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

Absa trials ‘tap-and-go’ payment cards

first_img23 September 2011Absa and Integrated Fare Collection Services, a DigiCore subsidiary, are working on an integrated transit payment solution South Africa’s public transport sector, including the taxi industry, with a pilot project currently underway in the Western Cape.The new “tap-and-go” payment cards will provide transit owners and commuters with a simple and efficient way to manage payments for transport services. The two companies are already exploring opportunities with associations in other provinces.The cards will use global card standards, namely MasterCard Paypass and Visa Paywave, and are designed to work seamlessly across a number of modes of public transport as they are brought online.“The tap-and-go payment method will also allow commuters and other consumers to conveniently pay for low value purchases in retail outlets,” said Absa Card’s Simon Just in a statement this week. “So, a customer can move from a taxi to a bus to a grocer using the same card on the same day.“As of 2012, commuters will even be able to have this payment option on their normal bank cards.”National transport infrastructure upgradesAs part of national transport infrastructure upgrades, the Department of Transport and local transport authorities have been driving new card-based approaches to fare collection, with the aim of providing commuters with speed, simplicity and convenience when they travel.These will require commuters to tap a prepaid card against readers to pay their transport fares as they enter public vehicles.“Although adoption of this trendsetting service will be gradual, it is gaining momentum,” said Just. “A few major city bus operators and key retailers are starting to roll out tap-and-go payments, and the bank will make it possible for its customers to obtain Absa tap-and-go cards from selected Absa branches as from November 2011.”No PIN or signature requiredTap-and-Go transactions will be limited to R200 per day and users will be able to load a maximum of R1 500 on the card at any time, while the total monthly transaction limit is R3 000.“This is in line with the special exemption from the provisions of the Financial Intelligence Centre Act, which makes for ease of issuing of contactless cards to under-banked consumers,” Just explained.Commuters will be able to load funds onto their cards from a bank account or with cash at a transit or station kiosk, vending machines, ATMs or selected merchants.Customers can then make purchases with their contactless card until the pre-loaded balance is used up by simply agreeing to the amount and tapping the card against a reader. No PIN or signature is required.Secure alternative to cashFor public transport operators, the new fare collection system reduces pilferage, provides a more secure alternative to cash and paper tickets and significantly enhances overall efficiencies – while also making a difference in the everyday life of the commuter.DigiCore’s Integrated Fare Collection Services (IFCS) has developed a robust fare collection solution called Tap-i-Fare for transit operators, which uses advanced route planning, GPS and vehicle tracking technology, to calculate fares and ensure that commuters are charged correctly for their journey.IFCS managing director Pierre Bruwer said that even though the system was up and running, there was still much work to do with taxi associations and other stakeholders in order to finalise the operating model and roll-out plans.“We have engaged a number of taxi owners, operators and associations,” he said. “They appreciate the benefits of the new approach to rapid transit payments.“We are confident that it will be embraced in the way that government has intended.”SAinfo reporterWould you like to use this article in your publication or on your website? See: Using SAinfo materiallast_img read more

India, Bangladesh ocean scientists to work together

first_imgOcean research scientists of the National Institute of Oceanography (NIO) would get an opportunity to work together with Bangladesh Oceanographic Research Institute (BORI) in areas where work has not been started in that country’s Exclusive Economic Zone(EEZ), said Director of NIO Sunil Kumar Singh here on Monday.He was addressing presspersons in the presence of a visiting delegation from Bangladesh led by Ashok Kumar Biswas, Director General, (BORI). The delegation was on a two-day visit to CSIR-National Institute of Oceanography, Dona Paula.Mr. Singh said that the visit was in connection with the recent Memorandum of Understanding (MoU) signed between the Council of Scientific and Industrial Research (CSIR) and Bangladesh Council of Scientific and Industrial Research (BCSIR), in Dhaka, towards a mutual co-operation between both the countries.The delegation visited CSIR-NIO to chalk out programme and plan towards training the manpower from Bangladesh for oceanographic research. “BORI is a new institute established three months back. They are going to start their research activity very soon. India has committed to help CHOGAM countries, Small Island Developing States (SIDS) countries and all Indian ocean countries,” said Mr. Singh.“We are going to help the new institute in all the aspects. Scientists from BORI will be visiting NIO on short and long-term duration to have training in oceanographic research and to have understanding of the subject. Similarly, NIO scientists will be visiting BORI to impart training in various fields of oceanography. It will not be limited to training, but we will be doing joint oceanographic research,” he said.“Bangladesh has got support since 1971 from Indian Government and have been getting full support from India since then. We feel that without India we will not be developed,’’ said Mr. Biswas.The delegation will also visit National Institute of Ocean Technology in Chennai.last_img read more

