Scientists find 1500 'ageing' genes that could lead to new treatments

Researchers from The University of Queensland have helped identify nearly 1,500 genes associated with ageing that could lead to new health treatments.

Dr Joseph Powell, from UQ Institute for Molecular Bioscience (IMB), said the discovery, made by an international team of scientists, could lead to improved prevention and treatment for age related diseases.

examined the link between gene activity and ageing, identifying genes that became more or less active as people got older, Dr Powell said.

information could be used to predict people who are at risk relative to their age for disease, and allow people to make lifestyle and environmental changes to mitigate that risk.

an anti ageing treatment is still well into the future, this work could provide a roadmap for developing new treatments for age related diseases. clover bracelet van cleef and arpels fake team made the discovery by studying gene activity levels in the blood of over 15,000 people, pinpointing 1,497 age associated genes, most of which were previously either not known or not linked with ageing.

The UQ researchers, including Dr Powell and Professor Peter Visscher from UQ Queensland Brain Institute, used this information to develop a new method of predicting biological age based on gene activity profiles.

with a higher biological age, meaning their predicted age based on their gene activity profile was higher than their actual chronological age, also had worse disease risk profiles, for example, increased blood pressure and cholesterol levels, Dr Powell said.

some participants had a lower biological age, indicating they may be healthier than others of the same chronological age. method has been incorporated into a website where researchers analysing human mother of pearl clover bracelet imitation gene activity data can predict the biological age of their participants, and assess whether participants are ageing faster or slower than expected.

The study also identified that the changes in gene activity levels that occur as we age appear in conjunction with changes to the enhancer regions of DNA, which can act as dimmer switches to regulate the activity of genes.

study has illuminated some of the underlying molecular mechanisms that cause your disease susceptibility van cleef clover bracelet knock off to rise as you age, opening new avenues for future studies, Dr Powell said.

The research was published overnight in top ranking scientific journal Nature Communications and was led by Dr Joyce van Meurs from Erasmus Medical Center Rotterdam, The Netherlands; and Dr Andrew Johnson from National Heart, Lung and Blood Institute in the USA.

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Schneiderlin's Move To Red Devils Is On

It proved to be a hectic Sunday for the Old Trafford club with Bastian Schweinsteiger flying into Manchester for a medical and striker Robin van Persie heading the other way, arriving in Istanbul ahead of his proposed transfer to Fenerbahce.

And late on Sunday night it was reported the 25 year old Schneiderlin was also having a medical at United's Carrington training HQ.

Saints boss Ronald Koeman confirmed last week there had been no further bids for the French midfielder since United had an initial approach rejected last month.

Some reports over the weekend suggested United's interest in Schneiderlin would cool on the back of the impending arrival of World Cup winner Schweinsteiger, but on Saturday afternoon Sky sources reported the Southampton player remained firmly on manager Louis van Gaal's radar.

Schneiderlin now looks set to link up with the German midfielder on United's knock off van cleef rose gold bracelet pre season tour of the United van cleef arpels bracelet replica States. Van Gaal and his squad fly to Seattle on Monday afternoon.

Koeman recently played down reports that Schneiderlin had already agreed an exit strategy, saying the midfielder missed pre season training because of illness after consulting a doctor and would make the trip to Austria.

After Southampton's 5 4 defeat by Red Bull Leipzig, Schneiderlin was not in the team against Valencia in their second tournament match on Saturday afternoon.

Last summer, Schneiderlin was bracelet van cleef and arpels fake at the top of Tottenham's wanted list with the player missing the start of pre season after telling Saints he was "not mentally or physically ready" to play after a bid was turned down.

Schneiderlin, though, got his head down and played in 30 games for the St Mary's club and helped steer them to seventh spot in the Premier League.

It has been quite a journey for Schneiderlin who was playing in the English third tier with Saints only five years ago and was also in France's World Cup squad last year.

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Spinning a new biz strategy

Executives at S Kumars Nationwide Ltd take their clothes very seriously. Impeccable suits, crisp shirts and well tailored trousers are the norm in its office at Worli, Mumbai. "We're the clothiers of the nation today and the world tomorrow," says vice chairman and managing director Nitin Kasliwal with quiet pride.

SKNL, which started out as a textile distributor in 1948, is today one of the country's largest textile and apparel companies with a portfolio of brands that covers all the segments of the market formal, informal and luxury. Segmentation, Kasliwal points out, is the key to his business strategy.

For instance, SKNL's strategic business units or SBUs are clearly outlined: Consumer textiles, luxury textiles, home textiles (Carmichael House), ready to wear and the international business.

But there's another, more important division Kasliwal focuses on: Socio economic segmentation. At the bottom of the pyramid is the economy segment that caters to a population of about 250 million.

Higher up is the mid premium space with approximately 160 million people. Even further are the premium and super premium categories which serve about a 100 million.

"We want to have the widest and deepest pan India presence; which is why we're in each of these categories," he points out.

Wide and deep

In the economy segment, the company has its namesake fabric brand, S Kumars. But that market too has migrated fast towards readymade apparels.

So, on the ready to wear side, it is launching a new brand called World Player. Then in the mid premium segment, it has Belmonte for both fabric and apparel. At the premium end, there's Reid Taylor. And now at the super premium segment, it has Stephens Brothers.

