 22 hours to go and has already sold over $2 million worth of coupons. Of course, Amazon isn’t simply just another major retailer dabbling in the daily deal business. It’s also a major investor in LivingSocial, having put $175 million into the company in December. Lightspeed Venture Partners’ Jeremy Lew calls today’s deal “the first step of operational integration from that investment.” If so, this deal may be less about selling Amazon wares than introducing Amazon customers to the daily deal company.Any predictions on how many $10 off coupons will be sold by the time the deal ends this time tomorrow?last_img read more

10 injured as militants trigger IED blast again in Pulwama

first_imgEight Army personnel and two civilians were injured when militants triggered an improvised explosive device (IED) fitted in a vehicle near an Army patrol in the militancy-hit Pulwama district of south Kashmir on Monday, officials said.They said the multi-vehicle patrol of the 44 Rashtriya Rifles was moving on the Arihal-Pulwama road when the IED was detonated, injuring the personnel travelling in a bullet-and-mine-proof Casper vehicle.The site of the IED blast is 27 km from the area where a convoy of vehicles carrying security personnel on the Jammu-Srinagar National Highway was attacked by a suicide bomber on February 14 in which 40 CRPF personnel were killed.Major killedIn another incident, an Army officer and a militant were killed during an encounter in Anantnag.A Srinagar-based police spokesman said Major Ketan Sharma, 32, from Meerut, Uttar Pradesh, was injured when a search party of the security forces encircled hiding militants and came under “heavy fire” at Badoora village in Anantnag’s Achabal area in the morning.“Sharma was evacuated to a hospital, where he succumbed to his injuries,” said the police.Two other Army officials, including Major Rahul Verma, suffered injuries in the day-long exchange of fire between the militants and the security forces in Anantnag. “One militant was killed in the ongoing operation. His body was retrieved and his identity and affiliation are being ascertained,” said the police.Referring to the IED blast, Army spokesman Colonel Rajesh Kalia said it was “a failed attempt” to attack the mobile vehicle patrol of the 44 Rashtriya Rifles. “Alertness of the patrol party helped to minimise the damage,” said the spokesman.The police spokesman confirmed that six soldiers were injured in the IED blast, which inflicted severe damage on the Army vehicle.The attack on the Army vehicle comes days after Pakistan intelligence agencies reportedly shared information on the Ansar Ghazwat-ul-Hind’s plans to carry out a major attack using a vehicle to “avenge” its chief Zakir Musa in Pulwama on May 24.(With inputs from PTI)last_img read more

Asian Games: Neha replaces Pooja in TT

first_imgPaddler Neha Aggarwal (in pic) has been included in the Asian Games squad after Pooja Sahasrabudhe pulled out due to personal reasons. The 10-member table tennis team will be spearheaded by Sharath Kamal. “The team was selected on the basis of the players’ national and international ranking besides taking into account their current form,” Bhawani Mukherjee told MAIL TODAY.Squad: Men: A. Sharath Kamal, Soumyajit Ghosh, Harmeet Desai, Anthony Amalraj & Sanil Shetty. Women: Ankita Das, Madhurika Patkar, Poulomi Ghatak, Manika Batra and Neha Aggarwal.last_img read more