Huge margins show shift towards BJP

first_imgThe huge margins with which most of the BJP candidates have won in the Lok Sabha election in Rajasthan depict a decisive shift in the voters’ preference for the party barely five months after the State Assembly elections. However, the factors which combined with the “national mood” varied in different regions of the State.The Congress was elected to power in the 2018 Assembly elections on the basis of people’s verdict that was perceived to be against the rule of then Chief Minister Vasundhara Raje. However, the BJP seems to have regained lost ground by recording a bigger victory than in 2014, increasing its overall vote share as well as its margin in 19 of the 25 seats which it has won.With a vote share of 58%, against 55.61% in 2014, the BJP candidates won with a margin of more than 4 lakh votes in nine LS constituencies. There were only two seats — Dausa and Karauli-Dholpur — where the margin was less than 1 lakh, probably because the candidates could not get sufficient time to campaign due to late decision on their names.Subhash Chandra Baheria won with the biggest margin of 6.12 lakh votes in Bhilwara, followed by Chandra Prakash Joshi in Chittorgarh (5.76 lakh votes) and Diya Kumari in Rajsamand (5.51 lakh votes). The 19 seats where the BJP has increased its margin include Pali, Barmer, Ajmer, Udaipur, Banswara, Alwar, Bharatpur, Jhunjhunu, Sikar and Jhalawar-Baran.Only two of the Ministers, who were given responsibility to mobilise the voters in favour of the Congress candidates, were able to ensure the party’s lead over the BJP in their Assembly constituencies. The Congress candidates got more votes at Sapotra, represented by Food & Civil Supplies Minister Ramesh Meena, and Sikrai, represented by Women & Child Development Minister Mamta Bhupesh.The vote share of the Congress, which had received 39.3% of the total votes in the 2018 Assembly elections, reduced to 34.2% in the Lok Sabha election and it could not win even a single seat in the State. While the caste combinations relied upon by the Congress did not succeed with major sections among Jats, Gujjars and Dalits apparently turning to the BJP, a number of factors helped the latter in scoring a landslide victory in different regions. Prime Minister Narendra Modi’s rally in Churu after the Balakot air strike on February 26 immensely helped the party in the Shekhawati region, from where a large number of youth are recruited in the armed forces every year.In the Marwar region, the alliance with the Rashtriya Loktantrik Party helped the BJP in mobilising Jats in its favour, as RLP chief Hanuman Beniwal wields considerable influence in Nagaur, Jodhpur and Barmer districts. The emergence of the Bharatiya Tribal Party in the Mewar region adversely affected the prospects of the Congress in Udaipur and Banswara, while the BJP depended on the influence of outfits like the Vanvasi Kalyan Parishad and the Bajrang Dal.Gujjars in eastern Rajasthan extended their support to the BJP after the community leader, Kirori Singh Bainsla, joined the party.last_img read more

Jacques Kallis rested for ODI series against England

first_imgSouth Africa have rested Jacques Kallis for the one-day international series against England.The 36-year-old Kallis, who scored an unbeaten 182 to help South Africa win the first Test against England by an innings and 12 runs at the Oval on Monday, has been replaced by the uncapped Dean Elgar.In naming their 15-man squad, Cricket South Africa(CSA) announced that Kallis is “being rested ahead of the ICC World Twenty20 in September.”The other changes to the squad that claimed a 3-0 ODI series win in New Zealand earlier this year sees spinner Imran Tahir and all-rounder Ryan McLaren recalled.last_img read more

Mayor Calls for Greater Synergy Between Municipal Corporations and Central Government

first_img “If we work together, surely our efforts will help us in our respective municipal corporations to push the agenda for national development. We can also learn from each other and adopt best practices that work,” the Mayor said. Story Highlights Speaking at the opening of the Ministry of Local Government and Community Development local governance conference in Montego Bay, St James, on July 17, Mayor Davis said he welcomes the conference, as it brings together the decision makers from the municipalities to make plans and positive changes to local government. Mayor of Montego Bay, Councillor Homer Davis, is calling for greater synergy between the municipal corporations and central government. Mayor of Montego Bay, Councillor Homer Davis, is calling for greater synergy between the municipal corporations and central government.Speaking at the opening of the Ministry of Local Government and Community Development local governance conference in Montego Bay, St James, on July 17, Mayor Davis said he welcomes the conference, as it brings together the decision makers from the municipalities to make plans and positive changes to local government.“If we work together, surely our efforts will help us in our respective municipal corporations to push the agenda for national development. We can also learn from each other and adopt best practices that work,” the Mayor said.He encouraged the mayors and administrative leaders of the municipal corporations to take the time to understand their roles and how they can contribute to their parishes to achieve the desired synergy and success.“As mayors and councillors, we are the ones that the citizens from our divisions hold accountable for issues related to garbage collection, for the repair and installation of street lights and for issues relating to drain cleaning. So, let us use our positions as public officers to be the positive change… Jamaica has been yearning for,” the Mayor said.He expressed concern about the local authorities not having the power to take corrective or disciplinary action against agencies, and requested Minister, Hon. Desmond McKenzie, to consider his petition.“The development of the parishes can be negatively impacted by the inaction of agencies. We must be able to hold agencies accountable when they fail the citizens. That is why I am urging all mayors, let us petition that we are given more teeth to manage the affairs of our parishes,” he said.The conference is being held under the theme ‘Strengthening responsiveness and accountability within the local governance framework’.last_img read more