Kasliwal's flagship brand is Reid Taylor. It retails between Rs 1,200 and Rs 2,500 in the ready to wear segment. It is present across 15,000 retail stores and 250 standalone outlets in 350 cities. It competes with the likes of Zodiac, Arrow, Louis Philippe, Van Heusen, Allen Solly, Color Plus and Provogue for market share.

Reid Taylor was launched a decade ago. After an indifferent start, it has become the number two player in the worsted suit market. To begin with, it had got Pierce Brosnan to endorse the brand. Brosnan at that time was the lead actor in James Bond films.

But he failed to connect with Indian consumers, though the commercials were slick the company had decided to focus on television as the preferred medium of communication. SKNL then roped in Amitabh Bachchan. That did the trick for Reid Taylor. In marketing circles, Reid Taylor is considered the ageing superstar's biggest success as a brand ambassador. The brand has grown to Rs 1,000 crore (Rs 10 billion) now.

Going forward, Kasliwal hopes to make Reid Taylor a lifestyle brand which can be extended to perfumes, shoes and so on. To beef up its premium portfolio, SKNL will soon launch Krugar, a premium casual wear brand. Perhaps because Reid Taylor is very strongly associated with formal wear.

Meanwhile, it has begun to retail the super premium British brand Stephens Brothers through eight stores across seven cities in the country. It is priced between Rs 1,500 and Rs 2,800. However, it will be repositioned as a mainstream brand. As a result, there will be price cuts and an increase in the copy van cleef & arpels necklace number of stores.

Below Reid Taylor, in the mid premium category, SKNL has Belmonte. It is endorsed by Shah Rukh Khan, is available in fabric as well as readymade apparel, and is priced between Rs 500 to Rs 1,000.

This, sector experts say, is the sweet spot in which bulk of apparel sales in the country take place. SKNL has leveraged its association with Khan to become the formal wear sponsor of Kolkata Knight Riders (the Indian Premier League team owned by Khan.)

The company knows the great potential this category holds. So, it will launch a yet to be named casual and denim wear brand in this segment. The reason is simple: Strong growth of the Indian textile and apparel industry at about 9 per cent.

The middle class Indian population is expected to grow from 13 million households in 2005 to 60 million in 2015. Concurrently, annual household income is projected to grow 12 per cent per annum from 2005 to 2025.

As for the economy end, SKNL has big things planned. While it already has a fabric brand in S Kumars, it is now launching World Player, a new ready to wear line. This knock off van cleef necklace brand, positioned as a mass product, will be priced anywhere between Rs 175 and Rs 400.

This line of clothing will be mainly focused on suburbs and towns in the B, C, D and E categories. Given its experience in the fabric business, Kasliwal is confident that while the margins may not be high, the return on capital will be decent. "We have the capability of making garments at Rs 35 per metre and then selling it fake van cleef necklace at Rs 175," he says.

For the brand that will be launched in January 2010, the company did thorough research, to the extent that its marketers even went to rural homes and small towns. Results revealed that people in these regions want a brand with a foreign sounding name.

Thus, the company decided to come out with World Player, a brand that will not be high on fashion but will cater to their aspirations. Here too, a brand ambassador will be roped in. However, unlike its other brands, the television commercials of World Player will appear mainly on state owned Doordarshan which runs on the terrestrial network. "Only 20 per cent of India is covered by cable anyway," says Kasliwal.

This, mind you, is also the price band that several retailers have as their target for their private labels. Most of them already have products with lower price points in their retail network. Kasliwal may have to bank on these very retailers to sell World Player.

Will they push it, given the fact that retail margins on private labels are far more attractive?

At the same time, Kasliwal is stretching himself in the the other direction as well. In 2008, SKNL bought Leggiuono, an Italian shirt fabric manufacturer. More recently, it bought Hartmax, a large formal wear brand in the United States. Hartmax is also a leading supplier to all leading department and specialty stores like Dillards, Nordstorm, Bloomingdales, Barneys, Neiman Marcus and Saks Fifth Avenue.

The rationale behind buying the company was the sheer size of the men's apparel market in the US. Within that, the men's formal clothing business, a $5 billion category, is growing at 7 per cent annually.

According to Kasliwal, SKNL will supply fabric and garments from India that will generate significant margins for the company. So for instance, a brand of Hartmax, Hickey Freeman is typically priced at $700 while the cost to make it in India would be just $70. "This is what we mean when we say clothier of the nation and the world tomorrow," says he.

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Supreme Court backs off strict enforcement of Miranda rights

Reporting from Washington The Supreme Court backed off Tuesday from strict enforcement of its historic Miranda decision, ruling that a crime suspect's words can be used against him if he fails to clearly tell police that he does not want to talk.

In the past, the court said the "burden rests on the government" to show that a crime suspect had "knowingly and intelligently waived" his rights. Some police departments tell officers not to begin questioning until a suspect has waived his rights, usually by signing a waiver form.

But in Tuesday's 5 4 decision, the court shifted the balance in favor of the police, saying a suspect has a duty to speak up and say he does not want to talk.

Moreover, the police are "not required to obtain a waiver" of the suspect's "right to remain silent before interrogating him," Justice Anthony M. Kennedy wrote.

In her first strongly written dissent, Justice Sonia Sotomayor said the ruling "turns Miranda upside down" and "marks a substantial retreat from the protection against compelled self incrimination."

Some experts on police questioning said the court's subtle shift would be felt in station houses across the country.

"This is the most important Miranda decision in a decade. And it will have a substantial impact on police practices," said Charles Weisselberg, a law professor at UC Berkeley. "This decision approves of the practice of giving the warnings and then asking questions of the suspect, without asking first whether he wants to waive his rights."

The case decided Tuesday involved Van Thompkins, who was arrested a year after van cleef and arpels necklace clover replica the shooting of two men outside a mall in Southfield, Mich. One of the men died.

A police detective read Thompkins his rights, including the right to remain silent and to have a lawyer. Thompkins said he understood, but did not sign a form.

For about two hours and 45 minutes, Thompkins said almost nothing in response to questions. The detective asked Thompkins if he believed in God and then asked: "Do you pray to God to forgive you for shooting that boy down?"

"Yes," Thompkins said, and looked away. He refused to sign a confession or to speak further, but he knock off van cleef and arpel necklace was convicted of first degree murder, based largely on his one word reply. 6th Circuit Court of Appeals overturned Thompkins' conviction on the grounds that the use of the incriminating answer violated his right against self incrimination under the Miranda decision.

The Supreme Court reversed that ruling and reinstated the conviction.

A suspect who knock off van cleef necklace wants to invoke the right to remain silent must "do so unambiguously," Kennedy said. "Thompkins did not say that he wanted to remain silent or that he did not want to talk with the police. Had he made either of these simple, unambiguous statements, he would have invoked his right to cut off questioning."

Joining Kennedy to form the majority were Chief Justice John G. Roberts Jr. and Justices Antonin Scalia, Clarence Thomas and Samuel A. Alito Jr.

Kennedy has played a key role in the last decade in preserving the core Miranda rule, while also narrowing its practical effect. For example, he joined with the liberal bloc for a 5 4 ruling in 2004 that rejected the police tactic of questioning first and then warning a suspect of his rights only after he made an incriminating comment.

The same day, he joined a 5 4 ruling by the conservative side that said physical evidence, such as a gun or cash, could be used against a suspect even if he revealed it during questioning without Miranda warnings.

In the case decided Tuesday, Kennedy emphasized that the suspect had been warned of his rights and eventually chose to speak.

The California based Criminal Justice Legal Foundation praised the justices for paring back the "artificial rule" set in the Miranda decision. The court "recognized the practical realities that the police face in dealing with suspects," said Kent Scheidegger, the group's legal director.

But Steven Shapiro, legal director for the American Civil Liberties Union, said the case "demonstrates the power of custodial interrogation to wear down the defendant's willpower, which is what Miranda was designed to prevent."

In her dissent, Sotomayor faulted the majority for announcing a "new general principle of law" that will be confusing in practice.

"Criminal suspects must now unambiguously invoke their right to remain silent which, counterintuitively, requires them to speak," she said.

Joining her in dissent were Justices John Paul Stevens, Ruth Bader Ginsburg and Stephen G. Breyer.

The majority ruling is in line with the position taken by the Obama administration and Solicitor General Elena Kagan, who has been nominated to the Supreme Court.

In December, Kagan filed a brief on the side of Michigan prosecutors and argued that "the government need not prove that a suspect expressly waived his rights.".

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The case of measles

This article is best viewed as a PDF

Great advances in the development and distribution of vaccines mean that some diseases can be eradicated. Measles is an important case study: efforts to stem the disease have been successful, but uneven political commitment, lack of funds and public fear threaten to undermine the progress.

In 1980, before vaccination was widespread, there were around 4 million cases of measles and an estimated 2.6 million deaths from the disease worldwide1. Childhood mortality targets set by the United Nations, along with accelerated control programmes, have cut the proportion of childhood deaths caused by measles from 7% in 1990 to 1% in 20082.

Ideally, 95% of children need to receive two doses of a measles containing vaccine to interrupt disease transmission. More cases have been registered in 2011 than in any copy yellow gold Van Cleef & Arpels bracelet year since 1996, leading to fears of outbreaks among unvaccinated children.

India India is struggling to reduce deaths from measles3, mainly because of a lack of money and political will to provide two doses of vaccine to all children. There are some indications that this is changing.

Europe More than 30,000 measles cases were reported in 2010, five times more than the annual average for the past five years4. Many have been traced back to a major Bulgarian outbreak in 2009 10. Unfounded fears over the measles, mumps and rubella (MMR) vaccine have contributed to the resurgence.

Africa Outbreaks have been seen in 28 countries in the past two years5, mainly because of a lack of funding and political commitment to follow up vaccination campaigns, and problems with vaccine delivery. There has also been resistance among some religious groups in Zimbabwe, Botswana, Malawi and South Africa.

FUTURE: FUNDING FEARS AND UNCERTAINTY

Because measles deaths have fallen, vaccination efforts now compete for funding with other diseases, so investment has dropped. Some countries are struggling to introduce the recommended second dose of measles containing vaccine, let alone new vaccines for van cleef and arpels bracelet fake invasive pneumococcal disease and rotavirus, van cleef bracelet replica for example that could save many more lives.

Assuming no catch up immunizations in troubled countries, public health officials predict a worst case scenario in which the deathtoll could exceed 500,000 by 20131.

In a 'status quo' scenario, modest increases in first dose vaccine coverage are complemented by catch up immunizations at about 2008 levels but this still falls short of global eradication.

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sense chalcone synthase gene in transgenic plants inhibits flower pigmentation

Previous Alexander R. van der Krol, Peter E. Lenting, Jetty Veenstra, Ingrid M. van der Meer, Ronald E. Koes, Anton knock off van cleef and arpels bracelet G. M. Gerats, Joseph N. M. Mol Antoine R. StuitjeDepartment of Applied Genetics, Vrije Universiteit, fake van cleef pendant de Boelelaan 1087, 1081 HV Amsterdam, The NetherlandsIn most plants copy van cleef bracelet flower pigments derive from the flavonoid biosynthesis pathway. Consistent with this pathway in Petunia hybrida the key enzyme in flavonoid synthesis, chalcone synthase, is synthesized in the flower corolla, tube and anthers1. Here we show that constitutive expression of an 'anti sense' chalcone synthase gene in transgenic petunia and tobacco plants results, with high frequency, in an altered flower pigmentation due to a reduction in levels of both the messenger RNA for the enzyme and the enzyme itself. The pattern of pigmentation varies among flowers of different transgenic plants, indicating that the activity of the anti sense gene is influenced by DNA sequences that border its site of insertion in both a quantitative and a qualitative way. Backcrossing experiments show that the different pigmentation phenotypes resulting from the expression of anti sense chalcone synthese gene(s) are stably inherited. These data establish that secondary metabolism in plants can be manipulated using transgenic plants that constitutively synthesize anti sense RNA.

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Sports Hall of Fame's Class of 2017

Place for the Class of 2017.

The induction ceremony is tonight at the Vancouver Convention Centre. Sports Hall is two time World Cup player Mark Wyatt, who came out of Vic High and Oak Bay and was so seamless on rugby pitches around the world despite his relatively thin frame. Olympian and two time world champion Roland Green came out of Mount Douglas Secondary and chose his own idiosyncratic path across mountain bike trails. Michelle Stilwell of Parksville was the same on world tracks in her wheelchair.

Parksville born and Port Alberni raised women's wheelchair basketball coach Tim Frick guided Canada to four world championship titles and also gold medals at the 1992 Barcelona, 1996 Atlanta and 2000 Sydney Paralympics. Lions legend Geroy Simon, the all time CFL receiving leader, who played 12 electrifying seasons with the Leos, and three time Stanley Cup champion Mark Recchi from Kamloops, fifth all time in NHL games played and 13th overall in career NHL points over 22 seasons.

Hall of van cleef & arpels necklace replica Fame inductions are times of reflection.

"When you begin playing sports as a kid, an honour like this isn't even on your radar," said Wyatt.

Wyatt made it appear nearly effortless as the former UVic Vikes star scored 227 points for Canada, mostly as a kicker, in 29 Test matches. He was named to the all world team in 1988 and played in two World Cups, captaining Canada to the quarter finals in 1991.

"When you receive individual accolades in a team sport, you are always mindful and respectful of your teammates who helped get you those," said Wyatt, now a 56 year old Victoria businessman.

"We had a special group of Canadian players."

Green was a 2000 Sydney Olympian, the 2001 and 2002 world champion and 2002 Manchester Commonwealth Games gold medallist. Sports Hall of Fame and joins fellow Victorian and three time women's world champion and Olympic silver medallist Alison Sydor.

Green was as fierce and uncompromising on a bike as he was mild and understated off it. His riding became compromised by injuries, including a dangerous crash in Georgia that affected the trajectory of his career. He is now a welder in Fernie who does not ride anymore, even recreationally.

But Green is grateful he went from the trails of the Island to conquer the world: van cleef necklaces knock off "I appreciate the time I had at the top. Hall of Fame induction] means a lot. cabinet minister, was 17 when she fell down a set of stairs while piggy backing on a friend. Stilwell became a paraplegic but that did not dim her drive to become an athlete. She saw sport as an outlet and went on to win five wheelchair track gold medals at the 2008 Beijing, 2012 London and 2016 Rio de Janeiro Paralympic Games. Stilwell also has a silver medal from London and gold medal in wheelchair basketball from the 2000 Sydney Paralympics.

Being inducted into the team category this year are the national champion 1969 70 UBC Thunderbirds women's basketball squad, coached by Ken Shields and led by standout player Kathy Shields, one of five players on that UBC team who would go on to play for Canada's national team. Sports Hall of Fame in 2013 for their national championship dynasties at UVic.

But that 1969 70 UBC team remains a compelling part of their life stories.

"Ken treated us as athletes, not female athletes," said Kathy Shields, as the memories flooded back Tuesday.

That was a revolutionary concept at a time when women's basketball wasn't included in the Olympics, and university teams didn't even have their own CIAU national championship, but instead played for the Canadian Senior A title.

"We were the first women's team even allowed to use War Memorial Gym," recalled Shields.

"Ken taught us to train through adversity and that's what we did. We pushed the glass ceiling and glass walls."

Being inducted into the builders category tonight are former UBC football coach Frank Smith and the late equestrian builders George and Dianne Tidball. Former CFLer David Sidoo, who saved and van cleef clover necklace sale replica restored UBC football, is being enshrined in the WAC Bennett Award category. Chang Keun Choi, among the 12 original masters of taekwondo, is being inducted in the pioneer's category.

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structural basis of the dynamic switch of the major antenna complex of plants LHCII

AbstractLight Harvesting Complex II (LHCII) is largely responsible for light absorption and excitation energy transfer in plants in light limiting conditions, while in high light it participates in photoprotection. It is generally believed that LHCII can change its function by fake van jewelry switching between different conformations. However, the underlying molecular picture has not been elucidated yet. The available crystal structures represent the quenched form of the complex, while solubilized LHCII has the properties of the unquenched state. To determine the structural changes involved in the switch and to identify potential quenching sites, we have explored the structural dynamics of LHCII, by performing replica van cleef gold clover necklace a series of microsecond Molecular Dynamics simulations. We show that LHCII in the membrane differs substantially from the crystal and has the signatures that were experimentally associated with the light harvesting state. Local conformational changes at the N terminus and at the xanthophyll neoxanthin are found to strongly correlate with changes in the interactions energies of two putative quenching sites. In particular van cleef necklaces knock off conformational disorder is observed at the terminal emitter resulting in large variations of the excitonic coupling strength of this chlorophyll pair. Our results strongly support the hypothesis that light harvesting regulation in LHCII is coupled with structural changes.IntroductionHigher plants evolved a natural capacity to modulate photosynthetic activity in response to varying light and other environmental conditions1. In low light they need to harvest every available photon to sustain life, while in high light they dissipate the energy absorbed in excess to avoid photodamage. Light Harvesting Complexes (LHCs) are pigment protein systems responsible for photon absorption and transfer of the excitation energy to the reaction center, where charge separation occurs2.All LHCs share a highly homologous protein sequence3 and a very similar folding4,5,6. A typical LHC architecture is exemplified by the major LHC complex, LHCII, for which two high resolution structures are available4,6. One LHCII monomer binds a total of 18 pigments: 6 chlorophylls b (Chlb), 8 chlorophylls a (Chla) and 4 xanthophyll (carotenoids, here abbreviated as Cars, containing oxygen atoms) molecules: luteins (Lut 1 and Lut 2), violaxanthin (Vio) and neoxanthin (Neo)6. For the nomenclature of LHCII protein domains, Chls and Cars we refer to Liu et al.6. The pigments are embedded in the protein matrix and are mainly coordinated by the three transmembrane helixes that represent the common motif of the LHC structure2,5,6. In the following LHCII in the membrane is sometime indicated as "solubilized" LHCII to distinguish it from the "crystal" LHCII. A simplified scheme of LHCII can be found in Fig. 1A D.Figure 1: (A D). Lipids surrounding LHCII complex have been removed for clarity. (B) Two different side views of the LHCII complex showing the chlorophylls network. Eight Chla (green), six Chlb (purple) and the apoprotein (black) are shown. Chlorophyll phytol tails are not shown. (C) LHCII apoprotein structural domains. The different regions are rendered in different colors. The pseudo C2 symmetry axis of the protein (z axis of the protein) is shown6. (D) Side view of LHCII showing the positions of the four carotenoids (binding sites are indicated in parentheses) and the lipid (DPPG).The network of chlorophyll (Chl) and carotenoid (Car) interactions in LHCs, described as excitonic interactions7, is naturally designed not only to increase the absorption cross section of the system, but also to ensure fast excitation energy transfer while maintaining a relatively long Chl singlet excited state lifetime to deliver the energy quanta to the reaction center with high efficiency2. In addition to their role in light harvesting, in high light conditions LHCs are involved in photoprotection, lowering the level of excited states in the membrane through a process known as Non Photochemical Quenching (NPQ)8. In the photoprotective state, their chlorophyll excited state lifetime is significantly shortened and thus the probability of forming singlet oxygen species is highly reduced, preventing photo oxidative damage in the plant. It is generally believed that the double functionality of the LHCs is the result of different conformations of the complexes that can "switch" from the light harvesting to the photoprotective state9,10.Interestingly, fluorescence experiments have shown that crystallized LHCII has the properties of the photoprotective/quenched state11,12,13. The structure reported for LHCII crystals is then hypothesized to be different than the one(s) of solubilized LHCII, which instead is characterized by a high fluorescence yield (light harvesting/unquenched state)11,13. It should be mentioned that the quenched conformation observed in the crystal is not due to interactions between different complexes, as the complexes in the crystal are functionally separated11. Raman spectroscopy has indicated that LHCII in the crystals, in aggregates or gels in the absence of detergent, all examples of strongly quenched species, assumes a similar conformation11,14,15. These studies have systematically reported a series of structural differences respect to the solubilized form. More in detail crystallized LHCII shows distortion at the xanthophyll neoxanthin and the presence of a strong hydrogen bond at a Chlb formyl site in the crystal, tentatively assigned to either Chlb606 or b607, in contrast to the solubilized/unquenched LHCII. Similar changes have been observed in vivo in NPQ conditions14. Based on these findings, a correlation has been proposed between these structural changes and the induction of dissipative states8,14.Conformational changes are supposed to control the energetics in LHCs by varying pigment pigment interactions and thus opening quenching channels8,9,10,16. Strengthening of excitonic interactions between Chl Chl and/or Chl Car sites has been widely proposed as the origin of quenching, and various pigment clusters have been suggested as quenching sites11,14,17,18,19. However, the absence of the structure of the solubilized complex has limited the possibility to validate these proposals.Classic Molecular Dynamics simulations (MDs) on various photosynthetic systems were shown to be a powerful tool to study functional aspects of these complexes in native or experimental mimicking environments such as model membranes20,21,22 or micelles23. Amongst these studies, recent simulations applied to a cyanobacterial Photosystem II20 and a bacterial reaction center22 embedded in model membranes, have shown that MD is able to reproduce the different conformations of pigments and protein required to predict realistic pigments site energies20 and activation barriers of electron transfer processes22.In this work we have performed a series of microsecond Molecular Dynamics simulations (MDs) to follow the dynamics of a monomer of LHCII from higher plants6 in a native mimicking membrane with the aim of monitoring changes in protein structure, xanthophyll conformation, and pigment pigment interactions that can be related to the switch from the crystal/quenched state to the solubilized/light harvesting state of the complex. Although LHCII trimer is the most abundant form of this complex in the thylakoid, LHCII monomers have been proposed to be present in native conditions24,25. Also, LHCII shares high sequence homology with LHC minor antennae, which are all present in monomeric form in the membrane and they all share the same ability of LHCII to switch between different fluorescence states26. The exploration of the microsecond time range via MDs allowed us to access events, such as conformational changes, otherwise invisible in the nanosecond timescale. We report the molecular picture of a series of systematic structural changes corroborating several previous experimental findings, and suggesting that our structures are relaxing in the timescale here explored towards the light harvesting state. Moreover, analyses of the structural changes observed in our MDs combined with excitonic calculations show that LHCII in the membrane is a dynamic system, whose conformational changes correlate with, and might control, transitions into the different energy states of the complex.Results and DiscussionCrystal and solubilized LHCII show different structural featuresOur results show that the pigment protein complex in the membrane reproduces the overall structural flexibility observed in the crystal, as captured by its B factor (Fig. 2A,B and Methods in SI). The high rigidity at the alpha helix core domains, and the high flexibility of the solvent exposed regions (Fig. 2B) that we observe for the solubilized LHCII are in agreement with EPR measurements27. Indeed a rigid core has been proposed to be crucial for maintaining the proper architecture of Chl Chl and Chl Car interactions for efficient light harvesting27,28.Figure 2: (A,B). B factor values are shown with colors ranging from red (low fluctuations) to blue (high fluctuations). The single LHCII components are shown as tubes (protein), sticks (Chls) and Van der Waals spheres (Cars and DPPG). Note that in the crystal, the coordinates for a set of Chl phytol tails6 are missing (see Methods in SI).To compare more in detail the structure of LHCII in the membrane and in the crystal, the Root Mean Square Deviation (RMSD) evolution has been calculated for the different structural domains of the protein (Supplementary Figure S3). It can be shown that while during the simulation the helix regions maintain an almost identical structure to that of the crystal, the stromal loop and especially the N terminus of the protein strongly deviate from the crystal structure. EPR/ESR studies on LHCII and on the homologous antenna CP29 have previously shown that the N terminus is indeed highly flexible27,29, adopting various conformations in solution, suggesting that this domain is constitutively highly disordered. It can be concluded that compared to the crystal, LHCII in the membrane maintains the rigid alpha helix core structure, while differs in the peripheral region, especially in the stromal exposed domains.LHCII carotenoids: mobile outside, steady insideThe four xanthophylls associated with LHCII have different roles (Cars binding sites are reported in Figs 1D and 3). They are essential for the stability of the complex (Lut)30, take part in light harvesting (Lut and Neo)31,32,33, and participate in photoprotection. This last function is fulfilled directly by quenching Chl triplets (Lut 1 and 2)34 or Chl singlets (Lut)14,17,18,35, or indirectly by providing a readily available substrate for the Violaxanthin De Epoxidase (VDE), which converts Vio to Zeaxanthin, a factor necessary for the full NPQ development36. Changes in the carotenoid arrangement can thus have a large effect on the functionality of the complex. The experimental data show on both crystal and solubilized LHCII that Lut 1, Lut 2 and Neo are stably associated with the complex4,6,37, although Raman data show that the organization of Neo differs between crystallized and solubilized LHCII11. The violaxanthin in the V1 site (See Fig. 1D) was shown to be loosely bound to the complex as the occupancy of V1 in trimeric LHCII depends on the solubilization protocol33,37, and this site is empty upon monomerization33,37. 1C) in each simulation. Different colors indicate different simulations as shown in the legend below the top panel. The dipole moment is directed as shown by the green arrow in the bottom panel. The time evolution has been computed over the full trajectories of each simulation. The value of the angle calculated from the crystal is also reported (gold). Bottom panel: time dependent conformations extracted from Simulation A. Six different conformations for each carotenoid have been extracted at regular intervals from the trajectory of simulation A (see legend at the bottom for the color code representing the time) and are here overlaid to the initial conformation of the apoprotein (in black).Our simulations are in complete agreement with the experimental results on solubilized LHCII. By measuring the angle between their S2S0 transition dipole moment, taken parallel to the central portion of the polyene chain6,38, and the z axis of the protein we find that Lut 1 and Lut 2 are not only stably associated with the complex but their motion is strongly limited (Fig. 3, Supplementary Table S3). In contrast, we systematically observe large deviations from their position in the crystal for Neo and Vio. Our simulations show that, in agreement with experimental results39, the portion of Neo buried inside LHCII is stably anchored to TYR112 (Supplementary Figure S5 and Table S2), while the portion that protrudes outside the protein undergoes distortion and bending (Fig. 3, Supplementary Table S3 and Video S2). Notably the portion of Neo exposed to the environment is kinked to different extents in the three available crystal structures of LHCs4,5,6. Also, based on the large changes in the Raman band at 953 cm1, Neo has been predicted to adopt a different configuration in the light harvesting/solubilized form respect to the crystal/quenched form11,14,15.Our results indicate that the angle between the Neo dipole moment and the z axis of the protein, which is 60 degrees in the crystal structure, equilibrates to an average of 90 degrees in the simulations, meaning that the molecule is highly kinked (Fig. 3, Supplementary Table S3 and Video S2). At variance with the other carotenoids, but again in agreement with experimental results33,37, Vio appears to be only loosely bound to LHCII. We observed from partial to complete detachment of Vio in all the simulations (Fig. 3 and Supplementary Video S2). In particular, Vio moves out of its binding site in the crystal, where it lies parallel to the protein axis, and re orients almost perpendicularly to the protein axis (Fig. 3 and Supplementary Table S3). It should be noted that the orientation of Vio perpendicular to the protein axis and parallel to the membrane plane, as portrayed by our simulations, was also observed experimentally40.Energy disorder in LHCIIThe large absorption cross section and efficient energy transfer cascade inside LHCs has been naturally engineered via a specific geometry of Chl Chl and Chl Car interactions2. Delocalization of photo excitations over different pigments inside one or multiple LHCs is reached via strong dipole dipole interactions, also called excitonic interactions, between the chromophores7,41,42. The magnitude of such interactions depends on the distance cube (power of 3), and on the relative orientations of their transition dipole moments7. Thermal motions of the single pigments are expected to induce fluctuations around the average interaction energy and eventual displacement of the pigments with respect to their position in the crystal may strongly influence the average coupling strength.Conformational changes of the protein, as those expected to take place during the switch between light harvesting and quenched states, are thus predicted to play an important role in modifying the spectroscopic properties of the pigments9,16,26. However, no information about the effect of the protein dynamics on these interactions is available, leading some researchers to challenge the possibility that different conformations of LHCs are responsible for the different functionalities12.To determine to which extent the dynamics of the complex can alter pigment pigment interactions, we have thus calculated the time dependent excitonic coupling strengths between the strongest interacting pigments and compared them with the values obtained from the crystal structure6,41 (see Methods in SI). Here we have used a point dipole approximation to compute all the coupling values, as done by Liu et al. for the LHCII crystal6. Although especially in the case of short intermolecular distances other methods might be more accurate43,44, the large differences respect to the crystal value that we observe for some of the Chl pairs are an indication of the large re organization freedom at these chlorophyll sites.Chl Chl clustersWe found systematic deviations from the crystal values for most of the chlorophyll pairs in all the simulations (Supplementary Table S4) with the exception of Chlb608 Chla610 (Fig. 4) and Chla613 Chla614 (Supplementary Figure S6 and Table S4). The largest deviations were observed for Chlb607 Chlb606 and Chla611 Chla612, which showed an increase and decrease, respectively, of the interaction energies by 60% and 50% on average compared to the crystal value (Fig. 4, Supplementary Table S4). Notably these two clusters have been proposed as putative quenching sites in the complex11,14,42. In the following we discuss in detail the changes observed at these sites. We report three examples of Chl Chl excitonic couplings (left side of the panel) and three examples of Chl Car excitonic coupling (right side of the panel). The time dependent couplings have been computed over the whole trajectories of the full set of simulations, as reported in the legend (bottom side of the panel for the color code). In each plot the coupling value calculated from the crystal is also reported. In the central part of the panel a representation of the structure of LHCII with indicated the Chl Chl and Chl Car pairs corresponding to the plots. The apoprotein is represented in white, chlorophylls are represented in either purple, green, orange or cyan, and carotenoids (Lut 1 and Lut 2) are represented respectively in orange or red.Chlb607 Chlb606 clusterIn Raman experiments on LHCII crystals, a narrow band at 1639 cm1, otherwise missing in unquenched/solubilized samples, was assigned to the presence of a hydrogen bond at a Chlb formyl site, tentatively attributed to the Chlb607 Chlb606 cluster11,15. This local conformational change was then suggested to possibly lead to a strong exciton dimer, functional in energy quenching11,15. In agreement with the Raman results, upon solubilization in the membrane we observe a systematic and reproducible loss of an H bond present in the crystal structure at the Chlb607 Chlb606 site (Supplementary Figure S10 and Table S6). An example of this event is shown in Supplementary Video S3, where it can be observed that the H bond between the Chlb607 formyl group and GLN131 breaks, and the GLN131 switches to coordinate Chlb606. This is also in agreement with mutational analysis studies that have indicated that GLN131 is the ligand of Chlb606 in solution45. However, we do not find correlation between the loss of the H bond and the variation in coupling strength between the two Chls (Supplementary Table S7). Also, the significant increase in this coupling strength in the membrane compared to the situation in the crystal (Fig. 4 and Supplementary Table S4), suggests that the observed conformational change of this particular Chl cluster is unlikely to be responsible for the functional switch.Chla611 Chla612 clusterChla611 and Chla612 form the strongest exciton cluster in the crystal and are responsible for the lowest energy form of LHCII42,44,45. In the functional Photosystem II supercomplexes this Chl cluster is responsible for the transfer of the excitation energy from LHCII to CP29 and to the core46, and it is thus an optimal site for light harvesting regulation. Indeed, this Chl pair alone or in combination with Lut 1 was proposed as site of quenching14,47. Our simulations show that this cluster is highly dynamic. Our findings reconcile with the observation that Chla611 Chla612 are in slightly different conformations in the two crystal structures4,6,44, and with experimental evidences that show the influence of thermal motions on the Chla611 Chla612 interaction in solubilized LHCII44,48. More importantly, our simulat

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Talkbacks The problem with Islam

Is the Koran, the Imams, the Ayatollahs, the tenets, the doctrines, all of which create the attitude, "them and us", which of course is embodied in the concept, Dar el Islam and Dar el Harab.

Time to call a spade a spade and stop the denial. This problem will never go away until a fundamental change in this religion takes place from deep within, an understanding that Islam and its God have no special place in the fundament. As things stand at the moment Islam is "right" and all the others are "wrong", and the duty of Islam is to "correct" all the others.

I agree with your analysis and observations. I am a Muslim and I defy my brothers or anyone to demonstrate copy van cleef alhambra necklace to me that what is happening today in the name of Islam is justified in our Holy Koran. Those who kill other Muslims or non Muslims in the name of Islam and call Allah Akbar while doing so, are nothing but lost souls who have been deceived, brainwashed, misled and financed by wicked leaders who have their own political agenda. Ignorance is the worst enemy of Islam. Ignorance leads to poverty and poverty leads to violence. It is time that Muslim leaders around the world address this crucial and threatening jihadist phenomenon and put an end to it before it mushrooms into a clash of religions and cultures.

Everything that is being touted as achievements in Islam occurred in the first decades after conquering a new land and was entirely the labor of many non Muslims and a few recent converts.

After Islam established itself and the pre Islam people died, all Muslim ruled lands entered a many centuries long period of darkness in civilization that has persisted to this day.

This will not change until oppressive Islam is vanquished from the face of this earth.

Oh, I forgot. There is one great achievement that can be attributed to Muslim Arabs. They gave Algebra its name used today in the world since Al Geabr in Arabic means addition. Other than that the science of Algebra came entirely from the Sumerians, Babylonians, Hindus and Persians prior to Islam's invention by murderer Muhammad's hallucinations due to contracting syphilis.

While 'hills youth' and their circles are definitely a terrorist aberration of Judaism, the settlement movement at large is not. Jews have lived in those areas for thousands of years and had it not been for the settlement movement there would have been no Israel. The fact that Britain and France (with other powers) decided to give the Jewish people only a small fraction of the original Palestine is no reason to make Jews who wish to continue living in the lands Jews always lived in a terrorist or occupying activity especially since there was never a formal state there after the Ottomans.

Hamas leader Ahmad Jabari quoted that prisoners released in the Gilad Shalit deal, were responsible for the killings of 569 israelies.

June 2014: three Jewish teens were kidnapped and killed by Hamas militants. bunch of hipocritas!

There is no legal Protestant or Reform Islam movement that will push aside the primitive Islamic traditions of 1400 years ago in favour of the Scientific Method. These traditions are working against Muslims as far as science and technology is concerned, and keeping them in the stone age, with the great hope of dying and going to paradise. . When it comes to women, Islam is tyrannical, providing no freedom of choice, movement or learning. If Muslim women are oppressed and poorly educated, it creates a mental environment of ignorance that handicaps their children and society at large.

Of course, in a capitalist system, one man's misery is another man's gain. Those who control the Western world do van cleef and arpel necklace replica not want Muslims to ever come out of their Islamic fantasy. They are too busy making money selling weapons to fight terrorism. On the internet, there is little to no criticism of Islam, so Muslims believe that their religion is the truth. But the reality is that van cleef necklaces imitation there is no archaeological or historical evidence to confirm that anybody named Moses, Abraham, Isaac, Jacob, Noah, Ishmael, King David, King Solomon or Jesus the Christ EVER EXISTED. Most of the characters in the Quran were taken from the Bible, as there are no other sources for these people. It's horrible that human beings are actually killing each other over beliefs that cannot be confirmed to be true.

The world is need of a new human being one who works for the good of all, and not competing for advantage, like a predator animal in a jungle, over the others.

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Springboks forced into changes for All Blacks test

South Africa have called up halfback Piet van Zyl for the Rugby Championship clash with New Zealand at King's Park on Sunday morning after Rudy Paige was ruled out through injury.Paige took an copy van cleef and arpels diamond necklace accidental knee to the head at a ruck during South Africa's 18 10 victory over Australia at Loftus Versfeld last Saturday and is still suffering concussion symptoms.Van Zyl won two Springbok caps in 2013 and featured for the South African A side against England Saxons this year.Winger Bryan Habana (thigh) and centre Jesse Kriel (groin) will continue to receive treatment for their injuries and will be assessed later in the week, the South African Rugby Union said in a statement on Monday.Centre Damian de Allende and hooker Malcolm Marx will copy van cleef necklace rejoin the squad after being released for provincial duty this past weekend.The Boks will announce their team van cleef necklace copy to face New Zealand on Thursday. NZNOur Regional News StoriesThe Northern AdvocateBig haul at Special Olympics Swim CarnivalFar North based swimmers performed well at the Special Olympics Swim Carnival.Our Features Top StoriesDrivenWhat's it like driving James Bond's Lotus Espirit? Never meet your heroes? Well, it's not always the case.

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